The Use of Photobiomodulation (PBM) in the Treatment for Diabetic Macular Edema

光生物调节 (PBM) 在治疗糖尿病性黄斑水肿中的应用

• 批准号: 10670790
• 负责人: CLARK E TEDFORD
• 金额: $ 23.97万
• 依托单位: LUMITHERA, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10670790
• 关键词: Activities of Daily Living; Address; Affect; Aftercare; Anatomy; Applications Grants; Area; Blindness; Clinical; Clinical Trials; Complication; Contrast Sensitivity; Detection; Devices; Diabetes Mellitus; Diabetic Retinopathy; Disease; Drusen; Ear; Environment; Exposure to; Eye; Flavoproteins; Fluorescence; Foundations; Frequencies; Image; Inflammation; Injections; Left; Light; Longevity; Masks; Measures; Medicine; Metabolic; Mitochondria; New York; Nonexudative age-related macular degeneration; Obesity; Operative Surgical Procedures; Outcome; Output; Pathology; Patients; Persons; Pilot Projects; Placebos; Population; Procedures; Radiation; Research; Retina; Safety; Small Business Innovation Research Grant; System; Thick; Time; Tissues; Universities; Vascular Endothelial Growth Factors; Vision; Visual; Visual Acuity; Visual impairment; bevacizumab; cost effective; diabetic; diabetic patient; experience; improved; innovation; laser photocoagulation; macular edema; mitochondrial dysfunction; novel; photobiomodulation; prospective

ABSTRACT Diabetes affects over 284 million people worldwide and 20% of diabetic patients develop diabetic macular edema (DME), a significant ocular complication that impairs visual function, eventually leading to blindness if left untreated. For patients with DME, current treatment involves laser photocoagulation surgery and intravitreal anti-VEGF injections, which are invasive and expensive procedures. Photobiomodulation (PBM) therapy consists of exposure to low levels of light radiation to targeted tissues resulting in beneficial effects to mitochondrial output and improvements in clinical outcomes. Dry age-related macular degeneration (AMD) shares overlapping pathology with DME including mitochondrial dysfunction and inflammation leading to significant vision loss. Several pilot studies in Dry AMD, e.g., TORPA I & II, LIGHTSITE I, have shown improvements in both visual and anatomical endpoints following PBM treatment. In the most recent LIGHTSITE I study, clinically and statistically significant improvement in visual acuity and contrast sensitivity, reductions in drusen thickness and drusen volume, and improvements in activities of daily living were observed immediately after PBM treatment. PBM treatment was administered using multiple pre-selected wavelengths to stimulate mitochondrial function and to suppress VEGF expression with the Valeda® Light Delivery System. Valeda is the only commercially approved device (CE mark) for dry AMD treatment. The current SBIR proposal aims to expand the utility of the Valeda treatment into the DME population and conduct a pilot prospective, double-masked clinical trial with LumiThera’s Valeda Light Delivery System, with two top retinal DME centers: Stanford (PI: Drs. Diana Do and Quan Nguyen) and the New York Eye and Ear Infirmary (NYEE, PI: Dr. Richard Rosen). Both centers have experience with the Valeda device, and the Study Specific Aims will establish the magnitude of clinical, anatomical and metabolic benefit of multi-wavelength PBM on 40 DME patients, divided into two groups. Approximately 20 subjects will receive PBM treatment and 20 subjects will receive sham treatment 3x per week for 3 weeks using the Valeda Light Delivery System. Stanford University and NYEE provide top DME research environments to conduct this innovative, exploratory clinical trial. All subjects will be assessed for clinical (visual acuity and contrast sensitivity) and anatomical (OCT and OCT-A imaging) outcomes at baseline and Months (M) 1, 3 and 6 post-treatment. Metabolic outcomes (flavoprotein fluorescence) will be measured after each PBM treatment as well as at M3 and M6 to establish the time course of mitochondrial improvement and long-term duration of effect. The findings will provide the basic safety and scientific foundation for a pivotal trial with a novel non- invasive, non-pharmaceutical therapy for DME.

抽象的 糖尿病在全球影响超过2.84亿人，其中20％的糖尿病患者患糖尿病黄斑 水肿（DME），这是一种损害视觉功能的重要眼部并发症，有时会导致失明 保持未经处理。对于患有DME的患者，当前治疗涉及激光光凝手术和玻璃体室内 反VEGF注射，是侵入性且昂贵的程序。光生物调节（PBM）治疗 包括暴露于低水平的光辐射对靶向组织，从而产生有益的影响 线粒体产量和临床结果的改善。与年龄相关的黄斑变性（AMD） 与DME的分享病理重叠，包括线粒体功能障碍和炎症，导致 巨大的视力丧失。在干燥AMD中进行了一些试点研究，例如Torpa I和II，Lightsite I，已显示 PBM处理后，视觉和解剖终点的改善。在最近的 我研究的Lightsite在临床和统计学上的视力和对比度敏感性上有显着改善， 观察到drusen厚度和drusen量的减少以及日常生活活动的改善 PBM治疗后立即。使用多个预选波长进行PBM处理 刺激线粒体功能并使用Valeda®光递送系统抑制VEGF表达。 Valeda是唯一获得干燥AMD处理的商业批准的设备（CE Mark）。 当前的SBIR提案旨在将Valeda治疗的效用扩展到DME人群，并 使用Lumithera的Valeda Light Offer System进行试验性，双掩蔽的临床试验，并带有 两个顶级视网膜DME中心：斯坦福（PI：Diana Do和Quan Nguyen博士）和纽约的眼睛和耳朵 医务室（Nyee，PI：Richard Rosen博士）。两个中心都有Valeda设备的经验，研究 具体目标将确定多波长的临床，解剖和代谢益处的大小 40名DME患者的PBM分为两组。大约20名受试者将接受PBM治疗，并且 使用Valeda Light递送系统，20名受试者每周将接受3倍的假治疗3周。 斯坦福大学和NYEE提供了顶级DME研究环境，以进行这种创新的探索性 临床试验。所有受试者均应评估临床（视敏度和对比灵敏度）和解剖学 （OCT和OCT-A成像）基线和几个月（M）1、3和6处理后的结果。代谢 每次PBM处理以及M3和M6的结局（黄素蛋白荧光）将测量 建立线粒体改善和长期效果持续时间的时间过程。 这些发现将为一项新型的非 - DME的侵入性，非药物治疗。