Physiologically Based Markers of Idiopathic Intracranial Hypertension

特发性颅内高压的生理标志物

• 批准号: 9343081
• 负责人: Heather Elspeth Moss
• 金额: $ 14.82万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9343081
• 关键词: Affect; Aftercare; Age; Analysis of Variance; Area; Award; Biological Markers; Blindness; Blood Pressure; Blood Vessels; Brain; Caliber; Caring; Cell physiology; Cerebrovascular Disorders; Clinical; Clinical Management; Clinical Research; Clinical Trials; Control Groups; Development; Diagnosis; Disease; Disease Outcome; Electrophysiology (science); Ensure; Environment; Equation; Eye; Foundations; Functional disorder; Glaucoma; Goals; Health; Height; Image; Impairment; Incidence; Injury; Institution; Intracranial Hypertension; Intracranial Pressure; K-Series Research Career Programs; Knowledge; Lasers; Leadership; Light; Measures; Mechanics; Mentors; Mentorship; Modeling; Monitor; Morbidity - disease rate; Nerve; Neurology; Obesity; Ophthalmologist; Ophthalmology; Optic Disk; Optic Nerve; Optical Coherence Tomography; Outcome; Outcome Measure; Papilledema; Patients; Perimetry; Peripheral; Physicians; Physiological; Physiology; Pilot Projects; Plant Roots; Population; Principal Investigator; Productivity; Pseudotumor Cerebri; Pupil; Recruitment Activity; Request for Applications; Research; Research Personnel; Research Project Grants; Retinal; Retinal Ganglion Cells; Risk; Scanning; Scientific Advances and Accomplishments; Scientist; Spinal Puncture; Spinal Tap; Structure; Swelling; Techniques; Testing; Therapeutic; Thick; Time; Training; Translational Research; Uncertainty; Veins; Vision; Vision research; Visual; Visual Pathways; Visual Psychophysics; Work; base; career; career development; clinical care; clinical epidemiology; experience; hypertension treatment; improved; interest; medical schools; non-invasive imaging; ophthalmic artery; optic nerve disorder; patient oriented; pressure; programs; response; retina blood vessel structure; retinal nerve fiber layer; success; tool; vision science; visual information; young woman

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.

描述（由申请人提供）：本申请要求为对特发性颅内高压（IIH）具有科学兴趣的学术神经眼科医生提供职业发展奖，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。 候选人是一个有成就的早期职业医生科学家。在短期内，她寻求在临床研究和流行病学，视觉心理物理学和电生理学和神经眼科成像领域的研究职业发展。她将通过课程，指导学习，实践经验和指导研究来发展她在这些领域的知识和能力。这将成为她在IIH建立独立研究计划的基础。从这个Vantage来看，她将追求她的长期目标，改善IIH和其他神经眼科疾病的临床护理，既作为一个独立的研究人员，具有强大的转化研究计划，并作为一个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业知识和生产力。有一个有效地培养早期职业医生科学家在眼科和视觉研究领域的良好记录。部门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。 有一个显着的临床需要的非侵入性生物标志物，将改善IIH的诊断和管理。该研究项目的目的是建立基于生理学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，以检测异常，监测治疗和区分周边视力结果。这一目标将通过两个具体目标来实现：1.为了检验IIH受试者与视觉正常对照受试者相比RGC功能受损和视网膜血管直径扩大的假设：将在颅内压升高的IIH受试者和对照受试者之间比较基于电生理和瞳孔光反应的RGC功能测量值和基于图像的视网膜血管直径测量值。这将确定这些标志物在IIH人群中异常。2.测试 IIH受试者短期和长期治疗后RGC功能受损和视网膜血管扩张恢复假设：当颅内压升高时，将在IIH受试者中比较基于电生理和瞳孔光响应的RGC功能测量值和基于图像的视网膜血管直径测量值，腰椎穿刺短期颅内压降低后即刻和标准临床治疗长期颅内压降低后即刻。这将确定这些标志物随着IIH的治疗而变化。拟议研究的结果将为开发这些标记物作为IIH的临床工具和临床试验结果指标奠定科学和技术基础。此外，研究结果将促进对IIH视神经功能障碍和损伤的病理生理学的科学理解。该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应用于神经病学和眼科学交叉的其他疾病，如青光眼和脑血管疾病。研究职业发展和指导计划将使候选人成为一名独立的研究人员，为视觉科学做出长期贡献。