3D RNFL Structure and High-resolution Perimetry for Assessing Glaucomatous Damage

描述（由申请人提供）：青光眼是可预防性失明的主要原因之一，目前可用的治疗方法不足以阻止青光眼的进展。 很多病人。虽然人们对青光眼的生物学了解很多，但新疗法的开发却受到三个障碍的阻碍：正常眼中神经节细胞数量的受试者间高变异性、青光眼患者的受试者内高变异性以及疾病进展速度缓慢。拟议的研究整合了神经建模和临床研究，以开发诊断青光眼和评估失明进展的改进方法。研究结果旨在改进临床试验和持续患者护理的措施，同时提高对青光眼病理生理学的基础科学理解，并为疾病过程的生物学研究提供指导。临床设备的创新使用将指导定制系统的测试，统计分析将利用青光眼损伤的结构和功能测量之间的协同作用。将使用定制的先进自适应光学扫描激光检眼镜 (AOSLO) 以及定制的频域眼相干断层扫描 (SD-OCT) 对青光眼患者进行视网膜神经纤维层 (RNFL) 的高分辨率视网膜成像。将使用可抵抗影响传统视野检查的光学伪影的定制刺激，在视野的相应区域进行高分辨率视野检查。结果将通过利用视野检查和成像测量之间的协同作用的创新统计方法进行评估。具体目标 1 将这些方法应用于没有眼病的人，建立 RNFL 的三维模型，捕获结构和厚度，目标是利用结构克服正常眼中神经节细胞数量的受试者间高变异性障碍。具体目标 2 将重点关注颞部视网膜，颞部视网膜具有独特的特征，可以从几个轴突开始定位视网膜神经纤维的起始位置。颞视网膜对应于鼻视野，早期青光眼中视野丧失很常见，重点是在纵向研究中检测一些最早的变化。具体目标 3 将重点关注黄斑，这非常重要，因为它提供了用于许多日常生活活动的高分辨率视觉。黄斑还具有独特的特征，可以对视网膜神经纤维的起始位置进行成像，并且非常适合高分辨率视野检查。具体目标 4 将通过检查患有“楔形”RNFL 缺陷的患者，将这种方法扩展到鼻部视网膜，这些缺陷在视盘处狭窄，然后在受损的 RNFL 楔形处变宽。具体目标 2 和 3 解决的是 RNFL 纤维开始的独特位置，而具体目标 4 将解决如何解释视网膜其余部分的 RNFL 缺陷。

DESCRIPTION (provided by applicant): Glaucoma is one of the leading causes of preventable blindness, and currently available treatments are not sufficient to halt progression in many patients. While much has been learned about the biology of glaucoma, development of new forms of treatment has been stymied by three barriers: high between-subject variability in ganglion cell number in normal eyes, high within-subject variability in patients with glaucoma, and the slow rate of progression of the disease. The proposed research integrates neural modeling and clinical research to develop improved methods for diagnosing glaucoma and for assessing progression towards blindness. The results are intended to improve measures for both clinical trials and ongoing patient care, while at the same time improving basic science understanding of the pathophysiology of glaucoma and providing guidance for biological studies of the disease process. Innovative uses of clinical devices will guide testing with custom systems, and statistical analyses will utilize the synergy between structural and functional measures of glaucomatous damage. High-resolution retinal imaging of retinal nerve fiber layer (RNFL) will be performed on patients with glaucoma using a custom advanced adaptive optics scanning laser ophthalmosope (AOSLO) as well as custom use of spectral domain ocular coherence tomography (SD-OCT). High-resolution perimetry will be performed in corresponding regions of the visual field, using custom stimuli that are resistant to optical artifacts that affet conventional perimetry. The results will be assessed with innovative statistical methods that utilize the synergy between perimetry and imaging measures. Specific Aim 1 will apply these methods to people free of eye disease, building three-dimensional models of RNFL that capture both structure and thickness, with the goal of using structure to overcome the barrier of high between-subject variability in ganglion cell number in normal eyes. Specific Aim 2 will focus on temporal retina, which has unique characteristics that make it possible to locate where retinal nerve fibers begin, starting with just a few axons. Temporal retina corresponds to nasal visual field, where visual field loss is common in early glaucoma, and the emphasis will be on detecting some of the earliest changes in a longitudinal study. Specific Aim 3 will focus on the macula, which is of great importance because it provides high-resolution vision used for many activities of daily living. The macula also has unique characteristics that make it possible to image the starting locations of retinal nerve fibers, and is well-suited for high-resolution perimetry. Specific Aim 4 will extend this approach to nasal retina, by examining patients with "wedge" RNFL defects that are narrow at the optic disc and then widen in a wedge of damaged RNFL. Whereas Specific Aims 2 & 3 address unique locations where RNFL fibers begin, Specific Aim 4 will address how to interpret RNFL defects across the rest of the retina.