Effect of viagra on retinal vein diameter in AMD patients

doi:10.1016/j.exer.2005.11.012

Experimental Eye Research

Volume 83, Issue 1, July 2006, Pages 128-132

https://doi.org/10.1016/j.exer.2005.11.012 Get rights and content

Abstract

The aim of the present study was to investigate the effect of sildenafil citrate (viagra) on retinal venous diameter in patients with age-related macular degeneration (AMD). We investigated 14 male patients in a double-masked, randomized, placebo-controlled, crossover study. In each subject, one eye with typical non-exudative AMD fundus features was studied. Each of the subjects received 100 mg dose of sildenafil or matching placebo on two separate study visits. Monochromatic fundus photographs were obtained in the study eye before dosing and then 30, 90, 180 and 300 min later. Measurements of the diameter of the major retinal veins from digitized negatives were carried out using “Vessel map” static vessel analysis program (IMEDOS GmbH, Weimar, Germany). Statistical analysis of the data comparing the effect of sildenafil and placebo on venous diameters was performed using analysis of variance (ANOVA) for repeated measures. An analysis of variance (ANOVA) comparing the effects of sildenafil citrate and placebo on retinal vein diameters showed a significant interaction between time and treatment (P = 0.03). In comparison to placebo, sildenafil citrate produced a statistically significant vasodilatation of major retinal veins of 4.7% at 90 min (P = 0.004), 5.5% at 180 min (P < 0.0001) and 5.8% at 300 min (P < 0.0001). At 30 min there was a 2.2% difference, which was not statistically significant (P = 0.14). Our results suggest that in patients with age-related macular degeneration, sildenafil citrate (viagra) produces a statistically significant vasodilatation of major retinal veins that is similar to what has been reported in normal subjects. Whether this vasodilatation is associated with changes in retinal blood flow needs to be further investigated.

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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A double blind, placebo-controlled, crossover study on 15 patients with AMD (category 3 or worse of AREDS study and without choroidal neovascular membrane) receiving 100 mg sildenafil demonstrated that foveolar choroidal circulation parameters (relative choroidal blood velocity, volume and flow) did not change significantly on laser doppler flowmetry.127 In the same cohort of patients, these authors conducted another study (same study design but separate study visits with a wash out period of 3 or more days) and demonstrated a significant dilation of major retinal veins.128 The difference between the two studies was due to the fact that the retinal and choroidal circulations have different concentrations of target receptors to PDE5 inhibitors and thus may react differently.
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Effect of viagra on retinal vein diameter in AMD patients

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Ophthalmology

Ophthalmology

Am. J. Ophthalmol.

Surv. Ophthalmol.

Exp. Eye Res.

Am. J. Ophthalmol.

Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction

Int. J. Impot. Res.

Endothelium-derived relaxing and contracting factors

FASEB J.