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Dorado Beach, Puerto Rico—Recently reported results from the European Glaucoma Prevention Study (EGPS) have taken the ophthalmology community by surprise, reported Richard K. Parrish II, MD, at the Current Concepts in Ophthalmology meeting.
The trial is generating considerable discussion both because of the apparent IOP-lowering efficacy of placebo that occurred in that trial and the study's failure to define a benefit of medical therapy for protecting against glaucoma development in patients with ocular hypertension at low to moderate risk for developing glaucoma, Dr. Parrish added.
The double-masked, vehicle-controlled EGPS, recently published in Ophthalmology [2005;112:366-375], randomly assigned 1,081 patients to three times daily treatment with dorzolamide 2% (Trusopt, Merck) or vehicle. Mean IOP was reduced significantly from baseline after 6 months in the dorzolamide group (14.5%) and continued to decrease thereafter to fall 22.1% from baseline at 5 years.
Mean IOP averaged across the visits was significantly lower in the dorzolamide group (19.3 mm Hg) versus placebo (20.4 mm Hg), and the percentage change in IOP at study conclusion was also significantly greater in the dorzolamide group.
However, the between-group differences were numerically small and no significant treatment-related difference in the cumulative probability of glaucoma onset during 5 years, as judged by visual field loss or optic disc change or both (dorzolamide 13.4%; placebo 14.1%), was demonstrated. No treatment-related difference in the cumulative probability of developing an efficacy or a safety endpoint was apparent (dorzolamide 13.7%; placebo 16.4%) (safety endpoint defined as IOP in one eye was ≥35 mm Hg on two separate visits within 1 week).
The EGPS authors referred to the "remarkable efficacy of placebo" and cited the "clinically significant effect of the placebo on IOP" as the reason for failure to detect a protective benefit of dorzolamide, Dr. Parrish said.
They concluded that the results "strongly support the need to evaluate or re-evaluate the efficacy of long-term medical therapy of ocular hypertension, primary open-angle glaucoma (POAG), or both by means of placebo-controlled, double-masked, randomized clinical trials."
They specifically suggested repeating the Early Manifest Glaucoma Trial (EMGT) with a placebo control group; the study which compared medical and laser treatment versus observation.
Based on his critical review, however, Dr. Parrish has gleaned a different take-home message from the EGPS, and he disagrees with the idea of repeating the EMGT using a placebo-controlled design. In his opinion, the EGPS results demonstrate that in a group of patients with ocular hypertension who are at low risk to develop glaucoma, IOP lowering in this range is not sufficient to avert field loss or disc changes in all patients.
"This is a hot topic, and for the time being, what we can say is that the results are a surprise. But, stay tuned," Dr. Parrish reported during the meeting, sponsored by Johns Hopkins University School of Medicine, Baltimore, and supported by Ophthalmology Times.
Reconciling EGPS with OHTS Dr. Parrish said that the main outcome of the EGPS runs against the grain of the findings of the Ocular Hypertension Treatment Study (OHTS). At first glance, the two studies appear similar, and in both trials medical treatment resulted in a similar IOP reduction, he said. However, important design and population differences between the studies might account for the apparently conflicting results, Dr. Parrish continued.