Early Detection of Keratoconus

描述（申请人提供）：圆锥角膜是影响角膜的最常见的退行性疾病。这种情况往往发生在青春期左右，并在接下来的几十年里不断发展，但其临床历史可能变化很大。随着圆锥角膜的发展，角膜变薄并隆起。最终，可能需要角膜移植来维持视力。在其早期阶段，即使使用最先进的诊断技术，如前/后表面地形学，也特别难以发现该疾病。这对角膜屈光外科医生非常重要，因为手术治疗隐匿性角膜斜视会使其变弱，并大大加速症状的发生。由于很难区分早期圆锥角膜和非典型正常角膜，许多被认为“可疑”的正常眼睛被拒绝治疗。同时，一些角膜形成的眼睛被遗漏并进行了手术，造成了灾难性的后果。由于最近发展了加强角膜基质和预防疾病进展的方法，圆锥角膜的早期检测也可能使患者受益。我们开发了一种基于使用高分辨率超声成像角膜并测量其组成层厚度的技术，包括上皮（厚度约50微米）和间质（厚度约500微米）。我们已经证明，角膜的表层上皮会自我重塑，以消除潜在的不规则性。在圆锥角膜早期，由于前间质表面开始向前隆起，上皮细胞在隆起顶端以上变薄，周围变厚，以保持前表面光滑。这种代偿机制阻止前表面地形在圆锥角膜的早期阶段检测。我们还开发了通过诱导和测量响应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，并将其与眼反应分析仪结合应用于临床，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。本建议将包括分析正常、圆锥角膜及圆锥角膜可疑眼睛的地形、厚度模式及弹性特性。我们将基于这些模式的多变量分析，基于明确分类的病例，开发一个指数，并根据疾病进展的临床文件验证可疑病例的风险指数。我们的目标是通过对早期圆锥角膜的明确诊断，减少被认为是圆锥角膜的筛查病例的百分比。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。早期发现，这是目前技术无法做到的，这将允许早期治疗，并防止因矫正视力而无意中对KC角膜造成严重损害。我们的目标是结合角膜弹性，地形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.