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The current study is only representative of visual safety following a single dose. There are some reports that have looked at visual function after longterm intermittent dosing with Sildenafil in patients with erectile dysfunction. Consistent with our findings, Zrenner et al[5] found no clinically significant changes from baseline in visual acuity, contrast: sensitivity, or photostress tests following administration of Sildenafil at doses of 50 to 200mg for 12 weeks, followed by doses of 25mg to 100mg for 40 weeks on an asneeded basis in men with erectile dysfunction. The most frequently reported AEs (flushing, rhinitis, and headache) are well known AEs of Sildenafil that are usually mildtomoderate in severity[6]. Openlabel longterm extension studies have not revealed any increase in ocularrelated AEs or any unusual ocular AEs that were not reported during doubleblind clinical trials[11]. Further reassuring postmarketing data have been obtained from a variety of sources, including new clinical research studies, spontaneous reports, surveillance studies, epidemiologic studies, and the National Registry of Drug Induced Ocular Side Effects[12].
However, testing of visual function after longterm treatment with Sildenafil has not been performed prospectively in subjects with eye disorders.
The most common type of visual AE, bluegreen color discrimination occasionally reported at higher doses of Sildenafil, was examined in some detail in a phase II study. In a doubleWind placebocontrolled crossover trial in 16 healthy male volunteers, significant changes in FM 100hue scores were observed only at 1 or 2 hours after a single acute dose of Sildenafil[4]. At 1 hour, mean FM 100hue total error scores were 75±40 for 100mg and 102±56 for 200mg, compared with a placebo score of 53±36(P<0.05). At 2 hours, the total error score for subjects receiving 200mg Sildenafil was 99±64 compared with 56±33 for subjects receiving placebo (P<0.05). No significant changes were measured at 4 hours postdose. These changes were regarded as mild, transient, and fully reversible occurrences that coincided with the time of the peak plasma drug concentration[4].
The effects of Sildenafil on blood flow in the eye could have important implications for patients with AMD or other eye disorders. Published reports thus far have indicated that Sildenafil has no significant effect on intra ocular pressure[13,14]. The effects on the ocular circulation specifically have, to this point, been variable. Grunwald et al[15] have reported no significant changes in choroidal or optic nerve head blood flow after acute doses of 100mg Sildenafil, whereas Sponsel et al[16] reported a significant increase in pulsatile ocular blood flow. Hence, the vasodilatory properties of Sildenafil do not seem to be producing a decrease in ocular blood flow. However, there are isolated case reports of nonarteritic anterior ischemic optic neuropathy (AION) in the literature since Sildenafil became available for clinical use in the United States[16,17]. In controlled clinical trials, no cases of AION were reported during 11000 personyears of exposure to Sildenafil[18]. Clear attribution has been difficult, because AION is the most common acute optic nerve disorder among middleaged and elderly adults. In most cases, risk factors such as predisposing illness, diabetes mellitus, hypertension, or an anatomic risk factor such as a small optic nerve head (disk at risk) has been present. Certainly, the appearance of these cases warrants careful monitoring to detect any emerging pattern.
In 2004 Herbert and associates investigated shortterm visual effects of a single oral 100mg dose of Viagra in healthy young men. The single dose led to small but statically significant transient changes of outer and inner retinal function, as detected by ERG and psychophysical methods. Although the acute effects were fully reversible within 24 hours, it would be worthwhile to compare them with those induced by other PDE5 and PDE6 inhibitors[19]. Favorable results from the current study showed that there were no significant acute changes in visual function after a single dose of Sildenafil in a sample of men with earlystage AMD which were similar to David and associates who studied the effect of a single 100mg dose of Sildenafil and came to the conclusion that it was well tolerated and produced no acute visual effects or exacerbation of preexisting visual impairment in nine men with earlystage AMD[20].
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