Comparison of the Early Effects of Brimonidine and Apraclonidine as Topical Ocular Hypotensive Agents

OBJECTIVE: To compare the mechanism of action of short-term administration of brimonidine tartrate and apraclonidine hydrochloride as topical ocular hypotensive agents. SUBJECTS AND METHODS: Two randomized, double-masked, placebo-controlled studies of 19 normal human subjects were carried out. The first study compared brimonidine with apraclonidine in timolol maleate-treated eyes, and the second study compared latanoprost with placebo in timolol-treated eyes. The rate of aqueous flow and intraocular pressure were measured in both studies. The topical drug combinations were instilled the night before and repeated the morning before the measurements. Aqueous humor flow was measured by the rate of disappearance of topically applied fluorescein. Intraocular pressure was measured by pneumatonometry every 2 hours from 8:15 AM to 4:15 PM. RESULTS: Both brimonidine and apraclonidine further reduced aqueous flow in timolol-treated eyes from 1.23 +/- 0.21 microL/min to 0.96 +/- 0.16 microL/min and 0.98 +/- 0.17 microL/min, respectively. Consistent reductions were observed in intraocular pressure, with average reductions of 19% with brimonidine and 17% with apraclonidine. Latanoprost had no effect on aqueous flow in timolol-treated eyes (P = .15), but showed an average reduction in intraocular pressure of 13%. CONCLUSIONS: Brimonidine and apraclonidine are similar in their effects on the aqueous system. Both reduce intraocular pressure in the timolol-treated eye, primarily, if not exclusively, by further suppressing aqueous flow. In contrast, latanoprost reduces intraocular pressure in the timolol-treated eye without affecting aqueous flow.