| This study investigated the value of a test for contrast letter acuity for possible inclusion in the Multiple Sclerosis Functional Composite (MSFC) for use in future MS clinical trials. Low Contrast Sloan Letter Charts at 100%, 5%, 1.25%, and 0.6% contrast were evaluated for construct, concurrent, and predictive validity against the currently used clinical outcome measures.;Two study cohorts were available, Study A and Study I. Study A was a follow-up to the AVONEXRTM NIH Registration Study, which validated the MSFC. Of the 172 patients eligible for follow-up 137 patients were seen in four clinics. Contrast letter acuity was assessed cross-sectionally only. Clinical outcome measures available were the Expanded Disability Status Scale (EDSS), the MSFC, Brain Parenchymal Fraction (BPF), and Sickness Impact Profile (SIP). Study I was a 2 year clinical trial to determine whether weekly intramuscular treatment with AVONEXRTM when compared to a placebo was effective in slowing the advancement of secondary progressive MS, as determined by the MSFC. Approximately 440 subjects were recruited nationally and internationally. In a sub-study to Study I, contrast letter acuity data was collected on 65 patients with baseline measures at varying time points. Clinical outcome measures available were the EDSS, the MSFC, and the Multiple Sclerosis Quality of Life Index (MSQLI) (Ritvo et al., 1997). In addition, contrast letter acuity was assessed in 149 healthy volunteers to obtain normal limits.;The 5% and the 1.25% contrast charts were able to significantly predict severity of disease, regardless of the patient's visual acuity as assessed by the 100% contrast chart. The 0.6% chart was not considered in examining construct validity, as it suffered from a floor effect. Both the 5% and the 1.25% contrast levels provided excellent construct validity when evaluated against the commonly used clinical outcome measures. Significant predictive validity against the EDSS, after adjusting for the MSFC, was observed for the 5% and the 1.25% chart, p = 0.0142 and p = 0.0038, respectively.;Given the small sample sizes in this study it is premature to recommend the 5% or the 1.25% contrast letter acuity chart for inclusion into the MSFC. Further studies are warranted, exploring other contrast levels in addition to the 5% and 1.25% contrasts. |
