Retinal Nerve Fiber Layer Thickness Correlates with Serum and Cerebrospinal Fluid Neurofilament Levels and is Associated with Current Disability in Multiple Sclerosis

Introduction: The main purpose of the present study is to confirm Peripapillary Retinal Nerve Fiber Layer (pRNFL) thickness is a biomarker of axonal degeneration in patients with Multiple Sclerosis (MS) and to evaluate its relationship with Neurofilament heavy chain (NfH) and Nitrotyrosine (NT). Method: We quantified serum (s) and/or cerebrospinal fluid (CSF) NfH and NT levels in 30 relapsing-remitting MS patients (RRMS), 16 secondary progressive MS (SPMS) patients and in 29 control subjects matched for age and gender. Optical coherence tomography (OCT) measurements of pRNFL were performed in all subjects. Clinical outcomes were tested by Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS). Results: RRMS patients exhibited significantly higher NfH/NT levels (99 pg/mL, 107.52 nM respectively) than controls (74 pg/mL, 48.72 nM) in CSF (p<0.0001), but not in sera. SPMS patients had significantly higher s NfH/NT values (111.25 pg/mL, 1251.77 nM respectively) and lower mean pRNFL thickness (79 mu m) than patients with RRMS (98.50 mu m) and controls (108 mu m) (p<0.0001). pRNFL thickness was significantly correlated with all clinical disability measurements (EDSS, Trail Making test, 9-Hole Peg Test, and PASAT) in both RRMS and SPMS (p<0.001, p=0.02, p=0.03, p=0.02 respectively). A positive correlation was also found between serum and/or CSF NfH levels and EDSS scores in RRMS and SPMS (p<0.001, p=0.02 respectively). The pRNFL thickness was also correlated significantly with serum and/or CSF NfH levels but not with s/CSF NT levels in both clinical forms of MS (p<0.01, p<0.001 respectively). Conclusion: The current study demonstrated that both pRNFL and s/CSF NfH are reliable and quantitative biomarkers that correlate with current disease course and cross-sectional measure of disability in patients with MS.