Severe Bilateral Vision Loss in 2 Patients With Coronavirus Disease 2019

Our knowledge of the coronavirus disease 2019(COVID-19) is rapidly evolving with new information being gathered daily. It has been widely reported thatCOVID-19 increases the risk of thrombotic and thromboembolic events, predisposing patients to pulmonary embolism, cerebrovascular accidents (CVAs), deep vein thrombosis, and myocardial infarction (1,2). A New York City health system recently reported a total of 5 young patients with COVID-19 presented with symptoms of large-vessel ischemic stroke over a 2-week period (3). We present here 2 cases of devastating visual consequences secondary to COVID-19-associated ischemic cerebral infarction occurring at 1 hospital center within 2 weeks.

Clinical Correspondence Severe Bilateral Vision Loss in 2 Patients With Coronavirus Disease 2019 Daniel G. Cyr, DO, Christina M. Vicidomini, DO, Nga Yan Siu, DO, Solly E. Elmann, MD O ur knowledge of the coronavirus disease 2019 (COVID-19) is rapidly evolving with new information being gathered daily. It has been widely reported that COVID-19 increases the risk of thrombotic and thromboembolic events, predisposing patients to pulmonary embolism, cerebrovascular accidents (CVAs), deep vein thrombosis, and myocardial infarction (1,2). A New York City health system recently reported a total of 5 young patients with COVID-19 presented with symptoms of large-vessel ischemic stroke over a 2-week period (3). We present here 2 cases of devastating visual consequences secondary to COVID-19-associated ischemic cerebral infarction occurring at 1 hospital center within 2 weeks. Our first patient is a 61-year-old man with a medical history of non-insulin-dependent diabetes mellitus, who was brought to the emergency department with a 7-day history of COVID-19-like symptoms, including cough, fever, and body aches. On presentation, he endorsed the chief complaint of bilateral, sudden, painless loss of vision for 2 days. The patient was noted to be tachypneic and disoriented. He denied any inciting events, nor any recent head trauma. On examination, his visual acuity was no light perception in both eyes, and the optokinetic response was negative. Pupils were equal, round, and reactive to light without relative afferent pupillary defect in both eyes. Extraocular movements were full. The intraocular pressures were 11 and 13 mm Hg in the right and left eyes, respectively. Anterior segment examination was essentially unremarkable. Dilated fundus examination demonstrated a few scattered dot-blot hemorrhages in the macula and the periphery of both eyes, consistent with mild nonproliferative diabetic retinopathy; the remainder of the examination was within normal limits. The primary diagnosis was confirmed by a positive COVID-19 polymerase chain reaction test and a chest X-ray showing bilateral ground glass opacities. Computed tomography of the head without contrast was significant for low attenuation changes and loss of gray-white matter differenti- Department of Ophthalmology (DGC, CMV, NYS, SEE), Brookdale University Hospital Medical Center, Brooklyn, New York; and Department of Ophthalmology (DGC, CMV, NYS), St John's Episcopal Hospital, Far Rockaway, New York. The authors report no conflicts of interest. Address correspondence to Nga Yan Siu, DO, 327 Beach 19th Street, Far Rockaway, NY 11691; E-mail: [e-mail] Cyr et al: J Neuro-Ophthalmol 2020; 40: 403-405 ation compatible with cytotoxic edema in the bilateral occipital polar regions without hemorrhage. These findings were consistent with acute bilateral occipital territorial ischemic infarct. Other laboratory tests were consistent with COVID19 including elevated white blood cells of 13.2 · 103/mL, aspartate aminotransferase of 67 U/L, alanine aminotransferase of 73 U/L, lactate dehydrogenase of 2118 IU/L, C-reactive protein (CRP) of 15 mg/dL, and a sedimentation rate of 32 mm. Coagulation studies revealed a normal partial thromboplastin time, international normalized ratio, and a slightly elevated prothrombin time at 13.8 seconds (normal 13.7 seconds). D-dimer was not obtained. Unfortunately, the patient's condition rapidly deteriorated requiring intubation within hours, and he died shortly after on Day 3 of hospitalization. Our second patient is a 34-year-old woman, with a medical history of systemic lupus erythematosus (SLE), hypertension, end-stage renal disease on hemodialysis, chronic obstructive pulmonary disease, and prior CVA in 2016 with resultant subjective peripheral visual field loss without any functional deficits (good central vision), was admitted to the hospital for confirmed positive COVID-19 pneumonia. The ophthalmology service was consulted on hospital Day 10 for sudden, bilateral, painless loss of vision of 2-day duration. On examination at her bedside, she was awake and oriented. The visual acuity was found to be light perception in both eyes. Both pupils were equal, round, and reactive to light with no relative afferent pupillary defect. Extraocular movements were full. Intraocular pressures were 16 and 14 mm Hg in the right and left eyes, respectively. The remainder of her anterior segment examination was unremarkable. Dilated fundus examination revealed trace optic disc pallor without cupping bilaterally. The remainder of her posterior examination was unremarkable. Her maximum D-dimer, erythrocyte sedimentation rate (ESR), and CRP levels were 15,941 ng/mL (normal 0- 230), 76 mm (normal 0-20), and 27.00 mg/dL (normal 0.50-1.00), respectively. Anticardiolipin antibody panel was weakly positive for IgM alone; however, IgG was negative as well as lupus anticoagulant and antinuclear antibody. The patient's home medications including hydroxychloroquine 200 mg twice a day and aspirin 81 mg daily were continued through her hospitalization. In addition, home dose of prednisone 10 mg daily was modified to 30-40 mg daily while inpatient. Of note, the patient 403 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence reported compliance with her home medications and rheumatology follow-up appointments and denied any SLE flare for "months." On admission, the patient was started on thromboembolism prophylactic dose of subcutaneous heparin, which was switched to daily renal dose of enoxaparin on hospital Day 5. MRI of the brain without contrast obtained 2 days after the patient's onset of visual disturbance revealed acute infarct in the right frontal lobe likely following the right middle cerebral artery territory, acute left posterior temporal-occipital territorial infarction following the posterior cerebral artery, and chronic infarction in the right temporal-parietal lobe and bilateral medial occipital lobes likely arterial in distribution. MRA of the brain revealed an occlusion of the M2 branches of the right middle cerebral artery, with otherwise normal flow in the other major intracranial arterial branches. MRA of the neck was unremarkable. Upper extremity venous duplex studies revealed superficial thrombophlebitis of the left cephalic vein and a partially occluded right arteriovenous fistula at the proximal forearm, but no evidence of deep vein thrombosis. Lower extremity venous duplex studies were unremarkable. Neurology was consulted and thrombolytic therapy was not initiated. On reassessment 4 days later, the patient's vision remained light perception, and the rest of her ophthalmic examination was unchanged. The patient's respiratory status continued to improve, and she was discharged home on dual antiplatelet therapy of aspirin and clopidogrel. In December 2019, the first case of COVID-19 was reported in Wuhan, China, and has since then rapidly spread to many countries around the world. In a retrospective case series study of 214 hospitalized patients with confirmed SARS-CoV-2 infection in Union Hospital in Wuhan, 36.4% of patients had neurological symptoms. The study categorized 88 patients as severe and 126 patients as nonsevere by using the American Thoracic Society guidelines for community-acquired pneumonia. Five severe patients had acute CVA, whereas only 1 nonsevere patient had CVA (1). A consecutive retrospective, observational analysis at the same hospital was performed including 221 patients. In this study group, 11 (5%) patients developed acute ischemic stroke, 1 (0.5%) developed cerebral venous sinus thrombosis, and 1 had (0.5%) cerebral hemorrhage. The group of patients with COVID-19 who developed CVA was more likely to have cardiovascular risk factors (including hypertension, diabetes, and medical history of cerebrovascular disease), increased inflammatory response, and a hypercoagulable state as reflected in elevated levels of CRP and D-dimer (2). Furthermore, a recent clinical correspondence published in the New England Journal of Medicine presented 5 cases of large-vessel ischemic stroke as a presenting feature in young patients with COVID-19 404 in New York City (3), again showing that our findings are not isolated. The pathogenesis of ischemic stroke in patients with COVID-19 or, more specifically, COVID-19-associated thrombotic complication is not clearly defined. A structural analysis performed by Lu et al suggests that SARSCoV-2 might be able to bind to the angiotensin-converting enzyme 2 (ACE 2) receptor (4). In addition to respiratory epithelial cells, ACE 2 receptors are also expressed on endothelial cells in several organs. Varga et al's (5) postmortem histological analyses of various organs demonstrated the presence of SARS-CoV-2 viral elements within endothelial cells and evidence of endotheliitis and inflammatory cell death, which subsequently lead to organ ischemia, tissue edema, and a procoagulant state. As suggested by Connors and Levy based on data collected from recent reports, elevated levels of interleukin-6, CRP, ESR, and elevated fibrinogen represent significant inflammation in patients with COVID-19, and subsequent activation of coagulation is the probable cause for the elevated D-dimer levels tracking with disease severity and inflammation. Elevated D-dimer at admission was also associated with increased mortality, and the authors recommended increased dose of venous thromboembolism prophylaxis especially in intensive care unit patients and patients with acute respiratory distress syndrome (6). As seen in both of our patients with pre-existing risk factors and a confirmed diagnosis of COVID-19, thrombotic events occurred leading to a devastating visual outcome secondary to occipital lobe ischemia as evidenced by neuroimaging. Although D-dimer was not obtained in our first patient, the severity of the disease was evidenced by the rapid deterioration of the patient. Our 34-year-old female patient with multiple comorbidities and high inflammatory markers was not maintained on therapeutic anticoagulation and unfortunately developed ischemic infarct on the side of the previously remaining visual pathway. Although the patient had a weak anticardiolipin IgM titer, it alone is not diagnostic of SLE-related hypercoagulability. In view of the relatively controlled status of SLE before hospital admission, and the significant elevated levels of acute phase inflammatory markers coinciding with COVID-19, this suggests that SARS-CoV-2 infection augmented our patient's risk for thrombotic occlusive event secondary to a perceivably lower threshold in patients with pre-existing endothelial dysfunction. As ophthalmologists, we witnessed another devastating consequence of SARS-CoV-2 infection. As seen in our 2 "at-risk" patients, superimposed COVID-19 potentially lowers the threshold for thrombotic complications. These COVID-19-related thromboembolic events can cause significant functional deficits, which may include debilitating vision loss. It is important as ophthalmologists to spread Cyr et al: J Neuro-Ophthalmol 2020; 40: 403-405 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence awareness of these potential neuro-ophthalmic consequences and help contribute to an interdisciplinary approach to appropriate management (i.e., anticoagulation). REFERENCES 1. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a retrospective case series study. JAMA Neurol. 2020;77:683- 690. 2. Wang M, Zhou Y, Chang J, Xian Y, Mao L, Hong C, Chen S, Wang Y, Wang H, Li M, Jin H, Hu B. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. SSRN Electron J. 2020. Available at: http://dx.doi. org/10.2139/ssrn.3550025. Accessed April 30, 2020. 3. Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, De Leacy RA, Shigematsu T, Ladner TR, Yaeger KA, Skliut M, Cyr et al: J Neuro-Ophthalmol 2020; 40: 403-405 Weinberger J, Dangayach NS, Bederson JB, Tuhrim S, Fifi JT. Large-vessel stroke as a presenting feature of Covid-19 in the young. New Engl J Med. 2020;382:e60. 4. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565-574. 5. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395:1417-1418. 6. Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020. Available at: https://doi.org/10.1182/blood.2020006000. Accessed April 30, 2020. 405 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.