Novel Treatment for Degenerative Myopia

描述（由申请人提供）： 近视影响美国和欧洲30%的人口，以及一些亚洲国家70-90%的人口。高度近视大于8屈光度影响0.2 美国人口的0.4%，亚洲国家人口的1%。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，导致后葡萄肿形成。随着巩膜组织拉伸和变薄，视网膜和脉络膜组织的相关拉伸促进视力丧失。事实上，退行性近视是中国大陆、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丧失在退行性近视中最常见，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。虽然世界范围内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进展并降低视力丧失率。 通过Visdex、加州理工学院和加州大学旧金山分校的合作开发的一种专有治疗方法成功地稳定了巩膜形状，并在体外防止了地球仪的扩大。治疗包括将配制的候选药物局部应用于巩膜表面，使药物分子扩散到组织中，然后用可见光照射巩膜。该过程需要大约10分钟，候选药物已被FDA批准用于患者。在兔中的初步体内实验表明，候选药物和照射对眼睛具有良好的耐受性。 这个II期STTR项目的目的是证明这种治疗可以转化为一种有临床意义的方案，在近视动物模型中显示出疗效。基于在I期中观察到的体外功效和体内生物相容性，该创新治疗将在体外优化以在完整的眼睛扩张试验中稳定巩膜形状（目标1），适应于用于施用候选药物和体内照射的外科手术，并在兔模型中评估毒性和功效（目标2），并在变性近视的豚鼠模型中测试其体内预防近视的能力（目的3）。 这项二期研究和开发工作将最终通过稳定巩膜来阻止退行性近视的进展。随后的III期开发将继续进行人体临床试验和FDA批准。公共卫生相关性：退行性近视是一种逐渐恶化的病症，其中巩膜变薄并拉伸，导致地球仪伸长以及视网膜和脉络膜组织的损伤。虽然退行性近视影响美国近100万人，全球约2000万人，但目前没有有效的治疗方法。该项目将产生一种创新的光激活治疗方法，可以阻止巩膜的拉伸，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.