title: Low-contrast letter acuity testing captures visual dysfunction in patients with multiple sclerosis.
abstract: OBJECTIVE
  To evaluate concurrent and predictive validity for low-contrast letter acuity (L-CLA) testing as a candidate visual component for the Multiple Sclerosis Functional Composite (MSFC).
  
  
  METHODS
  L-CLA testing was conducted in two MS patient cohorts. In the MSFC Validation Study, 137 participants from a Phase III trial of inteferon beta-1a (Avonex) for relapsing-remitting MS were followed. A second cohort included 65 patients with secondary progressive MS who participated in a substudy of the International MS Secondary Progressive Avonex Controlled Trial (IMPACT). The total number of letters read correctly at four contrast levels (100, 5, 1.25, and 0.6%) was correlated with Expanded Disability Status Scale (EDSS), MSFC, Sickness Impact Profile, Multiple Sclerosis Quality of Life Inventory, and brain parenchymal fraction (BPF), as determined by MRI.
  
  
  RESULTS
  Low- and high-contrast letter acuity scores correlated with BPF at follow-up in the MSFC Validation Study (5%: r = 0.40, p < 0.0001; 100%: r = 0.31, p = 0.0002). L-CLA also correlated with EDSS (5%: r = -0.35, p < 0.0001; 1.25%: r = -0.26, p = 0.0003) and MSFC (5%: r = 0.47, p < 0.0001; 1.25%: r = 0.45, p < 0.0001). In the IMPACT Substudy, change in L-CLA scores from baseline to year 1 predicted subsequent change in the EDSS from year 1 to 2 at the 5% (p = 0.0142) and the 1.25% (p = 0.0038) contrast levels, after adjusting for change in MSFC scores from baseline to year 1.
  
  
  CONCLUSIONS
  Low-contrast letter acuity (L-CLA) scores demonstrate concurrent and predictive validity in patients with relapsing-remitting and secondary progressive multiple sclerosis (MS). L-CLA testing provides additional information relevant to the MS disease process that is not entirely captured by the Multiple Sclerosis Functional Composite.
authors.affiliation: Center for Research Methodology and Biometrics, Cooper Institute, 14023 Denver West Parkway, 100, Golden, CO 80401, USA. mbaier@denver.cooperinst.org
authors.forename: M L
authors.initials: ML
authors.lastname: Baier
authors.forename: G R
authors.initials: GR
authors.lastname: Cutter
authors.forename: R A
authors.initials: RA
authors.lastname: Rudick
authors.forename: D
authors.initials: D
authors.lastname: Miller
authors.forename: J A
authors.initials: JA
authors.lastname: Cohen
authors.forename: B
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: M
authors.initials: M
authors.lastname: Mass
authors.forename: L J
authors.initials: LJ
authors.lastname: Balcer
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D015331:Cohort Studies; D015350:Contrast Sensitivity / Q000502:physiology*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D009460:Neurologic Examination / Q000379:methods; D010775:Photic Stimulation / Q000379:methods; D011237:Predictive Value of Tests; D011788:Quality of Life; D015203:Reproducibility of Results; D016896:Treatment Outcome; D014786:Vision Disorders / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D014795:Visual Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
chemical_list: D016899:Interferon-beta; D000068556:Interferon beta-1a