Retinal microvasculature as a predictor of neurodegeneration in multiple sclerosis

视网膜微血管作为多发性硬化症神经变性的预测因子

• 批准号: 10469365
• 负责人: Elizabeth Silbermann
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10469365
• 关键词: Accounting; Acute; Address; Affect; Age; Angiography; Anti-Inflammatory Agents; Atrophic; Biological Markers; Blood Vessels; Brain; Brain imaging; Caring; Cell Death; Cerebrovascular system; Cerebrum; Cholesterol; Chronic; Chronic Disease; Clinic; Clinical; Cross-Sectional Studies; Data; Dedications; Demyelinations; Disease; Disease Progression; Drops; Early Intervention; Early identification; Education; Enrollment; FDA approved; Foundations; Gait; Gender; Goals; Gold; Healthcare Systems; Hyperlipidemia; Hypertension; Hypoxia; Image; Impairment; Inflammation; Inflammatory; Intervention Trial; K-Series Research Career Programs; Leadership; Light; Magnetic Resonance Imaging; Measures; Methods; Microvascular Dysfunction; Mission; Modeling; Multiple Sclerosis; Nerve Degeneration; Neuraxis; Neurodegenerative Disorders; Neurologic; Neurons; Obesity; Observational Study; Optical Coherence Tomography; Outcome; Outpatients; Participant; Pathology; Patient Outcomes Assessments; Patient Participation; Patients; Performance; Persons; Play; Positioning Attribute; Procedures; Progressive Disease; Prospective cohort study; Quality of life; Questionnaires; Rehabilitation therapy; Reporting; Reproducibility; Research; Retina; Risk Factors; Role; Scanning; Spinal Cord; Statistical Data Interpretation; Structure; Swelling; System; Techniques; Technology; Testing; Thinness; Time; Training; Training Programs; Translating; United States; United States National Institutes of Health; Upper Extremity; Vascular Diseases; Veterans; Visual; Walking; aged; arterial spin labeling; base; brain magnetic resonance imaging; career; cerebral atrophy; cerebral hypoperfusion; clinical care; clinical examination; cognitive performance; cohort; comorbidity; density; disability; experience; gray matter; health related quality of life; improved; longitudinal analysis; military veteran; multiple sclerosis patient; multiple sclerosis treatment; neuron loss; primary outcome; progressive neurodegeneration; rehabilitation research; retina blood vessel structure; retinal imaging; secondary analysis; skills; standard measure; therapy development; trial design; white matter

Objectives: Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative illness that affects nearly 1 million people in the United States. Currently, there are no FDA-approved treatments that directly address neurodegeneration and its associated clinical impairment. Systemic vascular disease comorbidities, including hypertension, hyperlipidemia, and obesity, independently worsen MS-related walking limitations. In addition, MS pathology demonstrates microvascular dysfunction in the central nervous system (CNS). Our working model is that CNS vascular dysfunction accelerates neurodegeneration and thus limitations in activity and health-related quality of life. The purpose of this study is to quantify CNS vasculopathy in people with MS through microvascular changes in the retina as a first step to identify treatable modifiers of neurodegeneration. The overall study hypothesis is that retinal microvascular changes, measured by optical coherence tomography angiography (OCTA), in people with MS will correlate with patient-reported and objective measures of neurodegeneration. The long-term goal is to use OCTA as a surrogate of vascular dysfunction in trials of neuroprotective therapies. Plan: This is an observational study. The study procedures include a standard battery of neurologic and visual clinical exams to assess participant function, questionnaires to assess participant quality of life, and OCTA to assess CNS vasculature through the retina. Methods: This 2-year prospective cohort study features cross-sectional and longitudinal analyses to compare the impact of vascular comorbidities on retinal vascular density, determined by OCTA, as a measure of neuronal structural and functional integrity. Study MRI data will be collected at baseline and 2 years. We will enroll 44 subjects (accounting for 25% drop out for longitudinal aims) with a goal of 34 MS subjects with and without vascular comorbidities (V+, V- respectively). Data from an additional 22 healthy controls has already been collected and will be included for analysis. Subjects will be aged 30-70 and will be matched by age, gender, and use of disease modifying therapies. The primary outcome is to compare retinal vascular density in V+ and V- Veterans through cross-sectional analysis (Specific Aim 1). We will also explore if retinal vascular density correlates with increased rate of brain atrophy in V+ compared to V- Veterans (Specific Aim 2). Importantly, we will also determine if clinical impairment and quality of life deteriorates faster in V+ versus V- Veterans (Specific Aim 3). Relevance to VA’s Mission: The proposed study will have a profound impact on our Veteran population: of the 28,000 Veterans receiving care for MS within the VA system, approximately 50% have at least one vascular disease comorbidity. Since many of these comorbidities are modifiable, early identification of vascular dysfunction provides a window of opportunity for early interventions to optimize activity, participation and health-related quality of life. The VA Portland Health Care System (VAPORHCS) is an ideal place for my training program. We provide care for over 500 Veterans with MS annually. Additionally, we are one of only two national MS Centers of Excellence (MSCoE West) within the VA. With this designation, we have a particular dedication to setting the standards for clinical care, education, and high-quality collaborative research for Veterans with MS. Using the network of VA MS Clinics coordinated through the two VA MSCoE, findings from this study can be translated into improved care of all Veterans with MS. Through this experience, I will also gain the necessary skills in visual outcomes, statistical analysis, trial design, and team leadership to allow me to become a national leader in rehabilitation research and to ultimately improve the quality of life of Veterans with MS.

目的：多发性硬化症 (MS) 是一种慢性炎症和神经退行性疾病，影响近乎 目前，美国尚无 FDA 批准的直接针对 100 万人的治疗方法。 神经退行性变及其相关的临床损伤，包括全身性血管疾病合并症。 高血压、高脂血症和肥胖，独立恶化 MS 相关的步行限制。 我们的工作模式是 中枢神经系统血管功能障碍会加速神经退行性变，从而导致活动和健康相关的限制 本研究的目的是通过量化多发性硬化症患者的中枢神经系统血管病变。 视网膜微血管变化是确定神经退行性变可治疗调节剂的第一步。 总体研究假设是，通过光学相干断层扫描测量的视网膜微血管变化 多发性硬化症患者的血管造影 (OCTA) 将与患者报告的客观测量结果相关 长期目标是在试验中使用 OCTA 作为血管功能障碍的替代指标。 神经保护疗法。 计划：这是一项观察性研究，研究程序包括一系列标准的神经学和视觉研究。 评估参与者功能的临床检查、评估参与者生活质量的问卷以及评估参与者生活质量的 OCTA 通过视网膜评估中枢神经系统脉管系统。 方法：这项为期 2 年的前瞻性队列研究采用横断面和纵向分析来进行比较 血管合并症对视网膜血管密度的影响，由 OCTA 确定，作为衡量 我们将在基线和 2 年收集研究 MRI 数据。 招募 44 名受试者（占纵向目标退出的 25%），目标是 34 名 MS 受试者患有和 没有血管合并症（分别为 V+、V-）的数据已来自另外 22 名健康对照者。 被收集并将被纳入分析的受试者年龄将在 30-70 岁之间，并将按年龄进行匹配， 性别和疾病修饰疗法的使用主要结果是比较视网膜血管密度。 通过横断面分析 V+ 和 V- 退伍军人（具体目标 1）我们还将探讨视网膜血管是否存在。 与 V- 退伍军人相比，V+ 的密度与脑萎缩率增加相关（具体目标 2）。 重要的是，我们还将确定 V+ 患者的临床损伤和生活质量是否比 V- 患者恶化得更快 退伍军人（具体目标 3）。 与 VA 使命的相关性：拟议的研究将对我们的退伍军人群体产生深远的影响： 在 VA 系统内接受多发性硬化症护理的 28,000 名退伍军人中，大约 50% 的人至少患有一种 由于许多这些合并症是可以改变的，因此早期识别血管疾病。 功能障碍为早期干预提供了一个机会之窗，以优化活动、参与和 VA 波特兰医疗保健系统 (VAPORHCS) 是我的理想场所。 此外，我们每年还为 500 多名患有多发性硬化症的退伍军人提供护理，我们是仅有的两家之一。 VA 内的国家 MS 卓越中心 (MSCoE West) 凭借这一称号，我们拥有一个特殊的称号。 致力于为临床护理、教育和高质量合作研究制定标准 患有多发性硬化症的退伍军人使用通过两个 VA MSCoE 协调的 VA MS 诊所网络，研究结果来自 这项研究可以转化为改善对所有患有多发性硬化症的退伍军人的护理。 获得视觉结果、统计分析、试验设计和团队领导方面的必要技能，使我能够 成为康复研究领域的全国领导者，并最终提高退伍军人的生活质量 与 M.S.