New-Onset Retinal Vascular Occlusion Rare After mRNA COVID-19 Vaccination

Rishi P. Singh, MD

Credit: PRIME

The risk for a new-encounter diagnosis of retinal vascular occlusion (RVO) acute after the first dose of messenger RNA (mRNA) COVID-19 vaccination was observed to be extremely low, according to new research.¹

An investigative team, led by Rishi P. Singh, MD, Cleveland Clinic Cole Eye Institute, found that RVO diagnosed acutely after mRNA COVID-19 vaccination occurs extremely rarely and at rates similar to those historically observed with vaccinations, including influenza and tetanus, diphtheria, pertussis (Tdap) vaccines.

“The baseline risk for developing new RVO independent of any vaccine within a 21-day timeframe must be considered with the low number of observed RVO cases,” Singh and colleagues wrote.¹ “However, it remains possible that RVO is a direct adverse effect of the mRNA COVID-19 vaccine among certain patient populations that are too few to produce significant results at the population level or that electronic health record (EHR) data limitations mask an association.”

A growing interest in RVO as a possible adverse effect of mRNA COVID-19 vaccination has been reported, with recent literature describing an occurrence of RVO in patients within days of COVID-19 vaccination. The condition often manifests with variable vision loss, scotomas, and blurred vision. However, the association between COVID-19 vaccination and RVO remains unclear because the reported temporal association may be coincidental and epidemiologic evidence is scarce.

Singh and colleagues set out to analyze how often individuals are diagnosed with new RVO acutely after the mRNA COVID-19 vaccine compared with influenza and Tdap vaccines. A retrospective population-based cohort design using the TriNetX Analytics Platform, a federated health research network of more than 103 million patients, was queried for patients receiving vaccinations and examining diagnoses of RVO occurring within 21 days after each vaccination. Data were collected and analyzed in October 2022.

Four cohort groups were identified: group 1 received the first mRNA COVID-19 dose from December 2020 – June 2022; group 2 received the second dose of mRNA COVID-19 vaccine from December 2020 – June 2022; group 3 received influenza vaccine from June 2018 – December 2019; group 4 received Tdap vaccine from June 2018 to December 2019.

Each group was indexed to the respective vaccination event and any diagnosis of RVO within 21 days of vaccination was recorded. Singh and colleagues performed propensity score matching based on demographic characteristics (age, sex, race, and ethnicity) and comorbidities (diabetes, hypertension, and hyperlipidemia) between vaccination groups to evaluate relative risks (RRs).

Of 3,108,829 patients (mean age at vaccination, 50.7 years; 56.4% women) who received the mRNA COVID-19 vaccine, 104 patients (0.003%; 95% CI, 0.003 - 0.004) had a new diagnosis of RVO within 21 days of vaccination, or 3.4 individuals per 100,000.

After 1:1 propensity score matching, the RR for a new diagnosis of RVO after the first dose of mRNA COVID-19 vaccination was not significantly different from that after influenza (RR, 0.74; 95% CI, 0.54 - 1.01) or Tdap (RR, 0.78; 95% CI, 0.44 - 1.38) vaccinations.

However, the RR of a new-onset diagnosis of RVO after the first COVID-19 vaccination was 2.25 (95% CI, 1.33 - 3.81) times the RR of a new-onset diagnosis of RVO after the second COVID-19 vaccine. In a posthoc analysis, data showed COVID-19 infection may carry a higher risk for new RVO than mRNA vaccination, with a 4.25 (95% CI, 3.24 - 3.56) times higher risk.

Singh and colleagues called for further research on those experiencing RVO after vaccination, particularly those who have a history of RVO or a predisposition to the condition.

In an accompanying editorial, Lee M. Jampol, MD, Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, suggested that without a comparable group without mRNA COVID-19 vaccination, it is difficult to rule out an association based on the provided results. However, Jampol noted that the very low incidence is noteworthy.²

“We can be confident that the risk of retinal vascular occlusion is small and should definitely not deter the widespread use of appropriate vaccination for COVID-19,” Jampol wrote.² “It would be important to know whether the results with other COVID-19 vaccines are similar.”

References

1. 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. Published online April 13, 2023. doi:10.1001/jamaophthalmol.2023.0610
2. Jampol LM, Maguire MG. No Red Flags for Risk of Retinal Vascular Occlusion After mRNA COVID-19 Vaccination. JAMA Ophthalmol. Published online April 13, 2023. doi:10.1001/jamaophthalmol.2023.0925