Abstract
BACKGROUND: Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP) are emerging biomarkers of axonal damage and astrocytic activation. The value of sNfL and GFAP in predicting retinal layer thinning remains underexplored. OBJECTIVES: To evaluate the association between sNfL and GFAP levels and retinal layer thinning. METHODS: This prospective observational study included people with relapsing MS (pwMS) newly initiated on a disease-modifying therapy (DMT). Optical coherence tomography (OCT) scans were conducted 3-6 months after DMT initiation and at 12-month intervals measuring peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness. sNfL and GFAP levels were measured at baseline and after 6 months (M6) using single-molecule array (Simoa(®)) technology. RESULTS: A total of 116 pwMS (mean age 34.5 years [SD 8.6]), 73.3% female) were included. GFAP z-scores at M6 showed the strongest association with annualized loss of pRNFL (aLpRNFL: b = -0.24; 95% confidence interval [CI] -0.27, -0.21, p < 0.001) and GCIPL (aLGCIPL: b = -0.15; 95% CI: -0.18, -0.12, p < 0.001). Moreover, pwMS with low sNfL but high GFAP levels at M6 showed the most pronounced retinal layer thinning (aLpRNFL: -0.8%/year [1.1], aLGCIPL: -0.8%/year [0.9]; both p < 0.001). CONCLUSIONS: High GFAP levels - more than sNfL levels - are associated with retinal layer thinning in relapsing MS.