Post Vaccination Optic Neuritis: Observations From the SARS-CoV-2 Pandemic

Background: Vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first approved on the 8th of December 2020. Though safe and effective, very rare side effects continue to be identified as global vaccination advances. They do not necessarily leave “a signal” in public registries if the incidence remains below previously reported total incidence levels. Optic neuritis (ON) is a rare but recognised adverse event after immunisation. The risk of post-vaccination ON and visual outcome in the context of global vaccination efforts against SARS-CoV-2 are not known.  Methods: A global report on 73 deep-phenotyped individuals with post-SARS-CoV-2 vaccination ON observed in 15 of 55 countries with designated experts between 14 February to 18 July 2021. Statistical analyses were performed on type of vaccine, number of jabs, time to onset of ON, demographics, clinical features and treatment. Paraclinical data included immunological testing for autoantibodies against myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4, magnetic resonance imaging (MRI) of the brain and orbits, retinal optical coherence tomography (OCT). The primary outcome was the visual acuity (VA).  Findings: The characteristics of the 69 individuals included, differed from pre-COVID whole population-based incidence studies in frequency of bilateral presentation, age distribution and radiological features more commonly found in immune-mediated ON. Most events (67%) occurred after vaccination with AstraZeneca, followed by Pfizer-BioNTech (26%) and Sinovac (7%). In 56 this was after the first and in 13 after the second jab with the same vaccine. Autoantibodies against MOG were present in 15 and not detected for aquaporin-4. The condition was steroid responsive in most (58/62), requiring plasma exchange in a few (5) with spontaneous recovery in the remainder (7). The incidence was highest in the UK (0.036 per 100,000 persons) where vaccination commenced earliest. Importantly, the pattern of presentation in time lagged about 1-5 weeks behind the pattern of national age group vaccination. The median VA at presentation was logMAR 1.0 and recovered to 0.0.  Interpretation: Post-SARS-CoV-2 vaccination ON is an extremely rare adverse event with generally good outcome of visual function. The global incidence of post-vaccination ON (0.0017 per 100,000 persons) is lower than for ON (3.74 per 100,000 persons in the UK). A causal relationship is plausible, but the overall risk benefit balance is in favour of SARS-CoV-2 vaccination. Funding Information: None. Declaration of Interests: None. Ethics Approval Statement: Reporting of patients was approved by the Institutional Research Board at Moorfields Eye Hospital (study number CaRS_24).