title: Vision in a phase 3 trial of natalizumab for multiple sclerosis: relation to disability and quality of life.
abstract: BACKGROUND
  Low-contrast visual acuity (LCVA), a sensitive measure of visual function in multiple sclerosis (MS), demonstrated treatment effects as a secondary outcome measure in the Phase 3 trial of natalizumab, AFFIRM. In these posttrial analyses, we studied the relation of visual function to quality of life (QOL), magnetic resonance imaging (MRI) measures, and Expanded Disability Status Scale (EDSS) scores.
  
  
  METHODS
  At baseline and at 52 and 104 weeks in AFFIRM, patients underwent binocular testing of LCVA (1.25% and 2.5% contrast) and high-contrast visual acuity (HCVA). Vision-specific QOL was assessed by the Impact of Visual Impairment Scale (IVIS), whereas the SF-36 Health Survey and Visual Analog Scale were administered as generic QOL measures and the EDSS as a measure of neurologic impairment.
  
  
  RESULTS
  Among QOL measures, IVIS scores showed the most significant correlations with visual dysfunction at all time points in the trial (r= -0.25 to -0.45, P < 0.0001 for LCVA and HCVA). Higher MRI T1- and T2-lesion volumes were also associated with worse vision scores at all time points (P < 0.0001). Clinically meaningful worsening (progression) of LCVA was noted in substantial proportions of patients in AFFIRM and was prevalent even among those without EDSS progression over 2 years (21.9% with LCVA progression at 2.5% contrast; 26.2% at 1.25% contrast). HCVA worsened in only 3.7% of patients without EDSS progression.
  
  
  CONCLUSIONS
  Loss of visual function, particularly as measured by LCVA, was common in AFFIRM, occurring in >20% of patients. Both LCVA and HCVA scores reflect vision-specific aspects of QOL, but LCVA provides information about disability progression not entirely captured by the EDSS. Vision represents a key dimension of outcome assessment for MS and adds valuable information on disability and QOL that can be useful to clinicians.
authors.affiliation: Department of Neurology (SC), University of Pennsylvania, Philadelphia, Pennsylvania; Departments of Neurology and Population Health (LJB), New York University School of Medicine, New York, New York; Department of Neurology (DBM), Cleveland Clinic Foundation, Cleveland, Ohio; Biogen Idec Inc (AZ), Weston, Massachusetts; and Department of Neurology (SLG), New York University School of Medicine, New York, New York.
authors.forename: Salim
authors.initials: S
authors.lastname: Chahin
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Balcer
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Miller
authors.forename: Annie
authors.initials: A
authors.lastname: Zhang
authors.forename: Steven L
authors.initials: SL
authors.lastname: Galetta
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D006233:Persons with Disabilities; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy / Q000523:psychology; D000069442:Natalizumab; D011788:Quality of Life / Q000523:psychology*; D013997:Time Factors; D016896:Treatment Outcome; D014786:Vision Disorders / Q000188:drug therapy* / Q000209:etiology*; D014792:Visual Acuity; D064232:Visual Analog Scale; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab