Amblyopia in children (aged 7 years or less)

Abstract

Introduction

Amblyopia is reduced visual acuity not immediately correctable by glasses, in the absence of ocular pathology. It is commonly associated with squint (strabismus) or refractive errors resulting in different visual inputs to each eye during the sensitive period of visual development (aged <7–8 years). The cumulative incidence is estimated at 2% to 4% in children aged up to 7 years.

Methods and outcomes

We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of medical treatments for amblyopia in children aged 7 years or less? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).

Results

At this update, searching of electronic databases retrieved 70 studies. After deduplication and removal of conference abstracts, 51 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 37 studies and the further review of 14 full publications. Of the 14 full articles evaluated, two systematic reviews were updated and three RCTs and two follow-up studies were added at this update. We performed a GRADE evaluation for nine PICO combinations.

Conclusions

In this systematic overview we categorised the efficacy for three interventions, based on information about the effectiveness and safety of glasses, occlusion, or penalisation with atropine.

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 7 years.

• The key visual developmental period is up to the age of 7 years; therefore, this age group is the focus of the overview.

• Amblyopia is commonly regarded as less amenable to treatment after age 7 to 8 years. Although treatment may be effective in older children, recovery of normal vision becomes progressively less likely.

Wearing glasses 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) plus glasses may be more effective than no treatment in children aged 3 to 5 years. Further data assessing occlusion in combination with near-vision tasks, such as encouraging the child to do close work while wearing the patch, confirm that combined interventions are more effective than glasses alone.

• We don't know whether prescribing occlusion of the fellow eye for longer periods every day is more effective than prescribing for shorter periods of daily occlusion, but success rates do 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 younger than 7 years who are not fully treated with glasses.

Clinical context

General background

Amblyopia is decreased vision in one or both eyes due to abnormal development of vision in infancy or childhood. It affects up to 4% of children aged up to 7 years and can be amenable to treatment if detected early enough.

Focus of the review

This systematic overview analyses the treatment options available for this common condition, focusing on the key visual developmental period, which is up to the age of 7 years. Commonly used interventions assessed include the use of glasses and penalisation, either with occlusion or atropine alone or in combination with near vision tasks. This overview looks at how effective these treatments are in terms of visual acuity, interocular acuity difference, binocularity, and stereopsis, as well as any adverse effects.

Comments on evidence

The evidence base for amblyopia has improved in recent years and includes several randomised trials, longitudinal studies examining the effects of prolonged spectacle wear, and studies with objective monitoring of actual achieved patching treatment versus recommended patching treatment. These studies have informed clinical practice and are well known. However, for this overview, only RCTs are included and, as many of these are small trials with less than 200 participants, the quality of the evidence they provide is described as 'low' or 'very low' in many cases.

Search and appraisal summary

The update literature search for this review was carried out from the date of the last search, May 2010, to January 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 70 studies. After deduplication and removal of conference abstracts, 51 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 37 studies and the further review of 14 full publications. Of the 14 full articles evaluated, two systematic reviews were updated, and three RCTs and two follow-up studies were added at this update.

About this condition

Definition

Amblyopia is reduced visual acuity not immediately correctable by glasses, in the absence of ocular pathology.[1] 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.[2] Amblyopia is defined in terms of visual acuity, but other visual functions are affected as well.[3] This overview excluded studies with populations with an underlying ocular pathology (structural abnormality of the visual pathways or the eye itself: e.g., cataract, optic nerve pathology, retinal pathology such as retinoblastoma, malformed eye such as microphthalmia). Underlying pathology does not include strabismus or refractive errors.

Incidence/ Prevalence

It is estimated that the cumulative incidence is 2% to 4% in children aged up to 7 years.[4] [5] 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, caused either by high refractive error (unilateral refractive amblyopia or bilateral ametropic amblyopia), by different refractive errors in each eye (anisometropic amblyopia), or by conflicting visual inputs between the eyes because of squint (strabismic amblyopia).[2] Amblyopia can also be associated with an obstruction to the visual axis (e.g., by ptosis or cataract [known as stimulus deprivation amblyopia]). In a multi-centre 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.[6] 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.[7]

Prognosis

Amblyopia is commonly regarded as less amenable to treatment after age 7 to 8 years, although there is some evidence that treatment can be effective in children aged 7 to 12 years.[8] Recovery of normal vision becomes progressively less likely in older children. Successfully treated amblyopia might regress in about one quarter of children.[9] The lifetime risk of blindness because of loss of the better-seeing eye is 1% (95% CI 1.1% to 1.4%),[10] with a 5-year cumulative risk of 13% in those aged 75 to 84.[11] If the better-seeing eye is lost, the visual acuity of 10% of amblyopic eyes can improve.[12]

Aims of intervention

To initiate treatment for amblyopia at a stage when treatment is likely to be effective (ideally between the ages of 3 and 5 years and <7 years), with minimal adverse effects of treatment.

Outcomes

Visual outcomes, including visual acuity improvement, interocular acuity difference (between eyes), binocularity, and stereopsis; compliance with treatment; adverse effects.

Methods

Search strategy BMJ Clinical Evidence search and appraisal date January 2014. Databases used to identify studies for this systematic overview include: Medline 1966 to January 2014, Embase 1980 to January 2014, The Cochrane Database of Systematic Reviews 2014, issue 1 (1966 to date of issue), the Database of Abstracts of Reviews of Effects (DARE), and the Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this systematic overview were systematic reviews and RCTs published in English, any level of blinding, and containing at least 20 individuals (at least 10 per arm), of whom at least 50% were followed up. There was no minimum length of follow-up. BMJ Clinical Evidence does not necessarily report every study found (e.g., every systematic review). Rather, we report the most recent, relevant, and comprehensive studies identified through an agreed process involving our evidence team, editorial team, and expert contributors. Evidence evaluation A systematic literature search was conducted by our evidence team, who then assessed titles and abstracts, and finally selected articles for full text appraisal against inclusion and exclusion criteria agreed a priori with our expert contributor. In consultation with the expert contributor, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the overview. In addition, information that did not meet our pre-defined criteria for inclusion in the benefits and harms section may have been reported in the 'Further information on studies' or 'Comment' sections (see below). Adverse effects All serious adverse effects, or those adverse effects reported as statistically significant, were included in the harms section of the overview. Pre-specified adverse effects identified as being clinically important were also reported, even if the results were not statistically significant. Although BMJ Clinical Evidence presents data on selected adverse effects reported in included studies, it is not meant to be, and cannot be, a comprehensive list of all adverse effects, contraindications, or interactions of included drugs or interventions. A reliable national or local drug database must be consulted for this information. Comment and Clinical guide sections In the Comment section of each intervention, our expert contributor may have provided additional comment and analysis of the evidence, which may include additional studies (over and above those identified via our systematic search) by way of background data or supporting information. As BMJ Clinical Evidence does not systematically search for studies reported in the Comment section, we cannot guarantee the completeness of the studies listed there or the robustness of methods. Our expert contributors add clinical context and interpretation to the Clinical guide sections where appropriate. Structural changes this update At this update, we have removed the following previously reported question: What are the effects of interventions to detect amblyopia early?, and focused the population to include children aged 7 years or less only. Data and quality To aid readability of the numerical data in our overviews, 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). BMJ Clinical Evidence does not report all methodological details of included studies. Rather, it reports by exception any methodological issue or more general issue that may affect the weight a reader may put on an individual study, or the generalisability of the result. These issues may be reflected in the overall GRADE analysis. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Amblyopia in children (aged 7 years or less).

Important outcomes	Treatment compliance, Visual outcomes
Studies (Participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of medical treatments for amblyopia in children aged 7 years or less?
1 (118)	Visual outcomes	Glasses versus no treatment	4	–2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
1 (118)	Visual outcomes	Occlusion plus glasses versus no treatment	4	–2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
1 (180)	Visual outcomes	Occlusion plus near-vision tasks (plus glasses if needed) versus glasses alone	4	–2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results
1 (35)	Visual outcomes	Prescribed occlusion (for 3 or 6 hours) versus no occlusion (in children also wearing glasses and prescribed near-vision tasks)	4	–2	–1	0	0	Very low	Quality points deducted for sparse data and incomplete reporting of results; consistency point deducted as results may have been confounded by compliance
8 (726)	Visual outcomes	Longer versus shorter duration of prescribed occlusion (in children also wearing glasses and prescribed near-vision tasks)	4	–2	0	0	0	Low	Quality points deducted for weak methods (inclusion of additional interventions in some RCTs) and incomplete reporting of results in some RCTs
2 (245)	Treatment compliance	Longer versus shorter duration of prescribed occlusion (in children also wearing glasses and prescribed near-vision tasks)	4	–2	0	0	0	Low	Quality points deducted for weak methods (inclusion of additional interventions in some RCTs) and incomplete reporting of results
1 (24)	Treatment compliance	Different type of occlusion versus each other	4	–2	0	0	0	Low	Quality points deducted for sparse data and weak methods (cross-over design, no wash-out period between occlusion devices)
1 (419)	Visual outcomes	Penalisation with atropine versus occlusion (in children wearing glasses)	4	–1	0	–1	0	Low	Quality point deducted for incomplete reporting; directness point deducted for non-clinically important difference between groups in improvement in visual acuity
1 (168)	Visual outcomes	Daily penalisation with atropine versus less frequent regimens (in children wearing glasses)	4	–2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

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.

Very low-quality evidence

Any estimate of effect is very uncertain.

Visual acuity testing

This 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.