Regional retinal vulnerability in multiple sclerosis: integrating OCT, MRI, and clinical data for enhanced diagnosis and automated monitoring

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, often affecting the visual pathways. Optical coherence tomography (OCT) has emerged as a valuable, non-invasive imaging tool for assessing neuroaxonal damage in MS. This study investigates retinal neurodegeneration in MS patients, focusing on ganglion cell layer and inner plexiform layer (GCL+IPL) thinning, macular volume (MV), and retinal nerve fiber layer (RNFL) alterations, and their correlation with clinical and magnetic resonance imaging (MRI) parameters. A total of 43 MS patients and 38 healthy controls underwent three OCT investigations over three years, measuring GCL+IPL thickness, MV, and RNFL parameters. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS), and MRI data were available, with parameters such as lesion volume, whole brain volume, and white matter percentage analyzed. Statistical comparisons included t-tests, analysis of variance (ANOVA), and Pearson's correlation to evaluate OCT changes and their associations with clinical and MRI findings. MS patients exhibited significant GCL+IPL thinning, with quadrant analysis revealing regional disparities. Macular thickness showed no significant global differences; however, outer quadrant thinning was observed. RNFL analysis confirmed significant temporal quadrant thinning, further supporting its selective vulnerability in MS. Over three years, no significant longitudinal changes were detected in any OCT parameters (p>0.05). MRI lesion volume correlated strongly with EDSS (Pearson, r=0.61) and moderately with GCL+IPL thickness (Pearson, r=0.42), while a weaker correlation was found with temporal RNFL thickness. These findings reinforce OCT as an essential biomarker for MS-related neurodegeneration, particularly through GCL+IPL and temporal RNFL thinning. While macular changes were minimal, the observed selective temporal quadrant vulnerability aligns with previous research linking retinal alterations to trans-synaptic degeneration and optic radiation damage. The lack of significant longitudinal OCT progression over three years suggests that retinal atrophy may require longer monitoring periods to detect meaningful disease progression or to enable automated diagnosis. OCT is a reliable tool for detecting subclinical neurodegeneration in MS, particularly through temporal RNFL and GCL+IPL thinning. The moderate correlation between MRI lesion volume and retinal changes supports the integration of OCT with MRI for multimodal disease monitoring. The application of artificial intelligence (AI)-driven OCT analysis holds promise for enhanced MS diagnosis and automated progression monitoring. Future research should focus on long-term longitudinal studies, AI-assisted OCT diagnostics, and multimodal imaging approaches to optimize personalized MS management.

Keywords: MRI; OCT; automated diagnosis; multiple sclerosis; regional retinal vulnerability.

Figure 1

Normal appearance of OCT images across three scan types: GCL+IPL (A), the macula (B), and the RNFL (C), with all sections displaying the full retinal thickness from the ILM to the RPE. The fovea is located at the center of images (A) and (B), while the OD is at the center of image (C). GCL: Ganglion cell layer; I: Inferior; ILM: Inner limiting membrane; IPL: Inner plexiform layer; N: Nasal; OCT: Optical coherence tomography; OD: Optic disc; RNFL: Retinal nerve fiber layer; RPE: Retinal pigment epithelium; S: Superior; T: Temporal

Figure 2

Expanded Disability Status Scale (EDSS) Class distribution of the patients included in the study

Figure 3

Pathological appearance of OCT images across three scan types: GCL+IPL (A, D and G), macula (B, E and H), and RNFL (C, F and I). All images show the full thickness of the retina. The first row (A–C) illustrates mild changes, with slight thinning of the retinal layers and no clinical symptoms. The second row (D–F) shows moderate pathology, associated with limited clinical effects and a slight reduction in visual acuity. The third row (G–I) reveals severe alterations in the retinal layers, with significant clinical impact, potentially progressing to blindness. GCL: Ganglion cell layer; IPL: Inner plexiform layer; N: Nasal; OCT: Optical coherence tomography; RNFL: Retinal nerve fiber layer; T: Temporal

Figure 4

Macula thickness report example. Macular thickness map. Fundus image. Macular thickness measured between the ILM and the RPE. Table with macular parameters. ILM: Inner limiting membrane; OCT: Optical coherence tomography; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye); RPE: Retinal pigment epithelium

Figure 5

GCL thickness report example. The GCIPL thickness map shows the absolute thickness of the GCL and IPL. The GCIPL deviation map illustrates the deviation from the age-matched normative control group. The GCIPL thickness by sectors exhibits color-coded map for assessing different regions of the GCIPL. GCIPL quantification table includes the average GCIPL thickness compared to normative data for the same age group. GCL: Ganglion cell layer; IPL: Inner plexiform layer; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye)

Figure 6

RNFL report example. The RNFL thickness map shows the absolute thickness of the RNFL. The RNFL thickness deviation map shows comparison with age-matched normative values. Horizontal, vertical and circular RNFL thickness tomograms. Data table with average RNFL thickness and optic disc parameters. Graph of neuro-retinal and RNFL thickness with normative comparison. Thickness graph by quadrants and clock hours. C/D: Cup-to-disc; INF: Inferior; N (NAS): Nasal; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye); RNFL: Retinal nerve fiber layer; SUP: Superior; T (TEMP): Temporal