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.

Keywords: Multiple sclerosis; function; low-contrast letter acuity; optical coherence tomography; quality of life; vision.

Figure 1.

Low-contrast letter acuity chart (low-contrast Sloan letter chart, Precision Vision, LaSalle, IL). These charts have a standardized format based on Early Treatment Diabetic Retinopathy Study visual acuity charts, the standard used in ophthalmology clinical trials, and have several advantages over standard Snellen charts or near vision testing cards as traditionally used in MS trials: (1) letters (Sloan letters) are designed to be equally detectable for normal observers; (2) each line has an equal number of letters (five per line); (3) spacing between letters and lines is proportional to the letter size; (4) change in visual acuity from one line to another occurs in equal logarithmic steps (change of three lines constitutes a doubling of the visual angle); (5) visual acuity (for high-contrast (black letters on white) chart) may be specified by Snellen notation for descriptive purposes (i.e. 20/20), by the number of letters identified correctly. This figure shows the 25% contrast level for purposes of illustrating format; the actual contrast levels used in these trials, 2.5% and 1.25%, have substantially lighter gray letters. The charts measure 14 × 14 in for easy use and portability in the MS clinical trial setting; charts may also be mounted on a retro-illuminated cabinet, thus eliminating the need for standardization of room lighting levels. Reprinted with permission from Balcer et al.

Figure 2.

Pelli-Robson contrast sensitivity chart (Precision Vision, LaSalle, IL) The Pelli-Robson contrast sensitivity charts have uniformly large (20/680 Snellen equivalent size) letters of decreasing contrast in a series of triplets. There are two triplets per line and all letters within each triplet have the same contrast level. The Pelli-Robson chart is read at 1 m. It is wall or easel mounted; therefore, luminance of the environment must be accounted for when used for research. Reprinted with permission from Pelli et al. Copyright © 2014 D.G. Pelli and J.G. Robson. Manufactured by Precision Vision.