Ambylopia studies show value of various treatments at various ages

Baltimore

-Findings from an ongoing series of amblyopia treatment studies have provided results that can be applied to many aspects of clinical practice, such as the effectiveness of treatment options, appropriate dosages, and the ages at which treatment can be beneficial.

In a presentation here at the Current Concepts in Ophthalmology meeting, Michael X. Repka, MD, professor of ophthalmology and professor of pediatrics, Wilmer Eye Institute, Johns Hopkins University, Baltimore, reviewed a series of recent amblyopia treatment studies.

The series, conducted by the Pediatric Eye Disease Investigator Group (PEDIG), began with the Amblyopia Treatment Study 1 (ATS-1), comparing atropine with part-time patching as treatments for moderate amblyopia in children between 3 and 7 years old at enrollment. In this randomized, controlled, single-masked, multicenter trial, 419 children were assigned to receive daily treatment with 1% topical atropine or daily patching for 6 or more hours per day. Atropine is not FDA-approved for the treatment of amblyopia.

Visual acuity in the amblyopic eye and the fellow eye was measured at 6 months and at 2 years. Although initial improvement was faster in the patching group, by 6 months the difference between the two groups was clinically inconsequential. After 6 months, treatment was at the investigator's discretion, although most patients continued the treatment to which they had first been assigned.

Two-year results showed no difference between the groups. Visual acuity had improved 3.7 lines from baseline in the patching group and 3.6 lines in the atropine group. Mean acuity at 2 years was 20/32 in both groups, and improvement of >3 lines from baseline was seen in 86% of children in the patching group and 84% in the atropine group.

"Both are effective initial treatments," Dr. Repka said. "The one you initially choose may not be the treatment that you use in the end; you may end up choosing to prescribe the other. Some patients do not tolerate one or simply prefer another."

Follow-up exams in this group are continuing to determine if the early improvement persists. Examinations of children who have reached the age of 10 are complete, and exams for 15-year-olds have begun. These long-term outcome reports will be forthcoming.

Following ATS-1, PEDIG began a series of studies on dosage. The ATS-2 study evaluated 2 hours versus 6 hours per day of patching in moderate amblyopia and 6 hours versus full time in severe amblyopia. Children less than 7 years of age were followed for 4 months.

Investigators found that improvement in visual acuity for moderate amblyopia was identical in the two groups; from baseline to 4 months, improvement in the amblyopic eye averaged 2.4 lines in children who had been randomly assigned to 2 or 6 hours of patching. Results for severe amblyopia (20/100 to 20/400) also were similar; improvement averaged 4.8 lines in the 6-hour prescribed patching group and 4.7 lines in the full-time group.

"The truism 'more is better' did not seem to apply to this treatment," Dr. Repka said.

The PEDIG investigators also looked at different dosages of atropine, comparing daily doses with weekend-only treatment. In the randomized study, the outcome was the same in both treatment arms; at 4 months, improvement averaged 2.3 lines, mean acuity was 20/32, and 66% of children in both groups had >3 lines of improvement from baseline.

"All of the dosage studies found treatment effects to be so close that there was not even a hint of difference," Dr. Repka said. "The important thing is that lower dosages than have been traditional do work much of the time. It should be emphasized that you can start with a lower dosage, but if it does not work or the patient is not getting better, you should consider increasing the intensity. Do not just give up. We have not tested the question of what happens in patients who do not have a response to the lower doses, but there is a proportion in whom that would be the case."

In addition to the dosage studies, PEDIG has addressed the question of when to treat. It has been customary to treat children for amblyopia up to the age of 7 years, with the assumption that treatment after that age would have little or no effect, Dr. Repka explained. The dosage studies had shown no drop-off in the effectiveness of either patching or atropine up to age 7, so investigators decided to see if there was any benefit in older children.

ATS-3 looked at treatment in patients 7 to 18 years. Patients treated with spectacles alone were compared with those who received active treatment in addition to spectacles.

"Surprisingly, I think, to many, conventional treatments-patching and eyedrops combined-led to produced improvement significantly more often than glasses alone when patients were age 7 to 13,"

Dr. Repka said. "Beyond age 13 years, there was some improvement, but that was the same in both groups. You could get improvement with glasses alone in the older teens, so I think it is worth a try. In the younger kids, there is evidence now that a trial of treatment should be considered through age 13." Dr. Repka also pointed out that an important variable in these studies of treatment of older children was that therapy was more likely to be successful in all age groups if there has been no prior treatment. "We should treat older patients than we did before, and while we may be reluctant to treat every preteen or every teenager, at least the kids who have never had a trial of treatment should be given one because they are more likely have to improvement," Dr. Repka said.

Exploring yet another facet of amblyopia treatment, investigators then looked at whether treatment was more effective than no treatment beyond wearing glasses. This study (ATS-5) had a spectacles-only phase and a randomized phase. Both addressed important clinical issues: the role for spectacles and the effectiveness of patching. Outcomes of the spectacles-only phase showed that vision in 77% of children who were prescribed glasses improved at least 2 lines, and resolved in 27%.

"This means that you can treat a large proportion of kids with amblyopia with glasses alone for a time. Even if they are not cured by the glasses, the improved visual acuity of the amblyopic eye would make any subsequent treatment much easier," Dr. Repka said.

The second, randomized phase of this study looked at whether adding patching would benefit children whose vision was stable in spectacles, and the answer was yes-adding patching led to additional improvement compared with no additional treatment. The best vision attained with spectacles was 1.3 lines versus 2.2 lines with patching (p <0.001).

Dr. Repka also summarized the results of ATS-7, which looked at bilateral refractive amblyopia in children with 20/40 to 20/400 best-corrected binocular visual acuity. The prescribed treatment was to wear glasses for 1 year. The mean best corrected visual acuity at baseline was 20/63; at 1 year, it improved to 20/25, for a mean improvement of 3.9 lines.

As many physicians have long suspected, these results prove that glasses alone are a powerful intervention for these forms of bilateral symmetrical ametropic amblyopia, Dr. Repka said.

"Just as we have long known that refraction is an important part of the evaluation of a patient with amblyopia or strabismus, the importance of the refraction in providing the appropriate refractive correction is crucial to obtaining a good outcome," he concluded.