diagnostics Article Choriocapillaris Vascular Density Changes: Healthy vs. Advanced Exudative Age-Related Macular Degeneration Previously Treated with Multiple Anti-VEGF Intravitreal Injections Maria Cristina Savastano 1,2, * , Clara Rizzo 3, *, Gloria Gambini 1,2,† , Alfonso Savastano 1,2 , Benedetto Falsini 1,2 , Daniela Bacherini 4 , Carmela Grazia Caputo 1,2 , Raphael Kilian 5 , Francesco Faraldi 6 , Umberto De Vico 1 and Stanislao Rizzo 1,2,7   Citation: Savastano, M.C.; Rizzo, C.; Gambini, G.; Savastano, A.; Falsini, B.; Bacherini, D.; Caputo, C.G.; Kilian, R.; Faraldi, F.; De Vico, U.; et al. Choriocapillaris Vascular Density Changes: Healthy vs. Advanced Exudative Age-Related Macular Degeneration Previously Treated with Multiple Anti-VEGF Intravitreal Injections. Diagnostics 2021, 11, 1958. https://doi.org/10.3390/ diagnostics11111958 Academic Editor: José María Ruíz-Moreno Received: 26 July 2021 Accepted: 1 October 2021 Published: 22 October 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Unit of Ophthalmology, Fondazione Policlinico A. Gemelli, IRCCS, 00191 Rome, Italy; gambini.gloria@gmail.com (G.G.); asavastano21@gmail.com (A.S.); bfalsini@gmail.com (B.F.); carmelagrazia.caputo@gmail.com (C.G.C.); umbertodevico@gmail.com (U.D.V.); stanislao.rizzo@gmail.com (S.R.) 2 Unit of Ophthalmology, Università Cattolica Sacro Cuore, 00168 Rome, Italy 3 Ophthalmology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy 4 Department of Surgery and Translational Medicine, AOU Careggi, University of Florence, 50139 Florence, Italy; daniela.bacherini@gmail.com 5 Ophthalmology Unit,University of Verona, 37134 Verona, Italy; raphaelkilian8@yahoo.it 6 Torino, Eye Clinic, ASL Torino 5, 10024 Turin, Italy; faraldi@retinatorino.it 7 Consiglio Nazionale della Ricerca (CNR), Istituto di Neuroscienze, 56124 Pisa, Italy * Correspondence: mariacristina.savastano@gmail.com (M.C.S.); clararizzo2@gmai.com (C.R.) † Two authors equally contributed to the paper. Abstract: Purpose: To assess choriocapillaris vascular density (VD) in healthy and advanced ex- udative age-related macular degeneration (ae-AMD) patients by new full-range optical coherence tomography angiography (OCT-A). Method: In this observational, cross-sectional study, 21 healthy and 21 ae-AMD eyes, already treated with anti-VEGF, were enrolled. Angio-View retina patterns cen- tered on fovea (6.4 × 6.4 mm) were acquired for all participants using Solix full-range OCT (Optovue Inc., Freemont, CA, USA). The main outcome was to compare choriocapillaris VD between healthy and ae-AMD eyes. Automated measurements of whole image choriocapillaris VD (%) and fovea grid-based (%) were collected for the analysis. Angio-View patterns were used to assess the flow area (mm 2 ) of macular neovascularization (MNV) by contour flow measure algorithm. Best-corrected visual acuity (BCVA) of both groups was also used for the statistical analysis. Results: The mean age was 60.9 (±8.3) in healthy and 73.33 (±15.05) in ae-AMD eyes. The mean BCVA (ETDRS letters) was 98.47 (±1.50) in healthy and 7.04 (±5.96) in ae-AMD eyes. The Mann–Whitney test comparing choriocapillaries VD for whole and fovea healthy and ae-AMD eyes showed statistical significance (p < 0.0001 (t = 4.91; df = 40) and p < 0.0001 (t = 6.84; df = 40), respectively). Regarding, the correlation between MNV and VD of choriocapillaries, neither whole nor fovea areas were statistically significant (F = 0.38 (R 2 = 0.01) and 1.68 (R 2 = 0.08), respectively). Conclusions: Choriocapillaris VD showed a statistically significant reduction in comparison to healthy eyes in ae-AMD eyes. Choriocapillaris impairment can be seen in the early phase of MNV pathogenesis. Keywords: advanced exudative AMD; age-related macular degeneration; innovative biotechnologies; macular neovascularization; OCT angiography; personalized medicine; biomarkers 1. Introduction Biomarker identification for age-related macular degeneration is still a challenge for researchers. Recently, the introduction of deep learning in clinical practice allowed to Diagnostics 2021, 11, 1958. https://doi.org/10.3390/diagnostics11111958 https://www.mdpi.com/journal/diagnostics