Oral metformin for non-neovascular age-related macular degeneration

项目总结/摘要 视网膜相关性黄斑变性（AMD）是老年人严重视力丧失和法律的失明的主要原因。 美国50岁以上的人。在其晚期，患者从脉络膜或视网膜失去视力。 新血管形成或地图状萎缩。虽然在过去十年中取得了很大进展， 对于新生血管性AMD的治疗，目前还不存在减缓或逆转干性或非新生血管性AMD的疗法。 形式，其中玻璃疣（由脂质和蛋白质组成的沉积物）积聚在中央的关键细胞下方。 黄斑的一部分，导致进一步的功能障碍，可能容易导致晚期黄斑变性的并发症。 疾病，视力下降和中央暗点。干性AMD通常进展无情， 玻璃疣的体积每年都在增加，并发症和视力下降的风险也在增加。 二甲双胍是一种通用的口服药物，用于其降血糖作用，但也被发现具有 许多其他细胞作用，包括减少氧化应激和活性氧物质的产生， 炎症和线粒体应激--所有这些过程都是AMD发病机制的核心。值得注意的是，药物 已被发现具有多种抗衰老作用，最近已被广泛测试用于抗衰老 非糖尿病患者的终点。目前的研究旨在确定二甲双胍是否可以减少 AMD中玻璃疣积累的进展。入组研究的非糖尿病患者将随机分配至 安慰剂或每日口服二甲双胍。在24个月的过程中，两组将进行比较， 几个措施。在目标1中，将使用多模式成像（包括光学相干）评估AMD 断层摄影术、眼底自发荧光和眼底照相术。玻璃疣体积的立方根， 基线与18个月和24个月的比较将是评估口服 二甲双胍;还将比较新发脉络膜新生血管和地图状萎缩的发生率。在 目的2、糖尿病视网膜病变最佳矫正早期治疗视力及其他视力的研究 将比较两组之间的心理物理测试。这将确定对视觉表现的影响 与玻璃疣的解剖学变化无关。在目标3中，主观视觉功能，因为它与生活质量有关， 将使用国家眼科研究所视觉功能问卷和低亮度 问卷这一措施在AMD患者中尤其相关，因为该疾病显著影响 患者的生活质量下降。目前的规划拨款将使临床试验的准备工作， 可以评估这种廉价的药物治疗AMD。因此，目前的高回报研究 有可能成为一种具有成本效益的治疗方法，可以在世界范围内迅速采用， 迷失和盲目

Project Summary/Abstract Age-related macular degeneration (AMD) is the leading cause of severe vision loss and legal blindness in persons over age 50 in the United States. In its advanced stages, patients lose vision from either choroidal neovascularization or geographic atrophy. Although great progress has been made during the past decade in the treatment of neovascular AMD, currently no therapy exists to slow or reverse the dry or non-neovascular form, in which drusen (deposits consisting of lipid and protein) accumulate beneath key cells in the central portion of the macula, leading to further dysfunction that can predispose to the complications of advanced disease, with reduced visual acuity and central scotomata. Dry AMD generally progresses inexorably such that drusen volume increases each year, with increasing risk of these complications and worse vision. Metformin is a generic oral medication used for its hypoglycemic effects but which also has been found to have numerous other cellular actions, including reducing oxidative stress and reactive oxygen species production, inflammation, and mitochondrial stress -- all processes central to the pathogenesis of AMD. Notably, the drug has been found to have myriad anti-senescence effects and has recently been tested extensively for anti-aging endpoints in non-diabetic patients. The current study proposes to determine whether metformin can reduce the progression of drusen accumulation in AMD. Non-diabetic patients enrolled in the study will be randomized to either placebo or daily oral metformin. Over the course of 24 months, the two groups will be compared by several measures. In Aim 1, AMD will be assessed with multimodal imaging, including optical coherence tomography, fundus autofluorescence, and fundus photography. The cube root of the drusen volume at baseline versus 18 and 24 months will be the primary outcome measure for assessing the effect of oral metformin; incidence of new choroidal neovascularization and geographic atrophy will also be compared. In Aim 2, best-corrected Early Treatment of Diabetic Retinopathy Study visual acuity and other visual psychophysical tests will be compared between the two groups. This will identify effects on visual performance independent of anatomic changes in drusen. In Aim 3, subjective visual function, as it relates to quality of life, will be assessed using the National Eye Institute Visual Function Questionnaire and the Low Luminance Questionnaire. This measure is particularly relevant in patients with AMD, as the disease dramatically impacts patients' quality of life for the worse. The current planning grant will enable preparations for a clinical trial that can evaluate this inexpensive medication for the treatment of AMD. Therefore, the present high-reward study has the potential to enable a cost-effective treatment that could be rapidly adopted worldwide to prevent vision loss and blindness.