Ocular Adverse Events Following Coronavirus Disease 2019 Infection: A Self-controlled Case Series Study from the Entire Korean Population

Abstract

Purpose: This study aimed to assess the risk of ocular adverse events, including retinal artery occlusion (RAO), retinal vein occlusion (RVO), noninfectious uveitis (NIU), noninfectious scleritis (NIS), optic neuritis (ON), ischemic optic neuropathy (ION), and ocular motor cranial nerve palsy (OMCNP), after coronavirus disease 2019 (COVID-19) infection.

Design: Population-based self-controlled case series (SCCS).

Participants: The study included patients from the entire Korean population of 52 million who experienced incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP between January 1, 2021, and October 29, 2022.

Methods: This nationwide SCCS utilized data from the Korea National Health Insurance Service and the Korea Disease Control and Prevention Agency. The risk period after infection was defined as up to 24 weeks after COVID-19 infection. Conditional Poisson regression was used to calculate the relative incidence rate ratios (IRRs) for RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP during the designated risk periods.

Main outcome measures: The IRRs for RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP during the risk periods.

Results: The study included 9336, 103 362, 201 010, 25 428, 23 744, 3026, 69 933, and 16 335 cases of incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP, respectively. The IRRs (95% confidence interval) during the early risk period (1-8 weeks) were 0.94 (0.83-1.07), 1.01 (0.97-1.04), 1.00 (0.98-1.03), 0.96 (0.90-1.03), 1.00 (0.94-1.07), 0.97 (0.81-1.17), 0.97 (0.93-1.01), and 1.02 (0.94-1.11), respectively. In the late risk period (9-24 weeks), the IRRs were 1.02 (0.92-1.12), 1.01 (0.98-1.04), 1.01 (0.99-1.03), 1.02 (0.97-1.08), 1.02 (0.97-1.08), 0.99 (0.85-1.15), 1.02 (0.99-1.06), and 0.97 (0.90-1.03), respectively. Stratified analyses showed that in patients with a history of cerebro-cardiovascular disease, the risk of RAO increased during the late risk period, with an IRR (95% confidence interval) of 1.19 (1.02-1.40).

Conclusions: The risk of incident RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP did not increase after COVID-19 infection. The risk of incident RAO increased only in individuals with preexisting cardio-cerebrovascular disease.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: COVID-19; Coronavirus disease 2019; Ocular adverse events; Self-controlled case series.

Figure 1

Flow chart of subject selection for the self-controlled case series. COVID-19 = coronavirus disease 2019.

Figure 2

Illustration of self-controlled case series design in a common clinical scenario. The risk period was up to 24 weeks (168 days) after infection and was divided into an early risk phase (8 weeks or 56 days) and a late risk phase (9 to 24 weeks). All other times during the study were deemed control periods. The observation period was divided into 3 segments: before November 1, 2021; between November 1, 2021, and April 18, 2022; and after April 18, 2022. November 1, 2021, marked the start of the nationwide shift from social distancing to a gradual normalization, while April 18, 2022, marked the official end of social distancing measures in Korea. COVID-19 = coronavirus disease 2019.

Figure 3

Incidence rate ratios of ocular adverse events during the risk periods in the self-controlled case series study. There was no increase in the incidence rate among any disease group during the postinfection period. CI = confidence interval; IRR = incidence rate ratio.