Advanced transepithelial corneal collagen crosslinking

先进的跨上皮角膜胶原交联

基本信息

批准号：
10741684
负责人：
David Huang
金额：
$ 41.23万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10741684
关键词：
Acceleration Adoption Air Anterior Apical Area Blindness Cadaver Cicatrix Clinical Research Clinical Trials Collagen Collagen Fiber Cone Consumption Contact Lenses Cornea Corneal Diseases Corneal Stroma Data Devices Diffusion Drug Formulations Effectiveness Elements Epithelial Cells Epithelium Excision Eye Eye Banks Eye diseases Eyeglasses Fiber Optics Generations Goals Human Inferior Keratoconus Keratoplasty Kinetics Measures Mechanics Methods Modeling Modulus Optical Coherence Tomography Oryctolagus cuniculus Outcome Oxygen Oxygen saturation measurement Patients Penetration Performance Phase Physiologic pulse Procedures Protocols documentation Quality of life Reaction Reactive Oxygen Species Recovery Regimen Research Riboflavin Risk Risk Reduction Safety Severities Speed Surface System Technology Testing Thinness Ultraviolet Rays Vision Visual absorption chemical reaction corneal epithelium covalent bond crosslink elastography experimental study healing improved infection risk irradiation models and simulation novel ocular surface optical fiber predictive modeling preservation prevent sight restoration ultraviolet ultraviolet irradiation

项目摘要

PROJECT SUMMARY Keratoconus is an eye disease where the cornea is mechanically weakened, leading to progressive thinning, distortion, and degradation of vision. In severe cases, corneal transplantation may be required to restore vision. Corneal collagen crosslinking (CXL) is a procedure that uses riboflavin, oxygen and ultraviolet (UV) light to produce a chemical reaction that strengthens collagen fibers in the cornea stroma. CXL has been shown to halt keratoconus progression over the long term. A problem with the standard CXL procedure is that the surface epithelial cells must be removed first so that riboflavin, oxygen, and UV can easily enter the corneal stroma. It is common for epithelial healing to be delayed after CXL. This increases the chance that the cornea may become hazy. It also increases the risk of infections that can lead to scarring and loss of vision. To avoid these problems, some doctors perform CXL without removing the epithelium. This is called “transepithelial CXL” in contrast to the standard “epi-off CXL” procedure. Unfortunately, as currently practiced, transepithelial CXL is far less effective in strengthening the cornea. We have developed an advanced transepithelial CXL technology (Casey CXL) that overcomes the epithelial barrier to riboflavin, oxygen, and UV delivery. A computational finite- element model (FEM) of diffusion and reaction kinetics showed that Casey CXL can significantly exceed the performance of standard epi-off CXL. We propose to validate the advantages of Casey CXL in ex vivo experiments using both rabbit and human eye bank corneas: 1. Construct an oxygen-UV delivery system to enrich oxygen to >90% in the ambient air over the corneal surface during UV irradiation. 2. Measure oxygen concentration in the corneal stroma during CXL. We will use a fiber-optics oximetry probe to measure oxygen in the anterior and mid-stroma during UV irradiation. We will test the hypothesis that by using oxygen enrichment and pulsed UV, Casey CXL allows greater oxygen penetration to the mid-stroma than standard epi-off CXL. The FEM predicts a more than 2-fold advantage for Casey CXL, which would greatly improve the depth of corneal strengthening. 3. Use optical coherence tomographic elastography, a nondestructive testing technology, to measure cornea stiffness before and after experimental CXL. This would test the hypothesis that Casey CXL can stiffen the cornea more than standard epi-off CXL, as predicted by the FEM. These experiments would validate the Casey CXL protocol, including the drug formulation, procedure steps, and oxygen-UV delivery device, to prepare for clinical trials in human patients.

项目概要圆锥角膜是一种眼部疾病，角膜机械性变弱，导致严重时，角膜会逐渐变薄、变形和退化。恢复视力可能需要移植角膜胶原交联（CXL）。使用核黄素、氧气和紫外线 (UV) 产生化学反应的过程增强角膜基质中的胶原纤维已被证明可以阻止圆锥角膜。长期进步。标准 CXL 程序的一个问题是表面上皮细胞必须首先去除核黄素、氧气和紫外线可以很容易地进入角膜基质，这是常见的。 CXL 后上皮愈合延迟，这增加了角膜可能的机会。它还会增加感染的风险，从而导致疤痕和视力丧失。为了避免这些问题，一些医生在不去除上皮的情况下进行CXL，这称为。不幸的是，“跨上皮 CXL”与标准“表皮脱落 CXL”手术不同。目前所采用的跨上皮 CXL 在强化角膜方面的效果要差得多。我们开发了先进的跨上皮 CXL 技术 (Casey CXL) 克服了核黄素、氧气和紫外线输送的上皮屏障。扩散和反应动力学的元素模型（FEM）表明 Casey CXL 可以显着超过标准 Epi-Off CXL 的性能我们建议验证其优点。 Casey CXL 使用兔和人眼库角膜进行离体实验： 1. 构建氧气-紫外线输送系统，将环境空气中的氧气富集至 90% 以上紫外线照射期间角膜表面。 2. 在 CXL 过程中测量角膜基质中的氧气浓度我们将使用光纤。我们将使用血氧测定探头在紫外线照射期间测量前基质和中基质中的氧气。检验以下假设：通过使用富氧和脉冲紫外线，Casey CXL 可以实现更大的中基质的氧气渗透率高于标准外延 CXL，FEM 预测超过。 Casey CXL的优势是2倍，将大大提高角膜强化的深度。 3.利用光学相干断层弹性成像无损检测技术测量实验 CXL 之前和之后的角膜硬度，这将检验以下假设：正如 FEM 预测的那样，Casey CXL 可以比标准 Epi-off CXL 更加强角膜。这些实验将验证 Casey CXL 方案，包括药物配方、程序步骤和氧气-紫外线输送装置，为人类患者的临床试验做准备。