Early Detection of Keratoconus

描述(申请人提供)：圆锥角膜是最常见的影响角膜的退行性疾病。这种情况往往会在青春期前后发展，并在接下来的几十年里发展，但其临床病史可能会有很大的差异。随着圆锥角膜的发展，角膜变薄和凸起。最终，可能需要进行角膜移植来维持视力。在疾病的早期阶段，即使使用最先进的诊断技术，如前/后表面地形图，也特别难发现。这对角膜屈光外科医生来说非常重要，因为手术治疗隐匿性的圆锥角膜会削弱它，并极大地加速症状的发生。由于很难区分早期圆锥角膜和不典型的正常角膜，许多被认为“可疑”的正常眼睛被拒绝治疗。与此同时，一些圆锥角膜被漏掉并进行了手术，造成了灾难性的后果。早期发现圆锥角膜也可能使患者受益，因为最近发展了加强角膜基质和防止疾病进展的方法。我们开发了一种基于高分辨率超声波的技术，用于对角膜进行成像并测量其组成层的厚度，包括上皮(约50微米厚)和基质(约500微米厚)。我们已经证明，作为角膜表层的上皮细胞会自我重塑，以消除潜在的不规则性。在圆锥角膜早期，随着前基质表面开始向前凸起，凸起尖端上方的上皮变薄，周围变厚，以保持光滑的前表面。这种代偿机制阻止了前表面地形图在圆锥角膜早期发现。我们还开发了通过感应和测量响应于声辐射力脉冲的表面位移来表征角膜弹性特性的方法。我们将进一步开发和测试这项技术，并将其与眼球反应分析仪一起应用于临床，这是一种通过使用气压脉冲产生类似效果的仪器。这项建议将包括分析正常、圆锥角膜和可疑圆锥角膜的地形图和角膜厚度模式以及弹性特性。我们将根据明确分类的病例，基于对这些模式的多变量分析，制定一个指数，并根据疾病进展的临床文件，验证可疑病例的风险指数。我们的目标是通过允许早期圆锥角膜的明确诊断，将筛查的圆锥角膜可疑病例的百分比降低至少两倍。公共卫生相关性：圆锥角膜(KC)是一种角膜营养不良，在许多情况下最终将需要角膜移植来维持视力。早期发现是不可能的，这在目前的技术中是不可能的，这将使早期治疗成为可能，并防止无意中为矫正视力而进行的手术对KC角膜的严重损害。我们的目标是结合角膜弹性、地形图和上皮厚度的测量来开发早期检测KC的方法。

DESCRIPTION (provided by applicant): Keratoconus is the most common degenerative disease affecting the cornea. This condition tends to develop around puberty and to progress over the next few decades, but its clinical history can be quite variable. As keratoconus develops, the cornea thins and bulges. Eventually, a corneal transplant may be needed to maintain vision. In its earliest stages, the disease is particularly difficult to detect, even using state-of-the-art diagnostic techniques such as anterior/posterior surface topography. This is of great importance to the corneal refractive surgeon because surgical treatment of an occult keratoconic cornea will weaken it and greatly accelerate the occurrence of symptoms. Because of the difficulty in differentiating early keratoconus from atypical normal corneas, many normal eyes deemed 'suspicious' are denied treatment. At the same time, some keratoconic eyes are missed and operated upon, with disastrous consequences. Early detection of keratoconus may also benefit patients because of the recent development of methods for strengthening the corneal stroma and preventing disease progression. We have developed a technique based on the use of high resolution ultrasound for imaging the cornea and measuring the thickness of its component layers, including the epithelium (about 50 microns in thickness) and the stroma (about 500 microns in thickness). We have shown that the epithelium, which is the surface layer of the cornea, will remodel itself to smooth out underlying irregularities. In early keratoconus, as the anterior stromal surface begins to bulge forward, the epithelium will thin above the apex of the bulge and thicken around it, to maintain a smooth anterior surface. This compensatory mechanism prevents anterior surface topography from detecting keratoconus in its early stages. We have also developed methods for characterizing the elastic properties of the cornea by inducing and measuring surface displacements in response to a pulse of acoustic radiation force. We will further develop and test this technique and apply it clinically in conjunction with the Ocular Response Analyzer, an instrument that causes a similar effect by use of an air pressure pulse. This proposal will involve analysis of topographic and pachymetric patterns and elastic properties in normal, keratoconus and keratoconus-suspicious eyes. We will develop an index based on multivariate analysis of these patterns based on unambiguously classified cases, and validate the risk index on suspicious cases based on clinical documentation of disease progression. Our goal is to reduce the percentage of screened cases deemed keratoconus- suspicious by at least a factor of two by allowing an unambiguous diagnosis of early keratoconus. PUBLIC HEALTH RELEVANCE: Keratoconus (KC) is a corneal dystrophy will in many cases ultimately require corneal transplantation to maintain vision. Early detection, which is not possible with current technology, would allow early treatment and prevent sever damage to KC corneas inadvertently operated upon for correction of vision. Our aim is to combine measurements of corneal elasticity, topography and epithelial thickness to develop means for early detection of KC.