Structural and Functional Progression of Glaucomatous Damage to the Macula

 描述(由申请人提供)：有令人信服的证据表明，即使在疾病的早期阶段，青光眼对黄斑的损害也会发生。黄斑约占所有视网膜神经节细胞的30%，其信息相当于视皮层的50%以上。 然而，在临床实践中，青光眼对黄斑的损害经常被遗漏。其中一些原因是：1)传统的青光眼知识支持青光眼本质上是一种外周疾病；2)传统临床测试检测黄斑损害的固有局限性；以及3)缺乏描述青光眼黄斑损害性质的大型前瞻性研究。我们小组在过去两年发表了大量论文，表明如果使用适当的工具，即10-2视野和高分辨率光学相干断层扫描(OCT)，黄斑损害在早期青光眼患者中很常见。这些信息来自一个独特的预期横断面数据库和我们开发的技术，以产生结构和功能的客观度量。现在我们了解了黄斑损伤的横断面性质，这项建议的目的是：1)建立一个包括早期青光眼患者和健康对照组的纵向数据库，2)测试解释黄斑损伤进展的模型，3)应用新的统计方法，结合结构和功能测试，可以提高检测进展的准确性，并缩短临床试验的时间。我们的主要假设是，将10-2视野测试和高分辨率OCT黄斑扫描纳入临床实践中使用的传统技术体系，以及将最近描述的统计方法转换为可用于日常实践的软件，可以增强检测青光眼进展的性能和信心。在目标1中，我们计划定期跟踪健康受试者和青光眼患者，进行10-2、24-2视野和扫频源(Ss)OCT测试，并定义区分真实进展和噪音所需的短期和长期测试变异性的度量标准。到目前为止，还没有将这些技术结合在一起的数据库。在目标2中，我们计划使用两种方法从这个纵向数据库中结合结构和功能的度量：空间方法，最终将使用10-2和ssOCT数据产生联合结构-功能指数；时间方法，将使用贝叶斯统计方法，通过趋势分析来衡量进展速度。到研究结束时，我们对这一领域的贡献应该是：1)提供一个独特的、原始的纵向数据库，可用于其他假说检验；2)将最近文献中描述的技术转化为客观工具，以便在临床实践中随时有用；3)减轻青光眼患者进行性中心视力丧失的负担。

 DESCRIPTION (provided by applicant): There is compelling evidence that glaucomatous damage to the macula occurs even in early stages of the disease. The macula comprises about 30% of all retinal ganglion cells and its information corresponds to over 50% of the visual cortex. However, glaucomatous damage to the macula is often missed in clinical practice. Some of the reasons are: 1) traditional glaucoma knowledge supports that glaucoma is fundamentally a peripheral disease; 2) inherent limitations of conventional clinical tests to detect damage to the macula; and 3) the paucity of large, prospective studies that describe the nature of glaucomatous damage to the macula. Our group has published numerous papers in the past two years showing that macular damage is prevalent among patients with early glaucoma if one employs the appropriate tools to assess it, namely 10-2 visual fields and high-resolution optical coherence tomography (OCT). This information comes from a unique prospective cross- sectional database and techniques we developed to produce objective metrics of structure and function. Now that we understand the cross-sectional nature of macular damage, this proposal aims to: 1) develop a longitudinal database including patients with early glaucoma and healthy controls, 2) to test models that explain progression of macular damage, and 3) to apply new statistical methods combining structural and functional tests which could improve the accuracy to detect progression and shorten the length of clinical trials. Our main hypothesis is that incorporating 10-2 visual field testing and high-resolution OCT scans of the macula to the conventional repertoire of technologies used in clinical practice, in addition to translating recently described statistical methods into softwares that can be used in daily practice, enhances the performance and confidence to detect glaucoma progression. In Aim 1 we plan to follow healthy subjects and glaucoma patients at regular intervals with 10-2, 24-2 visual fields, and swept source (ss) OCT tests and define metrics of short- and long-term test variability that are needed to differentiate true progression from 'noise'. To date, there is no such database combining these technologies. In Aim 2 we plan to combine metrics of structure and function from this longitudinal database using two methods: a spatial approach, which will ultimately produce a joint structure-function index using 10-2 and ssOCT data; and a temporal approach, which will employ Bayesian statistics to measure rates of progression using trend analysis. By the end of the study, our contributions to the field should be: 1) to make available a unique and pristine longitudinal database that could be used for other hypotheses testing, 2) to translate techniques recently described in the literature into objective tools to be readily useful in clinicl practice, and 3) to mitigate the burdens of progressive loss of central vision in glaucoma.