Case Series: Atypical Optic Neuritis After COVID-19 Vaccination

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Case Series: Atypical Optic Neuritis After COVID-19 Vaccination Madina Tugizova, MD, Diane T. Siegel, MD, Sally Huang, MD, Elaine Su, MD, Prem S. Subramanian, MD, PhD, Shannon Beres, MD, Nirali Vora, MD T he global impact of the COVID-19 pandemic has led to the development of the highly efficacious Pfizer and Moderna vaccines. Because these messenger RNA (mRNA) vaccines are novel, there is limited knowledge about their potential adverse effects. Optic neuritis is an immunemediated disorder characterized by subacute onset painful vision loss, commonly associated with demyelinating conditions of the central nervous system, which may occur following infection or vaccination, and is usually steroid-responsive (1). In this case series, we describe 2 patients who developed atypical optic neuritis after COVID-19 vaccination. and C-reactive protein (CRP) were within normal limits. Antinuclear antibody (ANA), antineutrophil cytoplasmic antibodies (ANCA), and angiotensin-converting enzyme were negative. Serum myelin oligodendrocyte glycoprotein (MOG) IgG and aquaporin-4 IgG were negative. She was treated with a 5-day course of methylprednisolone 1 g IV every 24 hours and intravenous immunoglobulin (IVIG) 2 g/kg administered over 3 days. Five weeks later, the visual acuity improved to 20/100 in her right eye, but she perceived minimal recovery in central vision. Case 1 Case 2 A 65-year-old woman with a history of medullary thyroid cancer status post total thyroidectomy on levothyroxine, vitamin D deficiency on supplementation, prediabetes mellitus, and hyperlipidemia received her first dose of the Pfizer COVID-19 mRNA vaccine. Within hours after vaccination, she experienced a headache. Five days later, she developed vision loss in the right eye associated with pain with eye movements. She presented with light perception only vision and an afferent pupillary defect in her right eye, with 360-degree optic disc swelling associated with cotton wool spots and flame hemorrhages (Fig. 1). Her ophthalmologic and neurologic examinations were otherwise normal. Magnetic resonance imaging (MRI) orbits showed evidence of right optic neuritis (Fig. 2). MRI of the brain and cervical and thoracic spine showed no demyelinating lesions. COVID-19 polymerase chain reaction (PCR) was negative. Erythrocyte sedimentation rate (ESR) A 67-year-old man with a history of prediabetes mellitus, hyperlipidemia, glaucoma, and episcleritis received his second dose of the Moderna COVID-19 mRNA vaccine. The next day, he developed bilateral eye redness and chemosis with blurred vision. Hours later, he noted rapidly progressive vision loss in the left eye associated with pain with eye movements along with ocular surface irritation. He denied deep orbital or boring pain. He presented with a visual acuity of 20/40 in the right eye, no light perception in the left eye, and a left afferent pupillary defect. He also had temporal chemosis and injection in both eyes that improved but did not completely blanch with phenylephrine. His ocular ductions were full, and ophthalmologic and neurologic examinations were otherwise normal. MRI orbits showed evidence of left optic neuritis (Fig. 2). MRI of the brain was normal. COVID-19 PCR was negative. ESR was within normal limits. CRP was elevated to 57.2 mg/ L. ANA, ANCA, and rheumatoid factor were negative. Serum MOG IgG and aquaporin-4 IgG were negative. Thyroid stimulating hormone and thyroid antibodies were normal. He was given a 5-day course of methylprednisolone 1 g IV every 24 hours. Six weeks later, the visual acuity improved to 20/20 in the right eye with a normal visual field, but he continued to have no light perception in the left eye. These 2 patients developed optic neuritis within the first week of COVID-19 mRNA vaccination in the absence of MOG or aquaporin-4 antibodies. Both patients were older than the typical age of presentation for optic neuritis, usually in the third to fifth decades of life (2), and neither had rapid improvement in visual acuity with steroids. Department of Neurology and Neurological Sciences (MT, ES, SB, NV), Stanford University, Stanford, California; Sue Anschutz-Rodgers University of Colorado Eye Institute and Department of Ophthalmology (DTS, PSS), University of Colorado School of Medicine, Aurora, Colorado; Department of Psychiatry (SH), Stanford University, Stanford, California; Departments of Neurology (PSS) and Neurosurgery (PSS), University of Colorado School of Medicine, Aurora, Colorado; and Division of Ophthalmology (PSS), Uniformed Services University of the Health Sciences, Bethesda, Maryland. The authors report no conflicts of interest. Address correspondence to Madina Tugizova, MD, Department of Neurology and Neurological Sciences, Stanford University, Center for Academic Medicine, 453 Quarry Road, Palo Alto, CA 94304-5235; E-mail: [e-mail]. e120 Tugizova et al: J Neuro-Ophthalmol 2023; 43: e120-e122 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Optic discs on funduscopic examination. A. The right optic disc is pale and edematous with flame hemorrhages and obscuration of the major vessels. B. The left optic disc is normal in color with sharp margins and well-defined retinal vessels. Optic neuritis has been reported in patients with COVID-19 infection, including cases of MOG seropositivity (3,4). Optic neuritis has also occurred after vaccinations against influenza, measles–mumps–rubella, hepatitis A and B, and rabies (1). There is a case report of a patient who developed anti-MOG antibody positive bilateral optic neuritis and thyroiditis after vaccination with Sinovac’s inactivated COVID-19 vaccine (5). There is also a published case of a patient with multiple sclerosis who developed chiasmal optic neuritis and longitudinally extensive transverse myeli- tis after vaccination with the vector-based AstraZeneca COVID-19 vaccine (6). Multiple mechanisms have been proposed to explain such autoimmune phenomena, including molecular mimicry, epitope spreading, bystander activation, direct inflammatory damage, formation of immune complexes, and genetic predisposition to autoimmunity (1). To the best of our knowledge, this is the first report of optic neuritis after COVID-19 mRNA vaccination. This case series is limited in that it cannot determine whether the association between COVID-19 immunization FIG. 2. Magnetic resonance imaging orbits with and without contrast showing evidence of optic neuritis. T2 axial sequence (A) shows an enlarged right optic nerve (long arrow) and postcontrast T1 axial image (B) demonstrates contrast enhancement of the right optic nerve (arrowhead) in a 65-year-old woman who received the Pfizer COVID-19 vaccine. Postcontrast T1 axial (C) and coronal (D) sequences with fat saturation show enhancement of the left optic nerve (arrowhead) and bilateral retrobulbar fat (short arrows) in a 67-year-old man who received the Moderna COVID-19 vaccine. Tugizova et al: J Neuro-Ophthalmol 2023; 43: e120-e122 e121 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence and optic neuritis is causal or merely temporal. The development of optic neuritis in the days to weeks after vaccination is a rare event, and a case control study of 91 individuals who developed optic neuritis after vaccination between 2007 and 2012 found no increased risk of vaccine exposure when comparing patients with an initial episode of optic neuritis to their age-matched, sex-matched, and vaccine-matched controls (7). The Pfizer and Moderna COVID-19 mRNA vaccines have shown an excellent safety record and are anticipated to greatly reduce morbidity and mortality during the COVID19 pandemic. Thus, the benefits of vaccination will outweigh the risks in most people. However, as large-scale vaccination against COVID-19 continues, it is important for medical providers to be aware of the potential association between these mRNA vaccines and atypical optic neuritis. These 2 cases illustrate the need to study large data sets to determine the frequency and mechanisms by which mRNA vaccines may trigger immune-mediated reactions. STATEMENT OF AUTHORSHIP Conception and design: M. Tugizova, N. Vora; Acquisition of data: M. Tugizova, N. Vora, D. T. Siegel, S. Huang, E. Su, P. S. Subramanian, S. Beres; Analysis and interpretation of data: M. Tugizova, P. S. Subramanian. Drafting the manuscript: M. Tugizova, P. S. Subramanian, D. T. Siegel; Revising it for intellectual content: M. Tugizova, N. Vora, P. S. Subramanian, S. Beres. Final approval of the e122 completed manuscript: M. Tugizova, N. Vora, D. T. Siegel, S. Huang, E. Su, P. S. Subramanian, and S. Beres. REFERENCES 1. Stubgen J. A literature review of optic neuritis following vaccination against virus infections. Autoimmun Rev. 2013;12:990–997. 2. Optic Neuritis Study Group. The clinical profile of optic neuritis. Experience of the Optic Neuritis Treatment Trial. Arch Ophthalmol. 1991;109:1673–1678. 3. Benito-Pascual B, Gegundez J, Diaz-Valle D, Arriola-Villalobos P, Carreno E, Culebras E, Rodriguez-Avial I, Benitez-Del-Castillo J. Panuveitis and optic neuritis as a possible initial presentation of the Novel Coronavirus Disease 2019 (COVID-19). Ocul Immunol Inflamm. 2020;28:922–925. 4. Sawalha K, Adeodokun S, Kamoga G. COVID-19-induced acute bilateral optic neuritis. J Investig Med High Impact Case Rep. 2020;8:1–3. 5. 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