Predictive value of the serum albumin-to-globulin ratio combined with selected serum inflammatory cytokines for poor 3-month treatment response in immune-mediated noninfectious uveitis

To assess whether the serum albumin-to-globulin ratio (AGR), alone and in combination with selected serum inflammatory cytokines, predicts poor 3-month treatment response in patients with immune-mediated noninfectious uveitis. This prospective observational cohort study included 200 patients with immune-mediated noninfectious uveitis, comprising 50 patients each with ankylosing spondylitis-associated uveitis, Vogt–Koyanagi–Harada-associated uveitis, Behçet disease-associated uveitis, and noninfectious choroiditis-spectrum uveitis. Fifty healthy controls were frequency-matched to the patient cohort by age and sex. Baseline AGR, routine inflammatory indices, selected serum inflammatory cytokines, logMAR BCVA, OCT and FFA findings, and ocular inflammatory activity scores were recorded before systemic anti-inflammatory treatment. The primary outcome was poor treatment response at 3 months, defined as meeting at least one prespecified clinical, imaging, or visual criterion. Treatment escalation and inflammatory relapse were analyzed as supplementary outcomes. Logistic regression, ROC analysis, calibration assessment, bootstrap internal validation, and decision curve analysis were performed. AGR was lower in all four uveitis subgroups than in healthy controls. Descriptively, the lowest AGR values were observed in Behçet disease-associated uveitis and noninfectious choroiditis-spectrum uveitis. At 3 months, 52 of 200 patients (26.00%) had a poor treatment response. Compared with patients with a good treatment response, those with a poor response had lower baseline AGR and greater systemic and ocular inflammatory burden, reflected by higher cytokine levels, routine inflammatory indices, baseline logMAR BCVA, central macular thickness, FFA leakage scores, and revised ocular inflammatory activity scores. AGR was inversely correlated with IL-17 (rₛ=−0.521), IL-6 (rₛ=−0.506), and the revised ocular inflammatory activity score (rₛ=−0.500; all P < 0.001). In the final multivariable model, baseline logMAR BCVA (adjusted OR per 0.1-unit increase, 1.292; 95% CI, 1.098–1.520) and the revised ocular inflammatory activity score (adjusted OR per 1-point increase, 2.771; 95% CI, 1.843–4.167) remained independently associated with poor treatment response. By contrast, the associations of AGR, IL-17, the IL-6/IL-10 ratio, and CRP were attenuated after adjustment. AGR alone yielded an AUC of 0.775. The cytokine model comprising IL-17 and the IL-6/IL-10 ratio yielded an AUC of 0.738, which increased to 0.800 after AGR was added. The final model, which additionally included CRP, baseline logMAR BCVA, and the revised ocular inflammatory activity score, achieved an AUC of 0.903, with a bootstrap-corrected AUC of 0.887. The model showed acceptable calibration, with a Brier score of 0.103 and a Hosmer–Lemeshow P value of 0.675, and provided a positive net benefit across threshold probabilities of approximately 0.10–0.60. Low baseline AGR was associated with greater systemic and ocular inflammatory burden and poor 3-month treatment response. A multivariable model combining AGR with selected inflammatory and ocular variables showed good internal discrimination. External validation is required before clinical implementation.