Introduction

Sildenafil (Viagra, Pfizer) is an effective oral agent in treating erectile dysfunction. It inhibits the human cGMP-specific phosphodiesterase type 5 enzyme (PDE5) found in human corpus cavernosum.1, 2, 3, 4 Sildenafil also weakly inhibits phosphodiesterase type 6 (PDE6), that is, one-tenth of its affinity for PDE5. PDE6 is an important component of the phototransduction cascade and is present in high concentrations in cone and rod cells of the retina. Activated PDE6 hydrolyses cGMP, which reduces cGMP concentration in the outer segments of rods and cones. Reduction in cGMP concentration modulates sodium channels resulting in hyperpolarization of the photoreceptors.5, 6, 7, 8, 9, 10, 11, 12, 13 There are some reports in the literature reflecting the visual effects of sildenafil secondary to PDE6 inhibition. However, to our knowledge, there are no data on the effect of sildenafil on visual field analysis in long-term use.

This study was conducted to assess the effects of sildenafil on blue-on-yellow (B/Y) and white-on-white (W/W) Humphrey perimetry in a group of men with erectile dysfunction in 3 months regular use.

Materials and methods

A total of 14 men with erectile dysfunction were enrolled in this prospective study. Eligible patients were men older than 18 years of age who had a documented clinical diagnosis of erectile dysfunction based on clinical history, physical examination, and laboratory findings. The diagnosis was confirmed by a score of 25 or less on the international index of erectile function.14 All patients were in a stable sexual relationship. An informed consent was obtained from all subjects. The study was conducted in accordance with the tenets of the Helsinki Declaration.

All had a best-corrected visual acuity (BCVA) of 20/20 or better and normal intraocular pressure (IOP) of 21 mmHg or less. Anterior segment and fundus examinations of the patients were within the normal range. Patients were excluded if they had taken medications other than sildenafil. They were also excluded if they had eye disorders or previous ocular surgery

All patients received an oral dose of 50 mg sildenafil (given by Pfizer) two times per week regularly for 3 months. All underwent following examinations on both eyes before and after 3 months regular use of sildenafil: BCVA, colour vision (Ishihara), applanation tonometry, anterior segment, and dilated fundus examinations. The 30-2 program on the Humphrey visual field analyser (Humphrey Instruments Model 740, Carl Zeiss, USA) was used to assess visual fields. B/Y (FULLTHRESHOLD, size V stimulus) and W/W (SITA-STANDARD, size III stimulus) visual field testing was performed.

Baseline and after sildenafil treatment visual field tests were evaluated in terms of mean deviation (MD). Changes in MD were compared separately for both eyes after sildenafil treatment. The results were expressed as mean±standard deviation. Statistical analysis included a Wilcoxon rank-sum test. A P-value of less than 0.05 was considered statistically significant.

Results

Mean age of the patients was 48.5±7.2 (35–60) years. No significant changes in BCVA, colour vision, and IOP were observed after sildenafil treatment compared with baseline. None of the patients revealed any visual disturbances after sildenafil. Anterior and posterior segments examinations did not show any abnormality. There was no change on B/Y and W/W Humphrey perimetry tests. MD values of B/Y and W/W Humphrey perimetry tests remained nonsignificant for both eyes after 3 months regular use of sildenafil (P>0.05, Table 1).

Table 1 Mean deviation values in white-on-white and blue-on-yellow Humphrey perimetry tests at baseline and after sildenafil treatment
Full size table

Discussion

Sildenafil is a highly selective inhibitor of PDE5, responsible for the breakdown of cGMP in the corpus cavernosum.5, 15, 16 Sildenafil also weakly inhibits PDE6. The inhibition efficacy is about one-tenth of its affinity for PDE5. PDE6 is an important component of the phototransduction cascade.5, 6, 7, 8, 9

Many of the adverse effects of sildenafil may be related to the presence of PDE5 in tissues other than corpus cavernosum or to the effects of the drug on PDE6 which is present in cones and rods and plays a role in retinal light signal transduction. There are reports showing that some patients taking sildenafil have complained about increased sensitivity to light or a blue tinge to vision. Abnormal vision was dose dependent and reported by 3% of men receiving low doses of the drug (25–50 mg), 11% of men receiving 100 mg, and approximately 50% of men receiving more than 100 mg. These symptoms reach to the maximum level of 1 or 2 h after sildenafil administration and finally disappear in the 3rd or the 4th hour.4, 7, 17

Mild alternations were detected in colour vision after 100–200 mg sildenafil doses but this effect was transient.18, 19 Vobig et al20 studied electrophysiological and clinical tests after oral administration of 100 mg sildenafil and reported a decrease in the a-wave and b-wave amplitudes in the electroretinogram at 1 h after sildenafil administration, returning to normal at 6 h. They also found no effects of sildenafil on colour vision, visual acuity, and IOP. Zrenner et al21 evaluated the effect of long-term sildenafil treatment on ocular safety in patients with erectile dysfunction and found no significant changes from baseline in visual acuity, colour vision and contrast sensitivity. Our results are consistent with these reports.

The effects of sildenafil on visual field have been investigated recently. McCulley et al22 examined the effects of sildenafil on B/Y and W/W Humphrey perimetry. B/Y and W/W Humphrey perimetry tests were performed on healthy subjects before and 1 h after masked dosing of sildenafil 200 mg. Four of five sildenafil subjects had no change on Humphrey perimetry. However, one had a decrease in MD values both on B/Y and W/W Humphrey perimetry tests. Also, this subject reported more systemic side effects than other subjects. Birch et al23 evaluated the effects of a single 100 mg dose of sildenafil citrate on visual function in men with early stage age-related macular degeneration. They found that a single 100 mg dose of sildenafil produced no acute visual effects including no alternation on Humphrey visual field test or exacerbation of pre-existing visual impairment. Öner et al24 examined the effects of sildenafil citrate treatment on B/Y and W/W visual field analysis on 18 men with erectile dysfunction. All subjects (except for two who were administered 100 mg sildenafil to achieve satisfactory erection) received an oral dose of 50 mg sildenafil citrate. The visual field tests were done prior to treatment and 2 h after treatment with sildenafil citrate. They found that sildenafil causes no significant changes in Humphrey visual field analysis.

In the present study, unlike previous studies, we examined the effects of sildenafil on Humphrey perimetry in long-term use. We found that 14 of the 14 subjects had no change on W/W and B/Y Humphrey perimetry tests for both eyes after 3 months regular use of sildenafil. Also, MD values of W/W and B/Y Humphrey perimetry tests remained nonsignificant for both eyes after 3 months regular use of sildenafil.

In conclusion, this study shows that oral sildenafil in 3 months regular use seems to have no effect on the W/W and B/Y Humphrey perimetry in patients with erectile dysfunction. Further investigations are needed to clarify the effects of sildenafil on retinal function.