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

项目总结： 有强有力的证据表明血管成分在肿瘤的发生和发展中起作用。 原发性开角型青光眼。具体地说，青光眼与受损有关 视网膜血流量(RBF)及其自身调节。自动调节功能受损可能先于 视网膜神经节细胞(RGC)丢失，已被认为是一种潜在的早期、可逆的 生物标志物。这一提议背后的理由是高度精确和准确、直接 为了研究RBF的动态变化及其对RGCs的影响，有必要测量RBF。 目前量化RBF的方法仍然有限，因为大多数成像方式提供了 间接的、相对的RBF测量。我们将使用两个健壮的直接测量来直接测量RBF 测量：红细胞介导的血管造影术(EMAF)和多模式自适应光学 (毛)。这两种技术都允许高精度和高精度的RBF测量 活体内人眼的毛细血管水平。我们假设，这些直接衡量标准 测定绝对RBF可早期显示微血管RBF自我调节功能受损 青光眼，这与青光眼损害有关。我们的研究计划将测试 这一假说有两个具体目的。在具体目标1中，我们将确定 与早期青光眼相关的自我调节功能受损及其进一步预测的能力 青光眼损伤。在具体目标2中，我们将确定毛细血管密度与 青光眼患者和对照组的RGC密度。我们预测早期青光眼患者会 与对照组相比，显示出明显的可测量的血管自我调节受损 这些参数的局部变化将预测结构性青光眼缺陷。

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.