Cardioembolism as a Mechanism of Central Retinal Artery Occlusion

摘要 这是一份促进NIH研究连续性和保留的行政补充申请 职业发展（K）奖获得者。目的是提供主要研究者，博士。 Brian Mac Grory，在陪产假期间维持其研究成果所需的支持。 博士Mac Grory是一名血管神经学研究者，致力于以患者为导向的临床研究， 识别需要个性化治疗的脑血管疾病未充分研究的新人群 二级预防战略。根据令人信服的初步数据和最近的出版物， 该建议假设是视网膜中央动脉阻塞（CRAO）-一种缺血性中风， 视网膜-可能是潜在的心脏病的指标和未来的哨兵，潜在的致命， 心源性中风CRAO被正式认为是缺血性中风的一种形式，但目前还没有一个完整的 了解其机械基础，迄今为止的大多数研究都集中在其与 颈动脉狭窄母公司K23合同建议生成关键的初步数据，将CRAO与 心脏栓塞基质，并为未来的多中心观察性研究奠定基础， 测试这个假设。Mac Grory博士将利用一个非常大的基于人口的数据集（Medicare 5% 样本）以及回顾性和前瞻性机构队列。具体目标1A和1B将 确定房颤和左心室衰竭与CRAO发展的相关性 并构成当前行政补充申请的重点。具体目标2A和2B 将确定栓塞风险的心脏、血清和超声生物标志物与CRAO的相关性 以及它们与颈动脉狭窄的相互作用。作为这项提议的一部分，麦克·格罗里博士将进行一项相关的， 教学培训计划，目标是通过获得 以下关键技能：1）观察性研究中的生物统计学，包括高级因果推理 方法学，2）应用于行政索赔数据库的数据科学，3）前瞻性、观察性研究 设计和4）血管生物标志物解释。这些领域的高级培训将使麦克·格罗里博士能够 实现他的长期职业目标，成为一名独立的临床研究者， 跨学科的专业知识，为未充分研究的脑血管疾病的管理提供见解。 为了实现这一目标，Mac Grory博士组建了一个指导团队， 中风医学技能，比较有效性研究，因果推理方法，心脏 电生理学和神经眼科学。利用从 根据拟议的研究，Mac Grory博士将拥有独特的能力来执行未来更大规模的研究， 新的人群中，基于证据的，潜在的挽救生命的二级预防策略可能是 部署。科学目标和方法与最初的建议保持不变。

ABSTRACT This is an application for an Administrative Supplement to Promote Research Continuity and Retention of NIH Mentored Career Development (K) Award recipients. The purpose is to provide the principal investigator, Dr. Brian Mac Grory, with the support necessary to maintain his research output during a period of paternity leave. Dr. Mac Grory is a vascular neurology investigator pursuing patient-oriented clinical research focused on the identification of novel populations with underexplored cerebrovascular disorders requiring personalized secondary prevention strategies. Based on compelling preliminary data and recent publications, the central hypothesis of this proposal is that central retinal artery occlusion (CRAO) – a form of ischemic stroke affecting the retina – may be an indicator of underlying cardiac disease and a sentinel of future, potentially lethal, cardioembolic stroke. CRAO is formally recognized as a form of ischemic stroke but there is an incomplete understanding of its mechanistic underpinnings, with most research to-date focused on its association with carotid artery stenosis. The parent K23 award proposes to generate key preliminary data linking CRAO with cardioembolic substrates and set the stage for a future, multi-center, observational study that will definitively test this hypothesis. Dr. Mac Grory will leverage a very large population-based dataset (the Medicare 5% Sample) as well as both retrospective and prospective institutional cohorts. Specific Aims 1A & 1B will determine the association of each of atrial fibrillation and left ventricular failure with the development of CRAO and comprise the focus of the current application for an Administrative Supplement. Specific Aims 2A & 2B will determine the association of cardiac, serum and ultrasonographic biomarkers of embolic risk with CRAO and their interplay with carotid artery stenosis. As part of this proposal, Dr. Mac Grory will undertake a linked, didactic training plan with the goal of developing as an independent investigator through acquisition of the following key skills: 1) Biostatistics in observational research including advanced causal inference methodology, 2) Data science applied to administrative claims databases, 3) Prospective, observational study design, and 4) Vascular biomarker interpretation. Advanced training in these areas will permit Dr. Mac Grory to realize his long-term career goal of becoming an independent clinical investigator who leverages interdisciplinary expertise to provide insights in to the management of understudied cerebrovascular disorders. In pursuit of this goal, Dr. Mac Grory has assembled a mentoring team with distinct though complementary skillsets in stroke medicine, comparative effectiveness research, causal inference methodology, cardiac electrophysiology, and neuro-ophthalmology. With the preliminary data and training obtained from the proposed research, Dr. Mac Grory will be uniquely equipped to execute future, larger-scale studies uncovering novel populations in whom evidence-based, potentially life-saving secondary prevention strategies may be deployed. The scientific goals and approach remain unchanged from the original proposal.