Cerebrospinal fluid neurofilament light chain levels predict visual outcome after optic neuritis.
BACKGROUND
Optic neuritis is a good model for multiple sclerosis relapse, but currently no tests can accurately predict visual outcome.


OBJECTIVE
The purpose of this study was to examine whether cerebrospinal fluid (CSF) biomarkers of tissue damage and remodelling (neurofilament light chain (NF-L), myelin basic protein, osteopontin and chitinase-3-like-1) predict visual outcome after optic neuritis.


METHODS
We included 47 patients with optic neuritis as a first demyelinating episode. Patients underwent visual tests, optical coherence tomography (OCT), magnetic resonance imaging (MRI) and lumbar puncture. Biomarkers were measured in CSF by enzyme-linked immunosorbent assay (ELISA). Patients were followed up six months after onset and this included visual tests and OCT. Outcome measures were inter-ocular differences in low contrast visual acuity (LCVA), retinal nerve fibre layer (RNFL) and ganglion cell layer+inner plexiform layer (GC-IPL) thicknesses.


RESULTS
CSF NF-L levels at onset predicted inter-ocular differences in follow-up LCVA (β=13.8, p=0.0008), RNFL (β=5.6, p=0.0004) and GC-IPL (β=4.0, p=0.0008). The acute-phase GC-IPL thickness also predicted follow-up LCVA (β=12.9, p=0.0021 for NF-L, β=-1.1, p=0.0150 for GC-IPL). Complete/incomplete remission was determined based on LCVA from 30 healthy controls. NF-L had a positive predictive value of 91% and an area under the curve (AUC) of 0.79 for incomplete remission.


CONCLUSIONS
CSF NF-L is a promising biomarker of visual outcome after optic neuritis. This could aid neuroprotective/regenerative medical advancements.
The MS Clinic, Department of neurology, Glostrup Hospital, University of Copenhagen, Denmark/Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Denmark signe.modvig.stausboell@regionh.dk.
S
S
Modvig
The MS Clinic, Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark/Department of Diagnostics, Glostrup Hospital, University of Copenhagen, Denmark.
M
M
Degn
Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Denmark.
B
B
Sander
The MS Clinic, Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark/Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Denmark.
H
H
Horwitz
Department of Clinical Neurophysiology, Glostrup Hospital, University of Copenhagen, Denmark.
B
B
Wanscher
Danish MS Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
F
F
Sellebjerg
The MS Clinic, Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
J L
JL
Frederiksen
D000328:Adult; D001369:Axons / Q000473:pathology; D005260:Female; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000473:pathology; D009412:Nerve Fibers / Q000378:metabolism* / Q000473:pathology; D009902:Optic Neuritis / Q000134:cerebrospinal fluid* / Q000473:pathology*; D012160:Retina / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000166:cytology; D041623:Tomography, Optical Coherence / Q000379:methods; D014792:Visual Acuity / Q000502:physiology
Multiple sclerosis; biomarker; cerebrospinal fluid; neurofilament light chain; optic neuritis; outcome measurement