Association between Vaccination with the BNT162b2 mRNA Coronavirus Disease 2019 Vaccine and Noninfectious Uveitis: A Population-Based Study.

PURPOSE: To assess the association between BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine and the risk of active noninfectious uveitis (NIU). DESIGN: Retrospective, population-based study. PARTICIPANTS: Two million six hundred two thousand five hundred fifty-seven people who received the first vaccine dose between December 20, 2020, and April 30, 2021, and 2 441 719 people who received the second vaccine dose between January 10, 2021, and April 30, 2021. METHODS: Events of active NIU were included if they occurred within 21 days after either vaccine dose. Active NIU was defined as newly active or worsening ocular inflammation requiring initiation or increase in local or systemic corticosteroids. Observed cases were compared with the expected number, based on the experience of the population in 2019. MAIN OUTCOME MEASURES: Age- and sex-adjusted standardized incidence ratios (SIRs) and attributable risks after BNT126b2 vaccination. RESULTS: Overall, 100 and 88 events of active NIU were recorded within 21 days after the first and second vaccine doses, respectively. Using the experience of the population in 2019 as a reference, after the first dose, the estimated age- and sex-adjusted SIR was 1.41 (95% confidence interval [CI], 1.15-1.71) along with a 21-day attributable risk of 1.12 cases per 100 000 vaccinees. After the second dose, the SIR was 1.31 (95% CI, 1.05-1.62), with an estimated attributable risk of 0.86 cases per 100 000 vaccinees. Anterior uveitis was the most common site of inflammation, occurring in 90.96% of eyes, and idiopathic uveitis was the most common cause (56.38%). CONCLUSIONS: This study suggests that the BNT162b2 mRNA COVID-19 vaccine may be associated with an increased risk of active NIU. However, considering the small effect size and study limitations, this study does not provide proof for a cause-and-effect relationship. The small estimated attributable risks suggest that the impact on public health is relatively minor.

Association between Immunosuppressive Drugs and Coronavirus Disease 2019 Outcomes in Patients with Noninfectious Uveitis in a Large US Claims Database.

PURPOSE: To determine the dose-dependent risk of systemic corticosteroids (SCs) and the risk of other immunosuppressive therapies on coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in patients with noninfectious uveitis (NIU). DESIGN: A retrospective cohort study from January 20, 2020, to December 31, 2020 (an era before widespread COVID-19 vaccination), using the Optum Labs Data Warehouse, a US national de-identified claims database. PARTICIPANTS: Patients who had at least 1 NIU diagnosis from January 1, 2017. METHODS: Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models, with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of SC exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models as a continuous variable, in addition to the dichotomous variable. MAIN OUTCOME MEASURES: Incidence rates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death. RESULTS: This study included 52 286 NIU patients of whom 12 000 (23.0%) were exposed to immunosuppressive medications during the risk period. In adjusted models, exposure to SCs was associated with increased risk of COVID-19 infection (HR, 2.66; 95% confidence interval [CI], 2.19-3.24; P < 0.001), hospitalization (HR, 3.26; 95% CI, 2.46-4.33; P < 0.001), and in-hospital death (HR, 1.99; 95% CI, 0.93-4.27; P = 0.08). Furthermore, incremental increases in the dosage of SCs were associated with a greater risk for these outcomes. Although tumor necrosis factor-α (TNF-α) inhibitors were associated with an increased risk of infection (HR, 1.48; 95% CI, 1.08-2.04; P = 0.02), other immunosuppressive treatments did not increase the risk of COVID-19 infection, hospitalization, or death. CONCLUSIONS: This study from an era before widespread COVID-19 vaccination demonstrates that outpatient SC exposure is associated with greater risk of COVID-19 infection and severe outcomes in patients with NIU. Future studies should evaluate the impact of immunosuppression in vaccinated NIU patients. Limiting exposure to SCs and use of alternative therapies may be warranted.

The Association between Noninfectious Uveitis and Coronavirus Disease 2019 Outcomes: An Analysis of United States Claims-Based Data.

PURPOSE: To identify if noninfectious uveitis (NIU) is associated with a greater risk of Coronavirus Disease 2019 (COVID-19) infection, hospitalization, and death. DESIGN: A retrospective cohort study from January 20, 2020 to December 31, 2020, using a national claims-based database. PARTICIPANTS: Enrollees who had continuous enrollment with both medical and pharmacy coverage for 3 years before January 20, 2020. Patients with an NIU diagnosis within 3 years of the start of the study were included in the NIU cohort. Those with infectious uveitis codes or new NIU diagnoses during the risk period were excluded. METHODS: Cox proportional hazard models were used to identify unadjusted hazard ratios (HRs) and adjusted HRs for all covariates for each outcome measure. Adjusted models accounted for patient demographics, health status, and immunosuppressive medication use during the risk period. MAIN OUTCOME MEASURES: Rates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death identified with International Classification of Disease 10th revision codes. RESULTS: This study included 5 806 227 patients, of whom 29 869 (0.5%) had a diagnosis of NIU. On unadjusted analysis, patients with NIU had a higher rate of COVID-19 infection (5.7% vs. 4.5%, P < 0.001), COVID-19-related hospitalization (1.2% vs. 0.6%, P < 0.001), and COVID-19-related death (0.3% vs. 0.1%, P < 0.001). However, in adjusted models, NIU was not associated with a greater risk of COVID-19 infection (HR, 1.05; 95% confidence interval [CI], 1.00-1.10; P = 0.04), hospitalization (HR, 0.98; 95% CI, 0.88-1.09; P = 0.67), or death (HR, 0.90, 95% CI, 0.72-1.13, P = 0.37). Use of systemic corticosteroids was significantly associated with a higher risk of COVID-19 infection, hospitalization, and death. CONCLUSIONS: Patients with NIU were significantly more likely to be infected with COVID-19 and experience severe disease outcomes. However, this association was due to the demographics, comorbidities, and medications of patients with NIU, rather than NIU alone. Patients using systemic corticosteroids were significantly more likely to be infected with COVID-19 and were at greater risk of hospitalization and in-hospital death. Additional investigation is necessary to identify the impact of corticosteroid exposure on COVID-19-related outcomes.