Citation: Elnahry, A.G.; Al-Nawaflh, M.Y.; Gamal Eldin, A.A.; Solyman, O.; Sallam, A.B.; Phillips, P.H.; Elhusseiny, A.M. COVID-19 Vaccine-Associated Optic Neuropathy: A Systematic Review of 45 Patients. Vaccines 2022, 10, 1758. https://doi.org/10.3390/ vaccines10101758 Academic Editor: Rohan Bir Singh Received: 25 September 2022 Accepted: 19 October 2022 Published: 20 October 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Review COVID-19 Vaccine-Associated Optic Neuropathy: A Systematic Review of 45 Patients Ayman G. Elnahry 1,2, * , Mutaz Y. Al-Nawaflh 2,3 , Aisha A. Gamal Eldin 4 , Omar Solyman 5,6 , Ahmed B. Sallam 7 , Paul H. Phillips 7 and Abdelrahman M. Elhusseiny 7 1 Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo 11956, Egypt 2 Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA 3 Division of Ophthalmology, King Hussein Hospital, Jordanian Royal Medical Services, Amman 11855, Jordan 4 Maryland Eye Care Center, Silver Spring, MD 20910, USA 5 Department of Ophthalmology, Research Institute of Ophthalmology, Giza 11261, Egypt 6 Department of Ophthalmology, Qassim University Medical City, Al-Qassim 52571, Saudi Arabia 7 Department of Ophthalmology, Harvey and Bernice Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA * Correspondence: ayman.elnahry@nih.gov; Tel.: +1-2159667024 Abstract: We provide a systematic review of published cases of optic neuropathy following COVID-19 vaccination. We used Ovid MEDLINE, PubMed, and Google Scholar. Search terms included: “COVID-19 vaccination”, “optic neuropathy”, “optic neuritis”, and “ischemic optic neuropathy”. The titles and abstracts were screened, then the full texts were reviewed. Sixty eyes from forty-five patients (28 females) were included. Eighteen eyes from fourteen patients (31.1%) were diagnosed with anterior ischemic optic neuropathy (AION), while 34 eyes from 26 patients (57.8%) were di- agnosed with optic neuritis (ON). Other conditions included autoimmune optic neuropathy and Leber hereditary optic neuropathy. Fifteen patients (33.3%) had bilateral involvement. The mean age of all patients was 47.4 ± 17.1 years. The mean age of AION patients was 62.9 ± 12.2 years and of ON patients was 39.7 ± 12.8 years (p < 0.001). The mean time from vaccination to ophthalmic symptoms was 9.6 ± 8.7 days. The mean presenting visual acuity (VA) was logMAR 0.990 ± 0.924. For 41 eyes with available follow-up, the mean presenting VA was logMAR 0.842 ± 0.885, which improved to logMAR 0.523 ± 0.860 at final follow-up (p < 0.001). COVID-19 vaccination may be associated with different forms of optic neuropathy. Patients diagnosed with ON were more likely to be younger and to experience visual improvement. More studies are needed to further characterize optic neuropathies associated with COVID-19 vaccination. Keywords: CNS inflammation; COVID-19; ischemic optic neuropathy; ocular inflammation; optic neuritis; optic neuropathy; vaccination 1. Introduction In 2021, vaccination against severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) became a primary focus of public health efforts to control the COVID-19 pandemic. Even though they were generally found to be safe and effective in multiple large controlled clinical trials, the relatively fast and wide deployment of COVID-19 vaccines has made them a subject of considerable scrutiny and analysis since the time of their introduction to the public. The COVID-19 disease itself has affected the eye in many ways. Previous research demonstrated a link between COVID-19 infection and ophthalmic manifestations, both directly and indirectly. For example, it was reported that inflammatory conditions such as conjunctivitis, scleritis, orbital inflammation, keratitis, and retinal affection may be directly linked to COVID-19 infection [1–9]. Regarding indirect impact, several studies have Vaccines 2022, 10, 1758. https://doi.org/10.3390/vaccines10101758 https://www.mdpi.com/journal/vaccines