Amblyopia study provides new insight for older children

Baltimore-Results from the Amblyopia Treatment Study 3 (ATS3) support offering amblyopia treatment to children aged 7 to 12 years and considering it as well for children aged as many as 17 years who have not been treated previously, reported Michael X. Repka, MD, at the Current Concepts in Ophthalmology meeting here.

ATS3 was a multicenter, randomized study undertaken by the Pediatric Eye Disease Investigator group that enrolled 507 children aged 7 to <18 years with unilateral strabismic or anisometropic amblyopia, said Dr. Repka, professor of ophthalmology and pediatrics, Johns Hopkins University School of Medicine, Baltimore. The study compared optical correction alone (control) versus optical correction augmented with patching and near vision activities (active treatment).

In addition, children <13 years old in the active treatment group received atropine 1% daily.

After 6 months, about 25% of children had a response to optical correction alone. In the subgroup aged 7 to 12 years, the response rate was twice as high in the active treatment group compared with the controls (optical correction alone), and further analyses showed that benefit persisted regardless of previous treatment, amblyopia severity, or amblyopia cause. In addition, vision in patients in whom a response was seen remained stable overall during 1 year of follow-up after treatment cessation.

No difference in response rates was seen between the active treatment and control groups among children aged 13 to 17 years. Active treatment was beneficial, however, considering the subgroup that had no previous amblyopia treatment. Overall, the benefits of amblyopia treatment occurred with a low chance of complications, according to Dr. Repka.

Paradigm shift

“Prior to the mid-1990s, most experts would generally recommend not attempting to treat amblyopia once children reached 8 to 10 years of age based on the idea that the critical period for visual development had already passed,” he said. “The question, however, of when the critical period is actually over in children had not been well-studied, and results of this randomized clinical trial support a change in clinical practice.”

The ATS3 was funded by the National Eye Institute. First, however, a pilot study was conducted to evaluate the potential for treatment response in older children with amblyopia. It enrolled 66 patients aged 10 to 17 years and found that 27% of those children benefited with a 2-line or greater improvement in visual acuity after just 1 month of treatment with part-time patching combined with near visual activities. Analyses with the children divided into two subgroups by age (10 to <14 and 14 to <18) showed no decrease in response rate with older age. Then these data were used to create the ATS3 study.

The objectives of ATS3 were to determine the response rate to amblyopia treatment in children aged 7 to <18 years as well as the frequency of recidivism after successful treatment. Children were eligible if they had unilateral amblyopia associated with strabismus and/or anisometropia, best-corrected visual acuity (BCVA) ranging from 20/40 to 20/400 in the amblyopic eye and 20/25 or better in the sound eye with a minimum 3-line intereye difference, no more than –6 D of myopia in the amblyopic eye, no amblyopia treatment other than spectacles in the past month, and no more than 1 month of amblyopia treatment in the last 6 months. In addition, patients aged fewer than 13 years were required to have no more than –0.50 D of myopia in the sound eye.

Patients were followed every 6 weeks for 24 weeks following randomization. A treatment response was defined as a patient with a 10-letter or greater improvement from baseline in the amblyopic eye’s acuity with confirmation with a second measurement by an examiner in masked fashion. The analysis of response rates showed improvement even with optical correction only. A significant additional benefit was seen for the augmented strategy in children aged 7 to 12 years, however. In that subgroup, 53% of patients receiving the augmented treatment had a response compared with 25% of those treated with optical correction only. Among the older children, about one-fourth of patients in both the active and control groups had a response.

“Further subdivision of the younger age group showed rates of response to augmented treatment and optical treatment decreased with increasing age, but the relative benefit of the augmented treatment was similar across the age range of 7 to 12 years old,” Dr. Repka reported.

Data also were analyzed to determine whether prior amblyopia treatment influenced the chances of a response. Whether or not children had prior treatment, a significant benefit was seen for the augmented strategy compared with only optical correction among children aged 7 to 12 years. Response rates, however, to both augmented treatment and optical treatment in children who had no prior amblyopia treatment (67% and 36%, respectively) were higher than the corresponding rates observed in children who had prior amblyopia treatment (40% and 13%, respectively).

Among children aged 13 to 17 years, no significant difference was seen in response rates to augmented treatment and optical treatment in the subgroup with a history of amblyopia treatment. In the treatment-naïve children, however, 47% had a response to augmented treatment, and that rate was significantly higher than the 20% rate achieved with optical correction only.

“Although these findings support treating the older child who has never been treated before, it is important for clinicians to realize that patching compliance is tougher in this age group and atropine should be avoided if the child is driving,” Dr. Repka said.

Another subgroup analysis in children aged 7 to 12 years considered baseline amblyopia level and showed significant benefits of the active treatment compared with only optical correction for increasing response rates among children with BCVA of 20/40 to 20/80 (50% versus 22%, respectively) as well as in those with worse acuity (20/100 to 20/400) at baseline (60% versus 30%, respectively).

At the end of the randomized trial, patients with a response continued their assigned treatment until no further improvement was seen. At that point, patients in the active treatment group entered the observation phase and returned for visits after 13, 26, and 52 weeks while receiving no treatment.

A total of 80 patients aged 7 to <12 years entered the observation phase. At 1 year, five children (7%) experienced recurrence, defined as loss of 10 or more letters in visual acuity relative to the level at treatment discontinuation. For the entire group, the mean acuity decrease at 1 year was only 1.3 letters.

“Although ATS3 showed [that] visual acuity could be improved with amblyopia treatment, it was also important to know if the improvement would be sustained after treatment cessation,” Dr. Repka noted.

Diplopia risk studied

The safety analysis was reassuring regarding the risk of diplopia, he said. No patient reported constant diplopia and among the 13- to 17-year-olds, none reported binocular diplopia more than once a day. Among the younger children, four children in the augmented group and one in the optical correction group experienced binocular diplopia more than once a day. In three of the four children in the augmented group, diplopia, however, was not reported at the last visit, and the fourth child reported transient episodes of diplopia just once a day.

“We were concerned about the potential for diplopia because intractable, constant diplopia has been associated with amblyopia treatment in older children and adults,” Dr. Repka said. “In our study, this form of diplopia did not occur. What we saw was infrequent diplopia, which seemed inconsequential.”OT