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

摘要 糖尿病影响全球超过2.84亿人，20%的糖尿病患者发展为糖尿病黄斑 浮肿(DME)是一种严重的眼部并发症，会损害视觉功能，如果发生以下情况，最终会导致失明 不治身亡。对于DME患者，目前的治疗方法包括激光光凝手术和玻璃体内注射。 抗血管内皮生长因子注射，这是一种侵入性的昂贵程序。光生物调节(PBM)疗法 包括暴露于目标组织的低水平光辐射，从而对 线粒体输出和临床结果的改善。干性老年性黄斑变性 与DME有重叠的病理改变，包括线粒体功能障碍和炎症导致 严重的视力丧失。干性AMD的几项试点研究，例如TORPA I和II，LIGHTSITE I，已经表明 PBM治疗后视觉和解剖终点的改善。在最新的 LIGHTSITE I研究，在临床和统计学上显著改善视力和对比敏感度， 观察到玻璃体厚度和体积减少，日常生活活动能力改善。 PBM治疗后即刻。使用多个预先选择的波长进行PBM治疗 利用Valeda®Light Delivery System刺激线粒体功能并抑制血管内皮生长因子表达。 Valeda是唯一获得商业批准的干性AMD治疗设备(CE标志)。 目前的SBIR建议旨在将Valeda治疗的效用扩大到DME人群中，并 使用LumiThera的Valeda Light Delivery系统进行试点前瞻性双掩蔽临床试验， 两个顶级视网膜DME中心：斯坦福(PI：Diana Do博士和Quan Nguyen博士)和纽约眼耳 医务室(NYEE，PI：Richard Rosen博士)。这两个中心都有使用Valeda设备的经验，这项研究 具体目标将确定多波长的临床、解剖和代谢益处的大小 将40例DME患者分为两组，每组30例。大约20名受试者将接受PBM治疗和 20名受试者将使用Valeda Light Delivery系统每周接受3次假治疗，为期3周。 斯坦福大学和NYEE提供了顶尖的DME研究环境来进行这一创新的探索性研究 临床试验。所有受试者都将接受临床(视力和对比敏感度)和解剖方面的评估。 (OCT和OCT-A成像)基线和治疗后1个月、3个月和6个月的结果。新陈代谢 结果(黄素蛋白荧光)将在每次PBM治疗后以及在M3和M6至 建立线粒体改善的时间进程和作用的长期持续时间。 这一发现将为一项关键试验提供基本的安全性和科学基础，该试验采用一种新型的非 DME的侵入性非药物治疗。

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.