扫频光源OCT结合超声探索眼巩膜与近视眼轴延长的关联机制

Axial length elongation plays an important role in the progression of myopia. Basic researches confirmed that scleral extension was responsible for axial length elongation. Compared with the emmetropias, differences of sclerotic elasticity and creep rate were found in myopic human eyes through in vitro studies. Therefore, susceptible and progressive myopias can be hypothesized to show differences in the biomechanical properties, such as sclerotic structure, elasticity and creep rate. It would contribute to study the mechanism of scleral extension and myopia, once the differences were determinate. However, there were still some technical limitations to safely, accurately, and noninvasively detect scleral biomechanical properties in vivo. The aim of this project is to use custom-built swept-source optical coherence tomography combined with the high-frequency ultrasound to obtain real-time sclerotic biomechanical information in vivo human eyes. We will further explore the relationship between sclerotic biomechanical changes and axial length elongation utilizing this system. This project will provide a novel technique to qualitatively and quantitatively measure the biomechanical structures and functions of human sclera in vivo, which could overcome the previous technological shortages through the incorporation of optical detection and ultrasound radiation force. Based on the custom-developed technological system, the mechanisms of sclera structures and functions with axial elongation in myopia progression will be clarified through in vitro studies, animal experiments and human in vivo studies.

近视发生发展的关键生物参数改变是眼轴增长，基础研究证实眼轴增长的物质基础是巩膜扩延，人眼离体研究也发现近视与正视者巩膜弹性及蠕变速率存在差异。由此推测：近视易感或进展者相对正视其巩膜结构与弹性、蠕变等生物力学特性存在差异；该差异的确定及其与近视发展对应关联的获得，有助于揭示近视进展中巩膜延伸机制。然而如何安全、无损、准确获取在体人眼巩膜生物力学特性尚存在技术瓶颈。本课题拟采用自主研发的扫频光源相干断层扫描仪，结合高频超声激励，研发实时同步测量人眼巩膜组织形态和生物力学特性的技术和分析系统，探索近视眼巩膜形态及力学特性与近视眼轴延长的对应规律。巩膜生物力学测量技术平台的搭建，将解决光学扫描和超声激励结合后在人眼巩膜上无损检测的技术难题，实现生物结构及功能的定性定量。通过实验室离体研究、动物测试、近视人群测试分析三个层面的研究设计，探索眼巩膜生物形态与力学特性与近视进展中眼轴延长的关联机制。

眼轴增长是近视发生发展过程中关键环节，而巩膜生物力学性能下降是眼轴增长的主要原因。然而如何安全、无损、准确测量在体巩膜生物力学性能尚存在技术瓶颈。本课题采用100kHz扫频光源，搭建最新一代的高速扫频OCT系统，其成像速度超过当前商业OCT，可实现人眼眼后段组织的高速清晰成像。开发多普勒相位分辨算法来提高扫频OCT系统对组织形变位移的灵敏度。搭建具有自主知识产权的基于超声辐射力光学相干弹性成像（OCE）实验平台，其分为硬件整合和软件开发两部分。硬件整合上设计两种整合方式——同轴入射和斜轴入射，将超声辐射力发射装置和扫频OCT系统整合在一起，并通过NI函数发生卡的信号控制使超声辐射力发射刺激诱导组织形变和OCT系统的图像采集同步。在软件开发上，本课题开发剪切波和共振频率两种分析算法。其中剪切波分析算法通过计算组织中剪切波的传播速率来求得组织弹性模量；共振频率分析算法则分析组织受到不同激励频率的超声辐射力作用下的形变振幅，获得组织频率响应曲线，从而求得组织的固有频率来计算组织弹性模量。通过琼脂样品实验证实剪切波和共振频率分析算法可区分不同硬度的琼脂样品，验证其测量组织弹性模量的可行性。基于超声辐射力OCE实验平台对在体兔眼眼后段组织进行弹性成像，基于动态规划最短路径优化算法来对采集的眼后段组织OCT图像进行自动分层并提取不同亚层组织的多普勒相位信号，分别根据剪切波和共振频率分析算法来计算眼后段各亚层组织的弹性模量。上述两种分析算法都发现眼后段巩膜组织的弹性模量显著大于视网膜组织。本课题还利用超声辐射力OCE实验平台测量在体兔眼角膜弹性，验证基于超声辐射力OCE实验平台测量在体眼球组织的安全性和可行性。开展临床试验分析不同程度的轴性近视眼后段组织结构和微血管损伤与视功能的关系，建立相应的近视视力损伤模型来预测眼轴继续增长所造成的视力损伤。本课题已申请发明专利10项，发表22篇论文。