Comparative Efficacy of Type I Interferons and Monoclonal Antibodies in Experimental Autoimmune Uveitis: A Systematic Review and Meta-Analysis.

PURPOSE: Experimental autoimmune uveitis (EAU) is an animal model of non-infectious uveitis used to study immune-mediated ocular inflammation. Type I interferons and monoclonal antibodies (mAbs) represent distinct immunomodulatory strategies used in autoimmune diseases, including multiple sclerosis and associated uveitis. This study aimed to compare the therapeutic effects of these treatments in EAU.

METHODS

PRISMA guidelines were followed for systematic review and meta-analysis (PROSPERO ID-1320794). PubMed, EMBASE, and Cochrane Library databases were searched through April 2025 for studies evaluating Type I interferons or monoclonal antibodies in EAU. Inclusion was rodent models of EAU treated with Type I interferons or mAbs and reporting clinical eye inflammation (EI) or histologic inflammation (H) scores pre/post treatment. Effect sizes were calculated using standardized mean differences. Risk of bias was assessed using the SYRCLE tool.

RESULTS

Seven studies evaluating Type I interferons and fifty studies evaluating monoclonal antibodies were included. Type I interferon therapy significantly reduced EI scores compared with controls (SMD =  -0.68, p < 0.001) but did not significantly reduce histologic inflammation (SMD ≈  -0.55, p = 0.25). Meta-regression showed no relationship between interferon dose/frequency and treatment efficacy. In contrast, monoclonal antibodies produced larger reductions in inflammation (EI: Hedges' g =  -3.09 [95% CI - 3.70, -2.47]; H: Hedges' g =  -1.76 [95% CI - 2.26, -1.27]), with time-stratified analysis demonstrating greater histologic improvement during later disease stages. Both therapies reduce EAU inflammation, but monoclonal antibodies demonstrate greater efficacy.

CONCLUSION

These findings suggest that targeted cytokine or co-stimulatory pathway inhibition demonstrated larger anti-inflammatory effects than interferon-mediated immunomodulation in preclinical EAU models, though clinical applicability remains uncertain.