Effect of sildenafil citrate (viagra)on the ocular circulation

Sildenafil citrate induces vasodilation by enhancing the smooth muscle relaxant effects of nitric oxide. We have previously reported that nitrate compounds, a different group of nitric oxide–mediated vasodilators used mainly for the treatment of ischemic cardiac diseases, produce an increase in optic nerve head circulation and retinal venous vasodilation. The purpose of the present investigation was to evaluate the effect of sildenafil on ocular circulation.

METHODS: In a double-blind, randomized, crossover trial, 15 healthy male volunteers received 100-mg doses of sildenafil citrate ( Viagra ; Pfizer, Inc, New York, New York) or matching placebo on 2 separate days. Laser Doppler flowmetry was used to assess foveolar choroidal and optic nerve rim circulatory parameters. Measurements were obtained in one eye at baseline, 1 hour, and 5 hours after dosing. Blood pressure and intraocular pressure were monitored, and perfusion pressure was calculated.

RESULTS: Mean optic nerve head blood flow measurements at baseline, 1 hour, and 5 hours were 11.6 ± 2.2 arbitrary units (± SD), 12.5 ± 2.8, and 12.1 ± 2.4 after sildenafil and 11.9 ± 2.5, 12.6 ± 3.1, and 13.0 ± 3.0 after placebo, respectively. When compared with placebo, no significant change in mean blood pressure, intraocular pressure, perfusion pressure, or choroidal or optic nerve circulatory parameters were observed after sildenafil treatment. The power to detect a 20% change in optic nerve head and choroidal blood flow after sildenafil was approximately 90%.

CONCLUSIONS: In comparison with placebo, no significant change in optic nerve rim or foveolar choroidal blood flow was observed after treatment with sildenafil. This suggests that nitrate compounds and sildenafil may differentially affect ocular circulation. Furthermore, no significant effects on intraocular pressure, systemic blood pressure, or ocular perfusion pressure were detected after sildenafil treatment.

Sildenafil, a selective cyclic guanosine monophosphate–dependent phosphodiesterase type 5 inhibitor, induces vasodilation by enhancing the smooth muscle relaxant effects of nitric oxide.[1, 2, 3 and 4] The enhanced dilation of blood vessels and lacunar spaces in the corpus cavernosum leads to improved penile erection in patients with erectile dysfunction. [5] This compound was originally developed for treatment of cardiac ischemic conditions because of its vasodilatory effect. [6]

We have previously reported that nitrate compounds, another group of nitric oxide–mediated vasodilators used mainly for the treatment of ischemic cardiac diseases, produce an increase in optic nerve head circulation[7] and retinal venous vasodilation. [8] In addition to its vasodilatory properties, sildenafil also has a somewhat lower affinity for phosphodiesterase type 6, [3] an important component of the phototransduction cascade. This has led to some questions regarding some of the visual side effects of sildenafil, [9] such as difficulty in blue-green color discrimination and transient blurry vision. One of the questions we wanted to address was whether changes in the ocular circulation could perhaps explain some of these visual side effects. Thus, the main purpose of this investigation was to assess the effects of sildenafil on the circulation of the choroid and the optic nerve in a group of normal volunteers.

Patients and methods

A randomized, placebo-controlled, crossover study of the effects of sildenafil citrate (Viagra; Pfizer, Inc, New York, New York) was performed in 15 healthy male volunteers with normal eyes. Volunteers aged 30 years or older (39 ± 8 years, average ± SD) with visual acuity of 20/25 or better were included in the investigation. All subjects had a normal intraocular pressure of 21 mm Hg or less and a normal eye examination. None of the subjects was receiving nitrate therapy. Subjects provided written informed consent.

Laser Doppler flowmetry (Oculix, Inc, Berwyn, Pennsylvania), a noninvasive state-of-the-art technique was used to assess the circulation of the optic nerve and choroid. A very weak laser beam was delivered to the eye through a fundus camera. The light scattered back from the fundus was electronically analyzed to provide measurements of relative blood velocity, blood volume, and blood flow in the vascular tissues studied. Measurements of relative choroidal blood velocity, volume, and flow were obtained from the center of the foveola by asking subjects to fixate on the probing laser beam. Measurements of relative optic nerve blood velocity, volume, and flow were taken from the superotemporal and inferotemporal neuroretinal rim tissue, and the values of these two sites were averaged to provide the optic nerve head blood flow. Measurements were obtained in the right eye of each subject. Detailed descriptions of the technique have been previously reported.[10, 11 and 12]

After baseline flow determinations were obtained, intraocular pressure was measured by Goldmann applanation tonometry, and brachial artery systemic blood pressure was assessed by automated sphygmomanometry. Perfusion pressure was estimated as two thirds of the mean blood pressure minus the intraocular pressure. Immediately after these procedures, subjects received 100 mg of oral sildenafil or matching placebo. The placebo tablet was identical to the sildenafil tablet but did not contain the active compound. Measurements of blood flow and blood pressure were repeated 1 hour and 5 hours after subjects received the study drug. In every subject, all procedures were repeated on a second day (at least 3 days later), and the alternate study drug was tested. Procedures were performed in a blinded fashion. Patients and investigators did not know which drug was administered on each occasion. Individuals masked to the treatment modality carried out the analysis of the blood flow data. Individuals were not under fasting conditions during the study.

Statistical analysis of the data was performed using an analysis of variance (ANOVA) for repeated measures comparing the effects of sildenafil with those of placebo. Linear regression and correlation analyses were also performed. Statview software was employed in the analysis of these data. Findings with an error probability smaller that 0.05 were considered to be statistically significant.

References

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2. J.Y. Jeremy, S.A. Ballard, A.M. Naylor, M.A.W. Miller and G.D. Angelini, Effects of sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. Br J Urol 79 (1997), pp. 958–963. View Record in Scopus | Cited By in Scopus (164)

3. S.A. Ballard, C.J. Gingell, K. Tang, L.A. Turner, M.E. Price and A.M. Naylor, Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 159 (1998), pp. 2164–2171. Abstract | Full Text + Links | PDF (1074 K) | Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (352)

4. R.B. Moreland, I. Goldstein and A. Traish, Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells. Life Sci 62 (1998), pp. 309–318.

5. M. Boolell, M.J. Allen, S.A. Ballard et al., Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 8 (1996), pp. 47–52. View Record in Scopus | Cited By in Scopus (554)

Full article

American Journal of Ophthalmology
Volume 131, Issue 6, June 2001, Pages 751-755
Source: Health & Place
Volume 13, Issue 4, December 2007, Pages 904-911