Post-COVID-19 vax uveitis may be more common in Southeast Asia

COVID-19 vaccination-induced uveitis is uncommon, with cases mostly self-limiting and showing good responses to treatment with no long-term sequelae, according to a Singapore study. However, reactivation of such infections appears to occur at a higher proportion in Southeast Asia, where viral and toxoplasma infections are more common.

In a cohort of 431 individuals who completed primary vaccination as per Singapore's National COVID-19 Vaccination program over a 1-year period in 2021, six patients (1.39 percent; mean age 50 years, four women) developed uveitic flare within a mean of 9.7 days after their second dose. Three of them had noninfectious anterior uveitis, whereas the remaining three with infectious uveitis also presented with a reactivation of cytomegalovirus (CMV), toxoplasma chorioretinitis, and varicella-zoster virus (VZV), respectively. [Front Med 2022;doi:10.3389/fmed.2022.925683]

Five patients presented with blurring of vision, three with red eye, and one with eye pain. All of them responded to definitive treatment specific to their diagnosis, with the mean visual acuity improving from 0.36 logMAR at presentation to 0.75 logMAR (p=0.009).

“In our study, we used strict inclusion criteria to minimize the possibility of coincidental recurrences and better establish causality. Our patients were quiescent based on the Standardization of Uveitis Nomenclature (SUN) criteria for a mean of 3.3 years and were not on any topical or systemic treatment at the time of vaccination,” the investigators pointed out.

Of the six patients with COVID-19 vaccination-induced uveitis, five had received the BNT162b2b Pfizer-BioNTech vaccine while only one received the BBIBP-CorV Sinopharm vaccine. Four patients underwent a third booster dose 270 days after their second dose. One patient specifically experienced a recurrence after the third booster dose. None of the three patients with infectious uveitis developed recurrence, but each one of them had been on maintenance therapy up to or during the booster.

“Our low rates of COVID-19 vaccination-related uveitis also corroborates with rheumatologic series that report a low rate of rheumatological flares (4.4 percent) in patients with autoimmune and musculoskeletal disease,” according to the investigators. [Ann Rheum Dis 2021;doi:10.1136/annrheumdis-2021-221490]

At the same time, the data also reflect a higher proportion of infectious uveitis, in comparison to the reports from multinational groups, Israel, and the Middle East where a higher predominance of noninfectious anterior uveitis was reported, the investigators added.

“We also did not report significant posterior uveitis other than toxoplasma retinochoroiditis, although retinal involvement has been described,” they said. [J Ophthalmic Inflam Infect 2022;doi:10.1186/s12348-021-00275-x; Retina 2021;41:2462-2471; Am Med Assoc Ophthalmol 2021;139:1131-1135; Ocul Immunol Inflamm 2021;29:753-757]

Potential to trigger autoimmunity

While largely unknown, the underlying pathophysiology for why COVID-19 vaccine can induce uveitis in some patients is believed to involve autoimmunity triggered by the vaccines. [Int J Rheum Dis 2022;25:83-85; Rheumatology 2021;60:SI90- SI95]

“It can be possibly due to a combination of various mechanisms including molecular mimicry, production of particular autoantibodies, antigen-antibody hypersensitivity reactions, as well as the role of certain vaccine adjuvants. Vaccination triggers a cascade of pro-inflammatory Type 1 Interferon expression, which results in the protective immune response, but can also trigger the production of autoantibodies responsible for an autoimmune phenomena,” the investigators explained. [Ocul Immunol Inflamm 2019;27:517-520; Nat Rev Immunol 2021;21:195-197; Immunology 2022;165:386-401]

“For a latent viral reactivation (specifically for VZV and CMV), it has been postulated to be related to the robust T-cell response following vaccination which causes a massive shift and increased CD8+ T cell and T-helper type 1 (Th1) CD4+ T cells specific for the spike protein or other antigens of SARS-CoV-2… Likewise, the massive shift of T-cell shift following vaccination can similarly precipitate a toxoplasma reactivation,” they added. [Nat Rev Immunol 2021;21:195-197; Vaccines 2021;9:1013]

The investigators considered the potential of prophylactic treatment prior to COVID-19 booster shots, pointing out that while its role in preventing flares related to COVID-19 vaccination may not be warranted for all patients given the low incidence, it can help address vaccine or booster hesitancy.

“Although some of our patients were on prophylactic or maintenance doses for infectious uveitis during their booster, we suggest a balance of risk vs benefits discussion with individual patients and close monitoring in view of the low rates of recurrence in our series,” according to the investigators.

“As there is increasing need for booster vaccination with the recent emergence of the Omicron [variant], it is important for ophthalmologists and generalists to be cognizant of COVID-19-related uveitis and be ready to advise patients who may want to defer vaccination or booster injections for fear of uveitis flares as the benefits of COVID-19 vaccination and booster still outweigh the risk of uveitis,” they said.