Early Detection of Keratoconus

早期发现圆锥角膜

• 批准号: 7940934
• 负责人: RONALD H SILVERMAN
• 金额: $ 35.62万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7940934
• 关键词: Acoustics; Affect; Air Pressure; Algorithms; Anterior; Arts; Biological Preservation; Characteristics; Clinical; Cornea; Corneal Stroma; Corneal dystrophy; Data; Defect; Degenerative Disorder; Descriptor; Detection; Diagnosis; Diagnostic Procedure; Disease; Disease Progression; Documentation; Early Diagnosis; Early treatment; Elasticity; Epithelial; Epithelium; Eye; Frequencies; Goals; Keratoconus; Keratoplasty; Machine Learning; Maps; Measurement; Measures; Methods; Multivariate Analysis; Operative Surgical Procedures; Optics; Patients; Pattern; Physiologic pulse; Procedures; Property; Puberty; ROC Curve; Radiation; Recording of previous events; Resolution; Risk; Screening procedure; Staging; Stomas; Surface; Surgeon; Symptoms; System; Techniques; Technology; Testing; Thick; Time; Tissues; Translating; Ultrasonography; Vision; Visual Acuity; artemis; base; case-based; crosslink; expectation; human subject; improved; indexing; instrument; instrumentation; method development; prevent; public health relevance; response

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.

描述（由申请人提供）：角膜结构是影响角膜的最常见的退行性疾病。这种疾病往往会在青春期围绕并在未来几十年中进展，但是其临床病史可能会很大。随着圆锥角膜的发展，角膜薄薄和凸起。最终，可能需要进行角膜移植以保持视力。在最早的阶段，即使使用最先进的诊断技术，例如前/后表面地形，这种疾病也很难检测到。这对角膜屈光外科医生至关重要，因为对神秘性角膜角膜的外科手术治疗将削弱它并大大加速症状的发生。由于将早期角膜结构与非典型正常角膜区分开的困难，因此许多正常眼睛被认为是“可疑”的。同时，错过了一些圆锥角性的眼睛，并遭受灾难性的后果。由于最近开发了增强角膜基质和预防疾病进展的方法，因此早期发现角膜结构也可能使患者受益。我们已经开发了一种基于高分辨率超声对角膜成像并测量其组件层的厚度的技术，包括上皮（厚度约50微米）和基质（厚度约为500微米）。我们已经表明，上皮是角膜的表面层，将重塑本身以平滑潜在的不规则性。在早期的角膜结构中，随着前基质表面开始向前凸起，上皮将薄在凸起的顶端上方并在其周围变稠，以保持光滑的前表面。这种补偿机制可防止前表面形貌在早期阶段检测到角膜结构。我们还开发了通过诱导和测量表面位移来响应声学辐射力的脉冲来表征角膜弹性特性的方法。我们将进一步开发和测试此技术，并与眼反应分析仪一起临床应用，该仪器通过使用气压脉冲会引起相似效果。该建议将涉及对正常，圆锥角膜和角膜细胞震撼的眼睛中的地形和弹药模式以及弹性特性的分析。我们将根据对这些模式的多元分析制定指数，该指数基于明确的分类病例，并根据疾病进展的临床记录验证可疑病例的风险指数。我们的目标是通过允许明确诊断早期的角膜结构来减少至少两倍的被认为是圆锥角膜的筛查案例的百分比。公共卫生相关性：角膜结构（KC）是角膜营养不良，在许多情况下，最终需要角膜移植才能保持视力。当前技术无法进行早期检测，这将允许早期治疗并防止对KC角膜的严重损害，以纠正视力。我们的目的是结合角膜弹性，地形和上皮厚度的测量，以发展用于早期检测KC的手段。