Topical Eyedrop Therapy for Keratoconus

圆锥角膜的局部滴眼液治疗

• 批准号: 9409550
• 负责人: Sarah Abdulla Molokhia
• 金额: $ 22.48万
• 依托单位: IVEENA DELIVERY SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2018-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9409550
• 关键词: Amino Acids; Animal Model; Anterior; Aqueous Humor; Asthenopia; Astigmatism; Bilateral; Biochemical; Blood specimen; Chemicals; Clinical Trials; Collagen; Cone; Contact Lenses; Copper; Copper Sulfate; Cornea; Data; Descemet' s membrane; Development; Disease; Disease Progression; Dose; Drug Kinetics; Economic Burden; Elements; Evaluation; Eye; Eyedrops; Eyeglasses; Formulation; Frequencies; Glare; High Pressure Liquid Chromatography; High Prevalence; Histologic; Human; Hydrophilic Contact Lenses; Intervention; Intraocular Lens Implantation; Ions; Keratoconus; Keratoplasty; Lasers; Link; Mechanics; Methods; Modeling; Monocular Diplopia; Morphology; Operative Surgical Procedures; Optical Coherence Tomography; Oral; Orphan Drugs; Oryctolagus cuniculus; Pathway interactions; Patients; Pharmacologic Substance; Pharmacological Treatment; Pharmacotherapy; Phase; Photophobia; Photorefractive Keratectomy; Placebo Control; Procedures; Progressive Myopia; Protein-Lysine 6-Oxidase; Research; Retina; Rupture; Safety; Shapes; Small Business Innovation Research Grant; Structure; Technology; Testing; Therapeutic; Thinness; Time; Tissues; Toxic effect; Toxicology; Vision; Visual; Visual Acuity; base; corneal scar; cost; cost effective; crosslink; design; dosage; effective therapy; evidence base; health economics; implantation; in vivo; life time cost; man; safety study; success; tomography

Project Summary Keratoconus (KCN) is a progressive disorder associated with structural changes in corneal collagen organization that leads to corneal thinning and ruptures in Bowman’s layer and/or Descemet’s membrane. As the disease progresses, it leads to irregular astigmatism, progressive myopia, and subsequently poor visual acuity. Treatment options are surprisingly limited with no oral or topical pharmaceutical therapy. Most mild KCN can be corrected with glasses or soft contact lenses but very often patients will need toric or hard contacts as the disease progresses. Ultimately, 1 in 5 patients will require surgery. Our technology is based on a co-factor for lysyl oxidase (LOX activity) and that low LOX activity in the cornea has been linked to the development of keratoconus both genetically and biochemically. We provide the evidence in preliminary results of a new topical eye drop effect on human keratoconus corneas in increasing both LOX activity and cornea stiffening. We also show the first morphological evidence of induced central corneal flattening in rabbits with optical coherence tomography (OCT). Based on the current evidence base, we outline new proactive pathways for keratoconus management and enabling a non-invasive and relatively cost effective treatment for keratoconus. We propose a research plan under three specific aims that will a) study the safety and tolerability of the eye drops in rabbits in vivo, b) study the effect of dosing frequency on rabbit corneal shape and biochemical crosslinking in vivo and c) to determine whether the eye drops induce biochemical crosslinking on human keratoconic corneas ex vivo.

项目概要 圆锥角膜 (KCN) 是一种与角膜胶原蛋白结构变化相关的进行性疾病 导致角膜变薄和鲍曼层和/或后弹力层破裂的组织。 疾病进展，导致不规则散光、进行性近视，进而导致视力下降 治疗选择非常有限，没有口服或局部药物治疗。 可以用眼镜或软性隐形眼镜矫正，但患者通常需要复曲面或硬性隐形眼镜，因为 最终，五分之一的患者将需要手术。 我们的技术基于赖氨酰氧化酶（LOX 活性）的辅助因子以及角膜中的低 LOX 活性 在遗传和生化方面都与圆锥角膜的发展有关。 新型外用滴眼液对人圆锥角膜增加液氧浓度的初步结果 我们还首次展示了诱导中央角膜的形态学证据。 基于当前的证据基础，我们概述了光学相干断层扫描（OCT）对兔子扁平化的影响。 圆锥角膜管理的新主动途径，并实现非侵入性且相对具有成本效益的治疗 圆锥角膜的治疗。 我们提出了一项基于三个具体目标的研究计划，即 a) 研究眼睛的安全性和耐受性 兔体内滴眼液，b) 研究给药频率对兔角膜形状和生化的影响 体内交联和c)确定眼药水是否对人体产生生化交联 离体圆锥角膜。