Presence of both abnormal serum neurofilament light (sNfL) and a thin ganglion cell and inner plexiform layer (GCIP) was synergistically prognostic of future disease activity in early multiple sclerosis (MS). Abnormal sNfL alone was also a prognostic indicator, but with a smaller effect size.
Why this matters ?
MS has a highly variable clinical course that can be difficult to prognose in patients with early disease, including clinically isolated syndrome (CIS) and early relapsing-remitting (RR)MS.
Biomarkers of disease progression are under investigation. Optical coherence tomography (OCT) is a technique for visualizing retinal features. Reduced GCIP thickness per OCT has been associated with future disease activity in people with CIS. sNfL is a biomarker of neuroaxonal damage associated with increased risk of disability worsening in early MS.
It is possible that GCIP thickness and sNfL could both help to predict future disease activity in patients with early MS, perhaps with an additive effect.
Objective: To assess whether a combined measure of sNfL and retinal OCT is associated with future disease activity in early MS.
The study prospectively enrolled 78 patients with CIS or early RRMS; the median follow-up period was 24 months.
Patients were classified as either having normal or abnormal sNfL (per sNfL ≥ or <80th percentile of age-corrected reference values) and either thick or thin retinal layers (median split of cohort) based on OCT measures.
The primary outcome was violation of no evidence of disease activity (NEDA-3) criteria or its components.
Compared to those with normal sNfL, patients with abnormal sNfL had:
Increased risk of violating NEDA-3 (HR 2.28, 95% CI 1.27–4.09, P=0.006), and
Increased risk of developing a new brain lesion (HR 2.47, 95% CI 1.30–4.69, P=0.006), but
No increased risk of new relapse (HR 2.21, 95% CI 0.97–5.03, P=0.058).
However, compared to those with abnormal sNfL alone, patients with both abnormal sNfL and a thin GCIP had higher risk of:
NEDA-3 violation (HR 3.61, 95% CI 1.77–7.36, P=4.2e-4),
New brain lesion (HR 3.19, 95% CI 1.51–6.76, P=0.002), and
New relapse (HR 5.38, 95% CI 1.61–17.98, P=0.006).
The authors concluded that the presence of both abnormal sNfL and a thin GCIP was the strongest risk factor of all investigated for future disease activity in early MS.
The sample size was small.
Very few patients experienced Expanded Disability Status Scale (EDSS) worsening, meaning an analysis of sNfL and retinal thickness per EDSS could not be performed.
The study was underpowered to identify optimal cut-off values for either sNfL or retinal OCT.
Several important clinical factors, including body mass index, blood pressure, and hemoglobin A1c level, were not studied.