Retinal Vascular Occlusion Following COVID-19 Vaccination: A Comprehensive Review of Observational Study and Pathophysiological Mechanisms

TL;DR

This paper reviews whether retinal vascular occlusion is a rare side effect of COVID-19 vaccines and explores possible biological mechanisms.

Contribution

The study provides a comprehensive review of observational data and proposes potential pathophysiological mechanisms linking vaccines to retinal vascular occlusion.

Findings

Some studies found no association between vaccination and retinal vascular occlusion (OR 0.93).

Adenoviral vector vaccines like ChAdOx1 showed higher retinal artery occlusion incidence.

Proposed mechanisms include immune thrombocytopenia and endothelial dysfunction.

Abstract

Background: Retinal vascular occlusion (RVO) and retinal artery occlusion (RAO) have been reported as rare adverse events following COVID-19 vaccination, raising concerns about vaccine safety. This review synthesizes cohort and case–control studies assessing the association between COVID-19 vaccines and RVO/RAO, while exploring potential pathophysiological mechanisms. Methods: We analyzed large-scale population-based studies from South Korea, Europe, and the TriNetX database, focusing on odds ratios (OR), hazard ratios (HR), and relative risks (RR) across mRNA and adenoviral vector vaccines. Pathological processes were hypothesized based on molecular and clinical evidence. Results: Studies investigating the association between COVID-19 vaccination and retinal vascular occlusion show conflicting results; some studies report no association (e.g., OR 0.93, 95% CI 0.60–1.45), others suggest reduced risk (e.g., OR 0.80, 95% CI 0.64–0.99), and one indicates increased risk over two years (HR 2.19, 95% CI 2.00–2.39). Adenoviral vector vaccines, particularly ChAdOx1, show higher RAO incidence in specific cohorts. Proposed mechanisms include vaccine-induced immune thrombotic thrombocytopenia (VITT) via anti-PF4 antibodies, spike protein-mediated endothelial dysfunction, and adjuvant-driven inflammation. Conclusions: While causality remains unproven, temporal heterogeneity and vaccine type-specific risks warrant further investigation. Longitudinal studies with robust controls are needed to clarify these associations in the post-pandemic context.

Figures