Causation or Association: Important Considerations for mRNA Vaccines in Patients With Ophthalmic Disease: The COVID-19 Pandemic and Beyond : The Asia-Pacific Journal of Ophthalmology

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Scientific Correspondence

Causation or Association: Important Considerations for mRNA Vaccines in Patients With Ophthalmic Disease: The COVID-19 Pandemic and Beyond

Guo, Brad MBBS, MMed; Chakrabarti, Rahul BMedSc, MSurgEd

Author Information
Asia-Pacific Journal of Ophthalmology 12(4):p 415-416, July/August 2023. | DOI: 10.1097/APO.0000000000000532

The impact of the coronavirus disease 2019 (COVID-19) may be alleviated by dissemination of vaccines, of which messenger ribonucleic acid (mRNA) is an important subtype. As of January 2022, over 50% of the population is double vaccinated with developing policies that encourage the remainder of the population to complete vaccination. Vaccinations have demonstrated a 10-fold decrease in COVID-related hospitalizations and mortality, with recent evidence of boosters associated with another 10-fold decrease in COVID-related mortality.1 There is also an evolving necessity to understand mRNA vaccination beyond COVID-19, with its application in the prevention of other viral infections and cancer treatment, so ophthalmologists must be aware of possible associations with ocular conditions and be able to provide patients with well-informed advice in the future.2

This correspondence highlights important questions relevant to ophthalmologists to better understand the association of mRNA-based COVID-19 vaccination with ocular disease, and practical considerations in patient counselling and relevant clinical questions.3 Ultimately, any medical intervention should involve informed consent and the possibility of preemptive measures may be considered, while preserving the upmost necessity for vaccination.

The safety profiles of COVID-19 vaccines have been widely reported; however, there remains limited data for patients with ophthalmological disease. There is no unifying literature that definitively links ophthalmic disease and COVID-19 vaccination, so our understanding is limited to case reports and series, as presented in Supplementary Digital Content Table 1 ( Associations have been implicated for cornea and external eye, ocular inflammation, retina, neuro-ophthalmology, and orbital disease. Authors describe favorable outcomes and disease control for a vast majority of ophthalmic complications potentially associated with COVID-19 vaccination.

Hypothesized mechanisms that may cause ophthalmic events include the use of adjuvants in mRNA vaccinations that stimulate innate immunity through cytoplasmic nucleic acid receptors, and particularly affect autoimmune disease associated with altered nucleic acid metabolism.4 It is still important to consider whether the ocular conditions described are incidental in their timing from recently receiving a COVID-19 vaccination, or whether there is a true causative explanation. Careful pharmacovigilance of mRNA vaccinations, especially in the setting of rapid progression from development to utility is essential in firstly safeguarding our population with robust adverse event monitoring and establishing public trust.

There is significant scrutiny on COVID-19 vaccine adverse events; however, ophthalmic sequalae of vaccinations are not new. Well-established, yet broadly accepted vaccinations, such as the live-attenuated measles-mumps-rubella, nasal spray influenza vaccine, rotavirus vaccine, yellow fever vaccine, and original live attenuated varicella vaccine have been associated with complications too.5 Among these vaccines, major ophthalmic manifestations reported include uveitis, optic neuritis, corneal ulceration, and central retinal artery occlusion, estimated at 1 per 100,000.6

Ophthalmologists remain in ongoing dilemma for the treatment of patients with COVID-19 infection that have ocular conditions requiring immunosuppression.7 In terms of management, there is no evidence for prophylactic treatment of patients with preexisting disease, such as uveitis or herpes zoster ophthalmicus, who will be planning to have COVID-19 vaccination or have active infection.

Although ophthalmic complications from COVID-19 vaccination are undesirable, COVID-19 infection causing ocular disease are more common and may result in more severe outcomes. In addition to conditions associated with vaccination described in our supplmentary data (, COVID-19 infection can cause retinal disease, for example, acute retinal necrosis, nonspecific peripheral retinal hemorrhages, macular hyperpigmentation, retinal sectoral pallor, hard exudates, and cotton wool spots have been described.8 Serious orbital disease associated with COVID-19 infection have included orbital cellulitis and mucormycosis.9

There are currently no recommendations regarding the timing of COVID-19 vaccinations specifically in relation to ocular procedures or surgery. Preoperative vaccination at least 2 weeks before surgery has been associated with lower rates of postoperative morbidity across broad surgical disciplines.10

Understanding this topic is important so that ophthalmologists may appropriately counsel patients on potential associations with the COVID-19 vaccination and allow for early identification of disease requiring management. Beyond the COVID-19 pandemic, literature about ophthalmic associations of mRNA vaccination will additionally be valuable to guide risk management for its evolving utility in other therapy.

Brad Guo, MBBS, MMed and

Rahul Chakrabarti, BMedSc, MSurgEd


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3. Lin T, Ko C-N, Zheng K, et al. COVID-19: update on its ocular involvements, and complications from its treatments and vaccinations. Asia Pac J Ophthalmol (Phila). 2021;10:521–529.
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7. Thng ZX, De Smet MD, Lee CS, et al. COVID-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs. Br J Ophthalmol. 2020;105:306–310.
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9. Werthman-Ehrenreich A. Mucormycosis with orbital compartment syndrome in a patient with COVID-19. Am J Emerg Med. 2020;42:264.e5–264.e8.
10. Prasad NK, Lake R, Englum BR, et al. COVID-19 vaccination associated with reduced post-operative SARS-COV-2 infection and morbidity. Ann Surg. 2021;275:31–36.

Supplemental Digital Content

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