Comments on a Case Entitled "Gazing Into the Crystal Ball"

Letters to the Editor Andrew G. Lee, MD Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas Lynn K. Gordon, MD, PhD Ophthalmology, Stein Eye Institute, UCLA, Los Angeles, California Alfredo A. Sadun, MD, PhD Ophthalmology, Doheny Eye Institute, UCLA, Los Angeles, California Greg Van Stavern, MD Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, Missouri Comments on a Case Entitled “Gazing Into the Crystal Ball” W e read with interest the case report by Cherayil et al (1), detailing a patient with crystalline deposits, retinal arteriolar whitening, disc pallor, iris neovascularization, and calcinosis cutis. The authors attributed the constellation of findings to a rare condition called calciphylaxis. Clinically, calciphylaxis is characterized by the presence of intensely painful necrotic ulcerating lesions of the skin because of an obliterative intradermal and subcutaneous arteriolopathy (2). The authors do not report that their patient developed such lesions. The histological hallmark is of dermal and subcutaneous adipose capillary medial and intimal calcification, with frequent fibrin thrombi causing occlusion (2). The presented histological images demonstrate calcinosis cutis and not calciphylaxis, the former not being a histological precursor of the latter. It would be useful to know what the visual function and fundus appearance were preoperatively. The possibility of perioperative nonarteritic ischemic optic neuropathy (NAION) comes to mind. Patients with end-stage renal disease (ESRD) are already at a greater risk of NAION, even after adjustment for diabetes, hypertension, and hypotension (3). They are often anemic, have atherosclerosis, and widespread vascular calcification, visible on plain radiographs and even within the ophthalmic artery on computed tomography (4). Such considerations make ocular ischemia unsurprising in this patient. Similar retinal arteriolar calcification has been reported in 3 patients with ESRD, 2 of which did not have systemic calciphylaxis, but were more striking in appearance than the other (5–7). It is also noteworthy that 8 cases of vision impairment with clinically and histologically confirmed calciphylaxis in the ophthalmic literature do not report such a finding (6,8–14). Only one of these cases also had crystale536 The authors report no conflicts of interest. REFERENCES 1. Sadun A, Gordon L. Should tocilizumab be used routinely in new patients with a diagnosis of giant cell arteritis? J Neuroophthalmol. 2020;40:117–121. 2. Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Schett G, Schulze-Koops H, Spiera R, Unizony SH, Collinson N. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377:317–328. line retinal deposits (6). An optical coherence tomography might be useful in determining whether the crystals in the presented case were due to high oxalate (15). As the authors outlined, calciphylaxis has been suggested as the cause of a number of ischemic optic neuropathy cases (6,8–14). Three of these erroneously diagnosed calciphylaxis based on temporal artery calcification alone (16–18). Currently, the ophthalmic findings of patients with true calciphylaxis cannot be disentangled from those because of ESRD. Hence, the term “ocular calciphylaxis” is not truly defined, and its relationship with skin calciphylaxis is not determined, but warrants further study. In our view, the authors have made a significant leap from calcinosis cutis to calciphylaxis, and we would argue there was insufficient evidence presented in favor of this. The crystal ball is perhaps not always crystal clear. Rupa D. Patel, BSc, MSc, BM, FRCOphth Department of Neuro-Ophthalmology, Moorfields Eye Hospital, London, United Kingdom Smeeta Sinha, MBChB, MRCP, PhD Salford Royal Hospital NHS Foundation Trust, Salford, United Kingdom Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, United Kingdom There authors report no conflicts of interest. REFERENCES 1. Cherayil NR, Scoles D, Moran AM, Elder DE, Tamhankar MA. Gazing into the crystal ball: calciphylaxis causing striking retinal vascular calcification, ocular ischemic syndrome, crystalline retinopathy, and ischemic optic neuropathy. J Neuroophthalmol. 2021;41:e212–e214. Letters to the Editor: J Neuro-Ophthalmol 2022; 42: e533-e538 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor 2. Nigwekar SU, Thadhani R, Brandenburg VM. Calciphylaxis. N Engl J Med. 2018;378:1704–1714. 3. Chang YS, Weng SF, Chang C, Wang JJ, Su SB, Huang CC, Wang JY, Jan RL. Risk of nonarteritic anterior ischemic optic neuropathy following end-stage renal disease. Medicine (Baltimore). 2016;95:e3174. 4. Goldenberg-Cohen N, Naftaliev E, Millmond SH, Segev Y, Reider-Groswasser I. Ophthalmic artery calcification in a patient with renal failure. Neuroradiology. 2001;43:1005–1006. 5. Patel DV, Snead MP, Satchi K. Retinal arteriolar calcification in a patient with chronic renal failure. Br J Ophthalmol. 2002;86:1063. 6. Naysan J, Dansingani KK, Balaratnasingam C, Mrejen S, Levasseur S, Merkur A, Yannuzzi LA. Crystalline retinopathy and retinal vasculopathy in calcific uremic arteriolopathy (calciphylaxis). Retin Cases Brief Rep. 2018;12:331–335. 7. Mishra C, Kannan N, Chakrabarti A, Kumar M, Ramasamy K. Retinal arteriolar calcification and ischemic retinopathy in a patient with chronic kidney disease. Indian J Ophthalmol Case Rep. 2021;1:337. 8. Huerva V, Sánchez MC, Ascaso FJ, Craver L, Fernández E. Calciphylaxis and bilateral optic neuropathy. J Fr Ophtalmol. 2011;34:651–654. 9. Awwad ST, Ghosn S, Hogan RN. Calciphylaxis of the temporal artery masquerading as temporal arteritis. Clin Exp Ophthalmol. 2010;38:511–513. 10. Hepschke JL, Masselos K, Sandbach J, Fraser CL. Seeing the difference-Painless progressive vision loss in a vasculopath. Surv Ophthalmol. 2019;64:123–131. 11. Sivertsen MS, Strøm EH, Endre KMA, Jørstad ØK. Anterior ischemic optic neuropathy due to calciphylaxis. J Neuroophthalmol. 2018;38:54–56. 12. Komurcu HF, Basar E, Kucuksahin O, Uz E, Orhun Yavuz HS, Anlar O. Bilateral optic neuropathy, acral gangrene and visceral ischaemia as a rare presentation of calciphylaxis: a case report. J Pak Med Assoc. 2016;66:1324–1326. 13. Sekulic M, Truskinovsky AM. Metaplastic ossification of the temporal artery with osteoclast-like giant cells: a mimicker of giant cell (temporal) arteritis. Eur J Ophthalmol. 2017;27:e99–103. 14. Chi M, Kim HJ, Basham R, Yoon MK, Vagefi R, Kersten RC. Temporal artery calciphylaxis presenting as temporal arteritis in a case of rhinoorbitocerebral mucormycosis. Ophthalmic Plast Reconstr Surg. 2015;31:e132–e135. 15. Gershoni A, Dotan G, Gal-Or O. Multimodal imaging findings in primary hyperoxaluria. Ophthalmol Retina. 2018;2:1169. 16. Korzets A, Marashek I, Schwartz A, Rosenblatt I, Herman M, Ori Y. Ischemic optic neuropathy in dialyzed patients: a previously unrecognized manifestation of calcific uremic arteriolopathy. Am J Kidney Dis. 2004;44:e93–e97. 17. Roverano S, Ortiz A, Henares E, Eletti M, Paira S. Calciphylaxis of the temporal artery masquerading as temporal arteritis: a case presentation and review of the literature. Clin Rheumatol. 2015;34:1985–1988. 18. Farooqui S, Chan A, Cullen JF, Milea D. Too young to undergo temporal artery biopsy? Calciphylaxis-related anterior ischemic optic neuropathy. Neuroophthalmology. 2019;43:252–255. Gazing Into the Crystal Ball Photo Essay: Response tial involvement of the contralateral eye, are unique and would be unusual for ESRD alone. We speculate that cataract surgery likely served as an insult for progressive calcium deposition leading to patient's abrupt clinical presentation much as skin trauma is believed to be a potential trigger for the development of cutaneous calcifications in patients with ESRD with repeated insulin injections (3,4) and in a single animal model (5). Usually, however, no trigger is identified in those with cutaneous calcification or calciphylaxis in setting of ESRD. The readers point out several reported cases of histologically confirmed cases of calciphylaxis with ophthalmic involvement that did not have retinal vascular calcification (6–13), and conversely, retinal arteriolar calcification reported without systemic calciphylaxis (14,15). We believe appearance of retinal vascular calcification/crystalline retinopathy and bilateral optic neuropathy in conjunction with profound vision loss is particularly unique in our case. Several cases of biopsy-proven calciphylaxis report ischemic optic neuropathy mimicking GCA (7,8,10,11). There has also been a single case report of isolated crystalline and ischemic retinopathy in a patient with a history of confirmed cutaneous calciphylaxis (6). We did consider retinal oxalosis on the differential diagnosis of crystalline retinopathy, noting that oxalosis has a unique deposition pattern in the RPE, Bruch membrane, and choriocapillaris (6,16). Notably, intravascular crystalline deposition is a less common manifestation of oxalosis (6). Unfortunately, high-quality optical coherence tomography was unable to be performed because of poor fixation and poor view of the fundus in setting of corneal opacity. W e thank readers Dr. Patel and Dr. Sinha for their informative response to our case report. Before cataract extraction, our patient had a visual acuity of 20/400 pinhole to 20/70 in the right eye and 20/60 pinhole to 20/25 in the left eye. She was seen twice preoperatively by a comprehensive ophthalmologist with documentation of a normal fundus examination. After right-eye cataract extraction, there was precipitous right-eye vision loss to hand motion with sequential left-eye vision loss in the following weeks. The readers suggest perioperative nonarteritic anterior ischemic optic neuropathy (NAION) as a potential cause of this case presentation; NAION is classically characterized by painless segmental optic nerve head swelling often with flame-shaped disc hemorrhage and typically with altitudinal field loss. Nearly half of patients with NAION present with vision better than 20/70 at presentation (1,2). Our patient had severe bilateral vision loss with pallid swelling of the optic nerves at presentation more characteristic of arteritic ION rather than NAION. End-stage renal disease does put our patient at risk of ischemic complications and certainly contributes to her ocular condition. We agree that our patient did have perioperative ocular ischemia as mentioned in the title of the report; however, precipitous vision loss and the appearance of extensive widespread retinal vascular calcifications, cotton wool spots, crystalline retinopathy, and diffuse corneal opacity, as well as sequenLetters to the Editor: J Neuro-Ophthalmol 2022; 42: e533-e538 e537 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.