Physiologically Based Markers of Idiopathic Intracranial Hypertension

项目总结/摘要 此应用程序要求职业发展奖的学术神经眼科医生与科学 对特发性颅内高压（IIH）感兴趣，这是一种潜在的致盲性疾病， 年轻女性。该奖项将为候选人提供必要的指导，培训和经验 推动她的水平，以独立的病人为导向的研究人员专注于推进诊断，临床 IIH的护理和结果。 候选人是一个有成就的早期职业医生科学家。在短期内，她寻求研究 在临床研究和流行病学，视觉心理物理学和电生理学领域的职业发展 和神经眼科成像。她将通过以下方式发展自己在这些领域的知识和能力： 课程作业、指导学习、实践经验和指导研究。这将形成基础， 她将在IIH建立一个独立的研究项目。从这个Vantage的位置，她将追求她很长时间 长期目标是改善IIH和其他神经眼科疾病的临床护理， 他是一名研究人员，拥有强大的转化研究计划，并作为一名专家临床医生直接照顾病人。 该部门，医学院和机构创造的环境的特点是临床和 研究专长和生产力。有一个有效的培养早期职业生涯的良好记录 眼科和视觉研究领域的医生科学家。部门和医学院 领导层致力于提供物质，财政和智力支持，以确保候选人的 发展与成功。 有一个显着的临床需要的非侵入性生物标志物，将改善诊断和管理 的IIH。该研究项目的目的是建立视网膜神经节的生理学标记 细胞（RGC）功能和视网膜血管系统作为IIH的标志物，其检测异常、监测治疗和 区分周边视觉结果。实现这一目标将有两个具体目标： 1.为了验证RGC功能受损和视网膜血管直径扩大的假设， IIH受试者与视觉正常对照受试者的比较：电生理和瞳孔光 基于响应的RGC功能测量和基于图像的视网膜血管直径测量将被 颅内压升高的IIH受试者与对照受试者之间的比较。这将建立 这些标记在IIH人群中是异常的。 2.验证IIH患者RGC功能受损和视网膜血管扩张恢复的假设 接受短期和长期治疗的受试者：基于电生理和瞳孔光反应的测量 将在IIH内比较RGC功能和基于图像的视网膜血管直径测量 短期颅内压降低后即刻颅内压升高的受试者 通过腰椎穿刺和标准临床治疗长期降低颅内压。这 将确定这些标志物随IIH治疗而改变。 研究结果将为今后的发展奠定科学技术基础。 作为IIH的临床工具和临床试验结果测量的标志物。此外，结果将提前 对IIH视神经功能障碍和损伤的病理生理学的科学理解。的 项目具有更广泛的意义，因为获得的知识和开发的技术能力将具有 应用于神经病学和眼科学交叉点的其他疾病，如青光眼， 脑血管疾病研究职业发展和指导计划将改变候选人 成为一名独立的研究人员，为视觉科学做出长期的贡献。

Project Summary/Abstract This application requests a career development award for an academic neuro-ophthalmologist with a scientific interest in idiopathic intracranial hypertension (IIH), a potentially blinding condition that most commonly affects young women. This award will provide the candidate with the necessary mentorship, training and experience to propel her to the level of independent patient oriented researcher focused on advancing diagnosis, clinical care and outcomes of IIH. The candidate is an accomplished early career physician-scientist. In the short term she seeks research career development in the areas of clinical research & epidemiology, visual psychophysics & electrophysiology and neuro-ophthalmic imaging. She will develop her knowledge and capabilities in these areas through coursework, guided study, practical experience and mentored research. This will form the foundation upon which she will build an independent research program in IIH. From this vantage point she will pursue her long term goal of improving clinical care for IIH and other neuro-ophthalmic conditions both as an independent researcher with a strong translational research program and as an expert clinician caring directly for patients. The environment created by the Department, Medical School and Institution is characterized by clinical and research expertise and productivity. There is a proven track record of effectively nurturing early career physician scientists in the fields of ophthalmology and vision research. Departmental and Medical School leadership are committed to providing material, financial and intellectual support to ensure the candidate's development and success. There is a significant clinical need for non-invasive biomarkers that will improve diagnosis and management of IIH. The objective of the research project is to establish physiologically based markers of retinal ganglion cell (RGC) function and retinal vasculature as markers of IIH that detect abnormalities, monitor treatment and distinguish peripheral vision outcomes. This objective will be accomplished with two specific aims: 1. To test the hypothesis that RGC function is impaired and retinal vascular diameters are enlarged in IIH subjects as compared to visually normal control subjects: Electrophysiological and pupil light response based measures of RGC function and image based measures of retinal blood vessel diameter will be compared between IIH subjects with elevated intracranial pressure and control subjects. This will establish that these markers are abnormal in the IIH population. 2. To test the hypothesis that RGC function impairment and retinal vascular dilation recover in IIH subjects with short and long term treatment: Electrophysiological and pupil light response based measures of RGC function and image based measures of retinal blood vessel diameter will be compared within IIH subjects when intracranial pressure is elevated, immediately following short term intracranial pressure lowering by lumbar puncture and following long term intracranial pressure lowering by standard clinical therapy. This will establish that these markers change with treatment of IIH. The results of the proposed study will lay the scientific and technical foundation for the development of these markers as clinical tools and clinical trial outcome measures of IIH. Furthermore, the results will advance scientific understanding of the pathophysiology underlying optic nerve dysfunction and injury in IIH. The project has broader significance because the knowledge gained and technical capabilities developed will have applications to other diseases at the intersection of neurology and ophthalmology such as glaucoma and cerebrovascular disease. The research career development and mentoring plan will transform the candidate into an independent researcher who will make long-lasting contributions to vision science.