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, 2010, 542691

Phosphorylated Neurofilament Heavy Chain Correlations to Visual Function, Optical Coherence Tomography, and Treatment


Phosphorylated Neurofilament Heavy Chain Correlations to Visual Function, Optical Coherence Tomography, and Treatment

Joshua Pasol et al. Mult Scler Int.


Objective. To correlate visual and neurologic clinical scores and treatment of optic neuritis and multiple sclerosis (MS) patients with assays of serum phosphorylated neurofilament heavy chain (pNF-H) and optical coherence tomography (OCT) measurements of axonal loss. Design/Methods. The Optic Neuritis Treatment Trial (ONTT) randomized 457 patients with acute optic neuritis to intravenous methylprednisolone (IVMP) followed by oral prednisone, oral prednisone or placebo treatment arms. We quantified serum pNF-H levels in 175 ONTT patients 5 years after study entry. We performed OCT measurements of macular volume and the retinal nerve fiber layer (RNFL) in a subset of 51 patients at year 15. Results. Elevated pNF-H levels at year 5 correlated to poorer visual function at study entry. Lower 15 year macular volumes and RNFL thickness correlated better with follow-up than with baseline visual function measures. With IVMP treatment, 15 year RNFL differences of the fellow eye (FE) minus the affected eye (SE) RNFLFEmSE correlated with five-year pNF-H levels. PNF-H was reduced by half with IVMP relative to placebo or by 40% relative to prednisone. Conclusions/Relevance. Acute optic neuritis patients who have more severe visual loss during initial presentation have a higher incidence of axonal loss that was slightly suppressed with IVMP treatment.


Figure 1
Figure 1
Bar plots of pNF-H concentration (nanograms per mL) in optic neuritis patients by treatment group (a) and between optic neuritis cases with or without MS at 5 years (b). Error bars = standard deviation.
Figure 2
Figure 2
(a) A scatterplot shows the increasing pNF-H with worsening baseline visual acuity in the affected eyes with acute optic neuritis. (b) The scatterplot shows elevated serum pNF-H correlates with poorer contrast sensitivity at entry into the ONTT. (c) A scatterplot shows that higher pNF-H correlates with more severe visual field defects at baseline.
Figure 3
Figure 3
(a) A barplot of OCT RNFL thickness at 15 years in a subset of 51 patients shows no significant difference of mean RNFL with treatment of optic neuritis patients with MS or clinically isolated optic neuritis patients without MS. (b) A scatterplot of RNFL thickness difference of the fellow eye (FE) minus the study eye (SE) RNFLFEmSE correlated to serum pNF-H levels in the IVMP group.

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