Phd in INNOVATIVE BIOTECH SOLUTIONS FOR SENSORY ORGANS
DISEASES

Thesis title: Biomarcatori fenotipo-specifici per la selezione personalizzata di anti-VEGF di ultima generazione nella DMS essudativa

Abstract Abstract Background: Neovascular age-related macular degeneration (nAMD) represents the leading cause of irreversible vision loss in industrialized countries. Although anti-VEGF therapy has revolutionized disease management, variability in treatment response and the need for frequent injections continue to impose a significant clinical and healthcare burden. Recent therapeutic advances, including dual-pathway inhibition with faricimab and higher-dose aflibercept, have renewed interest in understanding how baseline anatomical features—particularly pigment epithelial detachment (PED)—may influence treatment efficacy and durability. Methods: This monocentric observational study included treatment-naïve nAMD patients managed with a treat-and-extend regimen. Three therapeutic cohorts were analyzed: bevacizumab (n=50), aflibercept (n=25), and faricimab (n=26), together with an exploratory brolucizumab group (n=6). Functional and anatomical parameters, including BCVA (ETDRS letters), central macular thickness (CMT), PED height and volume, retinal fluid (IRF/SRF), SHRM, and ellipsoid zone integrity, were assessed at baseline and at months 4, 9, and 12. Statistical analyses included mixed-effects models and ANCOVA, adjusting for baseline values and device. Interaction testing evaluated the modifying effect of baseline PED characteristics on visual and anatomical outcomes. Results: Faricimab demonstrated superior functional and anatomical performance, with a mean BCVA gain of +8.8 letters at 12 months versus +6 (aflibercept) and +4.8 (bevacizumab). CMT reduction was greatest with faricimab (−84.4 ± 22.5 μm), followed by aflibercept (−76 ± 21.2 μm) and bevacizumab (−64.6 ± 23.0 μm). PED regression was significantly more pronounced with faricimab (−82%) versus aflibercept (−65%) and bevacizumab (−48%). Faricimab also achieved the highest rate of fluid resolution (84.6%) and required fewer injections (6.3 ± 1.0) relative to aflibercept (7.2 ± 1.2) and bevacizumab (8.4 ± 1.2). Interaction analysis revealed that increased baseline PED height was associated with diminished visual gains across treatments, yet faricimab remained comparatively more effective than alternatives in eyes with large PEDs. Conclusion: Faricimab provides superior visual and anatomical outcomes compared to aflibercept and bevacizumab in real-world nAMD management, particularly in eyes with complex baseline anatomy and prominent PED. Dual VEGF/Ang-2 inhibition may offer enhanced tissue stabilization, improved fluid control, and reduced treatment burden. Further investigations are warranted to refine phenotype-guided therapeutic strategies and validate PED-based stratification as a predictive biomarker in precision retinal medicine.