Case Report Efficacy of CRISPR-Based Gene Editing in a Sickle Cell Disease Patient as Measured through the Eye Alexander Pinhas , 1 Davis B. Zhou , 1,2 Oscar Otero-Marquez , 1 Maria V. Castanos Toral , 1 Justin V. Migacz , 1 Jeffrey Glassberg , 3 Richard B. Rosen , 1,2 and Toco Y. P. Chui 1,2 1 Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA 2 Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA 3 Departments of Emergency Medicine,Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA Correspondence should be addressed to Toco Y. P. Chui; ychui@nyee.edu Received 29 April 2022; Accepted 2 August 2022; Published 22 August 2022 Academic Editor: Kostas Konstantopoulos Copyright © 2022 Alexander Pinhas et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Sickle cell disease (SCD) exists on a phenotypic spectrum with variable genetic expressivity, making it difficult to assess an individual patient’s risk of complications at any particular point in time. Current and emerging SCD treatments, including CRISPR-based gene editing, result in a variable proportion of affected red blood cells (RBCs) still vulnerable to sickling. Clinical serological indicators of disease such as hemoglobin, indirect bilirubin, and reticulocyte count and clinical metrics including number of emergency department visits and hospitalizations over time often fall short in their ability to objectively quantify ischemic disease activity and efficacy of treatments. Clearly, better clinical biomarkers are needed. e rapidly developing field of oculomics leverages the transparent nature of the ocular tissue to directly study the retinal microvasculature in order to characterize the status of systemic diseases. In this case report, we demonstrate the ability of optical coherence tomography angiography (OCT-A) to detect and measure micro-occlusive events within the retinal capillary bed before and after RBC exchange transfusion and following CRISPR-based gene editing, as an indicator of systemic ischemic disease activity and measure of treatment efficacy. e implications of these findings are discussed. 1. Introduction Sickle cell disease (SCD) is the most common inherited blood disorder in the world and causes significant body pains, morbidity secondary to ischemic end-organ damage, and mortality at a relatively young age [1]. Evidence suggests that SCD exists on a phenotypic spectrum with variable genetic expressivity, making it difficult to stratify risk of complica- tions for a given individual [2]. Even with current and emerging SCD treatments, including CRISPR-based gene editing of bone-marrow-derived hematopoietic stem cells, studies have shown that a variable degree of phenotypic mosaicism persists, with a variable proportion of red blood cells (RBCs) still able to sickle and cause disease [3]. Current indicators of disease severity and treatment re- sponse used in clinic and in clinical drug trials include se- rological biomarkers of hemolytic anemia and number of vaso-occlusive crises (VOCs), emergency room visits, and hospitalizations over time [4]. ese clinical indicators lack the ability to immediately and objectively measure ischemic dis- ease activity in SCD patients before or after treatment, which limits their ability to stratify patients according to prognosis and risk [5]. Improved biomarkers are clinically needed to help assess disease activity and response to therapy [6]. Oculomics, a rapidly developing field dedicated to identifying ocular biomarkers for systemic disease, is gaining attention for several cardiovascular and neurological ap- plications [7]. A variety of retinal microvasculature features Hindawi Case Reports in Hematology Volume 2022, Article ID 6079631, 6 pages https://doi.org/10.1155/2022/6079631