Increased risk of uveitis and optic neuritis after herpes zoster reactivation in COVID-19: a TriNetX database study

BACKGROUND: Herpes zoster (HZ) reactivation following COVID-19 suggests immune dysregulation, posing a risk for long-term neuro-ophthalmic sequelae. AIM: This study investigates the relationship between post-COVID HZ and the subsequent hazard of uveitis and optic neuritis. DESIGN: This retrospective analysis used the TriNetX Research Network, following patients for 3 years. METHODS: Propensity score matching (PSM) was performed on COVID-19 survivors, comparing the HZ-exposed group (n = 11 172) against a matched HZ-unexposed control group (n = 11 173). Cox proportional hazards models calculated the 3-year Hazard Ratios (HRs) for incident uveitis and optic neuritis. RESULTS: Post-COVID-HZ reactivation was associated with a significantly elevated and persistent risk of both outcomes. HZ was consistently related to a 3.06-fold increase in the hazard of uveitis (HR = 3.06; 95% CI, 2.56-3.65; P < 0.001) and a 2.10-fold increase in the hazard of optic neuritis (HR = 2.10; 95% CI, 1.62-2.71; P < 0.001). The relationships remained significant across sensitivity analyses, and the risk remained high even in the vaccinated subgroup. CONCLUSIONS: HZ reactivation after COVID-19 is related to a higher instantaneous risk of subsequent uveitis and optic neuritis, even among immunocompetent individuals. HZ may serve as a clinical marker for neuro-immune injury, supporting the consideration of targeted ophthalmic surveillance and timely antiviral intervention to prevent vision loss.