The effect of sildenafil citrate (Viagra ® ) on visual sensitivity Institute of Ophthalmology, University College London, London, UK Andrew Stockman Institute of Ophthalmology, University College London, London, UK Lindsay T. Sharpe Moorfields Eye Hospital, London, UK Adnan Tufail Whittington Hospital Highgate Hill and Institute of Urology, Middlesex Hospital, London, UK Philip D. Kell Institute of Ophthalmology, University College London, London, UK Caterina Ripamonti Institute of Ophthalmology, University College London, London, UK Glen Jeffery The erectile dysfunction medicine sildenafil citrate (Viagra ® ) inhibits phosphodiesterase type 6 (PDE6), an essential enzyme involved in the activation and modulation of the phototransduction cascade. Although Viagra might thus be expected to impair visual performance, reports of deficits following its ingestion have so far been largely inconclusive or anecdotal. Here, we adopt tests sensitive to the slowing of the visual response likely to result from the inhibition of PDE6. We measured temporal acuity (critical fusion frequency) and modulation sensitivity in four subjects before and after the ingestion of a 100-mg dose of Viagra under conditions chosen to isolate the responses of either their short-wavelength-sensitive (S-) cone photoreceptors or their long- and middle-wavelength-sensitive (L- and M-) cones. When vision was mediated by S-cones, all subjects exhibited some statistically significant losses in sensitivity, which varied from mild to moderate. The two individuals who showed the largest S-cone sensitivity losses also showed comparable losses when their vision was mediated by the L- and M-cones. Some of the losses appear to increase with frequency, which is broadly consistent with Viagra interfering with the ability of PDE6 to shorten the time over which the visual system integrates signals as the light level increases. However, others appear to represent a roughly frequency-independent attenuation of the visual signal, which might also be consistent with Viagra lengthening the integration time (because it has the effect of increasing the effectiveness of steady background lights), but such changes are also open to other interpretations. Even for the more affected observers, however, Viagra is unlikely to impair common visual tasks, except under conditions of reduced visibility when objects are already near visual threshold. Keywords: Viagra, sildenafil citrate, visual sensitivity, temporal sensitivity, temporal resolution, light adaptation, visual transduction, PDE6 Citation: Stockman, A., Sharpe, L. T., Tufail, A., Kell, P. D., Ripamonti, C., & Jeffery, G. (2007). The effect of sildenafil citrate (Viagra ® ) on visual sensitivity. Journal of Vision, 7(8):4, 1–15, http://journalofvision.org/7/8/4/, doi:10.1167/7.8.4. Introduction Since its approval in 1998, over 1 billion doses of sildenafil citrate (Viagra) have been prescribed as a treatment for erectile dysfunction (Pfizer, 2007). It works by inhibiting cyclic guanosine monophosphate (cGMP)- specific phosphodiesterase type 5 (PDE5), which is an enzyme expressed in the smooth muscle of the corpus cavernosa (Beavo, 1995; Moreland, Goldstein, & Traish, 1998). As an undesirable secondary effect, it inhibits a closely related phosphodiesterase enzyme PDE6 (e.g., Wallis, Casey, Howe, Leishman, & Napier, 1998). Estimates suggest that Viagra has about 10% of the effect on PDE6 that it has on PDE5 (Food and Drug Adminis- tration Joint Clinical Review, 1998a; see Table 1 of Laties & Zrenner, 2002). PDE6 plays an essential role in phototransduction, the process by which photons of light are absorbed and converted into electrical signals for transmission to the visual centers of the brain. Activated PDE6 (PDE6*) catalyzes the hydrolysis of cGMP to GMP. The reduction in cGMP results in the closure of ion Journal of Vision (2007) 7(8):4, 1–15 http://journalofvision.org/7/8/4/ 1 doi: 10.1167/7.8.4 Received September 22, 2006; published June 8, 2007 ISSN 1534-7362 * ARVO