Bilateral Reversible Optic Neuropathy After Influenza Vaccination

Clinical Correspondence Bilateral Reversible Optic Neuropathy After Influenza Vaccination Emily Li, MD, Adeniyi Fisayo, MD, PharmD O ptic neuritis after inactivated and live-attenuated influenza vaccination is rare, with fewer than 30 cases reported to date. The association and pathophysiology remain controversial. Although some authors have concluded that there is insufficient evidence to support a causal relationship between the influenza vaccine and optic neuritis, others have found the time course of symptom onset in the setting of a negative work-up for known causes of optic neuritis to be convincing support for an association (1,2). In this study, we present a case of bilateral optic neuritis occurring 1 week after influenza vaccination in a child whose identical twin received the same vaccine without visual or other adverse effects. A previously healthy 6-year-old girl developed bilateral vision loss 1 week after receiving the intramuscular quadrivalent (inactivated) influenza vaccine. Her identical twin received the same vaccination without subsequent changes in vision. There was no family history of autoimmune, ocular, or neurologic disorders. Our patient had no previous medical problems. At presentation to the emergency department, her visual acuities were hand motion in the right eye and counting fingers in the left with no afferent pupillary defect (APD). Examination revealed severe optic disc swelling with vessel obscuration bilaterally and peripapillary hemorrhages on the left. There were no anterior chamber cells, vitreous cells, or macular exudates in either eye. MRI of the brain, orbits, and spinal cord with and without intravenous (IV) contrast showed increased T2/FLAIR signal and abnormal enhancement in the retrobulbar optic nerves bilaterally (Fig. 1A, B), but no white matter lesions in the brain or spinal cord (Fig. 1C). Cerebrospinal fluid analysis revealed 1,000 red blood cells/ mL, 5 nucleated cells (WBC)/mL, protein level of 23 mg/ dL, and glucose level of 58 mg/dL. There were no oligoclonal bands, positive cultures, Lyme antibodies, aquaporin4 antibodies, or evidence of any of the following by polymerase chain reaction in the CSF: Epstein–Barr virus, herpes simplex virus, and varicella-zoster virus. Serologic testing was also negative for culture growth, Lyme antibodDepartments of Ophthalmology and Visual Science (EL, AF) and Neurology (AF), Yale University School of Medicine, New Haven, Connecticut. The authors report no conflicts of interest. Address correspondence to Emily Li, MD, 40 Temple Street, Suite 3D, New Haven, Connecticut 06510; E-mail: [e-mail] 496 ies, and aquaporin-4 antibodies; white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and angiotensin-converting enzyme levels were normal. After 5 days of IV methylprednisolone, visual acuities improved to 20/20, and she recognized 10/10 Ishihara color plates with each eye. The patient was discharged to home without a steroid taper. Six days after her last dose of IV steroids, the patient experienced decreased vision in the left eye. Examination showed visual acuities of 20/25 in the right eye and no light perception in the left eye. There was a left APD. Ophthalmoscopy showed mild atrophy of the right optic disc from her initial inflammation and swelling of the left optic disc (Fig. 2). Optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer showed average thicknesses of 144 mm in the right eye and 203 mm in the left eye, consistent bilateral disc edema. The patient started oral prednisolone 2 mg/kg/day; 2 weeks later, her visual acuities returned to 20/20 with normal color vision (14/14 Ishihara plates) in each eye. Optic disc swelling in the left eye had resolved, leaving mild pallor of both optic discs. The oral steroid dose was tapered over the subsequent 4 weeks without recurrence of vision loss. At her last follow-up evaluation (11 weeks after the influenza vaccination and 10 weeks after initial vision loss), neuro-ophthalmic examination was stable. To the best of our knowledge, she has remained without recurrence off steroids over the past 2 years. Although optic neuritis after influenza vaccination is extremely rare—reported to occur at a rate of 0.003 cases per 100,000 doses of H1N1 (influenza A) vaccine. Published cases have helped to characterize the clinical manifestations (3). Similar to our patient’s presentation, symptoms typically occur within 2–6 weeks of influenza vaccination. Vision typically deteriorates to hand motions or worse, but most patients experience full recovery after oral and/or IV steroids. By contrast, untreated patients in previous cases developed optic atrophy and permanent visual loss (4). Optic neuritis after influenza and other vaccinations has been hypothesized to fall under a spectrum of clinical syndromes known as autoimmune/inflammatory clinical syndromes induced by adjuvants (ASIA)—an immune reaction to adjuvants. Adjuvants are specific protein substances added to vaccines to augment antigen-specific immune responses to enhance vaccine efficacy (4). ASIA syndrome, also known as Shoenfeld syndrome, was first Li and Fisayo: J Neuro-Ophthalmol 2019; 39: 496-497 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. (A) Axial T1 MRI with fat suppression and (B) coronal T1 MRI with fat suppression sequences demonstrating enhancement and thickening of the retrobulbar optic nerves. C. Axial T2 sequence showing the absence of white matter lesions white matter lesions. FIG. 2. Color fundus photograph of the (A) right optic disc and (B) left optic disc at time of recurrence of visual loss and presentation to the neuro-ophthalmology clinic. The photos show mild optic atrophy in the right eye and mild swelling with blurring of disc margins in the left eye. described by Yehuda Shoenfeld in 2011. Since then, an international ASIA syndrome registry with more than 300 patients has been established (5). In this condition, vaccine adjuvants (common pathogenic denominators) are believed to trigger a hyperactive immune response that presents with similar clinical manifestations (4). Eightynine percent of patients analyzed from the registry had a concurrent rheumatologic or autoimmune condition, the most common of which was undifferentiated connective tissue disease associated with a positive antinuclear antibody test (5). The aberrant immune response leading to postinfluenza vaccination optic neuritis may be facilitated by genetic susceptibility (4). The divergent reactions to the influenza vaccine in our patient and her identical twin suggest that the interplay between environmental exposures and genetic predisposition in postinfluenza vaccination optic neuritis may be more complicated and warrants further research. Optic neuritis after influenza vaccination is a rare condition that results in severe vision loss typically reversible with prompt initiation of steroid therapy. The association in this phenomenon remains controversial, and further investigation is indicated to elucidate the pathophysiology of postvaccination optic neuritis. Li and Fisayo: J Neuro-Ophthalmol 2019; 39: 496-497 STATEMENT OF AUTHORSHIP Category 1: a. conception and design: E. Li and A. Fisayo; b. acquisition of data: E. Li and A. Fisayo; c. analysis and interpretation of data: E. Li and A. Fisayo. Category 2: a. drafting the manuscript: E. Li and A. Fisayo; b. revising it for intellectual content: E. Li and A. Fisayo. Category 3: a. final approval of the completed manuscript: E. Li and A. Fisayo. REFERENCES 1. Crawford C, Grazko MB, Raymond WRt, Rivers BA, Munson PD. Reversible blindness in bilateral optic neuritis associated with nasal flu vaccine. Binocul Vis Strabolog Q Simms Romano. 2012;27:171–173. 2. Stratton K, Ford A, Rusch E, Clayton EW, eds. Influenza vaccine. In: Adverse Effects of Vaccines: Evidence and Causality. Washington DC: National Academies Press, 2012:310–313. 3. Stubgen JP. A literature review on optic neuritis following vaccination against virus infections. Autoimmun Rev. 2013;12:990–997. 4. Jun B, Fraunfelder FW. 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