Effect of Dual Endothelin Receptor Blockade on Ocular Blood Flow in Patients With Glaucoma and Healthy Subjects

Abstract

Purpose: : There is evidence that altered blood flow regulation may contribute to the pathogenesis of glaucoma. Recent studies indicate that an altered endothelin system contributes to vascular dysregulation seen in glaucoma. In the current study we tested the hypothesis that bosentan, a dual endothelin receptor antagonist, alters ocular blood flow in patients with glaucoma and healthy subjects.

Methods: : A total of 28 subjects were included: 14 patients with primary open-angle glaucoma and 14 sex and age matched healthy volunteers. Both groups received bosentan 500mg daily for 8 days. At baseline and on the second trial day ocular hemodynamics were measured. Retinal vessel diameters and retinal blood cell velocity were assessed with a Retinal Vessel Analyser and a laser Doppler Velocimeter, respectively. Choroidal and optic nerve head blood flow were measured with a laser Doppler Flowmeter.

Results: : After administration of bosentan retinal arterial and venous diameters significantly increased in both groups (+5% to 8%). Retinal blood flow velocity and retinal blood flow showed an increase of up to +45% in glaucoma patients and healthy control subjects. Choroidal as well as optic nerve head blood flow increased significantly after bosentan administration in all subjects.

Conclusions: : Our study indicates that dual inhibition of endothelin receptors increases ocular blood flow in patients with glaucoma and healthy subjects. Further studies are required to characterize the role of specific endothelin receptor subtypes in the control of ocular blood flow. Additional studies are required to clarify whether endothelin receptor antagonists may be a treatment alternative in glaucoma.

Clinical Trial: : www.clinicaltrials.gov NCT00701597

Keywords: retina