Novel Glaucoma Diagnostics for Structure and Function

描述（由申请人提供）：青光眼是全球第二大常见致盲原因。我们广泛的长期目标是研究创新技术和方法，这些技术和方法将准确和可重复地提供青光眼及其进展的最早可能证据，以防止失明。我们在过去十年中以多种方式改进了我们所追求的计划，但重要的是，我们为这个项目组建了一个独特的合作小组。该小组包括匹兹堡大学、塔夫茨大学、马萨诸塞州理工学院和卡内基梅隆大学的眼科医生、工程师、计算机科学家和统计学家以及适当的支助人员。我们带来了来自不同领域的优秀研究人员，带来了眼科学以外的新见解，知识和技能，以实现青光眼疾病和进展检测技术的创新。我们将通过对健康人群、青光眼疑似患者和青光眼患者进行横断面和纵向研究来实现这一目标。我们的具体目标是：（1）检测出昏迷损害和进展的最早可能证据。我们将比较通过眼部成像和功能测量获得的客观、定量的眼部结构测量，以测试改变结构功能变化的预测，并表征这些变化;（2）先进的光学相干断层扫描（OCT）软件创新，评估视乳头周围和黄斑区以及视神经乳头（ONH）的视网膜内层。这一目标包括采用创新的图像处理和图像分析技术，以及事后改善扫描质量的新技术，（3）识别与特定青光眼诊断技术不同的特定临床特征群，从而最早检测青光眼及其进展。我们将使用创新的自动机器分类器和最先进的统计方法，这些方法使用成像设备生成的参数的最佳组合，以确定每种设备在评估疾病和进展中的最佳用途，（4）使用OCT推进微米级断层成像，以改善对ONH和内部的解剖和生物力学特性的理解。健康人和青光眼患者黄斑区和视乳头周围区的视网膜亚结构。这些是昏迷过程中的关键区域。这项实验旨在提高我们对青光眼的理解，并有可能创造一种新的青光眼诊断方法。扫描源和超高速谱域OCT将用于获得ONH、筛板和视网膜中的详细信息。通过这些设备的快速图像采集将最小化OCT扫描伪影，并且OCT光源波长的调制将允许在各种组织深度处的成像的优化。我们期望这些研究将使我们能够以高灵敏度和特异性比以往更早地检测青光眼及其进展，从而能够早期干预以预防青光眼失明。 公共卫生相关性：该提案的目标是优化使用客观、非侵入性、非接触式成像技术检测和监测青光眼，以防止失明。将对健康受试者、疑似青光眼受试者和青光眼受试者队列进行长期随访;我们将使用成像数据，通过软件创新、新型分析方法和新型扫描技术检测青光眼变化的最早可能证据。

DESCRIPTION (provided by applicant): Glaucoma is the second most common cause of blindness worldwide. Our broad, long-term objectives are to investigate innovative technologies and methods that will accurately and reproducibly provide the earliest possible evidence of glaucoma and its progression so as to prevent blindness. We have improved on the program that we have pursued for the past ten years in a number of ways, but importantly we have assembled a unique collaborative group for this project. This team includes ophthalmologists, engineers, computer scientists and statisticians, as well as appropriate support personnel, from the University of Pittsburgh, Tufts University, Massachusetts Institute of Technology and Carnegie Mellon University. We have brought excellent investigators from disparate fields to bring new insights, knowledge and skills from outside of ophthalmology to bear on innovations in technology for glaucoma disease and progression detection. We will accomplish this via cross-sectional and longitudinal studies using cohorts of healthy, glaucoma suspect and glaucomatous subjects. Our Specific Aims are to (1) detect the earliest possible evidence of glaucomatous damage and progression. We will compare objective, quantitative ocular structural measurements obtained by ocular imaging and functional measurements, to test the prediction that changes structural functional change, and to characterize those changes, (2) advance optical coherence tomography (OCT) software innovations that assess the intra-retinal layers in the peripapillary and macular areas as well as the optic nerve head (ONH). This aim includes employing innovative image processing and image analysis techniques, as well as new techniques to improve scan quality post hoc, (3) identify the particular clusters of clinical characteristics distinct to specific glaucoma diagnostic technologies resulting in the earliest detection of glaucoma and its progression. We will use innovative automated machine classifiers and state-of-the-art statistical methods which use the best combination of parameters generated by the imaging devices in order to determine the optimal use of each device in assessing disease and progression, (4) advance micron-scale tomographic imaging using OCT for improved understanding of the anatomical and biomechanical properties of the ONH and intra-retinal substructure in the macular and peripapillary regions in health and in glaucoma. These are key areas involved in the glaucomatous process. This experiment is designed to improve our understanding of glaucoma and potentially create a new glaucoma diagnostic. Swept-source and ultra-high speed spectral- domain OCT will be used to obtain detailed information in the ONH, lamina cribrosa and retina. Rapid image acquisition by these devices will minimize OCT scanning artifact, and modulation of OCT light source wavelengths will allow optimization of imaging at various tissue depths. We expect that these studies will lead to our ability to detect glaucoma and its progression earlier than ever before with high sensitivity and specificity, enabling early intervention to prevent glaucoma blindness. PUBLIC HEALTH RELEVANCE: The goal of this proposal is to optimize the use of objective, non-invasive, non-contact imaging technologies for the detection and monitoring of glaucoma in order to prevent blindness. Cohorts of healthy subjects, subjects suspected of having glaucoma and subjects with glaucoma will be followed over time; we will use imaging data to detect the earliest possible evidence of glaucomatous changes through software innovations, novel analysis methods and new scanning techniques.