title: Validity of low-contrast letter acuity as a visual performance outcome measure for multiple sclerosis.
abstract: Low-contrast letter acuity (LCLA) has emerged as the leading outcome measure to assess visual disability in multiple sclerosis (MS) research. As visual dysfunction is one of the most common manifestations of MS, sensitive visual outcome measures are important in examining the effect of treatment. Low-contrast acuity captures visual loss not seen in high-contrast visual acuity (HCVA) measurements. These issues are addressed by the MS Outcome Assessments Consortium (MSOAC), including representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. MSOAC goals are acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step is elucidation of clinically relevant benchmarks, well-defined degrees of disability, and gradients of change that are clinically meaningful. This review shows that MS and disease-free controls have similar median HCVA, while MS patients have significantly lower LCLA. Deficits in LCLA and vision-specific quality of life are found many years after an episode of acute optic neuritis, even when HCVA has recovered. Studies reveal correlations between LCLA and the Expanded Disability Status Score (EDSS), Multiple Sclerosis Functional Composite (MSFC), retinal nerve fiber layer (RNFL) and ganglion cell layer plus inner plexiform layer (GCL + IPL) thickness on optical coherence tomography (OCT), brain magnetic resonance imaging (MRI), visual evoked potential (VEP), electroretinogram (ERG), pupillary function, and King-Devick testing. This review also concludes that a 7-point change in LCLA is clinically meaningful. The overall goal of this review is to describe and characterize the LCLA metric for research and clinical use among persons with MS.
authors.affiliation: Department of Neurology, New York University School of Medicine, New York, NY, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Balcer
authors.affiliation: Department of Neurology, New York University School of Medicine, New York, NY, USA.
authors.forename: Jenelle
authors.initials: J
authors.lastname: Raynowska
authors.affiliation: Department of Neurology, New York University School of Medicine, New York, NY, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Nolan
authors.affiliation: Department of Neurology, New York University School of Medicine, New York, NY, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Galetta
authors.affiliation: National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Raju
authors.initials: R
authors.lastname: Kapoor
authors.affiliation: Department of Neurology, University at Buffalo, Buffalo, NY, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Benedict
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Glenn
authors.initials: G
authors.lastname: Phillips
authors.affiliation: National Multiple Sclerosis Society, New York, NY, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: LaRocca
authors.affiliation: Critical Path Institute, Tucson, AZ, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Hudson
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Rudick
authors.affiliation: Multiple Sclerosis Outcome Assessments Consortium (MSOAC), Critical Path Institute, Tucson, AZ, USA.
mesh_terms: D005074:Evoked Potentials, Visual / Q000502:physiology*; D006801:Humans; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000473:pathology; D009460:Neurologic Examination / Q000379:methods; D017063:Outcome Assessment, Health Care / Q000379:methods; D011788:Quality of Life; D014792:Visual Acuity / Q000502:physiology*
keywords: Multiple sclerosis; function; low-contrast letter acuity; optical coherence tomography; quality of life; vision