ABSTRACT
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.
ABSTRACT
OBJECTIVE: To evaluate volumetric changes and discriminative power of intra-retinal layers in early-stage multiple sclerosis (MS) using a 3D optical coherence tomography (OCT) imaging method based on an in-house segmentation algorithm. METHODS: 3D analysis of intra-retinal layers was performed in 71 patients with early-stage MS (mean disease duration 2.2 ± 3.5 years) at baseline and 40 healthy controls (HCs). All patients underwent a follow-up OCT scan within 23 ± 9 months. Patients with a clinical episode of optic neuritis (ON) more than 6 months prior to study entrance were compared with patients who never experienced clinical symptoms of an ON episode (NON). RESULTS: Significantly decreased total retinal volume (TRV), macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL) volumes were detected in ON patients compared to NON patients (all p values < 0.05) at baseline. Each parameter on its own allowed identification of prior clinical ON based on a discriminative model (ROC analysis). Over time, TRV decreased in both ON (p = 0.013) and NON patients (p = 0.002), whereas mRNFL volume (p = 0.028) decreased only in ON and GCIPL volume (p = 0.003) decreased only in NON patients. CONCLUSION: Our 3D-OCT data demonstrated that TRV, mRNFL and GCIPL allow discrimination between ON and NON patients in a cross-sectional analysis. However, the subsequent retinal atrophy pattern diverges in the initial phase of MS: Prior ON promotes sustained axonal thinning over time indicated by mRNFL loss, whereas longitudinal measurement of GCIPL volume better depicts continuous retrograde neurodegeneration in NON patients in early-stage MS.
