Cases of Vision-Threatening Clots Rare After COVID Shot, Study Finds

Retinal vascular occlusion (RVO) did not occur more frequently in the 3 weeks following administration of an mRNA COVID-19 vaccine compared with influenza and tetanus, diphtheria, and pertussis (Tdap) vaccines, a retrospective study showed.

In a propensity score-matched analysis using 3 million electronic health records (EHRs), a new diagnosis of RVO, a serious, potentially vision-threatening condition, occurred in 0.003% of patients within 21 days of COVID vaccination, reported Rishi P. Singh, MD, of the Cleveland Clinic Cole Eye Institute in Ohio, and colleagues.

The relative risk for a new RVO diagnosis after the first dose of mRNA COVID vaccine was not significantly different from that after influenza vaccination (RR 0.74, 95% CI 0.54-1.01) or Tdap vaccination (RR 0.78, 95% CI 0.44-1.38), they said in JAMA Ophthalmology.

Furthermore, a post-hoc analysis performed by the researchers showed a fourfold higher risk of RVO after COVID infection versus after mRNA vaccination (RR 4.25, 95% CI 3.24-5.56), in line with prior research showing an increased RVO risk after infection.

"The risk for new-encounter diagnosis of RVO acutely after the first dose of the mRNA COVID-19 vaccine, based on ICD-10 codes, was found to be extremely low," Singh and team wrote. "If there does exist an association between mRNA COVID-19 vaccination and new-encounter diagnoses for RVO, it occurs at similar rates experienced after influenza and Tdap vaccinations that have been administered for decades throughout the population."

Of note, the relative risk for a new RVO diagnosis after the first dose of COVID vaccination was greater when compared with the second dose of COVID vaccine (RR 2.25, 95% CI 1.33-3.81).

The higher relative risk after the first dose may mean that the first dose comes with more risk, the authors noted, but it could also mean that those who had symptoms after the first dose did not receive a second dose.

To date, over 650 million doses of mRNA COVID vaccine have been administered in the U.S., according to the CDC. Reports describing RVO cases after COVID vaccination have been published in 2021 and 2022.

"It is very difficult to determine whether the association of retinal vascular occlusion and prior vaccination is coincidental," wrote Lee M. Jampol, MD, of the Feinberg School of Medicine at Northwestern University in Chicago, and Maureen G. Maguire, PhD, of the University of Pennsylvania in Philadelphia, in an invited commentary.

RVOs, which occurs when a blood clot blocks the vein, are relatively rare, with an annual incidence of 150 per 100,000 people. Given that vaccine-induced immune thrombotic thrombocytopenia is a rare complication of adenoviral vector-based COVID vaccination (and even rarer with mRNA vaccines), there is a "biologic plausibility" for occurrence, Jampol and Maguire noted.

They said that to evaluate the incidence of RVO after COVID vaccination is difficult, and having done so through a comparison with the incidence after influenza and Tdap vaccination is "an ingenious approach."

However, they pointed out that this approach "does not provide a comparison with a group of people who did not receive any recent vaccination or especially those who did not receive COVID-19 vaccination."

"Without a comparable group of people without mRNA COVID-19 vaccination, it is difficult to rule out an association," Jampol and Maguire wrote, adding that "we should acknowledge that our understanding of retinal complications after any vaccination is incomplete."

For this study, Singh and colleagues used the TriNetX Analytics platform, a federated, aggregated EHR research network, to search for the presence of vaccination codes, and instances of newly diagnosed RVO within 21 days of vaccination.

Propensity score matching was performed for age, sex, race and ethnicity, and comorbidities, including diabetes, hypertension, and hyperlipidemia.

They included 3,108,829 people who received a COVID vaccine. Mean age at vaccination was 50.7, 56.4% were women, 64% were white, and 12% were Black. Of these people, 12.4% had diabetes, 28% had hypertension, and 20% had hyperlipidemia.

Singh and colleagues noted that the data are limited to what was recorded in the EHR, and do not describe the severity of symptoms or pathophysiologic connections. Furthermore, although a 21-day follow-up was "logical," there may be RVO diagnoses that occur after this time.

"Further detailed research on patients experiencing RVO after vaccination is necessary to elucidate risk factors for this vision-threatening condition," they wrote.