ABSTRACT
Carbonic anhydrase inhibitors (CAIs) lower IOP by decreasing aqueous humour production of the ciliary epithelial cells.55 Systemic administration of acetazolamide induces an increase in the cerebral and retinal flow.56 A similar effect on the ocular circulation was found after acute or short-term topical or systemic application of dorzolamide and brinzolamide in in-vivo animal models,57-61 as well as following their topical administration to healthy volunteers,62-66 or to patients suffering from normal tension glaucoma67
or primary open-angle glaucoma.31,68-73 Brinzolamide, which is more lipophilic than dorzolamide or acetazolamide at physiological pH, was found in 0.338 lg equivalents/g in the retina of the pigmented rabbits after a single instillation.75 This concentration and its relatively long half-life in the retina suggest that this molecule (and probably also the other CAIs) may directly influence the retinal vessels. In a laser Doppler flowmetric study on rabbits,61 bid instillation of brinzolamide 1% or dorzolamide 2% for 7 to 14 days resulted in a similar, significant increase in optic nerve head blood flow, and a decrease in IOP. These changes were associated with a mild but significant decrease of the arterial pH. In contrast, in another study using bid dorzolamide 1% instillation for 20 days on rabbits, no change of the optic nerve head circulation was measured with laser speckle analysis.60 In studies on domestic pigs, intravenous administration of acetazolamide and dorzolamide caused a dose-dependent increase in oxygen tension at the optic nerve head.57-59 This effect of the intravenously injected dorzolamide was maintained despite the acute experimental elevation of IOP,57 which shows that the increase in oxygen tension is independent from the IOP decrease induced by these molecules.
