Subjective visual halos after sildenafil (Viagra) administration: Electroretinographic evaluation

doi:10.1016/S0161-6420(00)00648-5

Ophthalmology

Volume 108, Issue 5, May 2001, Pages 877-881

https://doi.org/10.1016/S0161-6420(00)00648-5 Get rights and content

Abstract

Purpose

The ophthalmologic and electroretinographic (ERG) findings in one subject with subjective visual disturbances after sildenafil administration are described.

Design

Interventional case report.

Methods

A complete ophthalmologic examination was performed, including best-corrected visual acuity and ERG, repeated 1 and 2 hours after administration of 100 mg of sildenafil.

Main outcome measures

Rod responses were obtained over a range of retinal illuminances from those producing a minimum detectable response to those producing rod saturation. Intensity amplitude function was determined.

Results

At 2 hours after 100 mg of oral sildenafil, we observed significant variations from baseline in parameters of best-fit Naka-Rushton function; V_max was notably higher, and K was 0.14 log units lower than baseline.

Conclusions

Sildenafil administration resulted in a higher rod response to light stimuli and in a higher rod sensitivity. These findings are consistent with the weak PDE-6 inhibition induced by sildenafil.

Section snippets

Case report

A 69-year-old man was referred to our hospital. Family history was positive for glaucoma but negative for hereditary tapetoretinal degenerations.

Medical history showed hypertension that had been treated for 10 years. Four years previously, the subject underwent radical prostatectomy for adenocarcinoma with a bilateral nerve-sparing procedure. Eight months previously, after an endocrinologist consultation because of erectile dysfunction, he started 100 mg sildenafil at a dosage of one tablet

Discussion

To understand the effects of phosphodiesterase (PDE) inhibitors, it seems necessary to briefly summarize the role of cyclic guanine monophosphate (cGMP) in phototransduction.9 Bleached rhodopsin activates a guanosine-binding protein that then activates PDE of the rod outer segment, thereby inducing a light-dependent decrease in cGMP concentration and consequent rod hyperpolarization. PDE inhibition normally occurs in the dark. The inhibited PDE increases the intracellular concentration of cGMP,

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Cited by (35)

Sildenafil in ophthalmology: An update
2022, Survey of Ophthalmology
Citation Excerpt :
These parameters were still within normal limits. Gabrieli and coworkers reported a patient with ED on sildenafil for 8 months who complained of bluish vision and increased light sensitivity 1–2 hours after sildenafil intake.56 His electrophysiological testing revealed higher rod response to light and higher rod sensitivity.
Sildenafil citrate, a selective oral phosphodiesterase 5 inhibitor, is a widely used drug for erectile dysfunction that acts by elevating cGMP levels and causing smooth muscle relaxation. It also has 10% activity against PDE6, a key enzyme in phototransduction cascade in the retina. Recent ocular imaging developments have further revealed the influence of sildenafil on ocular hemodynamics, particularly choroidal perfusion. Choroidal thickness is increased, and choroidal perfusion is also enhanced by autoregulatory mechanisms that are further dependent on age and microvascular abnormalities. Studies demonstrating high intraocular pressure via a “parallel pathway” from increased choroidal volume and blood flow to the ciliary body have challenged previous concepts. Another new observation is the effect of sildenafil on bipolar cells and cyclic-nucleotide gated channels. We discuss potential deleterious effects (central serous chorioretinopathy, glaucoma, ischemic optic neuropathy, and risks to recessive carriers of retinitis pigmentosa), potential beneficial effects (ameliorate choroidal ischemia, prevent thickening of Bruch membrane, and promote recovery of the ellipsoid zone) in macular degeneration, as well as potential drug interactions of sildenafil.
Visual Hallucinations and Illusions
2018, Liu, Volpe, and Galetta's Neuro-Ophthalmology: Diagnosis and Management
Visual hallucinations and illusions comprise some of the most vivid and sometimes bizarre symptoms in neuro-ophthalmology. Hallucinations are defined as perceptions that occur in the absence of a corresponding external sensory stimulus. Visual hallucinations can be classified as unformed/simple (e.g., dots, flashes, zig-zags) or formed/complex (actual objects or people). In contrast, illusions are misinterpretations of a true sensory stimulus. Visual hallucinations and illusions are generally positive phenomena, in contrast to visual loss, which is a negative phenomenon.
The causes of visual hallucinations and illusions can be grouped into several major categories: migraine, release phenomena (in the setting of impaired vision), entoptic (ocular) phenomena, alcohol and drug-related, seizures, neurogenerative disease, central nervous system lesions, psychiatric disease, and narcolepsy. This chapter details the various categories, but first the history, examination, and diagnostic and therapeutic considerations in patients with hallucinations and illusions are reviewed.
Visual Loss: Retinal Disorders of Neuro-Ophthalmic Interest
2018, Liu, Volpe, and Galetta's Neuro-Ophthalmology: Diagnosis and Management
While a comprehensive review of all retinal disease is beyond the scope of this text, there are several entities that are particularly important in the neuro-ophthalmic differential diagnosis of central and peripheral visual loss and positive visual phenomenon. Patients with retinopathies may have symptoms and examination findings that may be similar to those that occur with optic nerve disease and cortically based conditions. These indicators may manifest as visual acuity loss, visual field defects, and a paucity of findings on ophthalmoscopic examination. Certain retinal disorders may also provide clues to the existence of an underlying neurologic illness or systemic disease. This chapter examines the relevant retinal anatomy, the distinction between maculopathy and optic neuropathies, maculopathies that may mimic optic neuropathy, retinal vascular occlusions, the photoreceptor disorders important in neuro-ophthalmic differential diagnosis (acute outer retinopathies, cancer-associated retinopathies), toxic and hereditary retinopathies of neuro-ophthalmic interest, and the retinal manifestations of neurologic and systemic diseases.
Effect of chronic administration of sildenafil citrate (Viagra) on the histology of the retina and optic nerve of adult male rat
2017, Tissue and Cell
Citation Excerpt :
Tests for visual performance, such as visual acuity and color discrimination are not particularly well suited for monitoring visual effects that are likely to be caused by the inhibition of PDE6. As sildenafil citrate is a treatment, not a cure, for erectile dysfunction, many men may choose to use it for an extended period (McMurray et al., 2007), and the implications of the long term-daily use of it on the retina and optic nerve are unclear (Sponsel et al., 2000; Gabrieli et al., 2001). So, this study was carried out to investigate the effect of chronic daily use of sildenafil citrate (Viagra), in a dose equivalent to men preferred therapeutic dose, on the histology of the retina and optic nerve of adult male rat using light and electron microscope.
Abnormal vision has been reported by 3% of patients treated with sildenafil citrate (Viagra). Although many men use Viagra for an extended period for treatment of erectile dysfunction, the implications of the long term-daily use of it on the retina and optic nerve are unclear.
To investigate the effect of chronic daily use of sildenafil citrate in a dose equivalent to men preferred therapeutic dose on the histology of the retina and optic nerve of adult male rat.
Eighteen adult male Wistar rats were equally divided into three groups. Group I: control. Group II: treated with sildenafil citrate orally (10 mg/kg/day) for 8 weeks. Group III (withdrawal): treated as group II and then left for 4 weeks without treatment. Specimens from the retina and optic nerve were processed for light and electron microscopy.
In sildenafil citrate treated group, the retina and optic nerve revealed vacuolations and congested blood capillaries with apoptotic endothelial and pericytic cells, and thickened basal lamina. Caspase-3 (apoptotic marker) and CD31 (endothelial marker) expression increased. Glial cells revealed morphological changes: Müller cells lost their processes, activated microglia, astrocytic clasmatodendrosis, degenerated oligodendrocytes surrounded by disintegrated myelin sheathes of the optic nerve fibers. The retina and optic nerve of the withdrawal group revealed less vacuolations and congestion, and partial recovery of the glial cells.
Chronic treatment with sildenafil citrate (Viagra) caused toxic effect on the structure of the retina and optic nerve of the rat. Partial recovery was observed after drug withdrawal.
Optic atrophy after sildenafil use
2007, Optometry
Citation Excerpt :
Vardenafil has a greater PDE-5 specificity and is the drug of choice to minimize related visual disturbances.15 A higher rod sensitivity and rod response to light has been measured by the electroretinogram (ERG) because of weak PDE-6 inhibition by sildenafil.16 The transient function changes of inner and outer retina, as detected by ERG, were fully reversible in healthy young men within 24 hours.2
It has been well-reported that phosphodiesterase-5 (PDE-5) inhibitors, originally investigated for their effect on smooth muscles and now used widely in treatment of erectile dysfunction, can cause mild transient visual disturbances because of their action on inhibiting enzymes involved in retinal transduction. Recently, these medications have been associated with the development of non-arteritic anterior ischemic optic neuropathy (NAAION) with attendant vision loss.
An older male patient, previously examined and ocularly healthy, presented asymptomatically with an occult optic neuropathy, not characteristic of NAAION. Neuroimaging and serology failed to reveal any other underlying cause. The patient did, however, report the use of sildenafil during the interval between his previously normal examination and the observation of his optic neuropathy.
This case details the development of an optic neuropathy with atrophy seemingly associated with the use of sildenafil, although no cause and effect could be conclusively found. This may indicate that medications used in the treatment of erectile dysfunction may be responsible for optic neuropathies other than NAAION.
Visual short-term effects of viagra: Double-blind study in healthy young subjects
2004, American Journal of Ophthalmology
Citation Excerpt :
This increased sensitivity during light adaptation may indicate either a decreased inhibitory action of the long wavelength (L+M)-cone system on the S-cone system or a change in inner retinal gain feedback, both of which would accord with a change in the inner retinal opponent processing of the cone signals.20 The possibility of inner retinal function being affected by sildenafil is also suggested by our ERG results, which do not accord with previous reports about significant, transient reductions in the a-wave and b-wave (rod-driven) ERG maximum response amplitudes.9,21 Like others,8,19 we found only small, nonsignificant changes in response amplitude in the sildenafil group.
To investigate short-term visual effects of a single 100-mg dose of Viagra (sildenafil citrate) in healthy men.
Randomized, double-blind, placebo-controlled clinical trial of drug effects on normal volunteers conducted by a single center.
Twenty men, aged 20 to 40 years, were treated with either a placebo or 100 mg sildenafil. Visual function tests included electroretinogram (ERG) recordings, on-/off- and 3.3 Hz-flicker-ERG recordings, anomaloscope matches, and measurements of cone contrast sensitivities and transient tritanopia.
Most visual tests did not differ between the sildenafil and placebo groups. However, statistically significant increases in sensitivity during transient tritanopia were observed as well as significant prolongations in the implicit times of scotopic a-wave, photopic b-wave, and 3.3 Hz-flicker a-wave and b-wave ERG recordings. The magnitude of the differences correlated with peak sidenafil plasma concentration. Although rod amplitudes of the ERG recordings tended to be higher and cone amplitudes lower in the sildenafil group after drug ingestion, the differences were nonsignificant. There were no reports of visual side effects, and all electrophysiologic and psychophysical measurements returned to the normal range within 24 hours.
A single oral dose of 100-mg sildenafil given to healthy young men led to small but statistically 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.

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¹: The authors have no affiliation with or financial interest in the subject matter or materials discussed in this article.

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Subjective visual halos after sildenafil (Viagra) administration: Electroretinographic evaluation

Abstract

Purpose

Design

Methods

Main outcome measures

Results

Conclusions

Section snippets

Case report

Discussion

Lancet

Surv Ophthalmol

Lancet

Lancet

Vision Res

J Urol

Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group [published erratum appears in N Engl J Med 1998;339:59]

N Engl J Med