Functional Imaging in Hypoxic-Ischemic Retinal Disease

项目摘要 缺血和缺氧在常见致盲疾病的病理生理学中起重要作用 如糖尿病视网膜病变(DR)和视网膜静脉阻塞(RVO)。不幸的是， 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，在临床环境中缺氧在很大程度上是未知的。 临床上几乎只有荧光素显示毛细血管血流灌注受损。 血管造影术(FA)，但组织学研究表明FA低估了毛细血管密度 因此，高达30-40%的患者未被诊断为“无血流灌注”。间接临床证据与动物 研究表明，缺氧是DR和RVO后遗症的基础。例如，对比度 呼吸氧气的糖尿病患者的敏感度缺陷和视网膜增厚发生逆转。 然而，由于侵袭性的原因，几乎没有直接证据表明人类存在视网膜缺氧。 需要测量视网膜内氧气水平的方法。因为没有直接的临床措施 适用于轻-中度缺氧和对毛细血管灌注受损的有限评估 (缺血)，目前对DR和RVO的治疗假设是直接和静态的关系 在这两个之间。然而，大量的临床证据表明，缺血和缺氧 不是直接相关的。这些观察结果证实了脑缺血、 视网膜血管疾病的缺氧和后遗症尚不完全清楚。我假设 微血管缺氧和缺血之间的关系不是静止的，也不是必然的 直接；我认为这是当前治疗的局限性和治疗失败的基础。 我建议进行基础和临床研究，将实时眼内血氧饱和度测量与 光学相干等非侵入性成像方法制作脑缺血动物模型 断层血管成像(OCTA)评估视网膜毛细血管血流灌注和高光谱 计算机断层成像光谱学(HCTIS)评估组织缺氧。这些 然后，这些方法被翻译到临床，在那里它们已经被证明是安全有效的 在我进行的先导研究中的成像方式。这些方法的组合 利用黄金标准眼内PO2测量来验证和校准非 可在人体内安全有效地使用的侵入性方法。最后，我建议 OCTA和HCTIS在人脑缺血缺氧程度和持续时间中的应用 因DR和RVO而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.