Early reduction of retinal thickness predicts physical and cognitive disability in newly diagnosed multiple sclerosis patients: results from a cross-sectional study

Introduction: Retinal nerve fiber layer (RNFL) thickness is a promising biomarker of axonal loss and a potential outcome predictor in Multiple Sclerosis (MS). Cognitive impairment (CoI) exhibits a high prevalence in patients with MS (pwMS), even in the early phases of the disease. Our aim was to explore the role of RNFL thickness as a predictor of physical and cognitive disability in pwMS. Methods: All newly diagnosed pwMS referred to the MS centre of the University-Hospital "Policlinico-San Marco" between 2015-2019 were evaluated at baseline and at 3 years. RNFL and ganglion cell layer (GCL) thickness for right (r.e.) and left eyes (l.e.) were measured with Optical Coherence Tomography (OCT). Disability level and cognitive profile were assessed, using the Expanded Disability Status Scale (EDSS) and the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, respectively. Results: We consecutively enrolled 487 pwMS, including 68 (14.0%) with primary progressive MS (PPMS). At baseline, RNFL and GCL were bilaterally thinner in PPMS (r.e. 90.4 +/- 12.7; l.e. 90.2 +/- 13.5, and r.e. 80.1 +/- 11.2; l.e. 80.3 +/- 12.6, respectively) compared to relapsing-remitting MS (RRMS) (r.e. 94.6 +/- 13.1; l.e. 94.3 +/- 14.8, and r.e. 85.1 +/- 9.5; l.e. 84.9 +/- 9.3, respectively) (p < 0.01). Both groups exhibited reduced RNFL and GCL thickness, worse cognitive performance and higher EDSS scores at 3-years follow-up compared with baseline. RNFL thickness <= 88.0 mu m was an independent predictor of CoI (OR = 5.32; 95% CI = 1.84-9.12; p = 0.02) and disability worsening (OR = 3.18; 95% CI = 1.21-10.33; p = 0.05). Discussion: RNFL thickness, as a biomarker of neurodegeneration, could be considered a predictive biomarker of cognitive degeneration and physical disability in MS.