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

描述(申请人提供)：青光眼是可预防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已经有了很多了解，但新的治疗形式的开发受到三个障碍的阻碍：正常眼睛的神经节细胞数量在受试者之间的高度变异性，青光眼患者的受试者内的高度变异性，以及疾病的缓慢进展。这项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。这些结果旨在改善临床试验和正在进行的患者护理的措施，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害的结构和功能措施之间的协同作用。青光眼患者将使用定制的先进自适应光学扫描激光眼底镜(AOSLO)和定制的光谱域眼睛相干断层扫描(SD-OCT)进行视网膜神经纤维层(RNFL)的高分辨率视网膜成像。高分辨率视野检查将在视野的相应区域进行，使用自定义刺激，这些刺激可以抵抗传统视野检查中的光学伪影。结果将通过创新的统计方法进行评估，这些方法利用视野检查和成像测量之间的协同作用。具体目标1将这些方法应用于没有眼病的人，建立同时捕捉结构和厚度的RNFL的三维模型，目的是利用结构来克服正常眼睛神经节细胞数量在受试者之间高度变异的障碍。特定目标2将专注于颞叶视网膜，它具有独特的特征，使得定位视网膜神经纤维开始的位置成为可能，只从几个轴突开始。颞叶视网膜对应于鼻视野，在早期青光眼中视野丧失是常见的，重点将放在纵向研究中检测一些最早的变化上。具体目标3将重点放在黄斑上，这一点非常重要，因为它为日常生活的许多活动提供了高分辨率的视觉。黄斑还具有独特的特征，使其能够成像视网膜神经纤维的起始位置，并且非常适合高分辨率视野检查。具体目标4将把这一方法扩展到鼻视网膜，通过检查患有“楔形”RNFL缺陷的患者，这些缺陷在视盘处狭窄，然后在受损的RNFL楔形区域变宽。而特定目标2和3解决了RNFL纤维起始的独特位置，而特定目标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.