Original article
Intercurrent Factors Associated with the Development of Open-Angle Glaucoma in the European Glaucoma Prevention Study

https://doi.org/10.1016/j.ajo.2007.04.040Get rights and content

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).

Section snippets

Methods

The EGPS is a multicenter, randomized, double masked, placebo-controlled clinical trial. The enrollment of the patients was between January 1, 1997 and May 31, 1999. The design and methods of the EGPS were described previously18 and are summarized as follows.

In brief, 1,081 individuals with IOP ≥22 mm Hg in at least one eye and no evidence of glaucomatous damage were randomized to either dorzolamide or placebo eye drops. All the analyses of the EGPS were performed with 1,077 patients, because

Results

Intercurrent factors in participants who did and did not develop OAG in the EGPS are reported in TABLE 1, TABLE 2. The percentages in Table 2 were calculated by dividing the number of participants who developed OAG by the number of randomized participants (1,077). These values are not adjusted for duration of follow-up.

Univariate HRs with 95% CIs for the development of OAG are reported for each putative intercurrent factor in Table 3. In univariate analyses, intercurrent factors associated with

Discussion

The mean IOP reduction, mean IOP, and the AUC of mean IOP during the follow-up, the presence of optic disk hemorrhages, and the use of systemic diuretics were significantly associated with the development of OAG in the EGPS. All of the baseline predictive factors except for older age retained their statistically significant association with the development of OAG. These results appear to be largely in agreement with previously reported findings from the OHTS10 and the Early Manifest Glaucoma

Stefano Miglior is a Professor of Ophthalmology at the University Milano Bicocca, Italy and Chair of the Ophthalmic Department of the Policlinico di Monza (MI), Italy. He is the author of several papers on the diagnosis of glaucoma and imaging of the disk and RNFL published in major international journals. Dr Miglior serves as a reviewer for all of the major international journals. Dr Miglior is the Principal Investigator of the European Glaucoma Prevention Study.

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    • Cited by (0)

    Stefano Miglior is a Professor of Ophthalmology at the University Milano Bicocca, Italy and Chair of the Ophthalmic Department of the Policlinico di Monza (MI), Italy. He is the author of several papers on the diagnosis of glaucoma and imaging of the disk and RNFL published in major international journals. Dr Miglior serves as a reviewer for all of the major international journals. Dr Miglior is the Principal Investigator of the European Glaucoma Prevention Study.

    See accompanying Editorial on page 290.

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