Network’s studies at forefront of amblyopia treatment

The findings of the PEDIG multicenter investigations have altered the practices of many pediatric ophthalmologists.

Issue: December 15, 2006

Multicenter trials conducted over the past 9 years by a consortium of clinics across North America have changed the way many pediatric ophthalmologists practice. The network of investigators has conducted landmark studies in large patient populations that are helping to shape more effective treatments for amblyopia, strabismus and other conditions.

The Pediatric Eye Disease Investigator Group (PEDIG) is a collaborative network that facilitates multicenter clinical research in eye disorders that affect children, according to Michael X. Repka, MD, of the Wilmer Eye Institute in Baltimore, one of the group’s chairmen. The other chairman is Jonathan M. Holmes, MD, of the Mayo Clinic.

Speaking at a symposium on amblyopia treatment at the American Academy of Ophthalmology meeting, Dr. Repka said the network, formed in 1997, is funded by the National Eye Institute. PEDIG has more than 60 participating sites with more than 120 pediatric ophthalmologists and pediatric optometrists in the U.S. and Canada.

How it works

According to Dr. Repka, the network was founded at a time when evidence-based medicine was becoming more important, and NEI officials sought a change from classical clinical research trial design to large, straightforward trials that asked clinically relevant questions. PEDIG was designed to conduct effectiveness trials that simulated experience in real-world, community-based practices, Dr. Repka said.

Michael X. Repka

“There are distinct advantages to a network,” he said. “It allows the involvement of community-based practitioners in research; it allows us to recruit large numbers of patients and study unusual diseases. The network funding mechanism allows a great deal of flexibility for the investigators.”

PEDIG has four core centers: the Wilmer Eye Institute and the Mayo Clinic, where the two chairmen are located, a coordinating center at Jaeb Center for Health Research, and the NEI.

Dr. Repka noted that 244 investigators have enrolled at least one patient in PEDIG protocol.

“The general principle of PEDIG is that it is open to all qualified investigators,” Dr. Repka said. “We intend, and have been successful at, performing multiple simultaneous studies, including randomized clinical trials and observational studies, and the investigators are free to select studies of interest to them.”

The network has standing committees that plan policy, allot funding and select studies. An operations committee handles management issues, and each study has a planning committee and a steering committee. The group’s infrastructure helps streamline study launches and engenders better communication, Dr. Repka said.

Some critics have raised concerns about the group’s methodology and the limitations of certain PEDIG studies (see related article).

Study results

David K. Wallace, MD, MPH, speaking at the same AAO session, reviewed the results of some of the PEDIG trials that have been completed and published to date.

Dr. Wallace said the group has conducted important research into treatment options for amblyopia, including patching and drug therapy. It has also examined the effectiveness of amblyopia treatment in older children, helping doctors better understand treatment options for this age group, he said.

According to Dr. Wallace, one PEDIG study attempted to determine the success of spectacles alone in previously untreated anisometropic amblyopia patients. It was one of many studies that the group conducted comparing methods of treatment, including patching, spectacle wear and atropine, he said.

That study of spectacles for anisometropic ambylopia examined issues related to the treatment of amblyopia in children aged 3 to 7 years, with visual acuities of 20/40 to 20/400.

The study was conducted in two phases. In the first phase, the spectacle phase, patients were prescribed spectacles and followed every 5 weeks until there was no change in visual acuity between two visits. Then, in a randomized second phase, researchers compared a group using patching treatment in conjunction with spectacle correction if needed with a control group that continued only with spectacle correction if needed.

In the spectacle phase, 84 children ages 3 to just under 7 years old with untreated anisometropic amblyopia were enrolled. Baseline visual acuity ranged from 20/40 to 20/250. Researchers found that amblyopia improved with optical correction alone by two or more lines in 59% of the patients after 5 weeks. Visual acuity in the amblyopic eye improved to 20/25 or better in 27%, Dr. Wallace said.

Because patients were followed until they no longer experienced improvement, researchers also recorded best visual acuity achieved at any visit with glasses alone. Improvement continued for up to 30 weeks, and the cohort mean best improvement was about three lines, he said.

“There are certainly some advantages of amblyopia treatment with spectacles alone,” Dr. Wallace said. “By wearing spectacles, some children will improve to the point that they do not need patching or atropine.”

If patching is required, visual acuity improves after patching begins in many cases, he said.

Dr. Wallace suggested that children might be more likely to comply with patching if their baseline visual acuity is better: for instance, 20/50 as opposed to 20/100. He also suggested that initiating one treatment at a time, such as glasses alone instead of glasses plus patching, may lead to better compliance.

In the second phase of the multicenter clinical trial, 180 children 3 to 7 years old with best corrected visual acuity in the amblyopic eye of 20/40 to 20/400 were randomized into two groups. In one group, patients were corrected with spectacles if needed and also underwent 2 hours of daily patching with 1 hour of near visual activities. In the other, patients were corrected with spectacles alone if needed.

Of the 180 patients in the study, 173 (96%) attended the 5-week primary outcome visit.

Researchers found that improvement in visual acuity of the amblyopic eye, from baseline to 5 weeks, averaged 1.1 lines in the patching group and 0.5 lines in the control group (P = .006). Patients continued in their treatment groups until there was no improvement between two visits. Improvement from baseline to best measured acuity at any visit averaged 2.2 lines in the patching group and 1.3 lines in the control group (P < .001).

Effectiveness of patching

PEDIG has also conducted studies to investigate different dosing regimens for patching, Dr. Wallace said.

One PEDIG trial investigated the difference between prescribing daily patching for 2 hours vs. 6 hours. The randomized, multicenter trial included 189 amblyopic children from 3 years to less than 7 years old with vision in the amblyopic eye of between 20/40 and 20/80. One group was patched for 2 hours a day and one for 6 hours each day, combined with at least 1 hour per day of near visual activities while patched, he said.

The improvement in acuity in the amblyopic eye from baseline to 4 months averaged 2.4 lines in each group (P = .98), according to Dr. Wallace.

A PEDIG study of 507 patients aged 7 to 18 at 49 sites found that “even the older amblyopes seemed to improve with treatment, particularly if they’ve had no prior treatment,” he said.

For more information:

Michael X. Repka, MD, can be reached at 233 Wilmer Ophthalmological Institute, 600 N. Wolfe St., John Hopkins Hospital, Baltimore, MD 21287-9028; 410-955-8314; fax: 410-955-0809; e-mail: mrepka@jhmi.edu.

David K. Wallace, MD, MPH, is an associate professor of ophthalmology and pediatrics at Duke University Eye Center. He can be reached at Box 3802, Durham, NC 27710; 919-684-4584; fax: 919-684-6096; e-mail: david.wallace@duke.edu.

More information about the Pediatric Eye Disease Investigator Group can be found at http://public.pedig.jaeb.org.

Erin L. Boyle is an OSN Staff Writer who covers all aspects of ophthalmology.