Effect of Viagra on the foveolar choroidal circulation of AMD patients

https://doi.org/10.1016/j.exer.2005.01.017Get rights and content

Abstract

To investigate the effects of sildenafil citrate (Viagra) on foveolar choroidal circulation in patients with age related macular degeneration (AMD).

Double-blinded, randomized, placebo-controlled, crossover study. Fifteen male AMD patients received a dose of 100 mg of sildenafil or matching placebo on two separate days. Laser Doppler flowmetry was performed to assess relative choroidal blood velocity (ChBVel), volume (ChBVol) and flow (ChBFlow) in the study eye prior to administration of the drug at baseline and 30, 90, 180, 300 min after dosing. Best corrected visual acuity (BCVA), contrast sensitivity (CS), mean arterial blood pressure (BPm), heart rate (HR), intraocular pressure (IOP) and ocular perfusion pressure (PP) were determined.

In comparison to placebo, sildenafil did not cause any statistically significant changes in mean ChBVel (ANOVA, P=0·12), ChBVol (ANOVA, P=0·24) or ChBFlow (ANOVA, P=0·46). There were no statistically significant changes in CS (ANOVA, P=0·59), BCVA (P=0·58), IOP (P=0·81) or HR (P=0·07) throughout the study. Significant decreases in BPm (P=0·006) and PP (P=0·006) were observed at 30 min after sildenafil.

Administration of sildenafil citrate didn't cause any statistically significant changes in the foveolar choroidal circulation of AMD patients.

Introduction

Sildenafil citrate (Viagra) is the first oral drug approved for the treatment of erectile dysfunction is a selective inhibitor of phosphodiesterase type 5 (PDE5), the predominant isozyme metabolizing cyclic GMP in the corpus cavernosum (Boolell et al., 1996). Endothelium-derived relaxing factors, such as nitric oxide (NO), (Furchgott and Vanhoutte, 1989, Ignarro et al., 1987) diffuse into the smooth muscle and increase levels of cGMP, producing smooth muscle relaxation and dilatation of blood vessels (Furchgott and Vanhoutte, 1989, Gruetter et al., 1981, Ignarro and Kadowitz, 1985). Sildenafil greatly enhances the dilating effects of NO by blocking PDE5 and because of this property it was initially designed to treat cardiac ischemic conditions (Jackson et al., 1999). As sildenafil has a direct effect on the blood vessels it is possible that it might affect ocular blood vessels.

Several investigators have studied the effects of sildenafil on ocular circulation in normal subjects (Dundar et al., 2001, Grunwald et al., 2001, Grunwald et al., 2002, Pache et al., 2002, Paris et al., 2001, Polak et al., 2003). The effect of sildenafil in disease, however, is less known. Because of previous reports suggesting that choroidal blood flow is decreased in age-related macular degeneration (AMD) (Boker et al., 1993, Chen et al., 1992, Friedman et al., 1989, Friedman et al., 1995, Grunwald et al., 1998, Holz et al., 1994, Pauleikhoff et al., 1990, Prunte and Niesel, 1988, Sarks, 1976, Sarks et al., 1988), we investigated the effect of sildenafil on this vascular tissue.

Theoretically, because sildenfil has a strong systemic vasodilating effect that decreases systemic blood pressure, such effect could potentially result in decreased choroidal blood flow. On the other hand, since the choroid is a vascular tissue analogous in many respects to the corpus cavernosum (Paris et al., 2001), sildenafil could have a strong vasodilatory effect resulting in increased choroidal blood flow. Thus the purpose of this study was to evaluate the effects of sildenafil on the foveolar choroidal circulation of patients with age-related macular degeneration.

Section snippets

Design

We conducted a double-blinded, randomized, placebo-controlled, crossover study that included 15 male subjects with different stages of AMD.

Methods

Fifteen male patients (14 Caucasians and 1 African-American) with AMD features similar to those of AMD category 3 or worse of the AREDS study and visual acuity of 20/40 or better in the study eye were included in this study. We chose subjects with relatively good vision in the study eye because good fixation is important when laser Doppler flowmetry is used to measure choroidal blood flow in the center of the foveola. Mean age of study subjects was 75±7 years (±1 sd). All 15 patients had

Results

Mean values of ChBVel, ChBVol and ChBFlow at baseline, 30, 90, 180 and 300 min are shown in Table 1. In comparison to placebo, administration of 100 mg of sildenafil citrate did not cause any statistically significant changes in mean ChBVel (ANOVA, P=0·12), mean ChBVol (ANOVA, P=0·24) or mean ChBFlow (ANOVA, P=0·46, Fig. 1) at any time points. Since no statistically significant changes in ChBFlow were found, we estimated that we have 95% power to detect a 12% difference in the change ChBFlow from

Discussion

Because of sildenafil's strong vasodilatory qualities we investigated whether this compound may have an effect on the ocular circulation. We were particularly interested in the possibility that sildenafil may have an effect on the choroidal circulation of patients with AMD, because our previous study and several other reports had suggested that the choroidal blood flow is decreased in AMD patients (Boker et al., 1993, Chen et al., 1992, Friedman et al., 1989, Friedman et al., 1995, Grunwald et

Acknowledgements

This research was supported by a grant from Pfizer Inc., the Vivian S. Lasko Research Fund, Research to Prevent Blindness, NIH grant EY01583 and the Paul and Evanina Mackall Trust.

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