Ocular Adverse Events after Coronavirus Disease 2019 mRNA Vaccination: Matched Cohort and Self-Controlled Case Series Studies Using a Large Database

Yohei Hashimoto; Hayato Yamana; Masao Iwagami; Sachiko Ono; Yoshinori Takeuchi; Nobuaki Michihata; Kohei Uemura; Hideo Yasunaga; Makoto Aihara; Toshikatsu Kaburaki

doi:10.1016/j.ophtha.2022.10.017

Ocular Adverse Events after Coronavirus Disease 2019 mRNA Vaccination: Matched Cohort and Self-Controlled Case Series Studies Using a Large Database

Ophthalmology. 2023 Mar;130(3):256-264. doi: 10.1016/j.ophtha.2022.10.017. Epub 2022 Oct 26.

Authors

Affiliations

¹ Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan. Electronic address: youhashi@m.u-tokyo.ac.jp.
² Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³ Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
⁴ Department of Eat-loss Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁵ Division of Medical Statistics, Department of Social Medicine, Faculty of Medicine, Toho University, Tokyo, Japan; Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁶ Department of Biostatistics and Bioinformatics, Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo, Japan.
⁷ Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan.
⁸ Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Abstract

Purpose: To investigate the risk of ocular adverse events after Coronavirus Disease 2019 (COVID-19) mRNA vaccination.

Design: Matched cohort and self-controlled case series (SCCS) studies.

Participants: We used a population-based database of medical claims and vaccination records in a large Japanese city. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from nonvaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events.

Methods: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio (IRR) of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared with the remaining periods.

Main outcome measures: Composite outcome of uveitis, scleritis, retinal vein occlusion (RVO), and optic neuritis.

Results: There were 99 718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100 000 persons and 51.3 (16.2-84.3) events/100 000 persons, respectively, for the first and second doses. The SCCS study showed the IRRs of 0.89 (0.62-1.28) and 0.89 (0.71-1.11) for the first and second doses, respectively.

Conclusions: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Keywords: COVID-19 vaccines; Drug-related side effects and adverse reactions; Optic Neuritis; Retinal vein occlusion; Scleritis; Uveitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
BNT162 Vaccine*
COVID-19 Vaccines
COVID-19*
Cohort Studies
Eye
Humans
Male

Substances

BNT162 Vaccine
COVID-19 Vaccines