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: 10672883
• 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/10672883
• 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; Thinness; Time; Training; Ultrasonographic Biomicroscopy; Variant; Vision; aqueous; career development; childhood cataract; clinical application; clinical care; cohort; comparison control; congenital cataract; design; diagnostic tool; early childhood; follow-up; imaging study; improved; infancy; innovation; lens; ocular imaging; pediatric patients; pressure; prevent; professor; prospective; risk prediction; skills; statistics; structural determinants; 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.

该K23申请由眼科助理教授珍妮特·L·亚历山大（Janet L. Alexander）提交 儿科。我的长期目标是成为专注于临床的独立临床研究者 在眼部成像中的应用和创新以增强眼科儿科患者的护理 疾病。该K23奖将为获得深入的专业知识所需的介绍职业发展。 研究设计，统计（最终在临床研究的科学硕士学位中达到最终），图像分析（尽管 课程和心态）以及专业发展。超过四分之一的青光眼发展 在白内障手术后的5年中，先天性白内障的儿童。几个结构性风险因素 先天性白内障手术后的青光眼（GFCC），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）具有 有可能彻底改变我们对这些结构风险因素的理解等等。一个关键的差距 该领域是我们无法利用术前数据来预测GFCC，以提供准确的个性化 预后以及较早的诊断和治疗。我的总体目标是确定结构的贡献 GFCC风险的解剖结构，并在白内障时为临床医生提供GFCC的预测风险。 基于UBM确定的前部结构特征（疾病发作之前）的手术（疾病发作） 图像。我假设在术前UBM图像中确定的结构性风险因素（生物标志物）将 反映结构不成熟并与GFCC相关。我们将以以下目的检验这一假设： 1）我们将确定健康受试者的基线定量结构特征0-5岁 使用UBM图像，2）我们将确定年龄0-5岁的受试者之间的结构特征 白内障，将白内障队列与年龄匹配的对照进行比较。白内障队列将遵循 纵向确定与GFCC发展相关的结构生物标志物。我的训练 努力平行于这些目标，并专注于获得临床研究，生物统计学，图像分析， 和专业发展。除教学课程外，我还将受益于 博士。史蒂文·伯恩斯坦（Steven Bernstein）和本尼·詹（Bennie Jeng），并在我预定的专业知识的每个领域中建立了领导者。 当前的研究很重要，因为鉴定了特定的可测量结构风险因素 与GFCC有关 用于治疗和预防。临床医生将在白内障前确定UBM的结构特征 量化青光眼发展风险的手术。拟议研究的结果将为 未来研究的基础研究基于GFCC的结构生物标志物的干预措施。这 我的研究的最终目标是开发定量诊断工具，以增强小儿的临床护理 患有前节疾病的患者，导致治疗改善并减少儿童失明。

项目成果

Congenital ankyloblepharon in a newborn with an IRF6 mutation.

具有 IRF6 突变的新生儿先天性眼睑强直。

• DOI: 10.1016/j.jaapos.2022.11.015
• 发表时间: 2023
• 期刊: Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus
• 作者: Uddin,Olivia;Choi,JamieH;Causey,Erin;Levin,MoranR;Alexander,JanetL
• 通讯作者: Alexander,JanetL