Effects of Dorzolamide on Choroidal Blood Flow, Ciliary Blood Flow, and Aqueous Production in Rabbits

Carbonic anhydrase inhibitors (CAIs) are commonly used in the treatment of glaucoma and ocular hypertension.1 When introduced in the 1950s, the ophthalmic community was interested in the IOP-lowering effect and then later started focusing on the vascular effects of CAIs.2,3 Although the ocular hypotensive effect of CAIs is undisputed, their effects on ocular blood flow are more ambiguous.4,5 Many of the CAI ocular blood flow studies examined the effects of the topically administered CAI dorzolamide,6–8 and those results are contradictory, with some studies indicating no or minor effects on ocular blood flow,9–14 whereas other studies report significant effects on ocular hemodynamics.15–18 There is also evidence that dorzolamide increases oxygen concentration in the optic nerve head and in the retina, which may be caused by a reduction in local metabolism or an increase in blood flow.19,20 In vitro studies also show a direct vasodilatory effect of CAIs on retinal arterioles.21,22 Given the ambiguity in the reported ocular blood flow responses to dorzolamide, one goal of the present study was to determine its effects on choroidal and ciliary blood flow at different perfusion pressures in an established rabbit model,23,24 which had not been done previously. The second goal of the study was to determine the effect of dorzolamide on the relationship between ciliary blood flow and aqueous production. Under control conditions, aqueous production is relatively constant until ciliary blood flow is reduced 20% to 30% below the control if ciliary blood flow is varied over a wide range by mechanical manipulations of blood pressure. With further reductions in ciliary blood flow, aqueous production decreases in a blood flow– dependent manner.25 Drugs that cause ciliary vasoconstriction and lower ciliary blood flow below the critical perfusion level decrease aqueous production to the same extent as mechanical blood flow reductions, indicating those drugs decrease aqueous production indirectly by depriving the ciliary epithelium of the blood flow needed to sustain ciliary metabolism.26 Dorzolamide decreases IOP by decreasing aqueous production, presumably by limiting bicarbonate availability.27–29 We hypothesized that dorzolamide would shift the blood flow–independent portion of the curve relating ciliary blood flow and aqueous production downward, consistent with a direct inhibitory effect on ionic transport within the cells of the ciliary epithelia.