Journal of Neuro-Ophthalmology:
Anterior Ischemic Optic Neuropathy Associated With Viagra
Cunningham, Ariana V. MD; Smith, Kyle H. MD
From the Department of Surgery, Division of Ophthalmology, Scott & White Memorial Hospital and Clinic, Scott, Sherwood and Brindley Foundation, Texas A&M University System Health Science Center College of Medicine, Temple, Texas.
Manuscript received September 19, 2000; accepted January 3, 2001.
Address correspondence and reprint requests to Ariana V. Cunningham, MD, Scott & White Clinic, 2401 South 31st Street, Temple, TX 76508.
A 42-year-old male presented with acute onset of an inferior visual field defect OD after sildenafil citrate use. Examination revealed a right relative afferent pupillary defect and a swollen disc with a 0.1 cup-to-disc ratio and a prominent disc hemorrhage.Anterior ischemic optic neuropathy (AION) is associated with acute episodes of hypotension in patients with structurally crowded discs. Sildenafil citrate may cause episodes of hypotension and was temporally related to the onset of symptoms in this patient. Because patients are often reluctant to volunteer their history of sildenafil citrate use, the physician may need to ask specifically about use of this medication. Physicians should counsel patients with crowded optic discs and a history of nonarteritic anterior ischemic optic neuropathy in one eye that use of sildenafil citrate might increase their risk of ischemic optic neuropathy in the fellow eye.
Studies have shown therapeutic doses of sildenafil (25–100 mg) reduce mean peak systolic and diastolic blood pressures by approximately 10 mm Hg (1). The male examined developed anterior ischemic optic neuropathy (AION) less than 24 hours after taking a dose (50 mg) of sildenafil citrate (Viagra; Pfizer US Pharmaceutical Group, New York, NY). We believe this case supports a possible association between the use of sildenafil citrate and AION. The rationale for this association is supported in our review of the pathophysiology of AION and the mechanism of action of sildenafil citrate.
A 42-year-old male with a history of depression and sexual dysfunction began taking sildenafil citrate (50 mg). The first dose was taken without adverse effect. One week later, he took a second dose. Twelve hours later, he noted the onset of an aching sensation behind the right eye that was exacerbated with eye movement. No discomfort was noted on the left. The following night, he took a third dose; the next morning, he noted blurred vision OD, which he described as dimness of the entire inferior half of his visual field. Ophthalmologic examination revealed a right-sided relative afferent pupillary defect and swelling of the right optic disc superiorly, suggesting a right-sided optic neuropathy. The patient was then referred to us for neuro-ophthalmologic evaluation.
The patient's past medical history was significant only for depression and sexual dysfunction. He had no history of hypertension or hypotension. The patient's only medication other than sildenafil was sertraline for depression.
Before this event, he had no history of ocular disease except for a congenital color vision deficiency. His family history showed no optic nerve problems or sudden blindness. His wife, a nurse, had positive results from a purified protein derivative (PPD) skin test. Review of systems was noncontributory.
Initial neuro-ophthalmologic examination revealed a best corrected visual acuity of 20/20 OU. Color vision testing with Hardy-Rand-Rittler (HRR) plates revealed only 7 of 10 correct OU. Automated visual fields (Humphrey 30-2) revealed a dense, inferior, altitudinal defect as well as a superior arcuate-type defect in the right eye (Fig. 1). Central vision above the midline was spared. The visual field OS was normal. Pupils were briskly reactive with a right-sided relative afferent pupillary defect. There was no proptosis. Ocular motility was normal. Biomicroscopy of the anterior segment was unremarkable. Intraocular pressures were 15 mm OU. Dilated fundus exam OD revealed prominent swelling of the superior aspect of the disc with a disc rim hemorrhage (Fig. 2). Funduscopy of the left eye revealed a healthy appearing, but crowded, disc with a cup-to-disc ratio of 0.1. The vessels, macula, and peripheral retina were normal OU.
Although the funduscopic picture was most consistent with AION, we also considered the possibility of an inflammatory optic neuropathy (optic neuritis), because the patient reported pain with eye movement. We, therefore, initiated an evaluation for possible inflammatory causes. Laboratory testing revealed a normal antinuclear antibody titer, an erythrocyte sedimentation rate of 10, a normal complete blood count, a nonreactive fluorescent treponemal antibody absorption test, and a normal tuberculosis skin test. A chest radiograph was unremarkable. A magnetic resonance image (MRI) scan of the brain with gadolinium and fat suppression demonstrated optic nerves that appeared normal and no white matter lesions suggestive of demyelinating disease.
The absence of any evidence of a systemic inflammatory disorder, and the presence of structurally crowded discs, led us to conclude that the patient had experienced an episode of AION rather than an inflammatory optic neuropathy. The patient was counseled to discontinue using sildenafil citrate and to monitor his blood pressure regularly. No other treatment was initiated. The patient noted a step-wise progression of visual loss OD for three weeks after the initial episode. Repeat visual fields at 1 month showed diffuse depression with loss of the central island of vision (Fig. 3). The visual acuity at last follow-up evaluation, 1 year after initial presentation, was 20/200 OD and 20/20 OS. The disc swelling and hemorrhage had resolved with residual superior optic atrophy (Fig. 4).
The pathophysiology of AION is poorly understood and remains the focus of considerable debate (2). Hayreh (3) suggested that the problem is localized to the posterior ciliary arteries in the disc and the retrolaminar area. He demonstrated that occluding the posterior ciliary arteries in monkeys causes infarction of the retrolaminar and laminar portions of the optic nerve. Axoplasmic flow is consequently reduced and disc swelling results (4). Hayreh later demonstrated that complete occlusion of the posterior ciliary arteries is not essential to produce AION. In 1970, he showed that the circulation in the optic disc, peripapillary choroid, and choroid is dependent upon the difference between the intraocular pressure and perfusion pressure in the posterior ciliary arteries. When an imbalance results, as in a sudden and marked systemic arterial hypotension, AION may result. Hayreh (5) also suggested that nocturnal hypotension may be an important precipitating factor in the pathophysiology of AION. He demonstrated through 24-hour ambulatory blood pressure monitoring that nocturnal hypotension may act as the final insult leading to ischemia and AION in optic nerves that have been rendered vulnerable to ischemia by predisposing factors. Clinical support for the role of nocturnal hypotension in triggering AION comes from other studies done by Hayreh (6) that found that 73.3% of patients with AION noticed their visual loss upon awakening, either in the morning or from a nap.
Hoyt (7) was the first researcher to note that some discs have certain anatomic features that seem to predispose them to AION. Burde (8) coined the term “disc at risk” to describe these structurally crowded discs characterized by a small nerve head with a small or absent physiologic cup, abnormal branching of the central vessels, and full nerve fiber bundles obscuring the disc margin.
The patient described in this report had optic discs with the structural anatomy described as disc at risk. His initial presentation was characteristic of AION with disc swelling and nerve fiber layer hemorrhages and subsequent optic atrophy. The altitudinal nature of his initial visual field defect was also typical for AION. His progressive visual field defect over time is a well-recognized phenomenon seen in as many as 29% of eyes during the first month after the initial event (9).
The retrobulbar pain with eye movement, although more suggestive of inflammatory optic neuropathy, is reported by 10% of patients with AION (10). Our laboratory evaluation revealed no evidence of an underlying autoimmune process, vasculitis, or infection. The initial disc appearance, absence of subsequent improvement in visual function, and eventual profound optic atrophy would be atypical for demyelinating optic neuritis. Furthermore, the patient had no history of neurologic symptoms or MRI lesions to suggest systemic demyelinating disease. For all of these reasons, we are confident that our patient had an ischemic, rather than inflammatory, optic neuropathy.
Sildenafil citrate is the first of a new group of oral agents approved for managing male erectile dysfunction that acts directly on the penile vasculature (11). During sexual stimulation, the cavernous nerves release nitric oxide (NO), which induces cyclic guanosine monophosphate (cGMP) formation and leads to smooth muscle relaxation and increased blood flow to the corpus cavernosum. The result is an erection (12). Phosphodiesterase type 5 (PDE5) is a naturally occurring enzyme, found in high concentrations in the corporis cavernosum, that breaks down cGMP. Sildenafil citrate selectively inhibits PDE5, thus blocking the breakdown of cGMP and facilitating the erectile process (13). The NO-cGMP pathway also plays an important role in modulating systemic blood pressure through its effect on basal vascular tone.
We believe that sildenafil citrate may have contributed to the episode of AION in our patient. The sildenafil citrate may have accentuated his physiologic nocturnal hypotension enough to decrease the perfusion pressure in the posterior ciliary arteries. This effect resulted in ischemia in a disc that was already predisposed to AION by the anatomic disc-at-risk configuration. The temporal relationship between the doses of sildenafil citrate and the onset of visual loss make it difficult to accept the notion that these were unrelated coincidental events.
To date, there has been only one other published case report temporally linking an episode of AION to sildenafil citrate (14). We are aware of two similar cases of anterior ischemic optic neuropathy related to sildenafil citrate use (oral communication with Howard Pomeranz, MD). We also examined another patient who reported sildenafil citrate use the night before experiencing acute visual loss in one eye from AION. However, the patient, a 60-year-old male, had experienced a previous episode of AION in the fellow eye several months before his first dose of sildenafil citrate. He, like our reported patient, had bilateral disc-at-risk anatomy.
We suggest that a complete review of medications, including specific questions about sildenafil citrate use, is essential in the evaluation of patients with signs and symptoms of AION. Some patients may be reluctant to volunteer information about their use of sildenafil citrate because of the stigma associated with erectile dysfunction. Our patient, for example, did not inform us about his sildenafil citrate use until his wife was absent on one of the follow-up visits. We believe sildenafil citrate is relatively contraindicated in patients with a history of AION. In addition, it may be reasonable to counsel patients with bilateral disc-at-risk anatomy to be cautious about using sildenafil citrate or any other medication that might cause hypotension.
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