Advanced CLAD PERG system with minimal patient preparation for clinical settings (Phase II)

先进的 CLAD PERG 系统，只需最少的患者准备即可进行临床设置（第二阶段）

• 批准号: 10698852
• 负责人: Jonathon Anthony Toft-Nielsen
• 金额: $ 47.91万
• 依托单位: JORVEC CORPORATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10698852
• 关键词: Adoption; Affect; Age; Algorithms; Blindness; Cell Death; Cell physiology; Cessation of life; Characteristics; Clinical; Clinical Management; Communities; Computer software; Data; Dependence; Detection; Development; Devices; Diagnostic; Disease; Dryness; Early Diagnosis; Electrodes; Electroretinography; Environment; Exhibits; Experimental Models; Eye; Foundations; Functional disorder; Glaucoma; Goals; Head; Health; Human; Individual; Investigation; Left; Measures; Methods; Monitor; Neuroanatomy; Noise; Optical Coherence Tomography; Optics; Patients; Pattern; Performance; Perimetry; Phase; Physiologic Intraocular Pressure; Population; Posture; Preparation; Public Health; Pupil; ROC Curve; Research; Research Personnel; Response to stimulus physiology; Retina; Retinal Degeneration; Retinal Diseases; Retinal Ganglion Cells; Scientist; Sensitivity and Specificity; Signal Transduction; Specificity; Standardization; Stimulus; Stress; Suspect Glaucomas; System; Techniques; Technology; Testing; Therapeutic; Time; Uncertainty; Vision research; Visual; Visual Fields; Visualization; Work; body position; clinical application; clinically relevant; cost; detection platform; diagnostic value; experimental study; functional loss; human model; human subject; improved; in vivo; innovation; light weight; miniaturize; neurophysiology; next generation; novel; operation; optic nerve disorder; portability; prevent; prototype; response; retinal damage; retinal ganglion cell degeneration; sample fixation; screening; tool; user-friendly; visual tracking

Abstract: Glaucoma is one of a number of optic nerve diseases which lead to retinal ganglion cells (RGC) degeneration, ultimately manifesting in a functional loss of vision if left untreated. There exist a number of therapeutic approaches to treat these conditions, but there are currently no clinical methods to detect the onset of RGC dysfunction. The Pattern Electroretinogram (PERG) is the only established tool to monitor RGC health in vivo in humans and experimental models of optic nerve diseases. The monitoring of PERG responses can potentially provide earlier detection of degenerative retinal disorders such as glaucoma, allowing for treatment paradigms to be initiated before irreversible functional vision loss has occurred. A critical barrier to the widespread adoption of PERG for research and clinical use involves suboptimal characteristics of conventionally available displays for eliciting visual responses. The goal of the proposed project is to produce commercially available device for use in both vision research and clinical applications, which is not only more compact, faster, cheaper and more user‐friendly, but also provides a higher quality of information through innovative display technology and processing techniques. As part of our Phase I efforts, we developed a miniaturized PERG visual display unit based on variable polarization. Additionally, we used the CLAD deconvolution technique to extract additional clinical information from the PERG response. Recording data from both glaucoma suspects and age matched controls, the CLAD extracted data was more significantly different between the two populations when compared to conventional techniques. Additionally, ROC curves generated from the CLAD data had higher AUC values than the conventional techniques (0.897 using CLAD, versus 0.74 and 0.683 for conventional transient and steady state PERG). During Phase II, the following specific aims will be pursued: 1) Refining the next generation PERG stimulator for humans. We will refine the prototype developed in the phase I effort into a head mounted, near eye display configuration. We will incorporate additional functionality, such as active fixation and pupil size monitoring and a disposable dry electrode interface (based on Phase I effort) which will minimize patient preparation and increase throughput and remove the need for sanitizing device between subjects. 2) Expanding CLAD in Glaucoma. As part of our phase I effort, we showed that the CLAD technique has the potential to increase the clinical utility of the well establish, but underutilized PERG response. In our Phase II effort, we will expand testing in glaucoma suspects, looking at the effects of temporal presentation rate, and the dynamic adaptation of the PERG response. Research has shown that both of these factors are affected in patients with retinal dysfunction. Looking at these additional applications of the CLAD analysis techniques in a larger patient pool will further expand on the work done in the Phase I effort and continue to expand on the clinical utility of the PERG response.

摘要： 青光眼是导致视网膜神经节细胞（RGC）的众多视神经疾病之一 退化，如果不治疗，最终表现为视力的功能丧失。存在多种 的治疗方法来治疗这些条件，但目前没有临床方法， 检测RGC功能障碍的发作。模式视网膜电图（PERG）是唯一建立的工具 监测人类和视神经疾病实验模型体内RGC的健康状况。的 监测PERG反应可以潜在地提供退行性视网膜疾病的早期检测 例如青光眼，允许在不可逆的功能性视力之前开始治疗范例 损失发生了。广泛采用PERG进行研究和临床使用的关键障碍 涉及常规可用显示器的次优特性以引起视觉响应。的 拟议项目的目标是生产可用于视觉研究的商用设备， 和临床应用，它不仅更紧凑，更快，更便宜，更用户友好， 还通过创新的显示技术和处理提供更高质量的信息 技术.作为我们第一阶段工作的一部分，我们开发了一个小型化的PERG视觉显示单元， 关于可变极化此外，我们使用CLAD反卷积技术来提取额外的 PERG反应的临床信息。记录青光眼疑似患者和年龄的数据 匹配的对照组，CLAD提取的数据在两者之间差异更显著 与传统技术相比，此外，从图1所示的方法生成的ROC曲线 CLAD数据具有比常规技术更高的AUC值（使用CLAD的0.897，对比使用CLAD的0.74和CLAD的0.897）。 对于常规瞬态和稳态PERG为0.683）。在第二阶段，以下具体目标 将追求：1）完善人类的下一代PERG刺激器。我们将完善 在第一阶段的努力中开发的原型变成头戴式近眼显示器配置。我们将 结合了附加功能，例如主动注视和瞳孔大小监测，以及一次性的 干电极接口（基于第一阶段的工作），这将最大限度地减少患者准备， 通过量，并且消除了对受试者之间的消毒设备的需要。2)在中扩展CLAD 青光眼作为我们第一阶段工作的一部分，我们证明了CLAD技术具有潜力， 增加已建立但未充分利用的PERG反应的临床效用。在我们的第二阶段努力中， 我们将扩大对青光眼嫌疑人的测试，观察时间呈现率的影响， PERG反应的动态适应。研究表明，这两个因素 影响视网膜功能障碍患者。看看CLAD的这些额外应用 在更大的患者库中使用分析技术将进一步扩展第一阶段工作中所做的工作 并继续扩大PERG反应的临床应用。