Novel visual outcome measures in optic neuritis and multiple sclerosis

描述(由申请人提供)：本申请建议扩大由Laura J.Balercer，M.D.，M.S.C.E.进行的以患者为导向的研究和指导计划，她是一位知名的临床研究员，其工作重点是开发多发性硬化症(MS)临床试验的可视结果。Balercer博士的研究已经证明了光学相干断层扫描(OCT)对MS的低对比字母敏感度、视网膜神经纤维层(RNFL)厚度和黄斑体积的有效性，但尚未确定这些参数在急性视神经炎(ON)预后评估中的作用，这些参数是MS急性脱髓鞘和轴突/神经元丢失的模型，也是检验神经保护治疗的理想靶点。该研究计划将实现以下目标： 具体目标1：改进和验证低对比度字母敏锐度和OCT作为新的视觉结果 多发性硬化症的临床试验，以及急性试验，作为未来神经保护剂测试的模型系统。 具体目标2：确定新的视觉结果，低对比度字母敏锐度和OCT如何反映 在MS和On的纵向研究中，研究特定视力和总体健康相关的生活质量，并检查新的包含10个条目的NEI视功能问卷(NEI-VFQ-25)在这些患者群体中的有效性和有用性。这些研究将进一步确定低对比字母敏锐度和OCT新指标在MS临床试验中的潜在作用，并将MS Vision研究的范例应用于急性ON的研究，作为评估自然病史和神经保护治疗试验结果的更具体的模型系统。受训者参与改进研究设计、实践测试、数据分析和手稿准备将是候选人指导计划的中心重点。这些拟议的新项目的设计和选择是为了促进学员的参与，并在范围上足够灵活和多样化，以将神经学的学员纳入所有级别的培训。公共卫生声明：多发性硬化症和视神经炎是美国年轻人和中年人视力丧失的主要原因。这项工作将为进一步的研究和指导初级临床医生科学家开发改进的这些条件下的视力测试方法提供支持。

DESCRIPTION (provided by applicant): This application proposes expanded programs of patient-oriented research and mentoring by Laura J. Balcer, M.D., M.S.C.E., an established clinical investigator whose work has focused on the development of visual outcomes for clinical trials in multiple sclerosis (MS). Dr. Balcer's research has demonstrated validity for low-contrast letter acuity and for retinal nerve fiber layer (RNFL) thickness and macular volume by optical coherence tomography (OCT) in MS, but has not established roles for these parameters in outcomes assessment for acute optic neuritis (ON), a model for acute demyelization and axonal/neuronal loss in MS and an ideal target for examining neuroprotective therapies. The research plan will accomplish the following aims: Specific Aim 1: Refine and validate low-contrast letter acuity and OCT as new visual outcomes for clinical trials in MS, and in acute ON as a model system for future testing of neuroprotective agents. Specific Aim 2: Determine how new visual outcomes, low-contrast letter acuity and OCT, reflect vision-specific and overall health-related quality of life in longitudinal studies of MS and ON, and examine the validity and usefulness of a new 10-ltem Neuro-Ophthalmic Supplement to the 25-ltem NEI Visual Functioning Questionnaire (NEI-VFQ-25) in these patient populations. These investigations will further define potential roles for new measures of low-contrast letter acuity and OCT in MS clinical trials, and will apply paradigms from MS vision research to the study of acute ON as a more specific model system for assessment of natural history and neuroprotective treatment trial outcomes. Participation by mentees in refinement of study design, performance of hands-on testing, data analysis, and manuscript preparation will be a central focus of the candidate's mentoring plan. These proposed new projects have been designed and selected to facilitate trainee involvement, and are sufficiently flexible and varied in scope to incorporate mentees in Neurology at all levels of training. Public Health Statement: MS and optic neuritis are leading causes of visual loss among young and middle-aged adults in the U.S. This work will provide support for additional research and for mentoring of beginning clinician scientists in the development of improved testing methods for vision in these conditions.