Intervention Review

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Occlusion for stimulus deprivation amblyopia

  1. Aileen Antonio-Santos1,*,
  2. Satyanarayana S Vedula2,
  3. Sarah R Hatt3,
  4. Christine Powell4

Editorial Group: Cochrane Eyes and Vision Group

Published Online: 6 FEB 2014

Assessed as up-to-date: 28 OCT 2013

DOI: 10.1002/14651858.CD005136.pub3


How to Cite

Antonio-Santos A, Vedula SS, Hatt SR, Powell C. Occlusion for stimulus deprivation amblyopia. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD005136. DOI: 10.1002/14651858.CD005136.pub3.

Author Information

  1. 1

    Grand Rapids Medical Education Partners, Grand Rapids, Michigan, USA

  2. 2

    Johns Hopkins University, Baltimore, Maryland, USA

  3. 3

    Mayo Clinic, Department of Ophthalmology, Rochester, Minnesota, USA

  4. 4

    Royal Victoria Infirmary, Department of Ophthalmology, Newcastle upon Tyne, UK

*Aileen Antonio-Santos, Grand Rapids Medical Education Partners, 25 Michigan Street NE, Grand Rapids, Michigan, 49301, USA. aileen.antonio@ht.msu.edu.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 6 FEB 2014

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Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Description of the condition

The term 'amblyopia' refers to bluntness of vision and is derived from the Greek words "amblys" (meaning blunt) and "ops" (meaning eye). Clinically, amblyopia denotes a reduction in vision in the absence of any retinal anomaly or any disorder of the afferent visual pathways (Duke-Elder 1973). Amblyopia typically affects only one eye but it sometimes affects both eyes. Amblyopia is usually classified according to its cause:

  • strabismic, caused by squint (eye misalignment);
  • anisometropic, caused by unequal refractive (focusing) error;
  • meridional, caused by astigmatism (irregular corneal curvature);
  • ammetropic, caused by high refractive error in both eyes;
  • stimulus deprivation, caused by an obstruction in the visual pathway.

Mixed amblyopia, which is a result of more than one cause, is typically due to a combination of strabismic and anisometropic amblyopia. This review is focused on interventions for stimulus deprivation amblyopia (SDA), also called amblyopia ex anopsia. Other Cochrane reviews have evaluated interventions for strabismic and anisometropic (refractive) amblyopia (Taylor 2011; Taylor 2012).

 

Pathophysiology

Visual experiences in early life determine the organization of the portion of the adult brain that processes visual stimuli (Wiesel 1963). The time within which abnormal visual input can lead to a disruption of the normal pattern of development is called the 'critical period' (Hockfield 1998). There are several critical periods, each associated with different visual functions (Harwerth 1990), which probably reflect development of different parts of the brain. These critical periods can be considered as a continuum from extreme sensitivity to almost no sensitivity to external stimuli. Amblyopia begins to develop in these critical periods at young ages when the brain and the visual system are immature and connections between neurons are still being formed and stabilized. During the critical period, most amblyopia is reversible, usually until the child is 10 years old (AAO 2002). The critical period varies considerably among children and depends on the type of amblyopia.

 

Etiology

Patients with SDA lose vision from disuse or lack of formation of clear retinal images, most commonly as a result of one of the following:

Patients with SDA may have either otherwise healthy eyes or other co-existing conditions, such as microphthalmos (small eye), coloboma (incomplete formation of the eye), optic nerve hypoplasia (under-developed optic nerve), or retinal abnormalities. Co-existing conditions often limit the visual prognosis. It is difficult to discern whether the visual loss is due to SDA or due to other co-existing conditions in the eye.

The most commonly reported cause of SDA is congenital or infantile cataract in one eye. Stimulus deprivation secondary to the cataract continues until the cataract is removed and optical correction is provided. Even after optical correction, the affected eye may continue to be anisometropic and anisekonic (forming unequal image sizes) (Enoch 1983). The early insult to the visual system is believed to make this type of amblyopia particularly severe and resistant to treatment. The visual prognosis has been reported to be poor (Kanski 1994; Taylor 1997).

 

Epidemiology

The prevalence of amblyopia in the general population ranges from 1% to 5% (Brown 2000; Hillis 1983). In European children, the prevalence ranges from 1% to 2.5% (Kvarnstrom 2001; Newman 2000). Amblyopia accounts for 29% of unilateral blindness in Copenhagen (Buch 2001) and as much as 8.3% of bilateral blindness in India following childhood cataract surgery (Dandona 2003). SDA accounts for less than 3% of amblyopic patients (Hillis 1983).

 

Presentation

Routine health checks of babies and toddlers are carried out by a variety of health care personnel (for example, pediatricians, nurses) and provide an opportunity for detection of the causative factors (for example, ptosis, cataract) associated with SDA. SDA itself is not likely to be noticed, but parents may detect the signs associated with causes of SDA such as leukocoria (white pupils) in children with congenital cataracts or droopy eyelid (ptosis). Children may also present with squint (misalignment) as a result of poor vision in one eye. In the developed world, most patients with SDA present for treatment while they are under the age of one (Mein 1991).

 

Diagnosis

There are four main steps in the diagnosis of SDA.

  1. Visual acuity testing: testing young children largely relies on objective observations that are limited by cognition and concentration. Qualitative methods (e.g., assessing fixation preference) may be used, however quantitative tests (e.g., preferential looking) are more precise. Preferential looking tests rely on the observation that infants prefer to look at patterned rather than plain surfaces (Fanz 1958). Children look at a striped panel when they can discern it. A Snellen equivalent can then be computed using the degree of visual angle subtended by the stripes in the panel. In older children, testing methods are more objective and rely on the child's identification of pictoral or letter optotypes in Snellen, decimal or logMAR notation.
  2. External and internal eye examination to identify any co-existing conditions: the examination must focus on identifying lesions such as optic nerve hypoplasia that could lead to inappropriate or unsuccessful treatment of the condition.
  3. Cycloplegic refraction and corrective prescription when indicated: amblyopia can be diagnosed only after correcting any significant refractive error.
  4. Rechecking visual acuity with any prescribed refractive correction in place: some improvement in visual acuity can be expected with refractive correction alone. There should be a period of adjustment to spectacles before retesting. Traditionally this adjustment period has been four to six weeks, but studies on refractive and strabismic amblyopia show this period may be as long as 24 weeks (Moseley 2002).

Definitions of amblyopia vary largely due to the fact that there is little evidence as to what constitutes normal vision at different ages based on successful performances on many commonly used tests. Amblyopia may be defined by comparing both eyes (inter-ocular difference) or by looking at monocular visual acuity alone. We have elected to define amblyopia as vision worse than 6/9 on a Snellen-based test, 0.2 LogMAR or its equivalent in one eye. Assuming that the fellow eye has normal vision, that is 6/6 or logMAR 0.0, this definition means that the difference in vision between the two eyes is greater than 0.2 log MAR.

 

Description of the intervention

Visual loss due to SDA can be difficult to quantify due to the limitations of the visual acuity tests available for young children but is believed to be severe in most cases. The aim of treatment is to maximize visual recovery without adversely affecting acuity in the better-seeing eye. The rationale for treatment is two-fold, to provide a good second eye should the better-seeing eye ever be visually compromised; and to maximize stereopsis (binocular co-operation between the eyes). Untreated or unsuccessfully treated amblyopia may affect adult life. For individuals with amblyopia, the lifetime risk of serious visual impairment due to loss or damage of the better-seeing eye is estimated to be between 1.2% and 3.3% (Rahi 2002). In addition, there are implications for employment prospects and, therefore, income. The number of jobs barred to individuals with reduced vision increases with the severity of the deficit (Adams 1999). Futhermore, stereopsis is required to participate in many sports and for some jobs.

 

Stages of treatment

  1. The first stage is to correct any factor degrading the quality of the visual image (e.g., infantile cataract extraction, ptosis repair). In cases of early unilateral deprivation, correction must be undertaken in the first eight to 12 weeks of life (Birch 1986; Birch 1988; Gregg 1992; Kanski 1994; McCulloch 1994; Taylor 1997).
  2. The second stage is to provide necessary refractive correction to maximize the quality of visual stimulation received by the child's amblyopic eye. Intraocular implants, contact lenses or both may be used after cataract surgery.
  3. The third stage is occlusion therapy. Occlusion of the unaffected eye forces the use of the amblyopic eye to stimulate the formation of functional connections in the brain (Boothe 2000).

 

How the intervention might work

 

Occlusion regimen

Protocols and practices for occlusion therapy vary considerably. Typically, occlusion therapy ranges in duration from an hour to more than six hours (full-time). Factors affecting the prescribed amount of occlusion include the level of visual deficit, the age of the child and the likely waiting time to the next appointment. Follow-up is recommended at intervals of one week per year of age during periods of aggressive patching (Simon 1987). Occlusion may be stopped when visual acuity becomes equal in the two eyes or if no progress has been made after three months of good compliance with occlusion (Pratt-Johnson 2001). Children may require monitoring until they reach the age of visual maturity (approximately seven years of age) to ensure that amblyopia does not recur. Some periods of maintenance occlusion may be required during that time (Mein 1991).

The following have been used as additions to occlusion therapy, but are not currently popular clinically.

  1. CAM visual stimulator: uses rotating high-contrast square wave gratings to stimulate the amblyopic eye.
  2. Pleoptics: employs after-images to encourage foveal fixation and normal projection in the amblyopic eye.

 

Types of occlusion

Atropine penalization and optical penalization (patching or use of lenses to reduce the acuity) are forms of occlusion that encourage use of the amblyopic eye by diminishing visual form. These treatments for amblyopia were evaluated in another Cochrane review, which showed that atropine penalization is as effective as conventional occlusion (Li 2009). Total occlusion is not without disadvantages in terms of discomfort, but it is relatively easy to control the dosage of treatment and is without the more complex side effects of alternatives such as occlusive contact lenses.

 

Measuring outcomes

In order to quantify amblyopia, visual acuity must be measured. Qualitative methods for assessing vision in preverbal children are based on the observation of their fixation patterns. These methods are often unreliable and require highly trained examiners (Wright 1986; Zipf 1976). Visual acuity assessed using an age-appropriate test (Fulton 1978; Sebris 1987) is the most commonly used outcome to evaluate treatment for amblyopia. Tests vary in the use of optotypes (pictures, letters, or symbols), presented with or without crowding. Crowded visual acuity tests are harder to perform but are more sensitive to amblyopia than uncrowded tests.

Developmental changes in young children complicate the evaluation of actual change in visual acuity before and after treatment. Alternative methods of measuring change have been suggested (Schmidt 1994; Stewart 2003), but we aimed to compare post-treatment visual acuity levels (defining restoration of normal visual acuity as better than or equal to 6/9 on Snellen, or 0.2 LogMAR or its equivalent).

 

Factors affecting outcome

Compliance with therapy is critical for successful treatment but often can be difficult to achieve. Young children can become distressed by being restricted to reduced visual acuity and from the discomfort of wearing an adhesive patch. It has been suggested that, if possible, compliance should be monitored to measure its affect on the response to treatment. Devices to objectively measure compliance have been developed (Awan 2005; Stewart 2005) but are not in common use; typically clinicians depend on parental reports. Other factors believed to affect treatment success are the duration of visual deprivation, the age at onset and timing of initiation of therapy (Maurer 1989); early onset of amblyopia, long duration of the condition and late initiation of therapy are associated with worse visual prognosis.

 

Harm from occlusion therapy

Potential adverse effects from occlusion therapy include inducing amblyopia in the occluded eye, skin allergies, infections or corneal abrasions from contact lens wear, diplopia (double vision) and psychological effects on the parents and children (for example, distress).

 

Why it is important to do this review

The reported success of treatment for SDA varies. Studies have reported good levels of vision following early treatment (Gregg 1992; McCulloch 1994) but there is a lack of standardization and poor agreement among experts as to the optimum amount of occlusion needed to achieve a good visual outcome. Commencing occlusion therapy in infants with very poor vision can be harrowing for the parents and stressful for the child. Realistic treatment goals are often poorly defined. It is thus necessary to establish the most effective occlusion regimen(s) for stimulus deprivation amblyopia and to define the degree of improvement that can reasonably be expected from this treatment.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Our objective was to evaluate the effectiveness of occlusion therapy for SDA in an attempt to establish realistic treatment outcomes. Where data were available, we also planned to examine evidence of any dose response effect and to assess the effect of the duration, severity and causative factor on the size and direction of the treatment effect.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Criteria for considering studies for this review

 

Types of studies

We planned to include randomized and quasi-randomized trials in this review, with no restriction on the number of participants in the trials.

 

Types of participants

We planned to include trials that recruited participants with the following characteristics.

  • Unilateral SDA, defined as best-corrected visual acuity in the affected eye worse than 6/9 Snellen, or its equivalent, after treatment for the causative factor had been undertaken and ensuing that refractive error had been corrected. We also planned to report other co-existing amblyogenic factors.
  • Unrestricted age, gender, ethnicity, co-morbidity, and medication use.

 

Types of interventions

We planned to include trials evaluating the following interventions:

  • total occlusion by adhesive patch;
  • total occlusion by occlusive contact lens;
  • pleoptic treatment;
  • partial occlusion (i.e., Bangerter filters);
  • CAM visual stimulation.

We planned to examine the following comparisons:

  1. total occlusion versus no occlusion;
  2. any method of total occlusion compared to another;
  3. total occlusion plus pleoptic treatment versus total occlusion alone;
  4. total occlusion plus CAM visual stimulator versus total occlusion alone;
  5. full-time occlusion (more than six hours/day) versus part-time occlusion (less than six hours/day);
  6. different durations of partial occlusion, for example two hours/day versus six hours/day;
  7. any partial occlusion compared to another;
  8. any total occlusion compared to any partial occlusion;
  9. any partial occlusion compared to no occlusion.

 

Types of outcome measures

 

Primary outcomes

The primary outcome for this review was best-corrected visual acuity (BCVA) of the amblyopic eye, assessed by an age-appropriate test 12 months after cessation of occlusion therapy.
Although the two are not directly equivalent, we planned to convert Snellen data into the logMAR equivalent for ease of interpretation and analysis.

We planned to dichotomize the outcomes as follows.

  1. Normal = better than or equal to 0.2 logMAR, 6/9 Snellen or its equivalent.
  2. Residual deficit = worse than 0.2 logMAR units.

Where possible, we planned to compare the proportions of children with the outcomes specified versus without.

 

Secondary outcomes

The secondary outcomes for this review were:

  1. visual acuity in the amblyopic eye at seven years of age or older;
  2. the proportion of the amblyopia deficit corrected (Stewart 2003);
  3. any measure of stereoacuity (three-dimensional (3-D) vision).

 
Cost data

We planned to summarize in the following categories the comparative costs of the treatment methods described in the included trials.

 
Adverse effects

We planned to summarize adverse effects related to treatment that were reported in the included trials.

Severe: occlusion amblyopia, contact lens-related problems (e.g., infection, corneal abrasions), adverse psychological effects (e.g., distress), treatment cessation due to poor compliance or failure to attend follow-up visits, or diplopia (double vision).

Minor: allergy to patches.

 
Quality of life measures

We planned to summarize any data on quality of life measures of both the parents and child, as described in the reports of the included trials.

 
Follow-up

We planned to include in our analyses data from trials with a minimum post-treatment follow-up of six months. For trials that did not meet this criterion, we planned to include the trials in our qualitative synthesis but exclude them from any meta-analyses.

 

Search methods for identification of studies

 

Electronic searches

In 2013, we revised the searches of electronic databases from the 2007 update. We searched PubMed which had not originally been searched. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) 2013, Issue 9, part of The Cochrane Library. www.thecochranelibrary.com (accessed 28 October 2013), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMEDLINE (January 1946 to October 2013), EMBASE (January 1980 to October 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2013), PubMed (January 1946 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 October 2013.

See: Appendices for details of search strategies for CENTRAL (Appendix 1), MEDLINE (Appendix 2), EMBASE (Appendix 3), LILACS (Appendix 4), PubMed (Appendix 5), mRCT (Appendix 6), ClinicalTrials.gov (Appendix 7), and ICTRP (Appendix 8).

 

Searching other resources

We did not conduct any manual searches for this review. In future updates of this review, we will search the Web of Science® for any articles that cited reports of trials included in this review. In addition, we also will handsearch references cited in reports of trials included in this review.

 

Data collection and analysis

 

Selection of studies

Two review authors independently assessed the titles and abstracts of all reports identified by the electronic searches as per the 'Criteria for considering studies for this review'. The review authors were aware of the report authors, institutions and trial results during this assessment.

We classified each abstract as (a) definitely include, (b) unsure, or (c) definitely exclude. We retrieved full-text articles for abstracts classified as (a) definitely include and (b) unsure. Two review authors independently screened the full-text articles and classified them as either (1) included, (2) awaiting clarification or (3) excluded. A third review author resolved any disagreements at each stage. We contacted the authors of studies classified as (2) awaiting assessment for further clarification. The table of excluded studies lists the details of full-text articles classified by both review authors as excluded.

 
Methods for future updates

If any randomized or quasi-randomized trials are identified in future updates of this review we will adopt the following methods.

 

Data extraction and management

Two review authors will independently extract data from the reports of the included trials. We will resolve discrepancies through discussion. We will contact the trial investigators about any missing data. One review author will enter data into RevMan 5.2 and a second review author will verify the entered data.

We will extract the following data from the included trials.

(1) Participants:

  • numbers of participants in the trial, age at onset of SDA and age at initiation of treatment for SDA, duration of stimulus deprivation, cause of stimulus deprivation, visual acuity before treatment, and details about refractive correction;
  • concomitant ocular pathology that may limit visual outcome (e.g., coloboma, optic nerve hypoplasia, retinal dystrophy). Data from studies including such participants will be included in subgroup analyses;
  • adjustment period to spectacle correction.

(2) Intervention: method of occlusion, regimes, use of CAM or pleoptics.

(3) Outcomes: test(s) used; length of follow-up; whether, when and how compliance was assessed.

 

Assessment of risk of bias in included studies

Two review authors will independently assess the sources of systematic bias in trials according to methods set out in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will evaluate reports of included trials for the following domains:

  • random sequence generation (selection bias);
  • allocation concealment (selection bias);
  • masking of outcome assessors (detection bias);
  • incomplete outcome data (attrition bias) - number of participants lost to follow-up and the methods used to account for losses to follow-up in the analyses;
  • selective outcome reporting (reporting bias);
  • other sources of bias.

Two review authors will grade each of the risk of bias domains as 'high risk'; 'low risk'; or 'unclear risk' of bias. A third review author will resolve any disagreements between the first two authors. We will not assess masking of participants and care providers because it is not feasible with interventions for SDA. We will contact authors of reports of included trials for any details that are not described in the published reports. We will use available information to assess the potential for risk of bias whenever the trial authors do not respond within four weeks of our communication.

 

Measures of treatment effect

For dichotomous outcomes, we will calculate odds ratios for rarer outcomes or risk ratios for more frequent outcomes. We will calculate mean differences for continuous outcomes. We will report 95% confidence intervals (CIs) for all summary effect estimates.

 

Unit of analysis issues

Patients with SDA mostly present with unilateral disease. Consequently, we expect one eye per individual to be the unit of analysis in trials of interventions for SDA. We will refer to available statistical resources such as the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) or the Cochrane Eyes and Vision Group for advise with any unit of analysis issues in data analysis.

 

Dealing with missing data

We will contact authors of reports for trials included in our review about any missing data. When the trial authors are unable to provide any details then we will include the trial in our qualitative analysis and omit it from meta-analyses for the outcomes with missing data. We will not impute data, rather we will use the available-case data and note the limitations with this method.

 

Assessment of heterogeneity

We will examine forest plots for overlap of 95% CIs of effect estimates for visual assessment of heterogeneity between effect estimates of the included trials. The I2 statistic and the Chi2 test for heterogeneity will be calculated.

 

Data synthesis

If we find no evidence of statistical or clinical heterogeneity across included trials, we will combine the results from the trials in meta-analyses using a fixed-effect model. If there is statistical heterogeneity in the absence of clinical heterogeneity, we will compute a summary measure using a random-effects model. In the case where we find substantial statistical (I2 > 50%) or clinical heterogeneity, we will not combine the study results and instead will present our findings in a tabulated or narrative summary.

 

Subgroup analysis and investigation of heterogeneity

When sufficient data are available and trials are stratified prior to randomization, the following subgroups will be explored:

  • participants with and without any co-existing ocular pathology (that might be expected to limit visual prognosis);
  • participants with stimulus deprivation amblyopia associated with a unilateral congenital cataract versus any other unilateral etiology.

 

Sensitivity analysis

Sensitivity analyses will be conducted, when appropriate, to determine the size and direction of effect when excluding the following:

  • outcomes measured on uncrowded vision tests;
  • studies where any risk of bias item has been graded as 'high risk';
  • unpublished studies or industry-funded studies.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Description of studies

 

Results of the search

The electronic searches conducted in 2004 identified 799 abstracts and titles of which seven appeared to be randomized controlled trials (RCTs) of interventions for amblyopia. Of these, three trials evaluated conventional occlusion therapy but did not include patients with SDA (Clarke 2003; Holmes 2003a; Repka 2003). There were four studies (Keith 1980; Mehdorn 1981; Nyman 1983; Tytla 1981) on the CAM visual stimulator but after reading the full-texts of the studies and contacting the authors, where necessary, it became apparent that only one trial (Nyman 1983) had included participants with SDA and the data relevant to this review were no longer available. All seven trials were therefore excluded (see table: Characteristics of excluded studies).

Full text copies of 25 additional references were obtained because the initial search information was insufficient to establish whether the studies were eligible for inclusion, either because only the title was available, the abstract was unclear, or the abstract or study was written in a language other than English. After further perusal or translation, all studies were found to be ineligible and were excluded. Reasons for exclusion have been documented (see table: Characteristics of excluded studies).

An updated search was done in November 2007 which yielded an additional 53 reports of studies. One RCT including five patients with SDA was found, but it had investigated the effectiveness of an educational program on the predictors of noncompliance to occlusion therapy (Loudon 2006). Five additional RCTs investigated occlusion therapy (Hertle 2007; Repka 2007; Stankovic 2007; Stewart 2007; Wallace 2006) but these included only strabismic or anisometropic amblyopia, or both. Thus, the search did not identify any new trials which met the inclusion criteria for the review.

The latest search was conducted in October 2013, which identified 954 additional titles and abstracts and 256 records from trial registers (Figure 1). After review of the records, we assessed 930 titles and abstracts and all trial register records as 'definitely exclude, and 24 as unsure. Five of the 24 references that were assessed as unsure were editorials or commentories that did not report original data and were excluded. We retrieved the remaining 19 full-text articles and further examined their eligibility. We excluded all 19 citations from the review and the reasons for excluding these citations are described in the table Characteristics of excluded studies.

 FigureFigure 1. Results from searching for studies for inclusion in the review.

 

Risk of bias in included studies

We found no randomized or quasi-randomized trials eligible for inclusion in the review.

 

Effects of interventions

None of the studies identified in our searches were eligible for inclusion, highlighting a significant gap in existing evidence for the treatment of stimulus deprivation amblyopia (SDA).

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

We did not find any RCT that had evaluated the effects of occlusion or any other treatment for SDA, highlighting a gap in the evidence and the need for rigorous studies to address this question. Because SDA is generally accepted to be more severe and resistant to treatment compared with amblyopia due to other causes, participants with SDA have been excluded from existing RCTs (Kanski 1994; Taylor 1997).

Because of co-existing pathology, the young age of afflicted patients, and limitations of clinical tests, it is difficult to quantify the degree of visual deficit, determine how much of it is attributable to amblyopia, and assess responses to treatment. Success with treatment for SDA is also affected by compliance and the stress for the parents and the child associated with using occlusion therapy.

Existing evidence on the effects of interventions for SDA is derived largely from non-randomized studies of children with SDA caused by unilateral congenital cataract. Although current practice favors aggressive patching in early life, its effectiveness is supported only by a few case-series (Birch 1988; Drummond 1989; Lundvall 2002; Mayer 1989; Robb 1987). Findings from these studies indicate wide variability in the patching regimen employed and the proportion of children who responded to treatment. Less intense occlusion regimens, while being easier to execute, have been advocated because they promote more binocular interaction and stereoacuity. Some of the less intensive occlusion regimens examined in previous studies include occlusion for one hour per day per month of age for the first six months of life (Brown 1999), and patching for six hours and 12 hours a day (Stewart 2007).

 

Occlusion regimens and treatment outcomes

Current practice generally favors aggressive patching for SDA in early life based on the knowledge that the visual system is much more sensitive to change at this age. Mayer 1989 reported a negative correlation between the number of hours patched and the inter-ocular difference in acuity when treating SDA due to congenital cataract. In non-randomized studies of SDA, the definition of intensive or aggressive patching varied from a minimum of six hours per day to as much as 100% of waking hours. The definition of success also varied across the different studies. Birch 1988 reported that 53% achieved a visual acuity of 20/80 (6/24) or better. Lundvall 2002 found that 20% attained visual acuity of 0.1 (6/7.5) or better, Drummond 1989 reported that 43% achieved better than 20/50 (6/9), and Robb 1987 found 46% achieved visual acuity of at least 20/70 (6/18). This brief summary of some previous studies highlights the different ways in which results can be categorized. These and other dissimilarities in study methodologies make it impossible to meaningfully compare results among these studies. Less intense occlusion regimens are easier to execute and have been advocated because they are expected to promote more binocular interaction and stereoacuity. One study (Brown 1999) reported good visual and binocular results with occlusion of one hour per day per month of age for the first six months of life in children with congenital cataract. Nevertheless, most studies of less intense occlusion regimes have been conducted in children with strabismic or anisometropic amblyopia, or both, and results are probably not generalizable to children with SDA.

 

Compliance

As with other types of amblyopia, treatment for SDA appears to rely on good compliance in order to achieve a satisfactory outcome. Studies on refractive and strabismic amblyopia have used objective methods to monitor how long occlusion is actually worn (Awan 2005; Loudon 2002; Stewart 2005). These show that the prescribed amount of occlusion is not always achieved. Unfortunately, compliance in treating SDA is often difficult to achieve due to the severity of the visual acuity deficit. While it is not surprising that a treatment that visually compromises a child by means of an adhesive patch is not easy to deliver, justification of adoption or rejection of a treatment must carefully consider evidence of harm alongside evidence of benefit. In a culture where justifying an intervention is increasingly required, the current absence of clear evidence of effectiveness in this area is concerning.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

 

Implications for practice

It is not possible to draw reliable conclusions from the data available from non-randomized studies since the study designs either do not compare treatment strategies or are subject to significant bias in the selection of participants for particular treatments. In addition, the variation between studies in treatment delivery and outcome measurement prevents any meaningful comparison or combination of results.

The general trend in practice, based on the proportion of papers we found reporting this treatment, favors an intensive occlusion therapy regimen to attain better visual outcomes. It is important to acknowledge that we did not systematically search for these papers and therefore they may represent a biased sample. It is currently difficult to objectively advise parents or formulate evidence-based guidelines for the management of SDA. Realistic expectations remain uncertain from the treatment for SDA and optimization of treatment regimens.

 
Implications for research

There is a clear and pressing need for randomized controlled trials (RCTs) to evaluate the effects of interventions for SDA. Occlusion therapy is usually considered the mainstay of treatment for SDA. Some may argue that withholding it from children in a RCT may be unethical. But use of occlusion therapy is not supported by evidence from RCTs, and results in significant stress for both the children and their parents. Because there is a lack of evidence about whether the treatment is effective and safe, it should be ethical to randomize children to no occlusion therapy or an alternative treatment in a trial. It is important to acknowledge that there are practical challenges to setting up a randomized trial for SDA; due to the low numbers, a multicenter study would be required. In addition, many years of follow-up, for example to age seven, would be required to determine long term, post-treatment visual acuity outcomes. Nevertheless, such a study would provide extremely valuable evidence for the management of this condition.

Unsuccessful treatment ultimately results in the same outcome as no treatment, that is, reduced sight in one eye and loss of stereopsis. Exposure to treatment also carries the potential for harm. Thus, future studies on treatment for SDA should report treatment effect and accurately measure any potential physical, emotional or psychological harm.

The following are specific questions that need to be addressed in prospective randomized studies (with appropriate stratification to study any subgroup analyses).

  • What is the safety and effectiveness of the interventions, including occlusion or patching for SDA?
  • What is the appropriate duration of treatment for SDA?
  • What is the level of vision that can realistically be achieved; what are the effects of age at onset and magnitude of visual defect?
  • What is the optimum occlusion regimen?
  • What are potential adverse effects from treatments for SDA?
  • What are the factors associated with satisfactory and unsatisfactory outcomes with various interventions for SDA?

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

The Cochrane Eyes and Vision Group (CEVG) devised the search strategies for this review and carried out the electronic searches.

We thank Richard Harrad, Catey Bunce, Sue Elliott and Suzanne Brodney-Folse for their peer review comments throughout the review process. We are also grateful to Milan Mathew for his guidance during the protocol stage and to the CEVG US Project during updates. In addition, we thank Ruthy Acosta for her assistance with screening articles written in Spanish, Qing Pan for her assistance with screening articles written in Chinese, and Kinnar Merchant for assistance with screening articles written in Russian.

Richard Wormald (Co-ordinating Editor for CEVG) acknowledges financial support for his CEVG research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

This review has no analyses.

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor: [Amblyopia] explode all trees
#2 amblyop* or anopsi* or lazy eye*
#3 MeSH descriptor: [Pupil Disorders] explode all trees
#4 MeSH descriptor: [Cataract] explode all trees
#5 cataract* or pseudoaphakia*
#6 MeSH descriptor: [Blepharoptosis] explode all trees
#7 blepharoptos* or ptosis or ptoses
#8 MeSH descriptor: [Vitreous Hemorrhage] explode all trees
#9 (haemorrhage* or hemorrhage*) near (vitreous)
#10 MeSH descriptor: [Hemangioma, Capillary] explode all trees
#11 (hemangioma* or haemangioma*) near (capillary)
#12 MeSH descriptor: [Aphakia] explode all trees
#13 aphaki*
#14 (stimul* or vision or visual or optical) near (deprivat*)
#15 (scar* or opac* or degenerat*) near (cornea*)
#16 media next opacit*
#17 (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #13 or #14 or #15 or #16)
#18 MeSH descriptor: [Sensory Deprivation] explode all trees
#19 patch* or shield*
#20 (stimul* or penalis*) near (optical*)
#21 (stimul* or penalis*) near (vis*)
#22 (therap* or treat* or lens* or complete* or partial*) near (occlus*)
#23 (therap* or treat* or lens* or complete* or partial*) near (pleoptic*)
#24 (#18 or #19 or #20 or #21 or #22 or #23)
#25 (#17 and #24)

 

Appendix 2. MEDLINE (OvidSP) search strategy

1. Randomized Controlled Trial.pt.
2. Controlled Clinical Trial.pt.
3. (randomized or randomised).ab,ti.
4. placebo.ab,ti.
5. drug therapy.fs.
6. randomly.ab,ti.
7. trial.ab,ti.
8. groups.ab,ti.
9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8
10. exp animals/ not humans.sh.
11. 9 not 10
12. exp amblyopia/
13. (amblyop$ or anopsi$ or lazy eye$).tw.
14. exp pupil disorders/
15. exp cataract/
16. (cataract$ or pseudoaphakia$).tw.
17. exp blepharoptosis/
18. (blepharoptos$ or ptosis or ptoses).tw.
19. exp vitreous hemorrhage/
20. ((haemorrhage$ or hemorrhage$) adj3 vitreous).tw.
21. exp hemangioma,capillary/
22. ((hemangioma$ or haemangioma$) adj3 capillary).tw.
23. exp aphakia/
24. aphaki$.tw.
25. ((stimul$ or vision or visual or optical) adj3 deprivat$).tw.
26. ((scar$ or opac$ or degenerat$) adj3 cornea$).tw.
27. (media adj2 opacit$).tw.
28. or/12-27
29. exp sensory deprivation/
30. (patch$ or shield$).tw.
31. ((stimul$ or penalis$) adj3 optical$).tw.
32. ((stimul$ or penalis$) adj3 vis$).tw.
33. ((therap$ or treat$ or lens$ or complete$ or partial$) adj3 occlus$).tw.
34. ((therap$ or treat$ or lens$ or complete$ or partial$) adj3 pleoptic$).tw.
35. or/29-34
36. 28 and 35
37. 11 and 36

The search filter for trials at the beginning of the MEDLINE strategy is based on the published paper by Glanville (Glanville 2006).

 

Appendix 3. EMBASE.com search strategy

#1 'randomized controlled trial'/exp
#2 'randomization'/exp
#3 'double blind procedure'/exp
#4 'single blind procedure'/exp
#5 random*:ab,ti
#6 #1 OR #2 OR #3 OR #4 OR #5
#7 'animal'/exp OR 'animal experiment'/exp
#8 'human'/exp
#9 #7 AND #8
#10 #7 NOT #9
#11 #6 NOT #10
#12 'clinical trial'/exp
#13 (clin* NEAR/3 trial*):ab,ti
#14 ((singl* OR doubl* OR trebl* OR tripl*) NEAR/3 (blind* OR mask*)):ab,ti
#15 'placebo'/exp
#16 placebo*:ab,ti
#17 random*:ab,ti
#18 'experimental design'/exp
#19 'crossover procedure'/exp
#20 'control group'/exp
#21 'latin square design'/exp
#22 #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21
#23 #22 NOT #10
#24 #23 NOT #11
#25 'comparative study'/exp
#26 'evaluation'/exp
#27 'prospective study'/exp
#28 control*:ab,ti OR prospectiv*:ab,ti OR volunteer*:ab,ti
#29 #25 OR #26 OR #27 OR #28
#30 #29 NOT #10
#31 #30 NOT (#11 OR #23)
#32 #11 OR #24 OR #31
#33 amblyopia'/exp
#34 amblyop*:ab,ti OR anopsi*:ab,ti OR (lazy NEAR/1 eye*):ab,ti
#35 'pupil disease'/exp
#36 'cataract'/exp
#37 cataract*:ab,ti OR pseudoaphakia*:ab,ti
#38 'ptosis'/exp
#39 blepharoptos*:ab,ti OR ptosis:ab,ti OR ptoses:ab,ti
#40 'vitreous hemorrhage'/exp
#41 ((haemorrhage* OR hemorrhage*) NEAR/3 vitreous):ab,ti
#42 'capillary hemangioma'/exp
#43 ((hemangioma* OR haemangioma*) NEAR/3 capillary):ab,ti
#44 'aphakia'/exp
#45 aphaki*:ab,ti
#46 ((stimul* OR vision OR visual OR optical) NEAR/3 deprivat*):ab,ti
#47 ((scar* OR opac* OR degenerat*) NEAR/3 cornea*):ab,ti
#48 (media NEAR/2 opacit*):ab,ti
#49 #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48
#50 'sensory deprivation'/exp
#51 'visual deprivation'/exp
#52 patch*:ab,ti OR shield*:ab,ti
#53 ((stimul* OR penalis*) NEAR/3 optical*):ab,ti
#54 ((stimul* OR penalis*) NEAR/3 vis*):ab,ti
#55 ((therap* OR treat* OR lens* OR complete* OR partial*) NEAR/3 occlus*):ab,ti
#56 ((therap* OR treat* OR lens* OR complete* OR partial*) NEAR/3 pleoptic*):ab,ti
#57 #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56
#58 #49 AND #57
#59 #32 AND #58

 

Appendix 4. LILACS search terms

(Amblyopia OR Ambliopia OR Lazy Eye AND MH:C10.228.140.055$ OR MH:C10.597.751.941.073$ OR MH:C11.966.073$ OR MH:C23.888.592.763.941.073$ OR "Pupil Disorders" OR "Trastornos de la Pupila" OR "Distúrbios Pupilares" OR MH:C10.597.690$ OR MH:C11.710$ OR MH:C23.888.592.708$ OR Cataract$ OR Catarata$ OR Pseudoaphakia$ OR MH:C11.510.245$ OR Blepharoptos$ OR Blefaroptos$ OR MH:C11.338.204$ OR Ptosis OR Ptoses OR "Vitreous Hemorrhage" OR "Hemorragia Vítrea" OR MH:C11.290.960$ OR MH:C23.550.414.756.887$ OR (Hemangioma AND (Capillary OR Capilar)) OR MH:C04.557.645.375.380$ OR Aphakia OR Afaquia OR Afacia OR MH:C11.510.103$ OR ((stimul$ OR vision OR visual OR optical) AND (deprivat$)) OR ((scar$ OR opac$ OR degenerate$) AND (cornea$)) OR (media AND opacity$)) AND ("Sensory Deprivation" OR "Privación Sensorial" OR "Privação Sensorial" OR MH:F02.463.593.696$ OR Patch* OR Shield* OR ((stimul$ OR penalis$) AND (optical$)) OR ((stimul$ OR penalis$) AND (vis$)) OR ((therap$ OR treat$ OR lens$ OR complete$ OR partial$) AND (occlus$)) OR ((therap$ OR treat$ OR lens$ OR complete$ OR partial$) AND (pleoptic$)))

 

Appendix 5. PubMed search terms

#1 ((randomized controlled trial[pt]) OR (controlled clinical trial[pt]) OR (randomised[tiab] OR randomized[tiab]) OR (placebo[tiab]) OR (drug therapy[sh]) OR (randomly[tiab]) OR (trial[tiab]) OR (groups[tiab])) NOT (animals[mh] NOT humans[mh])
#2 (amblyop*[tiab] OR anopsi*[tiab] OR lazy eye*[tiab]) NOT Medline[sb]
#3 (cataract*[tiab] OR pseudoaphakia*[tiab]) NOT Medline[sb]
#4 (blepharoptos*[tiab] OR ptosis[tiab] OR ptoses[tiab]) NOT Medline[sb]
#5 ((haemorrhage*[tiab] OR hemorrhage*[tiab]) AND vitreous[tiab]) NOT Medline[sb]
#6 ((hemangioma*[tiab] OR haemangioma*[tiab]) AND capillary[tiab]) NOT Medline[sb]
#7 aphaki*[tiab] NOT Medline[sb]
#8 ((stimulu*[tiab] OR stimulat*[tiab] OR stimuli*[tiab] OR stimulant*[tiab] OR vision[tiab] OR visual[tiab] OR optical[tiab]) AND deprivat*[tiab]) NOT Medline[sb]
#9 ((scar*[tiab] OR opac*[tiab] OR degenerat*[tiab]) AND cornea*[tiab]) NOT Medline[sb]
#10 (media[tiab] AND opacit*[tiab]) NOT Medline[sb]
#11 #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10
#12 (patch*[tiab] OR shield*[tiab]) NOT Medline[sb]
#13 ((stimulu*[tiab] OR stimulat*[tiab] OR stimuli*[tiab] OR stimulant*[tiab] OR penalis*[tiab]) AND optical*[tiab]) NOT Medline[sb]
#14 ((stimulu*[tiab] OR stimulat*[tiab] OR stimuli*[tiab] OR stimulant*[tiab] OR penalis*[tiab]) AND vision*[tiab] OR visual*[tiab]) NOT Medline[sb]
#15 ((therapy[tiab] OR therapie*[tiab] OR therapeut*[tiab] OR treat[tiab] OR treated[tiab] OR treatment*[tiab] OR lens*[tiab] OR complete*[tiab] OR partial*[tiab]) AND occlus*[tiab]) NOT Medline[sb]
#16 ((therapy[tiab] OR therapie*[tiab] OR therapeut*[tiab] OR treat[tiab] OR treated[tiab] OR treatment*[tiab] OR lens*[tiab] OR complete*[tiab] OR partial*[tiab]) AND pleoptic*[tiab]) NOT Medline[sb]
#17 #12 OR #13 OR #14 OR #15 OR #16
#18 #11 AND #17
#19 #1 AND #18

 

Appendix 6. metaRegister of Controlled Trials search strategy

Amblyopia

 

Appendix 7. ClinicalTrials.gov search strategy

Amblyopia

 

Appendix 8. ICTRP search strategy

Amblyopia

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Last assessed as up-to-date: 28 October 2013.


DateEventDescription

31 January 2014New search has been performedIssue 2, 2014: Updated searches yielded no new studies.

31 January 2014New citation required but conclusions have not changedSome sections of the review have been updated. The time point for the primary outcome has changed from 6 months to 12 months.



 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Protocol first published: Issue 1, 2005
Review first published: Issue 3, 2006


DateEventDescription

13 October 2008AmendedConverted to new review format.

27 November 2007New search has been performedAn update search was done in November 2007; 6 RCTs were excluded but no new trials were included in the review.

16 March 2006New citation required and conclusions have changedSubstantive amendment



 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Conceiving the review: AA
Designing the review: AA
Co-ordinating the review: AA, SSV
Data collection for the review
- Designing electronic search strategies: CEVG
- Undertaking searches: CEVG
- Screening search results: AA, CP, SSV
- Organizing retrieval of papers: AA, CP, SSV
- Screening retrieved papers against inclusion criteria: AA, CP, SSV, SH
- Appraising quality of papers: not applicable
- Extracting data from papers: not applicable
- Writing to authors of papers for additional information: CEVG
- Providing additional data about papers: not applicable
- Obtaining and screening data on unpublished studies: CEVG
Data management for the review
- Entering data into RevMan: not applicable
- Analysis of data: not applicable
Interpretation of data
- Providing a methodological perspective: SSV, SH
- Providing a clinical perspective: AA, CP, SH
- Providing a policy perspective: AA, CP, SH
- Providing a consumer perspective: AA, CP, SH
Writing the review: AA, SSV. CP, SH
Providing general advice on the review: AA, CP, SH, SSV
Securing funding for the review: not applicable
Performing previous work that was the foundation of the current study: AA, CP, SH

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

None known

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Internal sources

  • Michigan State University, Department of Neurology and Ophthalmology, USA.
  • Brown University, USA.
  • Johns Hopkins University, USA.

 

External sources

  • Grant 1 U01 EY020522-01, National Eye Institute, National Institutes of Health, USA.
  • Sightsavers International, UK.
  • Christian Blind Mission, Germany.

 

Differences between protocol and review

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

For the 2014 update, we changed the primary outcome time point from six months to 12 months to be consistent with other Cochrane Eyes and Vision Group reviews on amblyopia.

References

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Agafonov 2007 {published data only}
  • Agafonov VV. Development of a technique for ametropia correction with phakic intraocular lenses. Vestnik Rossiiskoi akademii meditsinskikh nauk / Rossiiskaia akademiia meditsinskikh nauk 2007, (8):52-6.
Arruga 1966 {published data only}
  • Arruga A. Occlusion therapy in children. International Ophthalmology Clinics 1966;6(3):435-52.
Botabekova 2004 {published data only}
  • Botabekova TK, Kurgambekova NS. A comparative analysis of the efficiency of different methods in the treatment of amblyopia. Vestnik Oftalmologii 2004;120(5):40-1.
Clarke 2003 {published data only}
  • Clarke MP, Wright CM, Hrisos S, Anderson JD, Henderson J, Richardson SR. Randomised controlled trial of treatment of unilateral visual impairment detected at preschool vision screening. BMJ 2003;327(7426):1251.
Cramer 1966 {published data only}
  • Cramer FE, Lamela N, Luqui Lagleyze J, Corsellas A. Use of the electronic flash in the pleoptic treatment of amblyopias [Uso del flash electronico en el tratamiento pleoptico de las ambliopias]. Arquivos Brasileiros de Oftalmologia 1966;29(3):83-8.
Cuppers 1967 {published data only}
  • Cuppers C. Effects of pleoptic therapy with special consideration of permanent results. II [Ergebnisse der pleoptischen Therapy unter besonderer Berucksichtigung der Dauerresultate. II]. Documenta Ophthalmologica 1967;23:570-605.
Fletcher 1969a {published data only}
  • Fletcher MC, Silverman SJ, Boyd J, Callaway M. Biostatistical studies. Comparison of the management of suppression amblyopia by conventional patching, intensive hospital pleoptics, and intermittent office pleoptics. American Orthoptic Journal 1969;19:40-7.
Fletcher 1969b {published data only}
  • Fletcher MC, Abbott W, Girard LJ, Guber D, Silverman SJ, Tomlinson E, et al. Biostatistical studies. Results of biostatistical study of the management of suppression amblyopia by intensive pleoptics versus conventional patching. American Orthoptic Journal 1969;19:8-30.
Flynn 1967 {published data only}
  • Flynn JT, Vereecken E. Effects of pleoptic therapy with special consideration of permanent results. I. Documenta Ophthalmologica 1967;23:550-69.
Flynn 1968 {published data only}
  • Flynn JT. Results with the use of pleoptics in the treatment of amblyopia. Southern Medical Journal 1968;61(11):1169-71.
Funghini 1973 {published data only}
  • Funghini G. Interest of orthoptic and pleoptic treatment [L'interesse del trattamento ortottico e pleottico]. Minerva Medica 1973;64(69):3612-5.
Gernet 1958 {published data only}
  • Gernet H. Controlled partial occlusion by polarized glasses in treatment of amblyopia and strabismus: preliminary report. Klinische Monatsblätter für Augenheilkunde und für Augenärztliche Fortbildung 1958;133(3):388-96.
Hartman 1982 {published data only}
  • Hartman DK. CAM vision stimulator; a controlled study. New York State Journal of Medicine 1982;82(5):723-4.
Hertle 2007 {published data only}
  • Hertle RW, Scheiman MM, Beck RW, Chandler DL, Bacal DA, Birch E, et al. Stability of visual acuity improvement following discontinuation of amblyopia treatment in children aged 7 to 12 years. Archives of Ophthalmology 2007;125(5):655-9.
Holmes 2003a {published data only}
  • Holmes JM, Kraker RT, Beck RW, Birch EE, Cotter SA, Everett DF, et al. A randomized trial of prescribed patching regimens for treatment of severe amblyopia in children. Ophthalmology 2003;110(11):2075-87.
Holmes 2003b {published data only}
  • Holmes JM, Beck RW, Kraker RT, Cole SR, Repka MX, Birch EE, et al. Impact of patching and atropine treatment on the child and family in the amblyopia treatment study. Archives of Ophthalmology 2003;121(11):1625-32.
Iacobucci 1977 {published data only}
Iturriaga 2012 {published data only}
  • Iturriaga H, Zanolli M, Damm C, Oporto J, Acuna O, Valenzuela F. Frequent evaluation to improve compliance in patients treated with occlusion for amblyopia: a randomized controlled trial. Binocular Vision and Strabismus Quarterly 2012;27(3):195-204.
Kamlesh 2008 {published data only}
  • Kamlesh GS, Bhola R, Fatima S, Goyal G, Dadeya SC. Levodopa as an adjuvant to conventional occlusion for treatment of amblyopia in children. American Academy of Ophthalmology. 2008:Abstract 176.
Kampf 2008 {published data only}
  • Kampf U, Shamshinova A, Kaschtschenko T, Mascolus W, Pillunat L, Haase W. Long-term application of computer-based pleoptics in home therapy: selected results of a prospective multicenter study. Strabismus 2008;16(4):149-58.
Keith 1980 {published data only}
Kuming 1982 {published data only}
  • Kuming BS, Klugman M. The value of CAM visual stimulation. South African Archives of Ophthalmology 1982;9(3-4):65-70.
Lang 1965 {published data only}
  • Lang J. "Increasing occlusion" in the treatment of amblyopia with eccentric fixation [Die "Ansteigeokklusion" zur Behandlung der Amblyopie mit exzentrischer Fixation]. Ophthalmologica 1965;149(6):456-62.
Lennerstrand 1983 {published data only}
  • Lennerstrand G. Recent advances in the management of amblyopia. International Rehabilitation Medicine 1983;5(3):128-31.
Loudon 2006 {published data only}
  • Loudon SE, Fronius M, Looman CW, Awan M, Simonsz B, van der Maas PJ, et al. Predictors and a remedy for noncompliance with amblyopia therapy in children measured with the occlusion dose monitor. Investigative Ophthalmology and Visual Science 2006;47(10):4393-400.
Loudon 2009 {published data only}
  • Loudon SE, Passchier J, Chaker L, de Vos S, Fronius M, Harrad RA, et al. Psychological causes of non-compliance with electronically monitored occlusion therapy for amblyopia. British Journal of Ophthalmology 2009;93(11):1499-503.
Lyon 2013 {published data only}
  • Lyon DW, Hopkins K, Chu RH, Tamkins SM, Cotter SA, Melia BM, et al. Feasibility of a clinical trial of vision therapy for treatment of amblyopia. Optometry and Vision Science 2013;90(5):475-81.
Mackensen 1965 {published data only}
  • Mackensen G, Kroner B, Postic G. On the change of eccentric fixation under occlusion treatment [Zur Anderung der exzentrischen Fixation unter der Okklusionsbehandlung]. Klinische Monatsblätter für Augenheilkunde 1965;147(2):213-30.
Malik 1970 {published data only}
  • Malik SR, Gupta AK, Grover VK. Occlusion therapy in amblyopia with eccentric fixation. British Journal of Ophthalmology 1970;54(1):41-5.
Medghalchi 2011 {published data only}
  • Medghalchi AR, Dalili S. A randomized trial of atropine vs patching for treatment of moderate amblyopia. Iranian Red Cresecent Medical Journal 2011;13(8):578-81.
Mehdorn 1981 {published data only}
  • Mehdorn E, Mattheus S, Schuppe A, Klein U, Kommerell G. Treatment for amblyopia with rotating gratings and subsequent occlusion: a controlled study. International Ophthalmology 1981;3(3):161-6.
Nyman 1983 {published data only}
Pistelka 1973 {published data only}
  • Pistelka Z. In-patient pleoptic and orthoptic treatment and its results in pre-school children [Ustavni pleopticko-ortopticka lecba a jeji vysledky u deti predskolniho veku]. Ceskoslovenska Oftalmologie 1973;29(1):41-9.
Prakash 1986 {published data only}
  • Prakash P, Karmacharya PC, Menon V. Evaluation of CAM vision stimulator in the therapy of amblyopia. Indian Journal of Ophthalmology 1986;34:300-3.
Priegnitz 1965 {published data only}
  • Priegnitz F, Zimmer R. On the occlusive treatment of amblyopia with eccentric fixation [Zur okklusivbehandlung von amblyopien mit exzentrischer fixation]. Das Deutsche Gesundheitswesen 1965;20(42):1915-8.
Repka 2003 {published data only}
  • Repka MX, Beck RW, Holmes JM, Birch EE, Chandler DL, Cotter SA, et al. A randomized trial of patching regimens for treatment of moderate amblyopia in children. Archives of Ophthalmology 2003;121(5):603-11.
Repka 2007 {published data only}
  • Repka MX, Melia M, Eibschitz-Tsimhoni M, London R, Magoon E, Pediatric Eye Disease Investigator Group. The effect on refractive error of unilateral atropine as compared with patching for the treatment of amblyopia. Journal of AAPOS 2007;11(3):300-2.
Repka 2010 {published data only}
  • Repka MX, Kraker RT, Beck RW, Atkinson SC, Bacal DA, Bremer DL, et al. A pilot study of levodopa as treatment for residual amblyopia in children 8 to 17 years old. Archives of Ophthalmology 2010;128:1215-7.
Roefs 2008 {published data only}
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Rutstein 2010 {published data only}
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Schor 1983 {published data only}
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Shroff 1983 {published data only}
  • Shroff AP, Billore OP, Dubey AK, Antani PR. A combined approach by spectacle correction, occlusion and active pleoptic treatment in management of amblyopia. Indian Journal of Ophthalmology 1983;31(5):568-9.
Sikder 2008 {published data only}
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Stankovic 2007 {published data only}
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Stewart 2007 {published data only}
Stojcevska 1975 {published data only}
  • Stojcevska V. Pleoptic orthoptic treatment of functional amblyopia [Pleopticko ortopticko lekuvanje na funkcionalnite amblyopii]. Godis̆en Zbornik na Medicinskiot Fakultet vo Skopje 1975;21:201-5.
Thomas 2004 {published data only}
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Tomlinson 1973 {published data only}
  • Tomlinson E, Jablonski M. Results of modified pleoptic therapy in eccentric fixation. American Orthoptic Journal 1973;23:60-4.
Tommila 1969 {published data only}
Tommila 1974 {published data only}
  • Tommila V. Occlusion therapy of amblyopia [Amblyopian peittohoito]. Duodecim 1974;90(4):295-304.
Tytla 1981 {published data only}
Veronneau 1974 {published data only}
  • Veronneau Troutman S, Dayanoff SS, Stohler T, Clahane AC. Conventional occlusion vs. pleoptics in the treatment of amblyopia. American Journal of Ophthalmology 1974;78(1):117-20.
Wallace 2006 {published data only}
  • Wallace DK, Pediatric Eye Disease Investigator Group, Edwards AR, Cotter SA, Beck RW, Arnold RW, et al. A randomized trial to evaluate 2 hours of daily patching for strabismic and anisometropic amblyopia in children. Ophthalmology 2006;113(6):904-12.
Wallace 2013 {published data only}
  • Wallace DK, Lazar EL, Holmes JM, Petersen D, Repka MX, Pediatric Eye Disease Investigator Group. A randomized trial of increased patching for amblyopia. Journal of AAPOS 2013;17(1):e10.
Walsh 2009 {published data only}
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Widder 1967 {published data only}
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Yan 2008 {published data only}
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Zang 1988 {published data only}

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
AAO 2002
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References to other published versions of this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Antonio-Santos 2004
  • Antonio-Santos A, Mathew M, Powell C, Hatt S. Interventions for stimulus deprivation amblyopia. Cochrane Database of Systematic Reviews 2004, Issue 4. [DOI: 10.1002/14651858.CD005136]
Antonio-Santos 2006