Anterior Ischemic Optic Neuropathy Due to Calciphylaxis

A 72-year-old woman experienced anterior ischemic optic neuropathy in her left eye. The funduscopic and fluorescein angiographic findings were strongly suggestive of giant cell arteritis. Temporal artery biopsy revealed extensive calcification in the vessel wall consistent with calciphylaxis. This unusual disorder should be considered in the differential diagnosis of anterior ischemic optic neuropathy, particularly the arteritic form.

Photo Essay Section Editor: Timothy J. McCulley, MD Anterior Ischemic Optic Neuropathy Due to Calciphylaxis Magne S. Sivertsen, MD, PhD, Erik H. Strøm, MD, Kim M. A. Endre, MD, Øystein K. Jørstad, MD FIG. 1. A. Left fundus shows pale optic disc swelling. B. Fluorescein angiogram at 32 seconds after injection reveals areas of delayed choroidal perfusion around the optic disc. Abstract: A 72-year-old woman experienced anterior ischemic optic neuropathy in her left eye. The funduscopic and fluorescein angiographic findings were strongly suggestive of giant cell arteritis. Temporal artery biopsy revealed extensive calcification in the vessel wall consistent with Departments of Ophthalmology (MSS, ØKJ), Pathology (EHS) and Dermatology (KMAE), Oslo University Hospital, Oslo, Norway. The authors report no conflicts of interest. Address correspondence to Øystein K. Jørstad, MD, Oslo University Hospital, Eye Department, P.b. 4950 Nydalen, 0424 Oslo, Norway; E-mail: [e-mail] 54 calciphylaxis. This unusual disorder should be considered in the differential diagnosis of anterior ischemic optic neuropathy, particularly the arteritic form. Journal of Neuro-Ophthalmology 2018;38:54-56 doi: 10.1097/WNO.0000000000000581 © 2017 by North American Neuro-Ophthalmology Society A 72-year-old woman was evaluated for what she believed was a change in the vision of her left eye. She had hypertension, chronic atrial fibrillation, type 2 Sivertsen et al: J Neuro-Ophthalmol 2018; 38: 54-56 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay FIG. 2. A. Temporal artery biopsy with calcifications within the intimal (black arrows) and muscular (white arrows) layers which were partially lost during processing (hematoxylin & eosin, ·100). B. Skin biopsy with calcifications (arrowheads) in the walls of subcutaneous small vessels and partial occlusion of the lumen (hematoxylin & eosin, ·400). C. Radiograph of the left foot shows calcification (arrowheads) in blood vessels posteriorly above the calcaneus and below the metatarsal bones. diabetes mellitus, and rheumatoid arthritis. She denied headache, jaw claudication, or symptoms of polymyalgia rheumatica, but had been repeatedly hospitalized during the last year for painful leg ulcers with recurrent bacterial infections. Medications included prednisolone, 5 mg/d and methotrexate, 17.5 mg/wk. Visual acuity (VA) was 20/25 FIG. 3. Lateroposterior view of right calf 3.5 (A) and 5 months (B) after initial evaluation by the dermatology service shows progression from severe skin necrosis to a large non-healing ulcer with necrosis. Sivertsen et al: J Neuro-Ophthalmol 2018; 38: 54-56 in both eyes. Apart from mild cataract and posterior vitreous detachment, examination of the left eye was normal including confrontation of visual fields. Two days later the patient awoke with dramatically reduced vision in her left eye. On examination, VA was hand motion in the left eye with a left relative afferent pupillary defect. VA of the right eye was 20/25. The appearance of the right fundus was normal with a cup/disc ratio of 0.4. In the left eye, there was pallid optic disc swelling (Fig. 1A). On physical examination, there was no tenderness over her temples or scalp with good pulsation of the temporal arteries. Fluorescein angiography exhibited choroidal hypoperfusion in a pattern suggestive of occlusion of one or more of the posterior cillary arteries (Fig. 1B) and late leakage from the optic disc. Erythrocyte sedimentation rate was 57 mm/h; C-reactive protein 28 mg/L (normal: ,4 mg/L); calcium corrected for albumin 2.56 mmol/L (normal: 2.17-2.53 mmo/L); phosphate 1.36 mmol/L (normal: 0.9-1.5 mmol/L); creatinine 33 mmol/L (normal: 45-90 mmol/L); and parathyroid hormone 3.5 pmol/L (normal: 1.4-8.6 pmol/L). Temporal artery biopsy showed extensive medial and intimal calcification consistent with calciphylaxis (Fig. 2A, B). There were no inflammatory signs of arteritis. The patient's leg ulcers had been treated for a year without signs of improvement (Fig. 3). Several diagnoses had been considered including calciphylaxis, given the results of skin biopsies, the presence of leg ulcers, and by arterial calcification visible on radiographs of the feet 55 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay (Fig. 2C). The temporal artery biopsy findings reinforced the calciphylaxis diagnosis and eventually intravenous sodium thiosulfate treatment was instituted. With the introduction of thiosulfate treatment, the leg ulcers showed signs of improvement over several months. VA of the left eye remained hand motion, whereas the right eye maintained normal visual function. Calciphylaxis is a rare but serious condition that initially causes intensely painful, necrotic skin lesions typically located on the arms and legs. First described in the 1960's (1,2), reports of calciphylaxis have increased considerably in recent decades (3-5). The proposed mechanism for the pain and necrosis is ischemia due to obstruction or severely reduced blood flow in affected arterial walls due to calcium deposition. Most patients diagnosed with calciphylaxis suffer from end-stage renal disease. Vascular calcification also has been reported on histologic examination of lungs, brain, eyes, skeletal muscle, mesentery, and intestines (3). Calciphylaxis may occur as a complication of various medications including corticosteroids, warfarin, calcitrol, calcium salt, and vitamin D (3). Comorbidities associated with calciphylaxis are diabetes mellitus, obesity, autoimmune and hypercoagulable conditions, and hepatitis (3). Our patient had been treated with corticosteroids, warfarin, vitamin D, and calcium carbonate for many years and had diabetes mellitus and rheumatoid arthritis. Six case reports of sudden visual loss in patients with calciphylaxis have been published (6-10). Two of these patients developed bilateral visual loss. In all the eyes examined, a swollen optic disc was described within days of the onset of symptoms. All patients had end-stage renal failure. Five patients received high-dose systemic corticosteroids as they were initially suspected of having giant cell arteritis (GCA). In summary, calciphylaxis can cause anterior ischemic optic neuropathy. Results of fluorescein angiography indicate that the underlying pathophysiologic mechanism is equivalent to that proposed for the other clinical manifestations of calciphylaxis, namely ischemia due to obstruction or severely reduced blood flow. In our patient, this led to the involvement of short posterior cillary arteries (11). Given the systemic consequences of calciphylaxis and its potential to mimic GCA, this disorder should be kept in mind when evaluating a patient with anterior ischemic optic neuropathy. 56 STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: Magne Sand Sivertsen; Erik H. Strøm; Kim Magnus Advocaat Endre; and Øystein Kalsnes Jørstad; b. Acquisition of data: Magne Sand Sivertsen; Erik H. Strøm; Kim Magnus Advocaat Endre; and Øystein Kalsnes Jørstad; c. Analysis and interpretation of data: Magne Sand Sivertsen; Erik H. Strøm; Kim Magnus Advocaat Endre; and Øystein Kalsnes Jørstad. Category 2: a. Drafting the manuscript: Magne Sand Sivertsen; Erik H. Strøm; Kim Magnus Advocaat Endre; and Øystein Kalsnes Jørstad; b. Revising it for intellectual content: Magne Sand Sivertsen; Erik H. Strøm; Kim Magnus Advocaat Endre; and Øystein Kalsnes Jørstad. Category 3: a. Final approval of the completed manuscript: Magne Sand Sivertsen; Erik H. Strøm; Kim Magnus Advocaat Endre; and Øystein Kalsnes Jørstad. ACKNOWLEDGMENTS The authors thank Rowan Thomas Faber for his assistance in proof-reading the manuscript. REFERENCES 1. Anderson DC, Stewart WK, Piercy DM. Calcifying panniculitis with fat and skin necrosis in a case of uraemia with autonomous hyperparathyroidism. Lancet. 1968;2:323-325. 2. Rees JK, Coles GA. Calciphylaxis in man. Br Med J. 1969;2:670-672. 3. Nigwekar SU, Kroshinsky D, Nazarian RM, Goverman J, Malhotra R, Jackson VA, Kamdar MM, Steele DJ, Thadhani RI. Calciphylaxis: risk factors, diagnosis, and treatment. Am J Kidney Dis. 2015;66:133-146. 4. Gertner E. Calciphylaxis: a not-so-rare pseudovasculitis syndrome. J Clin Rheumatol. 1999;5:210-214. 5. Kyttaris VC, Timbil S, Kalliabakos D, Vaiopoulos G, Weinstein A. Calciphylaxis: a pseudo-vasculitis syndrome. Semin Arthritis Rheum. 2007;36:264-267. 6. Hanna RM, Nabil JR, Lopez EA, Corry DB, Wilson J. 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Sivertsen et al: J Neuro-Ophthalmol 2018; 38: 54-56 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.