Citation: Donica, V.C.; Alexa, A.I.; Pavel, I.A.; Danielescu, C.; Ciap ˘ a, M.A.; Donica, A.L.; Bogd ˘ anici, C.M. The Evolvement of OCT and OCT-A in Identifying Multiple Sclerosis Biomarkers. Biomedicines 2023, 11, 3031. https://doi.org/10.3390/ biomedicines11113031 Academic Editors: Gabriele Thumann and Martina Kropp Received: 12 October 2023 Revised: 9 November 2023 Accepted: 10 November 2023 Published: 11 November 2023 Copyright: © 2023 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/). biomedicines Review The Evolvement of OCT and OCT-A in Identifying Multiple Sclerosis Biomarkers Vlad Constantin Donica 1 , Anisia Iuliana Alexa 1, *, Irina Andreea Pavel 1, *, Ciprian Danielescu 1 , Manuela Andreea Ciapă 2 , Alexandra Lori Donica 3 and Camelia Margareta Bogdănici 1 1 Department of Ophthalmology, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; vlad-constantin.donica@d.umfiasi.ro (V.C.D.); ciprian.danielescu@umfiasi.ro (C.D.); camelia.bogdanici@umfiasi.ro (C.M.B.) 2 Emergency Hospital “Dimitrie Castroian”, 735100 Husi, Romania 3 Clinical Recovery Hospital, 700661 Iasi, Romania * Correspondence: anisia-iuliana.alexa@umfiasi.ro (A.I.A.); andreea.niagu@umfiasi.ro (I.A.P.) Abstract: The prevalence of multiple sclerosis (MS) has been increasing among young people in developing countries over the last years. With the continuous development of new technology, the di- agnosis and follow-up of these patients has received new parameters that physicians may use in their practice. This paper reviews the main biomarkers identified through Optical Coherence Tomography Angiography (OCT-A) involved in the development and progression of MS and investigates the role it may have in detecting changes to the central nervous system (CNS). Keywords: optical coherence tomography; optical coherence tomography angiography; OCT; OCT-A; demyelinating disease; multiple sclerosis; retinal vascular density 1. Introduction 1.1. Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination and neuronal loss. It has a high prevalence amongst young people in developed and developing countries [1]. Recent studies found that the disease is more commonly found in the female population, a 3:1 female to male ratio, and has the highest prevalence amongst white, closely followed by black, individuals, with members of Hispanic and Asian descendance having a lower disease incidence [2,3]. Although the underlying cause is not well established, a series of genetic and environmental factors have been defined as increasing disease susceptibility. 1.2. Epidemiology Visual symptoms tend to appear in ~70% of the MS population, with optic neuritis being the onset symptom in ~20% of MS cases [4]. Optic neuritis (ON) is an acute disorder of the optic nerve characterized by inflammation and demyelination. The patient suffers from vision loss, periocular pain that is triggered by eye movement, contrast and color vision deficits. Visual field defects are present, central-cecal scotomas being the most common defect. The patients may also present with relative afferent pupillary deficit that should be easily diagnosed in cases without prior episodes of optic neuritis (NON) [5]. Posterior segment examination could be normal in retrobulbar neuritis, or there could be signs of papillary edema (in papillitis). 1.3. Anatomy The retina consists of different structural layers (Figure 1). The retinal ganglion cell has the soma in the ganglion cell layer (GCL) and their axons form the retinal nerve fiber layer (RNFL), which will form the optic nerve, exit the eye and travel into the optic canal Biomedicines 2023, 11, 3031. https://doi.org/10.3390/biomedicines11113031 https://www.mdpi.com/journal/biomedicines