A pilot clinical study to evaluate the use of photobiomodulation in patients with dry age-related macular degeneration

 描述（由申请人提供）：随着人口持续老龄化，退行性眼病变得越来越常见，并对医疗保健系统造成巨大负担。患有AMD的老年人的视力损害平均夺走5年的生活质量。视网膜相关性黄斑变性（AMD）代表了一个巨大的市场，仅在美国就有约200万患者和另外约800万人处于风险中。大约90%的AMD患者患有“干性”疾病。目前还没有针对干性AMD的批准治疗，因此它代表了医学中潜在的高影响力目标领域。 由来自多伦多和橡树岭光生物调节研究（TORPA）的Merry和Dotson博士领导的一项调查研究着眼于低水平光疗法（LLLT）治疗干性AMD的效果。干性AMD的TORPA数据显示，在治疗6周后立即在视觉敏锐度和对比敏感度方面有临床和统计学显著改善，证明LLLT在干性AMD中的潜在用途。TORPA研究结合了多个预先选择的波长来刺激线粒体CCO功能并抑制VEGF表达。研究结论是LED治疗是一种无创、易于管理和安全的治疗，未发现严重不良事件。更重要的是，该研究提供了唯一的1年随访数据的LED有效性在干性AMD。这些发现首次证明了干性AMD患者在长达1年的时间内具有统计学显著的临床获益（F（4，68）= 18.86，p < 0.0001） LLLT患者 LumiThera由在光生物调节方面具有广泛临床和开发专业知识的创始人组成，以领导商业化工作。多波长LED临床和原型商业仪器正在设计和建造的眼科医生办公室为基础的设置。 目前的SBIR提案是使用LumiThera眼科设计的LED仪器LT-300进行一项前瞻性、双盲临床试验。具体目标1将确定多个LED波长对20名干性AMD患者（分为两组）的临床和OCT成像益处的大小。第1组约10例受试者接受治疗，第2组约10例受试者接受假治疗，为期3周（每周3次，共3次）。LED治疗将由Merry医生进行，对结局指标设盲。Devenyi博士和Markowitz博士（多伦多大学）将作为共同研究者，提供患者招募、审查所有临床数据和AE以及成像扫描。所有受试者将在入组前接受视网膜专家评估、眼相干断层扫描（OCT）和静脉荧光血管造影（IVFA），以确保非新生血管性AMD。所有受试者均使用ETDRS logMAR视力（4米）、对比敏感度（1.5）和3个周期/度进行评估。临床和OCT测量将在治疗前、治疗方案后立即（3周）、3、6、12个月后进行。 这些发现将为一项针对干性AMD的新型非侵入性非药物疗法的关键试验提供基本的安全性和科学基础。

 DESCRIPTION (provided by applicant): As the population continues to age, degenerative ocular diseases become increasingly common and create tremendous burden on the health care system. Vision impairment in the elderly with AMD takes away an average of 5 quality years of life. Age-related macular degeneration (AMD) represents a large market with ~2 million patients and another ~8 million people at risk in the U.S. alone. Approximately, 90% of the AMD patients have the "dry" form of the disease. There are no approved treatments for dry AMD and, thus it represents a potential high impact, targeted area in medicine. A investigator study lead by Drs. Merry and Dotson from The Toronto and Oak Ridge Study of Photobiomodulation (TORPA) looked at the effect of low level light therapy (LLLT) in the treatment of dry AMD. The TORPA data for dry AMD shows clinically and statistically significant improvement in visual acuity and contrast sensitivity, immediately after treatment for 6 weeks, demonstrating the potential use of LLLT in dry-AMD. The TORPA study combined multiple pre-selected wavelengths to stimulate mitochondrial CCO function and suppress VEGF expression. The study conclusions were that LED treatment was a non- invasive, easily administered and safe treatment with no serious adverse events noted. More importantly, the study provides the only 1 year follow-up data of LED effectiveness in dry AMD. These findings are the first to demonstrate a statistically significant clinical benefit (F(4,68) = 18.86, p < 0.0001) at up to 1 yr in dry AMD patients with LLLT. LumiThera was formed from founders with extensive clinical and developmental expertise in photobiomodulation to lead in the commercialization efforts. Multiple wavelength LED clinical and prototype commercial instruments are being designed and built for an ophthalmologist office-based setting. The current SBIR proposal is to conduct a pilot prospective, double-masked clinical trial with LumiThera's ophthalmological designed LED instrument, LT-300. Specific Aim 1 will establish the magnitude of clinical and OCT imaging benefit of multiple LED wavelengths on 20 dry AMD patients, divided into two groups. Approximately 10 subjects will be treated in group 1, and approximately 10 subjects will be given a sham treatment in group 2 over a three-week period (3 times per week for 3). LED Treatments will be administered by Dr. Merry, masked to the outcome measures. Drs Devenyi and Markowitz (University of Toronto) will act as co-investigators and provide patient recruitment, review all clinical data and AEs and imaging scans. All subjects will undergo Retinal Specialist assessment, Ocular Coherence Tomography (OCT) and Intra-venous Fluoroscein Angiography (IVFA) prior to enrollment to ensure non-neovascular AMD. All subjects are assessed with ETDRS logMAR Visual Acuity at 4 meters, contrast sensitivity at 1.5 and 3 cycles per degree. Clinical and OCT Measurements will take place prior to treatment, immediately following the treatment protocol (3 weeks), 3, 6, 12 months after. The findings will provide the basic safety and scientific foundation for a pivotal trial with a novel non- invasive, non-pharmaceutical therapy for dry-AMD.