diagnostics Article OCT-Angiography Findings in Patients with Amblyopia: Comparison between Healthy Controls, Treatment-Responsive, and Treatment-Unresponsive Amblyopic Patients Annabella Salerni 1,2 , Gloria Gambini 1,2, *, Chiara Fedeli 1,2 , Ludovica Paris 1 , Emanuele Crincoli 1,2 , Gustavo Savino 1,2 , Maria Cristina Savastano 1,2 , Daniela Bacherini 3 , Umberto De Vico 1,2 , Clara Rizzo 4 , Raphael Killian 5 and Stanislao Rizzo 1,2,6   Citation: Salerni, A.; Gambini, G.; Fedeli, C.; Paris, L.; Crincoli, E.; Savino, G.; Savastano, M.C.; Bacherini, D.; De Vico, U.; Rizzo, C.; et al. OCT-Angiography Findings in Patients with Amblyopia: Comparison between Healthy Controls, Treatment-Responsive, and Treatment-Unresponsive Amblyopic Patients. Diagnostics 2021, 11, 1751. https://doi.org/10.3390/ diagnostics11101751 Academic Editor: Antonio Ferreras Received: 31 July 2021 Accepted: 20 September 2021 Published: 24 September 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 Ophthalmology Unit, “Fondazione Policlinico Universitario A. Gemelli IRCCS”, 00168 Rome, Italy; annabella.salerni@policlinicogemelli.it (A.S.); chiara.fedeli@policlinicogemelli.it (C.F.); ludovica.paris@libero.it (L.P.); emanuelecrincoli1@gmail.com (E.C.); gustavo.savino@unicatt.it (G.S.); mariacristina.savastano@gmail.com (M.C.S.); umbertodevico@gmail.com (U.D.V.); stanislao.rizzo@gmail.com (S.R.) 2 Ophthalmology Unit, Catholic University “Sacro Cuore”, 00168 Rome, Italy 3 Department of Surgery and Translational Medicine, AOU Careggi, University of Florence, 50139 Florence, Italy; daniela.bacherini@gmail.com 4 Ophthalmology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; clararizzo2@gmail.com 5 Ophthalmology Unit, University of Verona, 37134 Verona, Italy; raphaelkilian8@yahoo.it 6 Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche, 56124 Pisa, Italy * Correspondence: gambini.gloria@gmail.com Abstract: There is no consensus on whether amblyopia affects the retinal vascular plexus and mor- phology. Previous studies focused on the differences between amblyopic patients and normal controls without evaluating amblyopic eyes after patching. To evaluate differences in the superficial vascular density of amblyopic eyes, normal eyes, and amblyopic eyes reaching normal BCVA after patch therapy, OCTA was used. All patients underwent a comprehensive ophthalmological examination, including visual acuity, refraction, ocular motility tests, and anterior and posterior segment examina- tion. OCTA was performed by an expert physician using the Zeiss Cirrus 5000-HD-OCT Angioplex (Carl Zeiss, Meditec, Inc., Dublin, OH, USA). OCTA scans were performed using a 3 × 3 mm 2 and 6 × 6 mm 2 fovea-centered image setting. The mean outer macular vessel density in the previously amblyopic group was 19.15 ± 0.51%. This was statistically significantly higher than in both the amblyopic group (18.70 ± 1.14%) and the normal controls (18.18 ± 1.40%) (p = 0.014). The previously amblyopic group also significantly differed from both normal controls and amblyopic eyes with regards to the inner (p = 0.011), outer (p = 0.006), and full (p = 0.003) macular perfusion. Finally, linear regression analysis revealed that BCVA was linearly correlated to outer perfusion in ambly- opic (p = 0.003) and ex amblyopic eyes (p < 0.001). Considering the cross-sectional nature of our study, from our results, we can only hypothesize a possible correlation between light stimulation and retinal vasculature development. However, further longitudinal studies are needed to support this hypothesis. Keywords: amblyopia; optical coherence tomography angiography; pediatric ophthalmology; retina; innovative biotechnology; personalized medicine 1. Introduction Amblyopia is the most common cause of monocular and binocular vision loss in children and its population-based prevalence ranges from 0.5% to 3.5% [1–4]. Amblyopia is traditionally considered a cortical disease. The involvement of other structures in the visual pathway related to this disease is still to be determined [5,6]. Microscopic and functional Diagnostics 2021, 11, 1751. https://doi.org/10.3390/diagnostics11101751 https://www.mdpi.com/journal/diagnostics