Topical Eyedrop Therapy for Keratoconus

项目摘要 圆锥角膜（KCN）是一种进行性角膜病变，与角膜胶原结构改变有关 组织，导致角膜变薄和Bowman层和/或Descemet膜破裂。作为 疾病进展，导致不规则散光，进行性近视，随后视力下降 敏锐度治疗选择令人惊讶地有限，没有口服或局部药物治疗。最温和的KCN 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， 疾病进展。最终，五分之一的患者需要手术。 我们的技术是基于赖氨酰氧化酶（LOX活性）的辅助因子， 与圆锥角膜的发生有遗传和生物化学上的联系。我们提供证据 在一种新的局部滴眼液对人圆锥角膜的作用的初步结果中， 活动和角膜硬化。我们还显示了诱导中央角膜的第一个形态学证据， 用光学相干断层扫描（OCT）在家兔中进行扁平化。根据现有的证据基础，我们概述了 圆锥角膜管理的新的主动途径，并实现非侵入性和相对成本效益 圆锥角膜的治疗 我们提出了一个研究计划，根据三个具体目标，将a）研究眼睛的安全性和耐受性 B）研究给药频率对兔角膜形状和生物化学的影响 c）确定滴眼剂是否在人体上诱导生物化学交联 离体圆锥角膜。

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.