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.