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

基本信息

批准号：
10252917
负责人：
CLARK E TEDFORD
金额：
$ 67.47万
依托单位：
LUMITHERA, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10252917
关键词：
Activities of Daily Living Acute Address Adult Affect Aftercare Age Anatomy Angiography Applications Grants Area Blindness Chronic Chronic Disease Clinical Clinical Data Clinical Research Clinical Trials Clinical assessments Complication Contrast Sensitivity Degenerative Disorder Detection Devices Diabetes Mellitus Diabetic Retinopathy Disease Disease Progression Dose Drusen Ear Environment Etiology Exposure to Eye Flavoproteins Fluorescence Foundations Frequencies Image Inflammation Injections Label Left Light Light Coagulation Longevity Masks Measures Medical Medical Device Medicine Metabolic Mitochondria Molecular Target New York Nonexudative age-related macular degeneration Obesity Operative Surgical Procedures Optical Coherence Tomography Outcome Output Pathology Patients Persons Pilot Projects Placebos Population Preventive Procedures Publishing Radiation Randomized Clinical Trials Reporting Research Resources Retina Retinal Edemas Retreatment Review Literature Risk Safety Series Small Business Innovation Research Grant System Thick Time Tissues Universities Vascular Endothelial Growth Factors Vision Visual Visual Acuity Visual impairment age related aged base bevacizumab clinical outcome measures cost cost effective design diabetic diabetic patient experience improved innovation instrument laser photocoagulation macular edema mitochondrial dysfunction novel photobiomodulation prospective restorative treatment

项目摘要

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.

抽象的糖尿病影响全球超过 2.84 亿人，其中 20% 的糖尿病患者患有糖尿病黄斑水肿（DME），一种严重的眼部并发症，会损害视功能，如果出现以下情况，最终会导致失明：对于未经治疗的 DME 患者，目前的治疗包括激光光凝手术和玻璃体内注射。抗 VEGF 注射，这是一种侵入性且昂贵的光生物调节 (PBM) 疗法。包括对目标组织暴露于低水平的光辐射，从而产生有益的影响线粒体输出和临床结果的改善。与 DME 具有重叠的病理学特征，包括线粒体功能障碍和炎症，导致干性 AMD 的多项试点研究（例如 TORPA I 和 II、LIGHTSITE I）已显示出显着的视力丧失。 PBM 治疗后视觉和解剖学终点均得到改善。 LIGHTSITE I 研究显示，视力和对比敏感度在临床和统计学上有显着改善，观察到玻璃疣厚度和玻璃疣体积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先选择的波长进行 PBM 治疗。使用 Valeda® 光传输系统刺激线粒体功能并抑制 VEGF 表达。 Valeda 是唯一获得商业批准的用于干性 AMD 治疗的设备（CE 标志）。目前的 SBIR 提案旨在将 Valeda 治疗的效用扩大到 DME 人群，使用 LumiThera 的 Valeda 光传输系统进行试点前瞻性双盲临床试验，两个顶级视网膜 DME 中心：斯坦福大学（首席研究员：Diana Do 博士和 Quan Nguyen 博士）和纽约眼耳医院医务室（NYEE，PI：Richard Rosen 博士）。两个中心都有使用 Valeda 设备和研究的经验。具体目标将确定多波长的临床、解剖和代谢益处的大小对 40 名 DME 患者进行 PBM，分为两组，大约 20 名受试者将接受 PBM 治疗。 20 名受试者将使用 Valeda 光传输系统每周接受 3 次假治疗，持续 3 周。斯坦福大学和 NYEE 提供顶级 DME 研究环境来开展这一创新性、探索性的研究临床试验将对所有受试者进行临床（视力和对比敏感度）和解剖学评估。（OCT 和 OCT-A 成像）基线和治疗后第 1、3 和 6 个月 (M) 的结果。结果（黄素蛋白荧光）将在每次 PBM 治疗后以及 M3 和 M6 时测量确定线粒体改善的时间过程和长期效果。研究结果将为一项新型非药物关键试验提供基本的安全性和科学基础。 DME 的侵入性非药物治疗。