Amblyopia Treatment Study: Occlusion Versus Pharmacologic Therapy for Moderate Amblyopia

• To determine whether the success rate with drug treatment (atropine) of amblyopia due to strabismus or anisometropia in patients less than 7 years old is equivalent to the success rate with occlusion (patching) therapy
• To develop more precise estimates of the success rates of amblyopia treatment
• To identify factors that may be associated with successful treatment of amblyopia
• To collect data on the course of treated amblyopia to provide more precise estimates of treatment effects than are now available

Extended Follow up of Study Patients
• Primary: To determine the long-term visual acuity outcome at age 10 years and at age 15 years in patients diagnosed with amblyopia before age 7 years.
• Secondary: To determine whether the long-term visual acuity outcome at age 10 years and at age 15 years differs between patients who received patching followed by best clinical care and patients who received atropine followed by best clinical care

Amblyopia, or lazy eye, is the most common cause of visual impairment in children and often persists in adulthood. It is reported to be the leading cause of vision loss in one eye in the 20-70 year old age group, with a prevalence of 1-4 percent in various studies, indicating that both improved means of detection and treatment are needed.

Most of the available data on the natural history of amblyopia and success rates of its treatment with either patching or drug therapy are retrospective and uncontrolled. Despite the common occurrence of amblyopia, there is little quality data on treatment of this condition. Thus, there is much to be learned about the course of treated amblyopia, to provide more precise estimates of success rates and to identify factors that may be associated with successful and unsuccessful treatment.

Amblyopia, when diagnosed in children, is usually treated with occlusion (patching) of the sound eye. Occlusion therapy is subject to problems of compliance, due to the child’s dislike of wearing a patch for visual, skin irritation, and social/psychological reasons. There is evidence that compliance may be one of, if not, the most important determinant of success of amblyopia therapy.

An alternative treatment, drug therapy with a cycloplegic drug (atropine) that dilates the pupils and blurs the image seen by the sound eye, has been known for almost a century. This method has been widely used for the management of occlusion treatment failures and for maintenance therapy. However, it has seen little use as a primary treatment for amblyopia. Clinical experience has found that it has a high acceptability to patients and parents, and hence high compliance. In addition to its acceptability, pharmacologic therapy has the known advantage over occlusion of providing a wider visual field with both eyes, which may have safety and other functional implications. There is also clinical and laboratory evidence suggesting that drug therapy may maintain and improve the ability to see with both eyes (binocularity).

Available data suggest that the success rate with drug therapy is as good as, if not better than, the success rate with occlusion therapy for mild to moderate degrees of amblyopia. If this is true, for many children with amblyopia, drug therapy may be the preferred initial therapy since it appears to be more readily accepted by the children and parents. Despite data to support the use of drug therapy as a primary therapy for amblyopia, it has gained only limited use among pediatric ophthalmologists. A definitive study comparing the outcomes from occlusion therapy and drug therapy is justified in order to determine if new practice guidelines for treatment of amblyopia are needed.

Regardless of whether the trial determines that one therapeutic approach is better than the other, the data that are collected will provide valuable information about the course of amblyopia treatment that is not presently available. The study also is expected to provide data that will help to determine whether factors such as age, refractive status, cause of amblyopia, or fixation pattern should be considered in determining which procedure is best for a given patient.

The study is a randomized trial comparing patching and atropine therapies in the treatment of amblyopia. Patients in the patching group were initially started on 6 to 12 hours per day of occlusion; patching time was increased if the child did not improve. The atropine group received one drop of 1 percent atropine once a day. There were at least three follow-up visits for the first six months, and then at least one visit every six months until the end of two years. Visual acuity is the major study outcome. It is assessed after six months and at two years.

Extended Follow up of Study Patients
The extended follow up study consists of annual visits prior to age 10, followed by visits at age 10 years and at age 15 years. There is no amblyopia treatment that is required during the extended follow up period.

Patients must be less than 7 years old with amblyopia due to strabismus or anisometropia. Visual acuity in the amblyopic eye must be between 20/40 and 20/100, visual acuity in the sound eye or 20/40 or better, and there must be at least 3 lines of acuity difference between the two eyes. Patients must have had no more than two months of amblyopia therapy in the past two years.

No longer recruiting. Comments: Completed. Recruitment began in April of 1999 and closed in April 2001 after 419 patients were enrolled.

Completed, with results published. Comments: Completed. Six-month follow-up (primary outcome exam) was completed in November 2001. Two year follow up of patients was completed in July 2003.

Extended follow up of study patients is ongoing. 188 patients at 26 sites have re-consented to continue in follow up.

Between April 1999 and April 2001, 419 patients entered the trial, with 215 assigned to the patching group and 204 to the atropine group. The mean visual acuity in the amblyopic eye at enrollment was approximately 20/63, with a mean difference in acuity between eyes of 4.4 lines. The average age of the children was 5.3 years; 47 percent were girls and 83 percent Caucasian.

At six months, visual acuity was improved from baseline by about 3 lines of vision in both the atropine and patching groups. Improvement initially was faster in the patching group, but after six months, the difference in acuity between treatment groups was small. The mean visual acuity (Snellen approximation) at six months was 20/32 in the patching group and 20/32^-2 the atropine group. This small difference between groups was considered clinically inconsequential.

Both treatments were well tolerated, although atropine had a slightly higher degree of acceptability on a parental questionnaire. More patients in the atropine group than in the patching group had reduced acuity in the sound eye at six months but this did not persist with further follow up.

Both atropine and patching are effective treatments for moderate amblyopia in children in the age range of 3 to less than 7 years old. Patching has the potential advantage of a more rapid improvement in visual acuity and possibly a slightly better acuity outcome, whereas atropine has the potential advantage of easier administration and lower cost. Our data are inconclusive about whether atropine may cause a transient treatment-related reduction of acuity in the sound eye more often than does patching. However, we are reasonably confident that in our cohort atropine did not have a lasting adverse effect on acuity of the sound eye. Since incomplete responders to one treatment could later be given the other treatment, our results indicate that the initial choice of patching or atropine can be made by the eye care provider and parent. Both patching and atropine are appropriate treatment modalities for the initial management of moderate amblyopia in children.

Two year follow up data is not available at this time. Manuscript submitted to Archives of Ophthalmology in January 2004.