LIGHTSITE IIIB: Clinical Evaluation of Photobiomodulation (PBM) in dry AMD Patients

摘要 随着人口的不断老龄化，退行性眼病变得越来越普遍 给医疗系统造成巨大负担。视网膜相关性黄斑变性（AMD） 是一种进行性眼病，在最严重的情况下会导致视力受损和失明。 形式，其特征在于黄斑中的功能丧失和细胞死亡，这是一个中心和关键的 视网膜的一部分。在美国，大约有1100万人患有AMD。 仅在美国，全球患病率就达1.7亿。AMD是导致视力残疾的主要原因 在发达国家和全球第三大原因。AMD以两种形式发生：干性和 湿性AMD。大约85-90%的AMD患者患有这种疾病的“干性”形式。 光生物调节（PBM）是一种用于诱导有益细胞过程的低水平光疗法 导致显著的临床结果，包括组织修复、组织再生和抗- 炎症效应。在细胞水平上，PBM的机制归因于激活 线粒体呼吸链组分导致代谢功能的稳定。 LumiThera公司开发了Valeda®光传输系统， 用于眼部适应症的多波长PBM。对Valeda的多项研究表明， 改善干性AMD患者的生活质量、临床和解剖结局。背线 关键性LIGHTSITE III研究（148只眼; 24个月研究设计）的数据符合主要要求， 有效性终点证明PBM和假手术之间具有统计学显著性获益 治疗组，p = 0.003。此外，视觉检查结果较基线平均增加5.5个字母， PBM治疗组视力明显提高，P < 0.0001。 目前的SBIR第IIB阶段应用是为了扩展先前SBIR第I阶段的发现， II研究（SBIR 1 R43 EY 025508 -01和SBIR 1 R43 EY 025508 -03），以进行开放标签， 在退出主要LIGHTSITE III的患者中进行的前瞻性、多中心扩展研究 study.该扩展将继续评估PBM对疾病进展的长期影响， 在患有干性AMD的受试者（LIGHTSITE IIIB）中使用Valeda的安全性和功效。这项研究将 还能够比较和确定早期治疗与延迟治疗的PBM益处 允许延长PBM治疗3年或在假手术2年后开始PBM治疗 治疗具体目标将确定临床和解剖结局受益的程度 第一次以纵向的幅度。该补助金支持一种新型的非侵入性，非 药物，成本效益的治疗干性AMD。

ABSTRACT As the population continues to age, degenerative ocular diseases become increasingly common and create tremendous burden on the health care system. Age-related macular degeneration (AMD) is a progressive ocular disease that causes visual impairment and blindness in its most advanced form and is characterized by loss of function and cell death in the macula, a central and critical part of the retina. Approximately 11 million individuals are affected with AMD in the United States alone, with a global prevalence of 170 million. AMD is the leading cause of visual disability in the developed world and the third leading cause globally. AMD occurs in two forms: dry and wet AMD. Approximately 85-90% of AMD patients have the “dry” form of the disease. Photobiomodulation (PBM) is a low-level light therapy used to induce beneficial cellular processes resulting in significant clinical outcomes, including tissue repair, tissue regeneration and anti- inflammatory effects. At the cellular level, the mechanisms of PBM are ascribed to activation of mitochondrial respiratory chain components resulting in stabilization of metabolic function. LumiThera, Inc. has developed the Valeda® Light Delivery System which delivers multiwavelength PBM for ocular indications. Multiple studies with Valeda now demonstrated improvements in quality of life, clinical, and anatomical outcomes in dry AMD patients. Topline data from the pivotal LIGHTSITE III study (148 eyes; 24-month study design) has met the primary efficacy endpoint demonstrating a statistically significant benefit between PBM and Sham treatment groups, p = 0.003. In addition, a mean 5.5 letter change increase from baseline in visual acuity was seen in the PBM treatment group, P < 0.0001. The current SBIR phase IIB application is to extend the findings from previous SBIR phase I and II studies (SBIR 1R43EY025508-01 and SBIR 1R43EY025508-03) to conduct an open-label, prospective, multi-center extension study in patients that are exiting the main LIGHTSITE III study. The extension will continue to assess the long-term PBM impact on disease progression, safety, and efficacy in subjects with dry AMD (LIGHTSITE IIIB) using Valeda. The study will also be able to compare and establish PBM benefits of early treatment versus delayed treatment by allowing extended PBM treatment for 3 years or starting PBM treatment after 2 years of sham treatment. Specific Aims will establish the magnitude of clinical and anatomical outcome benefits in a longitudinal magnitude for the first time. The grant supports a novel non-invasive, non- pharmaceutical, cost-effective therapy for Dry AMD.