“Aqueous Humor Complement C3 And C4 As Predictive Biomarkers For Risk Of Rebound Inflammation In Uveitic Cataract Surgery”

To evaluate whether intraocular complement fractions C3 and C4 in aqueous humor can serve as predictive biomarkers of inflammatory activity and perioperative risk in patients with uveitic cataract undergoing surgery.

Cornea-Uveitis Department, S.V. Malayan Eye Center, Yerevan, Armenia

This prospective case–control study included 118 patients examined between March 2022 and November 2023. Fifty-eight patients had uveitis classified according to SUN criteria (idiopathic anterior, herpetic anterior, HLA-B27–associated, Behçet-related, and Fuchs uveitis). Sixty control patients undergoing routine cataract or pterygium surgery without inflammatory disease were included for comparison. Complement C3 and C4 levels were measured in serum and aqueous humor samples obtained at the time of surgery. Associations between complement levels, uveitis subtype, and clinical inflammatory severity were analyzed. Receiver operating characteristic (ROC) analysis was performed to determine predictive thresholds.

Serum C3 and C4 levels did not differ between groups (p>0.05). In contrast, aqueous humor C3 and C4 were detected only in uveitis patients and were significantly higher than in controls (p<0.05). Intraocular complement levels were highest in HLA-B27–associated and Behçet uveitis, subtypes linked to aggressive inflammation and increased postoperative risk. Fuchs uveitis showed absent C3 but elevated C4, suggesting differential pathway activation and a distinct surgical inflammatory profile. Aqueous complement levels correlated with clinical inflammation severity. ROC analysis showed C3 ≥0.005 g/L predicted active inflammation with 76% sensitivity and 100% specificity, while C4 ≥0.000825 g/L showed 82.8% sensitivity and 100% specificity.

Complement activation in uveitis appears to be a localized intraocular process not reflected by serum testing. Elevated aqueous C3 and C4 levels may serve as objective biomarkers of subclinical inflammatory activity and could help identify patients at higher risk of postoperative inflammatory complications in uveitic cataract surgery. Incorporation of aqueous complement analysis may assist in surgical timing decisions, perioperative anti-inflammatory optimization, and individualized risk stratification.