SMILE联合快速角膜胶原交联的生物力学效应及愈合机制研究

Femtosecond laser small incision lenticule extraction (SMILE) has become the mainstream of corneal refractive surgery. Corneal dilatation is one of the complications of refractive surgery which serious threat visual acuity, mainly with the corneal thinning and weaken of biomechanical stability. The use of collagen cross-linking to improve the mechanical stability of the cornea, can be used for combined with SMILE surgery to improve postoperative corneal mechanical stability. The biomechanical effect and wound healing of SMILE combined with collagen cross - linking are to be discussed. In this study,rabbit eyes underwent SMILE were kept safe, critical, too thin thickness of the residual matrix bed, respectively, different energy parameters of the UV - riboflavin corneal collagen cross - linking. The main contents were as follows: (1) Corvis ST, ORA, uniaxial stretch test, intermolecular adhesion test to measure corneal biomechanical parameters; ② Confocal microscopy observation of stromal cells, nerve repair, transmission electron microscopy observation of corneal ultrastructural changes, TUNEL detection of apoptosis, PCR, Western blot, immunohistochemical detection of corneal healing related genes, protein. And finally clear the key parameters and the effect of the dose-effect law of femtosecond combine cross-linked surgery for the treatment of thin cornea and high myopia patients and provide a theoretical basis.

飞秒激光小切口透镜取出术(SMILE)已成为角膜屈光手术的主流术式。角膜扩张是屈光手术严重威胁视力的并发症，主要与角膜变薄后生物力学稳定性减弱有关。课题组前期利用胶原交联术增加了角膜力学强度，可用于联合SMILE预防术后角膜扩张。目前SMILE联合胶原交联术的生物力学效应及创伤愈合机制仍有待阐述。为此，本研究将对兔眼行SMILE术，分别保留安全、临界、过薄厚度的残余基质床，进行不同能量参数的快速角膜胶原交联。主要研究内容包括：① Corvis ST、ORA、角膜单轴拉伸实验、层间粘合力试验检测角膜生物力学效应；② 活体共聚焦显微镜观察基质细胞、神经修复规律，透射电镜观察角膜超微结构变化，TUNEL检测细胞凋亡，PCR、Western blot、免疫组化检测角膜愈合相关基因、蛋白表达。最终明确手术关键参数及其效应的量-效规律，为薄角膜及高度近视患者行SMILE联合胶原交联手术提供理论依据。

本项目围绕飞秒激光小切口透镜取出术(SMILE)联合角膜交联术的生物力学效应及创伤愈合机制展开研究，先在动物模型眼上成功构建手术模型，探讨该技术对角膜结构生物力学、光学效应以及创伤愈合反应的影响，并转化初步应用于临床。主要研究内容和重要结果： 1）在动物模型眼中探索角膜扩张模型的建立及交联参数设置的剂量-效应关系，探索离体角膜生物力学测量方法。2）在相对薄角膜患者中行飞秒LASIK联合快速交联术，术后随访发现远期安全、有效、稳定。3）对跨上皮快速交联治疗进展期圆锥角膜的患者进行效果，发现术后远期圆锥稳定。4）在青少年进展期圆锥角膜行跨上皮快速交联，发现术后远期安全稳定。5）通过荟萃分析，对传统去上皮交联与跨上皮交联进行比较，发现两种手术方式治疗效果相似，而去上皮交联术后角膜曲率和中央角膜厚度的下降幅度比跨上皮交联更大。关键数据及其科学意义：本项目通过初步建立角膜扩张模型及交联参数设置，并在临床中对激光联合交联的患者进行先导研究，跨上皮快速交联的患者进行远期临床观察，为后续联合手术的临床开展提供依据。项目团队共发表SCI论文5篇（基金标注），参加国内相关领域会议并作发言报告10余人次，参加国际会议做大会发言及壁报交流4人次，培养研究生3人。其中项目负责人第一作者发表SCI论文3篇，主编眼科学术专著1本，获得“2018年复旦大学上海医学院优秀住院医师”。.