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

摘要： 青光眼是导致视网膜神经节细胞(RGC)的多种视神经疾病之一 变性，如果不治疗，最终表现为功能性视力丧失。存在一个数字 治疗这些疾病的治疗方法，但目前还没有临床方法 检测RGC功能障碍的发病情况。模式视网膜电信号(PERG)是唯一建立起来的工具 监测RGC在人体和视神经疾病实验模型中的健康状况。这个 监测PERG反应有可能提供对退行性视网膜疾病的早期检测 例如青光眼，允许在不可逆转的功能视力之前启动治疗范例 已经发生了损失。PERG广泛应用于研究和临床的关键障碍 涉及用于引起视觉响应的常规可用显示器的次优特性。这个 拟议项目的目标是生产商业上可用的设备，用于视觉研究 和临床应用，不仅更紧凑、更快、更便宜、更人性化，而且 还通过创新的显示技术和处理提供更高质量的信息 技巧。作为我们第一阶段工作的一部分，我们开发了一种基于 关于可变极化。此外，我们使用CLAD去卷积技术提取了额外的 来自PERG反应的临床信息。记录青光眼疑似患者和年龄的数据 与对照组相比，包衣提取的数据在两者之间有更显著的差异 与传统技术相比，这是一种新的技术。此外，ROC曲线由 CLAD数据具有比传统技术更高的AUC值(使用CLAD时为0.897，而使用CLAD时为0.74% 0.683用于常规的暂态和稳态PEGG)。在第二阶段，有以下具体目标 将致力于：1)提炼新一代人体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了头戴式、近眼显示配置。我们会 加入其他功能，如主动注视和瞳孔大小监测以及一次性 干式电极接口(基于第一阶段的工作)，将最大限度地减少患者的准备工作并增加 吞吐量，并消除了对象之间的消毒设备的需要。2)扩展包层 青光眼。作为我们第一阶段工作的一部分，我们展示了覆盖技术具有潜在的 提高建立良好但未充分利用的PERG反应的临床效用。在我们的第二阶段工作中， 我们将扩大对青光眼疑似患者的测试，观察时间表现率的影响，以及 PERG反应的动态适应。研究表明，这两个因素都是 受影响的患者有视网膜功能障碍。查看覆层的这些附加应用 更大患者池中的分析技术将在第一阶段工作中完成的工作基础上进一步扩展 并继续扩大PERG反应的临床应用。

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.