Non-linear Optical Collagen Cross-linking (NLO CXL) for Treatment of Keratoconus.

用于治疗圆锥角膜的非线性光学胶原交联 (NLO CXL)。

• 批准号: 8752184
• 负责人: James V Jester
• 金额: $ 37.44万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8752184
• 关键词: Acoustics; Affect; Anterior; Area; Bullous Keratopathy; Caliber; Cataract; Cells; Collagen; Complication; Cone; Cornea; Corneal Diseases; Corneal Endothelium; Corneal Stroma; Corneal Ulcer; Crystallins; Devices; Elasticity; Endothelium; Exposure to; Eye; Fluorescence; Free Radicals; Frequencies; Generations; Hydrogels; Infection; Keratoconus; Laser In Situ Keratomileusis; Laser Scanning Confocal Microscopy; Lasers; Lateral; Lead; Life; Light; Long-Term Effects; Maps; Measures; Mechanics; Microbubbles; Microscopic; Microscopy; Modification; Monitor; Optics; Organism; Oryctolagus cuniculus; Pathological Dilatation; Patients; Photons; Photosensitizing Agents; Positioning Attribute; Process; Radiation; Retina; Riboflavin; Safety; Scanning; Speed; Surface; System; Testing; Therapeutic; Thick; Time; Ultrasonography; Ultraviolet A radiation; Ultraviolet B Radiation; Visible Radiation; cell injury; computerized; crosslink; immunocytochemistry; improved; in vivo; lens; microbial; novel; novel strategies; photoactivation; public health relevance; repaired; two-photon; ultraviolet

Project Summary/Abstract The major objective of this proposal is to test the hypothesis that photoactivation of riboflavin by non- linear optical (NLO), two photon processes (TP) using femtosecond laser (FS) light induces spatially resolved (X-Y-Z) collagen cross-linking (CXL) and mechanical stiffening of intact, live rabbit eyes. Recent studies have established that photoactivation of riboflavin by 370 nm light (UVA) leads to the generation of free radical-induced collagen CXL and corneal stiffening that shows significant therapeutic benefits for patients suffering from Keratoconus. While UVA and riboflavin are themselves non-toxic, the generation of free radicals within the UVA collimated light path can lead to cellular damage affecting the corneal endothelium and crystallin lens, resulting in bullous keratopathy and potentially cataract. To avoid this complication, therapeutic administration of UVA CXL has been titrated to limit free radical generation to the anterior cornea, thus reducing the efficacy of CXL and limiting the therapeutic range to patients with affected corneas thicker than 400 ¿m. We propose that replacement of collimated UVA light with near-infrared FS laser light to induce NLO CXL within a spatially resolved focal volume determined by the focusing lenses would greatly improve the safety and efficacy of CXL. Major benefits of NLO CXL compared to conventional UVA CXL would included: 1) expanded application of corneal CXL to the treatment of thinner ectatic corneas (<400 ¿m) including post LASIK ectasia patients and other corneal disorders currently proposed for conventional UVA CXL including, bullous keratopathy, corneal ulceration and microbial infection; 2) additional treatment areas beyond that of the anterior stroma, including middle, posterior and full thickness corneal stroma; and 3) expanded use of alternative photosensitizers activated by low ultraviolet (UVB and UVC) and visible light (400 to 780 nm) that would be phototoxic to the retina using a single photon approach. To test this hypothesis we propose the following Specific Aims: 1) Adapt the current FS delivery system for live rabbit corneal NLO CXL, 2) Determine the effect of varying TP focal volume, FS laser power and scanning speed on NLO CXL corneal stiffening, 3) Determine the short-term affect (1 and 3 days) of NLO CXL on corneal CAF, 3D corneal elastic modulus, and cell damage compared to UVA CXL, 4) Determine the long-term affects (1 and 6 months) of NLO CXL on corneal CAF, 3D corneal elastic modulus, and cell repair compared to UVA CXL.

项目摘要/摘要 该提案的主要目的是检验以下假设：非 - 核黄素光活化 线性光学（NLO），使用飞秒激光（FS）光在空间上诱导的两个光子过程（TP） 已解决（X-Y-Z）胶原蛋白交联（CXL）和完整的活兔眼的机械僵硬。 最近的研究表明，370 nm光（UVA）将核黄素的光活化导致 产生自由基诱导的胶原蛋白CXL和角膜僵硬，显示出明显的治疗性 对患有圆锥角膜的患者的好处。而UVA和核黄素本身是无毒的，但 UVA准直路中的自由基产生会导致细胞损伤影响 角膜内皮和结晶透镜，导致角膜病和潜在白内障。为了避免这种情况 并发症，UVA CXL的理论给药已被滴定以将自由基产生限制为 前角膜，从而降低了CXL的效率并将治疗范围限制为受影响的患者 角膜厚度大于400€m。我们建议用近红外FS替换构造的UVA光 激光光在空间分辨的焦点体积中诱导NLO CXL 镜头将大大提高CXL的安全性和效率。 NLO CXL的主要好处 常规的UVA CXL将包括：1）角膜CXL的扩展应用于稀薄的治疗 当前包括Lasik ectasia患者和其他角膜疾病，包括肝角膜（<400€） 提议用于常规的UVA CXL，包括大胆的角膜病，角膜溃疡和微生物感染； 2）除前基质外的其他治疗区域，包括中间，后和全厚度 角膜基质； 3）扩大使用低紫外线（UVB和 UVC）和可见光（400至780 nm），使用单个光子方法对视网膜具有光毒性。 为了检验该假设，我们提出以下特定目的：1）适应当前的FS传递系统 兔角膜NLO CXL，2）确定不同TP焦距，FS激光功率和扫描的影响 NLO CXL角膜僵硬的速度，3）确定NLO CXL的短期影响（1和3天） 与UVA CXL相比，角膜CAF，3D角膜弹性模量和细胞损伤，4）确定长期 与角膜CAF，3D角膜弹性模量和细胞修复相比，NLO CXL的影响（1和6个月） UVA CXL。