Physiologically Based Markers of Idiopathic Intracranial Hypertension

描述（由申请人提供）：本申请要求对特发性颅内高压（IIH）有科学兴趣的学术神经眼科医生的职业发展奖励，这是一种最常影响年轻女性的潜在致盲疾病。该奖项将为候选人提供必要的指导，培训和经验，以推动她成为独立的以患者为导向的研究人员，专注于推进IIH的诊断，临床护理和结果。候选人是一位有成就的早期职业医师兼科学家。在短期内，她希望在临床研究和流行病学、视觉心理物理学和电生理学以及神经眼科成像领域进行研究。她将通过课程学习、指导学习、实践经验和指导研究来发展自己在这些领域的知识和能力。这将成为她在IIH建立独立研究项目的基础。从这个有利的角度来看，她将追求她的长期目标，即改善IIH和其他神经眼科疾病的临床护理，既作为具有强大转化研究计划的独立研究员，也作为直接照顾患者的专家临床医生。该系、医学院和研究所创造的环境以临床和研究专业知识和生产力为特点。在眼科和视觉研究领域，有效培养早期职业医师科学家有良好的记录。院系和医学院领导致力于提供物质、财政和智力支持，以确保候选人的发展和成功。临床迫切需要非侵入性生物标志物，以改善IIH的诊断和管理。该研究项目的目的是建立基于生理的视网膜神经节细胞（RGC）功能和视网膜血管的标志物，作为IIH的标志物，检测异常，监测治疗和区分周围视力结果。这一目标将通过两个具体目标来实现：为了验证与视觉正常对照组相比，IIH受试者RGC功能受损和视网膜血管直径增大的假设：将比较颅内压升高的IIH受试者和对照组之间基于电生理和瞳孔光反应的RGC功能测量和基于图像的视网膜血管直径测量。这将确定这些标记在IIH人群中是异常的。2. 为了测试

DESCRIPTION (provided by applicant): 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.