Abstract
Introduction
Amblyopia is commonly associated with squint (strabismus) or refractive errors resulting in different visual inputs to each eye during the sensitive period of visual development (<7-8 years of age). The cumulative incidence is estimated at 2% to 4% in children aged up to 15 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to detect amblyopia early? What are the effects of medical treatments for amblyopia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: active vision therapy; glasses alone or with occlusion; penalisation; screening; and targeted vision screening.
Key Points
Amblyopia is reduced visual acuity not immediately correctable by glasses, in the absence of ocular pathology.
It is commonly associated with squint (strabismic amblyopia), refractive errors resulting in different visual inputs to each eye during the sensitive period of visual development (refractive amblyopia), or with cataract or ptosis (stimulus deprivation amblyopia).
The cumulative incidence is estimated at 2% to 4% in children aged up to 15 years.
Vision screening before school entry may increase detection rates of amblyopia compared with no screening. However, pre-school screening may not improve treatment outcomes at 7 years compared with school-entry screening.
We don't know whether children with a higher risk of eye problems should be targeted for vision screening.
Most evidence is available for children under 7 years of age, in whom wearing glasses for up to 30 weeks can improve amblyopia and may cure it. Children with suspected amblyopia who have clinically important refractive error are prescribed glasses; therefore most data available on other interventions assess their effectiveness in combination with glasses.
Occlusion (covering the fellow eye using a patch) may be more effective than glasses alone in children up to 13 years of age not fully treated with glasses. Further data assessing occlusion in combination with near-vision tasks such as encouraging the child to do close work while wearing their patch confirm that combined interventions are more effective than glasses alone in younger children.
Some older children might improve with treatment, although there are few data available to support this.
Prescribing occlusion for the fellow eye for longer periods every day is no more effective at improving amblyopia than prescribing shorter periods of daily occlusion, but success rates increase in proportion to objectively measured compliance.
Penalisation with atropine may be as effective as occlusion when given in combination with other interventions for improving amblyopia in children aged under 7 years who are not fully treated with glasses.
We don't know whether near-vision tasks are effective alone as adjuvant treatment to glasses for amblyopia. Near-vision tasks may further enhance visual acuity when added to occlusion or penalisation but the contribution of near-vision tasks to the effects of these combination interventions remains unclear.
About this condition
Definition
Amblyopia is reduced visual acuity not immediately correctable by glasses, in the absence of ocular pathology. It is associated with complete or partial lack of clear visual input to one eye (stimulus deprivation amblyopia or unilateral/anisometropic refractive amblyopia), or, less often, to both eyes (bilateral refractive amblyopia), or to conflicting visual inputs to the two eyes (strabismic amblyopia).The severity of amblyopia is often classified according to the visual acuity in the affected eye, using visual-acuity testing. "Mild" amblyopia is often classified as being visual acuity of 6/9 to 6/12, "moderate" amblyopia as being worse than 6/12 to 6/36, and "severe" amblyopia as being worse than 6/36. Different studies use different definitions of severity, but most assume normal vision (6/6 or better) in the fellow eye. One line of letters or symbols (usually 4 or 5) in a visual-acuity chart constitutes 0.1 LogMAR units. A change in 0.2 LogMAR units is often quoted as being the smallest clinically important change in visual acuity, although some studies use a change of 0.1 LogMAR units or greater, which might be considered clinically marginal. Diagnosis: Amblyopia is diagnosed by testing visual acuity in each eye separately, with the person wearing an adequate refractive correction, and after exclusion of ocular pathology. Amblyopia is defined in terms of visual acuity, but other visual functions are affected as well.
Incidence/ Prevalence
It is estimated that the cumulative incidence is 2% to 4% in children up to 15 years of age. The population prevalence is affected by whether there have been any interventions to prevent or treat the condition.
Aetiology/ Risk factors
Amblyopia is associated with degraded visual input, either caused by high refractive error (unilateral refractive amblyopia, also known as ametropic amblyopia), by different refractive errors in each eye (anisometropic amblyopia), or by conflicting visual inputs between the eyes because of squint (strabismic amblyopia). Amblyopia can also be associated with an obstruction to the visual axis — for example, by ptosis or cataract (known as stimulus deprivation amblyopia). In a multicentre RCT of 409 children aged 3 to 6 years treated for amblyopia, 38% were strabismic, 37% were anisometropic, and 24% were both strabismic and anisometropic. Whereas strabismus and anisometropia are common causes of amblyopia, less common causes include ptosis, congenital cataract, and corneal injury or dystrophy, accounting for only up to 3% of cases.
Prognosis
Amblyopia is commonly regarded as untreatable after 7 to 8 years of age, although there is some evidence that treatment can be effective in children aged 7 to 12 years. Recovery of normal vision becomes progressively less likely in older children. Successfully treated amblyopia might regress in about a quarter of children. The lifetime risk of blindness because of loss of the better-seeing eye is 1.2% (95% CI 1.1% to 1.4%). If the better-seeing eye is lost, the visual acuity of 10% of amblyopic eyes can improve.
Aims of intervention
To detect amblyopia early; to initiate treatment for amblyopia at a stage when treatment is likely to be effective (ideally between 3 and 5 years of age, and under 7 years of age).
Outcomes
Early detection: number of cases of amblyopia detected and treated; treatment: visual acuity; interocular acuity difference; binocularity; stereopsis; compliance with treatment; adverse effects of treatment.
Methods
Clinical Evidence search and appraisal May 2008. The following databases were used to identify studies for this systematic review: Medline 1986 to May 2008, Embase 1986 to May 2008, and The Cochrane Library, Issue 2, 2008. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), and NICE. The contributor also performed a hand search for systematic reviews in The Cochrane Library, Issue 4, 2008. Abstracts of the studies retrieved were assessed independently by an information specialist using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: systematic reviews (including systematic reviews of observational studies), RCTs, and prospective and retrospective cohort studies in any language, containing more than 20 individuals, and with a follow-up of more than 50%. There was no minimum length of follow-up. We included open studies. We searched for studies including children and adults. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).
Table.
Important outcomes | Prevalence of amblyopia, visual acuity, and adverse effects | ||||||||
Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
What are the effects of interventions to detect amblyopia early? | |||||||||
1 (1590) | Prevalence of amblyopia | Screening v no screening | 2 | 0 | 0 | 0 | 0 | Low | |
1 (3490) | Prevalence of amblyopia | Repeated screening v usual care | 4 | 0 | 0 | 0 | 0 | High | |
1 (6081) | Prevalence of amblyopia | Pre-school screening v school-entry screening | 2 | –1 | 0 | 0 | 0 | Very low | Quality point deducted for very unequal distribution of children in comparison groups (results in 25% offered pre-school screening compared with those in 75% not offered it) |
1 (3490) | Visual acuity | Repeated screening v usual care | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for loss to follow-up in assessment of this outcome |
What are the effects of medical treatments for amblyopia? | |||||||||
4 (455) | Visual acuity | Glasses v no glasses | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for inclusion of non-randomised studies |
1 (164) | Visual acuity | Glasses plus occlusion v no treatment | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
1 (180) | Visual acuity | Occlusion plus glasses plus near-vision tasks v glasses alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
1 (507) | Visual acuity | Occlusion plus penalisation plus near-vision tasks v glasses alone | 4 | 0 | –1 | 0 | 0 | Moderate | Consistency point deducted for conflicting results for different age groups |
1 (60) | Visual acuity | Longer or shorter periods of prescribed occlusion v no occlusion | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted as finding of lack of difference with different duration of treatment may have been confounded by compliance |
4 (524) | Visual acuity | Longer v shorter duration of prescribed occlusion | 4 | 0 | 0 | 0 | 0 | High | |
1 (419) | Visual acuity | Penalisation with atropinev occlusion | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
2 (331) | Visual acuity | Daily penalisation with atropine v less frequent regimens | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for inclusion of non-randomised study |
1 (70) | Visual acuity | Penalisation with atropine v optical penalisation | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
3 (283) | Visual acuity | Near-vision tasks v no no near-vision tasks | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for inclusion of non-randomised evidence |
Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion.Consistency: similarity of results across studies.Directness: generalisability of population or outcomes. Effect size: based on relative risk or odds ratio.
Glossary
- High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Penalisation
involves blurring of the fellow eye with a cycloplegic agent (such as atropine) or with a spectacle lens that over or under corrects the true refractive error. Both methods of penalisation prevent the eye having a sharply focussed image, although light is still received as normal.
- Very low-quality evidence
Any estimate of effect is very uncertain.
- Visual acuity testing
is carried out with charts using letters or standard pictures or symbols. Modern tests that incorporate crowding and LogMAR (logarithm of the minimum angle of resolution) size scaling are more accurate. One line of letters or symbols (usually 4 or 5) constitutes 0.1 LogMAR units and roughly approximates to one line on a Snellen chart, although this conversion factor is inaccurate and should only be used as a crude guide to interpretation. Given the variability in test performance within individuals, a change in 0.2 LogMAR units is often quoted as being the smallest clinically important change, although some studies use a change of 0.1 LogMAR or greater, which might be considered clinically more marginal. Change of less than 0.1 LogMAR unit is not clinically important and could be accounted for by test–retest variability.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
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