Effect of viagra on retinal vein diameter in AMD patients
Introduction
Sildenafil citrate (viagra), the first oral drug approved for the treatment of erectile dysfunction, selectively inhibits phosphodiesterase 5 (PDE5), the isozyme that metabolizes cyclic guanosine monophosphate (c-GMP) in the corpus cavernosum (Boolell et al., 1996). In addition to the corpus cavernosum smooth muscle, PDE5 is also found in other human tissues including vascular smooth muscle (Pfizer, Investigative Brochure). Endothelium-derived relaxing factors, such as nitric oxide (NO) (Furchgott and Vanhoutte, 1989, Ignarro et al., 1987) produce smooth muscle relaxation and dilatation of blood vessels due to the increase in levels of cGMP (Furchgott and Vanhoutte, 1989, Gruetter et al., 1981, Ignarro and Kadowitz, 1985). By blocking PDE5 sildenafil increases the levels of c-GMP and thus greatly enhances the dilating effects of NO on the vascular smooth muscle.
This vasodilatory quality of sildenafil is of great interest because of the potential use of this type of compound in the treatment of vascular occlusive disease. Indeed several investigators have studied the effects of sildenafil on the retinal vessel diameter in normal subjects (Grunwald et al., 2002, Pache et al., 2002, Polak et al., 2003). Vasodilatation induced by sildenafil in the human retina was reported by some studies (Pache et al., 2002, Polak et al., 2003), but not all (Grunwald et al., 2002).
In this study we investigate the effect of sildenafil on the retinal vessel diameter in patients with age-related macular degeneration (AMD). Previous reports of Friedman et al., 1989, Friedman et al., 1995, Grunwald et al., 1998, Grunwald et al., 2005 and Pauleikhoff et al. (1990) have suggested that impairment of the choroidal circulation may play an important role in the etiology of this disease. Little is known however, about the retinal vasculature changes in this disease. Sato et al. (2005) has shown using laser Doppler velocimetry that pulsatily in retinal arteries is higher in patients with AMD than healthy controls. The exact implications of this finding are not known but suggest that perfusion abnormalities go beyond the choroid in patients with age-related macular degeneration. Because the vasculature of the fundus seems to be affected by AMD it is important to study whether sildenafil affects the vasculature of AMD patients. A previous study of Metelitsina et al. (2005) did not show any statistically significant effect of sildenafil on the choroid of AMD patients. In this study we investigate the effect of sildenafil on the retinal vasculature of AMD patients.
Section snippets
Materials and methods
Fourteen male AMD patients (13 Caucasians and 1 African-American) with a mean age of 75 ± 7 years (±1SD) were included in this double-masked, randomized, placebo-controlled, crossover study. AMD features of enrolled patients were similar or worse than those present in eyes graded as AMD category 3 in the AREDS study. Only one eye of each patient was included in the study. Study eyes had clear ocular media, intraocular pressure (IOP) of 21 mm Hg or less, pupillary dilatation of 5 mm or more, steady
Results
Mean retinal venous diameters at baseline, 30, 90, 180 and 300 min for sildenafil and placebo treatments are shown in (Table 1, Fig. 2). An analysis of variance (ANOVA) comparing the effects of sildenafil citrate and placebo on retinal veins diameters showed a significant interaction between time and treatment (P = 0.03), therefore, comparisons of both treatments at each time point were performed.
In comparison to placebo, sildenafil citrate caused a statistically significant vasodilatation of
Discussion
In this current study we investigated the effect of sildenafil on retinal vessel diameter in patients with AMD. Sildenafil citrate produced statistically significant dilatation of major retinal veins at 90, 180 and 300 min in this group of patients.
The effect of sildenafil on the retinal vessel diameters of AMD patients has not been studied before. Our previous study on the effects of sildenafil on the choroidal circulation of AMD patients did not show any statistically significant differences
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