Effect of Viagra on 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.
References (34)
- et al.
A double-blind placebo-controlled evaluation of the acute effects of sildenafil citrate (Viagra) on visual function in subjects with early-stage age-related macular degeneration
Am. J. Ophthalmol.
(2002) - et al.
Increased scleral rigidity and age-related macular degeneration
Ophthalmology
(1989) - et al.
Ocular blood flow velocity in age-related macular degeneration
Ophthalmology
(1995) - et al.
Effect of sildenafil citrate (Viagra) on retinal blood vessel diameter
Am. J. Ophthalmol.
(2002) - et al.
Effect of sildenafil citrate (Viagra) on the ocular circulation
Am. J. Ophthalmol.
(2001) - et al.
Bilateral macular drusen in age related macular degeneration: prognosis and risk factors
Ophthalmology
(1994) - et al.
Sildenafil (Viagra) and ophthalmology
Surv. Ophthalmol.
(1999) - et al.
Choroidal perfusion abnormality with age-related Bruch's membrane change
Am. J. Ophthalmol.
(1990) - et al.
Sildenafil-associated nonarteritic anterior ischemic optic neuropathy
Ophthalmology
(2002) - et al.
Laser-Doppler flowmetry in the optic nerve
Exp. Eye. Res.
(1992)
Refractive error and choroidal perfusion characteristics in patients with choroidal neovascularization and age-related macular degeneration
Ger. J. Ophthalmol.
Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction
Int. J. Impot. Res.
A case of nonarteritic ischemic optic neuropathy (NAION) in a male patient taking sildenafil
Int. J. Clin. Pharmacol. Ther.
Functional loss in age-related Bruch's membrane change with choroidal perfusion defect
Invest. Ophthalmol. Vis. Sci.
Anterior ischemic optic neuropathy associated with Viagra
J. Neuroophthalmol.
Effect of sildenafil on ocular haemodynamics
Eye
Sildenafil (Viagra) associated anterior ischemic optic neuropathy
Arch. Ophthalmol.
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