Novel Treatment for Degenerative Myopia

描述（由申请人提供）：近视影响着美国和欧洲30%的人口，在一些亚洲国家有70-90%的人口。美国0.2% 0.4%的人口和亚洲国家高达1%的人口患有高度近视，屈光度大于8度。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，导致后葡萄肿的形成。随着巩膜组织的拉伸和变薄，视网膜和脉络膜组织也随之拉伸，从而促进视力丧失。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出现视网膜脱离和黄斑孔形成。虽然世界范围内有大量的人群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的速度。Visdex、加州理工学院和加州大学旧金山分校合作开发的一种专有治疗方法成功地稳定了巩膜形状，防止了体外巩膜肿大。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。整个过程大约需要10分钟，候选药物已被FDA批准用于患者。在兔体内进行的初步实验表明，候选药物和照射对眼睛具有良好的耐受性。

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.