Amblyopia: the basics, the questions, and the practical management

Introduction

Amblyopia is the most common cause of visual impairment in children: it often persists into adulthood. The prevalence in childhood is estimated to be 1%−4%, depending on the population studied, with 2.4% as a best prevalence estimate. It is considered to be the leading cause of monocular vision loss in the 20–70 years of age group. The prevalence of visual loss from amblyopia in adults has been reported to be 2.9%.

Amblyopia is defined as a “decrease of visual acuity caused by pattern vision deprivation or abnormal binocular interaction for which no causes can be detected by the physical examination of the eye and which, in appropriate cases, is reversible by therapeutic measures.” Amblyopia may be unilateral or less often bilateral. It is most commonly associated with refractive error (anisometropia, high ametropia, high astigmatism) or eye misalignment, usually esotropia in infancy or early childhood, or a combination of strabismus and refractive error ( Table 74.1 ). Analyses of population-based data and a clinical data registry have found refractive error to be the most common cause. Visual loss in amblyopia varies from mild to severe. About 25% of cases have visual acuity worse than 6/30 and about 75% 6/30 or better. Strabismic amblyopia may represent a more severe physiologic deficit than anisometropic amblyopia and combined strabismic and anisometropic amblyopia is a more serious deficit still.

Methods of detection

The gold standard for detection is measurement of high contrast visual acuity using a crowded or linear letter optotype test. Single optotype presentation and picture optotypes are less sensitive and should be used only when a child is unable to perform a test using surrounded or line optotypes. Tests based on the four letters “H”, “O”, “T”, and “V” in a box or with contour surround bars are the basis of several popular test strategies. A defined protocol for testing children with single-surround HOTV has been developed and subsequently automated by the Pediatric Eye Disease Investigator Group (PEDIG). The strategy includes a second chance at threshold determination and a portion designed to get the child back on track with larger above-threshold stimuli. It has good testability and test−retest reliability. The Amblyopia Treatment Study HOTV (ATS-HOTV) protocol somewhat overestimated visual acuity compared with the electronic Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol (0.68 lines for amblyopic eyes; 0.25 lines for fellow eyes).

For children unable to read or match letter optotypes, clinicians have commonly used picture optotypes. However, standard picture optotypes substantially overestimate the visual acuity of amblyopic eyes and are not recommended for screening or diagnosis of amblyopia. Dr Lea Hyvärinen designed four picture-like optotypes to have similarities between optotypes and have contours like the Landolt C, making them more difficult to successfully recognize. The objects (apple, circle, house, square) chosen are common in Western children’s experience and eliminate cultural biases in those populations. In one study the single-surrounded Lea tests systematically overestimated acuity by 1.9 lines compared to the crowded Landolt C in normal eyes. A systematic comparison of the Lea symbols to line optotypes in amblyopic eyes has not been performed.

Fixation preference testing may be used for children unable to perform any optotype-based testing. For strabismic children the clinician compares the ability to hold fixation with each eye. The child may alternate, be unable to hold fixation after a blink, or be unable to hold fixation. For a patient with no misalignment, perform the test by placing a 10-diopter prism base down before one eye, having the child fixate a detailed target at distance or near, and assessing fixation preference. If there is a fixation preference for the eye without the prism, switch the prism to the fellow eye and again assess fixation preference. The prism might cause the other eye to be preferred. If the same eye is preferred under each testing condition, then the fellow eye is assumed to have amblyopia. A patient who fixates with the eye without the prism is alternating. Comparing fixation preference testing to optotype testing has shown fixation preference testing is unreliable as a means of diagnosing amblyopia, generally leading to an overdiagnosis of amblyopia. Optotype testing confirmed only 17 of 52 patients (33%) diagnosed with amblyopia by fixation preference testing. In another study 53 children had two or more lines of difference in visual acuity, yet 45 of those children were graded as normal by fixation preference. Amblyopia therapy is typically prescribed only in the presence of a strong fixation preference.

On occasion visual acuity testing consists of noting whether the child can centrally hold fixation on a target, has steady eye movements, and is able to maintain fixation on a target. This is recorded in the record as CSM (central steady maintained or not for each comment). The clinician uses this scale to compare the two eyes.

Forced-choice preferential looking (FPL) using Teller acuity cards has been used as an alternative method for infants and nonverbal children. This test requires sufficient time, a quiet space, and an experienced tester to assure reliable results. FPL systematically underestimates amblyopia, reducing its clinical utility as a means of screening for moderate amblyopia or detecting a successful treatment endpoint.

Methods of treatment

There are few data comparing the outcomes of amblyopia treatment to the natural history. Clinicians have noted improvement of acuity when children complied with therapy, but found little improvement when no therapy was actually completed. Simons and Preslan reported that among a case series of amblyopic patients who were not treated, there was no improvement in visual acuity. However, demonstration of improvement in acuity of the amblyopic eye with treatment of the contralateral eye, but without concurrent untreated or natural history controls is not sufficient to prove a benefit of therapy. This deficiency led to a controversial recommendation in the United Kingdom to stop screening for amblyopia as well as treating it because of a lack of a proven benefit.

Recent prospective studies have shown value in terms of visual acuity improvement. Two hours of daily patching modestly improves amblyopia in children 3–7 years old compared with no patching. Another study randomized a group of non-strabismic children with anisometropia to no treatment, treatment with glasses or treatment with glasses and occlusion if needed. This study found about one line of visual acuity improvement overall comparing glasses and occlusion treatment with no treatment after one year. Some limitations were present; not every child had amblyopia and addition of patching to the glasses was not randomized. However, there were 2.03 lines of improvement for children with vision of 20/60 to 20/100 at baseline.

Refractive correction

The initial intervention for amblyopia of any type is to prescribe necessary refractive correction. The diagnosis of amblyopia is not made until refractive correction is prescribed, the glasses obtained, and the visual acuity deficit confirmed while wearing the correction. The practice of prescribing spectacles for amblyopia varies with severity and age of the child, but most guidelines suggest correction of an anisometropia greater than 0.50 D and astigmatism of 1.50 D when amblyopia is suspected. Hypermetropia should be fully corrected in younger strabismic patients and corrected with the plus sphere reduced by up to 1.50 D in orthotropic patients. Myopic refractive errors should be fully corrected during office testing with trial frames or phoropter to confirm the diagnosis. Prescribed minus sphere may be cut in some cases, especially with younger children.

When should additional therapy such as occlusion be started? Some clinicians prescribe such therapy immediately, some wait a pre-specified time, others wait until improvement with spectacles alone ceases. This latter methods allows “refractive adaptation” to occur. The Monitored Occlusion Treatment of Amblyopia Study enrolled 65 untreated children aged 3–8 years (mean age 5.1 years), with mild to severe visual acuity (0.1–1.6 logMAR) in the amblyopic eye. The mean improvement with glasses alone was 2.4 logMAR lines (range = 0 to 6) from the eyeglasses-corrected baseline visit. PEDIG reported that amblyopia improved in previously untreated anisometropic patients (N = 84) with optical correction by at least 2 lines in 77% of the patients and resolved in 27%. Improvement took up to 30 weeks. A subsequent study (N = 146) of the impact of refractive correction on strabismic or combined amblyopia found a nearly identical outcome, 75% improved at least 2 lines, and 32% resolved. This improvement occurred even without alignment with the correction.

Based on these findings, the author prefers to prescribe any necessary spectacle correction and then wait for at least 6 weeks to re-evaluate visual acuity. As long as the acuity is improving, the child may continue with just glasses before prescribing additional therapy. This staged approach may improve patient compliance with each portion of the therapy.

Occlusion therapy

Occlusion has been the mainstay of treatment for a century despite the lack of meaningful data demonstrating superiority over other modalities. Treatment commonly employs an adhesive patch placed over the fellow eye so that the amblyopic eye must be used. Opinions vary on the number of hours of patching per day that should be prescribed, ranging from a few hours to all waking hours in many textbooks. The treatment dosages of patching prescribed vary based on training and region. For instance, more hours have been prescribed in German-speaking countries than in the United Kingdom, yet the same outcome is generally expected.

Flynn et al. found that the success rates were the same for part-time and full-time occlusion therapy based on their review combining 23 studies. Several authors have reported significant improvement in visual acuity using brief daily periods of occlusion (20 minutes to 1 hour). Campbell et al. noted that 20 minutes per day was effective in improving the vision of 83% of children to 6/12.

PEDIG has conducted several prospective multicenter randomized controlled clinical trials, including patients with strabismic and anisometropic forms of amblyopia. The first study compared occlusion to atropine treatment. The dosage of occlusion prescribed was a minimum of 6 hours up to full-time, but the investigator chose the actual occlusion dosage. Patients with acuity of 6/24 to 6/30 improved faster when more hours of patching were prescribed, but after 6 months the improvement was not significantly greater than that occurring with fewer hours of patching or with atropine ( Fig. 74.1 ).

Additional prospective randomized trials compared the efficacy of different occlusion dosages. There are two distinct studies, one for moderate amblyopia 6/12 to 6/24, and one for severe amblyopia 6/30 to 6/120, caused by strabismus, anisometropia, or both. For moderate amblyopia 2 hours of daily patching produced an improvement in visual acuity of similar magnitude to the improvement produced by 6 hours of daily patching in treating moderate amblyopia in children 3 to less than 7 years of age. Each treatment group improved 2.4 lines over 4 months. Unexpectedly, there was no benefit in terms of the rate of improvement from more hours of occlusion ( Fig. 74.2 ). When reviewing this study, it is important to consider that the visual acuity gain after 4 months does not represent the maximum improvement possible from either treatment, and treatment will be likely for many more months. For children with a residual deficit who have stopped getting better, increasing the occlusion dose of 2 hours per day to 6 hours per day for children 3–7 years of age for 10 weeks improved the outcome. The amblyopic eye VA improved an average 0.5 line in those continuing with 2 hours per day, but improved 1.2 lines in the 6-hour group.

The occlusion study for severe amblyopia compared 6 hours with full-time occlusion. The investigators found the improvement in the amblyopic eye acuity from baseline to 4 months averaged 4.8 lines in the 6-hour group and 4.7 lines in the full-time group ( P = 0.45). In a separate study, children with severe amblyopia (6/30 to 6/120) improved a mean of 3.6 lines with just 2 hours of daily patching for 17 weeks.

Children’s aversion to occlusion therapy is well known. Reported compliance rates range widely. Parents have used coercion and clinicians have on occasion recommended punitive measures such as elbow splints to enhance compliance. Lack of parental understanding seems to play a large role. In the United Kingdom, failure to comply with the prescribed regimen at least 80% of the time occurred in 54% of patients: the failure to comply related to the parents’ lack of understanding that there is a “critical period” for effective therapy.

Side effects from occlusion are uncommon, usually minor skin irritation or the social stigma of a patch. Adhesive sensitivity to the patches does occur. The clinician should discontinue the patch and treat with an emollient facial cream. Rarely, topical hydrocortisone cream may be needed. One year after patching treatment of children with refractive amblyopia, there were no reported negative psychosocial effects compared with glasses-only treatment.

More serious is occlusion (or “reverse”) amblyopia, a decrease in vision in the fellow (patched) eye of more than one line. It is more common with intense therapy and longer treatment intervals without monitoring. In one prospective study in which the majority of patients were treated with 6 or 8 hours of occlusion per day, only 1 of 204 patients was diagnosed with reverse amblyopia. In most cases occlusion amblyopia is reversible simply by stopping the treatment. Rarely, amblyopia therapy is needed for the original non-amblyopic eye.

An opaque adhesive patch is the best method currently available. Temperature-sensitive patches to monitor compliance may be available in the future. Spectacle-mounted patches and non-adhesive patches may be less successful because they are easily removed. Once an occlusion dosage is prescribed, the patient must return for visual acuity monitoring. Traditionally, these intervals have been 1 week per year of age (i.e. a 3-year-old patient would return in 3 weeks). This approach is necessary when full-time occlusion is prescribed, but the follow-up interval should be lengthened when part-time occlusion is recommended to reduce parental burden. An initial follow-up interval of 2–3 months for 2–6 hours per day prescribed patching is sufficient. If the amblyopic eye has improved and the fellow eye has not been impaired, the treatment interval can be increased. Therapy should be continued until no improvement occurs between two visits. Re-testing is always a good idea to be certain of the lack of improvement.

The value of occlusion therapy is well established for anisometropic and strabismic amblyopia. However, a much smaller but important group of patients experience form deprivation amblyopia, e.g. from a cataract or media opacity. For these patients, the amblyopia is often severe. The occlusion dosage should be individualized, as there is no clinical trial available to guide the clinician. For patients with unilateral deprivation amblyopia, occlusion dosages of half waking hours are reasonable to avoid damage to the binocular system or to the fellow eye. This dosage can be tapered as the child plateaus to maintain the improvement.