Vision related quality of life in multiple sclerosis: correlation with new measures of low and high contrast letter acuity.

OBJECTIVE: To examine the relation between low contrast letter acuity, a new visual function test for multiple sclerosis (MS) trials, and vision targeted health related quality of life (HRQOL). METHODS: Patients in this cross sectional study were part of an ongoing investigation of visual function in MS. Patients were tested binocularly using low contrast letter acuity and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) charts. The 25 Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), 10 Item Neuro-Ophthalmic Supplement to the NEI-VFQ-25, Impact of Visual Impairment Scale and Short Form 36 Health Survey (SF-36) were administered. RESULTS: Among 167 patients, mean age was 48 (10) years, with median Expanded Disability Status Scale (EDSS) 2.0 (range 1.0-7.5), and median binocular Snellen acuity equivalent (ETDRS charts) 20/16 (range 20/12.5 to 20/100). Reductions in vision specific HRQOL were associated with lower (worse) scores for low contrast letter acuity and VA (p<0.001, linear regression, accounting for age). Two line differences in visual function were associated, on average, with >4 point (6.7-10.9 point) worsening in the NEI-VFQ-25 composite score, reductions that are considered clinically meaningful. Scores for the 10 Item Neuro-Ophthalmic Supplement to the NEI-VFQ-25 also correlated well with visual function. Associations between reduced low contrast acuity and worse vision targeted HRQOL remained significant in models accounting for high contrast VA, EDSS and history of acute optic neuritis. CONCLUSIONS: Low contrast letter acuity scores correlate well with HRQOL in MS. Two line differences in scores for low contrast acuity and VA reflect clinically meaningful differences in vision targeted HRQOL. Low contrast acuity testing provides information on patient reported aspects of vision, supporting use of these measures in MS clinical trials.

Relation of vision to global and regional brain MRI in multiple sclerosis.

OBJECTIVE: To examine the relation between low-contrast letter acuity, an emerging visual outcome for multiple sclerosis (MS) clinical trials, and brain MRI abnormalities in an MS cohort. METHODS: T2 lesion volume and brain parenchymal fraction were determined for whole brain and within visual pathway regions of interest. Magnetization transfer ratio histograms were examined. Vision testing was performed binocularly using low-contrast letter acuity (2.5%, 1.25% contrast) and high-contrast visual acuity (VA). Linear regression, accounting for age and disease duration, was used to assess the relation between vision and MRI measures. RESULTS: Patients (n = 45) were aged 44 +/- 11 years, with disease duration of 5 years (range <1 to 21), Expanded Disability Status Scale score of 2.0 (0 to 6.0), and binocular Snellen acuity of 20/16 (20/12.5 to 20/25). The average T2 lesion volume was 18.5 mm(3). Patients with lower (worse) low-contrast letter acuity and high-contrast VA scores had greater T2 lesion volumes in whole brain (2.5% contrast: p = 0.004; 1.25%: p = 0.002; VA: p = 0.04), Area 17 white matter (2.5%: p < 0.001; 1.25%: p = 0.02; VA: p = 0.01), and optic radiations (2.5%: p = 0.001; 1.25%: p = 0.02; VA: p = 0.007). Within whole brain, a 3-mm(3) increase in lesion volume corresponded, on average, to a 1-line worsening of low-contrast acuity, whereas 1-line worsening of high-contrast acuity corresponded to a 5.5-mm(3) increase. CONCLUSIONS: Low-contrast letter acuity scores correlate well with brain MRI lesion burden in multiple sclerosis (MS), supporting validity for this vision test as a candidate for clinical trials. Disease in the postgeniculate white matter is a likely contributor to visual dysfunction in MS that may be independent of acute optic neuritis history.

Contrast letter acuity as a visual component for the Multiple Sclerosis Functional Composite.

BACKGROUND: Visual dysfunction is one of the most common causes of disability in multiple sclerosis (MS). The Multiple Sclerosis Functional Composite (MSFC), a new clinical trial outcome measure, does not currently include a test of visual function. OBJECTIVE: To examine contrast letter acuity as a candidate visual function test for the MSFC. METHODS: Binocular contrast letter acuity testing (Sloan charts) was performed in a subgroup of participants from the International Multiple Sclerosis Secondary Progressive Avonex Controlled Trial (IMPACT Substudy) and in MS patients and disease-free control subjects from a cross-sectional study of visual outcome measures (Multiple Sclerosis Vision Prospective cohort [MVP cohort]). High-contrast visual acuity was measured in both studies; MVP cohort participants underwent additional binocular testing for contrast sensitivity (Pelli-Robson chart), color vision (D-15 desaturated test), and visual field (Esterman test, Humphrey Field Analyzer II). RESULTS: Contrast letter acuity (Sloan charts, p < 0.0001, receiver operating characteristic curve analysis) and contrast sensitivity (Pelli-Robson chart, p = 0.003) best distinguished MS patients from disease-free control subjects in the MVP cohort. Correlations of Sloan chart scores with MSFC and Expanded Disability Statue Scale (EDSS) scores in both studies were significant and moderate in magnitude, demonstrating that Sloan chart scores reflect visual and neurologic dysfunction not entirely captured by the EDSS or MSFC. CONCLUSIONS: Among clinical measures, contrast letter acuity (Sloan charts) and contrast sensitivity (Pelli-Robson chart) demonstrate the greatest capacity to identify binocular visual dysfunction in MS. Sloan chart testing also captures unique aspects of neurologic dysfunction not captured by current EDSS or MSFC components, making it a strong candidate visual function test for the MSFC.