Direct Measures of Retinal Blood Flow and Autoregulation as Robust Biomarkers for Early Glaucoma

项目摘要： 有强有力的证据表明，血管成分在血管性心脏病的发展和进展中起着重要作用。 原发性开角型青光眼（POAG）。具体来说，青光眼与受损的 视网膜血流量（RBF）和RBF的自动调节。自身调节功能障碍可能先于 视网膜神经节细胞（RGC）的损失，并已提出作为一个潜在的早期，可逆的 生物标志物。该提案的基本原理是高度精确、准确、直接 径向基函数的测量对于研究径向基函数的动态变化及其对RGC的影响是必要的。 目前的定量RBF的方法仍然有限，因为大多数成像模式提供 RBF的间接、相对测量。我们将直接测量RBF使用两个强大的直接 测量：红细胞介导血管造影血流测定（EMAf）和多模式自适应光学 （mAO）。这两种技术都可以高度准确和精确地测量RBF， 人体内的毛细血管水平。我们假设，这些直接测量的 确定绝对RBF将显示早期微血管RBF的自动调节受损。 青光眼，这将与青光眼损害相关。我们的研究计划将测试 这一假设通过两个具体的目标。在具体目标1中，我们将确定 与早期青光眼相关的自身调节受损，并测量其预测进一步青光眼的能力。 青光眼损害在具体目标2中，我们将确定毛细血管密度与 青光眼受试者和对照者的RGC密度。我们预测，早期青光眼患者将 与对照组相比，显示出显著的可测量的血管自动调节受损， 这些参数的局部变化将预测结构性昏迷缺陷。

Project Summary: There is strong evidence for a vascular component in the development and progression of primary open angle glaucoma (POAG). Specifically, glaucoma is associated with impaired retinal blood flow (RBF) and autoregulation of RBF. Autoregulatory impairment may precede retinal ganglion cell (RGC) loss and has been proposed as a potentially early, reversible biomarker. The rationale underlying this proposal is that highly precise and accurate, direct measures of RBF are necessary to study dynamic changes in RBF and their effect on RGCs. Current methods of quantifying RBF remain limited as the majority of imaging modalities provide indirect, relative measurements of RBF. We will directly measure RBF using two robust direct measures: erythrocyte mediated angiography flowmetry (EMAf) and multimodal adaptive optics (mAO). Both techniques allow for the highly accurate and precise measurement of RBF down to the capillary level in the human eye in vivo. We hypothesize that these direct measures of determining absolute RBF will show impaired autoregulation of microvascular RBF in early glaucoma and that this will correlate with glaucomatous damage. Our research program will test this hypothesis through two specific aims. In Specific Aim 1, we will determine the extent of impaired autoregulation associated with early glaucoma and measure its ability to predict further glaucoma damage. In Specific Aim 2 we will determine the relationship of capillary density and RGC density in glaucoma subjects and controls. We predict that early glaucoma subjects will exhibit significant measurable impaired vascular autoregulation as compared to controls and that local changes in these parameters will predict structural glaucomatous deficits.