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

使用超声生物显微镜鉴定小儿白内障后青光眼的眼前节结构生物标志物

• 批准号: 10369360
• 负责人: Janet Leath Alexander
• 金额: $ 23.64万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10369360
• 关键词: 5 year old; Address; Adverse event; Affect; Age; Anatomy; Anterior; Area; Automobile Driving; Biological Markers; Biometry; Blindness; Caring; Cataract; Cataract Extraction; Characteristics; Child; Childhood; Chronology; Ciliary Body; Clinical; Clinical Investigator; Clinical Research; Cohort Studies; Complication; Cornea; Data; Data Set; Databases; Defect; Deformity; Development; Diagnosis; Disease; Drainage procedure; Early Diagnosis; Early treatment; Excision; Eye; Foundations; Funding; Future; Glaucoma; Goals; Growth; Human; Image; Image Analysis; Impairment; Incidence; Infant; Intervention; Iris; Knowledge; Master of Science; Measurable; Medical; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Onset of illness; Operative Surgical Procedures; Ophthalmology; Pediatrics; Populations at Risk; Prevention; Primary Prevention; Procedures; Prognosis; Research; Research Design; Research Personnel; Resolution; Risk; Risk Factors; Safety; Sclera; Structure; Testing; Time; Training; Ultrasonographic Biomicroscopy; Variant; Vision; aqueous; base; career development; childhood cataract; clinical application; clinical care; cohort; congenital cataract; design; diagnostic tool; early childhood; follow-up; imaging study; improved; infancy; innovation; lens; ocular imaging; pediatric patients; pressure; prevent; professor; prospective; skills; statistics; success; surgery outcome; targeted treatment; tool; treatment optimization

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.

此 K23 申请由眼科助理教授 Janet L. Alexander 医学博士提交 儿科。我的长期目标是成为一名专注于临床的独立临床研究者 眼科成像的应用和创新，以加强对眼科儿科患者的护理 疾病。该 K23 奖项将提供获得深入专业知识所需的指导职业发展 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 课程作业和指导）以及专业发展。青光眼发病时间超过四分之一 白内障手术后 5 年内患有先天性白内障的儿童的比例。几个结构性风险因素 先天性白内障手术后青光眼 (GFCCS) 的确定包括年龄、角膜 巩膜和睫状体的大小和解剖学异常。超声生物显微镜（UBM） 可能彻底改变我们对这些结构性风险因素等的理解。关键差距 该领域的问题是我们无法利用术前数据来预测 GFCCS，从而提供准确的个性化信息 预后及早期诊断和治疗。我的总体目标是确定结构的贡献 GFCCS 风险的解剖学，并为临床医生提供白内障发生时 GFCCS 的预测风险概况 根据 UBM 确定的眼前节结构特征进行手术（在疾病发作之前） 图像。我假设术前 UBM 图像中识别的结构风险因素（生物标志物）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定量结构特征 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。将跟踪白内障队列 纵向确定与 GFCCS 发展相关的结构生物标志物。我的训练 努力与这些目标并行，并专注于获得临床研究、生物统计学、图像分析、 和专业发展。除了教学课程之外，我还将受益于老师的密切指导 博士。史蒂文·伯恩斯坦 (Steven Bernstein) 和本尼·郑 (Bennie Jeng)，并在我想要的专业知识的每个领域建立了领导者。 当前的研究很重要，因为确定了具体的可测量的结构性风险因素 与 GFCCS 相关将帮助临床医生进行诊断并提供即时的高产量潜在目标 用于治疗和预防。临床医生将通过白内障之前进行的 UBM 确定结构特征 量化青光眼发生风险的手术。拟议研究的结果将提供 为未来研究基于 GFCCS 结构生物标志物的干预措施奠定基础。这 我研究的最终目标是开发定量诊断工具，以加强儿科的临床护理 患有眼前段疾病的患者，从而改善治疗并减少儿童失明。