Functional Imaging in Hypoxic-Ischemic Retinal Disease

项目摘要 缺血和缺氧在常见致盲性疾病的病理生理学中起关键作用 例如糖尿病视网膜病变（DR）和视网膜静脉阻塞（RVO）。可惜 毛细血管灌注受损（通常称为缺血或“无灌注”）与 由于有限的成像方法，缺氧在临床环境中很大程度上是未知的。 毛细血管灌注受损在临床上几乎完全通过荧光素来显示 血管造影（FA），但组织学研究表明，FA低估了毛细血管密度， 高达30-40%，从而低估了“无灌注”的诊断。间接临床证据和动物 研究表明缺氧是DR和RVO后遗症的基础。例如， 敏感性缺陷和视网膜增厚在呼吸氧气的糖尿病患者中被逆转。 然而，几乎没有直接的证据表明，视网膜缺氧在人类，因为侵入性 测量视网膜内氧含量的方法。由于没有直接的临床测量 对于轻度-中度缺氧和仅有限评估毛细血管灌注受损 （缺血），目前的治疗DR和RVO假定直接和静态的关系 在这两个人之间。然而，大量的临床证据表明，缺血和缺氧 并不直接相关。这些观察结果证实了缺血， 视网膜血管疾病的缺氧和后遗症还不完全清楚。我假设 微血管缺氧和缺血之间的关系不是静态的， 直接;我认为这是目前治疗和治疗失败的局限性的基础。 我建议进行基础和临床研究，将真实的时间眼内pO 2测量值与眼内pO 2测量值相关联， 使用非侵入性成像方法如光学相干法建立缺血动物模型 断层扫描血管造影术（OCTA）评估视网膜毛细血管灌注和高光谱 计算机断层成像光谱（HCTIS）评估组织缺氧。这些 然后将这些方法转化为临床，在临床上它们已经被证明是安全有效的。 我进行的试点研究中的成像模式。这些方法的结合 利用金标准眼内pO 2测量来验证和校准非 可以安全有效地用于人类受试者的侵入性方法。最后，我建议 利用OCTA和HCTIS来关联人体缺血缺氧的程度和持续时间 DR和RVO导致视力丧失的受试者。

Project Summary Ischemia and hypoxia play critical roles in the pathophysiology of common blinding diseases such as diabetic retinopathy (DR) and retinal vein occlusions (RVO). Unfortunately, the correlation between impaired capillary perfusion, often called ischemia or “nonperfusion,” and hypoxia is largely unknown in a clinical setting because of limited imaging methodologies. Impaired capillary perfusion is almost exclusively demonstrated in clinic by fluorescein angiography (FA) but histological studies show that FA underestimates capillary density as much as 30-40% thereby under-diagnosing “nonperfusion.” Indirect clinical evidence and animal studies suggest that hypoxia underlies sequelae of DR and RVO. For example, contrast sensitivity deficits and retinal thickening are reversed in diabetic subjects breathing oxygen. However, there is little direct evidence of retinal hypoxia in humans because of the invasive methods needed to measure intraretinal oxygen levels. Since there is no direct clinical measure for mild-moderate hypoxia and only limited assessments of impaired capillary perfusion (ischemia), current treatments for DR and RVO presume a direct and static relationship between these two. However, abundant clinical evidence suggests that ischemia and hypoxia are not directly correlated. These observations confirm that the correlation between ischemia, hypoxia and sequelae of retinal vascular diseases are incompletely understood. I hypothesize that the relationship between microvascular hypoxia and ischemia is not static nor necessarily direct; and I suggest that this underlies limitations in current treatments and therapeutic failures. I propose basic and clinical studies that correlate real time intraocular pO2 measurements in animal models of ischemia with non-invasive imaging methods such as optical coherence tomography angiography (OCTA) to assess retinal capillary perfusion and hyperspectral computed tomographic imaging spectroscopy (HCTIS) to assess tissue hypoxia. These methods are then translated to the clinic where they are already shown to be safe and effective imaging modalities in pilot studies I have performed. The combination of these approaches leverages the gold standard intraocular pO2 measurements to validate and calibrate non- invasive methods that can be used safely and effectively in human subjects. Lastly, I propose to use OCTA and HCTIS to correlate the extent and duration of ischemia and hypoxia in human subjects with vision loss from DR and RVO.