Acute versus chronic effects of brimonidine on aqueous humor dynamics in ocular hypertensive patients

PURPOSE: To report the acute vs chronic effects of brimonidine, a selective α₂-adrenergic receptor agonist, on aqueous humor dynamics in ocular hypertensive patients. METHODS: Brimonidine 0.2% was given topically twice daily for 29 days to one eye each of 28 ocular hypertensive volunteers in a randomized double-masked study. The fellow eye was similarly treated with vehicle. Aqueous flow (Fa) and outflow facility (C(fl)) were determined with fluorophotometry. Intraocular pressure, outflow facility (C(ton)), and episcleral venous pressure (Pev) were measured with pneumatonometry, tonography, and venomanometry, respectively. Uveoscleral outflow (Fu) was calculated from intraocular pressure, Fa, Pev, and C(fl) values. All measurements were taken on baseline day, day 8, and day 29 of treatment. Intraocular pressure and Fa only were measured after instillation of 1 drop of brimonidine on day 1. RESULTS: When measured 3 hours after instillation on days 1, 8, and 29 of treatment, brimonidine significantly (P < .001) reduced intraocular pressure by at least 5.0 ± 0.7 mm Hg (mean ± SEM) compared with baseline day, and by 2.7 ± 0.5 mm Hg compared with the vehicle-treated contralateral control eyes. The greatest decrease (6.0 ± 0.6 mm Hg) was observed at 3 hours after the first drop. Aqueous flow was reduced by 29% (P < .001) after the first application but was not significantly different from baseline when measured at day 29 of treatment. Uveoscleral outflow was increased 60% at day 8 (P < .06) and day 29 (P < .05) compared with baseline. There was no significant difference in outflow facility or episcleral venous pressure at day 8 or day 29 of treatment. CONCLUSIONS: The brimonidine- induced reduction in intraocular pressure in humans is associated initially with a decrease in aqueous flow, and after chronic-treatment with an increase in uveoscleral outflow.