Purpose: To evaluate the intercurrent factors for the development of open-angle glaucoma (OAG) in ocular hypertensive patients who were enrolled in the European Glaucoma Prevention Study (EGPS). Design: Randomized, double masked, controlled clinical trial. Methods: setting: Multicenter. study population: A total of 1,077 patients fulfilled a series of inclusion criteria, including intraocular pressure (IOP) 22 to 29 mm Hg, normal and reliable visual fields (VFs) and normal optic disks. intervention: Treatment with dorzolamide or placebo. main outcome measures: Glaucoma-related VF or optic disk changes. Clinical data were collected every six months during a five-year follow-up. Proportional hazards models were used to identify the factors that during follow-up (intercurrent factors) were associated with the development of OAG. Results: In multivariate analyses, adjusting for treatment arms and baseline predictive factors, mean follow-up IOP reduction (hazard ratio [HR] 0.89, 95% confidence intervals [CI] 0.80 to 0.98), mean follow-up IOP (HR 1.12, 95% CI 1.03 to 1.22), area under the curve of IOP (mm Hg per year) (HR 1.09, 95% CI 1.06 to 1.12), disk hemorrhages (HR 1.97, 95% CI 1.21 to 3.22), and use of systemic diuretics (HR 2.41, 95% CI 1.12 to 5.19) were associated with the development of OAG. Baseline central corneal thickness, vertical cup/disk ratio, vertical cup/disk ratio asymmetry, and pattern standard deviation remained statistically significant. Conclusions: These results suggest the need for future investigations to better elucidate the role of systemic diuretics in the development of OAG, because IOP and disk hemorrhages have already been shown to be important intercurrent factors in the Ocular Hypertension Treatment Study (OHTS) and Early Manifest Glaucoma Trial (EMGT).
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