Imaging of Retinal Oxygen Metabolism in Diabetic Retinopathy

摘要 糖尿病视网膜病变（DR）是目前工作年龄成人视力丧失的主要原因。与 糖尿病人口的预期增长，无法工作的视力受损糖尿病患者人数 或照顾自己将继续是一个主要的公共卫生问题。预防DR引起的视力丧失 需要早期诊断、定期监测和及时治疗干预。目前，未满足的临床 需要能够前瞻性地识别哪些糖尿病患者将发展为DR，发展为视力， 威胁阶段，或对治疗反应良好。一个公认的因素，有助于 由于DR而导致的威胁视力的病理的发展是视网膜缺氧，其随后可损害 氧代谢维持氧代谢是必不可少的能源生产是至关重要的细胞 来生存并进行视觉处理。视网膜内部的氧代谢是由 内视网膜氧输送和氧提取分数。虽然视网膜组织和微血管 已经从解剖学的角度进行了广泛的研究，但关于 视网膜氧代谢功能和能量生产由于DR的研究建议将克服这一点 通过创新、定量和全面的多模式成像方法来阐明 氧代谢的改变和调节机制的缺陷，发生在进行性阶段， DR，与治疗的应用，并与视网膜毛细血管丛形态。具体目标是 1）识别与DR的阶段相关联并且指示视网膜氧代谢的内视网膜氧代谢度量， 过去的血糖控制; 2）确定治疗前视网膜内层氧代谢指标，其预测 治疗结果; 3）阐明视网膜内层氧代谢指标、毛细血管丛 本研究结果将拓宽对DR的认识 病理生理学，改善诊断和预后评估，并推动寻找新的预防和 治疗干预。这项研究可能会改变DR的临床评估，从而 显著影响糖尿病患者的生活质量和视力受损者的护理成本 个体

Abstract Diabetic retinopathy (DR) is currently the leading cause of vision loss in working age adults. With the anticipated growth of the diabetic population, the number of visually impaired diabetic people who cannot work or care for themselves will continue to be a major public health concern. Vision loss prevention due to DR requires early diagnosis, regular monitoring, and timely therapeutic intervention. Currently, the unmet clinical needs are the ability to prospectively identify which diabetic individuals will develop DR, progress to vision- threatening stages, or respond favorably to therapy. A generally recognized factor that contributes to the development of vision-threatening pathologies due to DR is retinal hypoxia, which can subsequently impair oxygen metabolism. Maintenance of oxygen metabolism is essential for energy production that is vital for cells to survive and perform visual processing. Inner retinal oxygen metabolism is maintained by the balance of inner retinal oxygen delivery and oxygen extraction fraction. Although the retinal tissue and microvasculature have been extensively studied from an anatomical perspective, there is limited information about alterations in retinal oxygen metabolic function and energy production due to DR. The research proposal will overcome this limitation by an innovative, quantitative, and comprehensive multimodal imaging approach to elucidate alterations in oxygen metabolism and defects in regulatory mechanisms that occur at progressive stages of DR, with application of treatment, and in relation to retinal capillary plexus morphology. The specific aims are to: 1) identify inner retina oxygen-metabolic metrics that are associated with stages of DR and indicative of past glycemic control; 2) determine pre-treatment inner retina oxygen-metabolic metrics that are predictive of treatment outcome; 3) elucidate associations among inner retina oxygen-metabolic metrics, capillary plexus morphology and cell layer thickness at stages of DR. The findings will broaden knowledge of DR pathophysiology, improve diagnostic and prognostic evaluation, and propel search for new preventative and therapeutic interventions. The research study can potentially transform clinical assessment of DR, thereby significantly impacting the quality of life of diabetic people and the cost of caring for visually impaired individuals.