EARLY DETECTION OF GLAUCOMA DAMAGE

青光眼是世界范围内导致不可逆失明的主要原因之一。由于这是一种病程较长的慢性疾病，直到晚期才出现症状，因此诊断和监测对于防止视神经永久性损伤至关重要。美国国家眼科研究所在其“视觉研究：国家计划”中指出，发展“包括视觉功能、视神经和神经纤维层结构测量在内的改进诊断技术”是该项目的目标。为了寻找青光眼损伤早期诊断的更好工具，我们提出了一种基于评估后极视网膜组织损失的新方法，后极有大量的神经节细胞，这些细胞对中心视力至关重要，并且在青光眼中丢失。我们开发了一种计算机光学方法，视网膜厚度分析仪（RTA），以绘制视网膜后极的厚度。青光眼患者视网膜后极的RTA检测到视网膜厚度的大量减少，这是由于与视野缺损位置相对应的神经节细胞和神经纤维的丢失。此外，在没有视野缺陷的区域发现视网膜厚度下降。根据NEI的建议，我们将使用流行病学方法，在RTA的基础上，为原发性开角型青光眼的诊断和进展制定可靠、有效的标准。NEI已经确定了一个需要解决的重要研究问题：“青光眼的视觉功能丧失与视神经和视网膜神经纤维层的结构变化之间的关系是什么？”我们建议研究RTA在青光眼诊断和监测中的应用，并首次评估中央神经节细胞和神经纤维的损失。我们将研究：1)在横断面研究中，RTA是否可以检测到青光眼损伤区域视网膜厚度相对于正常厚度的下降；2)在一项纵向研究中，在已确诊的青光眼患者出现新的视野丧失之前RTA测量的特征。此外，第二项有前途的技术，GDx神经纤维分析仪（NFA），一种扫描激光偏振仪，测量乳头周围区域的神经纤维层延迟损失，将被评估并与RTA进行比较。总之，我们建议评估和比较RTA和NFA在识别青光眼和青光眼视野缺损进展风险增加的眼睛方面的敏感性、特异性、有效性和可靠性。对RTA和NFA的评估将有助于确立它们作为青光眼临床管理、流行病学研究和临床试验结果测量的效用。

Glaucoma is one of the leading causes of irreversible blindness worldwide. Because it is a chronic disease with a long course and is symptomless until the late stages, diagnosis and monitoring are essential to prevent permanent damage to the optic nerve. The National Eye Institute, in its "Vision Research: A National Plan", states that the development of "improved diagnostic techniques encompassing measures of visual function, optic nerve, and nerve fiber layer structure..." are program goals. In seeking better tools for the early diagnosis of glaucoma damage, we propose a new approach based on the assessment of retinal tissue loss at the posterior pole, where there is an abundance of ganglion cells which are essential to central vision and which are lost in glaucoma. We have developed a computerized optical method, the Retinal Thickness Analyzer (RTA), to map the retinal thickness at the posterior pole. Large losses in retinal thickness were detected by the RTA at the posterior pole of glaucoma patients due to the loss of ganglion cells and nerve fibers corresponding to the locations of documented visual field defects. Moreover, retinal thickness loss was found in areas devoid of visual field defects. In accordance with the NEI recommendation, we will use epidemiologic methods to develop reliable, valid criteria for the diagnosis and progression of primary open-angle glaucoma, based on the RTA. The NEI has identified an important research question to be addressed: "what is the relationship between visual function loss and structural changes to the optic nerve and retinal nerve fiber layer in glaucoma?". We propose to investigate the utility of the RTA for diagnosis and monitoring of glaucoma and assess, for the first time, the loss of the central ganglion cells and nerve fibers. We will examine: 1) in a cross-sectional study, whether the RTA can detect decreased retinal thickness, relative to normal thickness, in areas with well documented glaucomatous damage; 2) in a longitudinal study, the characteristics of RTA measurements which precede new visual field loss in established glaucoma patients. In addition, a second promising technology, the GDx Nerve Fiber Analyzer (NFA), a scanning laser polarimeter that measures nerve fiber layer retardation loss in the peripapillary area, will be evaluated and compared with the RTA. In sum, we propose to evaluate and compare the sensitivity, specificity, validity, and reliability of the RTA and the NFA in identifying eyes with glaucoma and in identifying eyes at increased risk of progression of glaucomatous visual field defects. This assessment of the RTA and NFA will help to establish their utility as outcome measures for clinical management of glaucoma, epidemiological research, and clinical trials.