Effect of COVID-19 and Vaccine on Retinal Disease

Multiple cases, case series, and cohort studies report the development of retinal disease after COVID-19 and COVID-19 vaccination, and knowledge that COVID-19 can cause vascular damage and coagulopathy provides biologic plausibility implicating the infection and vaccination in these events. Thus far, however, findings from research analysing clinical registry data show no proof of causality, according to Rahul N Khurana MD.

“Establishing causality is extremely challenging when there is a high incidence of both the possible causal factor and its effect,” Dr Khurana noted. “I think the answer for doing so lies with big data.”

Outlining the evidence

Reviewing research investigating a cause and effect relationship between COVID-19 infection and retinal disease, Dr Khurana discussed a study using the American Academy of Ophthalmology IRIS registry as a data source to determine rates of retinal vein occlusions (RVOs) in the 3 years preceding the start of the pandemic (2017–2019) and the first 3 years from its onset (2020–2022).¹ Results showed the number of branch RVOs and central retinal artery occlusions did not increase during the pandemic era, while central RVOs decreased. Another study using the Vestrum Health database of medical records from more than 65 private US retina clinics as a resource generated consistent findings.²

“Ophthalmic care utilisation was suppressed during the pandemic, and so more severe diagnoses accounted for a larger percentage of our clinic visits, which gives us the impression that their incidence was higher,” Dr Khurana explained.

Although the findings from both studies seem compelling, neither database had information on COVID-19 diagnosis. A nationwide population study in South Korea that included data from more than 8.5 million patients overcame that limitation. This more definitive study found no increase in either retinal artery occlusion (RAO) or RVO within 60 days after a COVID-19 diagnosis.³

Research investigating a cause and effect relationship between COVID-19 vaccination and retinal disease also provides reassuring findings, Dr Khurana said.

In a study using the TriNetX Analytics platform, which includes deidentified medical records of more than 100 million patients from 77 healthcare organisations across 9 countries, researchers found a very low rate of RVO (0.003%) 3 weeks after a first COVID-19 vaccination among 3 million vaccine recipients.⁴ Moreover, the RVO rate was similar after influenza or tetanus/diphtheria/pertussis vaccination in a propensity score-matched control group.

The study from South Korea provided further evidence that COVID-19 vaccination does not increase retinal vascular occlusive events by showing no increase in RAO or RVO within 60 days after vaccination.³ A subgroup analysis showed a possible small increase in RAO among women who received an mRNA vaccine, but the incidence was low (0.0028%), Dr Khurana said.

A third piece of evidence comes from a retrospective analysis of data in the Centers for Disease Control Vaccine Adverse Events Reporting System.⁵

“This system involves passive surveillance, and so there could be underreporting,” Dr Khurana stressed. “Nevertheless, a study reviewing more than 2 billion vaccines admin­istered globally found only 1,351 reported RVOs with very low crude rates for each of the three vaccine types. These data show a low concern about retinal safety of COVID-19 vaccination.”

Dr Khurana spoke about this topic at AAO 2024 Retina Subspecialty Day in Chicago, US.

Rahul N Khurana MD is Chief Executive Officer and Partner at North California Retina Vitreous Associates, Mountain View, California, US. rnkhurana@gmail.com

1. Lum F, Li C, Khurana RN. “Retinal vascular occlusions did not increase since the start of the coronavirus disease 2019 pandemic,” Ophthalmol Retina, 2024; 8(4): 415–417.

2. Al-Moujahed A, Boucher N, Fernando R, et al. “Incidence of retinal artery and vein occlusions during the COVID-19 pandemic,” Ophthalmic Surg Lasers Imaging Retina, 2022; 53(1): 22–30.

3. Park HS, Lee NK, Lee CS, et al. “Retinal artery and vein occlusion risks after coronavirus disease 2019 or coronavirus disease 2019 vaccination,” Ophthalmology, 2024; 131(3): 322–332.

4. Dorney I, Shaia J, Kaelber DC, Talcott KE, Singh RP. “Risk of new retinal vascular occlusion after mRNA COVID-19 vaccination within aggregated electronic health record data,” JAMA Ophthalmol, 2023; 141(5): 441–447.

5. Singh RB, Parmar UPS, Gupta R, et al. “Retinal vascular occlusion following SARS-CoV-2 vaccination: A VAERS database analysis,” Ophthalmol Sci, 2023; 4(1): 100354.