Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jul 7;13(7):733.
doi: 10.3390/vaccines13070733.

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

Yuchen Zhang  1   2 , Haoliang Zhang  1   2 , Kangjia Lv  1   2 , Xin Lin  1   3   4 , Feng'e Chen  1   2 , Hui Cao  1   2 , Chong Chen  1   5
Affiliations
Review

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

Yuchen Zhang et al. Vaccines (Basel). .

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.

Keywords: COVID-19 vaccination; PF4 antibodies; adenoviral vector vaccines; mRNA vaccines; pathophysiological mechanisms; retinal artery occlusion (RAO); retinal vascular occlusion (RVO); spike protein; vaccine-induced immune thrombotic thrombocytopenia (VITT).

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 2
Figure 2
The schematic diagram illustrates currently proposed hypotheses of pathophysiological mechanisms associated with thromboembolic events or vasculopathic responses following administration of adenoviral vector-based and mRNA COVID-19 vaccines. This image was drawn using Figdraw.
Figure 3
Figure 3
This figure delineates the pathophysiological mechanisms underlying hemodynamic disturbances and neurovascular architecture deconstruction in the delicate retinal tissue, mediated by systemic vascular risk factors, culminating in vision loss. This image was drawn using Figdraw.
Figure 1
Figure 1
Arrows denote causal directions (exposure→mediator→outcome). Four confounder groups (demographics/pre-existing conditions, indicated by purple boxes) affect both vaccine exposure (indicated by blue boxes) and RVO risk. Unmeasured variables (dashed boxes) indicate residual confounding. Green boxes represent possible pathologicalmechanisms.Excluded factors were intentionally controlled in some of studies. DAG guides bias adjustment and mechanistic analysis.
See this image and copyright information in PMC

Similar articles

  • Vaccines for preventing infections in adults with haematological malignancies.
    Zorger AM, Hirsch C, Baumann M, Feldmann M, Bröckelmann PJ, Mellinghoff S, Monsef I, Skoetz N, Kreuzberger N. Zorger AM, et al. Cochrane Database Syst Rev. 2025 May 21;5(5):CD015530. doi: 10.1002/14651858.CD015530.pub2. Cochrane Database Syst Rev. 2025. PMID: 40396505 Review.
  • Vaccines for preventing influenza in healthy children.
    Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V. Jefferson T, et al. Cochrane Database Syst Rev. 2018 Feb 1;2(2):CD004879. doi: 10.1002/14651858.CD004879.pub5. Cochrane Database Syst Rev. 2018. PMID: 29388195 Free PMC article.
  • Efficacy and safety of COVID-19 vaccines.
    Graña C, Ghosn L, Evrenoglou T, Jarde A, Minozzi S, Bergman H, Buckley BS, Probyn K, Villanueva G, Henschke N, Bonnet H, Assi R, Menon S, Marti M, Devane D, Mallon P, Lelievre JD, Askie LM, Kredo T, Ferrand G, Davidson M, Riveros C, Tovey D, Meerpohl JJ, Grasselli G, Rada G, Hróbjartsson A, Ravaud P, Chaimani A, Boutron I. Graña C, et al. Cochrane Database Syst Rev. 2022 Dec 7;12(12):CD015477. doi: 10.1002/14651858.CD015477. Cochrane Database Syst Rev. 2022. PMID: 36473651 Free PMC article.
  • COVID-19 Vaccines.
    [No authors listed] [No authors listed] 2025 Aug 15. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. 2025 Aug 15. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. PMID: 33355732 Free Books & Documents. Review.
  • Vaccines for preventing influenza in healthy adults.
    Demicheli V, Jefferson T, Ferroni E, Rivetti A, Di Pietrantonj C. Demicheli V, et al. Cochrane Database Syst Rev. 2018 Feb 1;2(2):CD001269. doi: 10.1002/14651858.CD001269.pub6. Cochrane Database Syst Rev. 2018. PMID: 29388196 Free PMC article.
See all similar articles

References

    1. Attaway A.H., Scheraga R.G., Bhimraj A., Biehl M., Hatipoğlu U. Severe covid-19 pneumonia: Pathogenesis and clinical management. BMJ. 2021;372:n436. doi: 10.1136/bmj.n436. - DOI - PubMed
    1. Leung N.H.L. Transmissibility and transmission of respiratory viruses. Nat. Rev. Microbiol. 2021;19:528–545. doi: 10.1038/s41579-021-00535-6. - DOI - PMC - PubMed
    1. Badawi A.E., Elsheikh S.S., Addeen S.Z., Soliman M.A., Abd-Rabu R., Abdella W.S., Gad E.A. An Ophthalmic Insight into Novel Coronavirus 2019 Disease: A Comprehensive Review of the Ocular Manifestations and Clinical Hazards. J. Curr. Ophthalmol. 2020;32:315–328. doi: 10.4103/JOCO.JOCO_255_20. - DOI - PMC - PubMed
    1. Ng H.W., Scott D.A.R., Danesh-Meyer H.V., Smith J.R., McGhee C.N., Niederer R.L. Ocular manifestations of COVID-19. Prog. Retin. Eye Res. 2024;102:101285. doi: 10.1016/j.preteyeres.2024.101285. - DOI - PubMed
    1. Modjtahedi B.S., Do D., Luong T.Q., Shaw J. Changes in the Incidence of Retinal Vascular Occlusions After COVID-19 Diagnosis. JAMA Ophthalmol. 2022;140:523–527. doi: 10.1001/jamaophthalmol.2022.0632. - DOI - PMC - PubMed

LinkOut - more resources