Dynamic changes in aqueous humor cytokines and OCTA parameters during aflibercept loading in treatment-naive neovascular age-related macular degeneration.

PURPOSE: To investigate dynamic changes in aqueous humor cytokines and retinal vessel density during aflibercept loading in treatment-naive neovascular age-related macular degeneration (nAMD), and to analyze their associations with visual improvement. METHODS: This single-center retrospective clinical study included 20 treatment-naive patients with nAMD (20 eyes) and 20 patients with cataracts (20 eyes). In the nAMD group, aqueous humor samples were collected at baseline and at the time of the third intravitreal aflibercept injection, while samples from the cataract control group were obtained before surgery. Relevant aqueous humor cytokines were measured using the Bio-Plex suspension bead array system. In the nAMD group, best-corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA) examinations were performed at baseline and at 1 and 2 months after treatment. Longitudinal changes in OCTA parameters were analyzed using mixed-effects models, followed by correlation analyses. According to the final BCVA outcome, eyes in the nAMD group were further classified into an obvious-improvement group and a non-obvious-improvement group for exploratory subgroup comparison. RESULTS: Compared with the cataract control group, eyes with nAMD showed significant differences in baseline aqueous humor levels of Ang-2, HGF, VEGF-C, IP-10, HB-EGF, IL-8, and PlGF. During aflibercept loading, aqueous humor levels of Ang-2, HGF, and IP-10 increased, whereas IL-8 decreased. At month 2, the superficial parafoveal vessel density and the superficial and deep perifoveal vessel density decreased significantly compared with baseline, while BCVA improved significantly. Baseline Ang-2, bFGF, and IL-8 showed nominal exploratory associations with OCTA changes, but these associations did not remain significant after FDR correction. In subgroup analysis of the nAMD cohort, only the change in deep perifoveal vessel density differed significantly between the obvious-improvement group and the non-obvious-improvement group. CONCLUSION: Treatment-naive nAMD eyes exhibited differential changes in aqueous humor cytokines during aflibercept loading, consistent with possible non-VEGF pathway involvement. Meanwhile, regional remodeling of retinal microcirculation was observed, and changes in deep perifoveal vessel density showed a trend consistent with short-term visual improvement.