Identification of Anterior Segment Structural Biomarkers in Glaucoma Following Pediatric Cataract Using Ultrasound Biomicroscopy

这份K23申请是由珍妮特·L·亚历山大医学博士提交的，她是眼科学和 儿科。我的长期目标是成为一名独立的临床研究员，专注于临床 眼部影像技术在加强儿童眼科疾病护理中的应用与创新 疾病。这项K23奖项将提供所需的指导职业发展，以获得深入的专业知识 研究设计、统计学(最终获得临床研究理学硕士学位)、图像分析(尽管 课程工作和指导)，以及专业发展。青光眼的发病率超过四分之一 儿童先天性白内障在白内障手术后的5年内。几个结构性风险因素 对于先天性白内障手术后的青光眼(GFCCS)已经建立了包括年龄、角膜 巩膜和睫状体的大小和解剖异常。超声生物显微镜(UBM) 有可能彻底改变我们对这些结构性风险因素和更多因素的理解。在…方面的严重差距 这个领域是我们无法利用术前数据来预测GFCCS，提供准确的个性化 预后及早期诊断和治疗。我的总体目标是确定结构性投资的贡献 对GFCCS的风险进行解剖，并为临床医生提供白内障时GFCCS的预测性风险概况 根据UBM确定的眼前段结构特征进行手术(发病前) 图像。我假设在术前UBM图像中确定的结构性风险因素(生物标记物)将 反映结构不成熟，并与GFCCS相关。我们将通过以下目标来检验这一假设： 1)我们将确定0-5岁健康受试者的基线数量结构特征 使用UBM图像，2)我们将确定0-5岁受试者的结构特征 白内障，将白内障队列与年龄匹配的对照组进行比较。白内障队列将被跟踪 纵向上确定与GFCCS发展相关的结构生物标志物。我的训练 这些努力与这些目标并行，并侧重于获得临床研究、生物统计学、图像分析、 和职业发展。除了授课之外，我还将受益于 史蒂文·伯恩斯坦博士和Bennie Jeng博士，在我计划的每个专业领域都建立了领导地位。 目前的研究很重要，因为确定了具体的可测量的结构性风险因素 与GFCCS相关联将帮助临床医生进行诊断，并提供立即的高收益潜在目标 用于治疗和预防。临床医生将从白内障前进行的UBM中确定结构特征 量化青光眼发展风险的手术。拟议研究的结果将提供 为未来研究基于GFCCS结构生物标记物的干预措施奠定基础。这个 我的研究的最终目标是开发量化诊断工具来加强儿科的临床护理 眼前节疾病的患者，导致治疗的改进和儿童失明的减少。

This K23 application is submitted by Janet L. Alexander, MD, Assistant Professor in Ophthalmology and Pediatrics. My long-term goal is to become an independent clinical investigator focusing on clinical applications and innovations in ocular imaging to enhance the care of pediatric patients with ophthalmic disease. This K23 award will provide the mentored career development needed to gain in-depth expertise in study design, statistics (culminating in a Master’s of Science in Clinical Research), image analysis (though coursework and mentorship), and professional development. Glaucoma develops in more than one quarter of children with congenital cataracts in the 5 years following cataract surgery. Several structural risk factors for glaucoma following congenital cataract surgery (GFCCS) have been established including age, corneal size, and anatomic abnormalities of the sclera and ciliary body. Ultrasound biomicroscopy (UBM) has potential to revolutionize our understanding of these structural risk factors and many more. A critical gap in the field is our inability to utilize pre-operative data to anticipate GFCCS, to provide accurate personalized prognosis and earlier diagnosis and treatment. My overall goal is to determine the contribution of structural anatomy in the risk of GFCCS and offer clinicians a predictive risk profile for GFCCS at the time of cataract surgery (prior to disease onset) based on anterior segment structural features determined from UBM images. I hypothesize the structural risk factors (biomarkers) identified in pre-operative UBM images will reflect structural immaturity and correlate with GFCCS. We will test this hypothesis with the following Aims: 1) We will determine baseline quantitative structural characteristics among healthy subjects age 0-5 years using UBM images, 2) We will determine structural characteristics among subjects age 0-5 years with cataracts, to compare the cataract cohort to age-matched controls. The cataract cohort will be followed longitudinally to determine the structural biomarkers that correlate with development of GFCCS. My training efforts parallel these Aims and focus on gaining expertise in clinical research, biostatistics, image analysis, and professional development. In addition to didactic coursework, I will benefit from the close mentorship of Drs. Steven Bernstein and Bennie Jeng, and established leaders in each area of my intended expertise. The current study is important because identification of the specific measurable structural risk factors associated with GFCCS will aid clinicians in diagnosis and provide an immediate high yield potential target for treatment and prevention. Clinicians will identify structural features from UBM performed prior to cataract surgery to quantify risk for development of glaucoma. The results of the proposed research will provide the foundation for a future study examining interventions based on structural biomarkers for GFCCS. The ultimate goal of my research is to develop quantitative diagnostic tools to enhance clinical care for pediatric patients with anterior segment disease, leading to improved treatments and reduced childhood blindness.