Effect of sildenafil on ocular hemodynamics in 3 months regular use

Abstract

The aim of this study was to evaluate the effect of sildenafil on ocular hemodynamics in a group of men with erectile dysfunction in 3 months regular use. A total of 15 patients with erectile dysfunction were included in this prospective study. All patients received 50 mg doses of sildenafil (Viagra, Pfizer) two times per week regularly for 3 months. The following examinations were performed on both eyes before and after sildenafil treatment: best-corrected visual acuity (BCVA), intraocular pressure (IOP), color vision, anterior segment, and fundus examination. Using color Doppler imaging, we measured hemodynamic variables in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary artery (SPCA). No significant changes in BCVA, color vision and IOP were found after sildenafil treatment. The anterior segment and fundus examinations showed no abnormalities. All Doppler parameters of OA, CRA, and SPCA remained nonsignificant for both eyes after sildenafil treatment. Oral sildenafil in 3 months regular use seems to have no effect on ocular hemodynamics.

Introduction

Sildenafil is an oral agent that is currently used in the treatment of erectile dysfunction. It is a potent and selective inhibitor of the human cGMP-specific phosphodiesterase type 5 enzyme (PDE 5) found in the vascular smooth muscle and also in human corpus cavernosum. The effect of sildenafil on natural erectile response to sexual stimulation is by potentiating the NO-cGMP pathway that increases corpus cavernosum smooth muscle relaxation.1, 2, 3, 4 There are some reports in the literature indicating the side effects of sildenafil on the ocular circulation. However, to our knowledge, there exists no data on the ocular hemodynamic effects of sildenafil in long-term use.

Color Doppler imaging (CDI) is a noninvasive, safe and easy method for measuring blood flow velocities of the retrobulbar circulation.

The purpose of this study is to analyze the effect of sildenafil on ocular hemodynamics in a group of men with erectile dysfunction in 3 months regular use.

Materials and methods

A total of 15 men with erectile dysfunction were included in the 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 exam, and laboratory findings. The diagnosis was confirmed by a score of 25 or less on the International Index of Erectile Function.5 All patients were in a stable sexual relationship. All patients had at least 6 months of erectile dysfunction. Patients with coronary artery disease, diabetes mellitus, systemic hypertension, and ocular diseases were excluded from the study. None of the participants were under any continous medication or any treatment with nitrates. An informed consent was obtained from all patients. The study followed the tenants of the Helsinki Declaration.

All patients had a best-corrected visual acuity (BCVA) of 20/20 or better and a normal intraocular pressure (IOP) of 21 mmHg or less. Anterior segment and fundus examinations of all patients were in the normal range. None of the patients had previous ocular surgery and were taking ophthalmological medication.

All patients received 50 mg doses of sildenafil (Viagra, Pfizer) two times per week regularly for 3 months. Sildenafil tablets were given by Pfizer. The following examinations were performed before and after 3 months regular use of sildenafil: BCVA, color vision, anterior segment biomicroscopy, applanation tonometry, and dilated fundus examination with 78 dioptri lens to evaluate the cup/disc ratio and color Doppler measurements.

CDI (EUB-555, Hitachi, Japan) was performed with a linear-array high-resolution 7.5 MHz probe. Evaluation was performed by an experienced radiologist (YD). While the patients were in the supine position looking straightforward with eyes closed, sterile ophthalmic gel was applied, and the probe was positioned gently with minimal pressure. Peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (MV) of ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCA) were measured in both orbits. During measurement of arterial flow velocities, angle correction was performed according to vascular flow direction. After measurement of the flow velocities, the resistivity index (RI) and pulsatility index (PI) were subsequently calculated by computer for each vessel measured. RI and PI are calculated as follows:

The results were expressed as mean±s.d. For statistical analysis, a Wilcoxon rank-sum test was used and P-value of <0.05 was considered statistically significant.

Results

Mean age of the patients was 49.6±7.9 (33–60). There was no significant effect of sildenafil on visual acuity, and color vision. None of the patients described any visual abnormalities after sildenafil. IOP and cup/disc ratios are shown in Table 1. No statistically significant difference in IOP was noted compared with baseline values (P>0.05, Table 1). Mean cup/disc ratio comparisons between baseline and after sildenafil did not reveal any significant difference (P>0.05, Table 1). After 3 months regular use, anterior and posterior segments examinations revealed no abnormalities. Tables 2, 3 and 4 present PSV, EDV, MV, RI and PI in the CRA, OA, and SPCA measured before and after 3 months regular use of sildenafil. All Doppler parameters of CRA, OA, and SPCA for both eyes remained nonsignificant compared with baseline (P>0.05, Tables 2, 3 and 4).

Table 1 Mean intraocular pressure and cup/disc ratio at baseline and after sildenafil treatment
Table 2 Color doppler ultrasound measurements at baseline and after sildenafil treatment in the ophthalmic artery
Table 3 Color doppler ultrasound measurements at baseline and after sildenafil treatment in the central retinal artery
Table 4 Color doppler ultrasound measurements at baseline and after sildenafil treatment in the short posterior ciliary artery

Discussion

Sildenafil is currently used in the treatment of erectile dysfunction. Sildenafil is a highly selective inhibitor of PDE5, responsible for the breakdown of cGMP in the corpus cavernosum.6, 7, 8 Inhibition of cGMP degradation induces the effect of nitric oxide on vascular smooth muscle relaxation in the corpus cavernosum and allows normal penile erection.9, 10

Sildenafil is an effective oral treatment agent in patients with impotence.11, 12 As this popular impotence drug is intended primarily in elderly patients, ophthalmologists need to know the pharmacological characteristics and potential side effects of the agent since age-related ocular diseases such as macular degeneration and numerous ocular vascular disorders threatens this population. Many of the adverse effects of sildenafil may be related to the presence of PDE5 in tissues other than the corpus cavernosum or to the effects of the drug on PDE6, which is an important component of the phototransduction cascade.4, 13, 14, 15 Vobig et al.16 evaluated electrophysiological and clinical tests after oral administration of 100 mg sildenafil and demonstrated a decrease in the a-wave and b-wave amplitudes in the electroretinogram. The alternations in the electroretinogram disappeared completely 6 h later. They did not observe any significant change in all other electrophysiological and clinical tests such as visual acuity, color vision, and IOP. Zrenner et al.17 investigated the effect of long-term sildenafil treatment on ocular safety in patients with erectile dysfunction and observed no statistically significant changes in visual acuity, color vision, and contrast sensitivity. Similar to these studies, we also did not observe any change in visual acuity, color vision, and IOP in our study.

The effect of sildenafil on ocular circulation has been investigated by various methods resulting in variant findings. Grunwald et al.18 found no significant change in optic nerve head or foveolar choroidal blood flow either 1 or 5 h after sildenafil treatment by laser Doppler flowmetry. However, Sponsel et al.19 reported a significant increase from baseline in pulsatile choroidal blood flow 110 min after administration of a 50 mg dose of sildenafil.

CDI is a safe, noninvasive and easy method to detect ocular blood flow velocities. It presents us peak systolic, end diastolic, mean velocities, pulsatility, and resistivity indices. CDI was found to present reproducible measures in the ophthalmic and central retinal arteries. However, the reproducibility of velocities from the posterior ciliary vessels is variable and thus less reliable.20

The hemodynamic effects of sildenafil in the eye have been investigated in humans by CDI. In our previous study, we examined the effect of a single oral dose of 50 mg sildenafil in a group of healthy young male volunteers by using CDI to measure hemodynamic variables in the OA, CRA, and SPCA before and 1 h after administration. Our results showed that while there was no change in Doppler indices for CRA and SPCA, PSV, EDV, and MV of OA increased significantly reflecting the vasodilator effect of sildenafil.21 Kurtulan et al.22 reported that after taking 100 mg of oral sildenafil citrate, there was no change on the hemodynamics of CRA on the basis of CDI at 60 and 75 min examination.

To our knowledge, no data are available on the ocular hemodynamic effects of sildenafil in long-term use in humans. Vatansever et al.23 studied the histopathologic effects of chronic use of sildenafil citrate on the retina and choroid of male rats. They found that chronic use of sildenafil citrate could cause dilatation and congestion in the choroidal vasculature of male rats. The results of the present study suggest that Doppler parameters of CRA, OA, and SPCA do not reveal any significant difference after 3 months regular use of sildenafil.

Sildenafil achieves its vasodilator effect by preventing the degradation of cGMP, thus augmenting the effect of NO, which is a potent vasodilator and plays an important role in the regulation of vascular tone.24, 25 There is evidence that ocular blood vessels are innervated by NO-producing neurons.26, 27 In acute phase, sildenafil may alter some Doppler parameters of ocular hemodynamics due to the vasodilator effect as reported in our previous study.21 Chronic use of sildenafil seems to have no effect on the ocular hemodynamics reflecting the temporary vasodilator effect not altering the orbital vasculature in chronic phase. Relatively small number of subjects and lack of a control group for comparison were the limitations of this study.

We conclude that sildenafil seems to have no effect on the ocular hemodynamics in long-term use. Further studies are needed to clarify the effects of sildenafil on ocular circulation and retinal function.

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Dündar, S., Dayanir, Y., Topaloğlu, A. et al. Effect of sildenafil on ocular hemodynamics in 3 months regular use. Int J Impot Res 18, 282–286 (2006). https://doi.org/10.1038/sj.ijir.3901416

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Keywords

  • sildenafil
  • color Doppler ultrasound
  • erectile dysfunction
  • central retinal artery
  • ophthalmic artery

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