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: 10483194
• 负责人: Sayoko E Moroi
• 金额: $ 40.91万
• 依托单位: OHIO STATE UNIVERSITY
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483194
• 关键词: Adrenergic beta-Antagonists; Aftercare; Age; Age of Onset; Aqueous Humor; Behavioral; Biological Markers; Blindness; Characteristics; Clinical; Clinical Sciences; Cornea; Data Set; Databases; Environmental Exposure; Environmental Risk Factor; Eye; FDA approved; Future; Genetic Risk; Genotype; Glaucoma; Goals; Grant; Health Services; Healthcare; Home; Individual; Knowledge; Latanoprost; Lead; Linear Models; Measures; Mediating; Medical; Methods; Newly Diagnosed; Ocular Hypertension; Office Visits; Open-Angle Glaucoma; Outcome; Outcome Measure; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Physical activity; Physiologic Intraocular Pressure; Positioning Attribute; Practice Guidelines; Predictive Factor; Prostaglandins; Protocols documentation; Randomized; Randomized Clinical Trials; Risk; Risk Factors; Safety; Testing; Timolol; Treatment Efficacy; Treatment Failure; Variant; Venous Pressure level; Visual Fields; aggressive therapy; aqueous; clinical decision-making; clinical risk; cohort; cost; design; disorder risk; experience; follow-up; improved; improved outcome; individual response; innovation; response; risk variant; secondary outcome; sex; trait; treatment response

Abstract Randomized clinical trials (RCTs) show that reducing intraocular pressure (IOP) slows glaucoma progression. Despite the clinician’s use of these RCTs, practice guidelines, and experience, patients still progress to blindness. A gap in clinical science is our lack of knowledge on other risk factors that impact outcomes. Our long-term goal is to improve outcomes by identifying biomarkers, behavioral and environmental factors, that together profile a patient at risk for disease by age-of-onset, rate of progression, poor response to treatment, and large IOP fluctuation. We focus on two IOP patterns that continue to confound the clinician’s ability to provide consistent and effective IOP treatments: (1) IOP response to medications, ranging from non-responder to super responder, and (2) IOP fluctuation, ranging from small to large, with the latter leading to progressive visual field loss. Unfortunately, biomarkers that foretell these IOP patterns, which could improve clinical decision-making have yet to be identified -- a critical barrier to the clinician identifying patients for whom earlier or more aggressive treatment will mitigate glaucoma-related vision loss. The scientific premise is that these mechanisms (i.e., aqueous flow, outflow facility, episcleral venous pressure, and calculated uveoscleral flow) predict a patient’s IOP patterns. We will test the central hypothesis that variations in IOP response to drugs and IOP fluctuation can be predicted by the aqueous humor dynamic (AHD) factors that regulate IOP. We propose to test our hypothesis in 200 patients with ocular hypertension (OHT) or open-angle glaucoma (OAG), as both conditions are investigated in drug trials for IOP drug response. There are two aims: Aim 1. Test the hypothesis that AHD factors predict the IOP drug response. In Protocol 1, AHD factors will be measured under baseline without treatment, and after a randomized order of 1-week treatments with timolol 0.5% followed by a washout period and then latanoprost 0.005% or vice versa. Aim 2. Test the hypothesis that aqueous flow and outflow facility predict IOP fluctuation. In Protocol 2, IOP fluctuation will be measured in the non-clinic setting using the Icare® Home tonometer over multiple days at baseline and under monotherapy treatment during Protocol 1. Clinical Impact: Our approach to apply AHD methods to understand variation in drug response and IOP fluctuation is innovative. We predict that AHD factors will explain drug response and IOP fluctuation. Tying-down these relationships will provide new knowledge that will form the basis of future phenotype-genotype studies to identify genetic risk alleles of drug response and IOP fluctuation, resulting in an integrated risk score combining clinical and genetic risk profiles for drug response and IOP fluctuation. The ability to determine which patient needs earlier and more aggressive treatment will ultimately lead to more efficient medical management with fewer follow-up office visits to assess treatment efficacy, fewer treatment failures, and decreased glaucoma-related blindness.

抽象的 随机临床试验（RCT）表明，降低眼内压（IOP）会减缓青光眼进展。 尽管使用了这些RCT，练习指南和经验，但患者仍在 失明。临床科学的差距是我们对影响结果的其他风险因素缺乏知识。我们的 长期目标是通过识别生物标志物，行为和环境因素来改善结果，这些因素 共同介绍了一个患者受疾病风险的患者，按年龄，进展速度，对治疗的反应不佳， 和大的IOP波动。我们专注于两种IOP模式，这些模式继续使临床的能力混淆 提供一致有效的IOP治疗：（1）IOP对药物的反应，从无反应器 超级响应者和（2）IOP波动，从小到大，后者导致了渐进式 视野损失。不幸的是，预言这些IOP模式的生物标志物可以改善临床 决策尚未确定 - 临床识别患者的关键障碍 早期或更具侵略性的治疗将减轻与青光眼相关的视力丧失。科学前提是 这些机制（即水流，出口设施，粘液静脉压力和计算的葡萄球菌 流程）预测患者的IOP模式。我们将测试中心假设，即IOP响应的变化 可以通过水性幽默动态（AHD）因素来预测药物和IOP波动 调节IOP。我们建议在200例眼高血压（OHT）或开眼性的患者中检验我们的假设 青光眼（OAG），因为在IOP药物反应的药物试验中都研究了这两种情况。有两个目标： 目标1。检验AHD因素预测IOP药物反应的假设。在协议1中，AHD因素 将在未经治疗的情况下在基线下测量 Timolol 0.5％，然后进行清洗期，然后拉坦前列体0.005％，反之亦然。目标2。测试 水流和出口设施预测IOP波动的假设。在协议2中，IOP波动 将在基线和 在协议期间单一治疗1.临床影响：我们将AHD方法应用于 了解药物反应的变化和IOP波动是创新的。我们预测AHD因素将 解释药物反应和IOP波动。将这些关系捆绑在一起将提供新的知识 构成未来表型基因型研究的基础，以鉴定药物反应的遗传风险等位基因和IOP 波动，导致综合风险评分结合了药物反应的临床和遗传风险特征 和IOP波动。确定哪些患者需要的能力和更具侵略性的治疗将 最终导致更有效的医疗管理，随访较少的评估治疗访问 效率，治疗失败的较少以及与青光眼相关的失明增加。

项目成果

Acetazolamide-Induced Bilateral Ciliochoroidal Effusion Syndrome in Plateau Iris Configuration.

• DOI: 10.1016/j.ajoc.2016.05.003
• 发表时间: 2016-10-01
• 期刊: American journal of ophthalmology case reports
• 作者: Man, Xiaofei;Costa, Raquel;Moroi, Sayoko E
• 通讯作者: Moroi, Sayoko E

Size Matters for Interplicata Diameter: A Case-Control Study of Plateau Iris.

尺寸对 Interplicata 直径很重要：高原虹膜的病例对照研究。

• DOI: 10.1016/j.ogla.2020.06.007
• 发表时间: 2020
• 期刊: Ophthalmology. Glaucoma
• 作者: Garza,PhilipS;Man,Xiaofei;Queen,JoannaH;Ayres,BernadeteM;McClendon,Tanya;Parrish,ElizabethA;Reed,DavidM;Moroi,SayokoE
• 通讯作者: Moroi,SayokoE