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Although prospective, randomized trials have their limitations, they have been successful at identifying a series of risk factors for development of primary open-angle glaucoma. Population-based studies and the acquisition of clinical data by high-tech instruments also may help identify patients at high risk of developing glaucoma.
Monza, Italy-Randomized, prospective clinical trials are a powerful tool to assess risk factors in glaucoma, but they have limitations, mainly that they are based on a selective population affected by increased IOP. For this reason, population-based studies may be useful in identifying other risk factors that cannot be discovered through prospective, controlled clinical trials, according to Stefano Miglior, MD, professor of ophthalmology, University of Milan Bicocca, Monza, Italy.
Several high-profile prospective studies have identified a series of baseline factors that predict the development of primary open-angle glaucoma, he said. These studies include the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS).
The OHTS included 1,600 patients with ocular hypertension who were followed for more than 5 years. In the EGPS, 1,100 patients were enrolled and followed for 5 years. Both studies relied on visual field and/or optic disk change to define glaucoma.
The same analysis conducted on the EGPS data consistently agreed with the results of the OHTS trial; the factors significantly associated with development of glaucoma were age, IOP, CCT, vertical cup-to-disk ratio, and PSD. In the EGPS, however, vertical cup-to-disk asymmetry also emerged as predictive.
The hazard ratios were similar in the American and European populations of the two studies. The only difference in predictors in the two studies was found in CCT measurements; this difference was explained by the lack of any patients of African-American descent in the EGPS, Dr. Miglior said, adding that African-Americans typically have thinner central corneas than do Caucasians. The hazard ratios for CCT were 1.92 (1.60 to 2.30) in OHTS and 1.40 (1.14 to 1.72) in EGPS.
Both studies also have assessed predictive factors by excluding those related to the disk and the visual field, such as early changes in PSD and vertical c/d ratio, which in some way might be part of the definition of the disease.
"In the OHTS, the other factors remained almost the same," Dr. Miglior said. "Age, IOP, and thinner cornea were associated with glaucoma, and diabetes was protective. In the EGPS, the factors remained the same-age and CCT-and IOP gained statistical significance." The hazard ratio was 1.18, he added.
Merging data sets
Several years ago, scientists began to collaborate on a merger of the data sets from the two studies. "The aim of this collaboration is to assess the predictive model only on the patients who were controls in the two studies. That means the observation arm in the OHTS and the placebo-treated arms in the EGPS," Dr. Miglior said. "Analysis of the merged database showed that there was no difference for any of these variables: age, IOP, CCT, PSD, and vertical c/d ratio."
Many of these findings, he added, have been confirmed in a third study, the Malmö study, which was smaller but had a longer follow-up, about 10 years. In this study, age, IOP, and suspect disk were identified as predictive factors for glaucoma.
Analysis of the OHTS data also has revealed that IOP asymmetry may be important in the development of glaucoma. "It has been shown that, in those eyes with higher IOP from asymmetric pairs, the risk of developing glaucoma was significantly higher as compared with the eyes with lower IOP," Dr. Miglior said.
In addition, other OHTS data showed that patients with abnormal baseline topographic optic disc measurements in tests performed with confocal scanning laser ophthalmoscopy had a very high risk of developing glaucoma over time; the hazard ratio was 3.37.
Along with population-based studies, the acquisition of clinical data by high-tech systems performing confocal scanning laser ophthalmoscopy may help identify patients with ocular hypertension who are at high risk for glaucoma, Dr. Miglior added.
Another recent analysis of OHTS data looked at the detection and prognostic significance of optic disk hemorrhages. The occurrence of disk hemorrhages during follow-up was associated with glaucoma, Dr. Miglior said, with a hazard ratio that was 3.7.