The methodology of several large, multicenter trials of amblyopia treatment leaves several questions unresolved, according to an orthoptist who reviewed the studies. These questions relate to the association between patient age and treatment results, the treatment protocol, measurement of therapy adherence, visual acuity results, and the definition of therapy success.
Iowa City, IA-The Pediatric Eye Disease Investigator Group (PEDIG) is conducting a series of clinical trials, many of which involve amblyopia treatment. The results of the trials should be interpreted cautiously, and more studies are needed to clarify unresolved issues, said Pamela J. Kutschke, CO.
Kutschke, director, orthoptic teaching program, and faculty adjunct lecturer, Department of Ophthalmology and Visual Sciences, University of Iowa Health Care, Iowa City, expressed concerns with the findings of various amblyopia studies, particularly a study of atropine versus patching known as Amblyopia Treatment Study 1 (ATS 1). In the trial, 419 patients aged fewer than 7 years who had a diagnosis of moderate amblyopia were randomly assigned to treatment with either patching or atropine for 6 months and were followed for 2 years.
At 2 years, the investigators found similar improvement levels in both treatment groups. Vision in the amblyopic eye improved from baseline by a mean of 3.7 lines in the patching group and 3.6 lines in the atropine group. In both groups, the mean amblyopic eye acuity was about 20/32.
"My first concern was with the age range," Kutschke said. "The authors infer that, as no association was found between age and the treatment results for the 3-to-less-than-7-year age range, these results would be found for other age groups as well. This can't be done. The age range of 3 to less than 7 years was just too limited, too small, to extend [the results] to other studies."
She also analyzed the treatment protocol. Kutschke said that that the large, multicenter PEDIG studies are a collaborative effort among numerous investigators, each with a different opinion on amblyopia treatment and how it should be done. The format results in concessions in the treatment protocol and discrepancies in the treatment regimen, she added.
In ATS 1, treatment initially was standardized at 1 drop of atropine per day, whereas patching was left to the investigator's discretion, with a minimum of 6 hours per day and a maximum of all but 1 waking hour. "For a controlled study, this produced a great amount of variability," Kutschke said.
"Full-time occlusion versus part-tine occlusion for moderate amblyopes was never studied," she continued. "This probably couldn't be done, as the investigators have their own ideas about how much patching should be done and won't prescribe any other amount."
Discussing the results from the atropine treatment arm, Kutschke noted that 28% of patients were switched to a plano lens in the sound eye when vision did not improve to a successful level after 16 weeks.
"This makes the study not just about atropine but [also about] pharmacologic and optical penalization," she said. "Penalization was shown to take longer to produce improvement than patching. We don't know what the effect of atropine alone would have been.
"Would a longer period of atropine alone have produced the desired results?" Kutschke continued. "If so, we could know just how long it takes atropine to produce improvement. It may have been shown that atropine can produce the desired effect, but only after a much longer time."
Kutschke said her third concern with the study involved therapy adherence, which she said could be affected by the way each physician presented the treatment approach. "Although I'm sure that a point was made to remove any bias, presentation can easily be used to sway a parent's or patient's feelings," she said. "With so many different centers participating in the study, the approach to treatment could not be standardized."
As much as the study tried to assess the issue, therapy compliance rates remained an unknown, she continued. Because the study was conducted in clinical practices, it was difficult to adhere to a scientific method of measuring compliance. Patients were asked to complete a calendar charting the hours that they spent on patching, but there is a natural tendency to exaggerate on this type of report to make the physician happy, Kutschke said.
"The study ended up being a test of what was prescribed and not what actually was done," she added.