Sildenafil-Induced Nonarteritic Anterior Ischemic Optic Neuropathy in a Patient With Pulmonary Hypertension

Letters to the Editor Facebook of a lotus pod flower. She began to see the same vivid image on walls, faces, and even with her eyes closed (Fig. 1). Although the patient understood the image was not real, it caused anxiety and insomnia. The lotus pod image appeared in different visual fields and would either appear randomly or triggered by patterns that reminded her of a lotus pod. She avoided coworkers who wore clothing similar to the lotus pod pattern and took precautions to avoid viewing flowers in her apartment complex. She reported a tactile sensation, described it as "feeling of things crawling on me but seeing nothing there," which differed from the "tingling or fuzzy" sensation associated with her paresthesias. Acetazolamide was discontinued with almost immediate resolution of all symptoms within 1 week. The patient refused a rechallenge. The pathophysiology of palinopsia is still unclear but hypotheses include an exaggeration of normal afterimage, seizure disorder, psychogenicity, or drug induction. Drugs with serotonin receptor activity, such as LSD, trazodone, and nefazodone, are known to cause drug-induced palinopsia (4). In our patient, palinopsia was induced by acetazolamide, a potent carbonic anhydrase inhibitor (5). After a thorough literature review, we found no other medications that inhibit carbonic anhydrase reported to induce palinopsia, except topiramate. The mechanisms of action of topiramate are unclear but include direct or indirect action on serotonin receptors and weak inhibition of Type II and Type IV carbonic anhydrase (5). Because topiramate and acetazolamide share carbonic anhydrase inhibition and not serotonin activity, it seems plausible that carbonic anhydrase inhibition maybe a mechanism that induces palinopsia. Our case highlights an unanticipated and previously undocumented side effect of acetazolamide. Palinopsia induced by medication maybe underreported due to patient Sildenafil-Induced Nonarteritic Anterior Ischemic Optic Neuropathy in a Patient With Pulmonary Hypertension W e read with interest the review article by Pomeranz (1) on the role of erectile dysfunction medications as a cause of nonarteritic anterior ischemic optic neuropathy (NAION). We evaluated a patient who developed NAION when taking sildenafil for the treatment of pulmonary hypertension. A 56-year-old woman reported segmental left visual field loss, which she described as a "veil." This was associated with heaviness in her left scalp. She had systemic lupus erythematous, which was treated with long-term low-dose corticosteroids. Complications of her lupus included glomerulonephritis and pulmonary hypertension with left ventricular failure, for which she had been prescribed sildenafil, 348 reluctance to report this unusual symptom. We encourage physicians to inquire about visual disturbances associated with acetazolamide. Peggy H. Vogt, BS FSU College of Medicine, Tallahassee, Florida Garrett Barr, BS TMH Foundation HealthCare, Tallahassee, Florida Charles G. Maitland, MD FSU College of Medicine, Tallahassee, Florida TMH Foundation HealthCare, Tallahassee, Florida The authors report no conflicts of interest. REFERENCES 1. Yun SH, Lavin PJ, Schatz MP, Lesser RL. Topiramate-induced palinopsia: a case series and review of the literature. J Neuroophthalmol. 2015;35:148-151. 2. Belcastro V, Aguglia U, Pisani LR, Ferlazzo E. Palinopsia and other reversible visual disturbances induced by topiramate. J Neuroophthalmol. 2015;35:329-330. 3. Meadows JC, Munro SS. Palinopsia. J Neurol Neurosurg Psychiatry. 1977;40:5-8. 4. Hoyt WF, Walsh FB, Miller NR, Newman NJ; Ovid Technologies Inc. Walsh and Hoyt's Clinical NeuroOphthalmology, 6th edition. Philadelphia, PA: Lippincott Williams & Wilkins, 2005. 5. Mula M. Topiramate and cognitive impairment: evidence and clinical implications. Ther Adv Drug Saf. 2012;3: 279-289. 10 mg 3 times daily. She had been on this medication for 7 years. She also had well-controlled blood pressure for which she was taking furosemide, 20 mg/d. On examination, visual acuity was 20/20 in left eye, with a left relative afferent pupillary defect and mild left optic disk swelling. She had a superior altitudinal visual field defect in her left eye and a cup-to-disc ratio of 0.7. Visual field testing in the right eye was entirely normal and the right cup-to-disc ratio was normal. She had a sedimentation rate of 42 mm/h and a C-reactive protein of 4 mg/L (normal #5.0 mg/L). Complete blood count and serum chemistries were normal, and there was no evidence of active lupus vasculitis. Because of rapid evolution of vision loss, she was admitted for further investigation and for pulsed intravenous methylprednisolone. Sildenafil also was discontinued. A temporal artery biopsy was performed and was negative for giant cell arteritis. At discharge from hospital, her visual field defect was slightly improved. Letters to the Editor: J Neuro-Ophthalmol 2016; 36: 343-352 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor To date there are 4 reported cases of patients developing NAION when on Sildenafil for pulmonary hypertension. The first was a 6-year-old girl who underwent surgical repair of coarctation of the aorta at age 2 years and mitral valve replacement with pacemaker insertion at age 4 years. She presented with a several month history of monocular vision loss and was found to only have light perception in her left eye. She was treated with sildenafil for 15 months before her presentation for pulmonary hypertension (2). The second report was that of a 63-year-old woman with a history of chronic renal failure on hemodialysis after cadaveric kidney transplant, aortic valve replacement, atrial fibrillation, peripheral vascular disease, arterial hypertension, and pulmonary hypertension managed with sildenafil 50 mg 3 times daily. She subsequently developed bilateral NAION. (3) The third case was a 7-month-old girl who was treated with sildenafil for recurrent chylothorax and presumed increased pulmonary vascular resistance on a background of a complex congenital cyanotic heart defect with cavopulmonary anastomosis surgery at age 4 months. Four weeks later, she went on to develop NAION, which resulted in bilateral visual loss despite sildenafil cessation and treatment with corticosteroids (4). It seems that patients with pulmonary hypertension treated with sildenafil may be at risk of developing NAION. We alert clinicians to this possible association. Linda Zheng, MBBS (Hons), MMed Katherine M. Miller, MBBS (Hons) Department of General Medicine, Sydney Eye Hospital, Sydney Hospital, Sydney, Australia Role of GABAergic System in Blepharospasm T wo articles "Benign essential blepharospasm is a disorder of neuroplasticity: Lessons from animal models" (1) and "Benign essential blepharospasm- There is more to it than just blinking" (2) clearly summarized the findings of recent animal and clinical studies about the potential candidate factors that may contribute to blepharospasm according to the so-called "2-hit" hypothesis. We propose the GABAergic system as an additional trigger factor that may be clinically relevant. Many hypotheses have been suggested about what may cause benign essential blepharospasm (BEB); however, the cause of this disorder is still unclear. To answer this question, we have been investigating cerebral functional alterations in patients with blepharospasm using positron emission tomography (PET). Letters to the Editor: J Neuro-Ophthalmol 2016; 36: 343-352 Eugene Kotlyar, MBBS, MD, MPVD, FRACP, FCSANZ, FPHSANZ Department of General Medicine, Sydney Eye Hospital, Sydney Hospital, Sydney, Australia Department of Cardiology, St Vincent's Hospital, Darlinghurst, Australia Raymond Garrick, MBBS (Hons), FRACP, FFPM, ANZCA Department of General Medicine, Sydney Eye Hospital, Sydney Hospital, Sydney, Australia Department of Neurology, St Vincent's Hospital, Darlinghurst, Australia The authors report no conflicts of interest. REFERENCES 1. Pomeranz HD. The relationship between phosphodediesterase-5 inhibitors and nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2016;36:193-196. 2. Sivaswamy L, Van Stavern GP. Ischemic optic neuropathy in a child. Pediatr Neurol. 2007;37:371-372. 3. Prat NM, Sanchez-Dalmau BF, Foroozan R. Not just for men. Surv Ophthalmol. 2011;56:173-177. 4. 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;3:2014. In one of our first studies, we analyzed cerebral glucose metabolism in 25 patients with BEB using PET and 18Ffluorodeoxyglucose and observed cerebral glucose hypermetabolism in the thalamus in patients with BEB compared with healthy subjects (3). Our findings suggested that hyperactivity of the thalamus and the basal ganglia-thalamocortical motor circuit may be contributing causes of BEB (4,5). Digre (2) discussed the 2-hit hypothesis with regard to BEB. This hypothesis includes both a predisposition (e.g., genetic) and an environmental trigger (e.g., dry eyes, blepharitis) to develop BEB. Blepharospasm also has been reported in individuals on long-term regimens of neuropsychiatric drugs, such as benzodiazepines and thienodiazepines (drug-induced blepharospasm) (6,7). We studied cerebral glucose metabolism in 21 patients with drug-induced blepharospasm, 24 healthy subjects with a long-term history of benzodiazepines use ("drug healthy" group), 21 patients with BEB, and 63 healthy control subjects (8). We observed glucose hypermetabolism in the 349 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.