角膜区域性形态及其生物力学性能变化在角膜胶原交联术后的规律研究

Keratoconus (KC) is one of the diseases that can cause blindness. The occurrence and development of keratoconus is closely related to regional weakening of corneal biomechanical properties, which causes local protrusion. Serious KC may require keratoplasty. Corneal collagen cross-linking (CXL) is an effective, minimally invasive technique to treat keratoconus, and the mechanism of which is based on increasing corneal stiffness. Many styles of such technique were invented, while topography-guided crosslinking treatment centred on the ectatic cone was proven to be more effective in improving the corneal shape in KC. As keratoconus is associated with regional reduction in corneal stiffness, the stiffness increase caused by the cross-linking treatment is expected to halt the progression of topography changes. However, the lack of in-vivo measurement of corneal biomechanical parameters (tangent modulus) has made it impossible to evaluate the amount of stiffness decrease in the ectatic area, and no way to enhance the corneal biomechanical properties regionally with different CXL irradiances accordingly, therefore can not get a perfect result. Our team have accumulated strong foundation on several aspects, such as measuring ev-vivo tangent modulus, analyzing corneal shape accurately, treating KC with CXL and so forth, based on which a method is developed to assess corneal shape and in-vivo tangent modulus regionally. Different types of CXL will be operated, and the influence of CXL on regional corneal shape and biomechanical properties will be analyzed. The efficiency of CXL on KC treatment in different regions will be evaluated, which can provide the evidence for personalized regional CXL treatment. This work will lead to a new method to evaluate the effectivess of CXL, combining in vivo regional corneal tangent modulus and corneal shape analysis. Regional information about corneal biomechanical properties and corneal shape could then be used to guide CXL treatments.

圆锥角膜(KC)是较常见的致盲性眼病，其发生发展与区域性角膜生物力学性能减弱相关，导致角膜局部扩张性突起，严重的需角膜移植；角膜胶原交联术(CXL)可加强角膜力学性能，被广泛用于防治KC，且术式逐渐变得多样。利用角膜地形图引导的区域差异性CXL，重点加固病灶部位，疗效更为显著；但由于当前没有可在体测量区域性角膜生物力学性能参量(正切模量)的技术，无法精准地在病变区域测算其力学性能减弱程度，不能据此分区域进行辐照能量差异化CXL弥补角膜力学性能不足而实现精准治疗。本研究组已在离体角膜正切模量测量、角膜形态分析和CXL治疗KC方面打下了良好前期基础，提出CXL应考虑区域性角膜力学性能变化。藉此开发角膜区域性形态及其在体正切模量检测手段，进行不同术式CXL方案，分析CXL对角膜局部形态和生物力学性能的影响规律。评估多种CXL治疗KC在不同区域的有效性，为后续发展个性化区域差异性CXL提供依据。

圆锥角膜(KC)是较常见的致盲性眼病，其发生发展与区域性角膜生物力学性能减弱相关，导致角膜局部扩张性突起，严重的需角膜移植；角膜胶原交联术(CXL)可加强角膜力学性能，被广泛用于防治KC，且术式逐渐变得多样。利用角膜地形图引导的区域差异性CXL，重点加固病灶部位，疗效更为显著；但由于当前没有可在体测量区域性角膜生物力学性能参量(正切模量)的技术，无法精准地在病变区域测算其力学性能减弱程度，不能据此分区域进行辐照能量差异化CXL弥补角膜力学性能不足而实现精准治疗。本研究组已在离体角膜正切模量测量、角膜形态分析和CXL治疗KC方面打下了良好前期基础，提出CXL应考虑区域性角膜力学性能变化。本项目通过流固耦合模拟，针对角膜形态不规则性和眼周阻尼情况进行了探索，创建了区域性在体角膜生物力学性能逆向分析的方法。同时，申请人利用多种CXL治疗方案手术前后的角膜形态和生物力学等临床数据，证明了经典和多种加速CXL方案的安全性和有效性。本研究为后续研发更精准的在体生物力学性能评估方法提供了基础，为KC使用CXL治疗和后续调整CXL的能量/时间组合提供了理论依据。