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The Cochrane Database of Systematic Reviews logoLink to The Cochrane Database of Systematic Reviews
. 2023 Feb 16;2023(2):CD014758. doi: 10.1002/14651858.CD014758.pub2

Interventions for myopia control in children: a living systematic review and network meta‐analysis

John G Lawrenson 1,, Rakhee Shah 1, Byki Huntjens 1, Laura E Downie 2, Gianni Virgili 3,4, Rohit Dhakal 5, Pavan K Verkicharla 5, Dongfeng Li 4,6, Sonia Mavi 4, Ashleigh Kernohan 7, Tianjing Li 8, Jeffrey J Walline 9
Editor: Cochrane Eyes and Vision Group
PMCID: PMC9933422  PMID: 36809645

Abstract

Background

Myopia is a common refractive error, where elongation of the eyeball causes distant objects to appear blurred. The increasing prevalence of myopia is a growing global public health problem, in terms of rates of uncorrected refractive error and significantly, an increased risk of visual impairment due to myopia‐related ocular morbidity. Since myopia is usually detected in children before 10 years of age and can progress rapidly, interventions to slow its progression need to be delivered in childhood.

Objectives

To assess the comparative efficacy of optical, pharmacological and environmental interventions for slowing myopia progression in children using network meta‐analysis (NMA). To generate a relative ranking of myopia control interventions according to their efficacy. To produce a brief economic commentary, summarising the economic evaluations assessing myopia control interventions in children. To maintain the currency of the evidence using a living systematic review approach. 

Search methods

We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE; Embase; and three trials registers. The search date was 26 February 2022. 

Selection criteria

We included randomised controlled trials (RCTs) of optical, pharmacological and environmental interventions for slowing myopia progression in children aged 18 years or younger. Critical outcomes were progression of myopia (defined as the difference in the change in spherical equivalent refraction (SER, dioptres (D)) and axial length (mm) in the intervention and control groups at one year or longer) and difference in the change in SER and axial length following cessation of treatment ('rebound'). 

Data collection and analysis

We followed standard Cochrane methods. We assessed bias using RoB 2 for parallel RCTs. We rated the certainty of evidence using the GRADE approach for the outcomes: change in SER and axial length at one and two years. Most comparisons were with inactive controls.

Main results

We included 64 studies that randomised 11,617 children, aged 4 to 18 years. Studies were mostly conducted in China or other Asian countries (39 studies, 60.9%) and North America (13 studies, 20.3%). Fifty‐seven studies (89%) compared myopia control interventions (multifocal spectacles, peripheral plus spectacles (PPSL), undercorrected single vision spectacles (SVLs), multifocal soft contact lenses (MFSCL), orthokeratology, rigid gas‐permeable contact lenses (RGP); or pharmacological interventions (including high‐ (HDA), moderate‐ (MDA) and low‐dose (LDA) atropine, pirenzipine or 7‐methylxanthine) against an inactive control. Study duration was 12 to 36 months. The overall certainty of the evidence ranged from very low to moderate.

Since the networks in the NMA were poorly connected, most estimates versus control were as, or more, imprecise than the corresponding direct estimates. Consequently, we mostly report estimates based on direct (pairwise) comparisons below.

At one year, in 38 studies (6525 participants analysed), the median change in SER for controls was −0.65 D. The following interventions may reduce SER progression compared to controls: HDA (mean difference (MD) 0.90 D, 95% confidence interval (CI) 0.62 to 1.18), MDA (MD 0.65 D, 95% CI 0.27 to 1.03), LDA (MD 0.38 D, 95% CI 0.10 to 0.66), pirenzipine (MD 0.32 D, 95% CI 0.15 to 0.49), MFSCL (MD 0.26 D, 95% CI 0.17 to 0.35), PPSLs (MD 0.51 D, 95% CI 0.19 to 0.82), and multifocal spectacles (MD 0.14 D, 95% CI 0.08 to 0.21). By contrast, there was little or no evidence that RGP (MD 0.02 D, 95% CI −0.05 to 0.10), 7‐methylxanthine (MD 0.07 D, 95% CI −0.09 to 0.24) or undercorrected SVLs (MD −0.15 D, 95% CI −0.29 to 0.00) reduce progression. 

At two years, in 26 studies (4949 participants), the median change in SER for controls was −1.02 D. The following interventions may reduce SER progression compared to controls: HDA (MD 1.26 D, 95% CI 1.17 to 1.36), MDA (MD 0.45 D, 95% CI 0.08 to 0.83), LDA (MD 0.24 D, 95% CI 0.17 to 0.31), pirenzipine (MD 0.41 D, 95% CI 0.13 to 0.69), MFSCL (MD 0.30 D, 95% CI 0.19 to 0.41), and multifocal spectacles  (MD 0.19 D, 95% CI 0.08 to 0.30). PPSLs (MD 0.34 D, 95% CI −0.08 to 0.76) may also reduce progression, but the results were inconsistent. For RGP, one study found a benefit and another found no difference with control. We found no difference in SER change for undercorrected SVLs (MD 0.02 D, 95% CI −0.05 to 0.09).

At one year, in 36 studies (6263 participants), the median change in axial length for controls was 0.31 mm. The following interventions may reduce axial elongation compared to controls: HDA (MD −0.33 mm, 95% CI −0.35 to 0.30), MDA (MD −0.28 mm, 95% CI −0.38 to −0.17), LDA (MD −0.13 mm, 95% CI −0.21 to −0.05), orthokeratology (MD −0.19 mm, 95% CI −0.23 to −0.15), MFSCL (MD −0.11 mm, 95% CI −0.13 to −0.09), pirenzipine (MD −0.10 mm, 95% CI −0.18 to −0.02), PPSLs (MD −0.13 mm, 95% CI −0.24 to −0.03), and multifocal spectacles (MD −0.06 mm, 95% CI −0.09 to −0.04). We found little or no evidence that RGP (MD 0.02 mm, 95% CI −0.05 to 0.10), 7‐methylxanthine (MD 0.03 mm, 95% CI −0.10 to 0.03) or undercorrected SVLs (MD 0.05 mm, 95% CI −0.01 to 0.11) reduce axial length.

At two years, in 21 studies (4169 participants), the median change in axial length for controls was 0.56 mm. The following interventions may reduce axial elongation compared to controls: HDA (MD −0.47mm, 95% CI −0.61 to −0.34), MDA (MD −0.33 mm, 95% CI −0.46 to −0.20), orthokeratology (MD −0.28 mm, (95% CI −0.38 to −0.19), LDA (MD −0.16 mm, 95% CI −0.20 to  −0.12), MFSCL (MD −0.15 mm, 95% CI −0.19 to −0.12), and multifocal spectacles (MD −0.07 mm, 95% CI −0.12 to −0.03). PPSL may reduce progression (MD −0.20 mm, 95% CI −0.45 to 0.05) but results were inconsistent. We found little or no evidence that undercorrected SVLs (MD ‐0.01 mm, 95% CI −0.06 to 0.03) or RGP (MD 0.03 mm, 95% CI −0.05 to 0.12) reduce axial length.

There was inconclusive evidence on whether treatment cessation increases myopia progression. Adverse events and treatment adherence were not consistently reported, and only one study reported quality of life.

No studies reported environmental interventions reporting progression in children with myopia, and no economic evaluations assessed interventions for myopia control in children.

Authors' conclusions

Studies mostly compared pharmacological and optical treatments to slow the progression of myopia with an inactive comparator. Effects at one year provided evidence that these interventions may slow refractive change and reduce axial elongation, although results were often heterogeneous. A smaller body of evidence is available at two or three years, and uncertainty remains about the sustained effect of these interventions. Longer‐term and better‐quality studies comparing myopia control interventions used alone or in combination are needed, and improved methods for monitoring and reporting adverse effects. 

Keywords: Child; Humans; Atropine; Atropine/therapeutic use; Myopia; Network Meta-Analysis; Refraction, Ocular; Refractive Errors

Plain language summary

Interventions to slow the progression of short‐sightedness in children

Key messages

• Medications such as atropine, given as eye drops, can slow the progression of short‐ or near‐sightedness (myopia) in children, and also reduce elongation of the eyeball due to myopia. Higher doses of atropine are most effective. We are uncertain about the effects of lower doses of atropine.

• Several treatments, including special types of lenses in eye glasses as well as contact lenses, may slow the progression of short‐sightedness, but their effect is still uncertain and there is insufficient information on the risk of unwanted effects.

• It is also unclear whether the reported benefit of medications or lenses on myopia progression is maintained over the years.

What is short‐sightedness?

Short‐sightedness (or near‐sightedness or myopia) means people struggle to see objects that are far away clearly, while objects that are near remain clear. It is very common worldwide, and  affects more than half of children in China and South‐East Asia. Short‐sightedness may impair many aspects of life, including educational and occupational activities. Moreover, short‐sighted people have longer eyes, which means that the retina is  stretched. This puts the eye at greater risk of eye diseases such as glaucoma, maculopathy and retinal detachment later in life.

How is short‐sightedness treated?

Although conventional eyeglasses or contact lenses are able to correct short sight, they do not slow its progression. A number of optical treatments (glasses and contact lenses) and medications are available that aim to slow the progression of short‐sightedness. But they need to be given in childhood, when short‐sightedness progresses most quickly. Medications such as atropine eye drops may be effective, but can cause increased sensitivity to glare and cause problems when reading, especially at higher doses. Special eyeglasses are also available, that include more than one focus power within the lens (multifocal or peripheral‐plus lenses). These can also be provided as soft contact lenses. Other contact lenses, called orthokeratology, aim to temporarily change the shape of the eye surface and are worn during sleep and removed during the day. Both soft contact lenses and orthokeratology may increase the risk of infections to the eye surface

What did we want to find out?

We aimed to find out whether medications used as eye drops, and special lenses in eyeglasses or contact lenses, can slow the progression of myopia, as well as the elongation of the eyeball. We also documented the risk of unwanted effects of such interventions.

What did we do?

We searched for studies that tested medications and lenses aiming to slow progression of short‐sightedness in children, compared with a control group or with other medications and lenses. The control group generally received a placebo (sham) treatment or single vision eye glasses or contact lenses.

What did we find?

• Higher doses of atropine may reduce the progression of short‐sightedness, but the effect of low‐dose atropine could be small and is uncertain. 

• Based on short‐term studies, orthokeratology is the most effective of the optical treatments in slowing elongation of the eyeball. These lenses were often difficult to tolerate, however, with more than half of children not completing the treatment in some studies. 

• Other types of contact lenses, known as multifocal soft contact lenses, may also reduce the progression of short‐sightedness, but, again, we remain uncertain about their beneficial effects. 

• Unwanted effects associated with myopia control interventions were not consistently reported. Eye discomfort in bright light and blurred near vision were the most common treatment‐related unwanted effects in studies using atropine. Lower doses of atropine appear to have fewer unwanted effects. 

• Although studies that tested contact lenses did not report any serious unwanted effects, it is unclear what the true rate of unwanted effects would be for children outside a research study or when wearing contact lenses for longer periods.

What are the limitations of the evidence?

Most of the evidence came from studies conducted in ways that may have introduced errors into their results, and potential unwanted effects were not well reported. The majority of the studies followed participants up for 2 years or less and therefore there is insufficient evidence on whether incremental benefits are found over the years and whether the effects are sustained.

How up to date is the evidence?

This review is up‐to‐date to February 2022.

Summary of findings

Summary of findings 1. Summary of findings 1: change in refractive error at 1 year .

Interventions for myopia control in children: a living systematic review and network meta‐analysis
Population: children with progressive myopia (38 studies, 6525 participants in analyses)
Interventions: optical and pharmacological
Comparator: control (36 studies, 2846 participants). Control arms for optical interventions are either single vision spectacles or contact lenses. Placebo eyedrops were the usual comparator for pharmacological interventions 
Outcome: progression of myopia (difference in change in spherical equivalent refraction (SER)) at 1 year (dioptres)
Setting: primary eye care
Assumed control risk: median change in SER in control arms at 1 year −0.65D 
Equivalence criterion: difference in change in spherical equivalent less than 0.25 D
Treatment (vs control) Number of studies in the treatment arm (participants) Corresponding intervention risk MD (95%CI). Direct estimates from pairwise MA Corresponding intervention risk MD  (95%CI).Estimates from NMA Certainty of evidence 
High‐dose atropine (≥ 0.5%) 3 (512) 0.90 (0.62 to 1.18) 0.89 (0.65 to 1.12) Moderatea
Moderate‐dose atropine (0.1% to < 0.5%) 2 (254) 0.65 (0.27 to 1.03) Moderatea
Low‐dose atropine (< 0.1%) 4 (497) 0.38 (0.10 to 0.66) 0.43 (0.24 to 0.61) Very lowb
Pirenzepine 2 (210) 0.32 (0.15 to 0.49) 0.27 (−0.13 to 0.67) Very lowb
7‐methyxanthine 1 (77) 0.07 (−0.09 to 0.24) 0.07 (−0.33 to 0.48) Lowc
Multifocal soft contact lenses 8 (712) 0.26 (0.17 to 0.35) 0.23 (0.09 to 0.37) Very lowb
Rigid gas‐permeable contact lenses 2 (178) 0.02 (−0.05 to 0.10) 0.17 (−0.12 to 0.46) Very lowb
Peripheral plus spectacle lenses 5 (480) 0.51 (0.19 to 0.82) 0.28 (0.05 to 0.51) Very lowb
Multifocal spectacle lenses 9 (729) 0.14 (0.08 to 0.21) 0.14 (−0.04 to 0.32) Lowc
Undercorrected single vision spectacles 2 (72) −0.15 (−0.29 to 0.00) −0.15 (−0.45 to 0.15) Lowc
GRADE Working Group grades of evidence
High‐certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate‐certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different.
Low‐certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low‐certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
Explanation
Negative mean differences for changes in refractive error represent faster progression of myopia in the intervention group compared to progression in the control group. Measurement of refractive error is not an appropriate outcome in orthokeratology (ortho‐K) studies. Overnight wear of ortho‐K lenses flattens the central cornea and temporally reduces refractive error. It is therefore not possible to assess the true progression of refractive error without ceasing lens wear for a period of time to allow the cornea to return to its pre‐treatment state
CI: confidence interval; MA: meta‐analysis; MD: mean difference; NMA: network meta‐analysis 

Reasons for downgrade

aDowngraded one level for risk of bias, not downgraded for inconsistency since all studies show clinically important effects.
b.Downgraded one level for risk of bias, imprecision and inconsistency.
cDowngraded one level for risk of bias and imprecision 

In each case, downgrading due to risk of bias was due to concerns arising from the randomisation process and in the selection of the reporting of the results; downgrading for imprecision was due to a confidence interval that included small and clinically unimportant effects or optimal information size not met (using fewer than 400 participants as a 'rule of thumb'); downgrading for inconsistency was due to substantial heterogeneity.

Summary of findings 2. Summary of findings 2: change in refractive error at 2 years.

Interventions for myopia control in children: a living systematic review and network meta‐analysis
Population: children with progressive myopia (26 studies, 4949 participants in the analysis)
Interventions: optical and pharmacological
Comparator: control (24 studies, 2282 participants). Control arms for optical interventions are either single vision spectacles or contact lenses. Placebo eyedrops were the usual comparator for pharmacological interventions
Outcome: progression of myopia (difference in change in spherical equivalent refraction (SER)) at 2 years (dioptres)
Setting: primary eye care
Assumed control risk: median change in SER in control arms at 2 years −1.02 D 
Equivalence criterion: difference in change in spherical equivalent less than 0.25 D
Treatment (vs control) Number of studies in the treatment arm (participants) Corresponding intervention risk MD (95%CI)Direct estimates from pairwise MA Corresponding intervention risk MD (95%CI)Estimates from NMA Certainty of evidence 
High‐dose atropine (≥ 0.5%) 2 (428) 1.26 (1.17 to 1.36) 0.74 (0.44 to 1.05) Moderatea
Moderate‐dose atropine (0.1% to < 0.5%) 2 (247) 0.45 (0.08 to 0.83) Lowb
Low‐dose atropine (< 0.1%) 2 (249) 0.24 (0.17 to 0.31) 0.31 (0.07 to 0.56) Lowb
Pirenzepine 1 (53) 0.41 (0.13 to 0.69) 0.41 (−0.05 to 0.87) Lowb
Multifocal soft contact lenses 5 (540) 0.30 (0.19 to 0.41) 0.31 (0.12 to 0.49) Lowb
Rigid gas‐permeable contact lenses 2 (154) One study showed no difference and the other a beneficial effect 0.22 (−0.09 to 0.53) Very lowc
Peripheral plus spectacle lenses 2 (188) 0.34 (−0.08 to 0.76) 0.34 (0.05 to 0.63) Very lowc
Multifocal spectacle lenses 8 (696) 0.19 (0.08 to 0.30) 0.19 (0.03 to 0.36) Lowb
Undercorrected single vision spectacles 2 (122) 0.02 (−0.05 to 0.09) −0.07 (−0.36 to 0.22) Very lowc
GRADE Working Group grades of evidence
High‐certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate‐certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different.
Low‐certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low‐certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
Explanation
Negative mean differences (MDs) for changes in refractive error represent faster progression of myopia in the intervention group compared to progression in the control group. Measurement of refractive error is not an appropriate outcome in orthokeratology (ortho‐K) studies. Overnight wear of ortho‐K lenses flattens the central cornea and temporally reduces refractive error. It is therefore not possible to assess the true progression of refractive error without ceasing lens wear for a period of time to allow the cornea to return to its pre‐treatment state
CI: confidence interval; MA: meta‐analysis; MD: mean difference; NMA: network meta‐analysis 

Reasons for downgrade

aDowngraded one level for risk of bias, not downgraded for inconsistency since all studies show clinically important effects.
bDowngraded one level for risk of bias and imprecision.
cDowngraded one level for risk of bias, imprecision and inconsistency 

In each case, downgrading due to risk of bias was due to concerns arising from the randomisation process and in the selection of the reporting of the results; downgrading for imprecision was due to a confidence interval that included small and clinically unimportant effects or optimal information size not met (using fewer than 400 participants as a 'rule of thumb'); downgrading for inconsistency was due to substantial heterogeneity.

Summary of findings 3. Summary of findings 3: change in axial length at 1 year.

Interventions for myopia control in children: a living systematic review and network meta‐analysis
Population: children with progressive myopia (36 studies, 6263 participants) in the analysis
Interventions: optical and pharmacological
Comparator: control (35 studies, 2732 participants). Control arms for optical interventions are either single vision spectacles or contact lenses. Placebo eyedrops were the usual comparator for pharmacological interventions 
Setting: primary eye care
Outcome: difference in change in axial length at 1 year (mm)
Assumed control risk: median change in axial length in control arms at 1 year 0.31 mm
Equivalence criterion: difference in change in axial length less than 0.1 mm
Treatment (vs control) Number of studies in the treatment arm
(participants)
Corresponding intervention risk MD (95%CI)Direct estimates from pairwise MA Corresponding intervention risk MD (95%CI)Estimates from NMA Certainty of evidence 
High‐dose atropine (≥ 0.5%) 3 (512) −0.33 (−0.35 to −0.30) −0.32 (−0.38 to −0.26) Moderatea
Moderate‐dose atropine (0.1% to <  0.5%) 1 (155)  −0.28 (−0.38 to −0.17) Moderatea
Low‐dose atropine (< 0.1%) 4 (497) −0.13 (−0.21 to −0.05) −0.14 (−0.19 to −0.08) Very lowb
Pirenzepine 2 (210) −0.10 (−0.18 to −0.02) −0.08 (−0.19 to 0.02) Very lowb
7‐methylxanthine 1 (35) −0.03 (−0.10 to 0.03) −0.03 (−0.15 to 0.08) Lowc
Orthokeratology 7 (402) −0.19 (−0.23 to −0.15) −0.18 (−0.24 to −0.12) Moderatea
Multifocal soft contact lenses 8 (712) −0.11 (−0.13 to −0.09) −0.11 (−0.14 to −0.07) Lowc
Rigid gas‐permeable contact lenses 2 (176) 0.02 (−0.05 to 0.10) 0.02 (−0.07 to 0.12) Lowc
Peripheral plus spectacle lenses 3 (340) −0.13 (−0.24 to −0.03) −0.14 (−0.20 to −0.07) Very lowb
Multifocal spectacle lenses 4 (445) −0.06 (−0.09 to −0.04) −0.04 (−0.16 to 0.08) Lowc
Undercorrected single vision spectacles 1 (47) 0.05 (−0.01 to 0.11) 0.05 (−0.06 to 0.16) Lowc
GRADE Working Group grades of evidence
High‐certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate‐certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different.
Low‐certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low‐certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
Explanation
For the measurement of changes in axial length, negative mean differencess for changes in axial length represent faster axial elongation in the control group compared to the intervention group.
CI: confidence interval; MA: meta‐analysis; MD: mean difference; NMA: network meta‐analysis 

Reasons for downgrade

aDowngraded one level for risk of bias.
bDowngraded one level for risk of bias, imprecision and inconsistency.
cDowngraded one level for risk of bias and imprecision.

In each case, downgrading due to risk of bias was due to concerns arising from the randomisation process and in the selection of the reporting of the results; downgrading for imprecision was due to a confidence interval that included small and clinically unimportant effects or optimal information size not met (using fewer than than 400 participants as a 'rule of thumb'); downgrading for inconsistency was due to substantial heterogeneity

Summary of findings 4. Summary of findings 4: change in axial length at 2 years.

Interventions for myopia control in children: a living systematic review and network meta‐analysis
Population: children with progressive myopia (21 studies, 4169 participants in the analysis)
Interventions: optical and pharmacological
Comparator: control (20 studies, 1894 participants). Control arms for optical interventions are either single vision spectacles or contact lenses. Placebo eyedrops are the usual comparator for pharmacological interventions. 
Outcome: median change in axial length in control arms at 2 years
Setting: primary eye care
Assumed control risk: change in axial length at 2 years 0.56 mm
Equivalence criterion: difference in change in axial length less than 0.1 mm
Treatment (vs control) Number of studies in the treatment arm
(participants)
Corresponding intervention risk MD (95%CI)Direct estimates from pairwise MA Corresponding intervention risk MD (95%CI) Estimates from NMA Certainty of evidence 
High‐dose atropine (≥ 0.5%) 2 (428) −0.47 (−0.61 to −0.34) −0.36 (−0.46 to −0.26) Moderatea
Moderate‐dose atropine (0.1% to < 0.5%) 1 (144) −0.33 (−0.46 to −0.20) Moderatea
Low‐dose atropine (< 0.1%) 2 (249) −0.16 (−0.20 to −0.12) −0.17 (−0.25 to −0.10) Lowb
Orthokeratology 2 (49) −0.28 (−0.38 to −0.19) −0.29 (−0.41 to −0.16) Moderatea
Multifocal soft contact lenses 5 (540) −0.15 (−0.19 to −0.12) −0.16 (−0.22 to −0.10) Moderatea
Rigid gas‐permeable contact lenses 2 (154) 0.03 (−0.05 to 0.12) 0.03 (−0.08 to 0.15) Lowb
Peripheral plus spectacle lenses 2 (188) −0.20 (−0.45 to 0.05) −0.23 (−0.33 to −0.12) Very lowc
Multifocal spectacle lenses 3 (404) −0.07 (−0.12 to −0.03) −0.09 (−0.17 to −0.01) Lowb
Undercorrected single vision spectacles 2 (122) −0.01 (−0.06 to 0.03) 0.01 (−0.09 to 0.10) Lowb
GRADE Working Group grades of evidence
High‐certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate‐certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different.
Low‐certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low‐certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
Explanation
For the measurement of changes in axial length, negative MDs for changes in axial length represent faster axial elongation in the control group compared to the intervention group
CI: confidence interval; MA: meta‐analysis; MD: mean difference; NMA: network meta‐analysis 

Reasons for downgrade

aDowngraded one level for risk of bias.
bDowngraded one level for risk of bias and imprecision.
cDowngraded one level for risk of bias, imprecision and inconsistency.

In each case, downgrading due to risk of bias was due to concerns arising from the randomisation process and in the selection of the reporting of the results; downgrading for imprecision was due to a confidence interval that included small and clinically unimportant effects or optimal information size not met (using fewer than 400 participants as a 'rule of thumb'); downgrading for inconsistency was due to substantial heterogeneity.

Background

Description of the condition

Myopia, or short‐ or near‐sightedness, is a common refractive anomaly of the eye that occurs when parallel rays of light are brought to a focus in front of the retina with accommodation at rest, causing distant objects to appear blurred and near objects to remain clear (Morgan 2012). Myopia most often results from the eyeball being too long (i.e. there is excessive axial elongation), but can also occur when the image‐forming structures of the eye are too strong (Flitcroft 2019).

The prevalence of myopia shows significant age, ethnic and regional variation (Rudnicka 2016). Currently, 30% to 50% of adults in the USA and Europe have myopia (Dolgin 2015). Myopia is already reaching 'epidemic' proportions in children and young adults in urban areas of East and South East Asia, with over 80% of children being myopic by the time they complete their high school education (Dolgin 2015). If current trends continue, it is estimated that by 2050 there will be approximately 5 billion (5000 million) people with myopia (i.e. about 50% of the world's population), with around 10% having high myopia (when defined as a spherical equivalent of −5.00 dioptres (D) or worse) (Holden 2016).

The aetiology of myopia involves a complex interaction between environmental and genetic factors. Although genetic inheritance is a well‐established predisposing factor for myopia, genetic factors cannot explain the rapidly rising prevalence of the condition (Williams 2019). A Mendelian randomisation study, using the UK Biobank cohort, provided strong evidence for the cumulative effect of additional years in education on myopia development (Mountjoy 2018). Mendelian randomisation is a statistical approach that uses genetics to provide information about the relationship between an exposure and outcome. This study estimated that for each additional year in education, myopic spherical equivalent increased by −0.27 D. Evidence from a number of observational studies further supports the causal association between environmental and social factors and myopia development (Morgan 2018).

Epidemiological studies have shown that myopia is an established risk factor for a number of ocular pathologies, including cataract, glaucoma and retinal detachment (Flitcroft 2012). Although myopia‐related complications can occur irrespective of age and degree of myopia (Dhakal 2018), the excessive axial elongation associated with higher degrees of myopia causes biomechanical stretching of the outer coat of the eye, increasing the risk of sight‐threatening pathologies such as posterior staphyloma and myopic maculopathy (Saw 2005Verkicharla 2015). A meta‐analysis of population studies reporting blindness and visual impairment due to myopic maculopathy (Fricke 2018), estimated that in 2015, approximately 10 million people had visual impairment due to myopic macular degeneration, of whom three million were blind. Although the sight‐threatening pathologies associated with myopia usually occur later in life, the underlying myopia develops during childhood and therefore interventions to reduce the progression of myopia have the potential to reduce future visual impairment.

Description of the intervention

Most cases of myopia develop during childhood and the prevalence of myopia begins to increase noticeably after the age of six years (McCullough 2016). Progression rates vary significantly, with rates in Asian children being approximately 0.20 D per year faster than their age‐matched European counterparts (Donovan 2012). Since myopia tends to stabilise in late adolescence, interventions to slow myopia progression need to be delivered in childhood.

Interventions to slow progression of myopia can be grouped into three broad categories: optical, pharmacological and environmental (Wildsoet 2019). Optical interventions include a variety of spectacle and contact lens designs. Spectacles are the least invasive and most accessible method for potentially slowing myopia progression. Spectacle options include refractive under‐correction, bifocal and progressive addition lenses and, more recently, specialised 'myopia control' designs. Soft multifocal and approved myopia control contact lenses are increasingly being used for myopia management in children (Efron 2020). Centre‐distance soft multifocal lens designs incorporate a central zone that contains the distance refractive correction, with peripheral regions of the lens having relatively increased positive power (myopic defocus). This is achieved by either a gradual increase in power towards the periphery or using concentric peripheral zones of alternating myopic defocus and distance correction. Orthokeratology involves the use of specialised rigid contact lenses that are worn during sleep to change the topography of the cornea to reduce myopic refractive error and also manipulate peripheral retinal defocus. Safety remains a concern because of the greater risk of sight‐threatening microbial keratitis with overnight wear compared with daily contact lens wear modalities (Dart 2008). 

The most commonly used topical pharmacological intervention for myopia control is atropine, a non‐selective muscarinic antagonist, which has been widely used in clinical trials in concentrations ranging from 0.01% to 1.0%. Although higher atropine concentrations have been shown to be effective in retarding myopia progression in children, the higher incidence of side effects with higher doses, including cycloplegia (inhibition of accommodation) and pupil dilation (which causes blur for near vision and photophobia) limits its use. Furthermore, a rebound effect (involving more rapid myopia progression) after discontinuation of therapy is more pronounced with higher concentrations of atropine (Chia 2014). More recent studies have evaluated the efficacy of lower concentrations to reduce side effects and lessen the likelihood of rebound. The results of these studies have led to a renewed interest in the clinical application of low‐dose atropine (i.e. 0.01% to 0.05%) for myopia control (Wu 2019). Other pharmacological agents that have been evaluated for myopia control include topical tropicamide, cyclopentolate and pirenzipine (a selective M1 muscarinic antagonist) and the oral adenosine antagonist, 7‐methylxanthine.

Evidence that more time spent on near work activities is associated with higher odds of developing myopia (Huang 2015), and the observation that increased time spent outdoors is protective against myopia, after adjusting for near work, parental myopia and ethnicity (Rose 2008), have raised the possibility that environmental or behavioural interventions could be effective for myopia control. Trials of school‐based programmes that promote outdoor activities, conducted in East Asia, have reported a lower incidence of myopia onset but have limited impact on progression following onset of myopia (Dhakal 2022).

How the intervention might work

Animal studies have shown that optically‐induced changes to the effective refractive status of the eye can regulate eye growth and influence refractive development (Troilo 2019). Specifically, the observation that imposed relative myopic defocus (image focused in front of the retina) can slow axial elongation has been the impetus for the development of novel multifocal spectacles and contact lenses that provide clear central vision, whilst at the same time presenting myopic defocus over a large proportion of the visual field. The critical area ratio required for these simultaneous competing defocus signals to dominate eye growth is currently unclear. However, the relative treatment effects reported for different optical treatment regimens suggest that there appears to be an eccentricity‐dependent decrease in the efficacy of myopic defocus beyond the near periphery (Smith 2014Smith 2020).

Orthokeratology involves corneal reshaping lenses that are worn overnight to flatten the central cornea and reduce its dioptric power. The geometry of these lenses also creates a corneal profile that produces relative myopic defocus.

The precise mechanism by which anti‐muscarinic agents reduce myopic progression is not fully understood. A non‐accommodative mechanism is thought to be the most likely, and alternative targets have been proposed, including eye growth regulatory pathways that arise in the retina and are relayed to the sclera via the retinal pigment epithelium and choroid (McBrien 2013Upadhyay 2020).

The protective effect of increased time outdoors on myopia development is thought to be related to the higher light intensity of sunlight and possibly its spectral composition (French 2013). Light levels have been shown to influence refractive development in animal models (Smith 2012). Higher light intensities stimulate retinal dopamine production, which is thought to inhibit axial elongation (Feldkaemper 2013).

Why it is important to do this review

As a result of its increasing global prevalence and association with sight‐threatening pathologies, myopia is emerging as a major public health concern. Myopia is predicted to affect almost half of the world’s population by 2050, and the pathologic consequences of high myopia increase the risk of irreversible visual impairment and blindness. There has been considerable interest in the development of strategies to delay the onset of myopia and slow its progression. Myopia control interventions are increasingly being used in routine clinical practice (Efron 2020Wolffsohn 2016). Evidence from randomised controlled trials (RCTs) indicates that the progression of myopia can be slowed by different interventions, although treatment efficacy is highly variable.

There is a broad consensus that the primary endpoints for judging efficacy in clinical trials of myopia control interventions should include change in axial length, in addition to change in refractive error (Brennan 2020Walline 2018Wolffsohn 2019). Myopia development and progression usually occur due to abnormal axial elongation. Therefore, axial length may be a better predictor of future progression and consequent risk of posterior pole complications (Brennan 2020). In terms of a minimal clinically important difference of the key efficacy outcomes in myopia control studies, an expert panel concluded that a mean difference between intervention groups of 0.25 D per year would be regarded as clinically significant (i.e. 0.75 D over the course of a three‐year study) (Walline 2018). This would correspond to a difference in axial length of approximately 0.3 mm.

An updated Cochrane systematic review, published in January 2020 (Walline 2020), evaluated the efficacy of a number of interventions, including spectacles, contact lenses and pharmaceutical agents, for slowing the progression of myopia in children. Walline 2020  concluded that topical anti‐muscarinic medication was effective in slowing myopia progression. Multifocal lenses, either spectacles or contact lenses, also conferred a small benefit. Although the update was published in 2020, the review only included evidence published up to the end of 2018. In this rapidly moving field, the results of additional important trials have subsequently been reported.

Eye care professionals often find it difficult to assimilate potentially conflicting evidence to inform their clinical decision‐making (Douglass 2020). It is therefore important that practitioners can access high‐quality and up‐to‐date evidence to inform practice. Moreover, parents of myopic children also need reliable information to help them to understand and interpret research findings. Given the large number of different interventions available for myopia control and the large number of completed and ongoing RCTs on this topic, there is an urgent need to evaluate the comparative effectiveness of different interventions. A network meta‐analysis (NMA) offers an advantage over a standard pairwise meta‐analysis in that it provides both direct comparisons of individual trials and indirect comparisons not directly evaluated in trials across a network of studies, thus generating the comparativeness of all interventions in a coherent manner. A NMA can also provide relative rankings of interventions to inform clinical decision‐making.

There are significant resource implications associated with myopia for both individuals and healthcare systems. This includes both corrected and uncorrected myopic refractive error. Lim 2009 estimated the mean direct costs of managing myopia in school‐aged children in Singapore. These costs included optometrist visits, spectacles, contact lenses and travel costs. The mean cost was estimated as USD 148 (median SGD 83.33) per year in 2006. In addition, Zheng 2013 estimated the lifetime costs for a person with myopia over an 80‐year lifespan to be USD 17,020 in 2011. There are also associated costs and quality‐of‐life impacts associated with uncorrected refractive error. Tahhan 2013 found a significant reduction in health state utility (a preference‐based quality‐of‐life measure) associated with uncorrected refractive error. Fricke 2012 estimated that the direct costs of correcting all cases of uncorrected refractive error globally would be approximately USD 28 billion (USD 28,000 million; price year not stated). Given these cost estimates, understanding the current evidence base for myopia control is key for both individuals and healthcare decision‐makers.

We plan to maintain this review as a living systematic review. This will involve searching the literature every six months and incorporating new evidence as it becomes available. This approach is appropriate for this review since it addresses an important clinical topic and there is currently significant uncertainty as to the most effective intervention. It is therefore important that consumers and healthcare providers have access to the most up‐to‐date evidence to make informed decisions. The review authors are aware of several relevant ongoing trials that will be important to incorporate in a timely manner.

Objectives

To assess the comparative efficacy of optical, pharmacological and environmental interventions for slowing myopia progression in children using network meta‐analysis (NMA). To generate a relative ranking of myopia control interventions according to their efficacy. To produce a brief economic commentary, summarising the economic evaluations assessing interventions for myopia control in children. To maintain the currency of the evidence using a living systematic review approach.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) of optical, pharmacological and environmental interventions used alone or in combination for slowing the progression of myopia in children.

Types of participants

This review considered studies that included children 18 years old and younger. We excluded studies in which the majority of participants were older than 18 years at the start of the study. We also excluded studies that included participants with spherical equivalent myopia less than −0.50 D at baseline. The spherical equivalent is calculated by the sum of the spherical power plus half the cylindrical power of the refractive error.

We included studies that compared interventions of interest and reported having measured the relevant outcomes, irrespective of whether data for the outcomes were available.

Types of interventions

We included studies that compared any of the interventions listed below with a control group, or with each other. For the purposes of the analysis, we defined a control group as a placebo intervention or single vision spectacles or contact lenses.

  • Undercorrection of myopia with single vision spectacle lenses

  • Multifocal (bifocal or progressive addition) spectacle lenses, peripheral defocus spectacle lenses

  • Multifocal soft contact lenses (MFSCL; concentric ring or progressive designs), rigid gas‐permeable contact lenses or corneal reshaping (orthokeratology) contact lenses

  • Atropine (stratified according to dosing regime as high (≥ 0.5%), moderate (0.1% to < 0.5%) and low (< 0.1%)

  • Other pharmaceutical agents (e.g. pirenzepine, 7‐methylxanthine)

  • Environmental interventions (e.g. time spent outdoors, modifications to the performance of near work)

Types of outcome measures

Critical outcomes
Progression of myopia

Progression of myopia was assessed by:

  • mean change in refractive error (spherical equivalent in D) from baseline for each year of follow‐up and measured by any method (e.g. objective or subjective refraction); and

  • mean change in axial length for each year of follow‐up in millimetres (mm) from baseline for each year of follow‐up and measured by any method (e.g. ultrasound or optical biometry).

Change in refractive error and axial length following cessation of treatment ('rebound')

Rebound was evaluated when children in the treatment group were switched to the control treatment and then followed for a minimum period of one year. 

Important outcomes
Risk of adverse events

We described adverse events relating to the interventions as reported in the included studies, irrespective of severity. These included but were not limited to blurred vision, photophobia, hypersensitivity reactions, corneal infiltrative events and infections. In studies that graded clinical signs using standard anterior eye grading scales from normal to severe, we recorded the number of clinically significant signs (grade 3 or 4) that would usually require a clinical action.

Where data were available we documented withdrawals due to adverse events and number of 'serious' events.

Quality of life

We documented vision‐related or health‐related quality of life when reported, measured by any validated questionnaire (e.g. National Eye Institute (NEI) Visual Function Questionnaire 25 (NEI VFQ‐25), or EuroQol questionnaire, EQ‐5D).

Treatment adherence

Studies evaluated adherence with the prescribed treatment regimen using a variety of compliance measures, including daily wearing time with contact lenses and spectacle interventions as reported by parents or children, or both, or the proportion of participants in pharmacological studies following the required dosing regime.

Follow‐up

We have reported outcomes at one year, two years and as available for the duration of the study. We imposed no restrictions based on the length of follow‐up.

Brief economic commentary

We present evidence regarding relevant economic evaluations, as a brief economic commentary.

Search methods for identification of studies

Electronic searches

The Cochrane Eyes and Vision Information Specialist searched the electronic databases below for RCTs and controlled clinical trials. There were no restrictions to language or date of publication. Given the similarity in the PICO and corresponding search strategies between the current review and a previous Cochrane Review on interventions for myopia control in children (Walline 2020), and the likelihood that studies included in Walline 2020 would meet the inclusion criteria for this review, we ran the search for the current review in parallel with the search strategy used by Walline 2020 up to the search date for the earlier review (26 February 2019) and removed duplicates. We combined the search results with all records identified up to 4 February 2022. 

We did not perform the generic search described in Electronic searches for adverse events, however we added a filter to the search strategy to identify systematic reviews of adverse events associated with myopia control interventions. We compared the findings of these reviews to the adverse events reported in the studies included in the current review.

In addition to these searches we carried out a MEDLINE and Embase search using economic search filters to specifically identify economic studies.

We have developed this review as a living systematic review, and we will re‐run the searches on a six‐monthly basis.

Searching other resources

We searched the reference lists of identified study reports to identify additional studies. We also contacted the principal investigators of included studies for details of other potentially relevant studies not identified by the electronic searches, and of recently completed or ongoing studies.

Data collection and analysis

Selection of studies

The Information Specialist at Cochrane Eyes and Vision downloaded all titles and abstracts retrieved from the electronic searches to EndNote (Endnote X9 2013) and removed duplicates before uploading to Covidence. Two review authors (from JGL, RS, BH, RD, PV) independently reviewed the titles and abstracts of the search results based on the eligibility criteria stated above. We categorised Abstracts for inclusion as 'Yes', 'Maybe' or 'No'. We obtained the full text of articles for the studies categorised as 'Maybe' and 'Yes', and reassessed them for final eligibility. After examining the full text, we labelled studies as 'include' or 'exclude'. Studies selected as 'exclude' by both authors were excluded from the review. We documented the reasons for exclusion. We resolved any screening discrepancies through discussion and, if necessary, through consultation with a third review author. One review author (AK) screened the economic search results.

Living systematic review considerations

We plan to screen any new citations retrieved by the six‐monthly searches immediately.

Data extraction and management

For eligible studies, two review authors independently extracted the data. We contacted the authors of the original reports to obtain further details if the data reported were unclear or incomplete. We exported the collected data into Review Manager Web (RevMan Web) (RevMan Web 2022). We extracted the following study characteristics.

  • Methods: study design, number and location of study centre(s), date of study and total duration

  • Participants: inclusion and exclusion criteria, number randomised, number lost to follow‐up or withdrawn, number analysed, mean age and standard deviation (SD), age range, gender

  • Interventions: description of intervention and comparator

  • Outcomes: primary and secondary outcomes specified and collected, and time points reported. Unit of analysis

  • Notes: funding for study and conflicts of interest of study authors

Assessment of risk of bias in included studies

Pairs of review authors (from JGL, BH, RS, RD, PV, SM, DL) independently assessed the risk of bias in the included studies for all outcomes using the revised Cochrane risk of bias tool for randomised trials (RoB 2) 22 August 2019 version, described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2022a). RoB 2 covers five domains of bias:

  • bias arising from the randomisation process;

  • bias due to deviations from intended interventions;

  • bias due to missing outcome data;

  • bias in measurement of the outcome; and

  • bias in selection of the reported result.

These domain‐level judgements provide the basis for an overall risk of bias judgement for the specific outcome being assessed. The response options for an overall risk of bias judgement in RoB 2 are the same as for individual domains (i.e. 'low risk of bias'; 'some concerns'; 'high risk of bias'). The following criteria were adopted:

  • Low risk of bias: low risk of bias for all domains;

  • Some concerns: 'some concerns' in at least one domain, but not at high risk of bias for any domain;

  • High risk of bias: high risk of bias in at least one domain or the study is judged to have some concerns for multiple domains in a way that substantially lowers confidence in the result.

To implement RoB 2 assessments we used the Excel tool available at https://www.riskofbias.info/welcome/rob-2-0-tool/current-version-of-rob-2.

We did not include cluster‐randomised trials. In the case of cross‐over trials, we only used data from the first phase prior to the cross over and therefore used the version of the tool for parallel trials. Should cluster‐randomised and cross‐over trials be included in future updates of the review, we will use the versions of RoB 2 with additional considerations for these designs.

For all outcomes we assessed the effect of assignment to intervention (the intention‐to‐treat effect).

Assessment of bias in conducting the systematic review

We conducted the review according to this published protocol and have reported any deviations from it in the Differences between protocol and review section of the review.

Measures of treatment effect

We used mean differences (MDs) as the measure of treatment effect for the critical outcome 'progression of myopia', that is, difference in mean change in refractive error (SER) and axial length from baseline at each year of follow‐up.

Unit of analysis issues

When studies randomised only one eye per participant, the unit of analysis was the individual eye (participant). When studies randomised both eyes from the same participant (either to the same or different interventions), we analysed data adjusted for clustering or paired‐eye design. In the NMA, we accounted for the correlation between the effect sizes derived from the same study.

In multiple‐arm trials, to overcome a unit‐of‐analysis error for a study that could contribute multiple, correlated data, we combined groups to create a single pair‐wise comparison.

If we identify cluster‐RCTs in future updates, we will include them in meta‐analyses directly, where the sample size has been adjusted for clustering. We will combine them with the results from individual studies if there is little heterogeneity between the study designs and the interaction between the effect of the intervention and the unit of randomisation is considered to be unlikely. If studies present outcomes at individual level (i.e. a unit of analysis error), we will use established methods to adjust for clustering by calculating an effective sample size by dividing the original sample size by the design effect. This can be calculated from the average cluster size and the intra‐class correlation coefficient (ICC). Where the ICC is unknown, we will use an estimation from similar trials (Higgins 2022b).

Dealing with missing data

We contacted study authors to verify key study characteristics and to obtain missing outcome data. If we did not receive a response within eight weeks, we analysed the studies based on available data. We used the RevMan calculator to calculate missing standard deviations using other data from the study (e.g. confidence intervals) based on methods outlined in Chapter 10 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2022). 

Assessment of heterogeneity

We assessed clinical and methodological heterogeneity for each pairwise meta‐analysis by comparing the characteristics of included studies and by visual inspection of forest plots. We assessed statistical heterogeneity quantitatively for pairwise comparisons using the values of the Chi2 test and the I2 statistic (Higgins 2003). We interpreted I2 statistic values according to Chapter 10 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2022), as follows:

  • 0% to 40% may not be important;

  • 30% to 60% may represent moderate heterogeneity;

  • 50% to 90% may represent substantial heterogeneity;

  • 75% to 100% represents considerable heterogeneity.

For the NMA, we assumed a common estimate for the heterogeneity variance across the different comparisons. The assessment of statistical heterogeneity was based on the magnitude of the heterogeneity variance parameter (Tau2) estimated from the NMA models.

Assessment of statistical inconsistency
Local approaches for evaluating inconsistency

To evaluate the presence of inconsistency locally, we used the node splitting approach (Dias 2010), which assesses the agreement between direct and indirect evidence for each treatment comparison.

Global approaches for evaluating inconsistency

To check the assumption of consistency across the entire network, we used the 'design by treatment' interaction model (White 2015). This method accounts for different sources of inconsistency that can occur when studies with different designs are incorporated into the network (e.g. two‐arm trials versus multi‐arm trials), as well as inconsistency between direct and indirect evidence. 

Assessment of reporting biases

 If there are sufficient studies in future updates, we plan to run network meta‐regression models to detect associations between study size and effect size.

Data synthesis

We initially carried out standard pairwise meta‐analyses to combine outcome data using random‐effects models in RevMan Web. For comparisons with three or fewer trials, we used a fixed‐effect model. We combined change from baseline data in meta‐analyses with mean outcome data using the generic inverse variance (unstandardised) MD method, as outlined in Chapter 10 of the Cochrane Handbook for Systematic Interventions (Deeks 2022). In the case of substantial clinical, methodological or statistical heterogeneity, we generally did not attempt to combine data from individual trials but reported study results separately, however, subtotals were included in some analyses when presenting subgroups with varying degrees of heterogeneity.

For cross‐over trials we only extracted data from the first phase prior to cross over.

We conducted a NMA using the network suite of programs available in STATA (http://www.stata.com) for myopia progression, as defined by difference in change in SER and axial length at 12 and 24 months, using random‐effects multivariate models (Chaimani 2013Chaimani 2015White 2015). An important concept in NMA is 'transitivity', which implies that the distribution of effect modifiers is similar across all sources of direct evidence. The statistical manifestation of transitivity is consistency, which refers to the statistical agreement between the direct and indirect sources of evidence.  We checked for consistency in the network both locally (node‐splitting approach) and globally (design by treatment model).

We assumed a common heterogeneity across all comparisons in the network. We used te surface under the cumulative ranking curve (SUCRA) to rank the interventions for all available outcomes. SUCRA values range from 0% to 100%. The higher the SUCRA value (i.e. the closer to 100%), the greater the probability of an intervention ranking best. (Chaimani 2015Salanti 2012).

In the primary NMA, we considered MFSCL, rigid gas‐permeable lenses and orthokeratology lenses as separate nodes. For spectacle lens interventions, there were separate nodes for undercorrected single vision spectacle lenses, multifocal spectacle lenses and peripheral plus spectacle lenses. We considered each pharmacological intervention as a separate node regardless of the dose. We did not anticipate a strong dose‐response effect except for atropine. We grouped atropine according to dosing regime as high (≥ 0.5%), moderate (0.1 % to < 0.5%) and low (< 0.1%).  We grouped all control arms (single vision spectacle lenses, single vision contact lenses, placebo eyedrops or no treatment) into a single node. 

When we were unable to perform a meta‐analysis, we undertook a narrative synthesis following guidance in Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (McKenzie 2022b). Specifically, we presented the effect estimates in structured tables and provided a descriptive summary of the range and distribution of the observed effects. In particular, we noted the direction of effects and whether these were consistent in the individual studies.

Brief economic commentary

Following the search outlined in the Search methods for identification of studies, we developed a brief economic commentary to summarise the availability and principal findings of the full economic evaluations assessing interventions for myopia control in children as outlined in Chapter 20 of the Cochrane Handbook for Systematic Reviews of Interventions (Aluko 2022). This brief economic commentary was planned to encompass full economic evaluations (i.e. cost‐effectiveness analyses, cost‐utility analyses and cost‐benefit analyses) conducted as part of a single empirical study, such as a RCT, a model based on a single such study or a model based on several such studies.

Living systematic review considerations

Whenever we identify new evidence in future updates (i.e. new studies, data, or other information) that is relevant to the review, we will extract the data and assess risk of bias, as appropriate. We will wait until the accumulating evidence changes one or more of the following components of the review before incorporating it and re‐publishing the review.

  • The findings of one or more outcomes (e.g. clinically important change in size or direction of effect)

  • Credibility (e.g. change in the overall confidence in the effect estimates for critical outcomes)

We will not use formal sequential meta‐analysis approaches for updated meta‐analyses.

Methods for future updates

We will review the scope and methods of this review annually in light of potential changes in the topic area or in evidence available for inclusion in the review. Each year, we will consider the necessity for the review to be a living systematic review by assessing ongoing relevance of the question to decision‐makers and by determining whether uncertainty is ongoing in the evidence and whether further relevant research is likely.

Subgroup analysis and investigation of heterogeneity

We performed predefined subgroup analyses for types of intervention modalities (i.e. spectacle and contact lens designs, and dose of particular pharmaceutical interventions (e.g. low‐, moderate‐ and high‐dose atropine)). There were insufficient data to carry out other proposed subgroup analyses.

Sensitivity analysis

We planned a sensitivity analysis on the exclusion of studies that we judged to be at high risk of bias or to raise some concerns in at least one domain of RoB 2. However, since we judged almost all the included studies at high risk of bias or with some concerns we did not seek to conduct a sensitivity analysis.

Summary of findings and assessment of the certainty of the evidence

 We planned to follow methods presented in Yepes‐Nunez 2019 to prepare summary of findings tables for the NMA, however because the network was not well‐connected, we primarily based our comparisons on direct evidence from classical pairwise meta‐analyses, except for moderate‐dose atropine.  We prepared summary of findings tables for progression of myopia at one and two years, with separate tables for change in spherical equivalent and change in axial length.

Evaluating confidence in the evidence

Instead of the planned CINeMA framework for evaluating confidence in the domains (Nikolakopoulou 2020Salanti 2014) we summarised four levels of confidence for each relative treatment effect, corresponding to the usual GRADE approach: very low, low, moderate, or high (Schünemann 2022). In fact, because most evidence was direct versus control in NMAs, we used NMA estimates only when direct evidence was not available.

Results

Description of studies

We considered that all studies that met the inclusion criteria for Walline 2020 would potentially meet the inclusion criteria for the current review.

Results of the search

The searches performed by Walline 2020 to 26 February 2020 identified 41 studies with 74 ongoing studies and 25 studies awaiting classification. Updated electronic searches for the current review identified a further 1473 potentially eligible studies after removal of duplicates. We independently screened these studies for inclusion. We discarded 1290 citations and examined the full texts of the remaining 183 records. In total, we included 64 studies (reported in 225 records) and two studies published as conference abstracts are awaiting classification (for a full description see Characteristics of included studies and Characteristics of studies awaiting classification). 

The economic search was carried out on 4 February 2022 and yielded 80 studies that were screened by AK. No studies met the inclusion criteria. 

A search for systematic reviews of adverse events was carried out on 8 July 2022 and yielded 79 studies. These were screened, and we discuss relevant reviews in Agreements and disagreements with other studies or reviews.

For a summary of the screening process, see the study flow diagram (Figure 1Liberati 2009).

1.

1

Study design

Sixty‐one studies used a parallel‐group design and three studies used a cross‐over design (Anstice 2011Fujikado 2014Hasebe 2008). The median sample size was 150 (range 24 to 660). Most participants were recruited from academic clinic settings, hospitals and in a few cases from private optometry or ophthalmology practices. The studies took place in China or other Asian countries (39 studies, 60.9%), North America (13 studies, 20.3%), Europe (7 studies, 10.9%), Australasia (2 studies, 3.1%), Israel (1 study, 1.6%) and Ghana (1 study, 1.6%); one multicentre study recruited participants in both Europe and Asia (1 study, 1.6%).

Fifty‐seven studies (89%) compared one or more myopia control interventions against a placebo intervention (generally single vision spectacles or contact lenses for optical interventions, and placebo or no treatment for pharmacological interventions). Four studies included a combined intervention group compared with control (Han 2019MIT Study 2001Schwartz 1981), and eight studies compared single or combined interventions with each other (ATOM 2 Study 2012Cui 2021Guo 2021Kinoshita 2020Shih 1999Swarbrick 2015Tan 2020Zhao 2021).

Twenty‐two (34.4%) of the studies were of 12‐month duration, five studies(7.8%) had a duration of 18 to 20 months, 25 (39.1%) studies were 24 months, 11 (17.2%) up to 36 months and only one reported data over 36 months (Zhu 2021).

Seven studies were conducted before the year 2000 (Fulk 1996Houston Study 1987Jensen 1991Pärssinen 1989Schwartz 1981Shih 1999Yen 1989). Of the 49 studies that declared a source of funding, 19 (38.8%) were funded by the optical or pharmaceutical industry.

Characteristics of the participants

The review included 64 studies that randomised a total of 11,617 children, aged between 4 and 18 years, with a pooled mean age of 10.35 (range 7.6 to 14.0) years and 48% of participants were male. In the 58 studies that documented the level of myopia for inclusion, all but five studies recruited low to moderate myopes of −6.00 D or less; the other five studies included participants with higher levels of myopia up to −8.75 D (Charm 2013Garcia‐del Valle 2021Lyu 2020Shih 1999Zhu 2021). Most studies adopted an upper astigmatism limit of 1.00 D or 1.50 D. Three studies specifically recruited myopes with both myopia and near esophoria (Fulk 1996Fulk 2002STAMP Study 2012). One study selectively recruited participants with anisomyopia with an interocular difference of 1.00 D or greater (Zhang 2021). Eight studies restricted recruitment to those demonstrating a minimum myopic progression rate of at least 0.50 D in the year prior to enrolment (ATOM 2 Study 2012Anstice 2011Cheng 2010CONTROL Study 2016Lu 2015Swarbrick 2015LAMP Study 2019Zhu 2021). Participants were sufficiently similar to satisfy the transitivity assumption for the NMA, that is, that there were no systematic differences between the available comparisons other than the treatments being compared.

Characteristics of the comparisons

Myopia control intervention versus control or placebo
Optical interventions
Spectacles
  • Undercorrection versus fully corrected single vision spectacle lenses (SVLs) (3 studies; Adler 2006Chung 2002Koomson 2016). These studies, conducted in Israel, China and Ghana, compared the effect of under correcting myopia by either 0.50 D or 0.75 D versus fully corrected SVL. The follow‐up periods were 18 months for Adler 2006 and 24 months for  Chung 2002 and Koomson 2016.

  • Multifocal spectacle lenses (MFSLs) versus single vision spectacle lenses (SVLs) (13 studies; Cheng 2010COMET Study 2003COMET2 Study 2011Edwards 2002Fulk 1996Fulk 2002Hasebe 2008Houston Study 1987Jensen 1991MIT Study 2001Pärssinen 1989STAMP Study 2012Yang 2009). These studies were conducted in North America (7 studies), Asia (4 studies) and Europe (2 studies). All studies enroled children aged 8 to 15 years. MFSLs were either bifocal (6 studies) or progressive addition lenses (7 studies) with near additions between +1.00 D and +2.00 D. The study durations were between 18 and 36 months. Eight studies had two arms and five studies had three arms. Hasebe 2008 compared bifocals with two add powers (+1.00 D and +2.00 D) to SVLs. Jensen 1991 randomised children to one of three groups, bifocals, SVLs or timolol maleate eye drops, and Pärssinen 1989 compared a group wearing bifocals (+1.75 D add) to a group wearing SVLs for distance vision only and a reference group wearing SVLs continuously. 

  • Peripheral plus spectacle lenses (PPSL) versus single vision spectacle lenses (SVLs) (6 studies; Bao 2021Hasebe 2014Han 2018Lam 2020Lu 2015Sankaridurg 2010). Novel spectacle lens designs have been developed that aim to reduce peripheral hyperopic defocus. These lenses, designated PPSLs, were compared to SVLs in Chinese and Japanese myopic children aged 6 to 16 years. Study durations were 1 to 2 years. Sankaridurg 2010 tested three lens designs (designated types I, II and III) that provided different relative peripheral power against SVLs in children aged 6 to 16 years. Hasebe 2014 compared two positively aspherised progressive addition lens designs, with +1.00 D or +2.00 D near add powers and a relative plus power in the upper portion of the lens, to SVLs. Lu 2015 randomised children to receive either PPSLs with up to a +2.50 D near addition or SVLs. Han 2018 conducted a three‐arm study in which children were randomised to PPSLs, SVLs, or orthokeratology lenses. Lam 2020 adapted a design that had previously been used in contact lenses (DISC Study 2011), to develop a spectacle lens with a clear central zone for distance correction and an annular peripheral zone consisting of a multiple array of segments approximately 1 mm in diameter, providing +3.50 D of myopic defocus. The lens, which is termed the ‘Defocus Incorporated Multiple Segments' (DIMS) lens, was tested in a two‐year study involving Chinese children aged 9 to 13 years, who were randomised to wear either DIMS lenses or SVLs. Finally, Bao 2021 tested a lens design based on the same principal that consisted of concentric rings of aspheric lenslets to provide myopic defocus. Children aged 8 to 13 years were randomised in a three‐arm study to receive either a lens with highly aspherical lenslets, a lens with slightly aspherical lenslets, or SVLs. The study reported interim results on myopia progression at one year.

Contact lenses
  • Multifocal soft contact lenses (MFSCL) versus single vision soft contact lenses (SVSCLs) (9 studies; Anstice 2011BLINK Study 2020Chamberlain 2019CONTROL Study 2016DISC Study 2011Fujikado 2014Garcia‐del Valle 2021Ruiz‐Pomeda 2018Sankaridurg 2019). Nine studies investigated the efficacy of a variety of MFSCL designs compared to SVSCL. The MFSCLs incorporated a central zone to provide clear distance vision with relatively more positive peripheral lens power, which either increased gradually towards the periphery (progressive design) or presented as discrete peripheral annular zones (concentric ring design). Three studies followed participants for 12 months, four provided data to 20 to 24 months, and two had a duration of 36 months (BLINK Study 2020Chamberlain 2019). Seven studies used a parallel‐group design, comparing MFSCLs with SVSCLs, and two studies used a cross‐over design (Anstice 2011Fujikado 2014). Six studies adopted similar eligibility criteria and randomised children, aged 6 to 18 years with low to moderate myopia up to −6.00 D; Garcia‐del Valle 2021 included myopes to −8.75 D. Anstice 2011 and CONTROL Study 2016) only included children with documented myopia progression of −0.50 D or greater in the previous year, and the CONTROL Study 2016 additionally restricted inclusion to myopic children with near esophoria. Three studies used a similar centre distance dual focus concentric ring design with alternating distance correction zones and peripheral zones providing +2.00 D of defocus (Anstice 2011Chamberlain 2019Ruiz‐Pomeda 2018). These studies were conducted in New Zealand (Anstice 2011), Spain (Ruiz‐Pomeda 2018) and at sites in Europe, Asia and Canada (Chamberlain 2019). Garcia‐del Valle 2021 tested a MFSCL with a progressive design (+2.00 D addition) compared to SVSCL in Spanish schoolchildren age 7 to 15 years. Two studies, conducted in the USA (CONTROL Study 2016BLINK Study 2020), used commercially available MFSCLs. The CONTROL Study 2016 evaluated children aged 8 to 18 years with progressive myopia, randomised to wear either a concentric bifocal soft contact lens or SVSCLs. The near add was selected based on the add power to neutralise the associated esophoria. The ‘Bifocal Lenses in Near‐sighted Kids' (BLINK) study (BLINK Study 2020), tested the efficacy of bifocal soft contact lenses with a central correcting zone for myopia and either a medium add (+1.50 D) or high add (+2.50 D) compared to SVSCLs. Three studies, conducted in China and Japan, used novel custom MFSCL designs (DISC Study 2011Fujikado 2014Sankaridurg 2019). The DISC Study 2011 tested the ‘Defocus Incorporated Soft Contact (DISC) lens’, a custom‐made bifocal soft contact lens of concentric ring design with a +2.50 D addition alternating with the normal distance correction. The DISC lens was compared to SVSCL in Chinese school children aged 8 to13 years, who were followed for two years. Fujikado 2014 used a cross‐over study design, in which Japanese children aged 6 to 16 years were randomised to wear a progressive MFSCL with a peripheral power of +0.50 D or SVSCLs in both eyes for 1 year and then were switched to the other type of lens for the second year. Sankaridurg 2019 randomised Chinese children aged 8 to 13 years to one of five groups: two groups wore MFSCLs that imposed peripheral myopic defocus of +1.50 D or +2.50 D with a stepped, relative positive power centrally of up to +1.00 D; and two groups wore extended depth of focus soft lens designs to optimise focus in front of and on the retina and degrade focus behind the retina. The control lens was a SVSCL.

  • Spherical aberration soft contact lenses versus single vision soft contact lenses (SVSCLs) (1 study; Cheng 2016). This study randomised children aged 8 to 11 years to receive soft contact lenses with or without positive spherical aberration. Although the study was conducted in the USA, it enroled mostly Asian children (91%). The study was planned for two years, but was stopped early and reported only one‐year data.

  • Rigid gas‐permeable (RGP) contact lenses versus single vision soft contact lenses (SVSCLs) or single vision spectacle lenses (SVLs) (2 studies; CLAMP Study 2004Katz 2003). Two studies investigated the impact of RGP lenses on myopia progression compared to SVLs. Katz 2003 randomised Singaporean children aged 6 to 12 years to SVLs or RGP lenses. Myopia progression was evaluated at 1 and 2 years. The Contact Lens and Myopia Progression (CLAMP) Study (CLAMP Study 2004), was conducted in the USA and randomised children to RGP or soft single vision contact lenses. Annual myopia progression was reported based on change in SER and axial length, for the three‐year duration of the study.

  • Orthokeratology lenses versus single vision spectacle lenses (SVLs) or contact lenses (9 studies; Bian 2020Charm 2013Han 2018Jakobsen 2022Lyu 2020Ren 2017ROMIO Study 2012Tang 2021Zhang 2021). Eight parallel‐group studies compared overnight orthokeratology contact lenses or SVLs, and in one study SVSCLs (Tang 2021). Participants were followed for 1 to 2 years. Seven studies enroled children with low to moderate degrees of myopia (up to −6.00 D), and two studies selectively recruited children with myopia 5.00 D or greater (Charm 2013Lyu 2020). Zhang 2021 included participants with anisomyopia with a difference in myopia between eyes of 1.00 D or greater. Eight of the nine studies were conducted in China and one in Denmark (Jakobsen 2022). Axial length was the primary outcome in all studies. The 'Retardation of Myopia in Orthokeratology' (ROMIO) Study (ROMIO Study 2012), randomised 102 Chinese children aged 6 to 12 years to overnight orthokeratology lenses or SVLs, who were followed for two years. Charm 2013 randomised 52 highly myopic children (aged 8 to 11 years), with a SER of at least −5.75 D to partial reduction overnight orthokeratology lenses and daily SVLs for residual myopia, or a control group who were fully corrected with SVLs. Axial length was measured at six‐monthly intervals for two years. Lyu 2020 similarly investigated partial reduction orthokeratology lenses in participants with myopia up to −8.75 D. They randomised 102 children aged 8 to12 years into three groups: (1) orthokeratology lenses with a target reduction of 6.00 D; (2) orthokeratology lenses with a 4.00 D target reduction; or (3) SVLs. Axial length was measured at baseline and at 12 months. Jakobsen 2022 randomised 60 Danish children aged 6 to 12 years to orthokeratology lenses or SVLs, and followed them for 18 months. Four studies compared orthokeratology lenses to SVLs in Chinese children aged 8 to 15 years with myopia (Bian 2020Han 2018Ren 2017Tang 2021). Ren 2017 also included a group that was treated with 0.01% atropine, and  Han 2018 included a group wearing PPSLs.

Pharmacological
Anti‐muscarinic agents
  • Atropine eye drops versus placebo or untreated control (11 studies; ATOM Study 2006Han 2019Hieda 2021LAMP Study 2019Moriche‐Carretero 2021Ren 2017Wang 2017Wei 2020Yen 1989Yi 2015Zhu 2021). Twelve parallel‐group studies compared atropine to either placebo or an untreated control. These studies enroled children with low to high myopia (up to −8.00 D), aged from 4 to 15 years. Eligibility criteria in LAMP Study 2019 and Zhu 2021 additionally included a documented level of myopic progression in the past year. All studies were conducted in Asia, except for Moriche‐Carretero 2021, which was conducted in Spain. Participants were followed for periods ranging from one to four years. 

    • High‐dose atropine (≥ 0.5%): four studies compared 1% atropine to placebo or untreated control. The 'Atropine in the Treatment of Myopia' (ATOM) Study (ATOM Study 2006), was conducted in Singapore and involved 400 children aged 6 to 12 years, who were randomised to receive either 1% atropine or placebo to one eye and were followed for two years. Yi 2015 randomised 140 Chinese children, aged 7 to 12 years with low myopia (−0.50 to −2.00 D) to 1% atropine or placebo eyedrops nightly for 12 months. Zhu 2021 compared 1% atropine to placebo using a novel dosing regime in 660 Chinese children. The study was divided into three phases. In Phase 1, the treatment group received 1% atropine once per month for 24 months, this was reduced to once every two months for 12 months (Phase 2), followed by no drops for 12 months in Phase 3. The placebo group received the same dosing regime. Wang 2017 compared daily 0.5% atropine with placebo in 126 Chinese children with low myopia, who were followed for one year. Two, three‐armed studies included a 1% atropine arm. Han 2019 randomised 150 Chinese children aged 6 to 12 years in a 1:2:2 ratio to either an untreated control group, 1% atropine or a combination of 1% atropine with 0.5% raceanisodamine (a non‐selective muscarinic antagonist, used as an ingredient of traditional Chinese medicines). Yen 1989 included a group receiving 1% cyclopentolate.

    • Low‐dose atropine (< 0.1%): five studies tested lower doses of atropine, ranging from 0.01% to 0.05%. The 'Low‐concentration Atropine for Myopia Progression' (LAMP) Study (LAMP Study 2019), randomised 438 Chinese children aged 4 to 12 years with myopia of at least −1.00 D to four groups (in a 1:1:1:1 ratio): low‐concentration atropine eye drops at 0.05%, 0.025%, or 0.01% concentration or placebo. Participants were followed for one year. Four studies tested the efficacy of 0.01% atropine eyedrops versus placebo or an untreated control in participants aged between 5 and 15 years with low or moderate myopia, who were followed for one or two years (Hieda 2021Moriche‐Carretero 2021Ren 2017Wei 2020). Participants in Hieda 2021 included 171 Japanese children, Wei 2020 included 220 Chinese children and Moriche‐Carretero 2021 randomised 339 Spanish children. In Ren 2017, 150 Chinese children were randomised (1:1:1 ratio) to 0.01% atropine, orthokeratology or single vision spectacle lenses. 

  • Pirenzepine eye drops versus placebo (2 studies; PIR‐205 Study 2004;  Tan 2005). These two studies compared 2% pirenzepine gel, a selective M1 muscarinic receptor antagonist, to placebo. PIR‐205 Study 2004 was a two‐year, multicentre study conducted in the USA that randomised 174 myopic children aged 8 to 12 years in a 2:1 ratio to twice‐daily pirenzepine gel or placebo. Tan 2005 was conducted in centres in Singapore, Thailand and China, and randomised 353 children aged 6 to 13 years to one of three arms: (1) 2% pirenzepine gel twice daily; (2) placebo once daily and 2% pirenzepine gel once daily; or (3) placebo twice daily.

Anti‐muscarinic agent with co‐intervention
  • Tropicamide and multifocal spectacles (MFSLs) (1 study; Schwartz 1981). This study was conducted in the USA and randomised 26 monozygous twin pairs aged 7 to 14 years to either a combination of MFSLs combined with 1% tropicamide or SVLs.

  • Atropine and multifocal spectacles (MFSLs) versus placebo (2 studies; MIT Study 2001Yen 1989). The 'Myopia Intervention Trial' (MIT) (MIT Study 2001), was conducted in Taiwan and evaluated SVLs, progressive addition lenses and progressive addition lenses combined with 0.5% atropine eyedrops. Yen 1989 randomly divided 247 Taiwanese children aged 6 to 14 years into three groups. Group 1 received 1% atropine and bifocal spectacles; group 2 received 1% cyclopentolate; and group 3 received saline eye drops. All groups were followed for 12 months.

Other pharmacological interventions
  • Timolol eyedrops versus single vision spectacle lenses (SVLs) (1 study; Jensen 1991). One arm of Jensen 1991 investigated topical 0.25% timolol maleate, a non‐selective beta antagonist. Timolol eyedrops were given twice a day for two years and compared to MFSL or SVL control.

  • Systemic 7‐methylxanthine versus placebo (1 study; Trier 2008). This study investigated the effectiveness of systemic 7‐methylxanthine, an adenosine receptor antagonist, in 83 Danish children aged 8 to 13 years. Participants were randomised to once daily 7‐methylxanthine or a placebo tablet.

Myopia control intervention versus myopia control interventions
  • Comparison of atropine doses (2 studies; ATOM 2 Study 2012Cui 2021). The ATOM 2 Study 2012 was conducted in Singapore and compared the efficacy and safety of three doses of topical atropine: 0.5%, 0.1%, and 0.01% in 400 children of Chinese ethnicity. Cui 2021 evaluated the safety and efficacy of 0.02% and 0.01% atropine in 400 myopic Chinese children, who were randomly allocated to atropine 0.02% (138 children) or 0.01% (142 children). The study also included a non‐randomised control group wearing single vision spectacle lenses (120 children). All participants were followed for two years.

  • Atropine and multifocal spectacle lenses (MFSLs) versus tropicamide (1 study; Shih 1999). This study evaluated low‐concentration atropine in Taiwanese children aged 6 to 13 years. It randomly allocated 200 children to one of three atropine groups (0.5%, 0.25% or 0.1%) or 1% tropicamide as a control. The 0.5% atropine group were advised to wear MFSLs and the 0.25% atropine group were advised to wear slightly undercorrected SVLs.

  • Combined orthokeratology plus atropine versus orthokeratology alone (3 studies; Kinoshita 2020; Tan 2020Zhao 2021).  Kinoshita 2020 randomly allocated 80 Japanese children with low to moderate myopia, aged 8 to 12 years, to receive either a combined orthokeratology and 0.01% atropine, or orthokeratology monotherapy. Tan 2020 randomised 72 Chinese children aged 6 to 11 years to receive combined orthokeratology/0.01% atropine compared to monotherapy. Similarly, Zhao 2021  included as a separate parallel‐group comparison, combined 0.01% atropine/orthokeratology versus orthokeratology alone. Zhao 2021 randomised 40 children who had been wearing orthokeratology lenses for three months to orthokeratology and 0.01% atropine or orthokeratology only.

  • Comparison of orthokeratology designs (1 study; Guo 2021). This study compared two designs of orthokeratology lenses with different back optic zone diameters. It randomly assigned 82 Chinese children aged 6 to 11 years to wear orthokeratology lenses with either a 6 mm or 5 mm back optic zone diameter and followed them for two years.

  • Orthokeratology versus rigid gas‐permeable contact lenses (RGP) (1 study; Swarbrick 2015). This study conducted a randomised, contralateral‐eye cross‐over study over a one‐year period. Although the study was conducted in Australia, all 26 children were of East Asian ethnicity. Participants were fitted with an orthokeratology lens in one eye, chosen at random, and a conventional RGP lens worn daily in the contralateral eye. Children wore the lenses for six months. After a two‐week washout period, the lenses were reversed and lens wear was continued for a further six months.

  • Orthokeratology versus atropine (2 studies; Ren 2017Zhao 2021). Both studies compared 0.01% atropine to orthokeratology. 

Environmental interventions

We excluded studies that reported the impact of environmental interventions (e.g. elevated light levels in classrooms, increased outdoor time or regulated near working distances) mostly because the populations included participants both with and without myopia, or the primary outcome was incident myopia. One ongoing study, The 'Shanghai Time Outside to Reduce Myopia' (STORM) Study (NCT02980445), is a two‐year, school‐based, prospective, cluster‐randomised study that is investigating the effect of two 'doses' of increased outdoor time (40 and 80 minutes over normal time outdoors). Outcomes include the incidence of myopia in non‐myopic children, and the progression of myopia in myopic children.

Characteristics of the outcomes

All the included studies evaluated progression of myopia, either by measuring the mean change in refractive error, defined as spherical equivalent refraction (SER), mean change in axial length or both. Nine studies reported SER only (Adler 2006Han 2018Hasebe 2008Jensen 1991Pärssinen 1989Schwartz 1981Shih 1999Yang 2009Yen 1989), six studies investigating the efficacy of orthokeratology lenses reported axial length only (Bian 2020Jakobsen 2022Kinoshita 2020ROMIO Study 2012Swarbrick 2015Zhang 2021), and the remaining 49 studies provided data on both SER and axial length.

Six studies investigated change in refractive error and axial length following cessation of treatment (commonly referred to as 'rebound'). In the STAMP Study 2012, children were randomly assigned to MFSL or SVLs for one year and all children wore SVLs in the second year. Cheng 2016 invited participants who had been randomised to soft contact lenses with positive spherical aberration or single vision soft lenses for one year to participate in a withdrawal phase where all children wore single vision contact lenses. To assess a potential rebound effect, Ruiz‐Pomeda 2018 invited children to participate in an additional year of follow‐up. Children were divided into three groups: a group in which children from the original study group continued wearing MFSCL; a group in which children discontinued MFSCL wear; and an SVL group, in which children from the original control group continued wearing SVLs. Three studies investigated the impact of terminating atropine treatment. In the ATOM Study 2006, children received 0.5%, 0.1% or 0.01% atropine for 12 months, after which treatment was terminated and the children were followed for a further 24 months. In the ATOM 2 Study 2012, children who received topical atropine 0.5%, 0.1% or 0.01% for 24 months entered Phase 2, the washout phase, where atropine was discontinued and SER and axial length assessed at 26, 32 and 36 months. In Zhu 2021, the frequency of 1% atropine eyedrop instillation was reduced from year 1 from once per month to once every two months in years 2 and 3, and withdrawn completely in year 4.

Twenty‐six studies provided data on safety outcomes in terms of the occurrence of adverse events. These included five studies reporting on adverse events with spectacle lens interventions, 11 reporting on contact lens interventions (including orthokeratology) and 10 studies reporting on various pharmacological interventions.

Only one study (LAMP Study 2019), which investigated the efficacy of low‐dose topical atropine, measured vision‐related quality of life. At the 12‐month follow‐up visit, the Chinese version of the 25‐Item National Eye Institute Visual Function Questionnaire was administered to all participants to determine the impact of different treatment groups on vision‐related quality of life.

Twenty‐one studies provided data on treatment adherence. Ten studies reported on compliance with spectacle lens wear including undercorrection with SVL, bifocal or progressive addition lenses. Compliance was typically based on parent or child, or both, self‐reporting wearing time (hours per day) and overall compliance, expressed as a % of participants in each arm. Similarly, six studies using contact lens interventions, reported on wearing time and percentage compliance between the intervention and control lenses. Four studies of pharmacological interventions provided data on self‐reported compliance with the study medication.

Ongoing studies

We identified 120 ongoing studies (see Characteristics of ongoing studies). These studies compare contact lenses or spectacle lenses (MFSCL, MFSL or orthokeratology) or pharmacological interventions to a control or other myopia control interventions. The majority of the ongoing studies investigate the efficacy of various doses of atropine used alone or in combination with other interventions.

Studies awaiting classification

We classified two studies published as conference abstracts as awaiting classification (see Characteristics of studies awaiting classificationWang 2005Viswanath 2022).

Excluded studies

We excluded a total of 137 studies. We excluded the Cambridge Anti‐Myopia Study 2013, which had been included in Walline 2020. The main reasons for exclusion were that the study was not randomised, population not eligible, intervention not eligible or ineligible outcome (see Characteristics of excluded studies for further details).

Risk of bias in included studies

We assessed risk of bias using the RoB 2 (Higgins 2022a). A graphical representation of risk of bias for each comparison for the critical outcome 'progression of myopia' can be seen in Analysis 1.1Analysis 1.2Analysis 2.1Analysis 2.2Analysis 2.3Analysis 3.1Analysis 3.2Analysis 4.1Analysis 4.2Analysis 5.1Analysis 5.2Analysis 6.1Analysis 7.1Analysis 7.3Analysis 7.2Analysis 7.4Analysis 7.5Analysis 8.1Analysis 8.2Analysis 9.1

1.1. Analysis.

1.1

Comparison 1: Undercorrection vs full correction spectacles, Outcome 1: Change in refractive error from baseline

1.2. Analysis.

1.2

Comparison 1: Undercorrection vs full correction spectacles, Outcome 2: Change in axial length from baseline

2.1. Analysis.

2.1

Comparison 2: Multifocal spectacle lenses vs single vision spectacle lenses, Outcome 1: Change in refractive error from baseline

2.2. Analysis.

2.2

Comparison 2: Multifocal spectacle lenses vs single vision spectacle lenses, Outcome 2: Change in axial length from baseline 

2.3. Analysis.

2.3

Comparison 2: Multifocal spectacle lenses vs single vision spectacle lenses, Outcome 3: Change in refractive error following cessation of treatment (1 year)

3.1. Analysis.

3.1

Comparison 3: Peripheral plus spectacles vs single vision spectacle lenses, Outcome 1: Change in refractive error from baseline 

3.2. Analysis.

3.2

Comparison 3: Peripheral plus spectacles vs single vision spectacle lenses, Outcome 2: Change in axial length from baseline

4.1. Analysis.

4.1

Comparison 4: Multifocal soft contact lenses vs single vision soft contact lenses, Outcome 1: Change in refractive error from baseline

4.2. Analysis.

4.2

Comparison 4: Multifocal soft contact lenses vs single vision soft contact lenses, Outcome 2: Change in axial length from baseline

5.1. Analysis.

5.1

Comparison 5: Rigid gas‐permeable lenses vs control, Outcome 1: Change in refractive error from baseline

5.2. Analysis.

5.2

Comparison 5: Rigid gas‐permeable lenses vs control, Outcome 2: Change in axial length from baseline

6.1. Analysis.

6.1

Comparison 6: Orthokeratology lenses vs single vision spectacle lenses lenses, Outcome 1: Change in axial length from baseline

7.1. Analysis.

7.1

Comparison 7: Anti‐muscarinics vs placebo, Outcome 1: Change in refractive error from baseline (1 year)

7.3. Analysis.

7.3

Comparison 7: Anti‐muscarinics vs placebo, Outcome 3: Change in refractive error from baseline (2 years)

7.2. Analysis.

7.2

Comparison 7: Anti‐muscarinics vs placebo, Outcome 2: Change in axial length from baseline (1 year)

7.4. Analysis.

7.4

Comparison 7: Anti‐muscarinics vs placebo, Outcome 4: Change in axial length from baseline (2 years)

7.5. Analysis.

7.5

Comparison 7: Anti‐muscarinics vs placebo, Outcome 5: Change in refractive error following cessation of treament (1 year)

8.1. Analysis.

8.1

Comparison 8: 7‐methylxanthine vs placebo, Outcome 1: Change in refractive error from baseline (1 year)

8.2. Analysis.

8.2

Comparison 8: 7‐methylxanthine vs placebo, Outcome 2: Change in axial length from baseline (1 year)

9.1. Analysis.

9.1

Comparison 9: Othokeratology plus atropine vs orthokeratology alone, Outcome 1: Change in axial length

The overall risk of bias across studies in each analysis reporting this outcome ranged from some concerns to high risk of bias depending on the particular intervention used.   

For the comparison 'undercorrection versus full correction spectacles', we assumed an overall high risk of bias, since two out of three studies had a high risk of bias in one domain, due to either an inappropriate method used to measure the outcome or no reasons given for missing data Table 188Table 189.

Risk of bias for analysis 1.1 Change in refractive error from baseline.

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 1.1.1 At 1 year
Adler 2006 Low risk of bias Randomisation was performed by tossing a coin. Allocation performed by someone uninvolved in the project. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants or investigators providing clinical care given the nature of the interventions but investigating optometrists were masked from previous results. Results analysed using ITT principles without imputation of missing data. Some concerns Outcome data available for 77.4% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms.  Three non‐compliant participants were excluded.  High risk of bias Inappropriate method used for outcome measurement (non‐cycloplegic refraction). Some concerns No pre‐registered method (registry or protocol) available.   High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Chung 2002 Some concerns Randomisation was performed using a block randomisation technique. Once participants were paired, allocation to intervention and control using a coin toss. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants, carers or investigating clinicians. Deviations from intended interventions are not reported and the analysis was appropriate. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value.  Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Subgroup 1.1.2 At 2 years
Chung 2002 Some concerns Randomisation was performed using a block randomisation technique. Once participants were paired, allocation to intervention and control using a coin toss. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants, carers or investigating clinicians. Deviations from intended interventions are not reported and the analysis was appropriate. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value.  Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Koomson 2016 Low risk of bias Randomisation was performed using the permuted block method and tossing a coin.  Sealed envelopes to conceal allocation. Baseline differences did not suggest a problem with the randomisation process. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the ITT principles. Low risk of bias Data available for all participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Risk of bias for analysis 1.2 Change in axial length from baseline.

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 1.2.1 At 1 year
Chung 2002 Some concerns Randomisation was performed using a block randomisation technique. Once participants were paired, allocation to intervention and control using a coin toss. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants,carers or investigating clinicians. Deviations from intended interventions are not reported and the method of analysis was not reported. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Subgroup 1.2.2 At 2 years
Chung 2002 Some concerns Randomisation was performed using a block randomisation technique. Once participants were paired, allocation to intervention and control using a coin toss. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants,carers or investigating clinicians. Deviations from intended interventions are not reported and the method of analysis was not reported. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Koomson 2016 Low risk of bias Randomisation was performed using the permuted block method and tossing a coin.  Sealed envelopes to conceal allocation. Baseline differences did not suggest a problem with the randomisation process. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the ITT principles. Low risk of bias Data available for all participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Of the 10 studies that reported on progression of myopia in the analysis 'multifocal spectacle lenses versus single vision spectacles', we judged one study to be at high risk of bias (Cheng 2010). We judged the remainder as 'some concerns', usually due to insufficient information concerning allocation concealment and lack of an a priori statistical analysis plan. We therefore assumed an overall bias of 'some concerns' (see Table 190Table 191). For 'peripheral plus spectacle lenses versus single vision spectacles', three of the six studies reporting this outcome had some concerns, with three studies judged to be at high risk of bias (Han 2018 Hasebe 2014Lu 2015); see Table 193Table 194).  

Risk of bias for analysis 2.1 Change in refractive error from baseline.

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 2.1.1 At 1 year
Cheng 2010 High risk of bias Randomisation was performed by randomly drawing file numbers written on slips of paper from a container. There was no allocation concealment and no analysis to investigate baseline differences that arose as a result of the allocation process. High risk of bias It was not possible to mask the participants, carers or investigating optometrists given the nature of the interventions. Nine participants and their parents did not accept their group allocations. Results analysed using ITT principles. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. However, not enough information in the protocol on a statistical plan and no published statistical plan found.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
COMET2 Study 2011 Some concerns Randomisation was performed using a permuted block design. Allocation concealment was not reported. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles Low risk of bias Data available for approx 93% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
COMET Study 2003 Low risk of bias Randomisation was stratified by coordinating center, using a random permuted block design. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the modified ITT principles. Low risk of bias Data available for approx 98% of participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Edwards 2002 Some concerns Randomisation was performed using a pre‐determined randomisation sequence. Allocation concealment was not reported. There were no significant differences in the baseline parameters that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. Deviations from intended interventions were not reported. Only participants who completed the study were analysed. Low risk of bias Outcome data available for 85.2% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Fulk 2002 Some concerns Randomisation was performed using the permuted block method and tossing a coin. Allocation concelament was maintained until after enrolment. There were baseline differences for initial myopia. There were no baseline differences for age, gender, axial length and vitreous chamber. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the Intention to Treat Principles. Low risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was biased by missing outcome data, and unlikely that missingness in the outcome depended on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Jensen 1991 Some concerns Randomisation was performed using block randomisation. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Masking of the investigatoris not reported. There were no deviations from intended interventions. Analysis were performed on the ITT principles. Low risk of bias Outcome data available for 91.8% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
MIT Study 2001 Some concerns Initial stratification based on age, sex and myopic severity followed by randomisation to one of three treatment groups. No information on allocation concealment.  Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. There were no deviations from intended interventions and the analysis was appropriate. Low risk of bias Outcome data available for 82.8% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Pärssinen 1989 Low risk of bias Randomisation was performed using stratified coding. Sealed envelopes for allocation concealment. No information on baseline differences between intervention groups was reported. Some concerns It was not possible to mask the participants or investigating clinicians. Deviations from intended interventions arose as a result of the trial context. Data were analysed for participants who completed the study. Low risk of bias Data available for approx 98% of participants. Some concerns No information provided on the methods used to measure SER (objective or subjective).  Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
STAMP Study 2012 Low risk of bias Adaptive randomisation using online software for sequence generation. Allocation was concealed until participants were enrolled and assigned to interventions.  Low risk of bias Participants, carers and those delivering the intervention were aware of intervention received. Unlikely that ther were deviations from the intended intervention due to  trial context. Results analysed using ITT principles. Low risk of bias Data available for approx 99% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 2.1.2 At 2 years
Cheng 2010 High risk of bias Randomisation was performed by randomly drawing file numbers written on slips of paper from a container. There was no allocation concealment and no analysis to investigate baseline differences that arose as a result of the allocation process. High risk of bias It was not possible to mask the participants, carers or investigating optometrists given the nature of the interventions. Nine participants and their parents did not accept their group allocations. Results analysed using ITT principles. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. However, not enough information in the protocol on a statistical plan and no published statistical plan found.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
COMET2 Study 2011 Some concerns Randomisation was performed using a permuted block design. Allocation concealment was not reported. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles Low risk of bias Data available for approx 93% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
COMET Study 2003 Low risk of bias Randomisation was stratified by coordinating center, using a random permuted block design. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the modified ITT principles. Low risk of bias Data available for approx 98% of participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Edwards 2002 Some concerns Randomisation was performed using a pre‐determined randomisation sequence. Allocation concealment was not reported. There were no significant differences in the baseline parameters that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. Deviations from intended interventions were not reported. Only participants who completed the study were analysed. Low risk of bias Outcome data available for 85.2% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Fulk 2002 Some concerns Randomisation was performed using the permuted block method and tossing a coin. Allocation concelament was maintained until after enrolment. There were baseline differences for initial myopia. There were no baseline differences for age, gender, axial length and vitreous chamber. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the Intention to Treat Principles. Low risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was biased by missing outcome data, and unlikely that missingness in the outcome depended on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Jensen 1991 Some concerns Randomisation was performed using block randomisation. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Masking of the investigatoris not reported. There were no deviations from intended interventions. Analysis were performed on the ITT principles. Low risk of bias Outcome data available for 91.8% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Pärssinen 1989 Low risk of bias Randomisation was performed using stratified coding. Sealed envelopes for allocation concealment. No information on baseline differences between intervention groups was reported. Some concerns It was not possible to mask the participants or investigating clinicians. Deviations from intended interventions arose as a result of the trial context. Data were analysed for participants who completed the study. Low risk of bias Data available for approx 98% of participants. Some concerns No information provided on the methods used to measure SER (objective or subjective).  Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Yang 2009 Some concerns Participants were randomised though no details of tthe exact method of randomisation are recorded. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the ITT principles. Low risk of bias Outcome data available for 83.7% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 2.1.3 At 3 years
Cheng 2010 High risk of bias Randomisation was performed by randomly drawing file numbers written on slips of paper from a container. There was no allocation concealment and no analysis to investigate baseline differences that arose as a result of the allocation process. High risk of bias It was not possible to mask the participants, carers or investigating optometrists given the nature of the interventions. Nine participants and their parents did not accept their group allocations. Results analysed using ITT principles. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. However, not enough information in the protocol on a statistical plan and no published statistical plan found.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
COMET2 Study 2011 Some concerns Randomisation was performed using a permuted block design. Allocation concealment was not reported. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles Low risk of bias Data available for approx 93% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
COMET Study 2003 Low risk of bias Randomisation was stratified by coordinating center, using a random permuted block design. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the modified ITT principles. Low risk of bias Data available for approx 98% of participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Pärssinen 1989 Low risk of bias Randomisation was performed using stratified coding. Sealed envelopes for allocation concealment. No information on baseline differences between intervention groups was reported. Some concerns It was not possible to mask the participants or investigating clinicians. Deviations from intended interventions arose as a result of the trial context. Data were analysed for participants who completed the study. Low risk of bias Data available for approx 98% of participants. Some concerns No information provided on the methods used to measure SER (objective or subjective).  Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Risk of bias for analysis 2.2 Change in axial length from baseline .

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 2.2.1 At 1 year
Cheng 2010 High risk of bias Randomisation was performed by randomly drawing file numbers written on slips of paper from a container. There was no allocation concealment and no analysis to investigate baseline differences that arose as a result of the allocation process. High risk of bias It was not possible to mask the participants,carers or investigating optometrists given the nature of the interventions. Nine participants and their parents did not accept their group allocations. Results analysed using ITT principles. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
COMET Study 2003 Low risk of bias Randomisation was stratified by coordinating center, using a random permuted block design. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the modified ITT principles. Low risk of bias Data available for approx 98% of participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Edwards 2002 Some concerns Randomisation was performed using a pre‐determined randomisation sequence. Allocation concealment was not reported. There were no significant differences in the baseline parameters that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. Deviations from intended interventions were not reported. Only participants who completed the study were analysed. Low risk of bias Outcome data available for 85.2% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
STAMP Study 2012 Low risk of bias Adaptive randomisation using online software for sequence generation. Allocation was concealed until participants were enrolled and assigned to interventions.  Low risk of bias Participants, carers and those delivering the intervention were aware of intervention received. It is unlikely that there were deviations from the intended intervention that arose due to trial context. Results analysed using ITT principles. Low risk of bias Data available for approx 99% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 2.2.2 At 2 years
Cheng 2010 High risk of bias Randomisation was performed by randomly drawing file numbers written on slips of paper from a container. There was no allocation concealment and no analysis to investigate baseline differences that arose as a result of the allocation process. High risk of bias It was not possible to mask the participants,carers or investigating optometrists given the nature of the interventions. Nine participants and their parents did not accept their group allocations. Results analysed using ITT principles. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
COMET Study 2003 Low risk of bias Randomisation was stratified by coordinating center, using a random permuted block design. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the modified ITT principles. Low risk of bias Data available for approx 98% of participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Edwards 2002 Some concerns Randomisation was performed using a pre‐determined randomisation sequence. Allocation concealment was not reported. There were no significant differences in the baseline parameters that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. Deviations from intended interventions were not reported. Only participants who completed the study were analysed. Low risk of bias Outcome data available for 85.2% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 2.2.3 At 3 years
Cheng 2010 High risk of bias Randomisation was performed by randomly drawing file numbers written on slips of paper from a container. There was no allocation concealment and no analysis to investigate baseline differences that arose as a result of the allocation process. High risk of bias It was not possible to mask the participants,carers or investigating optometrists given the nature of the interventions. Nine participants and their parents did not accept their group allocations. Results analysed using ITT principles. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
COMET Study 2003 Low risk of bias Randomisation was stratified by coordinating center, using a random permuted block design. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the modified ITT principles. Low risk of bias Data available for approx 98% of participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Risk of bias for analysis 3.1 Change in refractive error from baseline .

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 3.1.1 At 1 year
Bao 2021 Some concerns Adaptive randomisation with online software for sequence generation. No information relating to whether allocation was concealed until participants were enrolled and assigned to interventions. Observed imbalances of higher proportion of girls in one group and shorter AL could have occurred by chance. Low risk of bias Spectacles were not labelled to identify the treatment group assigned. Losses to follow up documented and no deviations due to trial context. Modified ITT analysis used to estimate the effect of assignment to intervention. Low risk of bias Data available for approx 95% of participants. Low risk of bias Methods of outcome measurement were appropriate. Comparable methods of outcome assessment were used. Assessors were masked to the intervention status. Some concerns Primary outcomes analysed as pre‐specified in trial registry.Primary outcomes analysed as pre‐specified in trial registry. No information to judge whether this result was analysed in accordance with a pre‐specified analysis plan Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Han 2018 Some concerns There was no information on the method of randomisation. There were no significant differences in the baseline parameters that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants or investigating clinicians. Deviations from intended interventions are not reported and the analysis was appropriate. Low risk of bias Data available for all participants. Some concerns No information provided on the methods used to conduct the eye examination. Masking of outcome assessors was not reported.  Some concerns No pre‐registered method (registry or protocol) available.  High risk of bias The study is judged as some concerns in four out of five domains for this result. We therefore judged that the study was at an overall high risk of bias.
Lam 2020 Some concerns Group allocation using random software sequence generated from Excel. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Low risk of bias Data was available for approx 87% of participants. No analysis performed to correct for bias due to missing data. Missing data occurred for documented reasons that were unrelated to the study outcome. Low risk of bias Appropriate and comparable methods of measuring outcome data were used.  Some concerns Trial registry entry available but no pre‐specified information on the statistical analysis plan. Outcomes included as pre‐specified. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Lu 2015 Some concerns Participants were randomly divided into two groups. No information was provided relating to method of allocation sequence, allocation sequence concealment and baseline differences between intervention groups. Some concerns It was not possible to mask the participants or investigating clinicians. Deviations from intended interventions are not reported and the analysis was appropriate. Low risk of bias Data available for all participants. Some concerns No information provided on the methods used to conduct the eye examination. Masking of outcome assessors was not reported.  Some concerns No pre‐registered method (registry or protocol) available.  High risk of bias The study is judged as some concerns in four out of five domains for this result. We therefore judged that the study was at an overall high risk of bias.
Sankaridurg 2010 Low risk of bias Randomisation was performed using website randomisation. Allocation concealment was maintained until after enrollment and participants assigned. No information on baseline differences between intervention groups was reported. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using mITT principles Low risk of bias Data available for approx 95% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No pre‐registered trail registry record or protocol available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 3.1.2 At 2 years
Hasebe 2014 Low risk of bias Randomisation was performed using a lens allocation table designed on Microsoft Excel. Allocation concealment was maintained until after enrollment and participants assigned. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Lam 2020 Some concerns Group allocation using random software sequence generated from Excel. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Low risk of bias Data was available for approx 87% of participants. No analysis performed to correct for bias due to missing data. Missing data occurred for documented reasons that were unrelated to the study outcome. Low risk of bias Appropriate and comparable methods of measuring outcome data were used.  Some concerns Trial registry entry available but no pre‐specified information on the statistical analysis plan. Outcomes included as pre‐specified. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Risk of bias for analysis 3.2 Change in axial length from baseline.

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 3.2.1 At 1 year
Bao 2021 Some concerns Adaptive randomisation with online software for sequence generation. No information relating to whether allocation was concealed until participants were enrolled and assigned to interventions. Observed imbalances of higher proportion of girls in one group and shorter AL could have occurred by chance. Low risk of bias Spectacles were not labelled to identify the treatment group assigned. Losses to follow up documented and no deviations due to trial context. Modified ITT analysis used to estimate the effect of assignment to intervention. Low risk of bias Data available for approx 95% of participants. Low risk of bias Methods of outcome measurement were appropriate. Comparable methods of outcome assessment were used. Assessors were masked to the intervention status. Some concerns Primary outcomes analysed as pre‐specified in trial registry. No information to judge whether this result was  analysed in accordance with a pre‐specified analysis plan Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Lam 2020 Some concerns Group allocation using random software sequence generated from Excel. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on Intention to Treat principles. Low risk of bias Data was available for approx 87% of participants. No analysis performed to correct for bias due to missing data. Missing data occurred for documented reasons that were unrelated to the study outcome. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Examiners masked to refractive status at enrolment and the group allocation of participants.  Some concerns Trial registry entry available, not analysis protocol. Outcomes included as pre‐specified. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Sankaridurg 2010 Low risk of bias Randomisation was performed using website randomisation. Allocation concealment was maintained until after enrollment and participants assigned. No information on baseline differences between intervention groups was reported. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. Low risk of bias Data available for approx 95% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns No pre‐registered trial registry record or protocol available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 3.2.2 At 2 years
Hasebe 2014 Low risk of bias Randomisation was performed using a lens allocation table designed on Microsoft Excel. Allocation concealment was maintained until after enrollment and participants assigned. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using mITT principles. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Lam 2020 Some concerns Group allocation using random software sequence generated from Excel. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on Intention to Treat principles. Low risk of bias Data was available for approx 87% of participants. No analysis performed to correct for bias due to missing data. Missing data occurred for documented reasons that were unrelated to the study outcome. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Examiners masked to refractive status at enrolment and the group allocation of participants.  Some concerns Trial registry entry available, not analysis protocol. Outcomes included as pre‐specified. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Seven of the eight studies reporting progression of myopia in the comparison 'multifocal soft contact lenses versus single‐vision soft contact lenses' were judged as 'some concerns', primarily due to failure to describe the method of allocation concealment and no information on the predetermined analysis plan. We gave an overall judgement of 'some concerns' for this outcome (see Table 195Table 196).

Risk of bias for analysis 4.1 Change in refractive error from baseline.

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 4.1.1 At 1 year
Anstice 2011 Some concerns Randomisation was performed using the permuted block design. Allocation concealment was not reported. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants or investigators providing clinical care given the nature of the interventions but investigating optometrists were masked from previous results. Results analysed using ITT principles without imputation of missing data. Low risk of bias Outcome data available for 88% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns Protocol registered. Insufficient information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
BLINK Study 2020 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Low risk of bias Outcome data were available for nearly all participants (97.5%).  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Low risk of bias Protocol registered, with a pre published protocol and statistical plan. Low risk of bias The study is judged to be at low risk of bias in all domains.
Chamberlain 2019 Some concerns Contract organisation used a a random number ‐ generating computer program. Investigators had access to randomisation codes. No statistically significant differences between the experimental and control groups. Low risk of bias Participants and their parents were masked. Modified ITT analysis. Low risk of bias Outcome data available for 75% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate and comparable methods of outcome measurement. Outcome assessors masked to intervention received. Low risk of bias Prospective registration. Data analysed according to a pre‐specified analysis plan. Reported outcomes and data analysis pre‐specified. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
CONTROL Study 2016 Low risk of bias Randomisation was performed by an off site clinical coordinator. Allocation concealment maintained until the end of the study. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns Participants, carers and those delivering the intervention were unaware of intervention received. Participants for whom only baseline data were available were excluded from the analysis. Low risk of bias Outcome data available for 90.7% of randomised participants.  Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team weremasked to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
DISC Study 2011 Some concerns Randomisation was performed using random software sequence in excel. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the ITT principles. Some concerns Outcome data available for 57.9% of children that were randomised. Analytical methods to correct for bias were not performed. Posspible that missingness could depend on its true value but missing data balanced across the two groups with similar reasons. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Garcia‐del Valle 2021 Some concerns There was no information on method of randomisation, there was no baseline imbalance that would suggest a problem with randomisation. Low risk of bias Both participants and those delivering the intervention were unaware of intervention received. There were no deviations from intended interventions and the analysis was appropriate. Some concerns Outcome data available for 82% of children that were randomised. Analytical methods to correct for bias were not performed. Posspible that missingness could depend on its true value but missing data balanced across the two groups with similar reasons. Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Ruiz‐Pomeda 2018 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the children or carers given the nature of the interventions. Results analysed using ITT principles  Low risk of bias Outcome data were available for nearly all randomized participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Sankaridurg 2019 Some concerns Permuted block randomisation with online software for sequence generation. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Some concerns Data was available for 61.4% of participants at 1 year and 46% at 2 years. No analysis performed to correct for bias due to missing data.  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 4.1.2 At 2 years
BLINK Study 2020 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Low risk of bias Outcome data were available for nearly all participants (97.5%).  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Low risk of bias Protocol registered, with a pre published protocol and statistical plan. Low risk of bias The study is judged to be at low risk of bias in all domains.
Chamberlain 2019 Some concerns Contract organisation used a a random number ‐ generating computer program. Investigators had access to randomisation codes. No statistically significant differences between the experimental and control groups. Low risk of bias Participants and their parents were masked. Modified ITT analysis. Low risk of bias Outcome data available for 75% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate and comparable methods of outcome measurement. Outcome assessors masked to intervention received. Low risk of bias Prospective registration. Data analysed according to a pre‐specified analysis plan. Reported outcomes and data analysis pre‐specified. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
DISC Study 2011 Some concerns Randomisation was performed using random software sequence in excel. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the ITT principles. Some concerns Outcome data available for 57.9% of children that were randomised. Analytical methods to correct for bias were not performed. Posspible that missingness could depend on its true value but missing data balanced across the two groups with similar reasons. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Ruiz‐Pomeda 2018 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the children or carers given the nature of the interventions. Results analysed using ITT principles  Low risk of bias Outcome data were available for nearly all randomized participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Sankaridurg 2019 Some concerns Permuted block randomisation with online software for sequence generation. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Some concerns Data was available for 61.4% of participants at 1 year and 46% at 2 years. No analysis performed to correct for bias due to missing data.  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 4.1.3 At 3 years
BLINK Study 2020 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Low risk of bias Outcome data were available for nearly all participants (97.5%).  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Low risk of bias Protocol registered, with a pre published protocol and statistical plan. Low risk of bias The study is judged to be at low risk of bias in all domains.
Chamberlain 2019 Some concerns Contract organisation used a a random number ‐ generating computer program. Investigators had access to randomisation codes. No statistically significant differences between the experimental and control groups. Low risk of bias Participants and their parents were masked. Modified ITT analysis. Low risk of bias Outcome data available for 75% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate and comparable methods of outcome measurement. Outcome assessors masked to intervention received. Low risk of bias Prospective registration. Data analysed according to a pre‐specified analysis plan. Reported outcomes and data analysis pre‐specified. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Risk of bias for analysis 4.2 Change in axial length from baseline.

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 4.2.1 At 1 year
Anstice 2011 Some concerns Randomisation was performed using the permuted block design. Allocation concealment was not reported. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants or investigators providing clinical care given the nature of the interventions but investigating optometrists were masked from previous results. Results analysed using ITT principles without imputation of missing data. Low risk of bias Outcome data available for 88% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns Protocol registered. Insufficient information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
BLINK Study 2020 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Low risk of bias Outcome data were available for nearly all participants (97.5%).  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Low risk of bias Protocol registered, with a pre published protocol and statistical plan. Low risk of bias The study is judged to be at low risk of bias in all domains.
Chamberlain 2019 Some concerns Contract organisation used a a random number ‐ generating computer program. Investigators had access to randomisation codes. No statistically significant differences between the experimental and control groups. Low risk of bias Participants and their parents were masked. Modified ITT analysis. Low risk of bias Outcome data available for 75% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate and comparable methods of outcome measurement. Outcome assessors masked to intervention received. Low risk of bias Prospective registration. Data analysed according to a pre‐specified analysis plan. Reported outcomes and data analysis pre‐specified. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
CONTROL Study 2016 Low risk of bias Randomisation was performed by an off site clinical coordinator. Allocation concealment maintained until the end of the study. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns Participants, carers and those delivering the intervention were unaware of intervention received. Participants for whom only baseline data were available were excluded from the analysis. Low risk of bias Outcome data available for 90.7% of randomised participants. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
DISC Study 2011 Some concerns Randomisation was performed using random software sequence in excel. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the ITT principles. Some concerns Outcome data available for 57.9% of children that were randomised. Analytical methods to correct for bias were not performed. Posspible that missingness could depend on its true value but missing data balanced across the two groups with similar reasons. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Garcia‐del Valle 2021 Some concerns There was no information on method of randomisation, there was no baseline imbalance that would suggest a problem with randomisation. Low risk of bias Both participants and those delivering the intervention were unaware of intervention received. There were no deviations from intended interventions and the analysis was appropriate. Some concerns Outcome data available for 82% of children that were randomised. Analytical methods to correct for bias were not performed. It is possible that misssingness could depend on its true value but missingness balanced across the two groups with similar reasons. Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were blined to the group allocation of patients.  Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Ruiz‐Pomeda 2018 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the children or carers given the nature of the interventions. Results analysed using ITT principles  Low risk of bias Outcome data were available for nearly all randomized participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Sankaridurg 2019 Some concerns Permuted block randomisation with online software for sequence generation. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Some concerns Data was available for 61.4% of participants at 1 year and 46% at 2 years. No analysis performed to correct for bias due to missing data.  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 4.2.2 At 2 years
BLINK Study 2020 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Low risk of bias Outcome data were available for nearly all participants (97.5%).  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Low risk of bias Protocol registered, with a pre published protocol and statistical plan. Low risk of bias The study is judged to be at low risk of bias in all domains.
Chamberlain 2019 Some concerns Contract organisation used a a random number ‐ generating computer program. Investigators had access to randomisation codes. No statistically significant differences between the experimental and control groups. Low risk of bias Participants and their parents were masked. Modified ITT analysis. Low risk of bias Outcome data available for 75% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate and comparable methods of outcome measurement. Outcome assessors masked to intervention received. Low risk of bias Prospective registration. Data analysed according to a pre‐specified analysis plan. Reported outcomes and data analysis pre‐specified. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
DISC Study 2011 Some concerns Randomisation was performed using random software sequence in excel. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the ITT principles. Some concerns Outcome data available for 57.9% of children that were randomised. Analytical methods to correct for bias were not performed. Posspible that missingness could depend on its true value but missing data balanced across the two groups with similar reasons. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Ruiz‐Pomeda 2018 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the children or carers given the nature of the interventions. Results analysed using ITT principles  Low risk of bias Outcome data were available for nearly all randomized participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Sankaridurg 2019 Some concerns Permuted block randomisation with online software for sequence generation. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Some concerns Data was available for 61.4% of participants at 1 year and 46% at 2 years. No analysis performed to correct for bias due to missing data.  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 4.2.3 At 3 years
BLINK Study 2020 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on ITT principles. Low risk of bias Outcome data were available for nearly all participants (97.5%).  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Low risk of bias Protocol registered, with a pre published protocol and statistical plan. Low risk of bias The study is judged to be at low risk of bias in all domains.
Chamberlain 2019 Some concerns Contract organisation used a a random number ‐ generating computer program. Investigators had access to randomisation codes. No statistically significant differences between the experimental and control groups. Low risk of bias Participants and their parents were masked. Modified ITT analysis. Low risk of bias Outcome data available for 75% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate and comparable methods of outcome measurement. Outcome assessors masked to intervention received. Low risk of bias Prospective registration. Data analysed according to a pre‐specified analysis plan. Reported outcomes and data analysis pre‐specified. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Only two studies evaluated progression of myopia following RGP wear. We judged one study at high risk (Katz 2003). We therefore gave an overall judgement of 'high risk' for this outcome (see Table 199Table 200).

Risk of bias for analysis 5.1 Change in refractive error from baseline.

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 5.1.1 At 1 year
CLAMP Study 2004 Some concerns Randomisation was performed using stratification and block allocation. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. No information on deviation from intended outcomes. Data were analysed using ITT methods. Low risk of bias Data available for approx 97% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns The outcome measurements were taken in accordance with the clinical trials registry record. No statistical analysis plan (SAP) was reported.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Katz 2003 Some concerns Randomisation was performed using the permuted block method. Allocation concealment using sealed envelopes. Baseline differences were identified between groups.  Low risk of bias Neither patients nor clinical observers were masked to treatment group. There were no deviations from intended interventions and the analysis was appropriate. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns No pre‐registered method (registry or protocol) available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Subgroup 5.1.2 At 2 years
CLAMP Study 2004 Some concerns Randomisation was performed using stratification and block allocation. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. No information on deviation from intended outcomes. Data were analysed using ITT methods. Low risk of bias Data available for approx 97% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns The outcome measurements were taken in accordance with the clinical trials registry record. No statistical analysis plan (SAP) was reported.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Katz 2003 Some concerns Randomisation was performed using the permuted block method. Allocation concealment using sealed envelopes. Baseline differences were identified between groups.  Low risk of bias Neither patients nor clinical observers were masked to treatment group. There were no deviations from intended interventions and the analysis was appropriate. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns No pre‐registered method (registry or protocol) available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Subgroup 5.1.3 At 3 years
CLAMP Study 2004 Some concerns Randomisation was performed using stratification and block allocation. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. No information on deviation from intended outcomes. Data were analysed using ITT methods. Low risk of bias Data available for approx 97% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns The outcome measurements were taken in accordance with the clinical trials registry record. No statistical analysis plan (SAP) was reported.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Risk of bias for analysis 5.2 Change in axial length from baseline.

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 5.2.1 At 1 year
CLAMP Study 2004 Some concerns Randomisation was performed using stratification and block allocation. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. No information on deviation from intended outcomes. Data were analysed using ITT methods. Low risk of bias Data available for approx 97% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns The outcome measurements were taken in accordance with the clinical trials registry record. No statistical analysis plan (SAP) was reported.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Katz 2003 Some concerns Randomisation was performed using the permuted block method. Allocation concealment using sealed envelopes. Baseline differences were identified between groups.  Low risk of bias Neither patients nor clinical observers were masked to treatment group. There were no deviations from intended interventions and the analysis was appropriate. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns No pre‐registered method (registry or protocol) available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Subgroup 5.2.2 At 2 years
CLAMP Study 2004 Some concerns Randomisation was performed using stratification and block allocation. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. No information on deviation from intended outcomes. Data were analysed using ITT methods. Low risk of bias Data available for approx 97% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns The outcome measurements were taken in accordance with the clinical trials registry record. No statistical analysis plan (SAP) was reported.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Katz 2003 Some concerns Randomisation was performed using the permuted block method. Allocation concealment using sealed envelopes. Baseline differences were identified between groups.  Low risk of bias Neither patients nor clinical observers were masked to treatment group. There were no deviations from intended interventions and the analysis was appropriate. High risk of bias Outcome data were not available for all, or nearly all, randomized participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns No pre‐registered method (registry or protocol) available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Subgroup 5.2.3 At 3 years
CLAMP Study 2004 Some concerns Randomisation was performed using stratification and block allocation. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. No information on deviation from intended outcomes. Data were analysed using ITT methods. Low risk of bias Data available for approx 97% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns The outcome measurements were taken in accordance with the clinical trials registry record. No statistical analysis plan (SAP) was reported.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

We judged four of the seven studies reporting change in axial length from baseline after wearing orthokeratology lenses as 'some concerns' (Analysis 1.2). We judged three studies at high risk of bias (Lyu 2020Ren 2017ROMIO Study 2012). We gave an overall judgement of 'some concerns' for this outcome (see Table 201).

Risk of bias for analysis 6.1 Change in axial length from baseline.

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 6.1.1 At 1 year
Bian 2020 Some concerns Randomisation was performed using a random number table. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Masking of investigators is not reported. No information on deviation from intended outcomes and appropriate analyses were conducted. Low risk of bias Outcome data were available for all randomized participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns No trial registry record or protocol available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Jakobsen 2022 Low risk of bias Randomisation was performed by a computer‐generated allocation sequence. Allocation concealment using sealed envelopes. There were no baseline imbalance that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the children or carers given the nature of the interventions. A greater number of dropouts in the intervention group mostly due to lack of motivation that could have happened outside the trial context. Analysis using ITT principles.  Low risk of bias Data available for 63% of participants in the intervention group and 93% of those in the control group. Statistical analysis performed to adjust for baseline differences in outcomes. Missingness occurred for documented reasons that were unrelated to the outcome. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. No information was available on masking of outcome assessors.Outcomes were measured objectively. Some concerns Trial registry entry available, not analysis protocol. Outcomes included as pre‐specified. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Lyu 2020 Some concerns Random group allocation though details not specified. No information on allocation concealment. No statistically significant baseline imbalances that would suggest a problem with randomisation. High risk of bias It was not possible to mask the children or carers given the nature of the interventions. Non‐compliant participants were excluded. Low risk of bias Reasons for exclusion stated but missing outcome data not available. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation. Some concerns No pre‐registered method (registry or protocol) available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Ren 2017 Some concerns Participants were randomised though no details of method of randomisation are recorded. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Masking of the investigator is not reported. No information on deviation from intended outcomes and appropriate analysis were conducted. Low risk of bias Data available for all participants. Some concerns No information about the methods of measuring the outcome or masking of the assessors were reported. Some concerns No registry record or protocol available.  High risk of bias The study is judged as some concerns in four out of five domains for this result. We therefore judged that the study was at an overall high risk of bias.
ROMIO Study 2012 High risk of bias Randomisation was performed using commercial spreadsheet random number generator. Random allocation sequence was revealed to the unmasked examiner after eligibility of subjects was confirmed. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants, carers or investigating clinicians given the nature of the interventions. There were no deviations from intended interventions. Results were not analysed using ITT principles, although unlikely to have substantial impact. High risk of bias Outcome data were not available for all, or nearly all, randomised participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Tang 2021 Some concerns Participants were randomised though no details of method of randomisation are recorded. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Masking of the investigator is not reported. No information was provided about masking investigators. No information on deviation from intended outcomes and appropriate analysis were conducted. Low risk of bias Outcome data available for 93.3% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors may have been aware of the group allocation, but bias is minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns No registry record or protocol available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Zhang 2021 Low risk of bias Randomisation was performed by sealed envelopes, with a computer‐generated allocation sequence. There were no baseline imbalance that would suggest a problem with randomisation. Low risk of bias Participants and their parents were masked. Analysis using ITT principles. Low risk of bias Outcome data were available for nearly all participants.  Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 6.1.2 At 2 years
Charm 2013 Some concerns Randomisation was performed using commercial spreadsheet random number generator. Method for allocation concealment unclear. There were no baseline imbalances that would suggest a problem with randomisation. High risk of bias Participants, carers and examiners were not masked to assigned intervention. Participants in the control group explored other myopia control interventions. ITT analysis aas not conducted. Some concerns Outcome data available for 53.8% of children that were randomised. Analytical methods to correct for bias were not performed. It is possible that misssingness could depend on its true value but missingness balanced across the two groups with similar reasons. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
ROMIO Study 2012 High risk of bias Randomisation was performed using commercial spreadsheet random number generator. Random allocation sequence was revealed to the unmasked examiner after eligibility of subjects was confirmed. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants, carers or investigating clinicians given the nature of the interventions. There were no deviations from intended interventions. Results were not analysed using ITT principles, although unlikely to have substantial impact. High risk of bias Outcome data were not available for all, or nearly all, randomised participants, and there is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation, but bias was minimised by using objective measurements. Therefore, it is unlikely that the outcome was influenced by knowledge of the intervention received.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.

For progression of myopia in the comparison 'anti‐muscarinics versus control', we assumed an overall risk of bias of 'some concerns' for studies using different doses of atropine, as we judged the majority of the studies reporting the outcome as 'some concerns'. However, we judged both of the studies reporting on 2% pirenzepine to be at high risk of bias (PIR‐205 Study 2004Tan 2005), which gave an overall judgement of 'high risk' for this outcome (see Table 202Table 204Table 203Table 205).

Risk of bias for analysis 7.1 Change in refractive error from baseline (1 year).

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 7.1.1 Atropine (high dose)
ATOM Study 2006 Low risk of bias Randomisation was performed using a computer generated randomisation list. It is unclear how allocation concelment was conducted. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. Low risk of bias Outcome data available for 86.5% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns No protocol and statistical analysis plan are available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Yi 2015 Some concerns Participants were randomised though no details of method of randomisation are recorded. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the ITT principles. Low risk of bias Data available for approx 95% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No registry record or protocol available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Zhu 2021 Low risk of bias Computer generated random sequence with allocation. No statistically significant baseline imbalances that would suggest a problem with randomisation. Some concerns No information on masking participants or parents. Results analysed using ITT principles. High risk of bias Data was available for 86.4% of participants.  Reasons for missingness not documented and imbalance in missing data between intervention and control. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. No information was available on masking of outcome assessors. Some concerns No registry record or protocol available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Subgroup 7.1.2 Atropine eyedrops (low dose)
Hieda 2021 Low risk of bias Permuted block method. The allocation table was generated and maintained by a contracted professional research organization There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to drug assignment until after study completion. Data analysed based on ITT principles. Low risk of bias 91.7% completion rate of intervention group and 96.4% for control group. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
LAMP Study 2019 Some concerns There was no information on the method of randomisation. No details of method of allocation concealment. There were no significant differences in the baseline parameters that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on Intention to Treat principles. Low risk of bias Data was available for approx 87% of participants in each intervention group. No analysis performed to correct for bias due to missing data. But proportions of missing outcome data were reasonably well balanced across the arms of the trial and reasons for missingness were clearly documented. Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were blinded to the group allocation of patients.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Ren 2017 Some concerns Participants were randomised though no details of method of randomisation are recorded. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the participants due to functional differences in interventions being studied. Masking of the investigator is not reported. . No information on deviation from intended outcomes and appropriate analysis were conducted. Low risk of bias Data available for all participants. Some concerns No information about the methods of measuring the outcome or masking of the assessors were reported. Some concerns No registry record or protocol available.  High risk of bias The study is judged as some concerns in four out of five domains for this result. We therefore judged that the study was at an overall high risk of bias.
Wei 2020 Some concerns Randomisation with online software for sequence generation by third person. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants and their parents were masked. Analysis using ITT principles. Some concerns Data was available for 69% of participants in the intervention group and 75% in the placebo group. Reasons for missingness well documented and balanced across arms. No analysis performed to correct for bias due to missing data.  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Low risk of bias Protocol registered, with a pre published protocol and statistical plan. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 7.1.3 Pirenzepine 2% gel
PIR‐205 Study 2004 Some concerns Randomisation was performed using a computer generated sequence. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. High risk of bias 22% of data missing from intervention group compared to 5% of control group. Reasons for missingness provided but missingness likely to depend on its true value. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No registry record or protocol available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Tan 2005 Low risk of bias Randomisation was performed using computer generated sequence. Allocation concealment was maintained until after enrollment and participants assigned. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. High risk of bias 18% of data missing from intervention group compared to 13% of control group. Reasons for missingness provided but missingness in outcome probably depends on its true value. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns No registry record or protocol available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.

Risk of bias for analysis 7.3 Change in refractive error from baseline (2 years).

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 7.3.1 Atropine eyedrops (high dose)
ATOM Study 2006 Low risk of bias Randomisation was performed using a computer generated randomisation list. It is unclear how allocation concelment was conducted. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. Low risk of bias Outcome data available for 86.5% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Zhu 2021 Low risk of bias Computer generated random sequence with allocation. No statistically significant baseline imbalances that would suggest a problem with randomisation. Some concerns No information on masking participants or parents. Results analysed using ITT principles. High risk of bias Data was available for 86.4% of participants. Reasons for missingness not documented and imbalance in missing data between intervention and control. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. No information was available on masking of outcome assessors. Some concerns No registry record or protocol available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Subgroup 7.3.2 Atropine eyedrops (low dose)
Hieda 2021 Low risk of bias Permuted block method. The allocation table was generated and maintained by a contracted professional research organization There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to drug assignment until after study completion. Data analysed based on Intention to Treat principles. Low risk of bias 91.7% completion rate of intervention group and 96.4% for control group. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Moriche‐Carretero 2021 Some concerns Randomisation using online software for sequence generation. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the children or carers given the nature of the interventions. Non compliant participants were excluded but unlikely to have substantial effect on outcome. Low risk of bias 95% completion rate of intervention group and 98% for control group. Reasons for missingness documented. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation. Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 7.3.3 Pirenzepine eyedrops 2% gel
PIR‐205 Study 2004 Some concerns Randomisation was performed using a computer generated sequence. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. High risk of bias Approx 40% of those randomised to the intervention provided data at 2 years. Reasons for missingness provided but missingness likely to depend on its true value. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No registry record or protocol available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.

Risk of bias for analysis 7.2 Change in axial length from baseline (1 year).

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 7.2.1 Atropine eyedrops (high dose)
ATOM Study 2006 Low risk of bias Randomisation was performed using a computer generated randomisation list. It is unclear how allocation concelment was conducted. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. Low risk of bias Outcome data available for 86.5% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Yi 2015 Some concerns Participants were randomised though no details of method of randomisation are recorded. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Investigator providing clinical care and obtaining measurements were masked to group allocation. There were no deviations from intended interventions. Analysis were performed on the ITT principles. Low risk of bias Data available for approx 95% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No registry record or protocol available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Zhu 2021 Low risk of bias Computer generated random sequence with allocation. No statistically significant baseline imbalances that would suggest a problem with randomisation. Some concerns No information on masking participants or parents. Results analysed using ITT principles. High risk of bias Data was available for 86.4% of participants. Reasons for missingness not documented and imbalance in missing data between intervention and control. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. No information was available on masking of outcome assessors. Some concerns No registry record or protocol available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Subgroup 7.2.2 Atropine eyedrops (low dose)
Hieda 2021 Low risk of bias Permuted block method. The allocation table was generated and maintained by a contracted professional research organization There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to drug assignment until after study completion. Data analysed based on ITT principles. Low risk of bias 91.7% completion rate of intervention group and 96.4% for control group. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
LAMP Study 2019 Some concerns There was no information on the method of randomisation. No details of method of allocation concealment. There were no significant differences in the baseline parameters that would suggest a problem with randomisation. Low risk of bias Everyone masked to group assignment until after study completion. Data analysed based on Intention to Treat principles. Low risk of bias Data was available for approx 87% of participants in each intervention group. No analysis performed to correct for bias due to missing data. But proportions of missing outcome data were reasonably well balanced across the arms of the trial and reasons for missingness were clearly documented. Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were blinded to the group allocation of patients.  Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Ren 2017 Some concerns Participants were randomised though no details of method of randomisation are recorded. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the participants due to functional differences in interventions being studied. Masking of the investigator is not reported. No information on deviation from intended outcomes and appropriate analysis were conducted. Low risk of bias Data available for all participants. Some concerns No information about the methods of measuring the outcome or masking of the assessors were reported. Some concerns No registry record or protocol available.  High risk of bias The study is judged as some concerns in four out of five domains for this result. We therefore judged that the study was at an overall high risk of bias.
Wei 2020 Some concerns Randomisation with online software for sequence generation by third person. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants and their parents were masked. Analysis using ITT principles. Some concerns Data was available for 69% of participants in the intervention group and 75% in the placebo group. Reasons for missingness well documented and balanced across arms. No analysis performed to correct for bias due to missing data.  Low risk of bias Methods of outcome measurement were appropriate and comparable. The team were masked to the group allocation of patients.  Low risk of bias Protocol registered, with a pre published protocol and statistical plan. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Subgroup 7.2.3 Pirenzepine 2% gel
PIR‐205 Study 2004 Some concerns Randomisation was performed using a computer generated sequence. There was no information relating to allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. High risk of bias 22% of data missing from intervention group compared to 5% of control group. Reasons for missingness provided but missingness likely to depend on its true value. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns No registry record or protocol available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Tan 2005 Low risk of bias Randomisation was performed using computer generated sequence. Allocation concealment was maintained until after enrollment and participants assigned. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. High risk of bias 18% of data missing from intervention group compared to 13% of control group. Reasons for missingness provided but missingness in outcome probably depends on its true value. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No registry record or protocol available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.

Risk of bias for analysis 7.4 Change in axial length from baseline (2 years).

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 7.4.1 Atropine eyedrops (high dose)
ATOM Study 2006 Low risk of bias Randomisation was performed using a computer generated randomisation list. It is unclear how allocation concelment was conducted. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. Low risk of bias Outcome data available for 86.5% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns No pre‐registered method (registry or protocol) available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Zhu 2021 Low risk of bias Computer generated random sequence with allocation. No statistically significant baseline imbalances that would suggest a problem with randomisation. Some concerns No information on masking participants or parents. Results analysed using ITT principles. High risk of bias Data was available for 86.4% of participants. There is no evidence that the result was not biased by missing outcome data, and no information on whether missingness in the outcome could depend on its true value. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. No information was available on masking of outcome assessors. Some concerns No registry record or protocol available.  High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.
Subgroup 7.4.2 Atropine eyedrops (low dose)
Hieda 2021 Low risk of bias Permuted block method. The allocation table was generated and maintained by a contracted professional research organization There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Everyone masked to drug assignment until after study completion. Data analysed based on ITT principles. Low risk of bias 91.7% completion rate of intervention group and 96.4% for control group. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Moriche‐Carretero 2021 Some concerns Randomisation using online software for sequence generation. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the children or carers given the nature of the interventions. Non compliant participants were excluded but unlikely would have substantial effect on outcome. Low risk of bias 95% completion rate of intervention group and 98% for control group. Reasons for missingness documented. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Outcome assessors are likely to have been aware of the group allocation. Some concerns No registry record or protocol available.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

For the outcome 'change in refractive error and axial length following cessation of treatment', three of the four included studies had some concerns and one was at high risk of bias (Zhu 2021; see Analysis 2.3Analysis 4.3Analysis 4.4Analysis 7.5Analysis 7.6).

4.3. Analysis.

4.3

Comparison 4: Multifocal soft contact lenses vs single vision soft contact lenses, Outcome 3: Change in refractive error following cessation of treatment (1 year)

4.4. Analysis.

4.4

Comparison 4: Multifocal soft contact lenses vs single vision soft contact lenses, Outcome 4: Change in axial length following cessation of treatment (1 year)

7.6. Analysis.

7.6

Comparison 7: Anti‐muscarinics vs placebo, Outcome 6: Change in axial length following cessation of treatment (1 year)

Detailed risk of bias assessments are available at: osf.io/ms83h/

Effects of interventions

See: Table 1; Table 2; Table 3; Table 4

See summary of findings tables for overall treatment effects for any myopia control intervention on progression of myopia compared to placebo. The certainty of the evidence is also provided and if appropriate, the reasons for downgrading (Table 1Table 2Table 3Table 4).

We performed standard pairwise and network meta‐analyses for optical and pharmacological interventions compared to a control group (consisting of either standard SVLs or contact lenses or a placebo) for the critical outcome 'progression of myopia'. We also compared myopia control interventions to each other. In total, we included 52 studies, analysing 8152 participants, in either the standard or network meta‐analysis. 

Twelve studies did not contribute directly to the quantitative synthesis (Cheng 2016Fulk 1996Houston Study 1987Han 2018Han 2019Hasebe 2008Lu 2015Schwartz 1981Shih 1999Swarbrick 2015Wang 2017Yen 1989). For these studies, we reported study‐specific results, as appropriate.

Quantitative synthesis was not possible for the outcomes 'risk of adverse events', 'quality of life', or 'treatment adherence' due to insufficient available data. For these outcomes we provided a descriptive summary of the range and distribution of the observed effects, and summarised the study‐level findings in structured tables.

Critical outcomes

Progression of myopia
Myopia control intervention versus control
Pairwise meta‐analysis results

Direct treatment estimates from pairwise meta‐analysis for optical and pharmacological interventions versus control/placebo are reported in Analysis 1.1Analysis 1.2Analysis 2.1Analysis 2.2Analysis 3.1Analysis 3.2Analysis 4.1Analysis 4.2Analysis 5.1 Analysis 6.1Analysis 7.1Analysis 7.3Analysis 7.2Analysis 7.4Analysis 8.1Analysis 8.2). We assessed progression of myopia as mean change in refractive error (defined as SER) from baseline for each year of follow‐up or change in axial length from baseline, or both. To facilitate interpretation of the forest plots, negative mean differences (MDs) for changes in refractive error represent faster progression of myopia in the intervention group compared to progression in the control group. Thus, point estimates to the left of the null on the forest plots favour the control group. For the measurement of changes in axial length, negative MDs for changes in axial length represent faster axial elongation in the control group compared to the intervention group, and therefore estimates to the left of the null favour the intervention group.

  • Optical interventions: spectacles

    • Spectacle interventions designed to reduce accommodative demand and lag during near work by undercorrection, or the use of MFSLs have been common in practice for many years. Three studies, involving 292 participants, compared spectacles that were undercorrected by −0.50 D to −0.75 D to fully corrected SVLs (Analysis 1.1Analysis 1.2). There was no evidence that undercorrection slowed myopic progression, based either on change in refractive error (MD at 1 year −0.15 D (95% CI −0.29 to 0.00); MD at 2 years 0.02 D (95% CI −0.05 to 0.09)) or change in axial length (MD at 1 year 0.05 mm (95% CI −0.01 to 0.11); MD at 2 years −0.01 mm (95% CI −0.06 to 0.03)).

    • Thirteen studies compared bifocal or progressive addition lenses to SVLs. We included 10 studies with 1612 participants in a quantitative synthesis (Analysis 2.1Analysis 2.2). Eight studies provided data up to two years and four studies followed participants for up to three years (Cheng 2010COMET Study 2003COMET2 Study 2011Pärssinen 1989). There was a small reduction in myopia progression at both one‐ and two‐year follow‐up (change in refractive error at 1 year, MD 0.14 D, 95% CI 0.08 to 0.21; and at 2 years, MD 0.19 D, 95% CI 0.08 to 0.30). The three‐year results showed considerable heterogeneity (I2 = 86%), however after removing two studies judged to be at high risk of bias (Cheng 2010Pärssinen 1989), heterogeneity was substantially reduced (I2 = 0%). The pooled three‐year MD after removing these studies was 0.21 D (95% CI 0.08 to 0.34). The three studies not included in the meta‐analysis reported inconsistent results (Fulk 1996Hasebe 2008Houston Study 1987). Hasebe 2008 reported significantly less myopia progression in children wearing progressive addition lenses over the first 18 months of a cross‐over study compared to children wearing SVLs, but no difference in the second 18‐month period. In another 18‐month study (Fulk 1996), children wearing bifocals progressed at a rate of −0.39 D per year compared to −0.57 D per year in the SVL group, however these differences were not significant (P = 0.26). The Houston Study 1987 found no significant difference between groups wearing bifocals (+1.00 D and +2.00 D add) and SVLs. We included four studies with 896 participants that reported change in axial length with progressive addition lenses in a quantitative analysis (Analysis 2.2). There was a small reduction in axial elongation in progressive addition lens wearers for each year of follow‐up (1‐year MD −0.06 mm, 95% CI −0.09 to −0.04; 2‐year MD −0.07 mm, 95% CI −0.12 to −0.03; 3‐year MD −0.12 mm, 95% CI −0.18 to −0.07).

    • The rationale for prescribing peripheral plus spectacle lenses (PPSL) is to reduce hyperopic defocus in the peripheral retina. Six studies compared PPSL to SVLs (Bao 2021Han 2018Hasebe 2014Lam 2020Lu 2015Sankaridurg 2010). Changes in refractive error from baseline showed considerable heterogeneity (I2 = 89% to 91%; Analysis 3.1). Mean differences at one year ranged from 0.02 D to 0.97 D. Only two studies followed children for two years (Hasebe 2014Lam 2020). These studies showed contrasting results. Hasebe 2014 found no difference in myopia progression with positively aspherised progressive addition lenses (MD 0.12 D, 95% CI −0.06 to 0.31). In contrast, Lam 2020 found a significant reduction in progression using the Defocus Incorporated Multiple Segments (DIMS) spectacle lens (MD 0.55 D, 95% CI 0.38 to 0.72). Four studies provided data on changes in axial length from baseline, showing similarly high heterogeneity (Analysis 3.2). The combination of all three novel lenses tested by Sankaridurg 2010 were not significantly different from SVLs at one year (MD −0.02 mm, 95% CI −0.08 to 0.04), contrasting with designs used by Lam 2020 and Bao 2021, which showed less axial elongation. Only two studies provided two‐year data for axial length. Hasebe 2014 reported no significant difference (MD −0.07mm, 95% CI −0.20 to 0.07), whereas Lam 2020 showed that the reduced axial elongation demonstrated at one year, continued into the second year (−0.32 mm, 95% CI −0.39 to −0.25).

  • Optical interventions: contact lenses

    • Studies tested a variety of contact lens design, including multifocal soft contact lenses (MFSCL), positive spherical aberration contact lenses, rigid gas‐permeable (RGP) and orthokeratology lenses. Conceptually, MFSCL use a progressive or concentric ring design to create myopic defocus and reduce myopia progression. Nine studies, compared MFSCL to single vision soft contact lenses (SVSCL). We excluded Fujikado 2014 from the quantitative analysis since it used a lens design that was distinct from the other lenses in the comparison. Consequently, we included eight studies with a total of 1135 participants in a quantitative synthesis (Analysis 4.1Analysis 4.2). Five studies provided data on change in refractive error and axial length up to two years and two studies followed children for up to three years (BLINK Study 2020Chamberlain 2019). Over the three‐year reporting period, there was a progressive reduction in myopia progression with MFSCL compared to SVCL, although there was a suggestion that the change in refractive error reduced over time (1‐year MD 0.26 D, 95% CI 0.17 to 0.35; 2‐year MD 0.30 D, 95% CI 0.19 to 0.41; 3‐year MD 0.47 D, 95% CI 0.13 to 0.82). A significant reduction in axial elongation was seen across all three years (1‐year MD −0.11 mm, 95% CI −0.13 to −0.09; 2‐year MD −0.15 mm, 95% CI −0.19 to −0.12; 3‐year MD −0.22 mm, 95% CI −0.34 to −0.10).

    • Cheng 2016 investigated the effect of soft contact lenses with positive spherical aberration. The mean reported change in refractive error in this study was 0.137 D (95% CI −0.007 to 0.281) amongst 52 children in the spherical aberration group compared with 57 children in the single vision contact lens group at one‐year follow‐up. In terms of axial elongation, children in the positive spherical aberration group showed 0.143 mm (95% CI −0.188 to −0.098) less elongation compared with the control at one year.

    • Two studies investigated the use of rigid gas‐permeable contact lenses (RGPs) in slowing the progression of myopia compared to single vision contact lenses in one study (CLAMP Study 2004), and SVLs in the other (Katz 2003) (Analysis 5.1Analysis 5.2). The CLAMP Study 2004 followed up participants for three years and Katz 2003 followed up participants for two years. We did not pool data on change in refractive error due to considerable heterogeneity (I2 > 90%). The two studies reported contrasting results, with the CLAMP Study 2004 showing significantly less myopia progression over three years with the RGPs compared to participants wearing single vision contact lenses (1‐year MD 0.40 D, 95% CI 0.19 to 0.61; 2‐year MD 0.54 D, 95% CI 0.27 to 0.81; 3‐year MD 0.63 D, 95% CI 0.30 to 0.96). By contrast, Katz 2003 observed no difference in myopia progression over two years (1‐year MD −0.02, 95% CI −0.14 to 0.10; 2‐year MD −0.05 D, 95% CI −0.25 to 0.15). Neither study was able to show any effect on axial elongation over three years (pooled estimate 1‐year MD 0.02 mm, 95% CI −0.05 to 0.10; 2‐year MD 0.03 mm, 95% CI −0.05 to 0.12; 3‐year MD 0.05 mm, 95% CI −0.12 to 0.22).

    • Eight studies, involving 787 participants, compared orthokeratology lenses to SVLs or SVSCLs and provided data up to two years (Analysis 6.1). Overnight wear of orthokeratology lenses flattens the central cornea and temporarily reduces refractive error. Since it is not possible to assess the true progression of refractive error without ceasing lens wear for a period of time to allow the cornea to return to its pre‐treatment state, the included studies presented change in axial length as the primary efficacy outcome. A significant reduction in axial elongation was seen across both years (1‐year MD −0.19 mm, 95% CI −0.23 to −0.15; 2‐year MD −0.28 mm, 95% CI −0.38 to −0.19).

  • Pharmacological interventions: antimuscarinics

    • Atropine: 11 studies compared topical atropine to control (placebo, no treatment or SVLs). These were grouped according to dosing regime into high dose (≥ 0.1%) or low dose (< 0.1%). The majority of studies testing atropine reported data at one year, with only four studies (ATOM Study 2006Hieda 2021Moriche‐Carretero 2021Zhu 2021) reporting at two years.  

    • Several studies tested atropine as a co‐intervention or in head‐to‐head dose comparisons and these are described below.

      • High‐dose atropine: three studies (1072 participants) compared high‐dose atropine (1%) to control (ATOM Study 2006Yi 2015Zhu 2021). At one year, effect sizes for change in refractive error ranged from MD 0.79 D to 1.1 7 D in favour of high‐dose atropine Analysis 7.1. A reduction in axial elongation was also seen with 1% atropine at one year (MD −0.31 to −0.35 mm; Analysis 7.2). Studies reporting at two years similarly showed that high‐dose atropine had greater efficacy. The ATOM Study 2006 showed a change in refractive error of MD 0.92 D (95% CI 0.75 to 1.09); and change in axial length of MD −0.40 mm (95% CI −0.48 to −0.32). Zhu 2021 showed a change in refractive error of MD 1.41 D (95% CI 1.30 to 1.52) and change in axial length of MD −0.54 mm (95% CI −0.57 to −0.51) (Analysis 7.3Analysis 7.4). Two studies, not included in the meta‐analysis, also investigated 1% atropine versus placebo and reported significantly less myopia progression in children in the atropine group at the end of the follow‐up period, however the data were not presented in a form that could be included in the meta‐analysis (Han 2019Wang 2017). We also excluded Yen 1989 and MIT Study 2001 since the atropine groups also wore MFSL.

      • Low‐dose atropine: five studies (1143 participants) compared lower atropine doses (0.01% to 0.05%) to control (Hieda 2021LAMP Study 2019Moriche‐Carretero 2021Ren 2017Wei 2020). Results for these comparisons for each year of follow‐up showed considerable heterogeneity (I2 > 90%), however all effects were in the same direction, and we included subgroup summary effect estimates in the forest plots as the best estimate of the intervention effect. At one year, effect sizes for change in refractive error were in the range 0.08 D to 0.80 D, and change in axial length ranged from −0.04 mm to −0.35 mm in favour of low‐dose atropine (Analysis 7.1Analysis 7.2). Studies reporting at two years similarly showed a greater efficacy for low‐dose atropine (Hieda 2021 change in refractive error MD 0.22 D, 95% CI 0.09 to 0.35; change in axial length −0.14 mm, 95% CI −0.20 to −0.08; Moriche‐Carretero 2021, change in refractive error MD 0.25 D, 95% CI 0.17 to 0.33; change in axial length −0.17 mm, 95% CI −0.22 to −0.12) in favour of atropine (Analysis 7.3Analysis 7.4).

    • Pirenzepine: two studies investigated 2% pirenzepine eyedrops (PIR‐205 Study 2004Tan 2005; see Analysis 7.1Analysis 7.2 Analysis 7.3). At one‐year follow‐up, average myopia progression was less for participants treated with pirenzepine compared to placebo (PIR‐205 Study 2004 MD 0.27 D, 95% CI 0.11 to 0.43; Tan 2005 MD 0.47 D, 95% CI 0.16 to 0.78). The difference in progression between groups continued at two years (PIR‐205 Study 2004 MD 0.41 D, 95% CI 0.13 to 0.69). Data for axial length were only available at one year. Tan 2005 found a slowing of axial elongation (MD −0.13 mm, 95% CI −0.14 to −0.12), whereas the PIR‐205 Study 2004 found no significant difference in axial length (MD −0.04 mm, 95% CI −0.15 to 0.07).

  • Other pharmacological interventions

    • One arm of Jensen 1991 investigated the non‐selective beta‐antagonist timolol maleate compared to a SVL control. The differences in myopia progression were not significant at one year (MD −0.05 D, 95% CI −0.21 to 0.11) or at two years (MD −0.04 D, 95% CI −0.30 to 0.22). This study did not measure axial length.

    • Trier 2008 compared systemic 7‐methylxanthine, an oral adenosine receptor antagonist, versus a placebo tablet for one year. At one‐year follow‐up, the differences in myopia progression were not significant (change in refractive error MD 0.07 D, 95% CI −0.09 to 0.24; change in axial length MD −0.03 mm, 95% CI −0.10 to 0.03; Analysis 8.1Analysis 8.2).

Network meta‐analysis results

We conducted NMAs for change in SER and axial length at 12 and 24 months. See Figure 2 for the network maps for each comparison, and Table 5 presenting the number of study arms (participants) for each intervention. Direct comparisons between interventions were limited to different doses of atropine, meaning that only indirect comparisons were possible. League‐tables presenting all indirect and mixed comparisons for SER and axial length at 12 and 24 months can be seen at https://osf.io/ms83h/Figure 3 presents forest plots of NMA comparisons with control.

2.

2

Network maps for change in spherical equivalent and change in axial length at 1 and 2 years 

7MX: 7‐methylxanthine; HDA: high‐dose atropine, LDA: low‐dose atropine; MDA: moderate‐dose atropine; MFSCL: multifocal soft contact lenses; MFSL: multifocal spectacle lenses; ORTHOK: orthokeratology; PIR: pirenzipine; PPSL: peripheral plus spectacle lenses ; RGP: rigid gas‐permeable contact lenses; UCSVL: undercorrected single vision spectacles

1. Number of trial arms and participants for each intervention and outcome in all NMAs.
  Outcome
Spherical equivalent at 1 year  
Number of treatment arms (participants)
Spherical equivalent at 2 years 
Number of treatment arms (participants)
Axial length at 1 year 
Number of treatment arms (participants)
Axial length at 2 years 
Number of treatment arms (participants)
Treatment arm        
Control 35
(2459)
22
(1899)
33
(2319)
20
(1730)
High‐dose atropine 3
(411)
3
(346)
3
(411)
2
(305)
Moderate‐dose atropine 1
(155)
2
(237)
1
(155)
1
(141)
Low‐dose atropine 5
(581)
3
(324)
5
(581)
3
(324)
Pirenzipine 2
(210)
1
(53)
2
(210)
1
(53)
7‐methylxanthine 1
(35)
1
(35)
Orthokeratology 5
(234)
2
(49)
Multiifocal soft contact lenses 9
(723)
5
(540)
9
(723)
5
(540)
Peripheral plus spectacle lenses 2
(188)
3
(340)
2
(188)
Rigid gas‐permeable contact lenses 2
(176)
2
(154)
2
(176)
2
(154)
Multifocal spectacle lenses 4
(445)
7
(622)
4
(445)
3
(404)
Undercorrected single vision spectacles 1
(47)
2
(122)
1
(47)
2
(122)
3.

3

Estimates of effect from network meta‐analyses for all treatments versus control for progression of myopia (based on spherical equivalent and axial length) at 1 and 2 years. Comparisons with control are less precise than direct meta‐analyses due to the lack of directly comparative evidence.

7MX: 7‐methylxanthine; HDA: high‐dose atropine; LDA: low‐dose atropine; MDA: moderate‐dose atropine; MFSCL: multifocal soft contact lenses; MFSL: multifocal spectacle lenses ; ORTHOK: orthokeratology; PIR: pirenzipine;PPSL: peripheral plus spectacle lenses; RGP: rigid gas‐permeable contact lenses; UCSVL: undercorrected single vision spectacles

  • Change in SER at 1‐year

    • The NMA included 30 studies (4694 participants) with two connected closed loops comparing different doses of atropine or control. There was no overall inconsistency (p=0.185). The only two closed loops were partly overlapping and showed no inconsistency.

    • The overall NMA between‐study SD was large (0.19 D), which made most NMA estimates versus control as, or more, imprecise than the corresponding direct evidence. For this reason, Table 1 presents direct and indirect evidence for all comparisons versus control, including the certainty of evidence assessment, except for moderate‐dose atropine versus control, for which only indirect evidence was available.

  • Change in axial length at 1‐year

    • The NMA included 31 studies (4864 participants) with two connected closed loops comparing different doses of atropine or control. There was no overall inconsistency  (P = 0.236). The only two closed loops were partly overlapping and showed no inconsistency.

    • The overall NMA between‐study SD was large (0.048 mm), which made most NMA estimates versus control as, or more, imprecise than the corresponding direct evidence. Table 3 presents direct and indirect evidence for all comparisons versus control, except for moderate‐dose atropine versus control, for which only indirect evidence was available.

  • Change in SER and change in axial length at 2‐years

    • The NMAs of the change in SER and change in axial length at two years included 24 studies (4485 participants) and 21 studies (4010 participants), respectively. Table 2 and Table 4 present the evidence from direct and indirect comparisons, except for moderate‐dose atropine versus control, for which only indirect evidence was available.

  • SUCRAs and mixed comparisons in NMAs

    • All indirect comparisons are presented for illustrative purposes as league‐tables at https://osf.io/ms83h/, where differences not including nil are marked in grey. 

Table 6 presents all SUCRA values for NMAs of change in SER and axial length at one and two years, where the three highest SUCRAs are highlighted in bold print. As can be seen, high‐dose atropine and moderate‐dose atropine were amongst the three best SUCRAs for all outcomes. Low‐dose atropine and PPSLs were third for SER at one and two years respectively, while orthokeratology was amongst the best three for axial length at one and two years.

2. SUCRAs in all NMAs.
Intervention SER 
1 year
SER 
2 years
 AL 
1 year
AL 
2 years
High‐dose atropine 98.9 97.9 98.1 94.2
Moderate‐dose atropine 87.8 72.3 92.2 88.1
Low‐dose atropine 74.5 55.9 64.9 54.9
Peripheral plus spectacle lenses 57.2 70.6 65.7 68.4
Pirenzepine 54.2 65.8 45.3 43.6
Multifocal soft contact lenses 50.6 56.5 52.8 51
Rigid gas‐permeable contact lenses 40.2 41.1 12.9 7.9
Multifocal spectacles 36.0 35.6 32.2 34.4
7‐methylxanthine 30.4 29
Control 14.9 9.2 19.5 13.6
Undercorrected single vision spectacles 5.3 6.5 8.5 12.8
Orthokeratology 79 81.1
The three highest ranking interventions for each outcome are highlighted in bold
NMA: network meta‐analysis; SUCRA: surface under the cumulative ranking curve
Antimuscarinics combined with multifocal spectacle co‐intervention versus single vision spectacles

Three studies compared antimuscarinics combined with MFSLs to SVLs (Schwartz 1981MIT Study 2001Yen 1989). Schwartz 1981 randomised monozygous twin pairs to receive either bifocal spectacles combined with 1% tropicamide or SVLs. The paper did not present any numerical results, but the study authors stated that control twins showed more progression of myopia than their co‐twins who received tropicamide and bifocals, but the difference was not statistically significant.

The Myopia Intervention Trial (MIT) (MIT Study 2001), evaluated progressive addition spectacle lenses combined with 0.5% atropine compared to placebo eyedrops plus SVLs. At the end of the 18‐month follow‐up period, participants in the atropine plus progressive addition spectacle lenses group showed significantly less myopia progression (MD 0.98 D, 95% CI 0.76 to 1.20) and significantly less axial elongation (MD −0.47 mm, 95% CI −0.47 to −0.27) than participants in the placebo plus SVL group.

Yen 1989 randomly divided children into three groups. Group 1 received 1% atropine and bifocal spectacles; group 2 received 1% cyclopentolate, and group 3 received placebo eyedrops plus SVLs. At one year there was less myopia progression in the atropine plus bifocal group compared to the control group (MD 0.70 D, 95% CI 0.43 to 0.97).

Myopia control intervention versus myopia control interventions

Three studies compared different doses of topical atropine to each other ( ATOM 2 Study 2012;  Cui 2021Shih 1999). The ATOM 2 Study 2012 compared the efficacy of 0.5%, 0.1%, and 0.01% atropine in children of Chinese ethnicity. The mean change in refractive error at two years was −0.30 D (95% CI −0.40 to −0.20); −0.38 D (95% CI −0.48 to 0.29) and −0.49 D (95% CI −0.64 to −0.35) in the atropine 0.5%, 0.1%, and 0.01% groups, respectively. Pairwise differences were statistically significant for the comparison between 0.01% and 0.5% atropine (P = 0.02). Changes in axial length were 0.27 mm (95% CI 0.21 to 0.33); 0.28 mm (95% CI 0.24 to 0.33) and 0.41 mm (95% CI 0.36 to 0.46) for the high, moderate and low doses.

Cui 2021 evaluated the efficacy of 0.02% and 0.01% atropine in Chinese children. The mean changes in refractive error at two years were −0.80 D (95% CI −0.90 to −0.70) for the 0.02% concentration and −0.93 D (95% CI −1.04 to −0.82) for the 0.01% concentration. The corresponding changes in axial length were 0.62 mm (95% CI 0.56 to 0.68) and 0.72 mm (95% CI 0.66 to 0.78). 

Shih 1999 compared three doses of atropine (0.1%, 0.25% and 0.5%) versus 1% tropicamide control. Participants in the 0.5% group wore bifocal spectacles, those in the 0.25% group were provided with slightly undercorrected SVLs and the 0.1% group wore fully corrected SVLs. Myopia progression at the end of the two‐year follow‐up period was significantly slowed for each atropine group compared with tropicamide, with the 0.5% atropine dose showing the least progression compared with the tropicamide group, MD 1.95 D (95% CI 1.60 to 2.30) for 0.1% atropine; MD 1.98 D (95% CI 1.68 to 2.28) for 0.25% atropine; and MD 2.42 D (95% CI 2.16 to 2.68) for 0.5% atropine.

Three studies evaluated the combination of low‐dose atropine (0.01%) combined with orthokeratology, compared to orthokeratology alone (Kinoshita 2020Tan 2020Zhao 2021). These studies were conducted in Japan and China and followed participants for up to two years. The primary outcome was change in axial length (Analysis 9.1). We found a reduction in axial elongation for the combination therapy group compared to monotherapy at each year of follow‐up (1‐year MD −0.13 mm, 95% CI −0.16 to −0.09; 2‐year MD −0.11 mm, 95% CI −0.21 to −0.01).

Two studies included treatment arms that compared low‐dose atropine (0.01%) to orthokeratology at one year. There was no significant difference in axial length between treatments (Ren 2017 MD 0.03 mm, 95% CI −0.17 to 0.03; Zhao 2021 MD 0.05 mm, 95% CI−0.02 to  0.12).

Guo 2021 compared two designs of orthokeratology lenses with 6 mm or 5 mm back optic zone diameters. The rationale was that a smaller back optic zone diameter would increase myopia control efficacy by inducing a steeper distribution of the relative corneal refractive power profile within the pupillary diameter and further increase higher order aberrations. Axial elongation was lower in the 5 mm group (MD 0.04 mm, 95% CI −0.005 to 0.08) than the 6 mm group (MD 0.17 mm, 95% CI 0.13 to 0.21).

Swarbrick 2015 conducted a randomised, contralateral‐eye cross‐over study comparing a regular RGP lens in one eye and an orthokeratology lens in the other, conducted over a one‐year period. Lenses were worn for six months and then crossed over after a two‐week washout period for a further six months. This study did not report data eligible for analysis.

Change in refractive error and axial length following cessation of treatment

Six studies investigated changes in refractive error and axial length following cessation of the myopia control intervention (ATOM Study 2006ATOM 2 Study 2012Cheng 2016Ruiz‐Pomeda 2018STAMP Study 2012Zhu 2021). These studies compared the rate of myopia progression in the intervention group after switching to the control intervention to progression in the original control group.

In the STAMP Study 2012, children wore MFSL or SVLs for one year and all children wore SVLs in the second year. At the end of year 2 there was no difference in myopia progression between groups (MD 0.00 D, 95% CI −0.17 to 0.17; Analysis 2.3). This study did not measure progression of axial length.

In Ruiz‐Pomeda 2018, children who had worn MFSCL or SVSCL for two years were invited to participate in an additional one‐year follow‐up study to investigate rebound. One group discontinued MFSCL wear and switched to SVLs and progression was then compared to the original control group, who continued wearing SVLs. After one year there was no significant difference in progression of refractive error (MD 0.09 D, 95% CI −0.16 to 0.34) or axial length (MD 0.01, 95% CI −0.05 to 0.07; Analysis 4.4). 

Cheng 2016 invited participants who had worn either novel soft contact lenses with positive spherical aberration or conventional single vision soft lenses to participate in a 12‐month withdrawal study, where all children wore single vision lenses. The study authors reported that they found no evidence of a rebound effect at one year.

Three studies investigated the impact of terminating atropine treatment. The ATOM Study 2006 discontinued atropine treatment after children had received 1% atropine for two years. Children were followed for a further year. At the end of this period, the study compared myopia progression to the placebo‐treated group. Progression of refractive error in the original 1% atropine‐treated group was significantly greater than the control group at the end of the second year (MD −0.76 D, 95% CI −0.90 to −0.62; Analysis 7.5). The study authors reported axial length data as change from baseline over the entire three‐year duration of the study and therefore these data were not suitable for evaluating rebound.

Zhu 2021 used a novel dosing regime. Participants received 1% atropine eye drops once per month for 24 months, then every other month for 12 months followed by no drops for 12 months. Progression at the end of the one‐year withdrawal period was evaluated and compared to the placebo group. One year after terminating treatment the atropine group still showed a slowing in the progression of refractive error (MD 0.34 D, 95% CI 0.26 to 0.42; Analysis 7.5) and a reduction of axial elongation (MD −0.21 mm, 95% CI −0.23 to −0.19; Analysis 7.6) compared to the placebo group.  

The ATOM 2 Study 2012 was a dose comparison study, with participants randomised to receive 0.5%, 0.1% or 0.01% atropine for 24 months followed by a 12‐month withdrawal phase. During the washout period, myopic progression was greater in participants treated with 0.5% atropine (MD −0.87 D, 95% CI −0.96 to −0.78) compared to 0.1% (MD −0.68 D, 95% CI −0.76 to −0.61) and 0.01% atropine (MD −0.28 D, 95% CI −0.36 to −0.20; P < 0.001). Axial elongation was also greater in the 0.5% group (MD 0.35 mm, 95% CI 0.32 to 0.38) compared to the 0.1% (MD 0.33 mm, 95% CI 0.30 to 0.36) and 0.01% (MD 0.19 mm, 95% CI 0.16 to 0.22) groups. 

Important outcomes

Risk of adverse events

The risk of adverse events was generally poorly reported. We extracted data on the frequency of adverse events from 26 studies (see Table 7Table 8Table 9), comprising five studies reporting on the effects of spectacle interventions (Adler 2006Bao 2021COMET2 Study 2011Hasebe 2008Sankaridurg 2010), 11 on contact lens interventions, including orthokeratology (BLINK Study 2020Chamberlain 2019Cheng 2016CLAMP Study 2004Garcia‐del Valle 2021Guo 2021Jakobsen 2022Kinoshita 2020Lyu 2020Ruiz‐Pomeda 2018Tan 2020) and 10 using pharmacological interventions (ATOM 2 Study 2012Cui 2021Hieda 2021LAMP Study 2019PIR‐205 Study 2004Shih 1999Tan 2005Wei 2020Yen 1989Zhu 2021). Multiple adverse events occurring in the same study participant, including events affecting both eyes, were counted as independent events.

3. Risk of adverse events: spectacle lens interventions.
Study Arm (participants) Total number of events 
 (participants)
Dizziness Blurred vision Distortion Headache Difficulty with stairs Other
Adler 2006 UC (25) 2 (2)
FC (23) 0 (0)
Bao 2021 PPSL (115) 0 (0)
SVL (55) 0 (0)
COMET2 Study 2011 MFSL (59) 3 (3) 
SVL (59) 14 (14) 9 3 2
Hasebe 2008a MFSL (87) 37 (37) 10  19  0
SVL (91) 24 (24) 14  0
Sankaridurg 2010 MFSL (160) 13 (13)
SVL (74) 3 (3) 0 0
FC: full correction; MFSL: multifocal spectacle lenses; PPSL: peripheral plus lenses;UC: undercorrection; SVL: single vision spectacle lenses

aResults of 6/12 questionnaire survey (reported in Suemaru 2008 (secondary reference to to Hasebe 2008 ).

4. Risk of adverse events: contact lens interventions.
Study Arm (number of participants) Total number of events (participants) Grade ≥ 3 slit‐lamp
findings
Corneal infiltrates Allergy/
hypersensitivity
reactions
Corneal erosions/staining Corneal neovascularisation Papillary reaction Other
Multifocal soft contact lenses
BLINK Study 2020a Total lens wearers (294 ) 35 (35) NR 10
MFSCL (196)
SVSCL (98)
Chamberlain 2019 MFSC  (70) 8 (6)
SVSCL (74) 7 (5)
Cheng 2016 PSASL (64) 2 (1) 0
SVSCL (63) 3 (2) 0 2 1 0
Garcia‐del Valle 2021 MFSCL (32) 10 (8) NR 1
SVSCL (26) 4 (4) NR 1 1 2 0
Ruiz‐Pomeda 2018b MFSCL (41) 11 (NR) 0
SVL (33 ) 3 (NR) 0 1 0 2
Rigid gas‐permeable lenses
CLAMP Study 2004 RGP (59) 0 (0) NR 0
SVSCL (57) 4 (4) NR 1 3
Orthokeratology
Guo 2021 Ortho‐K 6 mm (32) 26 (NR) 11  13 
Ortho‐K 5 mm (26) 16 (NR) 0 3 6 7
Jakobsen 2022 Ortho‐K (19) 2 (2)
SVL (28) 0 (0) 0 0
Kinoshita 2020 Ortho‐K + 0.01% atropine (38) 3 (3) NR
Ortho‐K monotherapy (35) 1 (1) NR 1 1
Lyu 2020 Ortho‐K (68) 16 (16) 14 
SVL (34) 3 (3) 0 3
Tan 2020 Ortho‐K + 0.01% atropine (35) 1 (1)
Ortho‐K (30) 2 (2) 0 1 1
MFSCL: multifocal soft contact lenses; NR: not reported; Ortho‐K: orthokeratology; PSASCL: positive spherical abberation soft contact lenses; SVL: single vision spectacle lenses; SVSCL: single vision soft contact lenses

aData combined for intervention and control lenses
bData at final 24‐month visit

5. Risk of adverse events: antimuscarinics .
Study Arm (number of participants) Total number of events (participants) Photophobia/glare Blurred vision Hypersensitivity
reactions
Ocular irritation Systemic complications Other
Higher‐dose atropine
ATOM 2 Study 2012 Atropine 0.5% (161) 43 (23) 13  10  15
Atropine 0.1% (155) 47 (41) NR 20 7 14
Atropine 0.01% (84) 15 (14) NR 11 0 3
Shih 1999 Atropine 0.5% (41) 10 (10)
Atropine 0.25%, (47) 3 (3) 3 0 0 0
Atropine 0.1% (49) 0 (0) 0 0 9
Yen 1989 Atropine 1% (32) 32 (32) 32 
Cyclopentolate 1% ((32) 0 (0)  0 0 0 0 0
Placebo (32) 0 (0)  0 0 0 0 0
Zhu 2021 Atropine 1% (330) 352 (330) 205  65  61  18 
Placebo (308) NR NR NR NR NR NR
Lower‐dose atropine
Cui 2021  Atropine 0.02% (138) 32 (32) 32 
Atropine 0.01% (142) 33 (33) 33 0 0
SVL (120 ) 3 (3) 3 0 0
Hieda 2021 Atropine 0.01% ((85) 2 (2) 0
Placebo (86) 1 (1) 0 1 0
LAMP Study 2019 Atropine 0.05% (93) 17 (17)
Atropine 0.025% (86) 14 (14)) 4 10
Atropine 0.01% (91) 17 (17) 6 11
Wei 2020 Atropine 0.01% (110) 8  (8) 3  
Placebo (110) 2 (2) 1 0 1
Pirenzepine
PIR‐205 Study 2004 Pirenzepine 2% (117) 163 (NR) 91  47  18  Several 'other' AEs documented. No significant difference between test vs placebo
Placebo (57) 29 (NR) 1 13 10 5
Tan 2005 Pirenzepine 2% (142) 178 (NR) 95  83  Several 'other' AEs documented. No significant difference between test vs placebo
Placebo (171) 16 (NR) 6 10
AEs: adverse events;NR: not reported; SVL: single vision spectacles

Studies used a variety of methods to record adverse events. Symptoms were usually elicited using questionnaires, telephone interviews or were self‐reported at follow‐up appointments by parents or children, or both. Objective clinical signs were usually based on clinical examination at each follow‐up visit, however in some studies, participants were advised to return to the clinic for unscheduled visits should adverse events arise.

Spectacle interventions

Data on adverse events were available from 446 participants wearing spectacle lens interventions (undercorrection, MFSLs and PPSLs) and 302 SVL‐wearing controls. Study duration was one to three years. MFSLs and PPLSs were usually well tolerated following a short adaptation period and the reported adverse events were generally mild. There were 55 events in the active arm and 41 in the control arm. Dizziness and blurred vision were the most commonly reported adverse events with similar rates in SVL controls (dizziness: active arm 13/446, controls 15/302; blurred vision: active arm 31/446, controls 18/302) see Table 7. Overall there were three withdrawals due to adverse events in studies using MFSLs. 

Contact lens interventions

Eleven studies provided safety data on 1068 participants receiving contact lens interventions, which included various soft contact lens designs (including MFSCLs and SVSCLs), RGP and orthokeratology. Study duration was one to three years. The control arm in orthokeratology studies was typically SVLs. Two studies compared orthokeratology monotherapy to combined orthokeratology and low‐dose atropine. Safety outcomes were monitored by clinical examination of the anterior segment of the eye using the slit‐lamp biomicroscope at follow‐up appointments. Many studies graded clinical signs using standard grading scales, which used either artist‐rendered or photographic images to grade corneal and conjunctival signs on a 0 to 4 scale from normal to severe. Grade 3 and 4 are regarded as clinically significant and usually require a clinical action. For the most part, studies using MFSCLs and SVSCLSs reported adverse events separately for each arm, however the largest study (BLINK Study 2020), reported safety data for all arms combined (294 children). The most commonly reported adverse events in studies involving soft contact lenses were corneal infiltrative events (17/664 wearers), conjunctival papillary reaction (20/664), and corneal staining (12/664), see Table 8. The number of events were similar for test and control lenses. These events were generally not serious, with only one grade 3 event, and one participant in the BLINK Study 2020 was reported as a 'probable microbial keratitis'. There were four reported adverse effect‐related withdrawals in these studies (incidence: approx 0.6%).

Adverse events in orthokeratology studies were more common: corneal infiltrates (7/254 wearers), corneal staining (36/254), with four cases of corneal staining graded 3 or higher. There were 12 withdrawals due to adverse events from these studies (incidence approx. 5%).

Pharmacological interventions
Atropine

Safety data were available for eight studies using various doses of atropine. The three most common adverse events were photophobia or glare, blurred vision (particularly for near vision) and hypersensitivity reactions see Table 9. Atropine studies used high (≥ 0.5%; 564 children), moderate (0.1% to < 0.5%; 251 children), and low (< 0.1%; 829 children) atropine doses, with study durations ranging from 12 to 48 months. Adverse events were generally dose dependent with a greater likelihood of adverse events with higher atropine doses (high‐dose 437 events in 564 children; moderate‐dose 150 events in 251 children; low‐dose 138 events in 829 children). There were higher numbers of withdrawals due to adverse events in studies using high‐dose atropine (7% over 1 year in ATOM Study 2006 and 21% over 2 years in Zhu 2021) compared to 2% or fewer in studies using lower atropine doses (Hieda 2021Moriche‐Carretero 2021Wei 2020).

Evaluating the rates of photophobia and difficulties with near vision was confounded by the use of photochromic spectacle lenses or sunglasses to mitigate photophobia, and multifocal lenses for near vision problems in some studies, which may have reduced reporting of symptoms. 

Pirenzepine

PIR‐205 Study 2004 and Tan 2005 (259 children in the active treatment arms) documented ocular and systemic adverse events. The three systemic adverse events most frequently reported were headache, common cold, and flu syndrome in the PIR‐205 Study 2004, and increased cough, respiratory infection, and rhinitis in Tan 2005. The three ocular adverse events most frequently reported by both studies were symptoms of decreased accommodation, papillae/follicles, and medication residue on the eyelids or eyelashes. Forty‐three children in the active treatment arms withdrew due to adverse events.

Quality of life

One study (LAMP Study 2019) reported on vision‐related quality of life using the Chinese version of the 25‐item National Eye Institute Visual Function Questionnaire (NEI VFQ‐25). This validated quality‐of‐life instrument assesses 11 subscales: general health, general vision, ocular pain, near vision, distance vision, social function, mental health, role limitations, dependency, colour vision and peripheral vision. LAMP Study 2019 evaluated quality of life in 438 participants receiving one of three doses of atropine (0.05%, 0.02% or 0.01%) or placebo. The study authors reported no difference between groups in vision‐related quality of life, with similar scores across all 11 domains.

Treatment adherence

Quantitative data on adherence to myopia control treatment were available in 21 studies, comprising 10 studies investigating spectacle interventions (Bao 2021COMET Study 2003COMET2 Study 2011Fulk 2002Hasebe 2008Koomson 2016Lam 2020Pärssinen 1989STAMP Study 2012Yang 2009), six studies evaluating contact lens interventions (Anstice 2011BLINK Study 2020Chamberlain 2019DISC Study 2011Fujikado 2014Katz 2003), and five using pharmacological interventions (ATOM 2 Study 2012Hieda 2021LAMP Study 2019PIR‐205 Study 2004Trier 2008). Where adherence data were available at multiple time points we report the results at the longest time point (see Table 10Table 11Table 12).

6. Adherence: spectacle interventions.
Study Arm
(number of participants)
Wearing time
hours per day
Mean (SD)
%  compliant (always or most of the time) P value
Bao 2021 PPSL HAL (54) 13.4 (2.1) P = 0.35
PPSL SAL (53) 13.4 (1.8)
SVL (50) 13.1 (1.7)
COMET Study 2003 MFSL (235) 93% NR
SVL (234) 96%
COMET2 Study 2011a MFSL (58) 72% NR
SVL (58) 90%
Fulk 2002 MFSL (42) 90% NR
SVL (40) 96%
Hasebe 2008 MFSL (87) 96% Reported as ‘not significant’
SVL (91) 94%
Koomson 2016 UC (75) 97% NR
FC (75) 96%
Lam 2020 PPSL (79) 15.5 (2.6) Reported as ‘not significantly different’
SVL (81) 15.3 (2.1)
Pärssinen 1989 MFSL (79) 77% NR
SVL (79) 82%
STAMP Study 2012 MFSL (40 93%a NR
SVL (43) 91%a
Yang 2009 MFSL (89) 87% (combined) NR
SVL (89)
FC: fully corrected single vision spectacles; HAL: highly aspheric; MFSL: multifocal spectacle lenses; NR: not reported; PPSL: peripheral plus spectacle lenses; SD: standard deviation; SVL: single vision spectacle lenses;PPSL: peripheral plus lenses; SAL: slightly aspheric; UC: undercorrected single vision spectacles

aCompliance during school hours.

7. Adherence: contact lens interventions.
Study Arm (number of participants) Wearing timehours per day
Mean (SD)
% compliant 
(always or most of the time)
P value
Anstice 2011 MFSCL (20) 13.2 (2.8) 100%  P = 0.41
SVSCL (20)
BLINK Study 2020 MFSCL (196) 11.0 (4.4)a NR
SVSCL (98)
Chamberlain 2019 MFSCL (70) 13.7 (1.5)  Reported P > 0.05
SVSCL (74) 13.3 (1.5)
DISC Study 2011 MFSCL (111) 6.5 (2.2) P = 0.644
  SVCL (110) 6.3 (1.7)
Fujikado 2014 MFSCL (11) 13.2(1.0)  P = 1.00
SVCL (13) 13.2(1.1)
Katz 2003** RGP (75) 31.5% NR
SVL (75) 98.4%
MFSCL: multifocal soft contact lenses; NR: not reported; RGP: rigid gas‐permeable lenses; SD: standard deviation; SVSCL: single vision soft contact lenses; SVL: single vision spectacle lenses

aBoth arms combined.

8. Adherence: pharmacological interventions.
Study Arm (number of participants) Compliance with medication P value
ATOM 2 Study 2012 Atropine 0.5% (161) 98.7% NR
Atropine 0.25% (155) 96.8%
Atropine 0.1% (84) 98.8%
Hieda 2021 Atropine 0.01% (85) 83.3% NR
Placebo (86) 85.7%
LAMP Study 2019 Atropine 0.05% (109) 93.6% NR
Atropine 0.025% (108) 95.4%
Atropine 0.01% (110) 90.9%
Placebo (111) 90.1%
PIR‐205 Study 2004 Pirenzepine 2% (117) 79% NR
Placebo (57) 79%
Trier 2008 7‐methylxanthine (35) 89% NR
Placebo (42) 92%
NR: not reported

Studies usually assessed adherence to optical interventions through an estimate by parents or children, or both, of wearing time per day of spectacles or contact lenses and the number of days per week the optical appliances were worn (6 to 7 days per week was usually judged as being fully compliant). Studies used a variety of methods for data collection, including questionnaires or discussion of compliance at follow‐up appointments. These data were available for 1731 participants wearing a variety of spectacle lens interventions (undercorrection, multifocal, peripheral plus and single vision). The range of daily wearing times were between 13.1 and 15.5 hours per day. The percentage of participants who were judged to be compliant were similar between test and control lenses, although the COMET Study 2003 and Pärssinen 1989 reported a lower proportion of participants wearing MFSL than the SVL controls.

Adherence data were available for 873 participants in contact lens studies, including MFSCL, SVSCL and RGP. Daily wearing times were between 6.3 and 13.7 hours per day, with no statistical differences between multifocal and single vision contact lenses. In Katz 2003, which investigated RGP lenses versus SVLs, the percentage compliance at 24 months in the RGP group was 31.5% compared to 98.4% in spectacle lens‐wearing controls. Adherence was not formally assessed in orthokeratology studies, but these studies were often associated with high dropout rates (over 50% in some studies).

For most pharmacological interventions, adherence was monitored by self‐reported questionnaires. Only PIR‐205 Study 2004 used electronic monitoring. Compliance was defined as using the study medication 75% to 80% of the time. Percentage compliance in 919 participants taking low‐dose atropine ranged from 83.3% to 98.8%, with similar levels of compliance between active and placebo arms. Compliance in the intervention arm of PIR‐205 Study 2004 and Trier 2008 were 79% and 89% respectively, which were similar to participants taking the placebo.

Discussion

Summary of main results

This review summarises evidence from 64 studies, involving a total of 11,617 participants with low to moderate myopia. Studies investigated 11 interventions to slow the progression of myopia in children. Participants were girls and boys aged between 4 and 18 years, with an average age of 10.4 years. Interventions were broadly categorised into optical, pharmacological and environmental modalities. Fifty‐seven studies compared one or more myopia control interventions relative to a control or placebo intervention. Four studies included a combined intervention arm compared to control, and seven studies compared single or combined interventions to each other. Over 60% of studies were conducted in China or other Asian countries. In terms of study duration, 34% of the studies had a 12‐month duration, 46% reported to 24 months, 17% up to 36 months and only one study measured outcomes over 36 months. We defined the critical outcome 'progression of myopia' as both change in refractive error (as SER from baseline) and the more clinically meaningful, change in axial length. We judged most of the studies to be at 'high' or 'some concern' for risk of bias. Because the network was not well‐connected, we based our comparisons on direct evidence from classical pairwise meta‐analyses, except for moderate‐dose atropine. 

In terms of SER and axial length at 12 and 24 months, all interventions, except for undercorrection with SVLs, RGP and the adenosine antagonist 7‐methylxanthine, were superior to placebo in reducing the change in SER and slowing axial elongation. The certainty of evidence ranged from very low to moderate, depending on the comparison (see Table 1Table 2Table 3Table 4). Although statistically significant, many of the efficacy estimates were small and clinically insignificant. There was evidence of retardation in efficacy of myopia control treatment over time, with most of the reduction in progression occurring in the first year.

Overall, high‐dose topical atropine (≥ 0.5 %) and orthokeratology were the most effective interventions in slowing axial elongation at two years of follow‐up, corresponding to a 0.3 mm to 0.5 mm slowing of axial elongation (moderate‐certainty evidence). MFSCLs were similar to low‐dose topical atropine (< 0.1%), with a reduction in axial elongation of 0.15 mm and 0.16 mm respectively (moderate‐certainty evidence).

The most commonly studied combination therapy was orthokeratology plus low‐dose atropine. Compared to orthokeratology monotherapy, the combination was associated with a significant reduction in axial elongation. 

We did not identify any relevant studies reporting on the effect of environmental interventions on childhood myopia progression.

Data on changes to SER and axial length following cessation of treatment ('rebound') were available in four studies. There was no evidence of rebound in two studies that investigated optical interventions (Ruiz‐Pomeda 2018STAMP Study 2012), but there was inconsistent evidence on rebound for topical atropine. One study, which abruptly terminated 1% topical atropine, found that there was a significant rebound effect (ATOM Study 2006), whilst another, which reduced the frequency of atropine instillation over time, reported a maintained slowing of myopia progression (Zhu 2021).

In terms of the risk of adverse events, based on limited evidence that was often poorly reported, spectacle interventions were well tolerated with minimal and mild adverse events, similar to controls. In contact lens studies, the incidence of adverse events for multifocal soft contact lenses was also similar to the single vision soft contact lens controls. Adverse events in these studies generally consisted of expected contact lens‐related adverse events that were generally non‐serious. However, the incidence and severity of corneal staining was higher in studies using orthokeratology. The most commonly reported adverse events with antimuscarinic agents were photophobia, blurred near vision and hypersensitivity reactions, which increased with increasing drug concentration.

Treatment adherence was generally high with levels of adherence that were similar across study arms.

Only one study provided information on the effect of myopia control treatment on vision‐specific quality of life (LAMP Study 2019). This study compared three doses of atropine to placebo and reported no difference between groups at 12 months.

Brief economic commentary

We found no economic evaluation studies comparing different methods of myopia control in children. The apparent shortage of relevant economic evaluations indicates that there is a paucity of evidence regarding the costs and consequences of measures of myopia control in children. Future research could consider economic as well as clinical evaluation of interventions for myopia control. 

Overall completeness and applicability of evidence

Several factors limit the applicability of the evidence in our review. Although we were able to include evidence from 64 RCTs, approximately 80% of the studies followed participants for two years or less. A consensus report produced by the International Myopia Institute (IMI), guiding principles of myopia control clinical study design, recommend three years as the minimum length to assess the efficacy of a treatment for myopia control, since treatment needs to be applied over multiple years during the period of most rapid myopia progression (Wolffsohn 2019 ). Extrapolation of efficacy data for outcomes measured at one year is therefore likely to overestimate the effectiveness of treatment.

A number of factors complicated the comparison of studies, including differences in the demographic characteristics of the participants, and variability in the parameters used within similar treatments (e.g. different add powers and lens designs for multifocal spectacles and soft contact lenses and variable doses of atropine). Although the majority of studies adopted similar eligibility criteria, recruiting children aged 6 to 13 years, other studies used a wider age range of up to 18 years. This is important since faster progression occurs in younger myopes and progression slows in older teenagers. Furthermore, studies were conducted in different ethnic groups, particularly in children from South East Asian countries that typically have faster progression of myopia (Morgan 2012Morgan 2018).

These factors may, at least in part, explain the considerable heterogeneity of treatment effects identified in the review for some comparisons. 

It was difficult to compare the incidence of adverse events across studies due to different methods used to classify and report them. Furthermore, the use of photochromic and multifocal spectacles in pharmacological studies to mitigate potential side effects of higher topical atropine doses (≥ 0.5%) may have underestimated the incidence of glare, photophobia and reading difficulties reported in these studies. Similarly, the evaluation of treatment adherence between studies was complicated by the use of different methods to measure compliance (e.g. retrospective self‐report by parents or children, questionnaires or diaries). Lastly, the short time frame of many studies may have overestimated compliance, since it is possible that compliance may reduce over time.

Quality of the evidence

The certainty of the evidence for the critical outcome 'Progression of myopia' at one and two years ranged from very low to moderate, depending on the intervention. The main reasons for downgrading the certainty of evidence was risk of bias (principally due to lack of reporting details) and unexplained heterogeneity or inconsistency in the results.

We were unable to conduct a quantitative analysis for other outcomes and we summarised the results for these outcomes at study level in summary tables with an indication of the overall risk of bias for each of the included studies.

Potential biases in the review process

We followed the Cochrane Handbook for Systematic Reviews of Interventions to conduct this systematic review (Higgins 2022c). We applied a broad search strategy to ensure that all relevant papers were included. Pairs of review authors independently extracted data and assessed risk of bias; we also followed prespecified methods for classical and network meta‐analyses. We therefore believe that there should be no bias in the review process with respect to study selection and analysis of available data. 

Whenever possible, we used random‐effects pairwise meta‐analyses to incorporate heterogeneity amongst studies. Since we were unable to carry out the planned subgroup and sensitivity analyses to explore heterogeneity, the presence of considerable unexplained heterogeneity for several comparisons reduces our confidence in effect estimates.

We judged many of the RoB 2 assessments as ‘some concerns’ across the studies in our review, which often reflected an inadequate reporting of information by the study authors, for example, no information on allocation concealment and lack of a prespecified analysis plan. Consequently, we may have overestimated the impact of bias on our findings by downgrading the certainty of evidence of the critical and important outcomes due to risk of bias.

Agreements and disagreements with other studies or reviews

A previous Cochrane systematic review on myopia control interventions in children (Walline 2020), reviewed evidence from 41 RCTs and concluded, similar to the current review, that there was moderate‐certainty evidence favouring antimuscarinic drugs to reduce myopia progression and axial elongation with inconclusive evidence for other interventions. By contrast, a NMA of 16 interventions for myopia control in children conducted in 2016 concluded that "a range of interventions can significantly reduce myopia progression when compared with single vision spectacle lenses or placebo" (Huang 2016). More recently, a systematic review and NMA comparing the efficacy and safety of different concentrations of topical atropine for myopia control reported that 1%, 0.5% and 0.05% atropine were the three most efficacious atropine concentrations (Ha 2022). 

Two systematic reviews and an Ophthalmic Technology Assessment by the American Academy of Ophthalmology (AAO) have considered safety outcomes of contact lens interventions for reducing myopia progression in children (Cheng 2020VanderVeen 2019Yu 2022). With respect to daily disposable soft contact lenses, a review of retrospective data of adverse events from six RCTs estimated an incidence of 4.5 adverse events per 100 patient years and suggested that soft contact lenses can be safely worn by children (Cheng 2020). Yu 2022 analysed data from three studies and found no difference in adverse events between MFSCLs and control single vision lenses. VanderVeen 2019 reviewed published evidence on orthokeratology treatment for an AAO Health Technology Assessment and identified a sparsity of evidence in paediatric populations; it was noted that orthokeratology carries a small but definite risk of sight‐threatening keratitis. Bullimore 2013 estimated the incidence of microbial keratitis associated with orthokeratology as 13.9 per 10,000 patient‐years (95% CI 1.7 to 50.4), which is similar to the overall incidence of microbial keratitis in overnight soft contact lens wear.

In their NMA of efficacy and safety of topical atropine for myopia control, Huang 2016 considered the safety profiles of different atropine concentrations based on changes in pupil size and accommodation. The authors found that based on these proxies for photophobia and near vision difficulties, lower atropine concentrations had higher safety ranking probabilities.

Authors' conclusions

Implications for practice.

Based on the best available evidence, topical antimuscarinic agents and orthokeratology (ortho‐K) currently appear to be the most effective treatments for slowing childhood myopia progression. There is some uncertainty as to the optimal dose of atropine, the most studied antimuscarinic agent. Although higher doses slow overall axial elongation by approximately 0.5 mm over two years, corresponding to an approximate 1.00 D reduction in myopia, higher concentrations are more likely to cause adverse events and may increase the risk of rebound following cessation of treatment. The current review found limited evidence that rebound could potentially be reduced by tapering the treatment prior to termination. 

There are logistical difficulties in assessing change in refractive error in ortho‐K studies and therefore evidence of efficacy is based on slowing axial elongation. Ortho‐k may also require more specialised knowledge by the eye care practitioner, and therefore it may not be as available as some of the other treatment modalities

Evidence on the efficacy of other treatments was limited by short study durations and considerable heterogeneity in treatment response. The finding that treatment efficacy reduces over time would add to the perception of greater efficacy in studies of short duration.

Uncertainty remains regarding the risk‐benefit of ortho‐K and other contact lens interventions in children. Adverse events across the included studies were generally poorly described with a lack of standardisation of reporting.  Although none of the included studies reported serious adverse events, the duration of follow‐up in trials may have been insufficient to capture long‐term or rare adverse events.

Myopia control is a rapidly moving field, which emphasises the need for a living systematic review in this area that is underpinned by continual and active monitoring of new evidence.

Implications for research.

There are a number of research priorities in this field. Epidemiological evidence has shown that the age of onset and rate of myopia progression in children varies considerably. There is a need to develop better predictive models to identify children who are most likely to progress rapidly and will therefore potentially derive most benefit from treatment. The absence of long‐term data provides little evidence as to when myopia control interventions can be stopped or modified during treatment.

Although topical atropine shows considerable promise as a treatment for myopia control, the optimal dose is yet to be established, which balances efficacy, safety and propensity to rebound. There are many ongoing trials investigating the efficacy of various doses of atropine, used either as monotherapy or in combination with another intervention, which may provide further data to determine the optimal drug dose for myopia control.

The International Myopia Institute has developed a consensus set of principles on study design to guide the development of myopia control trial protocols (Wolffsohn 2019). Many of the included trials in this review did not meet these recommendations and researchers should be encouraged to adopt these principles to facilitate harmonised reporting of outcomes, including standardised reporting of AEs. There was also a tendency for authors to report a relative percentage reduction in myopia progression to express treatment effect, which can be misleading.

To address uncertainty in the safety of myopia control interventions, particularly relating to rare and potentially sight‐threatening adverse events, it may be necessary to seek evidence from non‐randomised studies, since such events are unlikely to be seen in randomised controlled trials due to their small size and relatively short duration. Future systematic reviews considering safety could also, therefore, consider evidence from non‐randomised studies for a comprehensive evaluation of safety.

Only one of the included studies evaluated the impact of myopia control interventions on quality of life. There is therefore a need for further studies using validated instruments to measure vision‐related and health‐related quality of life as an outcome of myopia control studies.There is also a lack of health economic studies that could inform policy‐makers and healthcare decision‐makers, enabling them to identify which interventions, policies or services provide the best value for money.

History

Protocol first published: Issue 4, 2021

Risk of bias

Risk of bias for analysis 2.3 Change in refractive error following cessation of treatment (1 year).

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
STAMP Study 2012 Low risk of bias Adaptive randomisation using online software for sequence generation. Allocation was concealed until participants were enrolled and assigned to interventions.  Low risk of bias Participants, carers and those delivering the intervention were aware of the intervention received.  It is unlikely that there were deviations from the intended intervention that arose due to trial context. Results analysed using ITT principles Low risk of bias Data available for approx. 99% of participants Low risk of bias Appropriate methods of measuring outcomes were used. Some concerns Protocol registered. Not enough infformation in the protocol on a statistical plan and no published statistical plan found. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Risk of bias for analysis 4.3 Change in refractive error following cessation of treatment (1 year).

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Ruiz‐Pomeda 2018 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the children or carers given the nature of the interventions. The differences at baseline were subjected to analysis of variance. Low risk of bias Outcome data were available for nearly all randomised participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan used. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not at high risk of bias for any domain.

Risk of bias for analysis 4.4 Change in axial length following cessation of treatment (1 year).

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Ruiz‐Pomeda 2018 Low risk of bias Central registration system, permuted block method. Everyone masked to CL assignment until after study completion. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the children or carers given the nature of the interventions. The differences at baseline were subjected to analysis of variance. Low risk of bias Outcome data were available for nearly all randomised participants. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan used. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not at high risk of bias for any domain.

Risk of bias for analysis 7.5 Change in refractive error following cessation of treament (1 year).

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
ATOM Study 2006 Low risk of bias Randomisation was performed using a computer generated randomisation list. It is unclear how allocation concelment was conducted. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. Low risk of bias Outcome data available for 86.5% of randomised participants. No analysis to correct for bias due to missing data. Missingness balanced across arms. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were blinded to the group allocation of patients. Some concerns No protocol and statistical analysis plan are available. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Zhu 2021 Low risk of bias Computer generated random sequence with allocation. No statistically significant baseline imbalances that would suggest a problem with randomisation. Some concerns No information on masking participants or parents. Results analysed using ITT principles. High risk of bias Data was available for 86.4% of participants. Reasons for missingness not documented and imbalance in missing data between intervention and control. Some concerns Appropriate and comparable methods of measuring outcome data were used. No information was available on masking of outcome assessors. Some concerns No registry record or protocol available. High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.

Risk of bias for analysis 7.6 Change in axial length following cessation of treatment (1 year).

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Zhu 2021 Low risk of bias Computer generated random sequence with allocation. No statistically significant baseline imbalances that would suggest a problem with randomisation. Some concerns No information on masking participants or parents. Results analysed using ITT principles. High risk of bias Data was available for 86.4% of participants. Reasons for missingness not documented and imbalance in missing data between intervention and control. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. No information was available on masking of outcome assessors. Some concerns No registry record or protocol available. High risk of bias The study is judged to be at high risk of bias in at least one domain for this result.

Risk of bias for analysis 8.1 Change in refractive error from baseline (1 year).

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Trier 2008 Low risk of bias Randomisation was performed by the pharmacy (details not given). Allocation concealment was maintained until after enrollment and participants assigned. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. Low risk of bias Data available for approx 93% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns The outcome measurements were taken in accordance with the clinical trials registry record. No statistical analysis plan (SAP) was reported.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Risk of bias for analysis 8.2 Change in axial length from baseline (1 year).

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Trier 2008 Low risk of bias Randomisation was performed by the pharmacy (details not given). Allocation concealment was maintained until after enrollment and participants assigned. There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias Participants, carers and those delivering the intervention were unaware of intervention received. Results analysed using ITT principles. Low risk of bias Data available for approx 93% of participants. Low risk of bias Appropriate methods of measuring outcome data were used. Same study protocol for all participants and the team were masked to the group allocation of patients. Some concerns The outcome measurements were taken in accordance with the clinical trials registry record. No statistical analysis plan (SAP) was reported.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Risk of bias for analysis 9.1 Change in axial length.

Study Bias
Randomisation process Deviations from intended interventions Missing outcome data Measurement of the outcome Selection of the reported results Overall
Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement Authors' judgement Support for judgement
Subgroup 9.1.1 At 1 year
Kinoshita 2020 Low risk of bias Randomisation was performed by a third person.There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the children or carers given the nature of the interventions. Results were analysed using ITT principles. Low risk of bias 88% completion rate of intervention group 1 and 95% for intervention group 2. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Examiners masked to the group allocation of participants. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Tan 2020 Some concerns Adaptive randomisation with online software for sequence generation. Insufficient information to evaluate allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. Some concerns It was not possible to mask the children or carers given the nature of the interventions. A small numer refused allocation but unlikely would have substantial effect on outcome. Some concerns Data was available for approx 87% of participants in each intervention group. No analysis performed to correct for bias due to missing data. Reasons for missingness provided. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Low risk of bias Protocol registered, with a pre published protocol and statistical plan. Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.
Zhao 2021 Some concerns There was no information on the method of randomisation or allocation concealment. There were no significant differences in the baseline parameters that would suggest a problem with randomisation. Some concerns No attempt to mask participants or parents. Method of analysis unclear. Some concerns No information on missingness and unclear whether missingness in the outcome could depend on its true value. Some concerns Appropriate and comparable methods of measuring outcome data were used. No information was available on masking of outcome assessors. Unlikely that assessment of the outcome was influenced by knowledge of intervention received. Some concerns No registry record or protocol available.  High risk of bias The study is judged as some concerns in all 5 domains and therefore at high risk of bias overall
Subgroup 9.1.2 At 2 years
Kinoshita 2020 Low risk of bias Randomisation was performed by a third person.There were no baseline imbalances that would suggest a problem with randomisation. Low risk of bias It was not possible to mask the children or carers given the nature of the interventions. Results were analysed using ITT principles. Low risk of bias 88% completion rate of intervention group 1 and 95% for intervention group 2. Low risk of bias Appropriate and comparable methods of measuring outcome data were used. Examiners masked to the group allocation of participants. Some concerns Protocol registered. Not enough information in the protocol on a statistical plan and no published statistical plan found.  Some concerns The study is judged to raise some concerns in at least one domain for this result, but not to be at high risk of bias for any domain.

Acknowledgements

The Cochrane Eyes and Vision (CEV) Information Specialist designed the electronic search strategies. We thank Chameen Samarawickrama and Nicola Logan for their comments on the protocol and this review. We thank Anupa Shah and Jennifer Evans from CEV for their assistance throughout the editorial process and Denise Mitchell for copy eiditing the review.

This review was signed off for publication by Jennifer Evans, Co‐ordinating Editor for CEV and Professor Augusto Azuaro‐Blanco, Editor for CEV.

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor: [Myopia] explode all trees
#2 myop*
#3 short near sight*
#4 #1 or #2 or #3
#5 (undercorrect* or slow* or progress* or control* or retard* or funct*) near/5 (myopia or myopic or myopes)
#6 (bifocal or multifocal) near/4 (myopia or myopic) near/4 (slow* or progress* or control*)
#7 prismatic bifocal*
#8 prism near/2 bifocal*
#9 base‐in prism
#10 executive near/2 bifocal*
#11 progressive next addition near/3 lens*
#12 positive next lens* near/3 addition
#13 PA‐PALs
#14 peripheral near/2 defocus near/4 lens*
#15 Defocus Incorporated Multiple Segments
#16 MyoVision or MyopiLux or Myosmart
#17 #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16
#18 (Concentric or gradient) near/3 lens*
#19 dual near/2 focus*
#20 extend* near/2 depth near/3 focus
#21 extend* near/2 depth near/4 field*
#22 extend* near/2 range near/3 focus
#23 extend* near/2 range near/4 field*
#24 extend* near/2 DOF
#25 EDOF
#26 #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25
#27 #5 and #26
#28 MiSight or Biofinity Multifocal or Proclear Multifocal
#29 MeSH descriptor: [Orthokeratologic Procedures] explode all trees
#30 orthokeratology or Ortho‐K
#31 #28 or #29 or #30
#32 MeSH descriptor: [Atropine] explode all trees
#33 atropine*
#34 MeSH descriptor: [Cyclopentolate] explode all trees
#35 cyclopentolate*
#36 MeSH descriptor: [Pirenzepine] explode all trees
#37 pirenzepine*
#38 MeSH descriptor: [Tropicamide] explode all trees
#39 tropicamide*
#40 methylxanthine*
#41 #5 #32 or #33 or #34 or #35 #36 or #37 or #38 or #39 or #40
#42 MeSH descriptor: [Leisure Activities] explode all trees
#43 outdoor* or out door*
#44 outside or out side
#45 #42 or #43 or #44
#46 #5 or #17 or #27 or #31 or #41 or #45
#47 MeSH descriptor: [Child] explode all trees
#48 MeSH descriptor: [Adolescent] this term only
#49 MeSH descriptor: [Pediatrics] explode all trees
#50 boy* or girl* or child* or minor*
#51 adolescen* or juvenile* or teen or teens or teenage* or youth or youths or underage
#52 (primary or elementary or high or secondary) near/1 school*
#53 paediatric* or pediatric*
#54 #47 or #48 or #49 or #50 or #51 or #52 or #53
#55 #4 and #46
#56 #54 and #55

Appendix 2. MEDLINE Ovid search strategy

1. randomized controlled trial.pt.
2. (randomized or randomised).ab,ti.
3. placebo.ab,ti.
4. dt.fs.
5. randomly.ab,ti.
6. trial.ab,ti.
7. groups.ab,ti.
8. or/1‐7
9. exp animals/
10. exp humans/
11. 9 not (9 and 10)
12. 8 not 11
13. exp myopia/
14. (myopia or myopic or myopes).tw.
15. ((short or near) adj3 sight$).tw.
16. or/13‐15
17. ((undercorrect$ or slow$ or progress$ or control$ or retard$ or funct$) adj5 (myopia or myopic or myopes)).tw.
18. ((bifocal or multifocal) adj4 (myopia or myopic) adj4 (slow$ or progress$ or control$)).tw.
19. prismatic bifocal$.tw.
20. (near adj1 prism adj4 bifocal$).tw.
21. base‐in prism.tw.
22. (executive adj2 bifocal$).tw.
23. (progressive adj1 addition adj3 lens$).tw.
24. (positive adj1 lens$ adj3 addition).tw.
25. PA‐PALs.tw.
26. (peripheral adj2 defocus adj4 lens$).tw.
27. Defocus Incorporated Multiple Segments.tw.
28. (MyoVision or MyopiLux or Myosmart).tw.
29. or/18‐28
30. ((Concentric or gradient) adj3 lens$).tw.
31. (dual adj2 focus$).tw.
32. (extend$ adj2 depth adj3 focus).tw.
33. (extend$ adj2 depth adj4 field$).tw.
34. (extend$ adj2 range adj3 focus).tw.
35. (extend$ adj2 range adj4 field$).tw.
36. (extend$ adj2 DOF).tw.
37. EDOF.tw.
38. or/30‐37
39. 17 and 38
40. (MiSight or Biofinity Multifocal or Proclear Multifocal).tw.
41. Orthokeratologic Procedures/
42. (orthokeratology or Ortho‐K).tw.
43. or/40‐42
44. Atropine/
45. atropine$.tw.
46. Cyclopentolate/
47. cyclopentolate$.tw.
48. Pirenzepine/
49. pirenzepine$.tw.
50. Tropicamide/
51. tropicamide$.tw.
52. methylxanthine$.tw.
53. or/44‐52
54. exp Leisure Activities/
55. (outdoor$ or out door$).tw.
56. (outside or out side).tw.
57. (near adj2 work$).tw.
58. or/54‐57
59. 17 or 29 or 39 or 43 or 53 or 58
60. exp Child/
61. Adolescent/
62. exp Pediatrics/
63. (boy$ or girl$ or child$ or minor$).tw.
64. (adolescen$ or juvenile$ or teen or teens or teenage$ or youth or youths or underage).tw.
65. ((primary or elementary or high or secondary) adj1 school$).tw.
66. (schoolchild$ or schoolage or schoolboy$ orschoolgirl$ or highschool$).tw.
67. (paediatric$ or pediatric$).tw.
68. or/60‐67
69. 16 and 59
70. 12 and 69
71. 68 and 70

The search filter for trials at the beginning of the MEDLINE strategy is from the published paper by Glanville 2006.

Appendix 3. MEDLINE Ovid economics search strategy

1. Economics/
2. exp "costs and cost analysis"/
3. Economics, Dental/
4. exp economics, hospital/
5. Economics, Medical/
6. Economics, Nursing/
7. Economics, Pharmaceutical/
8. (economic$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$).ti,ab.
9. (expenditure$ not energy).ti,ab.
10. value for money.ti,ab.
11. budget$.ti,ab.
12. or/1‐11
13. ((energy or oxygen) adj cost).ti,ab.
14. (metabolic adj cost).ti,ab.
15. ((energy or oxygen) adj expenditure).ti,ab.
16. or/13‐15
17. 12 not 16
18. letter.pt.
19. editorial.pt.
20. historical article.pt.
21. or/18‐20
22. 17 not 21
23. exp animals/ not humans/
24. 22 not 23
25. bmj.jn.
26. "cochrane database of systematic reviews".jn.
27. health technology assessment winchester england.jn.
28. or/25‐27
29. exp myopia/
30. (myopia or myopic or myopes).tw.
31. ((short or near) adj3 sight$).tw.
32. or/29‐31
33. ((undercorrect$ or slow$ or progress$ or control$ or retard$ or funct$) adj5 (myopia or myopic or myopes)).tw.
34. ((bifocal or multifocal) adj4 (myopia or myopic) adj4 (slow$ or progress$ or control$)).tw.
35. prismatic bifocal$.tw.
36. (near adj1 prism adj4 bifocal$).tw.
37. base‐in prism.tw.
38. (executive adj2 bifocal$).tw.
39. (progressive adj1 addition adj3 lens$).tw.
40. (positive adj1 lens$ adj3 addition).tw.
41. PA‐PALs.tw.
42. (peripheral adj2 defocus adj4 lens$).tw.
43. Defocus Incorporated Multiple Segments.tw.
44. (MyoVision or MyopiLux or Myosmart).tw.
45. or/34‐44
46. ((Concentric or gradient) adj3 lens$).tw.
47. (dual adj2 focus$).tw.
48. (extend$ adj2 depth adj3 focus).tw.
49. (extend$ adj2 depth adj4 field$).tw.
50. (extend$ adj2 range adj3 focus).tw.
51. (extend$ adj2 range adj4 field$).tw.
52. (extend$ adj2 DOF).tw.
53. EDOF.tw.
54. or/46‐53
55. 33 and 54
56. (MiSight or Biofinity Multifocal or Proclear Multifocal).tw.
57. Orthokeratologic Procedures/
58. (orthokeratology or Ortho‐K).tw.
59. or/56‐58
60. Atropine/
61. atropine$.tw.
62. Cyclopentolate/
63. cyclopentolate$.tw.
64. Pirenzepine/
65. pirenzepine$.tw.
66. Tropicamide/
67. tropicamide$.tw.
68. methylxanthine$.tw.
69. or/60‐68
70. exp Leisure Activities/
71. (outdoor$ or out door$).tw.
72. (outside or out side).tw.
73. (near adj2 work$).tw.
74. or/70‐73
75. 33 or 45 or 55 or 59 or 69 or 74
76. 32 and 75
77. 28 and 76

Appendix 4. MEDLINE Ovid adverse events search strategy

1. (ae or co or de).fs.
2. (safe or safety or side effect$ or undesirable effect$ or treatment emergent or tolerability or toxicity or adrs).ti,ab.
3. (adverse adj2 (effect or effects or reaction or reactions or event or events or outcome or outcomes)).ti,ab.
4. or/1‐3
5. exp myopia/
6. (myopia or myopic or myopes).tw.
7. ((short or near) adj3 sight$).tw.
8. or/5‐7
9. ((undercorrect$ or slow$ or progress$ or control$ or retard$ or funct$) adj5 (myopia or myopic or myopes)).tw.
10. ((bifocal or multifocal) adj4 (myopia or myopic) adj4 (slow$ or progress$ or control$)).tw.
11. prismatic bifocal$.tw.
12. (near adj1 prism adj4 bifocal$).tw.
13. base‐in prism.tw.
14. (executive adj2 bifocal$).tw.
15. (progressive adj1 addition adj3 lens$).tw.
16. (positive adj1 lens$ adj3 addition).tw.
17. PA‐PALs.tw.
18. (peripheral adj2 defocus adj4 lens$).tw.
19. Defocus Incorporated Multiple Segments.tw.
20. (MyoVision or MyopiLux or Myosmart).tw.
21. or/10‐20
22. ((Concentric or gradient) adj3 lens$).tw.
23. (dual adj2 focus$).tw.
24. (extend$ adj2 depth adj3 focus).tw.
25. (extend$ adj2 depth adj4 field$).tw.
26. (extend$ adj2 range adj3 focus).tw.
27. (extend$ adj2 range adj4 field$).tw.
28. (extend$ adj2 DOF).tw.
29. EDOF.tw.
30. or/22‐29
31. 9 and 30
32. (MiSight or Biofinity Multifocal or Proclear Multifocal).tw.
33. Orthokeratologic Procedures/
34. (orthokeratology or Ortho‐K).tw.
35. or/32‐34
36. Atropine/
37. atropine$.tw.
38. Cyclopentolate/
39. cyclopentolate$.tw.
40. Pirenzepine/
41. pirenzepine$.tw.
42. Tropicamide/
43. tropicamide$.tw.
44. methylxanthine$.tw.
45. or/36‐44
46. exp Leisure Activities/
47. (outdoor$ or out door$).tw.
48. (outside or out side).tw.
49. (near adj2 work$).tw.
50. or/46‐49
51. 9 or 21 or 31 or 35 or 45 or 50
52. 8 and 51
53. 4 and 52

The search filter for trials at the beginning of the MEDLINE strategy is from the published paper by Golder 2006

Appendix 5. Embase Ovid search strategy

1. exp randomized controlled trial/
2. exp randomization/
3. exp double blind procedure/
4. exp single blind procedure/
5. random$.tw.
6. or/1‐5
7. (animal or animal experiment).sh.
8. human.sh.
9. 7 and 8
10. 7 not 9
11. 6 not 10
12. exp clinical trial/
13. (clin$ adj3 trial$).tw.
14. ((singl$ or doubl$ or trebl$ or tripl$) adj3 (blind$ or mask$)).tw.
15. exp placebo/
16. placebo$.tw.
17. random$.tw.
18. exp experimental design/
19. exp crossover procedure/
20. exp control group/
21. exp latin square design/
22. or/12‐21
23. 22 not 10
24. 23 not 11
25. exp comparative study/
26. exp evaluation/
27. exp prospective study/
28. (control$ or prospectiv$ or volunteer$).tw.
29. or/25‐28
30. 29 not 10
31. 30 not (11 or 23)
32. 11 or 24 or 31
33. myopia/
34. (myopia or myopic or myopes).tw.
35. ((short or near) adj3 sight$).tw.
36. or/33‐35
37. ((undercorrect$ or slow$ or progress$ or control$ or retard$ or funct$) adj5 (myopia or myopic or myopes)).tw.
38. ((bifocal or multifocal) adj4 (myopia or myopic) adj4 (slow$ or progress$ or control$)).tw.
39. prismatic bifocal$.tw.
40. (near adj1 prism adj4 bifocal$).tw.
41. base‐in prism.tw.
42. (executive adj2 bifocal$).tw.
43. (progressive adj1 addition adj3 lens$).tw.
44. (positive adj1 lens$ adj3 addition).tw.
45. PA‐PALs.tw.
46. (peripheral adj2 defocus adj4 lens$).tw.
47. Defocus Incorporated Multiple Segments.tw.
48. (MyoVision or MyopiLux or Myosmart).tw.
49. or/38‐48
50. ((Concentric or gradient) adj3 lens$).tw.
51. (dual adj2 focus$).tw.
52. (extend$ adj2 depth adj3 focus).tw.
53. (extend$ adj2 depth adj4 field$).tw.
54. (extend$ adj2 range adj3 focus).tw.
55. (extend$ adj2 range adj4 field$).tw.
56. (extend$ adj2 DOF).tw.
57. EDOF.tw.
58. or/50‐57
59. 37 and 58
60. (MiSight or Biofinity Multifocal or Proclear Multifocal).tw.
61. orthokeratology lens/
62. (orthokeratology or Ortho‐K).tw.
63. or/60‐62
64. atropine/
65. atropine$.tw.
66. cyclopentolate/
67. cyclopentolate$.tw.
68. pirenzepine/
69. pirenzepine$.tw.
70. tropicamide/
71. tropicamide$.tw.
72. methylxanthine/
73. methylxanthine.tw.
74. or/64‐73
75. exp recreation/
76. (outdoor$ or out door$).tw.
77. (outside or out side).tw.
78. (near adj2 work$).tw.
79. or/75‐78
80. exp child/
81. exp adolescent/
82. exp pediatrics/
83. (boy$ or girl$ or child$ or minor$).tw.
84. (adolescen$ or juvenile$ or teen or teens or teenage$ or youth or youths or underage).tw.
85. ((primary or elementary or high or secondary) adj1 school$).tw.
86. (schoolchild$ or schoolage or schoolboy$ orschoolgirl$ or highschool$).tw.
87. (paediatric$ or pediatric$).tw.
88. or/80‐87
89. 37 or 49 or 59 or 63 or 74 or 79
90. 36 and 89
91. 32 and 90
92. 88 and 91

Appendix 6. Embase Ovid economics search strategy

1. Health Economics/
2. exp Economic Evaluation/
3. exp Health Care Cost/
4. pharmacoeconomics/
5. or/1‐4
6. (econom$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$).ti,ab.
7. (expenditure$ not energy).ti,ab.
8. (value adj2 money).ti,ab.
9. budget$.ti,ab.
10. or/6‐9
11. 5 or 10
12. letter.pt.
13. editorial.pt.
14. note.pt.
15. or/12‐14
16. 11 not 15
17. (metabolic adj cost).ti,ab.
18. ((energy or oxygen) adj cost).ti,ab.
19. ((energy or oxygen) adj expenditure).ti,ab.
20. or/17‐19
21. 16 not 20
22. animal/
23. exp animal experiment/
24. nonhuman/
25. (rat or rats or mouse or mice or hamster or hamsters or animal or animals or dog or dogs or cat or cats or bovine or sheep).ti,ab,sh.
26. or/22‐25
27. exp human/
28. human experiment/
29. or/27‐28
30. 26 not (26 and 29)
31. 21 not 30
32. 0959‐8146.is.
33. (1469‐493X or 1366‐5278).is.
34. 1756‐1833.en.
35. or/32‐34
36. 31 not 35
37. Conference abstract.pt.
38. 36 not 37
39. myopia/
40. (myopia or myopic or myopes).tw.
41. ((short or near) adj3 sight$).tw.
42. or/39‐41
43. ((undercorrect$ or slow$ or progress$ or control$ or retard$ or funct$) adj5 (myopia or myopic or myopes)).tw.
44. ((bifocal or multifocal) adj4 (myopia or myopic) adj4 (slow$ or progress$ or control$)).tw.
45. prismatic bifocal$.tw.
46. (near adj1 prism adj4 bifocal$).tw.
47. base‐in prism.tw.
48. (executive adj2 bifocal$).tw.
49. (progressive adj1 addition adj3 lens$).tw.
50. (positive adj1 lens$ adj3 addition).tw.
51. PA‐PALs.tw.
52. (peripheral adj2 defocus adj4 lens$).tw.
53. Defocus Incorporated Multiple Segments.tw.
54. (MyoVision or MyopiLux or Myosmart).tw.
55. or/44‐54
56. ((Concentric or gradient) adj3 lens$).tw.
57. (dual adj2 focus$).tw.
58. (extend$ adj2 depth adj3 focus).tw.
59. (extend$ adj2 depth adj4 field$).tw.
60. (extend$ adj2 range adj3 focus).tw.
61. (extend$ adj2 range adj4 field$).tw.
62. (extend$ adj2 DOF).tw.
63. EDOF.tw.
64. or/56‐63
65. 43 and 64
66. (MiSight or Biofinity Multifocal or Proclear Multifocal).tw.
67. orthokeratology lens/
68. (orthokeratology or Ortho‐K).tw.
69. or/66‐68
70. atropine/
71. atropine$.tw.
72. cyclopentolate/
73. cyclopentolate$.tw.
74. pirenzepine/
75. pirenzepine$.tw.
76. tropicamide/
77. tropicamide$.tw.
78. methylxanthine/
79. methylxanthine.tw.
80. or/70‐79
81. exp recreation/
82. (outdoor$ or out door$).tw.
83. (outside or out side).tw.
84. (near adj2 work$).tw.
85. or/81‐84
86. 43 or 55 or 65 or 69 or 80 or 85
87. 42 and 86
88. 38 and 87

Appendix 7. Embase Ovid adverse events search strategy

1. DRUG/ae
2. (safe or safety or side effect$ or undesirable effect$ or treatment emergent or tolerability or toxicity or adrs).ti,ab.
3. (adverse adj2 (effect or effects or reaction or reactions or event or events or outcome or outcomes)).ti,ab.
4. or/1‐3
5. myopia/
6. (myopia or myopic or myopes).tw.
7. ((short or near) adj3 sight$).tw.
8. or/5‐7
9. ((undercorrect$ or slow$ or progress$ or control$ or retard$ or funct$) adj5 (myopia or myopic or myopes)).tw.
10. ((bifocal or multifocal) adj4 (myopia or myopic) adj4 (slow$ or progress$ or control$)).tw.
11. prismatic bifocal$.tw.
12. (near adj1 prism adj4 bifocal$).tw.
13. base‐in prism.tw.
14. (executive adj2 bifocal$).tw.
15. (progressive adj1 addition adj3 lens$).tw.
16. (positive adj1 lens$ adj3 addition).tw.
17. PA‐PALs.tw.
18. (peripheral adj2 defocus adj4 lens$).tw.
19. Defocus Incorporated Multiple Segments.tw.
20. (MyoVision or MyopiLux or Myosmart).tw.
21. or/10‐20
22. ((Concentric or gradient) adj3 lens$).tw.
23. (dual adj2 focus$).tw.
24. (extend$ adj2 depth adj3 focus).tw.
25. (extend$ adj2 depth adj4 field$).tw.
26. (extend$ adj2 range adj3 focus).tw.
27. (extend$ adj2 range adj4 field$).tw.
28. (extend$ adj2 DOF).tw.
29. EDOF.tw.
30. or/22‐29
31. 9 and 30
32. (MiSight or Biofinity Multifocal or Proclear Multifocal).tw.
33. orthokeratology lens/
34. (orthokeratology or Ortho‐K).tw.
35. or/32‐34
36. atropine/
37. atropine$.tw.
38. cyclopentolate/
39. cyclopentolate$.tw.
40. pirenzepine/
41. pirenzepine$.tw.
42. tropicamide/
43. tropicamide$.tw.
44. methylxanthine/
45. methylxanthine.tw.
46. or/36‐45
47. exp recreation/
48. (outdoor$ or out door$).tw.
49. (outside or out side).tw.
50. (near adj2 work$).tw.
51. or/47‐50
52. 9 or 21 or 31 or 35 or 46 or 51
53. 8 and 52
54. 4 and 53

The search filter for trials at the beginning of the MEDLINE strategy is from the published paper by Golder 2006.

Appendix 8. ISRCTN search strategy

myopia AND (undercorrect OR slow OR progress OR control)

Appendix 9. ClinicalTrials.gov search strategy

myopia AND (undercorrect OR slow OR progress OR control) | Interventional Studies | Child

Appendix 10. WHO ICTRP search strategy

myopia AND undercorrect OR myopia AND slow OR myopia AND progress OR myopia AND control

Data and analyses

Comparison 1. Undercorrection vs full correction spectacles.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
1.1 Change in refractive error from baseline 3   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.1.1 At 1 year 2 142 Mean Difference (IV, Fixed, 95% CI) ‐0.15 [‐0.29, ‐0.00]
1.1.2 At 2 years 2 244 Mean Difference (IV, Fixed, 95% CI) 0.02 [‐0.05, 0.09]
1.2 Change in axial length from baseline 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.2.1 At 1 year 1 94 Mean Difference (IV, Fixed, 95% CI) 0.05 [‐0.01, 0.11]
1.2.2 At 2 years 2 244 Mean Difference (IV, Fixed, 95% CI) ‐0.01 [‐0.06, 0.03]

Comparison 2. Multifocal spectacle lenses vs single vision spectacle lenses.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
2.1 Change in refractive error from baseline 10   Mean Difference (IV, Random, 95% CI) Subtotals only
2.1.1 At 1 year 9 1463 Mean Difference (IV, Random, 95% CI) 0.14 [0.08, 0.21]
2.1.2 At 2 years 8 1401 Mean Difference (IV, Random, 95% CI) 0.19 [0.08, 0.30]
2.1.3 At 3 years 4 835 Mean Difference (IV, Random, 95% CI) 0.26 [‐0.07, 0.59]
2.2 Change in axial length from baseline  4   Mean Difference (IV, Fixed, 95% CI) Subtotals only
2.2.1 At 1 year 4 896 Mean Difference (IV, Fixed, 95% CI) ‐0.06 [‐0.09, ‐0.04]
2.2.2 At 2 years 3 699 Mean Difference (IV, Fixed, 95% CI) ‐0.07 [‐0.12, ‐0.03]
2.2.3 At 3 years 2 558 Mean Difference (IV, Fixed, 95% CI) ‐0.12 [‐0.18, ‐0.07]
2.3 Change in refractive error following cessation of treatment (1 year) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected

Comparison 3. Peripheral plus spectacles vs single vision spectacle lenses.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
3.1 Change in refractive error from baseline  6   Mean Difference (IV, Random, 95% CI) Subtotals only
3.1.1 At 1 year 5 832 Mean Difference (IV, Random, 95% CI) 0.51 [0.19, 0.82]
3.1.2 At 2 years 2 329 Mean Difference (IV, Random, 95% CI) 0.34 [‐0.08, 0.76]
3.2 Change in axial length from baseline 4   Mean Difference (IV, Random, 95% CI) Subtotals only
3.2.1 At 1 year 3 522 Mean Difference (IV, Random, 95% CI) ‐0.13 [‐0.24, ‐0.03]
3.2.2 At 2 years 2 329 Mean Difference (IV, Random, 95% CI) ‐0.20 [‐0.45, 0.05]

Comparison 4. Multifocal soft contact lenses vs single vision soft contact lenses.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
4.1 Change in refractive error from baseline 8   Mean Difference (IV, Random, 95% CI) Subtotals only
4.1.1 At 1 year 8 1135 Mean Difference (IV, Random, 95% CI) 0.26 [0.17, 0.35]
4.1.2 At 2 years 5 843 Mean Difference (IV, Random, 95% CI) 0.30 [0.19, 0.41]
4.1.3 At 3 years 2 395 Mean Difference (IV, Random, 95% CI) 0.47 [0.13, 0.82]
4.2 Change in axial length from baseline 8   Mean Difference (IV, Random, 95% CI) Subtotals only
4.2.1 At 1 year 8 1143 Mean Difference (IV, Random, 95% CI) ‐0.11 [‐0.13, ‐0.09]
4.2.2 At 2 years 5 843 Mean Difference (IV, Random, 95% CI) ‐0.15 [‐0.19, ‐0.12]
4.2.3 At 3 years 2 394 Mean Difference (IV, Random, 95% CI) ‐0.22 [‐0.34, ‐0.10]
4.3 Change in refractive error following cessation of treatment (1 year) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
4.4 Change in axial length following cessation of treatment (1 year) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected

Comparison 5. Rigid gas‐permeable lenses vs control.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
5.1 Change in refractive error from baseline 2   Mean Difference (IV, Fixed, 95% CI) Totals not selected
5.1.1 At 1 year 2   Mean Difference (IV, Fixed, 95% CI) Totals not selected
5.1.2 At 2 years 2   Mean Difference (IV, Fixed, 95% CI) Totals not selected
5.1.3 At 3 years 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
5.2 Change in axial length from baseline 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
5.2.1 At 1 year 2 415 Mean Difference (IV, Fixed, 95% CI) 0.02 [‐0.05, 0.10]
5.2.2 At 2 years 2 394 Mean Difference (IV, Fixed, 95% CI) 0.03 [‐0.05, 0.12]
5.2.3 At 3 years 1 116 Mean Difference (IV, Fixed, 95% CI) 0.05 [‐0.12, 0.22]

Comparison 6. Orthokeratology lenses vs single vision spectacle lenses lenses.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
6.1 Change in axial length from baseline 8   Mean Difference (IV, Random, 95% CI) Subtotals only
6.1.1 At 1 year 7 759 Mean Difference (IV, Random, 95% CI) ‐0.19 [‐0.23, ‐0.15]
6.1.2 At 2 years 2 106 Mean Difference (IV, Random, 95% CI) ‐0.28 [‐0.38, ‐0.19]

Comparison 7. Anti‐muscarinics vs placebo.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
7.1 Change in refractive error from baseline (1 year) 9   Mean Difference (IV, Random, 95% CI) Subtotals only
7.1.1 Atropine (high dose) 3 1072 Mean Difference (IV, Random, 95% CI) 0.90 [0.62, 1.18]
7.1.2 Atropine eyedrops (low dose) 4 804 Mean Difference (IV, Random, 95% CI) 0.38 [0.10, 0.66]
7.1.3 Pirenzepine 2% gel 2 326 Mean Difference (IV, Random, 95% CI) 0.32 [0.15, 0.49]
7.2 Change in axial length from baseline (1 year) 9   Mean Difference (IV, Random, 95% CI) Subtotals only
7.2.1 Atropine eyedrops (high dose) 3 1072 Mean Difference (IV, Random, 95% CI) ‐0.33 [‐0.35, ‐0.30]
7.2.2 Atropine eyedrops (low dose) 4 804 Mean Difference (IV, Random, 95% CI) ‐0.13 [‐0.21, ‐0.05]
7.2.3 Pirenzepine 2% gel 2 326 Mean Difference (IV, Random, 95% CI) ‐0.10 [‐0.18, ‐0.02]
7.3 Change in refractive error from baseline (2 years) 5   Mean Difference (IV, Fixed, 95% CI) Subtotals only
7.3.1 Atropine eyedrops (high dose) 2 916 Mean Difference (IV, Fixed, 95% CI) 1.26 [1.17, 1.36]
7.3.2 Atropine eyedrops (low dose) 2 497 Mean Difference (IV, Fixed, 95% CI) 0.24 [0.17, 0.31]
7.3.3 Pirenzepine eyedrops 2% gel 1 84 Mean Difference (IV, Fixed, 95% CI) 0.41 [0.13, 0.69]
7.4 Change in axial length from baseline (2 years) 4   Mean Difference (IV, Random, 95% CI) Subtotals only
7.4.1 Atropine eyedrops (high dose) 2 916 Mean Difference (IV, Random, 95% CI) ‐0.47 [‐0.61, ‐0.34]
7.4.2 Atropine eyedrops (low dose) 2 497 Mean Difference (IV, Random, 95% CI) ‐0.16 [‐0.20, ‐0.12]
7.5 Change in refractive error following cessation of treament (1 year) 2   Mean Difference (IV, Fixed, 95% CI) Totals not selected
7.6 Change in axial length following cessation of treatment (1 year) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected

Comparison 8. 7‐methylxanthine vs placebo.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
8.1 Change in refractive error from baseline (1 year) 1 77 Mean Difference (IV, Fixed, 95% CI) 0.07 [‐0.09, 0.24]
8.2 Change in axial length from baseline (1 year) 1 77 Mean Difference (IV, Fixed, 95% CI) ‐0.03 [‐0.10, 0.03]

Comparison 9. Othokeratology plus atropine vs orthokeratology alone.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
9.1 Change in axial length 3   Mean Difference (IV, Fixed, 95% CI) Subtotals only
9.1.1 At 1 year 3 172 Mean Difference (IV, Fixed, 95% CI) ‐0.13 [‐0.16, ‐0.09]
9.1.2 At 2 years 1 73 Mean Difference (IV, Fixed, 95% CI) ‐0.11 [‐0.21, ‐0.01]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Adler 2006.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: urban private optometric practice in Jerusalem, Israel
Number randomised: 62 children
Study follow‐up: 18 months
Exclusions and losses to follow‐up: 5 (8%) children who were randomised were excluded from the analyses; 9 (14.5%) were lost to follow‐up
Participants Age: mean = 10.08 years (range 6‐15 years)
Gender: 34 boys, 14 girls
Culture: most children were orthodox Jews who attended school year‐round and performed a study method of swaying back and forth while learning and reading
Inclusion criteria: pediatric patients aged 6‐15 years from study centres with early‐onset myopia
Exclusion criteria: 
  • strabismus

  • amblyopia

  • VA < 6/9

  • spherical equivalent > ‐6.00 D or < ‐0.50 D in either eye

  • astigmatism > 1.50 D in either eye 

  • anisometropia > 1.50 D

  • a difference between objective and subjective refraction findings ≥ 0.75 D

  • any ocular pathological manifestations 

  • premature birth

Interventions Undercorrected group (n = 25): blurred by +0.50 D; glasses were to be worn continuously
Fully corrected group (n = 23): glasses were to be worn continuously
Note: changes in prescription were made if the subjective refraction had changed by ≥ 0.50 D for 1 or both eyes
Outcomes Progression of early‐onset myopia
  • Objective refractions without cycloplegia: static retinoscopy (spherical equivalent)

  • Subjective refractions without cycloplegia: endpoint of maximum plus for best acuity

  • Near lateral phoria: alternating cover test using 6/9 size picture target held at 40 cm from eye


Measurements taken at baseline, 6 months, 12 months, and 18 months
Unit of analysis: average values of both eyes used for all results
 
Notes Study dates: enrolment occurred over an 8‐month period
Trial registration: not reported
Materials: free spectacle lenses were supplied by Einit Optical Clinic
Additional data: study author provided unpublished data via email correspondence

Anstice 2011.

Study characteristics
Methods Study design: paired‐eye, cross‐over RCT
Study centre: 1
Number randomised: 40 children
Study follow‐up: 20 months (10 months for each period)
Exclusions and losses to follow‐up: no exclusions; 5 (12.5%) and 6 (15.0%) were lost to follow‐up at 10‐month visit and 20‐month visit, respectively
Participants Age: mean = 13.4 years (range 11‐14 years)
Gender: 11 boys, 29 girls
Culture: New Zealand, including East Asian ethnicity and others (European, Indian, and Maori/Pacifica)
Inclusion criteria: 
  • 11‐14 years old at recruitment

  • spherical equivalent between −1.25 and −4.50 D in the least myopic eye as determined by noncycloplegic subjective refraction

  • myopia progression ≥ 0.50 D in the previous 12 months

  • best‐corrected spectacle VA of Snellen 6/6 or better in each eye

  • willingness to wear contact lenses for ≥ 8 h/day during the study


Exclusion criteria: history of 
  • astigmatism ≥ 1.25 D

  • anisometropia ≥ 1.00 D

  • strabismus at distance or near as assessed by cover test

  • ocular or systemic pathology likely to affect refractive development or successful contact lens wear

  • birth weight ≤ 1250 g

Interventions Group 1 (n = 21): 10 months wearing 2.00 D DF contact lens in the dominant eye and SVSCL in the contralateral eye, followed by 10 months wearing the swapped lens assignment 
Group 2 (n = 19): 10 months wearing DF contact lens in the nondominant eye and SVSCL in the contralateral eye, followed by 10 months wearing the swapped lens assignment 
Outcomes Primary outcome:
  • Change in spherical equivalent refraction measured by cycloplegic autorefraction


Secondary outcome:
  • Change in AL measured by partial coherence interferometry


Measurements taken at baseline and every 5 months for 20 months
Unit of analysis: data analysed by dominant eye
Notes Study dates: 2005 to not reported
Trial registration: ACTRN12605000633684
Funding source: Maurice and Phyllis Paykel Trust; New Zealand Optometric and Vision Research Foundation; Cornea and Contact Lens Society of New Zealand
Notes: study is also known as the Dual‐focus Inhibition of Myopia Evaluation in New Zealand (DIMENZ) study

ATOM 2 Study 2012.

Study characteristics
Methods Study design: parallel‐group RCT, with 2‐week run‐in period
Study centre: 1
Number randomised: 400 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: 1 exclusion; 44 (11%) were lost to follow‐up
Participants Age: mean = 9.7 years (range 6‐12 years)
Gender: 211 boys, 189 girls
Culture: Chinese (91%) in Singapore
Inclusion criteria: 
  • age 6‐12 years

  • myopia with SER error −2.00 D or worse in each eye as measured by cycloplegic autorefraction

  • astigmatism not exceeding −1.50D

  • myopic progression of ≥ 0.5 D in the past year

  • distance vision correctable to logMAR 0.2 or better in both eyes

  • normal ocular health other than myopia

  • good general health with no history of cardiac or significant respiratory disease

  • normal binocular function and stereopsis


Exclusion criteria: 
  • ocular or systemic diseases that may affect vision or refractive error

  • any ocular condition wherein topical atropine is contraindicated

  • defective binocular function or stereopsis

  • amblyopia or manifest strabismus including intermittent tropia

  • previous or current use of atropine or pirenzepine

Interventions 0.01% atropine eyedrops (n = 84)
0.1% atropine eyedrops (n = 155)
0.5% atropine (n = 161)
Outcomes Primary outcome
  • Progression of myopia defined as the change in spherical equivalent refractive error from baseline and measured by cycloplegic autorefraction


Secondary outcomes
  • Change in axial length from baseline (Zeiss IOL Master)

  • Ocular symptoms

  • Changes in accommodative amplitude

  • Photoptic and mesopic pupil sizes)


Measurements taken at baseline and at 12 months and 24 months
Note: baseline measurements recorded 2 weeks after treatment began to allow for stabilisation of the cycloplegic effect of atropine
Unit of analysis: both eyes included in the analysis (Huber–White robust standard errors to allow for the correlation between eyes within person)
Notes Study dates: not reported
Trial registration: NCT00371124
Funding source: National Medical Research Council, Singapore and SingHealth

ATOM Study 2006.

Study characteristics
Methods Study design: parallel‐group RCT, with 2‐week run‐in period
Study centre: 1
Number randomised: 400 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: no exclusions; 54 (13.5%) were lost to follow‐up
Participants Age: mean = 9.2 years (range 6‐12 years)
Gender: 220 boys, 180 girls
Culture: Chinese (94%) and Indian children (4%) in Singapore
Inclusion criteria: 
  • age 6‐12 years

  • myopia with SER error between −1.00 D and −6.00 D in each eye as measured by cycloplegic autorefraction

  • distance vision correctable to logMAR 0.2 or better in both eyes

  • normal ocular health

  • good general health with no history of cardiac or significant respiratory disease

  • normal binocular function and stereopsis

  • willingness and ability to tolerate monocular cycloplegia and mydriasis


Exclusion criteria: 
  • astigmatism > −1.50 D by cycloplegic autorefraction

  • IOP ≥ 21 mmHg

  • allergies to atropine, cyclopentolate, proparacaine, or benzalkonium chloride 

  • previous or current use of contact lenses, BFs, PALs, or other forms of myopia treatment

  • amblyopia or manifest strabismus, including intermittent tropia

Interventions Atropine (n = 200): 1 eye was randomised to 1 drop of 1% atropine sulfate nightly; the other eye received nothing
Placebo control (n = 200): 1 eye was randomised to 1 drop of vehicle nightly; the other eye received nothing
Note: all children received single vision photochromatic lenses for correction of refractive errors
Outcomes Primary efficacy outcome
  • Progression of myopia defined as the change in SER error from baseline and measured by cycloplegic autorefraction


Secondary efficacy outcome
  • Change in AL from baseline and measured by A‐scan ultrasonography


Primary safety outcome
  • Occurrence of AEs


Secondary safety outcomes
  • BCVA, IOP, slit‐lamp biomicroscopy, fundus examination


Measurements taken at baseline and annually for 2 years
Note: baseline measurements recorded 2 weeks after treatment began to allow for stabilisation of the cycloplegic effect of atropine
Unit of analysis: only 1 eye per child randomised to receive treatment (fellow eyes were controls)
Notes Study dates: enrolment between April 1999 and September 2000
Trial registration: not reported
Materials: vehicle drops were prepared by Alcon Laboratories; spectacles were SOLA Transitions SVLs
Funding source: National Medical Research Council, Singapore
Additional data: study author provided unpublished data via email correspondence
 

Bao 2021.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Eye Hospital of Wenzhou Medical University, Wenzhou, China
Number randomised: 170 children
Study follow‐up: 24 months
Exclusions and losses to follow‐up: 9 (5%) were excluded or lost to follow‐up
Participants Age: mean = 10.4 years (range 8‐13 years)
Gender: 73 boys, 88 girls
Culture: Chinese
Inclusion criteria: 
  • cycloplegic SER between −0.75 D and −4.75 D

  • astigmatism of cycloplegic autorefraction not exceeding 1.50 D

  • anisometropia not exceeding 1.00 D based on SER 

  • monocular best corrected VA of 0.05 logMAR or better at distance for both eyes 

  • absence of ocular pathology

  • absence of binocular vision issues and no history of ocular surgery or use of myopia control measures


Exclusion criteria: 
  • history of PALs or BF use and no prior use of contact lenses 

  • strabismus by cover test at near and distance

  • ocular or systemic medicine, which might affect myopia progression or VA through known effects on retina, accommodation or significant elevation of IOP

Interventions HAL n = 58
SAL n = 57
SVL n = 55
Outcomes Primary outcomes
  • Change in SER error from baseline (cycloplegic autorefraction)

  • Change in AL from baseline (Topcon KR‐800)


Secondary outcomes
  • Distance and near BCVA (ETDRS Chart)

  • Time needed to adapt to the lenses

  • Compliance (self‐reported daily wearing hours)

  • AEs


Measurements at 6‐monthly intervals for 24 months
Unit of analysis: data from right eye analysed
Notes Study dates: no dates provided
Trial registration: ChiCTR1800017683
Funding source: International S&T Cooperation Program of China (grant number 2014DFA30940) and the collaborative research project with Essilor International (Wenzhou Medical University grant numbers 95013006 and 95016010).
Disclosures: "Jinhua Bao is an Associate Director of Wenzhou Medical University–Essilor International Research Centre. Adeline Yang, Ee Woon Lim, Daniel P. Spiegel and Björn Drobe are employees of Essilor International."

Bian 2020.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Chengdu Aier Eye Hospital, China
Number randomised: 200 children
Study follow‐up: 12 months
Exclusions and losses to follow‐up: not reported
Participants Age: mean = 12.2 years (range 8‐14 years)
Gender: 96 boys, 104 girls
Culture: Chinese
Inclusion criteria: 
  • spherical equivalent of −0.75 to −5.00D, ≤ 1.5 D with the rule astigmatism, ≤ 0.75 D against‐the‐rule astigmatism

  • BCVA in either eye ≥ 1.0

  • No history of OK wear


Exclusion criteria: 
  • ocular diseases such as strabismus, amblyopia, congenital cataract and optic nerve dysplasia

  • history of eye surgery

  • systematic disease, which can affect VA, such as diabetes and chromosome abnormality

  • history of using contact lens, BF, MF lens or using atropine

Interventions OK n = 100
SVLs n = 100
Outcomes Primary outcomes
  • Change in AL from baseline (Lenstar LS900)


Secondary outcomes
  • Change in central corneal thickness, anterior chamber depth and lens thickness


Measurements at 6 months and 12 months
Unit of analysis: data from 1 eye analysed
Notes Study dates: January 2018‐ August 2018
Trial registration: not reported
Funding source: not reported
Disclosures: no declarations of interest reported

BLINK Study 2020.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: University clinics in Houston Texas and Columbus Ohio, USA
Number randomised: 294 children
Study follow‐up: 36 months
Exclusions and losses to follow‐up: 2 (0.7%) lost to follow‐up
Participants Age: mean = 10.3 years (range 7‐11 years)
Gender: 117 boys, 177 girls
Culture: n = 200 (68%) white; n = 29 (10%) black; n = 25 (9%) Asian
Inclusion criteria: 
  • SER −0.75 to −5.00D

  • astigmatism < 1.00D

  • vision correctable to 20/25 or better

  • clinically acceptable fit with study contact lenses at baseline


Exclusion criteria: 
  • > 1 month of gas permeable, soft BF, or OK contact lens wear

  • > 1 month of myopia control (including atropine or BF spectacles)

  • systemic issues that could affect myopia or myopia progression

  • chronically using oral or ophthalmic steroids

Interventions BF soft contact lenses (high add power (+2.50 D)) n = 98
BF soft contact lenses (med add power (+1.50 D) n = 98
SVSCL n = 98
Outcomes Primary outcome
  • Change in SER error from baseline (cycloplegic autorefraction)


Secondary outcomes
  • Change in AL from baseline (Haag‐Streit Lenstar LS 900)

  • Association of peripheral defocus to myopic progression

  • Ocular shape change at 36 months

  • Adherence (parental report)

  • AEs


Measurements taken every 12 months for 36 months
Unit of analysis: data from both eyes included (correlation between eyes adjusted in statistical model)
Notes Study dates: enroled between 22 September 2014, and 20 June 2016. Follow‐up was completed on 24 June 2019.
Trial registration: NCT02255474
Funding source: "This study was funded by grants from NIH granted to Drs Berntsen (U10 EY023204), Jordan (U10 023206), Walline (U10 023208), Mutti (U10 023210), Frishman (P30 EY007551), and Jackson (UL1 TR001070), and Bausch + Lomb provided contact lens solutions for the study"
Disclosures: 7 authors declared support from Bausch and Lomb outside the submitted work

Chamberlain 2019.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: university and hospital clinics in Canada, Portugal, Singapore and the UK
Number randomised: 144 children
Study follow‐up: 36 months
Exclusions and losses to follow‐up: 40 (28%) were lost to follow‐up or withdrawn (includes 9 difficulty handling lenses/unacceptable fit and did not receive intervention)
Participants Age: mean = 10.1 years (range 8 to < 13 years)
Gender: 75 boys, 69 girls
Culture: 79 (55%) white European, 34 (24%) East Asian, 12 (8%) West Asian, 13 (9%) mixed, 6 (4%) other
Inclusion criteria: 
  • children with SER error between −0.75 and −4.00 D inclusive with < 1.00 D of astigmatism or anisometropia


Exclusion criteria: 
  • current or prior contact lens wear

  • current or prior use of any other myopia control intervention

  • use of medications that could affect contact lens wear

Interventions Dual focus soft contact lens (MiSight) (n = 70)
SVSCLs (n = 74)
Outcomes Primary outcomes
  • Change in SER error from baseline (cycloplegic autorefraction)

  • Change in ALfrom baseline (Zeiss IOL master)


Secondary outcomes
  • Number of particpants with biomicroscopic findings > grade 2

  • Ocular AE rate between groups


Measurements taken at 12, 24 and 36 months
Unit of analysis: data from both eyes included (correlation between eyes adjusted in statistical model)
Notes Study dates: recruitment between November 2012 and April 2014
Trial registration: NCT01729208
Funding source: the study was sponsored by Coopervision Inc
Disclosures: "PC is an employee of Coopervision"

Charm 2013.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Hong Kong Polytechnic University)
Number randomised: 52 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: 14 (27%) children who were randomised, 7 in each group, were excluded or lost to follow‐up
Participants Age: median = 10 years (range 8‐11 years)
Gender: not reported
Culture: children "recruited via advertisements posted on local newspapers and leaflets in the Optometry Clinic of the School of Optometry"
Inclusion criteria: 
  • aged 8‐11 years

  • myopia with SER error ≥ −5.00 D by cycloplegic manifest refraction

  • monocular Snellen VA 20/25 or better

  • willingness to wear OK and to be available for monthly follow‐up


Exclusion criteria: 
  • astigmatism > 1.25 D

  • binocular vision problems

  • any ocular or systemic condition that may affect vision or vision development

  • contraindications for contact lens wear 

  • previous experience with refractive surgery, PALs, or OK

Interventions OK (n = 26): partial reduction OK contact lenses of target 4.00 D (DreamLite, Procornea Ltd, The Netherlands); "residual refractive errors were corrected by a pair of single vision spectacles to be worn during daytime"
SVLs (n = 26)
Note: "spectacle prescription would be updated at any subsequent visit for either group of subjects if difference in residual refractive errors (sphere or astigmatism) obtained at that visit exceeded 0.50 D"
Outcomes Primary outcome
  • Change in AL


Secondary outcomes
  • Objective and subjective cycloplegic refraction

  • Fundus examination

  • VA

  • Slit‐lamp examination

  • Corneal topography


Measurements taken every 6 months for 2 years
Unit of analysis: child‐based (right eye)
Notes Study dates: not reported
Trial registration: NCT00977236
Funding source: "this study was supported by a Collaborative Research Agreement between The Hong Kong Polytechnic University (PolyU) and Procornea Nederland B.V. and a Niche Area Funding (J‐BB7P) from PolyU. We thank Menicon Company Limited for supplying Menicon O2 Care for the study"
Conflict of interest: "the authors have no proprietary interest in any of the products used in the study"

Cheng 2010.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (optometric practice in Mississauga, Ontario, Canada)
Number randomised: 150 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: 15 (10%) children who were randomised were excluded from the analyses; 4 (3%) were lost to follow‐up
Participants Age: mean = 10 years (range 8‐13 years)
Gender: 62 boys and 73 girls received treatment
Culture: Chinese Canadian children were recruited by reviewing clinical records and mailing invitation letters addressed to their parents, or by responding to poster in the practice or during regular eye examinations
Inclusion criteria: 
  • Chinese Canadian children who were seen at the practice in the last 9‐18 months

  • age 8‐13 years

  • myopia between −1.00 D and −5.50 D

  • myopia progression ≥ 0.50 D in the preceding year

  • distance monocular VA of 6/6 or better

  • near monocular VA of 6/6 or better

  • stereoacuity ≤ 40 s of arc at 40 cm

  • single vision distance lens wear

  • consent of child and parent for study participation


Exclusion criteria:
  • astigmatism > 1.50 D

  • anisometropia > 1.50 D

  • strabismus

  • inability to respond to subjective testing 

  • history of systemic or ocular disease

  • history of BF lens wear and/or contact lens use

Interventions SVLs (n = 50): single vision distance lenses
BF lenses (n = 50): BF lenses with +1.50 D near addition
Prismatic BF lenses (n = 50): prismatic BF lenses with +1.50 D addition and a 3‐prism diopter base‐in prism in the near segment
Note: distance prescription changes were made if subjective refraction changed by ≥ 0.50 D in either eye
Outcomes Primary outcome
  • Myopic progression defined as difference between the mean cycloplegic spherical equivalent measured by an automated refractor at the baseline visit and subsequent 6‐month visits for 24 months


Secondary outcome
  • Eye growth defined as difference between mean ALs measured by ultrasonography at the baseline visit and at subsequent 6‐month visits for 24 months


Measurements taken at baseline and every 6 months for 2 years
Unit of analysis: child‐based (right eye)
 
Notes Study dates: April 2003‐April 2008
Trial registration: NCT00787579
Funding source: Essilor International of France
Auxiliary data: "Parents and/or guardians completed questionnaires related to vision habits of the enroled child and the child's birth parents' refractive errors. The number of years the children were myopic before entering the study was estimated from clinical records. Auxiliary data were used as covariates for regression statistics and to test the hypothesis that bifocal treatment is more effective with a shorter duration of myopia"
Additional data: study author provided unpublished data via email correspondence

Cheng 2016.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Korb and Associates in Boston, Massachusetts, USA
Number randomised: 127 children
Study follow‐up: 12 months (planned for 24 months)
Exclusions and losses to follow‐up: 6 (4.7%) children who were randomised were excluded from the analyses; 15 (11.8%) were lost to follow‐up
Participants Age: mean = 9.7 years (range 8‐11 years)
Gender: 59 boys, 68 girls
Culture: 90.6% were Asian and 8.7% were white
Inclusion criteria: 
  • aged 8‐11 years

  • myopia −0.75 to −4.00 D sphere by cycloplegic refraction

  • ≤ 1.00 D astigmatism

  • ≤ 1.00 D difference between eyes in spherical equivalent

  • 20/25 + 2 or better VA in each eye with spherocylindrical refraction

  • 20/25 or better VA with best sphere


Exclusion criteria: 
  • ocular or systemic pathology

  • history of eye surgery

  • history of myopia control

Interventions Soft contact lens + SAL group (n = 64): soft daily disposable contact lenses with positive spherical aberration (0.175 μm)
Soft contact lens group (n = 63): soft daily disposable contact lenses without the positive spherical aberration
Note: control and test lenses had identical material and appearance; spherical aberration was chosen to negate the negative spherical aberration that occurred in myopes during accommodation
Outcomes Primary outcome
  • Change in spherical equivalent cycloplegic autorefraction


Secondary outcome
  • Change in AL


Measurements taken every 6 months for 2 years
Unit of analysis: child‐based (right eye)
Notes Study dates: April 2008‐October 2011
Trial registration: NCT01829230
Funding source: Johnson and Johnson Vision Care, Inc.
Disclosures of interest: "Xu Cheng, Jing Xu, Khaled Chehab, and Noel Brennan are all paid employees of Johnson and Johnson Vision Care, Inc. Joan Exford of Korb & Associates is a contract principal investigator paid by Johnson and Johnson Vision Care, Inc."; "We thank Dr. Jichang He of New England College of Optometry and Dr. Victor Finnemore of Korb & Associates for collecting data for the study and Dr. Myles Jaffe of Innova Medical Communications, LLC, who is a contract medical writer paid by Johnson and Johnson Vision Care, Inc. for preparing this manuscript"
Notes: "the study was terminated because sufficient data had been collected from concurrent internal studies of similar designs"

Chung 2002.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: patient care unit at the Department of Optometry, Faculty of Allied Health Science, National University of Malaysia
Number randomized: 106 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: no exclusions; 12 (11%) were lost to follow‐up
Participants Age: mean = 11.56 years (range 9‐14 years)
Gender: 39 boys, 55 girls
Culture: Malay and Chinese ethnic origin
Inclusion criteria: 
  • age 9‐14 years

  • myopia with SER error ≥ −0.50 D in both eyes, with no principal meridian being plano or having any amount of plus power

  • corrected VA of 6/6 or better in each eye 

  • normal ocular health

  • willingness to give written consent


Exclusion criteria: 
  • > 2 D of astigmatism in each eye

  • binocular vision problems, including anisometropia > 2.00 D, problems requiring refractive therapy, strabismus, and amblyopia

  • previous contact lens wear

  • family was planning to leave the area before the end of the study period

Interventions Undercorrected group (n = 47): monocular VA blurred to 6/12 (approximately +0.75 D) in each eye with spectacles
Fully corrected group (n = 47): monocular VA maintained at 6/6 or better in each eye with spectacles
Note: in the fully corrected group, changes in prescription were made if subjective refraction had changed by ≥ 0.50 D for 1 or both eyes. For the undercorrected group, changes in prescription were made to maintain a vision of 6/12 in each eye
Outcomes Progression of early‐onset myopia
  • Static retinoscopy without cycloplegia

  • Keratometry

  • Subjective cycloplegic refractions using the endpoint of maximum plus or minimum plus for best acuity

  • Ocular components measurements by means of A‐scan ultrasonography


Measurements taken at baseline and every 6 months for 2 years
Unit of analysis: average values of both eyes used for all results
 
Notes Study dates: not reported
Trial registration: not reported
Funding source: IRPA grant
Compliance in wearing glasses was monitored via questionnaires. Compliance was defined as wearing glasses for at least 8 h/day (40 children in the undercorrected group vs 41 in the fully corrected group). Partial compliance was defined as wearing glasses 6‐8 h/day (7 children in the undercorrected group vs 6 in the fully corrected group)

CLAMP Study 2004.

Study characteristics
Methods Study design: parallel‐group RCT, with run‐in period
Study centre: 1 (the Ohio State University College of Optometry, USA)
Number randomised: 116 children
Study follow‐up: 3 years
Exclusions and losses to follow‐up: none
Participants Age: mean = 10.7 years (range 8‐12 years)
Gender: 47 boys, 69 girls
Culture: Columbus, Ohio, USA; 84.5% white (not of Hispanic origin), 8.6% Asian or Pacific Islander, 4.3% black (not of Hispanic origin)
Inclusion criteria: 
  • 8‐11 years old at time of randomisation

  • myopia with SER error between −0.75 D and −4.00 D in each eye, as measured by cycloplegic refraction

  • corrected VA of 20/20 or better in each eye


Exclusion criteria: 
  • astigmatism > 1.50 DC in each eye by cycloplegic refraction or > 1.00 DC on manifest refraction 

  • previous or attempted history of contact lens wear

  • anisometropia > 1.00 D between eyes

  • eye disease and binocular vision problems

  • systemic disease that may affect vision or vision development


Note: all participants had to successfully complete a run‐in period before enrolment into the study to exclude those who could not adapt to rigid contact lenses; 32 children did not complete the run‐in period and were excluded. Success for the run‐in period was defined as wearing the lenses at least 40 h/week and stating that the lenses were "always comfortable" or "usually comfortable"
Interventions (n = 59): RGPs worn during waking hours for 3 years
(n = 57): soft contact lenses worn during waking hours for 3 years
Note: prescription changes were made by an unmasked examiner based on participant complaints and improvement in VA
Outcomes Primary outcome
  • Change in cycloplegic autorefraction during 3 years (spherical equivalent)


Secondary outcomes
  • Change in AL

  • Change in peripheral autorefraction

  • Change in crystalline lens curvatures

  • Change in corneal curvature and thickness

  • Change in accommodation

  • Change in IOP


Measurements taken at baseline and every 6 months for 3 years
Unit of analysis: data analysed for right eye only
Notes Study dates: enrolment 9 July 1998 to 26 February 2000
Trial registration: NCT00009529
Funding source: National Eye Institute, National Institutes of Health; Menicon Co, Ltd.; CIBA Vision Corporation; SOLA Optical; and Essilor
 

COMET2 Study 2011.

Study characteristics
Methods Study design: parallel‐group RCT
Study centres: 8 (including 7 optometry colleges and schools and 1 community‐based ophthalmology practice)
Number randomised: 118 children
Study follow‐up: 3 years
Exclusions and losses to follow‐up: no exclusions; 8 (7%) were lost to follow‐up
Participants Age: mean = 10.1 years (range 8‐12 years)
Gender: 54 boys, 64 girls
Culture: USA
Inclusion criteria: 
  • age 8 to < 12 years

  • refractive error determined by cycloplegic autorefraction, which meets all of the following: spherical equivalent −0.50 to −3.00 D in both eyes; astigmatism ≤ 1.5 D in both eyes; anisometropia ≤ 1.00 D difference between eyes in spherical equivalent

  • VA at least 20/20 with best subjective refraction in both eyes

  • accommodative response at near vision (33 cm) is < 2.0 D by noncycloplegic autorefraction

  • near esophoria (≥ 2.0 pupillary distance) present by alternate prism and cover test (APCT) at near vision using best refractive correction determined from noncycloplegic subjective refraction


Exclusion criteria: 
  • history of strabismus

  • current or prior use of PALs, BFs, or contact lenses in either eye (prior or current use of SVLs was permitted)

Interventions PAL group (n = 59): Varilux Ellipse PALs with a +2.00 D near addition; worn during all waking hours for 3 years
SVL group (n = 59): standard SVLs (spectacles); worn during all waking hours for 3 years
Notes: "The distance correction was changed if the endpoint of the noncycloplegic subjective refraction differed from the current prescription by 0.50 D or more in spherical equivalent. Prescription changes could be made for smaller differences at investigator discretion if the new prescription improved the patient’s visual acuity by at least 1 line over that in their current correction"
Outcomes Primary outcome
  • Change in SER error in D from baseline to 3‐year visit measured by cycloplegic autorefraction


Secondary outcomes
  • Main axis astigmatism (J₀, dioptric power of a Jackson cross‐cylinder with axis at 0°) and oblique astigmatism (J₄₅, dioptric power of a Jackson cross‐cylinder with axis at 45°) by using the power vector approach


Measurements taken at baseline and every 6 months for 3 years
Unit of analysis: child‐based (median for each eye averaged to obtain the spherical equivalent used for analysis)
Notes Study dates: enrolment from April 2005‐March 2007
Trial registration: NCT00320593
Funding source: National Institutes of Health, Department of Health and Human Services, USA
Materials: Essilor of America and Eyewear Designs provided spectacles at a reduced cost
Study name: Progressive addition lenses vs single vision lenses for slowing progression of myopia in children with high accommodative lag and near esophoria

COMET Study 2003.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: multicentre, including 
  • a study chair

  • a co‐ordinating centre

  • 4 clinical centres

  • the National Eye Institute, USA


Number randomised: 469 children
Study follow‐up: 3 years
Exclusions and losses to follow‐up: no exclusions; 7 (1.5%) were lost to follow‐up
Participants Age: mean = 9.3 years (range 6‐11 years)
Gender: 223 boys, 246 girls
Culture: 4 major cities in the USA (Birmingham, Alabama: n = 133; Boston, Massachusetts: n = 110; Philadelphia, Pennsylvania: n = 108; and Houston, Texas: n = 118)
Inclusion criteria: 
  • 6‐11 years old

  • myopia with SER error between −1.25 D and −4.50 D in both eyes, as measured by cycloplegic autorefraction

  • astigmatism ≤ 1.50 D

  • no anisometropia (difference in spherical equivalent < 1.00 D between eyes)

  • BCVA of 20/32 or better

  • no strabismus by cover test for far (4.0 m) and/or near (0.33 m) fixation

  • willingness to not wear contact lenses for study duration


Exclusion criteria: 
  • strabismus detected by cover test

  • any ocular, systemic, or neurodevelopmental conditions that could influence refractive development

  • chronic medication use that might affect myopia progression or VA

  • birth weight < 1250 g

  • previous use of BFs, PALs, or contact lenses

  • problems with adherence to the protocol or the follow‐up period

Interventions PAL group (n = 235): MF lenses (no‐line BFs) with gradual and progressive change toward less negative or more positive power from the distance portion to the near portion of the lens (power +2.00 D); worn during waking hours for 3 years
SVL (n = 234): SVLs with same focal power throughout the lens area; worn during waking hours for 3 years
Note: "Prescription changes were made if the subjective refraction had changed by at least 0.50 D for 1 or both eyes. Smaller prescription changes were made if clinically indicated. Both groups were offered single vision sports glasses to use while participating in sports activities"
Outcomes Primary outcome
  • Change in refractive error


Magnitude of change in SER error relative to baseline measured by cycloplegic autorefraction with 2 drops of 1% tropicamide
Secondary outcomes
  • AL (magnitude of change in AL relative to baseline using average 3‐5 measurements with the Sonomed A‐scan)

  • Changes in ocular components, including lens thickness, anterior chamber depth, vitreous chamber depth

  • Accommodation and phoria by Maddox rod

  • Corneal curvature based on keratometry measured with the autorefractor

  • Normal reading distance for standardised age‐appropriate text


Measurements taken at baseline and every 6 months for 3 years
Unit of analysis: child‐based
Average values of both eyes used if the correlation coefficient was > 0.85 between eyes and the mean difference was not statistically significant; otherwise the eye with greater myopic change used for each child
 
Notes Study dates: enrolment was from September 1997‐September 1998; follow‐up was designed for 3 years but continued for 7 years, including 5 years wearing original lens assignments and 2 years wearing either glasses or contact lenses
Trial registration: NCT00000113
Funding source: NEI grants, Essilor of America, Marchon Eyewear, Marco Technologies, and Welch Allyn
Sample of 150 children were followed up at 1 month to evaluate possible lens‐induced phoria changes; no problems were detected in either group
Compliance in wearing glasses was monitored via separate questionnaires for children and parents (93% compliance in PAL group, 96% compliance in SVL group). Attitude toward wearing glasses and self‐esteem were also measured
Additional data: study author provided unpublished data via email correspondence

CONTROL Study 2016.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1
Number randomised: 86 children
Study follow‐up: 1 year
Exclusions and losses to follow‐up: 8 children did not complete the study
Participants Age: mean = 13 years (range 8‐18 years)
Gender: 26 boys, 60 girls
Culture: California, USA
Inclusion criteria: 
  • myopia between −0.50 D and −6.00 D, with documented progression of ≥ −0.50 D since last examination

  • eso fixation disparity at 33 cm with distance correction

  • astigmatism ≤ 1.00 D

  • anisometropia ≤ 2.00 D

  • BCVA 20/20 or better in each eye

  • ability to wear SCLs and attend follow‐up visits


Exclusion criteria:
  • presence of ocular disease affecting eye growth or preventing wear of contacts

  • prior ocular surgery

  • history of wearing RGPs in previous 2 years or extended wear SCLs in previous 6 months

  • pregnancy or nursing

  • use of certain medications

Interventions BFSCL group (n = 39): Vistakon Acuvue Bifocal lenses (distance centre, alternating 5‐ring), worn on a daily basis
SVSCL group (n = 40): Vistakon Acuvue 2, worn on a daily basis
Outcomes Primary outcomes
  • Changes in cycloplegic autorefraction at 1 year

  • Changes in cycloplegic subjective refraction at 1 year

  • Changes in AL at 1 year


Secondary outcomes
  • Keratometric changes at 1 year

  • Changes in manifest refraction at 1 year

  • Relationship between residual fixation disparity and myopia progression


Measurements taken at baseline, 6 months, and 12 months
Unit of analysis: average values for both eyes
 
Notes Study dates: start date was October 2003; study was completed in 2006
Trial registration: NCT00214487
Funding source: Vistakon
Additional information: study author provided unpublished information via email correspondence

Cui 2021.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Hospital of Zhengzhou University, China
Number randomised: 400 children
Study follow‐up: 24 months
Exclusions and losses to follow‐up: 100 (25%) were lost to follow‐up by 24 months
Participants Age: mean = 9.4 years (range 6‐14 years)
Gender: 210 boys, 190 girls
Culture: Chinese
Inclusion criteria: 
  • aged 6–14 years

  • myopic SER of −1.25 to −6.00 D in both eyes

  • astigmatism of < 2.0 D

  • anisometropia of < 1.0 D

  • monocular BCVA of 16/20 or better

  • IOP 10‐21 mmHg

  • no other eye diseases or surgery


Exclusion criteria: 
  • previously used atropine, pirenzepine, or RGP or ortho‐K lenses or MF contact lens to control myopia progression

Interventions 0.02% atropine eyedrops (n = 138)
0.01% atropine eyedrops (n = 142)
SVLs (n = 120) (this was a non‐randomised comparison group)
Outcomes Primary outcomes
  • AL (IOLMaster; Carl Zeiss Meditec AG, Germany)

  • Corneal power (IOLMaster; Carl Zeiss Meditec AG, Germany)


Secondary outcomes
  • Anterior chamber depth (IOLMaster; Carl Zeiss Meditec AG, Germany)

  • Pupil diameter (NIDEK, AR‐1, Japan)

  • Accommodation amplitude (Push‐up technique)

  • Cycloplegic autorefraction (Topcon RM 8000A, CA)

  • Incidence of AEs


Measuremnents taken at 4‐monthly intervals for 24 months
Unit of analysis: child‐based (right eye)
Notes Study dates: January 2018‐August 2020
Trial registration: ChiCTR‐IPD‐16008844
Funding source: "Funding was provided by Medical Science and Technology Research Projects of Henan Province Health Commission (Grant No. 201602073), Key Research and Promotion Special Projects of Henan Provincial Science and Technology Department (Grant No. 201801591), Key School Research Projects of Henan Provincial Department of Education (Grant No. 19A320066), Health and Family Planning Science and Technology Talents Overseas Training Project of Henan Province (Grant No. 2018038)."
Disclosures: "The authors declare no competing interests."

DISC Study 2011.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Hong Kong Polytechnic University)
Number randomised: 221 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: 38 (34.2 %) in BFSCL group and 36 (32.7%) in SVSCL group were excluded; 8 (7.2 %) in BFSCL group and 11 (10.0%) in SVSCL group were lost to follow‐up
Participants Age: mean = 11 years (range 8‐13 years)
Gender: 85 boys, 136 girls
Culture: Hong Kong, China
Inclusion criteria: 
  • age 8‐13 years

  • spherical equivalent −1.00 to −5.00 D 

  • astigmatism ≤ 1.00 D

  • anisometropia ≤ 1.25 D

  • spectacle‐corrected monocular VA 0.0 logMAR or better

  • contact lens–corrected monocular VA 0.1 logMAR or better

  • willingness to wear contact lenses regularly and parents' understanding and acceptance of random allocation of intervention


Exclusion criteria: 
  • ocular or systemic abnormalities affecting visual function or refractive development

  • prior use of PALs or BF contact lenses

  • contraindication for contact lens wear

Interventions BFSCL group (n = 111): dual‐focus incorporated soft contact (DISC) lenses, which were custom‐made BFSCLs with distance correction in the centre and alternating rings of defocusing (+2.50 D addition) and distance correction zones
SVSCL group (n = 110): SVSCLs
Note: children were instructed to wear lenses for 5‐10 h/day and to wear spectacles with full prescription when not wearing contact lenses
Outcomes Primary outcomes
  • Refractive error (cycloplegic autorefraction)

  • AL


Secondary outcome
  • Corneal curvature


Measurements taken every 6 months over 2 years
Unit of analysis: individual (right eye used for analysis)
Notes Study dates: September 2007‐ October 2009
Trial registration: NCT00919334
Funding source: "the study was supported by grants of RGC GRF (B‐Q04G) and Niche Areas Fund (J‐BB7P) from The Hong Kong Polytechnic University"
Conflict of interest: reported "none"

Edwards 2002.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Centre for Myopia Research, Hong Kong)
Number randomised: 298 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: no exclusions; 44 (15%) were lost to follow‐up
Participants Age: mean = 9.09 years (range 7‐10.5 years)
Gender: 122 boys, 132 girls
Culture: Hong Kong children, recruited through newspaper advertisements
Inclusion criteria: 
  • 7‐10.5 years old

  • SER error between −1.25 D and −4.50 D, as measured under cycloplegia

  • BCVA of 0.00 logMAR or better

  • no previous use of contact lenses and willingness to not wear contact lenses

  • willingness to wear glasses constantly

  • parents' acceptance of randomisation


Exclusion criteria: 
  • astigmatism > 1.50 D

  • anisometropia > 1.50 D in spherical or cylindrical error

  • any ocular or systemic condition that might affect refractive development

  • previous use of BFs or PALs

  • problems with adherence to the protocol or the follow‐up period

Interventions PAL group (n = 138): SOLA MC PALs (add +1.50 D); worn constantly for 2 years
SVL (n = 160): SOLA SVLs; worn constantly for 2 years
Note: prescription changes were made if there was a reduction in aided vision of ≥ 0.10 logMAR units
Outcomes Primary outcomes
  • Refractive error measured under cycloplegia (by autorefraction for data analysis and by subjective refraction for spectacle prescription)

  • AL measured under cycloplegia


Secondary outcomes
  • Aided visual acuity in each eye

  • Mean monocular and binocular distance and near PD

  • Noncycloplegic refraction

  • Horizontal and vertical heterophoria

  • Normal reading distance for standardised age‐appropriate text


Measurements taken at baseline and every 6 months for 2 years
Unit of analysis: only data from right eyes reported
 
Notes Study dates: not reported
Trial registration: not reported
Materials: lenses provided by Sola (Hong Kong) Ltd
Funding source: Centre for Myopia Research (Area of Strategic Development), The Hong Kong Polytechnic University

Fujikado 2014.

Study characteristics
Methods Study design: cross‐over RCT
Study centre: 1 (Osaka University School of Medicine), Japan
Number randomised: 24 children
Study follow‐up: 12 months for each phase
Exclusions and losses to follow‐up: "in the second year, two children dropped out from the study because their families moved to another city"
Participants Age: mean = 14 years (range 6‐16 years)
Gender: 7 boys, 17 girls
Culture: Japan
Inclusion criteria: 
  • 6‐16 years of age

  • myopic refractive error between −0.75 D and −3.50 D

  • anisometropia ≤ 1.0 D

  • astigmatism ≤ 1.0 D

  • BCVA 20/20 or better

  • willingness to wear lenses


Exclusion criteria: 
  • amblyopia, strabismus, or other ocular disease other than refractive error

  • history of OK, BF spectacles, or PALs in past 12 months

Interventions BFSCL group (n = 11 in phase 1): progressive addition soft contact lenses (+0.50 D) with 8.6 mm base curve, 14.5 mm diameter, 3.25 mm central zone, and horizontal thick zones to prevent rotation (Mipafilcon A; Menicon, Nagoya, Japan)
SVSCL group (n = 13 in phase 1): SVSCLs
Outcomes Primary outcomes
  • AL

  • Spherical equivalent at 12 and 24 months (cycloplegic autorefraction)


Secondary outcomes
  • Peripheral refraction

  • Compliance


Measurements taken months 1, 3, 6, 9, and 12 in each phase
Unit of analysis: individual (average of both eyes except for 1 child whose right eye only was enroled)
Notes Study dates: January 2011‐March 2013
Trial registration: JPRN‐UMIN000007989
Funding sources: Menicon Corp., Itami Central Ophthalmology Clinic (Japan)
Conflict of interest: "AS and MN are employees of Menicon. The authors report no other conflicts of interest in this work"

Fulk 1996.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Indian Health Service Hospital, Optometry Department, Tahlequah, Oklahoma, USA)
Number randomised: 32 children
Study follow‐up: 18 months
Exclusions and losses to follow‐up: no exclusions; 4 (12.5%) were lost to follow‐up
Participants Age: range 6‐13 years
Gender: included boys and girls (numbers not reported)
Culture: children with myopia and near point esophoria identified from medical records and referred by local optometrists
Inclusion criteria: 
  • at least 0.50 D of myopia in both principal meridians of both eyes

  • ages 6‐13.99 years for boys and 6‐12.99 years for girls

  • near point esophoria

  • corrected acuity of at least 20/25 in each eye, distance and near, with SVLs

  • ability to respond to subjective tests


Exclusion criteria: 
  • strabismus

  • astigmatism > 2.00 D in either eye

  • anisometropia> 2 D

  • convergence insufficiency accompanied by symptoms

  • diabetes or other systemic disease with potential effects on refractive error

  • ocular disease other than mild inflammation of the adnexa

Interventions BFs (n = 16): BFs with +1.25 D addition
SVLs (n = 16): SVLs
Note: prescription changes were made if the spherical equivalent in either eye had changed by 0.50 D
Outcomes Primary outcomes
  • Change in refractive error (SER) measured by cycloplegic autorefraction

  • Change in AL measured by Humphrey A/B Scan under cycloplegia


Measurements taken at baseline and every 6 months for 18 months
Unit of analysis: average values of both eyes
 
Notes Study dates: not reported
Trial registration: not reported
Funding source: Northeastern State University Faculty Research Committee (Tahlequah, Oklahoma, USA)

Fulk 2002.

Study characteristics
Methods Study design: parallel‐group RCT and study of variables that may influence myopia progression in children
Study centre: 2 (Tahlequah and Tulsa, Oklahoma, USA)
Number randomised: 82 children
Study follow‐up: 30 months
Exclusions and losses to follow‐up: no exclusions; 7 (8.5%) were lost to follow‐up
Participants Age: mean = 10.7 years (range 6‐12 years)
Gender: 43 boys, 39 girls
Culture: children with myopia and near point esophoria recruited locally and through clinics operated by the Cherokee Nation: 58% white, 29% Native American, 5% Hispanic, 4% African American, 3% other, 1% Asian/Pacific Islander
Inclusion criteria: 
  • at least 0.50 D of myopia in both principal meridians of both eyes

  • ages 6‐12.99 years for boys and 6‐11.99 years for girls

  • near point esophoria

  • corrected VA of at least 20/25 in each eye at distance and binocularly with SVLs

  • corrected stereoacuity of at least 40 s arc with SVLs at 40 cm

  • assent of child and consent to participate


Exclusion criteria: 
  • strabismus

  • astigmatism or anisometropia > 2.00 D

  • diabetes or other systemic disease with potential effects on refractive error

  • ocular disease other than mild inflammation of the adnexa

  • known history of allergic reaction to proparacaine or tropicamide

  • history of use of RGPs

  • current use of bifocals or use within the last year

  • high myopia of ≥ −6.00 D for children < 9 years or ≥ −8.00 D for children ≥ 9 years

  • inability to respond to subjective testing or hold fixation sufficiently to allow for study measurements

Interventions BFs (n = 42): BF lenses with +1.50 D add
SVLs (n = 40)
Note: prescription changes were made if (1) the spherical equivalent in either eye had changed by 0.50 D, or (2) any combination of sphere or cylinder change could improve the distance acuity by ≥ 3 letters in either eye
Outcomes Primary outcome
  • Change in refractive error (SER) (cycloplegic autorefraction)


Secondary outcomes
  • Change in AL (A‐scan ultrasonography)

  • Change in vitreous chamber depth (A‐scan ultrasonography)

  • Changes in cylinder component (J₀ and J₄₅)

  • Variables associated with myopia progression: parental myopia, season, near point habits, and academic achievement


Measurements taken at baseline and every 6 months for 30 months
Unit of analysis: average values of both eyes
 
Notes Study dates: enrolment 20 August‐15 October 15 1996; original follow‐up was for 30 months; some children remained for 54 months
Trial registration: NCT00000128
Funding source: National Eye Institute, National Institutes of Health
Notes: study was also known as the Myopia Progression Study

Garcia‐del Valle 2021.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 7 university and hospital clinics in Spain: Madrid (n = 3), Andalucía (n = 3), and Murcia (n = 1)
Number randomised: 70 children
Study follow‐up: 12 months
Exclusions and losses to follow‐up: 12 (21%) were lost to follow‐up
Participants Age: mean = 12.1 years (range 7‐15 years)
Gender: 21 boys, 37 girls
Culture: European (Spanish)
Inclusion criteria: 
  • children aged 7‐15

  • SER −0.50 to −8.75

  • BCVA = 1.0 (20/20

  • good ocular and general health

  • able to handle and wear contact lenses


Exclusion criteria: 
  • uncontrolled psychiatric or neurological disorders and manifest disability due to age

  • physical or mental conditions to wear contact lenses

Interventions MFSCLs (n = 36)
SVSCLs (n = 34)
Outcomes Primary outcomes
  • Change in SER error from baseline (cycloplegic autorefraction)

  • Change in AL from baseline (Zeiss IOL Master 700)


Secondary outcomes
  • Proportion of participants reporting good comfort and good quality of vision

  • Frequency of ocular AEs


Measurements taken at 12 months
Unit of analysis: data from both eyes included (correlation between eyes adjusted in statistical model)
Notes Study dates: May 2014‐April 2017
Trial registration: not reported
Funding source: "Tiedra Farmacéutica S.L. was the sponsor for this study. Tiedra Farmacéutica S.L. is the owner of the patent for Esencia design and provided the study contact lenses and maintenance solutions"
Disclosures: not reported

Guo 2021.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Optometry Clinic of The Hong Kong Polytechnic University
Number randomised: 82 children
Study follow‐up: 12 months
Exclusions and losses to follow‐up: 24 (30%) were excluded or lost to follow‐up
Participants Age: mean = 9.2 years (range 6 to <11 years)
Gender: 28 boys, 42 girls
Culture: Chinese
Inclusion criteria: 
  • age 6 to <11 years

  • Chinese ethnicity (both parents)

  • myopia between −4.00 D to −0.75 D; astigmatism; axes 180 30: ≥ −2.50 D; other axes: ≥ −0.50 D; < 1.00 D difference in spherical equivalent between the two eyes

  • BCVA logMAR 0.10 or better in both eyes

  • symmetrical corneal topography with corneal toricity < 2.00 D in either eye

  • normal ocular health other than myopia


Exclusion criteria: 
  • history of myopia control treatment

  • strabismus or amblyopia

  • systemic condition, which might affect refractive development

  • contraindications to contact lens wear

  • history of ocular inflammation or infection 

  • corneal dystrophy

Interventions OK lenses of BOZD 6 mm (n = 42)
OK lenses of BOZD 5 mm (n = 40)
Outcomes Primary outcomes
  • Change in AL from baseline (Zeiss IOL Master 500)


Secondary outcomes
  • Change in cycloplegic refraction

  • Change in BCVA


Measurements taken at 6 and 12 months
Unit of analysis: data from right eye analysed
Notes Study dates: June 2017‐March 2021
Trial registration: NCT03191942
Funding source: The Hong Kong Polytechnic University Research Residency Scheme of the School of Optometry
Disclosures: "R Kojima is a Clinical Research and Development Director for Precision Technology Services (Vancouver, Canada), a partner in the KATT Design Group (Vancouver, Canada) and a clinical advisor to Medmont International Pty, (Nunawading, Australia)"

Han 2018.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Affiliated Yixing People Hospital of Jiangsu University)
Number randomised: 240 children
Study follow‐up: 1 year
Exclusions and losses to follow‐up: none
Participants Age: mean = 9.8 years (range 9‐14 years)
Gender: 117 boys, 123 girls
Culture: China
Inclusion criteria: children with myopia treated in the study authors’ hospital
Exclusion criteria: not reported
Interventions Ordinary frame glasses (n = 90)
M‐OK lenses (n = 90): Mouldway OK lenses; described as “four‐district seven‐arc reverse geometric design. The main component is Boston XO (Bausch + Lomb, USA [Hexafocon A, main component fluorosiliconepropenylphenol ester]) and the standard piece was the Mouldway IV‐DF type”
Medcall lenses (n = 60):  “fitted with a new paracentral defocus‐reducing lens”
Note: none
Outcomes Primary outcome
  • Outcomes not clearly specified as primary or secondary. Outcomes reported included “diopter, accommodative lag, and accommodative facility”


Secondary outcome
  • Not reported


Measurements taken at 1 year
Unit of analysis: individual (1 eye per person enroled)
Notes Study dates: May 2013‐May 2015
Trial registration: not reported
Funding source: “the authors have no funding or conflicts of interest to disclose”

Han 2019.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Shanghai Tongji Hospital, China
Number randomised: 150 children
Study follow‐up: 24 months
Exclusions and losses to follow‐up: 16 (11%) were lost to follow‐up by 24 months
Participants Age: mean = 9.4 years (range 6‐12 years)
Gender: 75 boys, 75 girls
Culture: Chinese
Inclusion criteria: 
  • aged 6‐12 years

  • myopia −0.25 D to −6.00 D

  • no ocular and underlying diseases


Exclusion criteria: 
  • anisometropia

  • amblyopia

  • allergy or intolerance to the use of anticholinergic drops

Interventions 1% atropine eyedrops (n = 60)
Combined treatment (0.5% racanisodamine eye drops and 1% atropine eyedrops) (n = 60)
No treatment (n = 30)
Outcomes Primary outcomes
  • SER

  • Corneal curvature

  • AL

  • IOP and AEs


Measurements taken at 6‐monthly intervals for 24 months
Unit of analysis: not reported
Notes Study dates: July 2013‐June 2014
Trial registration: not reported
Funding source: Shanghai Municipal Commision of Health and Family Planning (General program) (201540252)
Disclosures: not reported

Hasebe 2008.

Study characteristics
Methods Study design: cross‐over RCT
Study centre: 1 (Okayama University Medical School)
Number randomised: 92 children
Study follow‐up: 3 years
Exclusions and losses to follow‐up: no exclusions; 6 (6.5%) were lost to follow‐up
Participants Age: mean = 9.85 years (range 6‐12 years)
Gender: 47 boys, 45 girls
Culture: Okayama, Japan
Inclusion criteria: 
  • age 6‐12 years

  • SER error between −1.25 D and −6.00 D in both eyes, as measured by noncycloplegic autorefraction

  • BCVA of 20/20 or better in each eye

  • no other eye disease

  • experience wearing spectacles

  • willingness to wear glasses constantly and attend follow‐up visits

  • acceptance of randomisation


Exclusion criteria: 
  • astigmatism > 1.50 D in both eyes

  • anisometropia > 1.50 D

  • manifest strabismus;

  • birth weight < 1250 g

  • heterotropia or severe ophthalmic disease that may affect refractive development

  • previous use of PALs or contact lenses

Interventions PALs (n = 46): 18 months wearing PALs (add +1.50 D), followed by 18 months wearing SVLs
SVLs (n = 46): 18 months wearing SVLs, followed by 18 months wearing PALs (addition +1.50 D)
Note: prescription changes were made if corrected distance VA was < 20/30 in at least 1 eye
Outcomes Primary outcome
  • Progression of myopia measured by cycloplegic autorefraction


Secondary outcomes
  • Noncycloplegic autorefraction

  • Noncycloplegic subjective refraction

  • Cycloplegic subjective refraction

  • Distant vision and myopia place

  • Corrected distant vision

  • Lags of accommodation measured by noncycloplegic, open‐field autorefraction

  • Near point of accommodation

  • Reaction of accommodation by open‐field autorefraction


Measurements taken at baseline and every 6 months for 3 years
Unit of analysis: child‐based (mean of both eyes or right eye only)
 
Notes Study dates: enroled July 2002‐June 2003
Trial registration: ISRCTN28611140
Funding source: Japanese Ministry of Education, Culture, Sports, Science and Technology, and Megane Tanaka Chain, Ltd

Hasebe 2014.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 3 (Okayama University Medical School, Japan; Eye Hospital of Wenzhou Medical College, China; Eulji University, South Korea)
Number randomised: 197 children (120 from China and 77 from Japan)
Study follow‐up: 2 years
Exclusions and losses to follow‐up: the trial in South Korea was terminated after 12 months due to protocol violation and the data were not included; 28/197 (14%) did not complete 2 years of follow‐up
Participants Age: mean = 10 years (range 6‐12 years)
Gender: 95 boys, 74 girls
Culture: Chinese and Japanese children
Inclusion criteria: 
  • age 6‐12 years

  • SER error between −0.50 D and −4.50 D

  • astigmatism ≤ 1.50 D

  • anisometropia ≤ 1.50 in spherical or cylindrical error

  • BCVA of 6/9 (20/30) or better in each eye

  • normal ocular and general health

  • willingness to wear spectacle lenses continuously

  • willingness and ability to tolerate cycloplegia

  • informed parental consent


Exclusion criteria: 
  • amblyopia or manifested squint

  • history of rigid contact lens or BF contact lens wear

  • use of BF or progressive lenses or other myopia treatment in previous 12 months

  • abnormal binocular function

  • vestibular disorders or motor imbalance

  • any systemic condition affecting refractive development or vision, or any condition precluding adherence to the study protocol (e.g. not available for follow‐up for 2 years)

Interventions PA‐PALs +1.0 D (n = 67): positively aspherised PALs with +1.00 D add
PA‐PALs +1.5 D (n = 63): positively aspherised PALs with +1.50 D add
SVLs (n = 67)
Note: all lenses are worn during normal waking hours
Outcomes Primary outcomes
  • Refractive error, measured by cycloplegic autorefraction

  • AL, measured by IOL Master (Carl Zeiss Meditec)


Secondary outcome: peripheral refractive error, measured using an open field autorefractor
Measurements taken at baseline and at 6, 12, 18, and 24 months
Unit of analysis: eye (both eyes of each child analysed)
Notes Study dates: July 2008‐June 2009
Trial registration: ACTRN12608000566336
Funding source: "supported by Carl Zeiss Vision"
Conflict of interest: "S. Hasebe, Carl Zeiss Vision Australia Holdings Ltd. (F); J. Jun, Carl Zeiss Vision Australia Holdings Ltd. (F); S.R. Varnas, Carl Zeiss Vision Australia Holdings Ltd. (E), P"

Hieda 2021.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 7 university hospitals in Japan
Number randomised: 171 children
Study follow‐up: 24 months
Exclusions and losses to follow‐up: 13 (8%) were withdrawn or lost to follow‐up
Participants Age: mean = 9.0 years (range 6‐12 years)
Gender: 74 boys, 94 girls
Culture: Japanese
Inclusion criteria: 
  • aged 6‐12 years

  • cycloplegic SER between −1.00 D and −6.00 D in both eyes

  • anisometropia of objective spherical equivalent ≤ 1.50 D

  • astigmatism of ≤ 1.50 D (5) corrected VA ≥ 1.0

  • children with normal IOP


Exclusion criteria: 
  • abnormal binocular function; amblyopia or manifest strabismus

  • children with ocular diseases other than myopia

  • children with ocular or systemic diseases that potentially have an effect on myopia or refractive power

  • previous or current use of contact lenses, BFs, progressive lenses, or other forms of treatment (including atropine) for myopia

  • children with a history of cardiac or respiratory disease

  • children with a history of pharmacotherapy for asthma over the past year

Interventions Atropine 0.01% eyedrops (n = 85)
Placebo eyedrops (n = 86)
Outcomes Primary outcomes
  • Change in SER error from baseline (cycloplegic autorefraction)

  • Change in AL from baseline (Zeiss IOL Master)


Secondary outcomes
  • Incidence of AEs


Measurements taken every 6 months for 24 months
Unit of analysis: data from both eyes included (correlation between eyes adjusted in statistical model)
Notes Study dates: December 2014‐September 2019
Trial registration: JPRN‐UMIN000018041
Funding source: "This study was supported by Eye‐Lens Pte., Ltd., Singapore. The sponsor had no role in the design or conduct of this research."
Disclosures: several authors declared support in the form of lecture fees or honoraria from pharmaceutical companies

Houston Study 1987.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (University of Houston, Texas, USA)
Number randomised: 207 children
Study follow‐up: 3 years
Exclusions and losses to follow‐up: 83 (40%) children were excluded from or dropped out of the study
Participants Age: range 6‐15 years
Gender: 58 boys and 66 girls completed the study
Culture: children were recruited from patients, from family members of faculty and staff, and from the racially diverse Houston community
Inclusion criteria: 
  • myopia of −0.25 D in 1 or both eyes

  • ages 6‐15 years

  • BCVA of 20/20 or 20/15

  • normal ocular health

  • ability to provide informed consent


Exclusion criteria: 
  • strabismus or amblyopia

  • contact lens wearers

  • astigmatism of ≥ 2.00 D 

  • particularly high or low gradient AC/A ratios

Interventions BFs 1: BFs with +1.00 D addition
BFs 2: BFs with +2.00 D addition
SVLs
Note: prescription changes were made if (1) there was a change in spherical power of ≥ 0.50 D in one or both eyes, or (2) there was an improvement of 1 line of VA. 1 participant was allowed to wear contact lenses when playing basketball
Outcomes Patient care team outcomes (unmasked)
  • Change in refractive error (SER, noncycloplegic subjective refraction)

  • Characteristics of children for whom BFs were most effective in reducing the progression of myopia


Evaluation team outcomes (masked)
  • Change in refractive error (cycloplegic retinoscopy, noncycloplegic autorefraction, and cycloplegic autorefraction)

  • Change in corneal refracting power

  • Change in anterior chamber depth

  • Change in lens radii of curvature and thickness

  • Change in vitreous chamber depth

  • Change in AL of the eye


Measurements taken at baseline and every 6 months for 3 years
Unit of analysis: data from right eyes
 
Notes Study dates: "subjects were admitted to the study over a period of 20 months, in five 'accrual groups.' The first group of subjects entered the study in February, 1981 and completed the study in February, 1984, whereas the last group of subjects entered the study in October, 1982," and completed the study in October, 1985
Trial registration: not reported
Materials: BFs were executive 1‐piece lenses in CR‐39 plastic (American Optical Corporation); SVLs were polycarbonate lenses (Gentex Corporation)

Jakobsen 2022.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Department of Ophthalmology, Vejle Hospital, University Hospital of Southern Denmark
Number randomised: 60 children
Study follow‐up: 18 months
Exclusions and losses to follow‐up: 12 (5%) were excluded or lost to follow‐up
Participants Age: mean = 9.97 years (range 6‐12 years)
Gender: 26 boys, 34 girls
Culture: European (Scandinavian)
Inclusion criteria: 
  • myopia –0.5 to –4.75 D cycloplegic spherical in both eyes

  • regular astigmatism ≤ 2.5 D in cycloplegia in both eyes

  • age 6‐12 years at time of inclusion

  • anisometropia < 1.5 D spherical equivalent

  • BCVA of 78 ETDRS letters or better in both eyes


Exclusion criteria: 
  • manifest or latent squint

  • contraindications to the use of OK lenses (keratoconus, allergic conjunctivitis, keratoconjunctivitis sicca)

  • previous eye surgery

  • chronic eye disease demanding daily use of eye drops

  • 1 or both parents being ethnic Middle Eastern, Asian, African, Latin American, Hispanic or Spanish

Interventions OK lenses (n = 30)
SVLs (n = 30)
Outcomes Primary outcomes
  • Change in AL from baseline (Zeiss IOL Master)


Secondary outcomes
  • Change in SER from baseline

  • QoL (PREP 2)

  • Safety evaluation (Efron grading scale


Measurements taken at 6, 12 and 18 months
Unit of analysis: average of both eyes analysed
Notes Study dates: March 2017‐April 2020
Trial registration: NCT03246464
Funding source: grants from the Region of Southern Denmark; The Danish Eye Research Foundation; Fight for Sight, Denmark; The Danish Eye Research Foundation; 
Disclosures: the study authors declare no conflicts of interest

Jensen 1991.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Odense University Hospital, Denmark)
Number randomised: 159 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: 4 (2.5%) children who were randomised were excluded from the analyses; 16 (10%) were lost to follow‐up
Participants Age: mean = 10.9 years
Gender: 87 boys, 72 girls
Culture: medical records of children from schools in Odense, Denmark, were screened for myopia (n = 8769). Possible cases of myopia underwent a primary examination (n = 1216). Myopic children with at least −1.0 D in either eye, and in 2nd to 5th grades, were examined at the eye clinic (n = 361). Children meeting inclusion/exclusion criteria at the eye exam were mailed invitations to participate in the trial (n = 227)
Inclusion criteria: 
  •  in 2nd to 5th grades at screening

  • myopia with SER error between −1.25 D and −6.00 D in both eyes

  • normal corrected vision

  • Danish parents

  • affirmative response to mailed invitation for study


Exclusion criteria: 
  • unilateral myopia

  • eye disease or general illness, especially heart/lung disease

  • experience in pilot study

Interventions BFs (n = 57): constant wear of BFs with +2.0 D addition to upper edge of reading segment
Timolol (n = 51): 1 drop of 0.25% timolol maleate in each eye twice daily and constant wear of SVLs for corrected VA ≥ 0.8
Control (n = 51): constant wear of SVLs for corrected VA ≥ 0.8
Note: participants were permitted to wear their own SVLs if corrected VA was ≥ 0.8
Outcomes Primary outcomes
  • Rate of myopia progression and changes in refractive components (SER measured by cycloplegic autorefraction)

  • Prevention or delay of myopia with BFs

  • Prevention or delay of myopia with pressure‐lowering eye drops


Secondary outcomes
  • Changes in the fundus

  • IOP

  • Phoria status

  • Accommodation

  • Close work

  • Body growth


Measurements taken at baseline and every 6 months for 2 years
Unit of analysis: right eyes and left eyes analysed separately
Notes Study dates: screening January‐April 1983; eye clinic exams October 1984‐April 1985
Trial registration: not reported
Notes: children who chose not to participate in the study (n = 44) did not statistically differ from those examined with regard to age and degree of myopia

Katz 2003.

Study characteristics
Methods Study design: parallel‐group RCT, with 3‐month adaptation period
Study centre: 1 (Myopia Clinic of the Singapore Eye Research Institute)
Number randomised: 564 children (428 children attended initial visit; 383 children completed the adaptation period)
Study follow‐up: 2 years
Exclusions and losses to follow‐up: 136 (24%) children who were randomised did not attend the initial visit, and 45 (8%) more did not complete the adaptation period; 86 (22%) of the 383 children who completed the adaptation period were lost to follow‐up
Participants Age: mean = 8.3 years (range 6‐12 years)
Gender: 204 boys, 179 girls
Culture: Singaporean children with Chinese ethnicity
Inclusion criteria: 
  • age 6‐12 years

  • myopia with SER error between −1.0 D and −4.0 D

  • Chinese ethnicity

  • provided informed consent


Exclusion criteria: 
  • astigmatism > 2.0 D

  • previous contact lens wear

  • other ocular pathologies


Note: all participants were provided a 3‐month period to adapt to assigned intervention
Interventions Contact lenses (n = 158): RGPs worn daily for at least 8 h/day
Spectacles (n = 225): SVLs worn daily for at least 8 h/day
Note: prescription changes were made if corrected VA fell below 20/40
Outcomes Primary outcome
  • Change in refractive error (SER)


Measured by subjective cycloplegic refraction from post adaption through 2 years of follow‐up
Secondary outcomes
  • Change in keratometry (autokeratometry)

  • Change in AL (A‐scan ultrasonography)


Measurements taken at baseline and every 3 months over a 24‐month period
Unit of analysis: only data from right eyes reported
Notes Materials: Asian Design Lens, Baush and Lomb, Rochester, New York, USA
Trial registration: not reported
Adherence to treatment was measured for children and parents (agreement was almost 100%) and was defined as use of contact lenses or spectacle use for at least 8 h/day, 7 days/week
Notes: study is also known as the Contact Lens‐Myopia Treatment Study (CL‐MTS)
Additional data: study author provided unpublished data via email correspondence

Kinoshita 2020.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Konno Eye Clinic and Omiya Hamada Eye Clinic, Japan
Number randomised: 80 children
Study follow‐up: 24 months
Exclusions and losses to follow‐up: 7 (9%) were withdrawn or lost to follow‐up
Participants Age: mean = 10.3 years (range 8‐12 years)
Gender: 36 boys, 37 girls
Culture: Japanese
Inclusion criteria: 
  • cycloplegic SER of −1.00 D to −6.00D in both eyes 

  • astigmatism of ≤ 1.50 D in both eyes

  • anisometropia of ≤ 1.50 D

  • BCVA of ≤ 0.00 logarithm of the minimum angle of resolution (logMAR) unit in each eye


Exclusion criteria: 
  • presence of ocular disorders such as strabismus and amblyopia

  • systemic disorders such as cardiac or respiratory illness

  • low birth weight of ≤ 1500 g

  • a history of hypersensitivity to atropine

  • using OK and/or atropine ophthalmic solutions

Interventions Combination group: OK + 0.01% atropine eyedrops (n = 38)
Monotherapy group: OK only (n = 35)
Outcomes Primary outcomes
  • Change in AL from baseline (Zeiss IOL Master)


Secondary outcomes
  • Corneal endothelial cell density


Measurements taken every 6 months for 24 months
Unit of analysis: child‐based average of both eyes
Notes Study dates: June 2014‐December 2016
Trial registration: UMIN000014362
Funding source: JSPS KAKENHI (Grant No. JP26462646) from the Japan Society for the Promotion of Science, Tokyo,
Disclosures: the study authors declare no competing interests

Koomson 2016.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Kumasi, Ghana)
Number randomised: 150 children
Study follow‐up: 24 months
Exclusions and losses to follow‐up: 1 child in the fully corrected group dropped out before the 24‐month visit
Participants Age: mean = 12.39 years (range 10‐15 years)
Gender: 60 boys, 90 girls
Culture: recruited from "eight purposively chosen high socioeconomic schools in the Kumasi metropolis" in Ghana
Inclusion criteria: 
  • healthy children, ages 10‐15 years

  • spherical equivalent −1.25 to −4.50 D as measured by cycloplegic refraction

  • VA of 0.20 logMAR or worse with habitual spectacles and logMAR 0.00 or better with full correction

  • willingness to wear study spectacles only and to wear them during waking hours


Exclusion criteria: 
  • strabismus

  • amblyopia

  • astigmatism > 1.25 D

  • anisometropia > 1.00 D

  • parental myopia

  • allergy to cycloplegic agents

  • use of MF optical lenses or pharmacological agents history of contact lens wear

Interventions Undercorrected group (n = 75): SVLs blurred by +0.50 D
Fully corrected group (n = 75): SVLs
Note: changes in prescription were made if refraction had changed by at least 0.50 D for 1 or both eyes
Outcomes Primary outcome
  • Change in refractive error (SER) measured by cycloplegic autorefraction at 24 months of follow‐up


Secondary outcomes
  • Change in AL at 24 months of follow‐up

  • Correlation between baseline accommodative lag and SER changes at 24 months and between average lag (average of the 6th, 12th, 18th, and 24th months near lags) and SER changes at 24 months


Measurements taken at 6‐month intervals for 2 years
Unit of analysis: child‐based (right eye)
 
Notes Study dates: enrolment September 2010‐March 2011
Trial registration: not reported
Funding source: not reported
Disclosures of interest: not reported

Lam 2020.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University
Number randomised: 183 children
Study follow‐up: 24 months
Exclusions and losses to follow‐up: 14 (8%) lost to follow‐up 9 (5%) withdrawn by 24 months
Participants Age: mean = 10.1 years (range 8‐13 years)
Gender: 105 boys, 78 girls
Culture: Chinese
Inclusion criteria: 
  • SER −1.00 to −5.00D

  • astigmatism and anisometropia of ≤ 1.50 D

  • monocular best VA of 0.00 logMAR or better


Exclusion criteria: 
  • strabismus and binocular vision abnormalities

  • ocular and systemic abnormalities

  • prior experience of myopia control

Interventions Defocus incorporated Multiple Segments (DIMS) spectacle lenses (n = 93)
SVSs (n = 90)
Outcomes Primary outcomes
  • Change in SER error from baseline (cycloplegic autorefraction)

  • Change in AL from baseline (Zeiss IOL Master)


Secondary outcomes
  • Distance and near VA (EDTRS charts)

  • Near phoria and accommodative lag

  • Vision quality, comfort and frequency of visual symptoms with lens wear


Measurements taken every 6 months for 24 months
Unit of analysis: data from right eye analysed
Notes Study dates: August 2014‐July 2017
Trial registration: NCT02206217
Funding source: "This was a collaborative research supported by HOYA, Tokyo, Japan (PolyU grant numbers H‐ZG3B and 1‐87LK). In addition to the financial support, the sponsor also provided manufacturing spectacle lenses and frames. It was a joint collaboration in the design of the DIMS lens"
Disclosures: the study authors declare no conflicts of interest

LAMP Study 2019.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: CUHK Eye Centre of the Chinese University of Hong Kong, Hong Kong, China
Number randomised: 438 children
Study follow‐up: 12 months
Exclusions and losses to follow‐up: 55 (13%) were withdrawn or lost to follow‐up
Participants Age: mean = 8.4 years (range 4‐12 years)
Gender: 248 boys, 190 girls
Culture: Chinese
Inclusion criteria: 
  • aged 4‐12 years

  • myopic refraction of at least 1.0 D in both eyes

  • astigmatism of < 2.5 D

  • documented myopic progression of at least 0.5 D in the past 1 year


Exclusion criteria: 
  • ocular diseases (e.g. cataract, congenital retinal diseases, amblyopia, and strabismus)

  • previous use of atropine or pirenzepine, or OK lens or other optical methods for myopia control

  • allergy to atropine

  • systemic diseases (e.g. endocrine, cardiac, and respiratory diseases)

Interventions Atropine 0.05% eyedrops (n = 102)
Atropine 0.025% eyedrops (n = 91)
Atropine 0.01% eyedrops (n = 97)
Placebo eyedrops (n = 93)
 
Outcomes Primary outcomes
  • Change in SER error from baseline (cycloplegic autorefraction)

  • Change in AL from baseline (Zeiss IOL Master)


Secondary outcomes
  • Change in photopic pupil size

  • Change in accommodative amplitude

  • Change in distance VA (logMAR)

  • Change in near VA (logMAR)

  • Change in vision‐related quality of life


Measurements taken 4 monthly intervals for 12 months
Unit of analysis: data from both eyes included (correlation between eyes adjusted in statistical model)
Notes Study dates: January 2016‐November 2017
Trial registration: CUHK_CCT00383
Funding source: supported in part by the General Research Fund, Research Grants Council, Hong Kong (14111515 [J.C.Y.]); the Direct Grants of the Chinese University of Hong Kong (4054197 [C.P.P.], 4054193 [L.J.C.], and 4054121 and 4054199 [J.C.Y.]); the UBS Optimus Foundation Grant 8984 (J.C.Y.); and the CUHK Jockey Club Children Eye Care Programme
Disclosures: the study authors declare no competing interests

Lu 2015.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Guangzhou Red Cross Hospital, School of Medicine, Jinan University, China)
Number randomised: 80 children
Study follow‐up: 1 year
Exclusions and losses to follow‐up: not reported
Participants Age: mean = 11.21 years (range 9‐14 years)
Gender: 43 boys, 37 girls
Culture: Chinese
Inclusion criteria: 
  • age 9‐14 years

  • progressive (≥ 0.50 D change) myopia from −1.00 D to −5.00 D

  • astigmatism with ≤ 1.50 D with‐rule, ≤ 0.75 D against‐rule

  • BCVA 1.0 or better in both eyes by Snellen chart

  • ocular pressure < 21 mmHg

  • compliance with examination and treatment


Exclusion criteria: 
  • other ocular condition (glaucoma, cataract, iritis, congenital small cornea, keratoconus, fundus lesions, congenital amblyopia, dominant strabismus)

  • family history of hereditary eye disease (e.g. high myopia, Leber disease)

  • recent or current use of drugs that may affect myopia development

  • previous RGP wear

  • other systemic disease (diabetes, Marfan syndrome, albinism, severe sinusitis, etc.)

Interventions Mid‐periphery additional lenses (n = 40): addition up to +2.50 D and adjustment training
SVLs (n = 40): frame glasses
Outcomes Primary outcomes
  • Change in VA

  • Change in D

  • Change in AL

  • Accommodation amplitude

  • Adjustment reaction index

  • AC/A value


Secondary outcomes
  • Not distinguished


Measurements taken every 3 months for 1 year
Unit of analysis: eye (both eyes of each child analysed)
Notes Study dates: January 2014‐July 2015
Trial registration: not reported
Funding source: Guangdong Medical Science and Technology Research Foundation (No. A2014557); Department of Ophthalmology, Guangzhou Red Cross Hospital Affiliated to School of Medicine, Jinan University, China

Lyu 2020.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Zhengzhou University People’s Hospital, Henan Eye Hospital, Zhengzhou University, China
Number randomised: 102 children
Study follow‐up: 13 months
Exclusions and losses to follow‐up: 15 (15%) excluded or lost to follow‐up
Participants Age: mean = 12.6 years (range 8‐12 years)
Gender: 49 boys, 42 girls
Culture: Chinese
Inclusion criteria: 
  • SER error −6.00 to −8.75 D

  • astigmatism < 1.50 D

  • BCVA ≤ 0 (logarithmic acuity)

  • normal IOP (10–21 mm Hg)

  • tear break‐up time ≥ 10 s and Schirmer test ≥ 10 mm


Exclusion criteria: 
  • ocular or systematic diseases that could cause impaired vision or the progression of myopia

Interventions OK lenses (target myopia reduction −6.00D) (n = 34)
OK lenses (target myopia reduction −4.00D) (n  =34)
SVLs (n = 34)
Outcomes Primary outcomes
  • Change in SER error from baseline (cycloplegic autorefraction)

  • Change in AL from baseline (Zeiss IOL Master)


Secondary outcomes
  • Satety evaluation (biomicroscopiic examination and Efron grading scales)

  • Change of corneal curvature

  • Change in corneal endothelial density


Measurements taken 6 months and up to 13 months
Unit of analysis: average of both eyes analysed
Notes Study dates: January 2014‐March 2015
Trial registration: not reported
Funding source: The Medical Sciences Project of Henan Province, China (201503203)
Disclosures: not reported

MIT Study 2001.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (National Taiwan University Hospital Vision Care Center)
Number randomised: 227 children
Study follow‐up: 18 months
Exclusions and losses to follow‐up: 39 (17%) children were excluded or lost to follow‐up
Participants Age: range 6‐13 years
Gender: 105 boys, 122 girls
Culture: school children in Taiwan with an average myopia of −3.27 D
Inclusion criteria: 
  • age 6‐13 years

  • provided informed consent

  • willing to wear glasses

  • available for follow‐up period


Exclusion criteria: 
  • tropia or amblyopia

  • increase of > 2 D in any eye during the treatment period

Interventions SVLs (n = 76): regular SVLs worn all the time and placebo drops
PALs (n = 75): MF lenses with the near addition part for reading and placebo drops
PALs plus atropine (n = 76): 0.5% atropine instilled once a day at bedtime, in addition to PALs
Note:  'prescription changes were made for any child whose refractive error increased by > 0.75 D'
Outcomes Primary outcome
  • Myopic progression measured by cycloplegic autorefraction (SER)


Secondary outcomes
  • Change in IOP (Tonopen)

  • Change in biometric AL (A‐scan ultrasonography)

  • Change in corneal radius (autorefraction)


Measurements taken at baseline and every 3 months over an 18‐month period
Unit of analysis: data from right eyes analysed
Notes Study dates: 1997‐2000
Trial registration: not reported
Materials: Hoyalux plastic lenses were used for PALs; polycarbonate plastic lenses were used for SVLs
Additional data: study author provided unpublished data via email correspondence. PALs plus atropine arm was omitted from the analysis.

Moriche‐Carretero 2021.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Spanish outpatient hospital
Number randomised: 339 children
Study follow‐up: 24 months
Exclusions and losses to follow‐up: 12 (4%) were lost to follow‐up
Participants Age: mean = 7.3 years (range 5 ‐11 years)
Gender: 155 boys, 184 girls
Culture: Spansh
Inclusion criteria: 
  • age 5‐11 years inclusively at baseline

  • cycloplegic SER between −0.50 and −4.50 D in each eye

  • astigmatism ≤ 1.50 D in both eyes

  • anisometropia ≤ 1.00 D

  • no strabismus as confirmed in a cover test

  • BCVA 20/30 or better


Exclusion criteria: 
  • systemic disease

  • prematurity

  • prior corneal surgery

  • ocular motility anomalies (e.g. corneal transplant or trauma) or ocular inflammation or infection

Interventions 0.01% atropine eyedrops (n = 171)
Control (no treatment) (n = 168)
Outcomes Primary outcomes
  • SER error by cyloplegic autorefraction (Potec PRK 5000, Potek, Korea)

  • AL (IOL Master 500, Carl Zeiss Meditec)


Secondary outcomes
  • Anterior chamber depth

  • Corneal curvature

  • AEs


Measurements taken at baseline and 24 months
Unit of analysis: child‐based (random eye)
Notes Study dates: 2016‐2017
Trial registration: not reported
Funding source: not reported
Disclosures: "The authors declare that they have no competing interest"

Pärssinen 1989.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (outpatient clinic of the Central Hospital of Central Finland)
Number randomised: 240 children
Study follow‐up: 3 years
Exclusions and losses to follow‐up: 1 (0.4%) child who was randomised was excluded from the analyses; 2 (0.8%) were lost to follow‐up
Participants Age: mean = 10.9 years (range 8.8 ‐12.8 years)
Gender: 119 boys, 121 girls
Culture: schoolchildren with suspected myopia were referred by school nurses and doctors after routine vision check‐ups
Inclusion criteria: 
  • in 3rd‐5th grade

  • myopia with SER error between −0.25 D and −3.0 D in both eyes and ≥ −0.50 D in the worst eye

  • corrected VA of 6/6 or better in both eyes


Exclusion criteria: 
  • astigmatism > 2.0 D

  • anisometropia > 2.0 D

  • manifest strabismus

  • horizontal phorias more than −10 or +9 Δ or vertical > 1 Δ

  • previous use of spectacles for myopia

  • eye disease or serious general disease

  • plans to move out of the area in the near future or the child not wanting to have spectacles

Interventions Distant use (n = 80): minus lenses with full correction to be used for distant vision only; advised to read at greatest distance possible
Bifocals (n = 80): clear plastic bifocal lenses with +1.75 D addition for continuous use
Continuous use (n = 79): minus lenses with full correction for continuous use; advised to remove spectacles only if there was danger of breaking them
Note: prescription changes were made if corrected VA fell below 20/40
Outcomes Primary outcome
  • Change in SER (subjective cycloplegic refraction)


Secondary outcomes
  • Change in spherical refraction

  • Change in VA

  • Change in astigmatism

  • Change in reading distance


Measurements taken at baseline and annually for 3 years
Unit of analysis: right eyes and left eyes analysed separately
 
Notes Study dates: enrolment March 1983‐April 1985
Trial registration: not reported
Funding source: Academy of Finland
Compliance was measured by questionnaires and participants were classified as compliant, partly compliant, or noncompliant

PIR‐205 Study 2004.

Study characteristics
Methods Study design: parallel‐group RCT
Study centres: 13 (US academic clinics and private practices)
Number randomised: 174 children
Study follow‐up: 1 year (planned), plus 1 year extension
Exclusions and losses to follow‐up: 27 (15.5%) children who were randomised were excluded from the analyses; 2 (1%) were lost to follow‐up
Participants Age: mean = 9.9 ± 1.3 years (range 8‐12 years)
Gender: 71 boys, 103 girls
Culture: children from USA cities of study centres: 73% white, 7% black, 4% Asian, 12% Hispanic, 4% other
Inclusion criteria: 
  • age 8‐12 years

  • myopia of −0.75 D to −4.00 D

  • BCVA of 20/25 or better

  • normal pupils

  • good general health


Exclusion criteria: 
  • anisometropia or astigmatism > 1.00 D

  • any manifest tropia

  • current use of either contact lenses or BFs

  • history of ocular surgery, trauma, or chronic ocular disease, including allergic conjunctivitis

  • disease requiring long‐term or regular intermittent medication

  • behavioural or neurological disorder that would interfere with the study

  • participation in any study that involved an investigational drug within 1 month of enrolment

  • intolerance or hypersensitivity to topical anaesthetics, mydriatics, or components of the formulations

  • contraindications to antimuscarinic agents

  • pregnancy or planned pregnancy

Interventions Pirenzepine (n = 117): 2% pirenzepine ophthalmic gel applied twice a day
Control (n = 57): vehicle‐placebo gel applied twice a day
Outcomes Primary outcome
  • Change in refractive error measured by cycloplegic autorefraction (SER)


Secondary outcome
  • Change in AL measured by A‐scan ultrasonography


Measurements taken at baseline and every 3 months for 1 year
Unit of analysis: average of both eyes
Notes Study dates: 1 March 2000‐28 February 2002
Trial registration: not reported
Funding source: Valley Forge Pharmaceuticals, Inc.
Notes: study is also known as the Collaborative Assessment of Myopia Progression with Pirenzepine (CAMPP) study
 

Ren 2017.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Changsha Honglang Eye Hospital, Changsha 410000, Hunan Province, China
Number randomised: 150 children
Study follow‐up: 12 months
Exclusions and losses to follow‐up: not reported
Participants Age: mean = 11.96 years (range 8‐15 years)
Gender: 72 boys, 78 girls
Culture: Chinese
Inclusion criteria: not reported
Exclusion criteria: not reported
Interventions Low concentration atropine (0.01%) (n = 50)
OK lenses (n = 50)
Single vision spectacle lenses (n = 50)
Outcomes Primary outcomes
  • Change in AL from baseline

  • Change in SER from baseline


Measurements taken at 12 months
Unit of analysis: not reported
Notes Study dates: January 2014‐March 2015
Trial registration: not reported
Funding source: not reported
Disclosures: not reported

ROMIO Study 2012.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Hong Kong Polytechnic University)
Number randomised: 102 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: 24 (24%) children who were randomised (14 in the OK group and 10 in the control group) were excluded from the analyses, of whom, 9 (8.8%) were lost to follow‐up
Participants Age: mean = 9 years (range 6‐10 years)
Gender: 52 boys, 50 girls
Culture: Hong Kong
Inclusion criteria: 
  • aged 6‐10 years

  • myopia between 0.50 D and 4.00 D in at least 1 eye and between 0.50 D and 4.50 D in both eyes

  • astigmatism < 1.50 D, with‐the‐rule astigmatism (axes 180 ± 30) ≤ 1.25 D, astigmatism of other axes ≤ 0.50 D in both eyes

  • anisometropia ≤ 1.50 D)

  • BCVA logMAR 0.10 or better in both eyes

  • symmetrical corneal topography with corneal toricity < 2.00 D in either eye

  • agree to randomisation


Exclusion criteria: 
  • strabismus at distance or near

  • history of contact lens wear or myopia control treatment

  • contraindication for contact lens wear and OK

  • history of ocular surgery, trauma, or chronic ocular disease

  • concurrent use of medications that may affect tear quality

  • systemic or ocular conditions that may affect tear quality or contact lens wear or that may affect refractive development

  • poor compliance with tests

  • lack of willingness to comply with allocated treatment and follow‐up schedule

Interventions OK (n = 51): OK lenses
SVLs (n = 51)
Participants wore assigned treatment on a daily basis
Outcomes Primary outcome
  • Axial elongation


Secondary outcome
  • AEs


Measurements taken at baseline and at 6, 12, 18, and 24 months
Unit of analysis: child‐based (right eye)
Notes Study dates: enrolment March 2008‐November 2009
Trial registration: NCT00962208
Funding source: "supported by a collaborative agreement between The Hong Kong Polytechnic University and Menicon Co. Ltd., Japan; contact lenses and solutions and spectacles were sponsored by Menicon Co. Ltd., NKL Contactlenzen B.V., Alcon Hong Kong, Bausch & Lomb Hong Kong, Skyview Optical Co. Ltd., Hong Kong, and Hong Kong Optical Lens Co., Ltd.; and Niche Myopia Funding Grant J‐BB7P for facilities at the Centre for Myopia Research"

Ruiz‐Pomeda 2018.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Novovision ophthalmologic clinic and the Universidad Europea [European University] of Madrid, Spain
Number randomised: 79 children
Study follow‐up: 24 months
Exclusions and losses to follow‐up: 5 (6%) lost to follow‐up
Participants Age: mean = 10.6 years (range 8‐12 years)
Gender: 33 boys and 41 girls
Culture: European (Spanish) "87.3% of fathers and 86.1% of mothers were Caucasian [white]"
Inclusion criteria: 
  • SER −0.75 to −4.00D

  • astigmatism < 1.00 D

  • monocular best VA of +0.10 logMAR or better


Exclusion criteria: 
  • current or prior contact lenses wear; current or prior use of BFs, PALs, atropine, pirenzepine, or any other myopia control treatment ; regular use of ocular medications and artificial tears; current uses of systemic medications, which may significantly affect contact lens wear, tear film production, pupil size, accommodation, or refractive state

  • a history of corneal hypoesthesia, corneal ulcer, corneal infiltrates, ocular viral or fungal infections, or other recurrent ocular infections

  • strabismus by cover test at far (4 m) or near (40 cm) wearing distance correction; systemic or ocular disease affecting ocular health; keratoconus or an irregular cornea

  • CCLRU grade ≥ 2 for any given anterior segment ocular clinical signs; having pathological myopia; and connective tissue disorders

Interventions Dual focus soft contact lens (MiSight) (n = 46)
SVSCLS (n = 33)
Outcomes Primary outcomes
  • Change in SER error from baseline (cycloplegic autorefraction)

  • Change in AL from baseline (Zeiss IOL Master)


Measurements taken every 6 months for 24 months
Unit of analysis: data from the dominant eye analysed
Notes Study dates: September 2013‐June 2016
Trial registration: NCT01917110
Funding source: CooperVision S.L. Spain provided financial support. CooperVision S.L. provided the study contact lenses and the funding to carry out the clinical trial
Disclosures: the study authors declare no conflicts of interest

Sankaridurg 2010.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Zhongshan Ophthalmic Center, Sun Yet Sen University, China)
Number randomised: 210 children
Study follow‐up: 12 months (study was originally planned to be 2 years in duration)
Exclusions and losses to follow‐up at 12‐month visit: 2 children who were randomised were excluded from the analyses; 7 (3.3%) were lost to follow‐up
Participants Age: mean = 11 years (range 6‐16 years)
Gender: 110 boys, 100 girls
Culture: Chinese children in Guangzhou, China
Inclusion criteria: 
  • age 6‐16 years

  • bilaterally myopic (spherical component range from −0.75 D to −3.50 D inclusive) with astigmatism not exceeding −1.50 D and maximum of 1.00 D of anisometropia

  • vision correctable to 6/9.5 or better in each eye 

  • ocular findings considered to be normal 

  • willingness to wear study spectacles and adhere to the protocol schedule

Interventions Novel spectacle lens type I (n = 50): a rotationally symmetrical design; featured a clear central aperture of 20 mm diameter, with maximum spherical equivalent of +1.0 D relative peripheral power achieved 25 mm from its axis
Novel spectacle lens type II (n = 60): a rotationally symmetrical design; featured a clear central aperture of 14 mm diameter, with maximum spherical equivalent of +2.00 D relative peripheral power achieved 25 mm from its axis
Novel spectacle lens type III (n = 50): an asymmetrical design; a clear central aperture extended approximately 10 mm either side of centre along the horizontal meridian and a similar distance inferiorly, with positive additional peripheral power of 1.9 D 25 mm from the axis in that meridian
SVLs (n = 50): conventional, single vision design
Note: lenses were fitted to spectacle frames that ranged in eye‐size from 45 mm to 55 mm with depths from 27 mm to 33 mm
Outcomes Primary outcome
  • Cycloplegic autorefraction assessed with an open‐field autorefractor


Secondary outcome
  • AL


Measurements taken at baseline, 6 months, and 12 months
Unit of analysis: average of both eyes
Notes Study dates: recruitment October 2007‐January 2009
Trial registration: not reported
Funding source: Australian Federal Government; Institute for Eye Research, Sydney, Australia; Vision CRC, Australia
Lenses were provided by industry

Sankaridurg 2019.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Brien Holden Vision Institute clinical trial facility located at Zhongshan Ophthalmic Centre, Guangzhou, China
Number randomised: 508 children
Study follow‐up: 24 months
Exclusions and losses to follow‐up: 118 (27%) lost to follow‐up
Participants Age: mean = 10.4 years (range not reported)
Gender: 246 boys, 262 girls
Culture: Chinese
Inclusion criteria: 
  • SER −0.75 to −3.50D

  • astigmatism ≤ 0.7D

  • vision correctable to 6/9.5 or better

  • normal ocular health


Exclusion criteria: 
  • pre‐existing ocular or systemic conditions that precluded lens fitting and safe wear of lenses 

  • those who underwent corneal refractive surgery

  • those with keratoconus

  • systemic/syndromic conditions associated with myopia such as Marfan syndrome

  • those that underwent atropine treatment, or other forms of myopia control such as PALs or OK

Interventions Silicon hydrogel contact lenses that imposed myopic defocus across peripheral and central retina (test CL I +1.00 D centrally and +2.50 at 3 mm semi‐chord) (n = 103)
Silicon hydrogel; contact lenses that imposed myopic defocus across peripheral and central retina (test CL II; +1.00 D centrally and +1.50 for CL at 3 mm semi‐chord) (n = 101)
Extended depth of focus (EDOF) hydrogel contact lenses incorporating higher order aberrations to modulate retinal image quality (test CL III; extended depth of focus of up to +1.75 D) (n = 98)
Extended depth of focus (EDOF) hydrogel contact lenses incorporating higher order aberrations to modulate retinal image quality (test CL IV; extended depth of focus of up to +1.25 D) (n = 104)
Single vision, silicone hydrogel contact lenses (n = 102)
Outcomes Primary outcomes
  • Change in SER error from baseline (cycloplegic autorefraction)

  • Change in AL from baseline (Haag‐Streit Lenstar 900)


Measurements taken every 3 months for 24 months
Unit of analysis: data from both eyes included (correlation between eyes adjusted in statistical model)
Notes Study dates: February 2014‐January 2017
Trial registration: ChiCTR‐TRC‐14004227
Funding source: grant support from the Brien Holden Vision Institute. Some of the contact lenses used in the study were supplied by Sauflon Pharmaceuticals
Disclosures: none

Schwartz 1981.

Study characteristics
Methods Study design: parallel‐group RCT in twins
Study centre: not reported
Number randomised: 52 children (26 twin pairs)
Study follow‐up: 3 years (planned), extended 6 months
Exclusions and losses to follow‐up: 2 (4%) children (1 twin pair) who were randomised were excluded from the study; none were lost to follow‐up
Participants Age: mean = 11.2 years (range 7‐14 years)
Gender: 26 boys (13 twin pairs) and 24 girls (12 twin pairs) completed the study
Culture: pairs of monozygotic (MZ) twins identified from the Twin Registry of Eye Examinations from the Washington, DC area; all were white
Inclusion criteria: 
  • MZ twins with bilateral myopia

  • age 7‐13 years

  • shared domicile in local area

  • good general health

  • vision correctable to 20/20 or better

  • third‐degree fusion

  • no other significant abnormality


Exclusion criteria: 
  • astigmatism or anisometropia > 1.00 D

  • difference in refraction between co‐twins of ≥ 1.50 D in the more advanced eye

Interventions Treatment group (n = 26): combined treatment of BF spectacles with 1.25 D addition and 2 drops of 1% tropicamide ophthalmic solution instilled to each eye nightly
Control group (n = 26): standard spectacle correction (SVLs)
Note: full cycloplegic correction in the treatment group was sometimes reduced up to 0.50 D when it did not impair vision below 20/20
Outcomes Primary outcome
  • Change in refractive error (SER) (cycloplegic refraction)


Secondary outcome
  • Compliance with treatment regimen (child and parent interviews)


Measurements taken at baseline and every 6 months for 3 years
Unit of analysis: average values of both eyes
 
Notes Study dates: not reported
Trial registration: not reported
Materials: 1% tropicamide (Mydriacyl) ophthalmic solution supplied by Alcon Laboratories Inc.

Shih 1999.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (National Taiwan University Hospital)
Number randomised: 200 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: 14 (7%) children who were randomised were excluded from the study; none were lost to follow‐up
Participants Age: mean = 9.2 years (range 6‐13 years)
Gender: included boys and girls
Culture: children recruited from the vision care centre at National Taiwan University Hospital
Inclusion criteria: 
  • age 6‐13 years

  • myopia with refractive error between −0.50 D and −6.75 D


Exclusion criteria: 
  • amblyopia or tropia

  • astigmatism ≥ −2.00 D 

  • anisometropia ≥ −2.00 D

Interventions Atropine 0.5% (n = 50): 1 drop of 0.5% atropine nightly; advised to wear BF spectacles
Atropine 0.25% (n = 50): 1 drop of 0.25% atropine nightly; advised to wear slightly undercorrected spectacles
Atropine 0.1% (n = 50): 1 drop of 0.1% atropine nightly; advised to wear fully corrective spectacles
Control (n = 50): 1 drop of 0.5% tropicamide nightly
Note: all children were advised to wear sunglasses with UV protection in bright light
Outcomes Primary outcome
  • Change in refractive error measured by cycloplegic autorefraction (SER)


Measurements taken at baseline and every 3 months for 2 years
Unit of analysis: average values of both eyes
Notes Study dates: 1994
Trial registration: not reported
Funding source: Department of Health grant (Taiwan)
Additional data: study author provided unpublished data via email correspondence

STAMP Study 2012.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (The Ohio State University College of Optometry, USA)
Number randomised: 85 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: 2 (2.3%) children did not complete the study
Participants Age: mean = 9.8 years (range 6‐11 years)
Gender: 41 boys, 44 girls
Culture: Ohio, USA: 20% black, 68% white, 7% Asian, 5% other
Inclusion criteria: 
  • 6‐11 years of age

  • at least −0.75 D myopia in each meridian measured with cycloplegic autorefraction but not more than −4.50 D in each meridian in each eye

  • ≥ 1.30 D accommodative lag (4 D stimulus) without correction

  • esophoria at near if > −2.25 D spherical equivalent

  • astigmatism ≤ 2.00 DC in each eye

  • anisometropia ≤ 2.00 D

  • BCVA of at least 20/32 logMAR equivalent

  • birth weight ≥ 1250 g by parental report


Exclusion criteria: 
  • strabismus

  • history of contact lens wear or previous BF wear

  • diabetes mellitus

Interventions PALs (n = 42): PALs with + 2.00 D addition (Varilux Ellipse; Essilor of America, Dallas, TX)
SVLs (n = 43)
Note: children were randomly assigned to wear either PALs or SVLs for the first year of the study; all children wore SVLs for the second year of the study
Outcomes Primary outcome
  • 1‐year change in SER (cycloplegic autorefraction) of the right eye after 1 and 2 years


Secondary outcomes
  • AL

  • Peripheral ocular shape

  • Central and peripheral aberrations

  • Accommodative lag

  • AC/A ratio

  • Corneal shape and thickness

  • Anterior chamber depth

  • Crystalline lens thickness and curvatures

  • Phoria

  • IOP


Measurements taken at baseline and at 6‐month intervals for 2 years
Unit of analysis: the individual (right eye only)
Notes Study dates: study recruitment from December 2006‐May 2008
Trial registration: NCT00335049
Funding source: National Eye Institute, National Institutes of Health, USA; Essilor of America, Inc.; American Optometric Foundation Ezell Fellowship
Study name: study of theories about myopia progression (STAMP)

Swarbrick 2015.

Study characteristics
Methods Study design: paired‐eye, cross‐over RCT
Study centre: 1 (School of Optometry and Vision Science, University of New South Wales, Australia)
Number randomised: 32 children
Study follow‐up: 12 months (two 6‐month periods)
Exclusions and losses to follow‐up: 6 (19%) during first period and 8 (25%) during 12‐month study
Participants Age: mean = 13.4 years (range 8‐16 years)
Gender: 14 boys, 12 girls
Culture: East Asian ethnicity
Inclusion criteria: 
  • 8 ‐16 years of age

  • myopic refractive error between −1.00 D and −4.00 D in both eyes with < 0.75 D difference between eyes

  • evidence of myopic progression in 12 months before enrolment

  • with‐the‐rule astigmatism < 1.50 D and no against‐the‐rule astigmatism

  • anisometropia ≤ 0.75 D

  • BCVA of 6/9 or better

  • East Asian ethnicity

  • good general and ocular health


Exclusion criteria: 
  • contraindications for rigid contact lens wear

  • history of previous rigid contact lens wear 

  • abnormal corneal topography

  • abnormal BF function

  • ocular pathology or active ocular surface disease precluding contact lens wear

Interventions OK (n = 26): OK lens in 1 eye (overnight wear)
RGP (n = 26): RGP contact lens in the other eye (daily or extended wear)
Note: children were randomly assigned to wear the OK lens in 1 eye and the RGP lens in the other eye for 6 months; at 6 months, the lenses were switched for each eye. The clinical trials registry record also mentioned a matched control group of children who wore spectacles for 12 months; this group was not mentioned in the journal article
Outcomes Primary outcome
  • AL change at 6 months, measured by the IOLMaster ocular biometer


Secondary outcomes
  • Refractive error (noncycloplegic autorefraction)

  • Corneal curvature

  • Corneal epithelial cell exfoliation during gentle eye wash with sterile saline

  • Amount of bacterial binding

  • Peripheral refractive status


Measurements taken at baseline and at 3, 6, 9, and 12 months
Unit of analysis: the eye
Notes Study dates: not reported
Trial registration: ACTRN12608000007336
Funding sources: Australian Research Council (ARC) Linkage Project Grant Scheme, BE Enterprises Pty Ltd., Capricornia Contact Lens Pty Ltd. (Australia); Boston Products Group of Bausch & Lomb (USA)
Disclosures of interest: "the authors have no proprietary or commercial interest in any materials discussed in this article"

Tan 2005.

Study characteristics
Methods Study design: parallel‐group RCT
Study centres: 7 (academic centres and clinical practices in Singapore, Hong Kong, and Thailand)
Number randomised: 353 children
Study follow‐up: 1 year
Exclusions and losses to follow‐up: 55 (16%) children who were randomised were dropped from the analyses
Participants Age: mean = 8.7 years (range 6‐13 years)
Gender: 177 boys, 176 girls
Culture: 99.4% Asian
Inclusion criteria: 
  • age 6‐12 years

  • myopia of −0.75 D and −4.00 D

  • good general health

  • round pupils

  • refractive to light

  • BCVA of 20/25 or better in each eye


Exclusion criteria: 
  • astigmatism > 1.00 D

  • anisometropia > 1.00 D

  • strabismus

  • current use of either contact lenses or BFs

  • history of ocular surgery, trauma, or chronic ocular disease, including allergic conjunctivitis

  • previous use of atropine for myopia

  • disease requiring long‐term or regular intermittent medication

  • behavioural or neurological disorder that would interfere with the study

  • participation in any study that involved an investigational drug within 1 month of enrolment

  • intolerance or hypersensitivity to topical anaesthetics, mydriatics, or components of the formulations

  • contraindications to antimuscarinic agents

  • pregnancy or planned pregnancy

Interventions Gel/gel (n = 142): 2% pirenzepine ophthalmic gel applied twice a day
Placebo/gel (n = 140): 2% pirenzepine ophthalmic gel applied once a day and placebo gel applied once a day
Placebo/placebo (n = 71): vehicle‐placebo gel applied twice a day
Outcomes Primary outcome
  • Change in refractive error measured by cycloplegic autorefraction (SER)


Secondary outcome
  • Change in AL measured by A‐scan ultrasonography


Measurements taken at baseline and every 3 months for 1 year
Unit of analysis: average of both eyes
Notes Study dates: November 2000‐July 2002
Trial registration: not reported
Funding source: Valley Forge Pharmaceuticals, Inc., and Novartis Ophthalmics AG
 

Tan 2020.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: HKU eye clinic at Grantham Hospital, Hong Kong, China
Number randomised: 72 children
Study follow‐up: 12 months
Exclusions and losses to follow‐up: 9 (13%) were withdrawn or lost to follow‐up
Participants Age: mean = 9.0 years (range 6‐11 years)
Gender: 23 boys, 36 girls
Culture: Chinese
Inclusion criteria: 
  • 6‐11 years of age

  • low‐to‐moderate myopia (1.00–4.00 D, inclusive) in both eyes

  • refractive astigmatism (negative cylinder) no greater than 2.50 D

  • anisometropia < 1.00 D


Exclusion criteria: 
  • any contraindications to atropine (e.g. allergy, cardiovascular disease, epilepsy)

  • contact lens wear 

  • any history of prior myopia control treatment

  • any ocular or systemic conditions that might influence refractive developments

Interventions Combined atropine 0.01% eyedrops + OK (n = 36)
OK only (n = 36)
Outcomes Primary outcomes
  • Rate of axial elongation (Zeiss IOL Master)


Secondary outcomes
  • BCVA (ETDRS)

  • SER

  • Accommodation (push‐up method ‐ Royal Air Force Rule)

  • Pupil size (OPD‐Scan III)

  • Corneal topography (Medmont E300)


Measurements taken at 6 and 12 months
Unit of analysis: child‐based‐(right eye)
Notes Study dates: not reported
Trial registration: NCT02955927
Funding source: OK lenses were sponsored by Precision Technology Services, Vancouver, B.C., Canada, and contact lens solutions by Ophtecs Corporation, Japan. Atropine eye drops were partially supported by Aseptic Innovative Medicine Co., Ltd., Taiwan
Disclosures: the study authors declare no competing interests

Tang 2021.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Department of Ophthalmology, First affiliated Hospital of Chengdu Medical College, Chengdu 610500, Scichuan Province, China
Number randomised: 104 children
Study follow‐up: 12 months
Exclusions and losses to follow‐up: not reported
Participants Age: mean = 11.04 years (range not reported)
Gender: 48 boys, 49 girls
Culture: Chinese
Inclusion criteria: 
  • spherical equivalent of −1 D to −6.00 D and with‐the‐rule astigmatism ≤ 1.00 D against‐the‐rule astigmatism ≤ 0.50 

  • ≤ 1.0D anisometropia

  • no history of OK wear

  • no other eye system disease and ocular disease

  • decimal BCVA of at least 1.0 in each eye and ocular movement were normal


Exclusion criteria: not reported
Interventions OK lenses (n = 52)
SVSCLs (n = 52)
Outcomes Primary outcomes
  • Change in AL from baseline

  • Change in relative peripheral refraction


Measurements taken 12 months
Unit of analysis: not reported
Notes Study dates: not reported
Trial registration: not reported
Funding source: Grant of Education Department of Sichuan Province
Disclosures: not reported

Trier 2008.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1
Number randomised: 83 children
Study follow‐up: 3 years (intervention 12 months)
Exclusions and losses to follow‐up: 6 (7.2%), 9 (10.8%), and 7 (8.4%) were lost to follow‐up during the first year, the second year, and the third year, respectively
Participants Age: mean 11.3 years (range 8‐13 years)
Gender: not reported
Culture: Denmark
Inclusion criteria: 
  • age 8‐13 years

  • minimum myopia of −0.75 D in 1 eye

  • average AL growth rate 0.075 mm‐0.39 mm per 6‐month period


Exclusion criteria: 
  • severe general ailment (e.g. diabetes, epilepsy, psychiatric disease)

  • other eye disease (e.g. cataract, keratoconus, chronic iritis, glaucoma)

Interventions Systemic 7‐mx (n = 35): one 400 mg 7‐mx tablet every morning
Placebo (n = 42): 1 placebo tablet every morning
Notes: children received either 7‐mx or placebo for the first 12 months; all participants received 7‐mx after 12 months (400 mg 7‐mx tablet once or twice per day); "all children used single vision lenses"
Outcomes Primary outcome
  • Axial growth rate measured with noncontact, partial coherence interferometer (Zeiss IOL‐Master)


Secondary outcome
  • Spherical equivalent measured with autorefractor (Retinomax, Nikon) 30 min after 1 drop of 1% cyclopentolate


Measurements taken at −6, 0, 12, 24, and 36 months
Unit of analysis: the individual (average of both eyes)
Notes Study dates: October 2003
Trial registration: NCT00263471
Funding source: "supported by grants from 'Jørgen Bagenkop Nielsens Myopi‐Fond' and 'Generalkonsul Einar Høyvalds Fond', and by 'Øjenlæge Klaus Trier ApS'"
Declarations of interest: 2 study authors affiliated with Trier Research Laboratories

Wang 2017.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (The People’s Hospital of Yan’an and Affiliated Hospital of Yan’an Medical University, China)
Number randomised: 126 children
Study follow‐up: 1 year
Exclusions and losses to follow‐up: 7 (11.1%) in intervention group and 5 (7.9%) in control group discontinued intervention; 2 (3.2%) in intervention group and 3 (4.8%) in control group were lost to follow‐up
Participants Age mean (SD): 9.1 (1.4) years in intervention group; 8.7 (1.5) years in control group
Gender: 36 (57.1%) boys and 27 (42.9%) girls in intervention group; 31 (49.2%) boys and 32 (50.8%) girls in control group
Culture: China
Inclusion criteria: 
  • diagnosis of low myopia (SER between −0.50 D and −2.00 D by cycloplegic autorefraction)

  • age 5‐10 years

  • normal IOP < 21 mmHg

  • not on any other treatment within 1 month before study enrolment

  • provided informed consent


Exclusion criteria:
  • abnormal binocular function or stereopsis

  • other eye disease

  • history of hemostatic or other systemic disorder

  • contact lens or any other intervention for myopia

  • allergy to atropine

Interventions Atropine (n = 63): 0.5% eye drops once daily at night
Placebo (n = 63): vehicle eye drops once daily at night
Outcomes Primary outcome
  • Progression of myopia, measured as a change in SER


Secondary outcome
  • AL


Safety outcome
  • AEs


Measurements taken at 4, 8, and 12 months
Unit of analysis: individual (eye with more severe myopia used)
Notes Study dates: January 2014‐December 2016
Trial registration: not reported
Funding source: none

Wei 2020.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Beijing Tongren Hospital, Beijing, China
Number randomised: 220 children
Study follow‐up: 12 months
Exclusions and losses to follow‐up: 61 (28%) were excluded or lost to follow‐up by 12 months
Participants Age: mean = 9.6 years (range 6‐12 years)
Gender: 117 boys,103 girls
Culture: Chinese
Inclusion criteria: 
  • aged 6‐12 years

  • SER −1.00 D to −6.00 D in both eyes

  • astigmatism of ≤ −1.50 D both eyes

  • distance BCVA 0.20 logMAR or better in both eyes

  • IOP < 21 mm Hg


Exclusion criteria: 
  • children with ocular diseases (eg, amblyopia, strabismus, corneal scar, cataract, glaucoma, or ocular tumour)

  • previous or current treatment with atropine, pirenzepine, contact lenses, BFs, or PALs for myopia

  • allergy to atropine, cyclopentolate, or excipients

Interventions 0.01% atropine eyedrops (n = 110)
Placebo eyedrops (n = 110)
Outcomes Primary outcomes
  • SER (HRK7000 A; Huvitz)

  • AL (Haag Streit Lenstar LS900)


Measurements taken at baseline 6 and 12 months
Unit of analysis: child‐based (right eye)
Notes Study dates: April 2018‐July 2020
Trial registration: ChiCTR‐IOR‐17013898
Funding source: supported by grants from the Integration, Translation and Development on Ophthalmic Technology (Jingyiyan 2016‐5), the Capital Health Research and Development of Special (2016‐4‐2056), the Ministry of Science and Technology, Beijing Nova Program (Z121107002512055), the National Natural Science Foundation of China (81300797), Sanming Project of Medicine in Shenzhen (SZSM201512045) and the Beijing University‐CMU, Advanced Innovation Centre for Big Data‐Based Precision Medicine, Ophthalmic Subcenter (BHME2018‐2019)
Disclosures: the study authors declared no competing interest

Yang 2009.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Guangzhou City, China)
Number randomised: 178 children
Study follow‐up: 2 years
Exclusions and losses to follow‐up: no exclusions; 29 (16%) were lost to follow‐up
Participants Age: range 7‐13 years
Gender: 94 boys, 84 girls
Culture: urban children from Guangzhou City, China
Inclusion criteria: 
  • age 7‐13 years

  • myopia with SER error between −0.50 D and −3.00 D in both eyes, as measured under cycloplegia

  • astigmatism ≤ 1.50 D

  • no anisometropia (difference in SER ≤ 1.00 D between eyes)

  • BCVA 6/6 or better

  • no strabismus

  • normal IOP

  • willingness to wear glasses constantly for study duration

  • understanding of random assignment and willingness to not use other medications


Exclusion criteria: 
  • any ocular or systemic condition known to influence refractive development

  • use of medication that might affect refractive development

  • moderately or highly myopic (< −3.00 D) parents

  • birth weight ≤ 1250 g

  • previous use of BFs, PALs, or contact lenses

Interventions PAL group (n = 89): MFl lenses with +1.50 D near addition worn constantly
SVL group (n = 89): SVLs worn constantly
Note: prescription changes were made if subjective refraction had changed by at least 0.50 D for 1 or both eyes or if clinically indicated
Outcomes Primary outcome
  • Progression of myopia


Change in SER error relative to baseline measured by cycloplegic autorefraction with 0.5% tropicamide + 0.5% phenylephrine hydrochloride
Secondary outcomes
  • Change in vitreous chamber depth by A‐scan ultrasonography

  • Distance (5 m) and near (33 cm) horizontal heterophobia by cover test

  • Accommodative response by open‐field autorefractor

  • Near workload, compliance, and adherence assessed by questionnaire


Measurements taken at baseline and every 6 months for 2 years
Unit of analysis: not reported
 
Notes Study dates: enrolment was from July 2004‐March 2005
Trial registration: not reported
Funding source: National Natural Science Grant, China
Materials: lenses provided by Sola (China) Ltd
Compliance in wearing glasses was monitored with separate questionnaires for children and parents (87% overall compliance)

Yen 1989.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (Refraction Clinic, Veterans General Hospital, Taipei, Taiwan)
Number randomised: 247 children
Study follow‐up: 1 year
Exclusions and losses to follow‐up: 151 (61%) children were excluded or lost to follow‐up
Participants Age: mean = 9 years (range 6‐14 years)
Gender: 118 boys, 129 girls
Culture: children with simple myopia were randomly selected from clinic records
Inclusion criteria: 
  • age 6‐14 years

  • myopia with refractive error between −0.5 D and −4.0 D


Exclusion criteria: 
  • amblyopia or tropia

  • cylinder refraction > 1.0 D

Interventions Atropine: 1% atropine drops every other night; BF spectacles prescribed 2 weeks after treatment began
Cyclopentolate: 1% cyclopentolate drops every night; SVLs prescribed if necessary
Saline control: normal saline eye drops every night; SVLs prescribed if necessary
Outcomes Primary outcome
  • Change in refractive error measured by cycloplegic refraction (SER)


Secondary outcomes
  • Changes in vision, fundoscopy, and IOP


Measurements taken at baseline and every 3 months for 1 year
Note: baseline for atropine group was measured 2 weeks after treatment began
Unit of analysis: right eyes only
Notes Study dates: enrolment from 1 July 1985‐31 October 1986
Trial registration: not reported
Funding source: not reported
Additional data: study author provided unpublished data via email correspondence
 

Yi 2015.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: 1 (The Third People’s Hospital of Chongqing City, China)
Number randomised: 140 children
Study follow‐up: 12 months
Exclusions and losses to follow‐up: 6 (8%) in treatment group and 2 (3%) in control group withdrew from the study
Participants Age: mean = 9.8 years (range 7‐12 years)
Gender: 65 boys, 67 girls
Culture: China
Inclusion criteria: 
  •  children with low myopia: refractive error between −0.50 and −2.00 D in both eyes as measured by cycloplegic autorefraction

  • normal binocular function and stereopsis

  • normal IOP < 21 mmHg

  • willingness and ability to tolerate cycloplegia and mydriasis


Exclusion criteria: 
  • astigmatism > −1.00 D

  • other ocular disease, such as amblyopia, strabismus, congenital cataract, glaucoma, corneal scar, optic neuropathy, traumatic ocular injury, uveitis, or ocular tumour

  • history of any ocular surgery

  • any systemic disease or condition that could affect visual function and development, including diabetes mellitus and/or chromosome anomaly

  • previous or current use of contact lenses, BFs, PALs, or other forms of treatment (including atropine) for myopia

Interventions Atropine (n = 70): 1% atropine sulfate once nightly in both eyes
Placebo (n = 70): vehicle eye drops (Tears Naturale Free; Alcon, Fort Worth, TX) once nightly in both eyes
Outcomes Primary outcomes
  • Uncorrected distance VA

  • SER (cycloplegic autorefraction)

  • AL

  • Ophthalmoscopy

  • Slit‐lamp biomicroscopy

  • Fundus examination

  • AEs


Secondary outcomes
  • Not distinguished


Measurements taken at baseline and every 3 months up to 1 year
Unit of analysis: individual (right eye)
Notes Study dates: enrolment from January‐October 2012
Trial registration: not reported
Funding source: not reported
Declarations of interest: not reported

Zhang 2021.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Peking University Third Hospital, China
Number randomised: 60 children
Study follow‐up: 24 months
Exclusions and losses to follow‐up: 22 (28%) were excluded or lost to follow‐up
Participants Age: mean = 11 years (range 8‐14 years)
Gender: 29 boys, 31 girls
Culture: Chinese
Inclusion criteria: 
  • 8‐14 years old; myopia (both eyes)

  • − 0.75 D to − 5.00 D; astigmatism

  • ≤ 1.50 D; anisometropia

  • ≥1.00 D

  • BCVA logMAR: 0.10 or better in both eyes


Exclusion criteria: 
  • previous experience wearing contact lenses

  • contraindication for contact lenses (e.g. dry eye, trichiasis)

  • intermittent or constant strabismus

  • a history of ocular surgery, trauma

  • concurrent use of medications that may affect refractive development (e.g. atropine)

  • systemic conditions that may affect tear quality or contact lens wear (e.g. diabetes, allergies)

Interventions OK lenses (n = 30)
SVLs (n = 110)
Outcomes Primary outcomes
  • AL


Secondary outcomes
  • AEs


Measurements taken at baseline 6 and 12 months
Unit of analysis: not reported
Notes Study dates: not reported
Trial registration: ChiCTR 1800017535
Funding source: Capital’s Funds for Health Improvement and Research (grant number 2018‐2‐4092)
Disclosures: "The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper."

Zhao 2021.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: Affiliated Hospital of Dalian Medical University, China
Number randomised: 80 children
Study follow‐up: 12 months
Exclusions and losses to follow‐up: not reported
Participants Age: mean = 10.3 years (range 5‐14 years)
Gender: 40 boys, 40 girls
Culture: Chinese
Inclusion criteria: 
  • cycloplegic SER at least −1.00 D and within −1.00 to −6.00 DS 

  • astigmatism ≤ −1.00 DC


Exclusion criteria: 
  • wearing contact lenses within 3 days at the start of examination

  • children with ocular disorders such as glaucoma, cataract, keratopathy, strabismus, and amblyopia, and systemic disorders such as cardiac and respiratory illnesses

  • IOP > 21 mm Hg and difference between the eyes > 8 mm Hg

  • use of anticholinergic and cholinergic drugs within the past 1 month

  • wearing OK lenses

  • therapy of traditional Chinese medicine 

  • low birth weight (< 1500 g)

  • history of hypersensitivity to atropine or anticholinergic drugs

Interventions Atropine 0.01% eyedrops (n = 20)
SVLs (n = 20)
OK lenses (n = 20)
Combination OK lenses + atropine 0.01% eyedrops (n = 20)
Outcomes Primary outcomes
  • AL (LS 900 biometer)

  • SER (TOPCON (KR‐800))


Secondary outcomes
  • IOP (TOPCON (CT‐IP))

  • Corneal topography (OPD‐Scan III)


Measurements taken at baseline 3, 6 and 12 months
Unit of analysis: eye (both eyes of each child analysed)
Notes Study dates: January 2019‐April 2020
Trial registration: not reported
Funding source: "This study was funded by Life Science Society of Liaoning."
Disclosures: "The authors declare that they no conflict of interest."

Zhu 2021.

Study characteristics
Methods Study design: parallel‐group RCT
Study centre: The Second People’s Hospital of Yunnan Province, China
Number randomised: 660 children
Study follow‐up: 48 months
Exclusions and losses to follow‐up: 90 (14%) were excluded or lost to follow‐up
Participants Age: mean = 9.1 years (range 5‐14 years)
Gender: 286 boys, 284 girls
Culture: Chinese
Inclusion criteria: 
  • age 6‐12 years

  • initial myopic SER −2.0D to−8.00D

  • astigmatism ≤ 1.0 D

  • SE progression rate ≥ 1 D/year in the last year

  • normal binocular function and stereopsis

  • normal IOP


Exclusion criteria: 
  • ocular diseases, such as amblyopia, strabismus, congenital cataract, glaucoma, corneal scar, optic neuropathy, traumatic ocular injury, uveitis, or ocular tumour

  • history of any ocular surgeries; any systemic diseases or conditions that could affect visual function and development, including diabetes mellitus and/or chromosome anomaly

  • previous or current use of contact lenses, BFs, PALs, or other forms of treatment, including atropine, for the control of myopia

Interventions Atropine 1% eyedrops (n = 262); years 1 and 2: once monthly dosing, year 3: once every 2nd month, year 4: no treatment
Placebo eyedrops (n = 308); same dosing schedule as for the active comparator
Outcomes Primary outcomes
  • SER (cycloplegic autorefraction)

  • AL (Zeiss IOL Master 500)


Secondary outcomes
  • IOP (Nidek Co. Ltd, Tokyo, Japan)


Measurements taken every 6 months for 48 months
Unit of analysis: not reported
 
Notes Study dates: December 2014‐December 2018
Trial registration: not reported
Funding source: "This work is supported by the National Natural Science Foundation of China, Grant No. 81560168."
Disclosures: "The authors declare that they no conflict of interest."

7‐mx: 7‐methylxanthine; AC/A: accommodative‐convergence (AC) over accommodation (A); AE: adverse event; AL: axial (eye) length; BCVA: best corrected visual acuity; BF: bifocal; BOZD: back optic zone diameter; D: dioptre; DF: dual focus: EDTRS: standardised chart for measuring visual acuity (Early Treatment of Diabetic Retinopathy Study); HAL: highly aspheric spectacle lenses; IOP: intraocular pressure; MF: multifocal; OK: orthokeratology; PAL: progressive addition lens; QoL: quality of life; RCT: randomised controlled trial; RGP: rigid gas‐permeable (contact lenses); SAL: slightly aspheric spectacle lenses; SER: spherical equivalent refraction; SVL: single vision spectacle lenses; SVSCL: single vision soft contact lenses; VA: visual acuity; 

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion
Abraham 1966 Not randomised: case report
ACHIEVE Study 2008 Not intended to control progression of myopia: glasses vs contacts for self‐esteem in school children
ACTRN12620000159954 Not randomised
ACTRN12620001046998 Not randomised
Aller 2008 Interventional twin case series: included only 1 pair of twins: 1 randomised to wear BF SCLs and the other to wear SVSCLs for 1 year; both wore BFSCLs for the second year
Anderson 2016 Ineligible outcome
Andreo 1990 Not randomised: not intended to control progression of myopia; participants > 18 were included
Avetisov 2019 Not randomised
Bakaraju 2015 6‐month data only
Baldwin 1969 Not randomised: participants selected treatment assignment
Baltimore Myopia Project 1946 Interventions not eligible: vision training for myopia; interventions of vision training were not prespecified in the protocol
Baronet 1979 Notr andomised: retrospective review of patients treated with atropine at a medical practice with no comparison group
Bedrossian 1979 Not randomised: method of allocation was not specified. Cross‐over study of atropine in 1 eye for 1 year, with the fellow eye serving as the control, then alternated treatment after each year for 4 years
Berkeley OK Study 1983 Population not eligible: participants were 21‐28 years old
Bier 1988 Not randomised: sequential assignment to groups
Brodstein 1984 Not randomised: "the lack of randomization permits a possibility for bias"
Cambridge Anti‐Myopia Study 2013 Ineligible population (included children and young adults)
Chan 2014 Interventional twin case series: included only 1 pair of twins: 1 randomised to wear OK lens and the other to wear SVLs for 2 years
Chan 2020 Outcome not eligible
Chen 2012 Not randomised: allocation was done by parental decision
Chen 2014 Not randomised: cohort study of children wearing SVLs with full correction or undercorrection
Chen 2016 Not randomised: treatment group included participants who chose to wear OK lenses; controls included participants who had never worn OK lenses
Cheung 2018 Wrong outcome
ChiCTR2000034760 Population not eligible
ChiCTR2000038078 Population not eligible
ChiCTR2100052322 Intervention not eligible
ChiCTR‐IOC‐17010525 Population not eligible
ChiCTR‐OON‐17010470 Not randomised
ChiCTR‐TRC‐070000297 Intervention not eligible
Cho 2012 Interventions not eligible: comparison of fenestrated OK lenses vs nonfenestrated OK lenses; interventions comparing types of OK lenses were not prespecified in the protocol
Cho 2017 Interventions not eligible: comparison of continuing vs discontinuing OK wear after 2 years; interventions comparing length of OK wear were not prespecified in the protocol
Choi 2005 Not randomised: study was reported only as a conference abstract and randomisation was not specified ("We prescribed 1% atropine once a day with bifocal glasses to the treated group (41 patients) and prescribed only glasses to the control group (43 patients)")
Chou 1997 Not randomised: allocation was by parental decision
Diaz‐Llopis 2018 Not randomised
Dumbleton 1999 Interventions not eligible: lenses with different oxygen permeability; interventions comparing oxygen permeability not prespecified in the protocol
Dyer 1979 Not randomised: case‐control study
Ebri 2007 Not intended to control progression of myopia: cycloplegic effect and pupillary dilation outcomes, as well as cost‐effectiveness; follow‐up 3 days
Eissa 2018 Interventions were not eligible
Filip 2000 Population was not eligible: myopia progression in adults
French 2016 Letter/commentary
Gimbel 1973 Not randomised: comparison of patients vs an historical cohort
Goss 1984 Not randomised: treatment group included patients with overcorrection; controls included random patients selected retrospectively
Grosvenor 1991 Not randomised: historical control group
He 2015 Population not eligible
He 2016 Not randomised: retrospective cohort study; comparison of OK lenses vs SVLs
Horner 1999 Not intended to control progression of myopia: comparison of soft spherical contact lenses vs spectacles; SCLs not expected to slow myopia progression. In fact, the study was conducted because researchers believed that SCLs may increase myopia progression
Hosaka 1982 Not randomised: interventional case series of children aged 6‐14 years treated with labetalol ophthalmic solution
Hosaka 1988 Not randomised: interventional case series
Hua 2017 Interventions not eligible: cluster‐RCT of elevated light levels in classrooms to prevent myopia onset or progression; interventions of light levels were not prespecified in the protocol
Huang 2015a Intervention not eligible
Huang 2020 Not randomised
Huffman 2002 Not intended to control progression of myopia: aspheric vs spheric lenses; outcome to decrease spherical aberration; adults were included
Jiang 2018 Not randomised
Jiang 2021 Not randomised
Jin 2015 Not randomised
Jones Jordan 2012 Not randomised
Jong 2015 Ineligible outcome
JPRN‐jRCTs032180418 Intervention not eligible
Kao 1988 Not randomised: children were enroled in 2 separate series of participants
Keller 1996 Not randomised: all children wore RGPs
Kennedy 1995 Not randomised: treatment was atropine; controls were patients matched by medical records
Khoo 1999 Not randomised: study reported that "children were randomly selected from the various schools in Singapore. They were then randomly selected for contact lens wear"
Children in the RGP cohort who completed 3 years of follow‐up were compared with a cohort of children who wore spectacles
Kubena 2002 Not randomised: cohort study that compared spectacle lenses that filtered non‐visible light vs conventional spectacle lenses
Lakkis 2006 Not intended to control progression of myopia: 2‐week randomised cross‐over trial to evaluate visual performance and satisfaction of clear and photochromic spectacle lenses in children aged 10‐15 years wearing fully corrected spectacles
Lam 2018 Ineligible outcome
Lee 2016 Not randomised: dosing study conducted to compare 0.125% or 0.25% atropine; controls were patients who preferred SVLs
Leung 1999 Not randomised: odd or even case numbers determined the 2 groups
Li 2005 Not randomised: experimental group received progressive MF lenses; control group wore common glasses; participants were 6‐23 years old
Liang 2008 Interventions not eligible: RCT comparing atropine eye drops alone vs combined treatment with atropine and stimulation of the auricular acupoints in school‐aged children with myopia
Lu 2010 Not randomised: case‐control study comparing myopic children treated with seasonal doses of atropine vs nonmyopic children
Lu 2019 Outcome not eligible
Lyu 2021 Ineligible study design
Ma 2014 Interventions not eligible: cluster‐RCT with 3 groups: free spectacles provided in class; vouchers for free spectacles; and prescriptions for spectacles; interventions of accessibility to spectacles were not prespecified in the protocol
Mandell 1959 Not randomised: historical cohort, including adults
Marcotte Collard 2019 Outcome not eligible
Meythaler 1971 Not randomised: interventional cases series (70 eyes in people from 8‐35 years of age were checked); 3 groups were based on age; youngest group was 8‐19 years old
Mori 2021 Intervention not eligible
NCT00348166 Not randomised
NCT00848900 Population not eligible
NCT02055378 Ineligible intervention
NCT03372551 Ineligible patient population
NCT03512626 Ineligible patient population
NCT03761758 Ineligible patient population
NCT04126057 Outcome not eligible
NCT04238897 Intervention not eligible
NCT04301323 Intervention not eligible
NCT04492397 Outcome not eligible
NCT04923841 Population not eligible
NCT05156190 Ineligible outcome
Neetens 1985 Not randomised: control group consisted of participants who could not use BFs
Nesterov 1990 Not randomised: comparison of a group using cycloplegics and ocular hypotensives vs a reference group for progression of myopia
Ng 2019 Outcome not eligible
Oakley 1975 Not randomised: control group consisted of children (or parents) who refused BFs
Parker 1958 Not randomised: comparison of author's practice vs other practices
Perrigin 1990 Not randomised: treatment group was given silicone lenses; control consisted of an historical cohort
Pirenzepine 2003 Not randomised: review of pirenzepine studies and mechanism of action
Plowright 2015 Not intended to control progression of myopia: RCT to evaluate daily disposable contact lenses vs SVLs for 2 weeks
Pritchard 1999 Not intended to control progression of myopia: extended wear for low Dk vs high Dk lenses in adults
Rah 2002 Population not eligible: overnight OK in adults (LOOK study); not randomised
Rainey 2000 Interventions not eligible: vision therapy vs control; interventions for vision training were not prespecified in the protocol
Ritchey 2005 Population not eligible: included adults aged ≥ 18 (COLM study)
Sankaridurg 2003 Not intended to control progression of myopia: RCT conducted to compare AEs for SCLs vs SVLs; participants were 16‐35 years old
Santodomingo‐Rubido 2012 Not randomised: allocation was done by parental decision
Savoliuk 1968 Not randomised: comparison of groups using SVLs continuously or for distance use only vs no spectacles
Saxena 2021 Letter/commentary
Shen 2011 Allocation method not clear, randomisation not specified: compared groups using 0.25% atropine vs no atropine
Shimmyo 2003 Allocation method not clear, randomisation not specified: atropine vs control for 2 years
Shum 2003 Not randomised: comparison of groups using OK vs no OK
SMART Study 2009 Not randomised: comparison of groups using OK lenses vs daily wear silicone hydrogel SCLs
Soni 2006 Not randomised: included adults
Stone 1976 Not intended to control progression of myopia: study authors state that "the research team is not purposely attempting to flatten the cornea in order to arrest the myopia"
Sun 2007 Not randomised: case‐control study of spectacle users vs controls
Syniuta 2001 Not randomised: intervention group included patients whose parents requested treatment for myopic progression; control group comprised the next myopic child by alphabetical order after study child’s record number
Takano 1964 Not randomised: cohort study comparing treatment with Mydrine (tropicamide + phenylephrine) eye drops with or without Neosynesin (phenylephrine) eye drops; included boys and girls with myopia ages 7‐19 years; follow‐up was 20 days
Tan 2012 Not randomised
Tan 2019 Outcome not eligible
Tang 2020 Ineligible study design
Tian 2022 Outcome not eligible
Tilia 2018 Ineligible outcome
Toki 1960 Not randomised: cohort study of patients receiving 5% Neosynesin (phenylephrine) eye drops; included boys and girls with myopia ages 7‐21 years; follow‐up was 14‐28 days
Tokoro 1964 Not randomised: non‐randomised study of treatment with Mydrine (tropicamide + phenylephrine) eye drops + 5% Neosynesin (phenylephrine) eye drops + low‐frequency electro stimulus in children ages 7‐15 years; included children with hyperopia
Tokoro 1965 Not randomised: retrospective cohort comparing full correction spectacles vs undercorrection (< −1 D) spectacles or full correction in case of need in children ages 7‐14 years; included children with hyperopia
TO‐SEE Study 2013 Not randomised: prospective cohort study of children wearing OK lenses vs SVLs
Wan 2020 Ineligible study design
Wu 2018 Letter/commentary
Xiao 2009 Not randomised: observational study of 2 groups of children who wore RGPs vs spectacles
Yamada 2004 Not randomised: review article with some cohort data on children with high myopia
Yamaji 1967 Not randomised: observation of children treated with Mydrine‐M; no control group
Yang 2017 Not intended to control progression of myopia: evaluated accommodative lag in groups using OK vs SVLs for 1 year
Yi 2011 Population not eligible
Young 1992 Not intended to control progression of myopia: comparison of overnight lenses for 12 months in adults only
Zeng 2009 Not intended to control progression of myopia: RCT to evaluate visual performance and satisfaction of ready‐made spectacles vs custom spectacles in Chinese school‐aged children with uncorrected refractive error
Zhang 2019 Outcome not eligible
Zhao 2017 Ineligible intervention
Zhou 2015 Not intended to control progression of myopia: evaluated accommodative lag in groups using RGPs vs SVLs for 1 year
Zhou 2016 Not randomised: 400 children wearing OK lenses or SVLs selected from patient records
Zhou 2021 Not randomised

AE: adverse event; BF: bifocal;Dk: oxygen permeability; MF: multifocal; OK: orthokeratology; RCT: randomised controlled trial; RGPs: rigid gas‐permeable (contct lenses); SCL: soft contact lens; SVSCL: single vision soft contact lenses; SVL: single vision spectacle lenses

Characteristics of studies awaiting classification [ordered by study ID]

Viswanath 2022.

Methods Study design: parallel‐group RCT
Study centre: not reported
Number randomised: 60 children
Study follow‐up: 12 months
Exclusions and losses to follow‐up: not reported
Participants Age: mean = intervention group 11.33 ± 3.31 years, placebo 10.8 ± 3.41)
Gender: not reported
Culture: Indian
Inclusion criteria: baseline myopia ≥ −2.00 D to −6.00 D
Exclusion criteria: not reported
Interventions 0.01% atropine (n = 30)
Placebo (n = 30)
Outcomes Primary outcomes
  • SER

  • AL


Unit of analysis: child‐level
Notes Study period: not reported
Trial registration: not reported
Funding source: not reported

Wang 2005.

Methods Study design: parallel‐group RCT
Study centre: 1 (Shanghai, China)
Number randomised: 104 children
Study follow‐up: 18 months
Exclusions and losses to follow‐up: not reported
Participants Age: mean = 11.6 years (range 6‐15 years)
Gender: 51 boys, 53 girls
Culture: recruited from outpatient department of Eye & Ear, Nose, Throat Hospital in Shanghai, China
Inclusion criteria: 
  • age 6‐15 years

  • myopia


Exclusion criteria: not reported
Interventions PAL group (n = 50): add not reported
SVL (n = 54)
Outcomes Primary outcomes
  • Refractive error (cycloplegic autorefraction)

  • AL

  • Anterior chamber depth

  • Lens thickness

  • Corneal curve (vertical and horizontal)

  • Heterophoria (vertical and horizontal)


Secondary outcomes
  • Not distinguished


Measurements taken at baseline and every 6 months for 18 months
Unit of analysis: not reported
 
Notes Study period: enrolment from April 1999‐April 2000
Trial registration: not reported
Funding source: not reported

AL: axial length; PAL: progressive addition lenses; SER: spherical equivalent refracton; SVL: single vision spectacle lenses

Characteristics of ongoing studies [ordered by study ID]

ACTRN12605000633684.

Study name Trial of an experimental soft contact lens designed to inhibit the progression of axial myopia in children
Methods Randomised cross‐over design (within‐person study)
Participants Inclusion criteria: 40 children aged 11‐14 years with progressing myopia, SER of −1.50 to −4.00, VA of 6/6 or better
Exclusion criteria: children with astigmatism > 0.75 D, anisometropia > 1.00 D, abnormal binocular vision, ocular pathology, systemic disease with ocular complications, active anterior surface disease that would preclude contact lens wear, inadequate fit of soft contact lenses
Interventions Intervention: frequent replacement soft contact lens that both corrects vision and simultaneously produces myopic retinal defocus
Comparison intervention: standard frequent replacement SVSCLs
Outcomes Primary outcome: myopia progression rate
Secondary outcomes: SER, AL
Maximum follow‐up: 20 months
Starting date November 2005
Estimated end date: not reported
Contact information anzctr.org.au/ACTRN12605000633684.aspx
Notes  

ACTRN12608000566336.

Study name Myopia control lens efficacy trial
Methods Randomised parallel‐group design
Participants Inclusion criteria: 300 children aged 6‐12 years with SER error of –0.50 to ‐4.50 D, astigmatism of not > −1.50 D, anisometropia of not more than −1.50 D in spherical or cylindrical error, BVCA of at least 6/9 (20/30) in each eye, normal ocular health other than myopia, no prior use of BF or progressive lenses in the last 12 months, no rigid contact lenses or BF contact lens experience, willingness not to wear contact lenses, in satisfactory health, willingness and ability to tolerate cycloplegia, informed parental consent
Exclusion criteria: no availability for follow‐up for at least 2 years, absence of parental consent to the random assignment of their child to 1 of 3 spectacle lens groups, any systemic condition that might affect refractive development or systemic disease that may affect vision or refractive error, previous use of contact lens/PALs or other treatment for myopia within the last 12 months, defective binocular function, amblyopia and or manifested squint, vestibular disorders or motor imbalance, any other conditions precluding adherence to the protocol
Interventions Intervention 1: binocular 1.00 D PALs
Intervention 2: binocular 1.50 D PALs
Comparison intervention: single vision binocular lens
Outcomes Primary outcomes: SER, AL
Secondary outcome: peripheral refractive error
Maximum follow‐up: 24 months
Starting date September 2008
Estimated end date: September 2009
Contact information anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83124
Notes  

ACTRN12611000499987.

Study name Duplex orthokeratology (DOK) and myopia progression in children
Methods Randomised parallel‐group design
Participants Inclusion criteria: 
  • 10‐14 years of age

  • SER error between −1.25 D and −4.00 D

  • myopia progression of at least 0.50 D in previous 12 months

  • astigmatism < 1.50 D

  • anisometropia < 1.00 D

  • BCVA of 6/6 or better in both eyes

  • good general and ocular health

  • parents and child able to communicate in English


Exclusion criteria: 
  • recent rigid contact lens wear

  • history of corneal surgery

  • active eye disease including keratoconus

  • severe dry eye symptoms

  • systemic disease affecting VA

  • taking medication that could affect ocular health

Interventions Intervention: duplex (dual focus optic zone) OK lens in 1 eye (overnight wear)
Intervention comparison: conventional OK lens in the other eye (overnight wear)
Note: children were randomly assigned to wear the OK lens in the dominant eye or the nondominant eye
Outcomes Primary outcome: change in vitreous chamber depth, measured by non‐contact Optical Low‐Coherence Reflectometry (Lenstar LS 900, Haag Streit, Switzerland)
Secondary outcomes: magnitude of central and peripheral refractive error, amplitude of accommodation, contrast sensitivity
Starting date May 2011
Estimated end date: not reported
Contact information John Phillips, PhD, or
Martin Loertscher
Department of Optometry and Vision Science
The University of Auckland
85 Park Road Grafton, Auckland 1023
email: j.phillips@auckland.ac.nz; m.loertscher@auckland.ac.nz
anzctr.org.au/ACTRN12611000499987.aspx
Notes  

ACTRN12611000582954.

Study name Myopia control with progressive spectacle lenses trial (MCPAL‐3)
Methods Randomised parallel‐group design
Participants Inclusion criteria: 167 children aged 7‐12 years with refractive error between −1.00 D and −4.50 D, BCVA of at least 6/9 or 20/30 in each eye, and anisometropia not more than −1.50 D, astigmatism not greater than −1.50 D, no other ocular conditions, no history of using BF or PALs in 12 months preceding study, and tolerant to cycloplegia, with parental consent
Exclusion criteria: systemic condition affecting vision or refractive errors, history of contact lens or other treatment for myopia in the preceding 12 months, impaired binocular function, history of amblyopia, manifest squint, vestibular disorders or motor imbalance, other conditions that prevent adherence to protocol
Interventions Intervention: PALs
Comparison intervention: SVLs
Outcomes Primary outcome: progression in refractive error (SER using cycloplegic autorefraction)
Secondary outcome: AL
Maximum follow‐up: 24 months
Starting date June 2011
Date of last participant enrolment: June 2012
Contact information anzctr.org.au/Trial/Registration/TrialReview.aspx?id=343027
Notes  

ACTRN12611001148965.

Study name To determine the rate of refractive error change in children wearing multifocal soft contact lens as compared to those wearing single vision soft contact lenses
Methods Randomised parallel‐group design
Participants Inclusion criteria: 40 children aged 8‐14 years with cycloplegic autorefraction: sphere −0.50 D to −4.00 D; cylinder 0 to −0.75 D; BCVA 6/9 or better; ability to safely wear contact lenses; distortion‐free keratometric readings; no active corneal infection, inflammation, or infection of the anterior chamber, eye disease, injury or abnormality of the cornea; conjunctiva or eyelids affecting wearing of contact lenses; no previous ocular surgery; no severe insufficiency of lacrimal secretion; no evidence of corneal hypoesthesia; no systemic disease or use of medications that may affect the eye or produce an adverse response by the wearing of contact lenses
Exclusion criteria: binocular vision problems, strabismus, amblyopia, external ocular problems that may impact lens fit (i.e. lid ptosis, chalazia, swollen lids)
Interventions Intervention: MFSCLS
Comparison intervention: SVCLs
Outcomes Primary outcome: rate of myopia progression
Secondary outcomes: fitting characteristics of, and ocular response to, soft contact lenses
Maximum follow‐up: 3 years
Starting date November 2005
Estimated end date: not reported
Contact information anzctr.org.au/Trial/Registration/TrialReview.aspx?id=347659
Notes  

ACTRN12617000598381.

Study name A pilot study to evaluate the effectiveness of daily 0.01% atropine eye drop therapy in modifying the progression of myopia, in Australian children
Methods Randomised parallel‐group design
Participants Inclusion criteria: aged 6‐16 years, myopia with SER error ≥ −1.5 D in each eye, documented myopic progression of ≥ −0.5 D over the previous 12 months in either eye, astigmatism < −1.5 D, intraocular difference in spherical equivalent < 1 D, corrected VA > logMar 0.2, normal IOP, normal ocular health, no history of cardiac/respiratory disease, willingness and ability to provide details of parents' country of origin, ability to provide appropriate parental/carer consent
Exclusion criteria: astigmatism of ≤ 1.5 D; ≥ 1 D anisometropia; severe developmental delay (inability to participate in subjective refraction of testing); ocular comorbidities such as glaucoma, aphakia, pseudophakia, uveitis, keratoconus, or connective tissue disease (e.g. Marfan syndrome, vitreoretinal dystrophies); severe ocular surface disease; previous atropine treatment for amblyopia at any time in the past
Interventions Intervention: 0.01% atropine eye drops
Comparison intervention: placebo eye drops
Outcomes Primary outcome: mean change in SER error
Secondary outcomes: amplitude of accommodation, choroidal thickness, corneal curvature and AL, Wilkins Rate of Reading test comparison, IOP, stereovision assessment, QoL
Maximum follow‐up: 24 months
Starting date January 2017
Estimated end date: December 2020
Contact information anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372668
Notes  

ACTRN12618000242224.

Study name Prospective, contralateral, randomized, cross‐over dispensing clinical trial to compare the myopia progression rate between a myopia control contact lens and single vision contact lenses
Methods Randomised cross‐over design (within‐person study)
Participants Inclusion criteria: 45 participants aged 6‐17 years, spherical equivalent −0.75 D to −3.50 D, cylinder no more than −1.00 D, anisometropia ≤ 0.75 D, vision correctable to 6/9.5 or better
Exclusion criteria: pre‐existing ocular irritation precluding contact lens fitting, systemic or ocular condition or injury, corneal refractive surgery, keratoconus, allergy to cyclopentolate, astigmatism > 1.00 D in either eye, strabismus, amblyopia, any ocular or systemic disease associated with myopia, retinopathy of prematurity, current orthoptic treatment or vision training, eye injury or surgery within 12 weeks before enrolment, atropine treatment for myopia control, previously worn BF or PAL spectacles or antimyopia contact or OK lenses, anisometropic by > 0.75 D
Interventions Intervention: experimental contact lens (lens type not reported)
Comparison intervention: single vision contact lens
Outcomes Primary outcome: change in cycloplegic autorefraction spherical equivalent
Secondary outcomes: change in axial length
Maximum follow‐up: 12 months
Starting date January 2018
Estimated end date: not reported
Contact information anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374450
Notes  

Azuara‐Blanco 2020.

Study name Low‐dose (0.01%) atropine eye‐drops to reduce progression of myopia in children: a multicentre placebo‐controlled randomised trial in the UK (CHAMP‐UK)—study protocol
Methods Randomised parallel‐group design
Participants Inclusion criteria: aged 6–12 years, myopia ‐0.50 D or greater, SER error in both eyes, BCVA distance 0.20 logMAR or better in both eyes, and no other significant ocular or systemic morbidities
Exclusion criteria: children with myopia ≥ −10.00 D or astigmatism ≥ 2.00 D in either eye will be excluded
Interventions Intervention: atropine 0.01% eyedrops 1 drop in the randomised eye for 2 years
Comparison intervention: placebo
Outcomes Primary outcome: SER after 24 months
Secondary outcome: AL BCVA distance (uniocular and binocular), uniocular and binocular near VA (ETDRS), reading speed, pupil diameter, accommodation, AE rates and allergic reactions, QoL (EQ‐5D‐Y) and tolerability
Maximum follow‐up: 24 months
Starting date April 2019
Estimated end date: February 2024
Contact information clinicaltrials.gov/ct2/show/NCT03690089
Notes Trial registration numberS: ISRCTN99883695, NCT03690089

ChiCTR1800016504.

Study name Clinical effect of vitamin B12 eye drops on myopia in children
Methods Randomised parallel‐group design
Participants Inclusion criteria: age 6‐12 years; the refractive power of the eyes after dilation is between −1.0 and −3.0 D; no refractive error (binocular D within −1.0 D); binocular astigmatism < −1.5 D; far vision of the eyes can be corrected to at least 0.8; the IOP is < 21 mmHg; no allergy to dilated pupils; no corneal plasticiser has been used to treat myopia; no amblyopia, squint, etc.
Exclusion criteria: failing to meet the inclusion criteria; unwilling to participate in this study
Interventions Intervention: vitamin B12 eye drop
Comparison intervention: no intervention
Outcomes Primary outcome: dioptre
Secondary outcomes: not reported
Maximum follow‐up: 12 months
Starting date July 2018
Estimated end date: June 2019
Contact information chictr.org.cn/showprojen.aspx?proj=26962
Notes  

ChiCTR1800017535.

Study name Randomized controlled trial for orthokeratology lens to correct anisometropia in children
Methods Randomised parallel‐group design
Participants Inclusion criteria: aged 8‐14 years, myopia in both eyes −0.75 D to −5.00 D, astigmatism ≤ 1.50 D, interocular difference in spherical equivalent ≥ 1.00 D
Exclusion criteria: wearing any type of contact lenses for > 3 months, eye diseases such as trichiasis, conjunctivitis, dry eye, incomplete eyelid closure, intermittent or manifest strabismus, diabetes, asthma, low immunity or other general diseases, systemic or local application of atropine or other drugs that may affect AL; intolerance of corneal contact lenses or spectacles
Interventions Intervention: OK lenses worn overnight
Comparison intervention: SVLs
Outcomes Primary outcome: AL, SER
Maximum follow‐up: 12 months
Starting date September 2018
Estimated end date: December 2020
Contact information chictr.org.cn/showproj.aspx?proj=29222
Notes  

ChiCTR1800017683.

Study name A double‐masked comparative study of peripheral defocus lenses
Methods Randomised parallel‐group design
Participants Inclusion criteria: age 8‐13 years; SER of −0.75 to −4.75 D in each eye, as measured by cycloplegic autorefraction; astigmatism of not more than 1.50 D; anisometropia of not more than 1.00 D; BCVA ≥ 0.05 LogMAR (≥ 0.9 as Snellen)
Exclusion criteria: history of PALs or BFl use and no prior use of contact lenses; strabismus by cover test at near and distance; ocular disease with full ophthalmic examination, such as retinal disease, cataract and ptosis; systemic or neurodevelopmental conditions; ocular or systemic medicine, which might affect myopia progression or VA through known effects on retina, accommodation or significant elevation of IOP
Interventions Intervention 1: "defocus lenses"
Intervention 2: "defocus lenses"
Comparison intervention: SVLs
Outcomes Primary outcome: refractive power; AL; contrast VA
Secondary outcomes: not reported
Maximum follow‐up: not reported
Starting date July 2018
Estimated end date: November 2020
Contact information chictr.org.cn/hvshowproject.aspx?id=13585
Notes  

ChiCTR1800018092.

Study name Comparison of myopia control effect between single use ortho‐k and combined with 0.01% atropine eye drops in children
Methods Randomised parallel‐group design
Participants Inclusion criteria: children with myopia were included in the randomised control, with no gender limitation, aged 7‐12 years old, clear refractive media, equivalent spherical lens ≤−5.00D, 40.00D ≤ corneal base curvature < 45.50 D, and corneal astigmatism ≤ 1.50 D
Exclusion criteria: rule out basic eye diseases that may affect vision, corneal plasticiser and potion
Interventions Intervention: OK glass
Comparison intervention: 0.01% atropine eye drops once per night
Outcomes Primary outcome: AL
Secondary outcomes: SER, corneal curvature
Maximum follow‐up: not reported
Starting date  
Contact information  
Notes Study name: Comparison of myopia control effect between single use ortho‐k and combined with 0.01% atropine eye drops in children

ChiCTR1900021316.

Study name Clinical observation for auricular acupoint stimulation combined with low‐concentration atropine in myopia control and its effect on accommodative microfluctuations
Methods Randomised parallel‐group design
Participants Inclusion criteria: age 6‐11 years children; male or female; with simple myopia; 0.5% tocarbamide mydriatic optometry: +0.5 DS to −6.0 DS; corneal topography Kmax: 42‐44 D; astigmatism of < 1.50 D, anisometropia of < 1.00 D, IOP of 10‐21 mmHg; patient with good compliance who volunteers to join the study and signs informed consent
Exclusion criteria: patient with other ocular diseases (e.g. cataract, congenital retinal disease, strabismus, amblyopia) or systemic diseases; patient with active eye lesions or undergoing eye surgery; allergy to atropine; patient whose skin of the auricular acupoint area is broken or patient who has allergy to auricular plaster; guardians do not hold reasonable expectations
Interventions Intervention: 0.01% atropine eyedrops combined with auricular acupoint stimulation
Comparison intervention: 0.01% atropine eyedrops
Outcomes Primary outcome: uncorrected distance VA; dioptre; AL
Secondary outcomes: anterior chamber depth; accommodation amplitude; accommodative microfluctuations
Maximum follow‐up: not reported
Starting date February 2019
Estimated end date: May 2020
Contact information chictr.org.cn/hvshowproject.aspx?id=15141
Notes  

ChiCTR2000033904.

Study name Clinical study of combined orthokeratology (OK lens) and 0.01% atropine solution to control myopia progression in children
Methods Randomised cross‐over design
Participants Inclusion criteria: children aged 8‐12 years; spherical equivalent myopia −1 D to −4 D; astigmatism < 1.5 D; anisometropia < 1.0 D; corrected vision ≥ 1.0; no history of eye surgery; no eye or systemic disease affecting vision
Exclusion criteria: congenital or pathological myopia; premature infants and low birth weight; allergic to atropine; using other drugs or treatments to control myopia
Interventions Intervention: combined OK and 0.01% atropine eye drops
Comparison intervention: OK and placebo (blank solvent)
Outcomes Primary outcome: myopia progression (AL, SER)
Maximum follow up: not reported
Starting date June 2020
Estimated end date: February 2022
Contact information chictr.org.cn/com/25/hvshowproject.aspx?id=160051
Notes  

ChiCTR2000036880.

Study name A multicenter, double‐blind, randomized controlled clinical trial for defocused spectacle lenses in controlling progression of high myopia in children
Methods Randomised parallel‐group design
Participants Inclusion criteria: children aged 8‐14 years, SER −5 to −8 D, astigmatism ≤ 1.5 D, anisometropia ≤ 1.50 D, progression of myopia in the last year ≥ 0.5 D; BCVA ≥ 0.8, near acuity ≥ 1.0, birth weight ≥ 1500 g
Exclusion criteria: ocular or systemic diseases (e.g. Marfan's syndrome, retinopathy of prematurity, etc.) that may affect vision or refractive development; other treatment for myopia control in the last year, corneal refractive surgery
 
Interventions Intervention: defocussed spectacle lenses
Comparison intervention: SVLs
Outcomes Primary outcome: AL
Secondary outcome: refractive status, VA, accomodative amplitude, pupil diameter, contrast sensitivity, AES
Maximum follow‐up: not reported
Starting date October 2020
Estimated end date: September 2022
Contact information chictr.org.cn/showproj.aspx?proj=59891
Notes  

ChiCTR2000036917.

Study name A multicenter, double‐blind, randomized controlled clinical trial for defocused soft contact lens in controlling progression of high myopia in children
Methods Randomised parallel‐group design
Participants Inclusion criteria: children aged 8‐14 years, SER −8 D to −5 D, astigmatism ≤ 1.5 D, anisometropia ≤ 1.5 D, progression of myopia in the last year ≥ 0.5 D; BCVA  ≥ 0.8
Exclusion criteria: ocular or systemic diseases (e.g. Marfan's syndrome, retinopathy of prematurity, etc.) that may affect vision and refractive development, patients with xerophthalmia, allergic conjunctivitis, entropion, trichiasis, severe keratoconjunctival infection, keratoconus and other eye diseases, allergies or contraindications to cycloplegia drug, received other treatment for myopia control in the last year, such as atropine and other anticholinergic drugs, OK, defocused soft contact lens, defocused spectacles, etc), prior corneal refractive surgery
Interventions Intervention: defocussed soft contact lenses
Comparison intervention: SVSCLs
Outcomes Primary outcome: AL
Secondary outcome: refractive status, VA, accomodative amplitude, pupil diameter, contrast sensitivity, AEs
Maximum follow‐up: not reported
Starting date October 2020
Estimated end date: September 2022
Contact information chictr.org.cn/showproj.aspx?proj=59881
Notes  

ChiCTR2000037113.

Study name Precise intervention of progressive myopia in children, adolescents and young adults. A randomized clinical trial
Methods Randomised parallel‐group design
Participants Inclusion criteria: children and adolescents aged 8‐15 years, equivalent spherical power (8‐9 years old −6.00 D to −2.00 D, 10 years old: −6.00 D to −3.00 D, 11‐12 years old: −6.00 D to −4.00 D, 13‐15 years old: −6.00 D to −5.00 D), astigmatism ≤ 1.50 D; spherical anisometropia ≤ 1.50 D
Exclusion criteria: eye diseases that may affect vision or ametropia, systemic disease (immune system diseases, central nervous system diseases, Down's syndrome, asthma, severe cardiopulmonary function, severe liver and kidney dysfunction), contraindications to atropine, use of anticholinergic drugs within the past month e.g. atropine or pirenzipine; use of OK, multifocal soft lens or myopia control spectacles within the past month
 
Interventions Intervention: 0.01% atropine eyedrops
Intervention: 1% atropine eyedrops
Intervention: combined OK and 0.01% atropine eyedrops
Intervention: combined OK and 1% atropine eyedrops
Outcomes Primary outcome: SER, AL
Secondary outcome: choroidal thickness, BCVA, near VA, accommodation amplitude, pupil size
Maximum follow up: not reported
Starting date October 2020
Estimated end date: not reported
Contact information chictr.org.cn/showproj.aspx?proj=60282
Notes  

ChiCTR2000037443.

Study name A randomized parallel controlled trial of the effect of peripheral myopia defocus lens for preventing and controling myopia in children
Methods Randomised parallel‐group design
Participants Inclusion criteria: aged 6‐15 years, emmetropia (equivalent spherical power between +0.75 and −0.50 D), myopia (equivalent spherical power between −0.75 to −8.00 D), astigmatism ≤ 1.50 D, spherical anisometropia ≤ 2.00 D, VA ≥ 1.0, clear refractive media, no nystagmus, good fixation
Exclusion criteria: narrow anterior chamber or IOP > 20 mmHg or glaucoma, keratitis, acute infection or inflammation, contact lens wear (including those wearing contact lens during the study)
Interventions Intervention: peripheral defocus spectacle lenses (Hoya Myosmart)
Comparison intervention: SVLs
Outcomes Primary outcome: ocular health evaluation, cycloplegic refraction, AL, VA, contrast sensitivity
Maximum follow up: not reported
Starting date September 2020
Estimated end date: December 2021
Contact information chictr.org.cn/com/25/hvshowproject.aspx?id=59371
Notes  

ChiCTR2000040990.

Study name The effect of myopia control and influence of visual quality in children treated with orthokeratology of aspherical base curve design
Methods Randomised parallel‐group design
Participants Inclusion criteria: age between 8‐12 years old, BCVA (ETDRS) in a single eye ≥ 20/25, SER −0.75 D ~ −4.00 D, corneal astigmatism ≤ 1.50 D, anisometropia ≤ 1.00 D, no other methods of myopia control, no history of wearing contact lenses
Exclusion criteria: narrow anterior chamber or IOP > 21 mmHg; suffering from keratitis, keratoconus, glaucoma, strabismus or amblyopia; accommodative insufficiency
Interventions Intervention: aspherical base curve designed OK lenses
Intervention: spherical base curve designed OK lenses
Outcomes Primary outcome: AL, objective refraction, relative peripheral refraction, choroidal thickness, ocular comfort (OSDI questionnaire), AEs
Maximum follow up: not reported
Starting date December 2020
Estimated end date: June 2022
Contact information chictr.org.cn/hvshowproject.aspx?id=84332
Notes  

ChiCTR2100041788.

Study name The effect of peripheral defocus modifying spectacle lenses on myopia control
Methods Randomised cross‐over trial
Participants Inclusion criteria: 8‐14 years old, myopia −1.00 to −4.00 D, astigmatism ≤ −2.00: BCVA ≥ 1.0, anisometropia ≤ 2 D
Exclusion criteria: wearing contact lenses, peripheral defocus modifying spectacle lenses or using 0.01% atropine, strabismus, intermittent exotropia
Interventions Intervention: peripheral defocus modifying spectacle lenses
Comparison intervention: OK lenses
Outcomes Primary outcome: AL
Maximum follow up: not reported
Starting date January 2021
Estimated end date: August 2023
Contact information chictr.org.cn/hvshowproject.aspx?id=82249
Notes  

ChiCTR‐INR‐17013794.

Study name The effectiveness safety of corneal contact lens used to correct myopia: a multi‐center, randomized, open and positive parallel control clinical trial
Methods Randomised parallel‐group design
Participants Inclusion criteria: 41 patients aged 8‐40 years with myopia ≤ 4.00 D, astigmatism with‐the‐rule of < 1.75 D, and astigmatism against‐the‐rule of < 1.00 D; BCVA not less than 20/20; corneal curvature at 40.00 D‐46.00 D; dioptre stay stability before trial; has not worn hard contact lenses in the past 2 months
Exclusion criteria: systemic disease that causes low immunity or effects on corneal shape; corneal abnormality; corneal surgery; history of corneal or ocular trauma; hypocorneal sensory impairment; intraocular surgery; fundus lesions; ocular disease; pregnant or lactating; use of drugs that cause dry eyes or affect corneal curvature; allergy to contact lens or its solution; pupil diameter > 6.2 mm
Interventions Intervention: corneal contact lens 2 (not specified)
Comparison intervention: corneal contact lens 2 (not specified)
Outcomes Primary outcome: VA
Secondary outcomes: not reported
Maximum follow‐up: not reported
Starting date May 2017
Estimated end date: December 2018
Contact information chictr.org.cn/showprojen.aspx?proj=23702
Notes  

ChiCTR‐INR‐17013853.

Study name Effects of orthokeratology and combined with 0.01% atropine on myopia control: a multicenter comparative study
Methods Randomised parallel‐group design
Participants Inclusion criteria: 216 children aged 8‐15 years; spherical degree without dilation ≥ −1.00 D and ≤ −5.50 D; equivalent spherical degree ≥ −1.00 D and ≤ −5.50 D; astigmatism ≤ −1.50 D; BCVA ≥ 1.0 D; no strabismus; no contact lens wearing history; no history of myopia control by optical or drug route; no active inflammation or ocular surface disease; no serious ocular appendage lesions and eye organic disease; co‐operation with researchers
Exclusion criteria: systemic connective tissue disease and autoimmune disease; history of ocular trauma or surgery; history of severe ocular infection
Interventions Intervention 1: OK at night
Intervention 2: OK at night and 0.01% atropine eye drops before sleep
Comparison intervention: SVLs
Outcomes Primary outcomes: AL, refraction, eyesight
Secondary outcomes: IOP, corneal topography
Maximum follow‐up: 12 months
Starting date December 2017
Estimated end date: June 2019
Contact information chictr.org.cn/showprojen.aspx?proj=22940
Notes  

ChiCTR‐IOR‐17010432.

Study name Myopia progression with invisible round segment bifocal spectacle lenses
Methods Randomised parallel‐group design
Participants Inclusion criteria: BCVA of 6/9.5 or better with spectacles in each eye; normal ocular health; ability to comply with trial protocol; parental ability to understand English and Mandarin and parental consent
Exclusion criteria: history of allergy to topical anaesthetics; strabismus; eye surgery; ocular or systemic condition affecting vision; ocular injury; use of BFs, spectacles, OK, vision training, orthoptic training, or conditions that affect ability to wear spectacles
Interventions Intervention: BF spectacles
Comparison intervention: SVLs
Outcomes Primary outcome: SER
Secondary outcome: AL
Maximum follow‐up: not reported
Starting date February 2017
Estimated end date: September 2018
Contact information chictr.org.cn/showproj.aspx?proj=17727
Notes  

ChiCTR‐IOR‐17011993.

Study name Prospective, masked, contralateral, randomized, cross‐over dispensing clinical trial to compare the myopia progression rate between myopia control contact lenses and single vision contact lenses
Methods Randomised cross‐over design
Participants Inclusion criteria: aged 7‐13 years inclusive; spherical component −0.75 D to −3.50 D with cylinder no more than −0.75 D; anisometropia ≤ 0.75 D; informed consent; parent or guardian who is able to read and comprehend Mandarin and give informed consent as demonstrated by signing a record of informed consent by both parent/guardian and participant; ocular health findings considered to be normal and that would not prevent patient from safely wearing contact lenses; vision correctable to 6/9.5 or better in each eye with study contact lenses
Exclusion criteria: pre‐existing ocular irritation that would preclude contact lens fitting; any systemic or ocular condition or ocular injury that may preclude safe wearing of contact lenses; having undergone corneal refractive surgery; at baseline, astigmatism > 0.75 D in either eye; past strabismus and/or current ongoing amblyopia; any ocular, systemic, or other condition or disease with possible associations with myopia or affecting refractive development; current orthoptic treatment or vision training; eye injury or surgery within 12 weeks immediately before enrolment for this study; having undergone atropine treatment for myopia control, worn BF or PALs or antimyopia contact lenses previously; having worn OK lenses previously; requiring anticholinergic medication for gastrointestinal or other conditions; at baseline, anisometropic by > 0.75 D
Interventions Intervention 1: single vision contact lenses in both eyes
Intervention 2: myopia control contact lens in 1 eye, and single vision contact lens in the other eye; contact lenses swapped between eyes after 6 months
Comparison intervention: myopia control contact lens in 1 eye, and single vision contact lens in the other eye; contact lenses swapped between eyes after 6 months
Outcomes Primary outcome: SER, AL
Secondary outcomes: not reported
Maximum follow‐up: not reported
Starting date Not reported
Estimated end date: not reported
Contact information http://www.chictr.org.cn/showprojen.aspx?proj=20301
Notes  

ChiCTR‐IPD‐16008844.

Study name Clinical study of low‐concentration atropine in controlling child myopia
Methods Randomised parallel‐group design
Participants Inclusion criteria: 400 children aged 6‐12 years; myopia spherical equivalent degree: −1.25 to −6.0; astigmatism < 2.0; distance corrected VA ≥ 0.8, without significant skew and other eye disease; no ocular inflammation; no history of ocular trauma; no history of ocular surgery
Exclusion criteria: congenital myopia and pathological myopia; premature and low birth weight myopia patients, with no other related myopia drugs and training method in the past 6 months
Interventions Intervention 1: 0.005% concentration atropine
Intervention 2: 0.01% concentration atropine
Intervention 3: 0.02% concentration atropine
Intervention 4: 0.02% concentration atropine, once every 2 days
Comparison intervention: spectacles
Outcomes Primary outcomes: "myopia degree"
Secondary outcome: not reported
Maximum follow‐up: not reported
Starting date July 2016
Estimated end date: July 2020
Contact information chictr.org.cn/com/25/hvshowproject.aspx?id=11127
Notes  

ChiCTR‐TRC‐07000029.

Study name Double‐blinded, randomized controlled trial about the influence of new lenses on the progress of children's myopia
Methods Randomised parallel‐group design
Participants Inclusion criteria: 200 children aged 6‐16 years; degree of myopia > −0.50 D and < −4.50 D; astigmatism degree < −1.50 D; binocular anisometropic degree < 1 D; healthy ocular region; VA can be corrected to 6/9 (20/30) or higher
Exclusion criteria: strabismus or amblyopia; history of allergy to tropicamide; any ophthalmopathy, previous ophthalmic surgery, systemic disease that may be related to myopia; using anticholinergic drugs; taking part in other myopia‐controlled study; previous wearing of OK lenses in the last 2 weeks; accepted or are participating in orthophoria treatment or vision training
Interventions Intervention 1: type A lenses
Intervention 2: type B lenses
Intervention 3: type C lenses
Comparison intervention: routine lenses
Outcomes Primary outcomes: axial length
Secondary outcome: "diopter"
Maximum follow‐up: not reported
Starting date October 2007
Estimated end date: November 2009
Contact information chictr.org.cn/showproj.aspx?proj=9496
Notes  

ChiCTR‐TRC‐07000044.

Study name Clinical randomized controlled trial of progressive addition lenses on control of myopia in Chinese adolescents
Methods Randomised parallel‐group design
Participants Inclusion criteria: 178 adolescents aged 7‐18 years; computer optometry after cycloplegia; binocular myopia; spherical equivalent degree between −0.75 and −3.00 D; astigmatism degree ‐1.50 D; binocular anisometropic degree < 1.00 D; bilateral corrected VA > 1.0; normal IOP: binocular IOP < 21 mmHg, and difference < 2 mmHg; no history of wearing contact lenses, BFs, or multifocal lenses; term infants; birth weight > 1250 g; agree to wear lenses and follow up for > 2 years; understand the study objective and accept the randomised allocation
Exclusion criteria: manifest strabismus or other ophthalmopathy; systematic disease; use of drugs that may influence the refractive status; myopia degree of either parent > 3 D; use of contact lenses or other myopia treatment methods in the study
Interventions Intervention: gradual focal lens
Comparison intervention: routine single lens
Outcomes Primary outcomes: myopic degree, eyeball biotest
Secondary outcome: heterophoria
Maximum follow‐up: not reported
Starting date July 2004
Estimated end date: May 2007
Contact information chictr.org.cn/showproj.aspx?proj=9481
Notes  

ChiCTR‐TRC‐09000476.

Study name Novel spectacle lenses vs single vision spectacle lenses on progression of myopia in children: a randomized clinical trial
Methods Randomised parallel‐group design
Participants Inclusion criteria: children aged 6‐12 years with SER between −0.75 D and −3.50 D; astigmatism ≤ −1.50 D; BCVA of at least 6/9.5 with spectacles; ability to comply with study protocol; normal ocular health
Exclusion criteria: anisometropia ≤ 1.00 D; history of allergy to topical anaesthetics; strabismus; eye surgery; ocular or systemic conditions affecting vision; ocular injury; use of BFs, spectacles, OK, vision training, orthoptic training, or conditions that affect ability to wear spectacles; concurrent participation in another clinical trial
Interventions Intervention: not reported (“Iteration E”)
Intervention: not reported (“Iteration G”)
Intervention: not reported (“Iteration F”)
Intervention: not reported (“Iteration H”)
Comparison intervention: SVLs
Outcomes Primary outcomes: cycloplegic autorefraction
Secondary outcome: not reported
Maximum follow‐up: not reported
Starting date August 2009
Estimated end date: December 2011
Contact information chictr.org.cn/showprojen.aspx?proj=9058
Notes  

ChiCTR‐TRC‐10000914.

Study name Progression of refractive error in myopic Chinese children wearing commercially available single vision spectacles
Methods Randomised parallel‐group design
Participants Inclusion criteria: children aged 7‐14 years; SER between −0.50 D and −3.50 D; astigmatism ≤ 0.75 D; BCVA in each eye of at least 6/9.5; ability to comply with protocol; parental ability to comprehend Mandarin; parental ability to consent
Exclusion criteria: anisometropia not greater than 1.50 D; prior use of atropine for myopia control; prior use of BF or PAL spectacles or concurrent use of OK contact lenses in the previous 12 months; prior eye surgery or ocular trauma; history of ocular or systematic condition that affects refractive development
Interventions Intervention: spherical profile spectacle lenses
Comparison intervention: aspheric front surface spectacle lenses
Outcomes Primary outcomes: SER, AL
Secondary outcome: not reported
Maximum follow‐up: not reported
Starting date July 2010
Estimated end date: September 2013
Contact information chictr.org.cn/showprojen.aspx?proj=8624
Notes  

ChiCTR‐TRC‐11001463.

Study name Efficacy of MyoVision spectacle lenses for slowing the progression of myopia
Methods Randomised parallel‐group design
Participants Inclusion criteria: 200 children aged 6‐12 years; myopic; spherical component −0.75 D to −3.50 D with astigmatism no more than −1.50 D; having at least 1 parent who is myopic; willingness to comply with wearing and visit schedule; having normal ocular health findings; having vision correctable to 6/9.5 or better in each eye with spectacles
Exclusion criteria: allergy to tropicamide or topical anaesthetics; anisometropic by > 1.00 D; strabismus or amblyopia; previous eye surgery; ocular or systemic disease with possible associations with myopia; any ocular injury or condition of the cornea or conjunctiva or eyelids; having worn BFs or MyoVision spectacles in the last 12 months; having worn OK or BF contact lenses in the last 12 months; current orthoptic treatment or vision training
Interventions Intervention: MyoVision spectacles
Comparison intervention: SVLs
Outcomes Primary outcome: myopia progression
Secondary outcome: AL
Maximum follow‐up: not reported
Starting date August 2011
Estimated end date: January 2014
Contact information chictr.org.cn/hvshowproject.aspx?id=1096
Notes  

ChiCTR‐TRC‐11001746.

Study name Assessment of myopia progression rates in children wearing either a multifocal center near or single vision soft contact lens
Methods Randomised parallel‐group design
Participants Inclusion criteria: 100 children aged 10‐17 years; Chinese ethnicity; myopic (short‐sighted) up to −8.00 D of spherical equivalent; willingness to comply with wearing and clinical trial visit schedule as directed by the investigator; having ocular health findings considered to be “normal” and that would prevent the patient from safely wearing contact lenses; having distance vision correctable to 6/9.5 or better in each eye with study contact lenses
Exclusion criteria: pre‐existing ocular irritation, injury, or condition; any systemic disease that adversely affects ocular health; eye surgery within 12 weeks immediately before enrolment for this study; previous corneal refractive surgery; keratoconus; known allergy to, or history of, intolerance to tropicamide or topical anaesthetics; past strabismus and/or amblyopia; any ocular, systemic, or other condition or disease with possible associations with myopia or affecting refractive development; current orthoptic treatment or vision training; having undergone atropine treatment for myopia control; having worn BF or PAL spectacles in the previous 12 months; having worn OK lenses in the previous 12 months; requiring anticholinergic medication for gastrointestinal or other conditions; pregnant or lactating female patients
Interventions Intervention 1: multifocal silicone hydrogel contact lens
Intervention 2: spherical silicone hydrogel contact lens
Outcomes Primary outcomes: cycloplegic autorefraction, AL
Secondary outcomes: not reported
Maximum follow‐up: not reported
Starting date December 2011
Estimated end date: December 2015
Contact information chictr.org.cn/hvshowproject.aspx?id=1766
Notes  

ChiCTR‐TRC‐13003396.

Study name Myopia progression with sedentary use, small segment, concentric bifocals
Methods Randomised parallel‐group design
Participants Inclusion criteria: children aged 6‐12 years, with spherical equivalent of −0.75 D to −3.50 D; astigmatism not greater than −1.50 D; normal ocular health; parental willingness to comply with the protocol; ability to consent
Exclusion criteria: anisometropia ≤ 1.00 D; history of allergy to topical anaesthetics; strabismus; eye surgery; ocular or systemic conditions affecting vision; ocular injury; use of BFs, spectacles, OK, vision training, orthoptic training, or condition that affects ability to wear spectacles; concurrent participation in another clinical trial
Interventions Intervention: intermittent alternate use of spectacles with concentric BF lenses and SVLs
Comparison intervention: SVLs
Outcomes Primary outcome: change in SER
Secondary outcome: change in AL
Maximum follow‐up: not reported
Starting date August 2013
Estimated end date: March 2015
Contact information chictr.org.cn/hvshowproject.aspx?id=6324
Notes  

ChiCTR‐TRC‐13004032.

Study name Chinese university low dose atropine for myopia progression study (CU‐LAMP)
Methods Randomised parallel‐group design
Participants Inclusion criteria: age 4‐12 years; myopia: SE −1 to −10 D; astigmatism: < 2.5 D; anisometropia: < 2.0 D; myopia progression > 1 D for BE in one year; informed parental consent
Exclusion criteria: ophthalmic diseases other than refractive errors; previous use of treatment of atropine; allergy or intolerance to atropine; inability to attend