Serum neurofilament levels reflect outer retinal layer changes in multiple sclerosis

• Published in: Therapeutic advances in neurological disorders Vol. 14; p. 17562864211003478
• Main Authors: Seitz, Caspar B., Steffen, Falk, Muthuraman, Muthuraman, Uphaus, Timo, Krämer, Julia, Meuth, Sven G., Albrecht, Philipp, Groppa, Sergiu, Zipp, Frauke, Bittner, Stefan, Fleischer, Vinzenz
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 2021; SAGE PUBLICATIONS, INC; SAGE Publishing
• Subjects: Advances in Neuroimaging; Atrophy; Learning algorithms; Machine learning; Multiple sclerosis; Neuritis; Neurodegeneration; Optic neuritis; Retina; serum neurofilament; translation; neuroimmunology; optical coherence tomography; multiple sclerosis; optic neuritis
• ISSN: 1756-2864; 1756-2856; 1756-2864
• DOI: 10.1177/17562864211003478

Background: Serum neurofilament light chain (sNfL) and distinct intra-retinal layers are both promising biomarkers of neuro-axonal injury in multiple sclerosis (MS). We aimed to unravel the association of both markers in early MS, having identified that neurofilament has a distinct immunohistochemical expression pattern among intra-retinal layers. Methods: Three-dimensional (3D) spectral domain macular optical coherence tomography scans and sNfL levels were investigated in 156 early MS patients (female/male: 109/47, mean age: 33.3 ± 9.5 years, mean disease duration: 2.0 ± 3.3 years). Out of the whole cohort, 110 patients had no history of optic neuritis (NHON) and 46 patients had a previous history of optic neuritis (HON). In addition, a subgroup of patients (n = 38) was studied longitudinally over 2 years. Support vector machine analysis was applied to test a regression model for significant changes. Results: In our cohort, HON patients had a thinner outer plexiform layer (OPL) volume compared to NHON patients (B = −0.016, SE = 0.006, p = 0.013). Higher sNfL levels were significantly associated with thinner OPL volumes in HON patients (B = −6.734, SE = 2.514, p = 0.011). This finding was corroborated in the longitudinal subanalysis by the association of higher sNfL levels with OPL atrophy (B = 5.974, SE = 2.420, p = 0.019). sNfL levels were 75.7% accurate at predicting OPL volume in the supervised machine learning. Conclusions: In summary, sNfL levels were a good predictor of future outer retinal thinning in MS. Changes within the neurofilament-rich OPL could be considered as an additional retinal marker linked to MS neurodegeneration.