The Risk of Optic Neuritis following mRNA Coronavirus Disease 2019 Vaccination Compared to Coronavirus Disease 2019 Infection and Other Vaccinations

Purpose: To determine the risk of optic neuritis (ON) after mRNA Coronavirus Disease 2019 (COVID-19) vaccine administration. Design: U.S. National aggregate database retrospective cohort study. Participants: Patients were placed into cohorts based on mRNA COVID-19 vaccination status (no vaccine and positive history of COVID-19 infection, 1 vaccine, or 2 vaccines received) from December 2020 to June 2022. Two control cohorts were created with patients vaccinated against influenza or tetanus, diphtheria, and pertussis (Tdap) from June 2018 to December 2019. Patients with any history of ON or significant risk factors for ON development including infectious, inflammatory, and neoplastic diseases were excluded. Methods: A large deidentified database was queried for the Common Procedural Technology codes for immunization encounters specific to first dose and second dose of mRNA COVID-19 vaccine, influenza, or Tdap. Cohorts were 1:1 propensity score matched on age, sex, race, and ethnicity. The risk of ON development after vaccination was calculated and compared for all 5 cohorts with 95% confidence intervals (CIs) reported. Main Outcome Measures: Risk ratio (RR) of ON 21 days after vaccination (or COVID-19 infection) and incidence of ON per 100 000 individuals. Results: After matching, the first dose COVID-19 and influenza vaccine cohorts (n = 1 678 598, mean age [standard deviation] at vaccination of 45.5 [23.3] years and 43.2 [25.5] years, 55% female) the RR of developing ON was 0.44 (95% CI, 0.28-0.80).- 0.80). The first dose of COVID-19 and Tdap vaccinations (n = 797 538, mean age 38.9 [20.0] years, 54.2% female) cohort had 10 and 16 patients develop ON (RR, 0.63; 95% CI, 0.28-1.38).- 1.38). Comparison of COVID-19-vaccinated- vaccinated patients (n = 3 698 848, 48.2 [21.5] years, 54.7% female) to unvaccinated and COVID-19-infected- infected patients (n = 3 698 848, 49.6 [22.0] years, 55.2% female) showed 49 and 506 patients developing ON, respectively (RR, 0.09; 95% CI, 0.07-0.12).- 0.12). The incidence per 100 000 for ON was 1 in the first dose COVID-19 vaccine cohort, 2 in the influenza cohort, and 2 in the Tdap cohort, and 14 in the COVID19-infected- infected and unvaccinated cohorts. Conclusions: Risk of ON after mRNA COVID-19 vaccination is rare and comparable to Tdap vaccination, decreased compared with influenza vaccination, and decreased compared with COVID-19 infection in the absence of vaccination.