title: Optic nerve diffusion tensor imaging after acute optic neuritis predicts axonal and visual outcomes.
abstract: BACKGROUND
  Early markers of axonal and clinical outcomes are required for early phase testing of putative neuroprotective therapies for multiple sclerosis (MS).
  
  
  OBJECTIVE
  To assess whether early measurement of diffusion tensor imaging (DTI) parameters (axial and radial diffusivity) within the optic nerve during and after acute demyelinating optic neuritis (ON) could predict axonal (retinal nerve fibre layer thinning and multi-focal visual evoked potential amplitude reduction) or clinical (visual acuity and visual field loss) outcomes at 6 or 12 months.
  
  
  METHODS
  Thirty-seven patients presenting with acute, unilateral ON were studied at baseline, one, three, six and 12 months using optic nerve DTI, clinical and paraclinical markers of axonal injury and clinical visual dysfunction.
  
  
  RESULTS
  Affected nerve axial diffusivity (AD) was reduced at baseline, 1 and 3 months. Reduced 1-month AD correlated with retinal nerve fibre layer (RNFL) thinning at 6 (R=0.38, p=0.04) and 12 months (R=0.437, p=0.008) and VEP amplitude loss at 6 (R=0.414, p=0.019) and 12 months (R=0.484, p=0.003). AD reduction at three months correlated with high contrast visual acuity at 6 (ρ = -0.519, p = 0.001) and 12 months (ρ = -0.414, p=0.011). The time-course for AD reduction for each patient was modelled using a quadratic regression. AD normalised after a median of 18 weeks and longer normalisation times were associated with more pronounced RNFL thinning and mfVEP amplitude loss at 12 months. Affected nerve radial diffusivity (RD) was unchanged until three months, after which time it remained elevated.
  
  
  CONCLUSIONS
  These results demonstrate that AD reduces during acute ON. One month AD reduction correlates with the extent of axonal loss and persistent AD reduction at 3 months predicts poorer visual outcomes. This suggests that acute ON therapies that normalise optic nerve AD by 3 months could also promote axon survival and improve visual outcomes.
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia ; Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia ; Department of Neuro-ophthalmology, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia ; Melbourne Brain Centre at Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Anneke
authors.initials: A
authors.lastname: van der Walt
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Kolbe
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Yejun E
authors.initials: YE
authors.lastname: Wang
authors.affiliation: Save Sight institute, Sydney University, Sydney, New South Wales, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Klistorner
authors.affiliation: Department of Neuro-ophthalmology, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
authors.forename: Neil
authors.initials: N
authors.lastname: Shuey
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Gelareh
authors.initials: G
authors.lastname: Ahmadi
authors.affiliation: Department of Neuro-ophthalmology, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Paine
authors.affiliation: Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Marriott
authors.affiliation: Department of Radiology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Mitchell
authors.affiliation: Monash University, Melbourne, Victoria, Australia.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Egan
authors.affiliation: Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia ; Melbourne Brain Centre at Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia ; Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Kilpatrick
mesh_terms: D000293:Adolescent; D000328:Adult; D001369:Axons / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications; D009900:Optic Nerve / Q000473:pathology* / Q000503:physiopathology*; D009902:Optic Neuritis / Q000150:complications / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D011379:Prognosis; D015203:Reproducibility of Results; D012306:Risk; D014792:Visual Acuity; D014794:Visual Fields; D014796:Visual Perception; D055815:Young Adult