title: Quantifying visual pathway axonal and myelin loss in multiple sclerosis and neuromyelitis optica.
abstract: The optic nerve is frequently injured in multiple sclerosis and neuromyelitis optica, resulting in visual dysfunction, which may be reflected by measures distant from the site of injury.
  
  
  
  To determine how retinal nerve fiber layer as a measure of axonal health, and macular volume as a measure of neuronal health are related to changes in myelin water fraction in the optic radiations of multiple sclerosis and neuromyelitis optica participants with and without optic neuritis and compared to healthy controls.
  
  
  
  12 healthy controls, 42 multiple sclerosis (16 with optic neuritis), and 10 neuromyelitis optica participants (8 with optic neuritis) were included in this study. Optical coherence tomography assessment involved measurements of the segmented macular layers (total macular, ganglion cell layer, inner plexiform layer, and inner nuclear layer volume) and paripapillary retinal nerve fiber layer thickness. The MRI protocol included a 32-echo T2-relaxation GRASE sequence. Average myelin water fraction values were calculated within the optic radiations as a measure of myelin density.
  
  
  
  Multiple sclerosis and neuromyelitis optica eyes with optic neuritis history had lower retinal nerve fiber layer thickness, total macular, ganglion cell and inner plexiform layer volumes compared to eyes without optic neuritis history and controls. Inner nuclear layer volume increased in multiple sclerosis with optic neuritis history (mean = 0.99 mm(3), SD = 0.06) compared to those without (mean = 0.97 mm(3), SD = 0.06; p = 0.003). Mean myelin water fraction in the optic radiations was significantly lower in demyelinating diseases (neuromyelitis optica: mean = 0.098, SD = 0.01, multiple sclerosis with optic neuritis history: mean = 0.096, SD = 0.01, multiple sclerosis without optic neuritis history: mean = 0.098, SD = 0.02; F3,55 = 3.35, p = 0.03) compared to controls. Positive correlations between MRI and optical coherence tomography measures were also apparent (retinal nerve fiber layer thickness and ganglion cell layer thickness: r = 0.25, p = 0.05, total macular volume and inner plexiform layer volume: r = 0.27, p = 0.04).
  
  
  
  The relationship between reductions in OCT measures of neuro-axonal health in the anterior visual pathway and MRI-based measures of myelin health in the posterior visual pathway suggests that these measures may be linked through bidirectional axonal degeneration.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada. Electronic address: p.manogaran@alumni.ubc.ca.
authors.forename: Praveena
authors.initials: P
authors.lastname: Manogaran
authors.affiliation: Department of Radiology, University of British Columbia, Vancouver, Canada. Electronic address: lees@ubc.ca.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Vavasour
authors.affiliation: Department of Ophthalmology, University of British Columbia, Vancouver, Canada. Electronic address: alex@lange.ch.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Lange
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada. Electronic address: yinshan@mail.ubc.ca.
authors.forename: Yinshan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada. Electronic address: katrina.mcmullen@ubc.ca.
authors.forename: Katrina
authors.initials: K
authors.lastname: McMullen
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, Canada. Electronic address: rauscher@phas.ubc.ca.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rauscher
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada. Electronic address: robert.carruthers@ubc.ca.
authors.forename: Robert
authors.initials: R
authors.lastname: Carruthers
authors.affiliation: Department of Radiology, University of British Columbia, Vancouver, Canada. Electronic address: david.li@ubc.ca.
authors.forename: David K B
authors.initials: DKB
authors.lastname: Li
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada. Electronic address: t.traboulsee@ubc.ca.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Traboulsee
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada. Electronic address: shannon.kolind@ubc.ca.
authors.forename: Shannon H
authors.initials: SH
authors.lastname: Kolind
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009471:Neuromyelitis Optica / Q000000981:diagnostic imaging / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014795:Visual Pathways / Q000000981:diagnostic imaging / Q000473:pathology*
keywords: Magnetic resonance imaging; Multiple sclerosis; Myelin water imaging; Neuromyelitis optica; Optic neuritis; Optical coherence tomography