title: Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis.
abstract: OBJECTIVE
  To examine the relation of visual function to retinal nerve fiber layer (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis (MS), and to compare RNFL thickness among MS eyes with a history of acute optic neuritis (MS ON eyes), MS eyes without an optic neuritis history (MS non-ON eyes), and disease-free control eyes.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Patients with MS (n = 90; 180 eyes) and disease-free controls (n = 36; 72 eyes).
  
  
  METHODS
  Retinal never fiber layer thickness was measured using optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision testing was performed for each eye and binocularly before OCT scanning using measures previously shown to capture dysfunction in MS patients: (1) low-contrast letter acuity (Sloan charts, 2.5% and 1.25% contrast levels at 2 m) and (2) contrast sensitivity (Pelli-Robson chart at 1 m). Visual acuity (retroilluminated Early Treatment Diabetic Retinopathy charts at 3.2 m) was also measured, and protocol refractions were performed.
  
  
  METHODS
  Retinal nerve fiber layer thickness measured by OCT, and visual function test results.
  
  
  RESULTS
  Although median Snellen acuity equivalents were better than 20/20 in both groups, RNFL thickness was reduced significantly among eyes of MS patients (92 mum) versus controls (105 mum) (P<0.001) and particularly was reduced in MS ON eyes (85 mum; P<0.001; accounting for age and adjusting for within-patient intereye correlations). Lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 mum.
  
  
  CONCLUSIONS
  Scores for low-contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker, supporting validity for these visual function tests as secondary clinical outcome measures for MS trials. These results also suggest a role for ocular imaging techniques such as OCT in trials that examine neuroprotective and other disease-modifying therapies. Although eyes with a history of acute optic neuritis demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes have less RNFL thickness than controls, suggesting the occurrence of chronic axonal loss separate from acute attacks in MS patients.
authors.affiliation: Division of Neuro-ophthalmology, Departments of Neurology, Ophthalmology, and Biostatistics, University of Pennsylvania School of Medicine, Scheie Eye Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Fisher
authors.forename: Dina A
authors.initials: DA
authors.lastname: Jacobs
authors.forename: Clyde E
authors.initials: CE
authors.lastname: Markowitz
authors.forename: Steven L
authors.initials: SL
authors.lastname: Galetta
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Volpe
authors.forename: M Ligia
authors.initials: ML
authors.lastname: Nano-Schiavi
authors.forename: Monika L
authors.initials: ML
authors.lastname: Baier
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Frohman
authors.forename: Heather
authors.initials: H
authors.lastname: Winslow
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Frohman
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Maguire
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cutter
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Balcer
mesh_terms: D000208:Acute Disease; D000328:Adult; D015350:Contrast Sensitivity / Q000502:physiology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009412:Nerve Fibers / Q000473:pathology*; D009902:Optic Neuritis / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology*