基于OCT的三维全角膜细微结构形态信息在圆锥角膜早期诊断中的研究

Keratoconus is a non-inflammatory corneal disease characterized by corneal thinning and a cone-like-shaped protrusion of the corneal surface which may eventually result in loss of vision. The early diagnosis of keratoconus remains the major concern of its treatment, prognosis and the preoperative refractive surgery screening. However, the identification of patients with keratoconus at the subclinical forms or suspected keratoconus can be challenging, although the changes of corneal epithelium and bowman layer have been reported by pathological research. Previous clinical diagnostic methods for keratoconus mostly focus on the information of the entire cornea, but not the precise measurement of microstructural changes at different corneal layers. We have accumulated a lot of experience in screening, diagnosis and treatment of keratoconus and have built up ultra-high speed, ultra-high solution and ultra-long scan depth domain OCT system for the anterior segment eye research. This program will detect the entire cornea and its microstructure using OCT system. Then we will build up and validate the diagnosis model of keratoconus based on a series of indicators filtered from OCT three dimension data. Futhermore, we will verify the sensitivity and specificity of the diagnosis model, and finally perfect and determine the effectiveness of the early diagnosis model by clinical follow-up of the subclinical or suspected keratoconus patients. Through transverse and longitudinal studies, we aimed to determine the significance of OCT diagnosis model in the early diagnosis of keratoconus. The outcome will provide the evidence for the establishment of the OCT diagnostic database, and the improvement in the effectiveness of early diagnosis combining existing diagnostic methods.

圆锥角膜是一种角膜进行性变薄并呈圆锥状突起扩张的可致盲疾病。其早期诊断在屈光手术术前筛查及其自身的治疗预后方面有重要意义，虽然病理研究已发现上皮、前弹力层的改变在疾病早期即有发生，但亚临床期或可疑圆锥角膜的临床诊断仍然困难。以往的活体临床诊断方法多局限于角膜整体，尚无法涉及大范围分层细微结构变化的精确测量。本课题组在圆锥角膜筛查、诊治方面积累了大量经验，并已搭建了超快速、超高分辨率、超长扫描深度的频域OCT系统。本项目拟将该系统用于全角膜及其细微结构（上皮、前弹力层）的探测，根据OCT三维影像信息，筛选参数经判别分析建立诊断模型并验证，判定其早期诊断的敏感性和特异性，且通过对纳入的亚临床期或可疑圆锥角膜眼的随访，进一步确定其诊断效能并完善模型；联合横纵向研究，明确该模型在疾病早期诊断中的意义，为建立圆锥角膜OCT的诊断数据库，辅助现有诊断方法，提高早期诊断效能提供依据。

圆锥角膜是一种角膜非炎症性进行性变薄并表现为圆锥状突起扩张的变性疾病，可导致高度不规则散光、角膜瘢痕甚至视力丧失。临床上对该疾病的确诊通常是在病情进入中晚期或进展期后。此外，圆锥角膜是角膜屈光手术前严格筛查的禁忌症之一，如果对未明确诊断的亚临床期圆锥角膜者施行手术，可能导致病情加速发展，因此其早期诊断在屈光手术术前筛查及其自身的治疗预后方面有重要意义。本研究旨在利用OCT系统和Pentacam HR系统建立基于角膜分层细微结构形态参数和角膜整体形态学不规则性指标的诊断模型，并确定该模型在圆锥角膜早期诊断中的效能。本课题完成了较大样本量的亚临床期圆锥角膜眼、圆锥角膜眼和正常眼的收集工作，利用OCT系统获得角膜上皮层、前弹力层、基质层的厚度相关参数并筛选出诊断参数，建立诊断模型。同时应用Pentacam HR系统测量眼前节形态，导出角膜前后表面高度以及全角膜厚度数据。以Zernike多项式拟合方法分析一定范围内的角膜前后表面高度及全角膜厚度分布的不规则性并筛选出诊断参数，也建立诊断模型。分别对上述诊断模型的曲线下面积以及敏感性和特异性进行分析，评价其诊断效能。通过本课题的研究，我们发现角膜分层细微结构和整体的不规则性信息对圆锥角膜的早期诊断有重要意义，OCT系统提示角膜上皮层和前弹力层的角膜不对称性指数或角膜扩张指数对于亚临床期圆锥角膜的诊断效能较高，Pentacam HR系统提示角膜后表面高度或全角膜厚度联合角膜后表面高度不规则性指标对于亚临床圆锥角膜的诊断效能较高。该结果能够对现有的圆锥角膜诊断方法起辅助作用，从而提高诊断效能，同时也提示将角膜细微结构变化和角膜整体形态学不规则指标结合起来，可能在现有基础上进一步提高圆锥角膜早期诊断的效能。