Novel Treatment for Degenerative Myopia

描述(申请人提供)：近视在美国和欧洲影响30%的人口，在一些亚洲国家影响70%-90%的人口。屈光度大于8的高度近视影响了0.2-0.4%的美国人口和高达1%的亚洲国家人口。与退行性近视相关的主要变化是巩膜组织的进行性拉伸和变薄，导致后部葡萄肿的形成。随着巩膜组织的伸展和变薄，视网膜和脉络膜组织也会随之伸展，从而导致视力丧失。事实上，退行性近视是中国、台湾和日本无法治愈的失明的主要原因，在美国排名第七。虽然黄斑萎缩和脉络膜新生血管导致的视力损失在退行性近视中最为常见，但患有这种疾病的患者也更容易发生视网膜脱离和黄斑裂孔形成。虽然全世界有大量人口受到这种疾病的影响，但目前还没有有效的方法来阻止病情发展和降低视力丧失的比率。通过Visdex、加州理工大学和加州大学旧金山分校的合作开发的一种专利治疗方法成功地稳定了巩膜形状，并防止了体外眼球扩大。治疗包括将候选配方药物局部涂抹在巩膜表面，使药物分子扩散到组织中，然后用可见光照射巩膜。这一过程大约需要10分钟，候选药物已被FDA批准用于患者。初步的兔体内实验表明，候选药物和辐射对眼睛的耐受性很好。 这个第二阶段STTR项目的目标是证明这种治疗方法可以转化为一种具有临床意义的方案，在近视动物模型中显示疗效。基于第一阶段观察到的体外疗效和体内生物相容性，这一创新疗法将在体外进行优化，以在完整的扩眼试验(AIM 1)中稳定巩膜形状，适应候选药物的给药和体内照射的手术程序，并在兔模型(AIM 2)中评估毒性和有效性，并在豚鼠退行性近视模型(AIM 3)中测试预防近视的能力。这项第二阶段的研究和开发工作将达到顶峰，通过稳定巩膜来阻止退行性近视的进展。随后的第三阶段开发将是导致人体临床试验和FDA批准的继续。与公众健康相关：退行性近视是一种渐进性恶化的情况，巩膜变薄和拉伸，导致眼球延长和视网膜和脉络膜组织受损。尽管退行性近视在美国影响着近100万人，全球约有2000万人，但目前还没有有效的治疗方法。该项目将产生一种创新的、光激活的治疗方法，它将阻止巩膜的拉伸，并防止导致失明的相关视网膜并发症。

DESCRIPTION (provided by applicant): Myopia affects 30% of the population in the U.S. and Europe, and 70-90% of the population in some Asian countries. High myopia of greater than 8 diopters affects 0.2 0.4% of the US population and up to 1% of the population in Asian countries. The principal change associated with degenerative myopia is progressive stretching and thinning of scleral tissues leading to posterior staphyloma formation. As scleral tissues stretch and thin, there is associated stretching of retinal and choroidal tissues that promote visual loss. Indeed, degenerative myopia is the leading cause of untreatable blindness in China, Taiwan, and Japan, and is ranked 7th in the United States. While visual loss from macular atrophy and choroidal neovascularization are most common in degenerative myopia, patients with this disease are also more prone to retinal detachment and macular hole formation. Although a large population is affected by this disease worldwide, there is currently no effective method to arrest progression and reduce the rate of visual loss. A proprietary treatment developed through collaboration of Visdex, Caltech and UCSF successfully stabilizes scleral shape and prevents globe enlargement in vitro. The treatment consists of topical application of the formulated drug candidates to the surface of the sclera, allowing the drug molecules to diffuse into the tissue and then irradiating the sclera with visible light. The procedure requires approximately 10 minutes and the drug candidates have been approved by the FDA for use in patients. Initial in-vivo experiments in rabbits show that the drug candidates and irradiation are well tolerated by the eye. The objective for this Phase II STTR project is to demonstrate that such a treatment can be translated into a clinically meaningful protocol that shows efficacy in an animal model of myopia. Based on in-vitro efficacy and in-vivo biocompatibility observed in Phase I, this innovative treatment will be optimized in vitro for stabilizing scleral shape in an intact eye expansion test (Aim 1), adapted to surgical procedures for administration of the drug candidates and irradiation in vivo and evaluated for toxicity and efficacy in a rabbit model (Aim 2), and tested for the ability to prevent myopia in vivo in a guinea pig model of degenerative myopia (Aim 3). This Phase II research and development effort will culminate in a treatment that halts progression of degenerative myopia by stabilizing the sclera. The subsequent Phase III development will be a continuation leading to human clinical trials and FDA approval. PUBLIC HEALTH RELEVANCE: Degenerative myopia is a progressively worsening condition in which the sclera thins and stretches, leading to globe elongation and damage of retinal and choroidal tissues. Although degenerative myopia affects nearly 1 million people in the United States, and approximately 20 million people worldwide, there is currently no effective treatment method. This project will result in an innovative, light-activated treatment that will arrest stretching of the sclera and prevent the associated retinal complications that lead to blindness.