Uveitis History Linked to Recurrence After COVID Vaccination

People with a history of uveitis were more likely to experience recurrences of the potentially dangerous eye inflammation after vaccination against COVID-19, a retrospective population-based cohort study from South Korea found.

Of 473,934 vaccinated individuals with a prior case of uveitis, 16.8% developed it again within a year of vaccination, with an overall 21% elevated risk compared with the pre-vaccination period, Seong Joon Ahn, MD, PhD, of Hanyang University Seoul Hospital in South Korea, and colleagues reported in JAMA Ophthalmology.

The risk was especially high in the initial 30 days after the first shot as compared with the pre-vaccination period (HR 1.64, 95% CI 1.55-1.73) and in patients who received the Johnson & Johnson Ad.26.COV2.S vaccine, which is no longer available in the U.S. (HR 2.07, 95% CI 1.40-3.07).

"These findings suggest that there was an elevated risk of uveitis following COVID-19 vaccination, with the vaccine type and period mediating this risk," the authors wrote. "For individuals with a history of uveitis, clinicians should consider the potential risk of uveitis recurrence in vaccination strategies and clinical monitoring."

Although rare, uveitis remains a leading cause of legal blindness in the U.S.

Prior findings on a link between uveitis and COVID-19 vaccines have been mixed. A 2023 analysis of the CDC's Vaccine Adverse Event Reporting System concluded it's a "low safety concern," with estimated incident rates per million persons of 0.57 with Pfizer's BNT162b2 mRNA vaccine (Comirnaty) vaccine, 0.44 with Moderna's mRNA-1273 (Spikevax), and 0.35 with the Johnson & Johnson vaccine. However, a similar 2024 study from British regulators found no links between the vaccines and uveitis in the general population.

The new study aimed to determine if uveitis risk is higher in those with a history of the condition and whether the risk levels differ by type of vaccine or timing of doses.

Within the 3 months after vaccination, 8.6% of patients had anterior uveitis, and 1.6% nonanterior uveitis. The total rates grew to 12.5% at 6 months and 16.8% at 12 months. The ratio of anterior to nonanterior forms remained about the same at 4.4 and 4.8, respectively.

Overall, the post-vaccination rate was higher than pre-vaccination (HR 1.21, 95% CI 1.19-1.24), although it decreased after the initial 30 days after the first vaccine dose. The researchers speculated that an "increased immune response following the initial dose might activate inflammatory pathways, resulting in conditions like uveitis, particularly in individuals prone to autoimmune reactions or with a uveitis history." Later, they wrote, the declining risk "may stem from the immune system adapting to the vaccine antigen, resulting in a more controlled immune response that mitigates inflammatory side effects."

In a commentary accompanying the paper, Anika Kumar, BA, and Nisha Acharya, MD, MS, of the University of California San Francisco, noted that it's important to consider the study findings in light of the risk of not getting vaccinated against COVID-19. On the ocular front alone, conjunctivitis is a well-known symptom in COVID-19, which is also linked to a long list of other ocular conditions.

For their study, the researchers tracked all 473,934 patients in South Korea who were vaccinated, had a history of uveitis, and did not develop COVID-19 during the study period using national healthcare databases. Among these patients, 51.3% were female, the mean age was 59 years, 74.3% had rheumatic diseases, and 45.7% had hypertension. Nearly 40% had four vaccine doses.

By type of vaccine, 36.3% of the individuals received the AstraZeneca ChAdOx1 shot, and 9.3% of those developed uveitis in the 30 days after the first dose. Those numbers were 51.2% and 9.9%, respectively, for Pfizer's vaccine; 10.3% and 10.4% for Moderna's shot; and 2% and 11.7% for the single-dose Johnson & Johnson vaccine.

The uveitis hazard ratios for the 30 days after the first dose versus the pre-vaccination period were:

• Pfizer: HR 1.68 (95% CI 1.52-1.86)
• Moderna: HR 1.51 (95% CI 1.21-1.89)
• AstraZeneca: HR 1.60 (95% CI 1.43-1.79)
• Johnson & Johnson: HR 2.07 (95% CI 1.40-3.07)

The authors noted limitations such as a reliance on diagnostic codes and lack of information about uveitis severity or use of anti-inflammatory drugs that could decrease the risk of uveitis. The commentary authors also noted that the approach used "did not account for the healthy vaccinee bias, which refers to how individuals in better health are more likely to receive vaccinations."

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