Increased Optic Nerve Head Blood Flow After 1 Week of Twice Daily Topical Brinzolamide Treatment in Dutch-Belted Rabbits

Abstract 

Objectives: Using a three-way crossover study design, we compared the effects of brinzolamide 2%, dorzolamide 2%, and placebo (vehicle) on microvascular optic nerve head (ONH) blood flow, intraocular pressure (IOP), blood pressure, heart rate, and acid-base balance in nine acepromazine-tranquilized Dutch-belted rabbits. Methods: Baseline measurements were taken before treatment and after drug-free washout periods of 7–14 days. Microvascular ONH blood flow was measured with a fundus camera-based laser Doppler flowmeter (LDF). Intraocular pressure was measured with a Tono-Pen XL. One drop of brinzolamide, dorzolamide, or vehicle was administered twice daily (9 a.m. and 5 p.m.) in right eyes only for 7 days. Experimental measurements were made 90 minutes after the 9 a.m. topical dose was administered on day 8. Results: ONH blood flow was significantly increased (P ≤ 0.05) in carbonic anhydrase inhibitor (CAI)-treated rabbits, as compared with vehicle-treated controls. The percent increase from baseline was 11.2 ± 1.8% in brinzolamide-treated animals and 8.4 ± 4.3% in dorzolamide-treated animals. Compared with controls, IOP in the brinzolamide- and dorzolamide-treated groups was significantly decreased (P ≤ 0.05). The changes in ONH blood flow and IOP were not significantly different between the CAI treatment groups. Small but significant changes in systemic blood gas tensions and pH were present in both CAI treatment groups, as compared with the vehicle group. Systemic blood pressure and heart rate were not significantly changed. Conclusions: Topical ocular CAI treatment for 1 week with either brinzolamide or dorzolamide significantly reduced IOP and significantly increased ONH blood flow in tranquilized Dutch-belted rabbits, while eliciting minimal systemic acid-base balance disturbances.

Keywords:  brinzolamide, carbonic anhydrase inhibitors, dorzolamide, glaucoma, intraocular pressure, ocular blood flow