Nonarteritic Anterior Ischemic Optic Neuropathy and Erectile Dysfunction Drugs: Is There an Elephant in the Bedroom?

Since 2002, various reports have proposed an association between phosphodiesterase-5 (PDE-5) inhibitors and nonarteritic anterior ischemic optic neuropathy (NAION) (1). It has been suggested that the vasodilatory effects of the drug promote nocturnal hypotension, which itself is a suspected trigger of NAION (2).

Letters to the Editor Nonarteritic Anterior Ischemic Optic Neuropathy and Erectile Dysfunction Drugs: Is There an Elephant in the Bedroom? S ince 2002, various reports have proposed an association between phosphodiesterase-5 (PDE-5) inhibitors and nonarteritic anterior ischemic optic neuropathy (NAION) (1). It has been suggested that the vasodilatory effects of the drug promote nocturnal hypotension, which itself is a suspected trigger of NAION (2). Many individuals who experience NAION after PDE-5 inhibitor use likely engaged in another activity in the hours preceding their vision loss—namely sexual intercourse. The very fact that men were using erectile dysfunction drugs suggests that intercourse was not a routine activity. Sexual activity has been associated with vision loss due to retinal hemorrhage (3) and angle closure glaucoma (4). It is a recognized risk factor for myocardial infarction (5). Should we not consider it as a possible risk factor for NAION? There is a scientifically plausible rationale why sexual activity may predispose to NAION. Studies have demonstrated that the physical exertion during sex is comparable to exercise (6,7), and postexercise hypotension is a well-established entity (8). It is, therefore, likely that a phenomenon of postcoital hypotension also exists. Should it occur during sleep, it would exacerbate nocturnal hypotension and predispose to NAION. How could it be that such a “routine” activity be overlooked for consideration as a risk factor? The vision loss would likely not occur during sexual activity or even while the individual was conscious afterward. The injury would occur during postcoital sleep. The person would only become aware of the injury many hours after it occurred, greatly reducing the possibility of considering an association with the previous night's activities. Furthermore, sexual intercourse may only be a minor risk factor, relevant in a predisposed individual with the recognized risk factors for NAION. Perhaps it is the combination of PDE-5 inhibitor use and sexual activity that “tips the balance” because both could independently cause nocturnal hypotension. The reality is that we generally do not ask our patients with NAION about their sexual behavior and, therefore, we cannot altogether rule out a connection. In fact, of the 22 case reports/series considered in a recent review of PDE-5 inhibitor use and NAION (1), the question of sexual activity was not documented in 28 of the 39 described patients. In the 11 remaining cases, sexual activity was reported for 5 patients (patient 5 (9), patients 1 and 2 (10), and case reports (11) and (12)), specifically denied in 3 patients, (patient 1 in (9) and (13) [same patient], patient 3 in (9) and (14) [same patient] and case report (15)), in one case 104 the patient was unable to achieve erection (16), and two of the cases occurred in children being treated for pulmonary hypertension (17,18). The fact that PDE-5 inhibitor–associated NAION has occurred independent of sexual activity justifies considering a direct effect of the drug. However, the possibility of an additional association between sexual activity and NAION may be worth exploring. Despite extensive research regarding NAION, the disorder remains an enigma both in terms of etiology and management. The issue of a possible association with PDE-5 inhibitors is relevant to many of our patients, and 16 years after the issue was raised (13), we are still advised to caution our patients against using these drugs despite the skepticism (1). Perhaps studies should be initiated to assess for a possible association between NAION and sexual activity. In the event that a causal relationship is found, patients might be advised to dissociate intimacy from sleep. The possibility that individuals with small cup–disc ratios are more likely to experience NAION after intercourse may force neuro-ophthalmologists to consider an age-long question in a different light: Does size really matter? Joshua M. Kruger, MD, PhD Department of Ophthalmology, Hadassah Medical Center, Kiryat Hadassah, Jerusalem, Israel Howard D. Pomeranz, MD, PhD Department of Ophthalmology, North Shore Long Island Jewish Health System, Great Neck, New York The authors report no conflicts of interest. REFERENCES 1. Pomeranz HD. The relationship between phosphodiesterase-5 inhibitors and nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 36;2:193–196. 2. Hayreh SS, Zimmerman MB, Podhajsky P, Alward WL. Nonarteritic anterior ischemic optic neuropathy: role of nocturnal arterial hypotension. Arch Ophthalmol. 1997;115:942–945. 3. Friberg TR, Braunstein RA, Bressler NM. Sudden visual loss associated with sexual activity. Arch Ophthalmol. 1995;113:738–742. 4. Markovits AS. Ophthalmodynia hypertonica copulatonis a new syndrome? Can J Ophthalmol. 1974;9:484–485. 5. Cheitlin MD. Sexual activity and cardiac risk. Am J Cardiol. 2005;96:24–28. 6. Palmeri ST, Kostis JB, Casazza L, Sleeper LA, Lu M, Nezgoda J, Rosen RS. Heart rate and blood pressure response in adult men and women during exercise and sexual activity. Am J Cardiol. 2007;100:1795–1801. 7. Frappier J, Toupin I, Levy JJ, Aubertin-Leheudre M, Karelis AD. Energy expenditure during sexual activity in young healthy couples. PLoS One. 2013;8:e79342. Letters to the Editor: J Neuro-Ophthalmol 2017; 37: 104-109 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor 8. MacDonald JR. Potential causes, mechanisms, and implications of post exercise hypotension. J Hum Hypertens. 2002;16:225–236. 9. Pomeranz HD, Smith KH, Hart WM, Egan RA. Sildenafilassociated nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 2002;109:584–587. 10. Pomeranz HD, Bhavsar AR. Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (viagra): a report of seven new cases. J Neuroophthalmol. 2005;25:9–13. 11. Tarantini A, Faraoni A, Menchini F, Lanzetta P. Bilateral simultaneous nonarteritic anterior ischemic optic neuropathy after ingestion of sildenafil for erectile dysfunction. Case Rep Med. 2012;2012:747658. 12. Bollinger K, Lee MS. Recurrent visual field defect and ischemic optic neuropathy associated with tadalafil rechallenge. Arch Ophthalmol. 2005;123:400–401. 13. Egan R, Pomeranz H. Sildenafil (Viagra) associated anterior ischemic optic neuropathy. Arch Ophthalmol. 2000;118: 291–292. 14. Cunningham AV, Smith KH. Anterior ischemic optic neuropathy associated with viagra. J Neuroophthalmol. 2001;21:22–25. 15. Dheer S, Rekhi GS, Merlyn S. Sildenafil associated anterior ischaemic optic neuropathy. J Assoc Physicians India. 2002;50:265. 16. Pepin S, Pitha-Rowe I. Stepwise decline in visual field after serial sildenafil use. J Neuroophthalmol. 2008;28:76–77. 17. Gaffuri M, Cristofaletti A, Mansoldo C, Biban P. Acute onset of bilateral visual loss during sildenafil therapy in a young infant with congenital heart disease. BMJ Case Rep. 2014;2014. 18. Sivaswamy L, Vanstavern GP. Ischemic optic neuropathy in a child. Pediatr Neurol. 2007;37:371–372. Invasive Aspergillosis Mimicking Sphenoid Wing Meningioma nerve were performed. Permanent sections demonstrated dense plasmacytic infiltrates, scattered regions of necrosis, and hyphae with positive Gomori methenamine silver staining and positive immunostaining for Aspergillus (Fig. 2). The patient was begun on amphotericin and posaconazole and then switched to voriconazole for long-term treatment of invasive aspergillosis. He underwent an unremarkable immune workup, including testing negative for HIV. Our case underscores that aspergillosis is a great mimicker, with highly variable neuroimaging patterns, and biopsy should be strongly considered in any case of presumed meningioma with atypical features such as vascular occlusion. Cavernous sinus meningioma is known to infiltrate or encase the wall of the internal carotid artery, but vascular occlusion is not a typical W e read with interest the recent articles by Hersh et al (1) on “Optic neuropathy and stroke secondary to invasive aspergillosis in an immunocompetent patient” and by Zhou et al (2) on “Apical orbital aspergillosis complicating giant cell arteritis.” We present a case of invasive aspergillosis, in which the diagnosis was delayed because of a protracted clinical course and neuroimaging findings suggestive of a sphenoid wing meningioma. A 68-year-old man from Nicaragua, with well-controlled hypertension and diabetes mellitus, was evaluated for a 1-year history of right-sided headaches, followed by diplopia, and sudden vision loss in his right eye. Brain computed tomography (CT) and cerebral angiography performed in Central America revealed a sphenoid wing and cavernous sinus lesion, suspected to be a meningioma, as well as occlusion of the right internal carotid artery. After neurosurgical evaluation, the patient was offered the option of pursuing radiation therapy for meningioma and traveled to the United States for radiation oncology evaluation. On our examination, vision was no light perception, right eye, and 20/40, left eye with an amaurotic right pupil. The right eye had complete ptosis and ophthalmoplegia, and there was decreased facial sensation in the distribution of the ophthalmic division of the right trigeminal nerve. Brain MRI demonstrated an abnormality along the right sphenoid wing with involvement of the right cavernous sinus and orbital apex (Fig. 1). The patient underwent a right pterional craniotomy, with frozen sections showing fungal hyphae. Exenteration of the right cavernous sinus, removal of the anterior and posterior clinoid processes, and excision of involved segments of the thrombosed right cavernous carotid artery and right optic Letters to the Editor: J Neuro-Ophthalmol 2017; 37: 104-109 FIG. 1. Postcontrast axial T1 MRI shows a right sphenoid wing lesion (arrows) with involvement of the right cavernous sinus and orbital apex. 105 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.