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Differential Remodeling of the Macular Neovascular Network under Different Anti-VEGF Agents in Age-Related Macular
Emanuele Crincoli1,2, Enrico Borrelli3,4, Maria Cristina Savastano1,2
1Ophthalmology Department, "Fondazione Policlinico Universitario A. Gemelli, IRCCS", Rome, Italy.
Purpose:
To compare treatment-induced changes in OCT B-scan and OCT angiography (OCTA)-derived characteristics of the macular neovascular (MNV) network among different anti-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 every 4 weeks (n = 30), aflibercept 2.0 mg every 4 weeks (n = 30), aflibercept 8.0 mg every 12 weeks (n = 30), or faricimab 6.0 mg every 8 weeks (n = 30) in a treat-and-extend regimen.
Methods:
Eyes with good-quality OCT B-scan and OCTA acquisitions at baseline and 1-year follow-up were included. OCT B-scan variables included pigment epithelium detachment (PED) height, PED homogeneity, and presence of intraretinal cystoid lesions and hyperreflective foci. OCT angiography variables included greatest linear diameter (GLD), MNV area, vessel density (VD), vessel length density (VLD), and VD index (VDI).
Main Outcome Measures:
Between-group differences in OCT B-scan and OCTA parameters at 1-year 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 1-year values for all OCTA endpoints, with a mean VDI of 1.150 ± 0.07 compared with 1.453 ± 0.05 for ranibizumab, 1.334 ± 0.06 for aflibercept 2 mg, and 1.231 ± 0.06 for 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 MNV 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 anatomical suppression translates into improved clinical outcomes or influences the trajectory of macular atrophy.
Financial Disclosures:
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
