Differential remodeling of the macular neovascular network under different anti-VEGF agents in age-related macular degeneration

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Purpose: To compare treatment-induced changes in optical coherence tomography (OCT) B-scan and OCT angiography (OCTA)-derived characteristics of the macular neovascular (MNV) network among different anti-vascular endothelial growth factor (VEGF) agents in neovascular age-related macular degeneration (nAMD). Design: Multicenter retrospective observational cohort study.Subjects: A total of 120 eyes from 102 patients with nAMD treated with ranibizumab 0.5 mg Q4 (Rq4, n=30), aflibercept 2.0 mg Q4 (A2q4, n=30), aflibercept 8.0 mg Q12 (A8q12, n=30), or faricimab 6.0 mg Q8 (F6q8, n=30) in a treat-and-extend regimen.Methods: Eyes with good-quality OCT B-scan and OCTA acquisitions at baseline and 1-year followup were included.OCT B-scan variables included pigment epithelium detachment (PED) height, PED homogeneity, and presence of intraretinal cystoid lesions and hyperreflective foci.OCTA variables included greatest linear diameter (GLD), MNV area, vessel density (VD), vessel length density (VLD), and vessel diameter index (VDI). Main Outcome Measures:Between-group differences in OCT B-scan and OCTA parameters at 1year follow-up, adjusted for baseline values and clinical covariates using multivariable regression with cluster-robust standard errors.Results: Baseline characteristics were comparable across groups.Significant between-group differences were observed at 1 year for GLD (p=0.003),MNV area (p=0.001),VD (p<0.001),VLD (p=0.002), and VDI (p<0.001).Faricimab-treated eyes consistently showed the lowest adjusted 1year values for all OCTA endpoints, with a mean VDI of 1.150±0.07compared with 1.453±0.05for ranibizumab, 1.334±0.06for aflibercept 2 mg, and 1.231±0.06for aflibercept 8 mg.Structural OCT outcomes differed significantly for PED height (p=0.001) and PED homogeneity (p=0.007), with faricimab showing the lowest PED height and highest homogeneity.No significant differences were observed for qualitative variables.Conclusions: Dual VEGF-A/angiopoietin-2 inhibition with faricimab induces greater anatomical remodeling of the macular neovascular network compared with VEGF-A inhibition alone, with a distinct pattern characterized by preferential impact on larger-caliber vessels.These findings suggest that targeting the angiopoietin-2 pathway extends the morphological effects of anti-VEGF therapy beyond peripheral capillary pruning.Long-term studies are needed to determine whether deeper J o u r n a l P r e -p r o o f anatomical suppression translates into improved clinical outcomes or influences the trajectory of macular atrophy.

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