Risk of Uveitis After COVID-19 Vaccination Exists, But Is Low

Researchers have identified a low incidence of uveitis associated with the US Food and Drug Administration (FDA) emergency-use-approved COVID-19 vaccines, with approximately 1094 cases reported, between December 11, 2020 and May 9, 2022, according to a study published in Ophthalmology.

Investigators examined publicly-available, deidentified data posted in the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS). Analysis outcomes included reporting rates and characteristics of uveitis cases following exposure to BNT162b2 (Pfizer and BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen) vaccines. The crude reporting rate is estimated using number of uveitis diagnoses for every million doses — from 40 countries, this rate was gauged at 0.57 for Pfizer-BioNTech, 0.44 Moderna, and 0.35 for Janssen vaccines. 

Although developing uveitis after one of the vaccines is uncommon, the analysis suggests it is more likely after the first dose (41.32%) than second or subsequent injections, and more often occurs in the first week (54.02%) after the vaccine. Since incidence of vaccine-associated uveitis is rare, physicians may at first suspect a case has another etiology, but “amongst the patients diagnosed with VAU, very few had a history of prior COVID-19 infection (9, 0.8%), uveitis (106, 9.6%), or systemic autoimmune diseases (14, 1.2%).”

Worldwide, the mean age of individuals with VAU was 46.24±16.93 years (68.65% were women). Close to 1.5 billion Pfizer-BioNTech doses have been administered, compared with almost 502 million Moderna, and more than 60 million Janssen shots. Of patients who developed uveitis, 77.9% received Pfizer-BioNTech, 20.1% Moderna, and 1.9% Janssen. Also, for those who received the Moderna vaccine, there was a significantly longer mean time to uveitis onset, 21.22±42.74 days, compared with Pfizer-BioNTech in 11.42±23.16 days, and Janssen at 12.69±16.02 days (P <.0001).

Ocular diagnoses included uncategorized uveitis, along with more specifically named disorders. Anterior uveitis was frequently identified — iridocyclitis, ocular herpes, and iritis. Reports also documented the HLA B-27 protein marker for autoimmune disease. Panuveitis included cases of Behcet’s disease and Vogt-Koyanagi-Harada (VKH). Posterior uveitis involved chorioretinitis, retinitis, and choroiditis. No large differences emerged between anterior, posterior, or panuveitis and the vaccine administered.

Prior studies theorize VAU may be prompted by one of several mechanisms; an immune response to the adjuvants in vaccines that stimulate a stronger response, or molecular similarities of peptides in vaccines with peptides in uveal tissue, prompting an immune reaction. Alternatively, SARS-CoV-2 RNA has been found in ocular tissues such as aqueous, potentially causing an inflammatory response. 

VAERS is a passive system which can entail delayed or under-reporting, limiting the analysis, as well as some nonuniform points of data. Developing countries often have fewer resources with which to report cases. Investigators add that VAERS uses a broadly categorized classification based on Medical Dictionary for Regulatory Activities (MedDRA) definitions. And although a temporal association is indicated in this study, it does not prove causality.