区域性在体测量：一种角膜生物力学性能评估的新方法及其在研究圆锥角膜发生发展机制中的作用

Keratoconus (KC) is a degenerative corneal ectasia disease that largely influences visual quality due to an associated regional corneal conical protrusion. KC usually develops during puberty and is one of the main conditions requiring keratoplasty. Currently, diagnosis of KC mainly depends on changes in corneal topography, which are hard to detect in the preclinical phase of KC. The occurrence and development of KC are closely related to regional deterioration in corneal biomechanical properties, which occur ahead of the changes in corneal geometric features. Corneal biomechanical metrics provided by the Ocular Response Analyzer and Corvis ST have been widely used to assess the general biomechanical response of the cornea, however they can not be used to evaluate the regional variation of corneal biomechanical properties. Also, these metrics may be influenced by corneal shape and the intraocular pressure (IOP) making them unreliable in diagnosis of KC. Keratoconus development mechanism will be analyzed though determining the regional mechanical condition of human eye globes under IOP using numerical modelling, developing the material constitutive models for different regions of the cornea, comparing the regional variation of biomechanical constitutive parameters between normal corneas and KC, analyzing the development mechanism of KC and calculating the diagnosis threshold values of biomechanical constitutive parameters for the different stages of KC. Ultimately, this work will lead to a new method for the early detection of KC based on regional corneal biomechanical parameters.

圆锥角膜(KC)发病年龄早，局部圆锥形突起严重影响成像质量，是角膜移植的常见病因。KC的早期诊断困难，其前期体征不易被角膜地形图所发现。局部角膜生物力学性能的改变与KC的发生发展密切相关，并早于角膜表面形态出现异常。现有在体测量仪器如眼反应分析仪和Corvis ST仅能表征角膜的整体性能，而无法评估其局部力学性能在不同区域间的差异；且两种仪器获取的角膜生物力学行为参量受某些因素影响，无法区分正常角膜和KC。本课题拟通过在体施压的手段测量角膜的区域性形变，基于该数据进行有限元模拟和逆向建模，获取角膜的区域化力学参数，实现区域性在体测量角膜生物力学本构参量；利用上述方法，比较正常角膜和KC在体角膜力学性能的区域性差异，分析不同阶段KC区域性角膜生物力学本构参量的变化规律及诊断阈值，探索KC发生发展的生物力学机制。区域性角膜生物力学本构参量可用于辅助诊断KC，为KC的早期诊断和治疗提供理论依据。

圆锥角膜(KC)通常起病于青春期，亚洲人相对多发；以局部(多见于颞下方和中央区)角膜基质变薄和圆锥形突起为主要临床体征，导致近视和高度不规则散光使得视力下降，是角膜移植的常见病因。中晚期的KC体征明显，较易诊断；对于早期KC来说，角膜地形图仍是辅助诊断的主要设备，该手段仍有较大的提高空间。研究显示KC的发生发展与局部角膜生物力学性能的改变密切相关，但现有在体测量仪器如眼反应分析仪和Corvis ST自身提供的参数仅能表征角膜的整体性能，而无法对局部力学性能在不同角膜区域间的差异进行评估。本研究有三个目的：①运用迭代最近点(ICP)算法评估KC和正常角膜Pentacam地形图检查的重复性，评估该方法在辅助KC诊断的可行性。②利用现有临床设备Corvis ST通过在体施压的手段测量角膜的区域性形变，基于该数据进行有限元模拟和逆向建模，获取角膜的区域化力学参数，二次开发实现区域性在体测量角膜生物力学本构参量。③通过对实验兔实施不同的角膜胶原交联方案(CXL)，利用角膜膨胀实验评估不同CXL方案的有效性，验证本森-罗斯科定律是否适用于CXL。结果显示KC患者两次地形图检查的误差要远远大于正常角膜，重复性较差，该方法可用于KC患者的辅助诊断。自行开发的区域性在体测量角膜生物力学本构参量有望成为后续KC诊断和CXL疗效评判的有力手段。采用高能量/短时间照射的搭配方式，使得CXL强化角膜生物力学性能和影响胶原纤维间距的作用逐渐降低，本森-罗斯科定律可能不适用于角膜组织的胶原交联，临床医师在选择CXL治疗方案时应该加以考虑。