Longitudinal Assessment of Visual Function in MS

描述（由申请人提供）：视力丧失是多发性硬化症（MS）最常见的临床表现之一。然而，MS试验中视力损害的定量评估仅限于Snellen视力。MS的纵向视觉轮廓，使用敏感但临床实用的视觉功能措施，尚未定义。随着时间的推移，免疫调节治疗对视力的影响程度也不清楚，并且难以使用传统的神经功能缺损量表（如扩展残疾状态量表（EDSS））进行评估。即使是MS功能复合（MSFC），MS试验的最新临床结局指标，也尚未包括视觉功能的评估。 我们来自宾夕法尼亚大学正在进行的MS视觉功能横断面研究的初步数据提供了强有力的证据，在5个候选视力测试中，对比字母敏锐度和对比敏感度最能区分MS患者和无疾病对照组，即使在详细的屈光和年龄分析之后。 然而，视觉功能测试预测MS疾病纵向变化的能力尚未在临床异质性队列中进行研究。这项建议将实现三个具体目标： 目标1：在一个大的队列中定义MS的纵向视觉特征，并确定哪些视觉功能测试对随时间的变化表现出最大程度的反应。 目标二：通过EDSS和MSFC测量，确定基线视功能测试评分与后续神经功能缺损的关系，以及视功能变化与神经功能缺损变化随时间的关系。 目标3：检查基线视功能测试评分与后续研究访视时健康相关生活质量（HRQOL）的关系，以及视功能变化与HRQOL随时间变化之间的关系，通过25项国家眼科研究所视功能问卷（VFQ-25）和多发性硬化症生活质量量表（MSQLI）进行测量。 总的来说，这些目标将导致识别敏感，有效和临床实用的视觉功能测试，这些测试对MS疾病随时间的变化有反应，并且能够在未来的MS治疗试验中捕获治疗效果。

DESCRIPTION (provided by applicant): Visual loss is one of the most common clinical manifestations of multiple sclerosis (MS). Quantitative assessment of visual impairment in MS trials, however, has been limited to Snellen acuity. The longitudinal visual profile of MS, using sensitive yet clinically practical visual function measures, has not been defined. The extent to which vision is affected over time by immunomodulatory therapies is also not known, and has been difficult to assess using traditional scales of neurologic impairment, such as the Expanded Disability Status Scale (EDSS). Even the MS Functional Composite (MSFC), the newest clinical outcome measure for MS trials, does not yet include an assessment of visual function. Our preliminary data from an ongoing cross-sectional study of visual function in MS at the University of Pennsylvania provide strong evidence that, among 5 candidate vision tests, contrast letter acuity and contrast sensitivity best distinguish MS patients from disease-free controls, even following detailed refractions and analyses accounting for age. The capacity for visual function tests to predict changes in MS disease longitudinally, however, has not been examined in clinically heterogeneous cohorts. This proposal will accomplish three specific aims: Aim 1: Define the longitudinal visual profile of MS in a large cohort, and determine which visual function tests demonstrate the greatest degree responsiveness to change over time. Aim 2: Determine the relation of baseline visual function test scores to subsequent neurologic impairment, and the relation between changes in visual function and changes in neurologic impairment over time, as measured by the EDSS and MSFC. Aim 3: Examine the relation of baseline visual function test scores to health-related quality of life (HRQOL) at subsequent study visits, and the relation between changes in visual function and changes in HRQOL over time, as measured by the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25) and the Multiple Sclerosis Quality of Life Inventory (MSQLI). Collectively, these aims will lead to the identification of sensitive, valid, and clinically practical visual function tests that are responsive to changes in MS disease over time, and will be capable of capturing treatment effects in future trials of MS therapies.