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

Abstract

Purpose To determine the effects of topical dorzolamide (a carbonic anhydrase inhibitor) on choroidal and ciliary blood flow and the relationship between ciliary blood flow and aqueous flow. Methods The experiments were performed in four groups of pentobarbital-anesthetized rabbits treated with topical dorzolamide (2%, 50 μL). In all groups, intraocular pressure (IOP) and mean arterial pressure (MAP) at the eye level were measured continuously by direct cannulation. In group 1, aqueous flow was measured by fluorophotometry before and after dorzolamide treatment. In group 2, aqueous flow was measured after dorzolamide at normal MAP and while MAP was held constant at 80, 55, or 40 mm Hg with occluders on the aorta and vena cava. In group 3, the same MAP levels were used, and ciliary blood flow was measured transsclerally by laser Doppler flowmetry (LDF). In group 4, choroidal blood flow was measured by LDF with the probe tip positioned in the vitreous over the posterior pole during ramp increases and decreases in MAP before and after dorzolamide. Results Dorzolamide lowered IOP by 19% (P < 0.01) and aqueous flow by 17% (P < 0.01), and increased ciliary blood flow by 18% (P < 0.01), which was associated with a significant reduction in ciliary vasculature resistance (−7%, P < 0.01). Dorzolamide shifted the relationship between ciliary blood flow and aqueous flow downward relative to the previously determined control relationship in the rabbit. Dorzolamide did not alter choroidal blood flow, choroidal vascular resistance, or the choroidal pressure flow relationship. Conclusions Acute topical dorzolamide is a ciliary vasodilator and has a direct inhibitory effect on aqueous production, but it does not have a detectable effect on choroidal hemodynamics at the posterior pole in the rabbit.

Effects of dopamine on retinal and choroidal blood flow parameters in humans

“…This is in accordance with data published in rabbits, where even at relatively lower doses an increase in choroidal blood flow was observed 21. When interpreting our data of FPA measurement one needs, however, to consider that dopamine increased the pulse pressure amplitude and increased peak systolic velocity in the OA more than the end diastolic velocity.…”

“…Dopamine antagonists have been shown to increase ocular blood flow in rabbit1 13 whereas dopamine agonists had no effect 2. There is also evidence for dopamine increasing choroidal blood flow 14 21. In humans, a dopamine agonist induced a decrease of cerebral blood flow 15…”

Comparison of Choroidal and Optic Nerve Head Blood Flow Regulation during Changes in Ocular Perfusion Pressure

“…41,54,55 More recently, this concept was challenged by animal experiments in the rabbit, which showed autoregulatory behavior compatible with myogenic control of choroidal perfusion during mechanical changes in OPP. [2][3][4][56][57][58] The contribution of metabolic and myogenic mechanisms in autoregulatory responses in the brain still is a matter of debate, [59][60][61] and the situation is even more unclear for the eye. 1 Usually, it is assumed that the upper and lower levels of autoregulation are reached when maximum vasoconstriction and vasodilatation are achieved, respectively.…”

Measurement and Modeling of Diffusion Kinetics of a Lipophilic Molecule Across Rabbit Cornea

“…The values of V aq and A cornea for rabbits were assumed to be 0.311 mL and 1.54 cm 2 , respectively (26). K clearance is approximated as the aqueous humor outflow in rabbits, which is reported to vary from 0.411 μL/min (27) to about 3 μL/min (28,29). A value of 0.411 μL/min was used in the simulations reported here, but higher values would result in similar predictions for corneal concentrations as the aqueous humor concentrations are close to perfect sink (i.e., close to zero concentration).…”