To compare the 5-year longitudinal risk of major ocular complications—specifically secondary glaucoma, corneal edema, and cystoid macular edema (CME)—between herpetic and non-herpetic anterior uveitis (AU) using a global federated health research database.

A retrospective cohort study was conducted using the TriNetX Research Network. Two cohorts were identified: (1) Herpetic AU (n=5,385) and (2) Non-Herpetic AU (n=52,634). To ensure the analysis captured new-onset complications, 22,118 patients with pre-existing conditions prior to the index uveitis diagnosis were excluded. Primary outcomes included the development of glaucoma, corneal disorders, or CME within 5 years of diagnosis. Risk ratios (RR) and Kaplan-Meier (KM) survival analyses were utilized for comparison.

The cumulative risk of developing at least one secondary complication was significantly higher in the herpetic AU cohort (21.45%) than in the non-herpetic cohort (13.39%). Herpetic etiology was associated with a 1.6-fold increased risk of complications (RR: 1.602; 95% CI: 1.515-1.693; p < 0.0001). KM analysis demonstrated a lower probability of remaining complication-free at 5 years for herpetic patients compared to controls (75.03% vs. 81.81%; Log-Rank Test p < 0.0001).

Herpetic anterior uveitis is associated with a significantly higher burden of both anterior and posterior segment morbidity compared to other etiologies of anterior inflammation. These findings suggest that herpetic patients require long-term, multi-modal monitoring for glaucoma, endothelial health, and macular edema in this population.