Exploring the relationship between retinal damage and cognition in multiple sclerosis: a cross-sectional OCT-MRI study

BACKGROUND: Cognitive impairment (CI) is a common and disabling feature of multiple sclerosis (MS), closely linked to brain neurodegeneration (e.g., brain atrophy). Optical coherence tomography (OCT) may offer a rapid and cost-effective method to evaluate neurodegeneration and its relationship with CI in MS. OBJECTIVE: To explore the relationship between cognitive performance, retinal layer thickness, and brain volumetric measures in people with MS (pwMS), focusing on the relative contribution of individual retinal layers. METHODS: In this cross-sectional study, 100 pwMS underwent: neurological and neuropsychological evaluation; brain 3T-MRI scan to compute brain volumes; spectral-domain OCT to assess peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer (GCL), inner plexiform layer (IPL), and combined ganglion cell-inner plexiform layer (GCIPL) thickness. Correlation, t-tests, and regression analyses were performed to explore the abovementioned associations. RESULTS: Thinner retinal layers were associated with reduced brain volumes and lower cognitive performance. Among OCT-derived measures, GCL thickness showed the strongest association with both global cognitive Z-scores and domain-specific Z-scores for processing speed and executive functions. GCL also emerged as the only retinal predictor in regression models of cognitive outcomes. Classifying pwMS based on cognitive performance, cognitive impaired pwMS showed significantly lower GCL and pRNFL thickness compared to cognitive preserved pwMS. CONCLUSION: OCT-derived metrics of retinal damage linked to brain atrophy and CI in pwMS. Among retinal layers, GCL thickness is associated with both domain-specific and global cognitive performance and may potentially outperform GCIPL as an OCT-based marker of neurodegeneration, although findings should be interpreted with caution.