Effects of antiglaucoma drugs on ocular hemodynamics in healthy volunteers

Background and purpose: There is evidence that ocular blood flow plays a critical role in the clinical course of glaucoma. Hence a reduction in ocular blood flow due to topical antiglaucoma treatment should be avoided. The purpose of this study was to characterize the effect of antiglaucoma drugs on ocular hemodynamics. Methods: In a double-blind, placebo-controlled, randomized crossover study, we investigated the effects of single topical doses of five β-blocking agents (befunolol, betaxolol, levobunolol, metipranolol, and timolol), two adrenergic agents (clonidine and dipivefrin [INN, dipivefrine]), and a parasympathomimetic agent (pilocarpine) on ocular and systemic hemodynamics in healthy subjects (n = 10). Fundus pulsation amplitudes in the macula and the optic disc were measured to characterize pulsatile choroidal and optic disc blood flow, respectively. Moreover, central retinal and ophthalmic artery blood flow velocities were measured by Doppler ultrasound. Results: Befunolol, metipranolol, timolol, clonidine, and dipivefrin reduced fundus pulsations in the macula and the optic disc (-9% to -14% versus baseline). In contrast, betaxolol, levobunolol, and pilocarpine had no effect on fundus pulsations. Antiglaucoma drugs had no effect on either blood flow velocities in the central retinal or the ophthalmic artery or systemic hemodynamics. Conclusions: Our results indicate that befunolol, metipranolol, timolol, clonidine, and dipivefrin reduce choroidal and optic disc blood flow. This could be caused by drug diffusion to the choroid, which may cause vasoconstriction. Ocular blood flow reduction was not observed with betaxolol, levobunolol, or pilocarpine. The lack of effect of all drugs under study on central retinal blood flow velocity might partially be the result of autoregulative mechanisms. Because optic nerve head blood flow likely plays a critical role in the clinical course of glaucoma, the use of antiglaucoma drugs, which reduce blood flow, should be reconsidered.