Functional Imaging in Hypoxic-Ischemic Retinal Disease

缺氧缺血性视网膜疾病的功能成像

• 批准号: 10456440
• 负责人: Amir H Kashani
• 金额: $ 10.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456440
• 关键词: Functional; Imaging; Hypoxic; Ischemic; Retinal

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.

项目总结

项目成果

Surgically Induced Focal Retinal Detachment Does Not Cause Detectable SD-OCT Retinal Changes in Normal Human Retina.

• DOI: 10.1167/iovs.17-22737
• 发表时间: 2017-10-01
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: Kogachi K;Wolfe JD;Kashani AH
• 通讯作者: Kashani AH

Quantitative microvascular analysis of retinal venous occlusions by spectral domain optical coherence tomography angiography.

• DOI: 10.1371/journal.pone.0176404
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Koulisis N;Kim AY;Chu Z;Shahidzadeh A;Burkemper B;Olmos de Koo LC;Moshfeghi AA;Ameri H;Puliafito CA;Isozaki VL;Wang RK;Kashani AH
• 通讯作者: Kashani AH