Bilateral Posterior Ischemic Optic Neuropathy Associated With Use of Sildenafil

Abstract

We report a case of sequential posterior ischemic optic neuropathy after the use of sildenafil. A 76-year-old man with a history of systemic hypertension, hyperlipidemia, and stroke presented to our clinic with the sudden onset of sequential visual loss in his eyes. His usual medications were 50 mg atenolol daily and 90 mg diltiazem daily for hypertension and 10 mg simvastatin daily for hyperlipidemia. In addition, he had started taking a Chinese “health product” 7 weeks earlier. His usual dose was one capsule once a day or one capsule every other day, but he had stopped it 20 days earlier until 2 days before presentation, when he consumed three capsules all at once one morning. Approximately 36 hours after ingesting the three capsules, he experienced sudden visual loss in the left eye. He awoke the next morning and discovered blurred vision in the right eye and presented to our clinic. He reported no pain or headache or any symptoms of systemic hypotension such as dizziness, cold sweats, or feeling faint. He admitted to habitually drinking approximately 500 mL of beer a day but did not smoke. He had been compliant with his antihypertensive medications. Toxicologic analysis revealed 32.22 mg sildenafil in each capsule of the Chinese health product. He had no light perception in either eye. Both pupils were dilated and unreactive to light. Intraocular pressures were normal, and apart from the presence of mild cataracts and cup-to-disc ratios of 0.8 bilaterally, anterior and posterior segments were normal including the retinas. Both optic discs appeared pink. Blood pressure throughout his subsequent 5-day stay in hospital averaged 130/80 mm Hg, ranging between 120/60 and 130/90 mm Hg. Complete blood count, erythrocyte sedimentation rate, and C-reactive protein, creatinine, VDRL, folate, and vitamin B12 levels were normal. Results of liver function testing were normal apart from decreased albumin (32 g/L; normal = 37-51 g/L) and elevated -glutamyltransferase (80 IU/L; normal = 11-63 IU/L). No mitochondrial DNA mutation at nucleotides 3460, 11778, or 14484 was found. Contrast-enhanced MRI scans with angiography of the brain and orbits was normal. Electroretinography was normal, and visual evoked potentials were absent. After 6 weeks, visual acuity improved to count fingers in the right eye and hand movements in the left eye. Both optic discs were pale. Nonarteritic anterior ischemic optic neuropathy has been reported to occur 30 minutes to 36 hours after ingestion of the phosphodiesterase-5 (PDE-5) inhibitor sildenafil (1,2), and a cause-and-effect relationship has been suggested.(3) We believe our patient suffered sequential nonarteritic posterior ischemic optic neuropathy (PION), which may occur in the setting of systemic vascular disease as well as systemic hypotension. Visual loss in our patient began approximately 36 hours after a relatively large dose (96.66 mg) of sildenafil. The short duration between the onset of visual loss in both eyes in the absence of other events that would have caused a drop in blood pressure, within a relatively short interval of taking the increased dose of sildenafil, suggests a possible role for that agent in the development of his visual loss. Diltiazem may have contributed by inhibiting cytochrome P450 3S4, the isoenzyme predominantly responsible for the metabolism of sildenafil (4) and prolonging the duration of action of sildenafil. To our knowledge, PION has not been reported in association with sildenafil. We postulate that a sildenafil-induced decrease in blood pressure (6), together with vasculopathic risk factors and antihypertensive therapy, contributed to its development. Daniel Hsien-Wen Su, FRCSEd *Singapore National Eye Centre Singapore Pei-San Ang, BSc (Pharm) †Centre For Drug Administration Health Sciences Authority Singapore Sharon Lee-Choon Tow, FRCSEd ‡Singapore National Eye Centre Singapore [email protected]