Modulation of aqueous humor cytokine profile by faricimab in patients with diabetic macular edema

To explore how intravitreal faricimab reshapes aqueous humor cytokines in diabetic macular edema (DME), and analyze correlations between cytokine shifts and clinical efficacy.

This prospective study recruited 10 DME patients and 10 age-matched cataract controls. Aqueous humor was harvested from DME patients at baseline and 12 weeks after three faricimab injections, and from controls during cataract surgery. Multiplex immunoassay measured 12 aqueous cytokines. Clinical indicators included best-corrected visual acuity (BCVA), central macular thickness (CMT) and retinal vessel density detected by spectral-domain OCTA.

Baseline aqueous VEGF, Ang-2, IL-8 and PlGF were markedly higher in DME eyes (all p < 0.05). Post-treatment, VEGF and Ang-2 fell below control levels, whereas HGF, IP-10, IL-8 and PlGF further increased (all p < 0.05). Longitudinal analysis validated reduced VEGF/Ang-2 and elevated HGF after intervention. The original tight cytokine correlations (Ang-2-VEGF, Spearman's ρ = 0.890, raw p = 0.001) were disrupted, while new associations such as HGF-IL-6 (Spearman's ρ = 0.888, raw p = 0.001) formed. CMT decreased and BCVA improved significantly (both p < 0.05); declines in Ang-2 and VEGF strongly correlated with CMT thinning (Spearman's ρ = 0.824, raw p = 0.003; Spearman's ρ = 0.660, raw p = 0.034).

Faricimab potently remodels DME aqueous cytokine microenvironment via inhibiting the VEGF/Ang-2 pathway and upregulating HGF, restructuring cytokine crosstalk. There was a significant correlation between reduced target cytokines and improved macular anatomy, which provides preliminary observational evidence supporting dual-pathway inhibition in DME.