Aqueous Humor Dynamic Components that Determine Intraocular Pressure Variance

决定眼压变化的房水动态成分

• 批准号: 8548511
• 负责人: Sayoko E Moroi
• 金额: $ 9.73万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-03 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8548511
• 关键词: Accounting; Address; Adrenergic beta-Antagonists; Age of Onset; Aqueous Humor; Biological Markers; Blindness; Circadian Rhythms; Commit; Data; Databases; Disease Progression; Dose; Drug Prescriptions; Drug usage; Environmental Risk Factor; Experimental Designs; Eye; Frequencies; Future; Glaucoma; Goals; Individual; Knowledge; Latanoprost; Linear Models; Measures; Mediating; Medical; Medicine; Modeling; Molecular; Ocular Hypertension; Office Visits; Onset of illness; Open-Angle Glaucoma; Outcome; Outcome Measure; Patients; Pharmaceutical Preparations; Phase; Physiologic Intraocular Pressure; Physiological; Physiology; Placebos; Predictive Factor; Prostaglandins; Publishing; Randomized; Regimen; Risk; Staging; Testing; Time; Timolol; Treatment Efficacy; Treatment Failure; Treatment outcome; Variant; Venous Pressure level; Work; aqueous; base; cohort; follow-up; improved; new therapeutic target; response; wasting

DESCRIPTION (provided by applicant): Glaucoma is a major cause of blindness. The inability to predict a patient's IOP response to medications is a critical barrier for the clinician to consistently provide highly effective IOP-based treatments. Current trial-and- error approaches to glaucoma management are inefficient and have not addressed this barrier as there are no predictive factors for drug response. Our long-term goal is to improve outcomes by identifying biomarkers and environmental factors that profile a patient at risk for glaucoma by age-of-onset, rate of disease progression, "poor response" to treatment, and large IOP fluctuation. Our objective is to address this critical barrier by focusing on physiological factors that predict IOP response to drugs. Our central hypothesis is that individual aqueous humor dynamic components predict IOP response to medications. We will achieve our objective and work toward our goal by testing the central hypothesis through two aims. Aim 1: Test the hypothesis that aqueous humor inflow is a physiological marker of variation in timolol-mediated IOP response between individuals. Aim 2: Test the hypothesis that aqueous humor outflow is a physiological marker of variation in latanoprost-mediated IOP response between individuals. The overall experimental design will be a comprehensive comparison of physiological components of IOP in the same individual under control conditions without treatment and under experimental conditions with treatment using the two most commonly used drug classes, beta-blockers (Aim 1) and prostaglandins (Aim 2). The main outcome measures are the physiological components of IOP, namely, aqueous humor inflow, outflow facility, episcleral venous pressure, and uveoscleral outflow. The relationships among these four physiological components to IOP will be analyzed by generalized linear models. These results will provide a critically needed database on physiological components of IOP under baseline and treated conditions in the same cohort. Our team is committed to build upon these extensive physiology data from controls to the next phase by studying patients with ocular hypertension and early stages of open-angle glaucoma. Such a model would form the basis for future studies to investigate molecular and environmental interactions on IOP-based treatment outcomes and new therapeutic targets. Our results will advance understanding of IOP response variance to medications by dissecting the physiological components of drug response variations between individuals. This knowledge will bring us closer to predicting therapeutic efficacy, and decreasing treatment failures by identifying patients who are poor responders a priori. Prescribing medications based on a patient's profile of drug response will eliminate time wasted on ineffective drug prescriptions and result in more efficient medical management with fewer follow-up office visits to assess poor efficacy.

描述（由申请人提供）：青光眼是导致失明的主要原因。无法预测患者对药物的 IOP 反应是临床医生持续提供高效的 IOP 治疗的关键障碍。目前青光眼管理的试错方法效率低下，并且没有解决这一障碍，因为没有药物反应的预测因素。我们的长期目标是通过识别生物标志物和环境因素来改善治疗结果，这些生物标志物和环境因素通过发病年龄、疾病进展速度、对治疗的“反应差”和大的眼压波动来描述青光眼患者的风险。我们的目标是通过关注预测眼压对药物反应的生理因素来解决这一关键障碍。我们的中心假设是个体房水动态成分可预测眼压对药物的反应。我们将通过两个目标检验中心假设来实现我们的目标并努力实现我们的目标。目标 1：检验以下假设：房水流入是个体之间噻吗洛尔介导的 IOP 反应变化的生理标志。目标 2：检验以下假设：房水流出是拉坦前列素介导的个体之间 IOP 反应变化的生理标志。总体实验设计将全面比较同一个体在未经治疗的对照条件下和使用两种最常用药物类别 β 受体阻滞剂（目标 1）和前列腺素（目标 2）进行治疗的实验条件下 IOP 的生理成分。 ）。主要结果指标是眼压的生理成分，即房水流入量、流出量、巩膜外静脉压和葡萄膜巩膜流出量。这四个生理成分与眼压之间的关系将通过广义线性模型进行分析。这些结果将为同一队列中基线和治疗条件下眼压的生理成分提供急需的数据库。我们的团队致力于通过研究高眼压症和开角型青光眼早期患者，以从对照到下一阶段的广泛生理学数据为基础。这样的模型将为未来研究分子和环境相互作用对基于眼压的治疗结果和新治疗靶点的研究奠定基础。我们的研究结果将通过剖析个体之间药物反应差异的生理成分，促进对药物反应差异的理解。这些知识将使我们更接近于预测治疗效果，并通过先验地识别反应不佳的患者来减少治疗失败。根据患者的药物反应情况开出药物将消除浪费在无效药物处方上的时间，并导致更有效的医疗管理，同时减少评估不良疗效的后续办公室访问。