Purpose: To investigate risk factors associated with visual field progression in the Low-pressure Glaucoma Treatment Study, a prospective trial designed to compare the effects of the alpha2-adrenergic agonist brimonidine tartrate 0.2% to the beta-adrenergic antagonist timolol maleate 0.5% on visual function in low-pressure glaucoma. Design: Prospective cohort study. Methods: Low-pressure Glaucoma Treatment Study patients with <5 visual field tests during follow-up were included. Progression was determined using pointwise linear regression analysis, defined as the same 3 or more visual field locations with a slope more negative than -1.0 dB/year at P < 5%, on 3 consecutive tests. Ocular and systemic risk factors were analyzed using Cox proportional hazards model and further tested for independence in a multivariate model. Results: A total of 253 eyes of 127 subjects (mean age, 64.7 ± 10.9 years; mean follow-up, 40.6 ± 12 months) were analyzed. Eyes randomized to timolol progressed faster than those randomized to brimonidine (mean rates of progression, -0.38 ± 0.9 vs 0.02 ± 0.7 dB/y, P <.01). In the final multivariate model adjusting for all tested covariates, older age (hazard ratio [HR] = 1.41/decade older, 95% confidence interval [CI] = 1.05 to 1.90, P =.022), use of systemic antihypertensives (HR = 2.53, 95% CI = 1.32 to 4.87, P =.005), and mean ocular perfusion pressure (HR = 1.21/mm Hg lower, 95% CI = 1.12 to 1.31, P <.001) were associated with progression whereas randomization to brimonidine revealed a protective effect (HR = 0.26, 95% CI = 0.12 to 0.55, P <.001). Conclusions: While randomization to brimonidine 0.2% was protective compared to timolol 0.5%, lower mean ocular perfusion pressure increased the risk for reaching a progression outcome in the Low-pressure Glaucoma Treatment Study. This suggests that the beneficial effect of randomization to the brimonidine arm was independent of possible differences in ocular perfusion pressures between the 2 treatment arms. The current results and large number of drop-outs in the brimonidine 0.2% arm suggest that more research is necessary before altering clinical practice paradigms.
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