Early Detection of Keratoconus

描述（由申请人提供）：圆锥角膜是影响角膜的最常见退行性疾病。这种情况往往在青春期左右发展，并在未来几十年内发展，但其临床病史可能相当多变。随着圆锥角膜的发展，角膜变薄和隆起。最终，可能需要角膜移植来维持视力。在其早期阶段，该疾病特别难以检测，即使使用最先进的诊断技术，如前/后表面地形图。这对角膜屈光外科医生来说非常重要，因为隐匿性圆锥角膜的手术治疗会使其变弱，并大大加速症状的发生。由于早期圆锥角膜与非典型正常角膜难以区分，许多被认为“可疑”的正常眼睛被拒绝治疗。与此同时，一些圆锥角膜的眼睛被遗漏并进行手术，造成灾难性的后果。圆锥角膜的早期发现也可能使患者受益，因为最近开发了加强角膜基质和预防疾病进展的方法。我们已经开发了一种基于使用高分辨率超声的技术，用于对角膜进行成像并测量其组成层的厚度，包括上皮（厚度约50微米）和基质（厚度约500微米）。我们已经证明，上皮细胞，这是角膜的表层，将重塑自己，以消除潜在的不规则。在早期圆锥角膜中，随着前基质表面开始向前凸出，上皮将在凸出的顶点上方变薄并在其周围变薄，以保持光滑的前表面。这种代偿机制阻止了前表面地形图检测早期圆锥角膜。我们还开发了用于表征角膜的弹性特性的方法，通过诱导和测量响应于声辐射力的脉冲的表面位移。我们将进一步开发和测试这项技术，并将其与眼反应分析仪一起应用于临床，眼反应分析仪是一种通过使用气压脉冲产生类似效果的仪器。这项建议将涉及分析正常，圆锥角膜和圆锥角膜可疑的眼睛的地形和厚度模式和弹性特性。我们将根据明确分类的病例对这些模式进行多变量分析，并根据疾病进展的临床记录验证可疑病例的风险指数。我们的目标是通过对早期圆锥角膜的明确诊断，将被认为是圆锥角膜可疑的筛查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，在许多情况下最终需要角膜移植来维持视力。早期检测，这是不可能的与目前的技术，将允许早期治疗，并防止严重损害KC角膜无意中操作矫正视力。我们的目标是将角膜弹性、地形图和上皮厚度的测量联合收割机，以开发早期检测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.