The Predictive Value of Pre-plus Disease in ROP

描述（由申请人提供）：该K23奖将允许候选人获得必要的培训和技能，以开发和领导儿童眼科以患者为导向的研究项目，包括多中心临床试验。候选人将学习研究设计、方案开发、拨款申请、项目管理、数据分析、统计方法、结果沟通和医学伦理。为了实现这些目标，候选人将(1)在Roy Beck博士的直接指导下参与儿科眼病调查员小组进行的多项临床试验，(2)获得公共卫生硕士学位，主修流行病学，辅修生物统计学，(3)在Graham Quinn博士的指导下完成一项关于早产儿视网膜病变（ROP）的研究项目，ROP是美国儿童失明的主要原因之一。拟议的研究项目将利用数字视网膜图像来验证我们的假设，即患有pre-plus疾病（轻度至中度异常血管扩张和视网膜中央、后血管扭曲）的眼睛更容易发生威胁视力的ROP。具体目的是：(1)调查pre-plus是否能预测严重ROP（阈值疾病）的进展，(2)确定pre-plus是否在已建立的ROP位置（区域）和严重程度（阶段）描述符提供的预测价值之外增加了预测价值，以及(3)研究pre-plus疾病的自然史。为了解决这些问题，两位蒙面ROP专家将对150名婴儿的间接视镜视频生成的数字视网膜图像中的血管扩张和扭曲程度进行分级。pre-plus的眼睛将与正常的眼睛进行比较，比较其进展到阈值的比例。如果pre-plus能准确预测进展到阈值，则具有重要的临床意义。这些措施包括提高识别高危婴儿的能力，这些婴儿可能受益于比常规激光治疗更早的治疗，对一些婴儿更有效的筛查方案，以及更准确地向父母提供有关疾病进展风险的咨询。

DESCRIPTION (provided by applicant): This K23 Award will allow the candidate to obtain the training and skills necessary to develop and lead patient-oriented research projects in pediatric ophthalmology, including multi-center clinical trials. The candidate will learn study design, protocol development, grant application, project management, data analysis, statistical methods, communication of results, and medical ethics. To achieve these objectives, the candidate will (1) work under the direct supervision of Dr. Roy Beck on several clinical trials conducted by the Pediatric Eye Disease Investigator Group, (2) obtain a masters degree in public health with a concentration in epidemiology and a minor in biostatistics, and (3) complete a research project with the guidance of Dr. Graham Quinn in retinopathy of prematurity (ROP), one of the leading causes of childhood blindness in the United States. The proposed research project will utilize digital retinal images to test our hypothesis that eyes with pre-plus disease (mild to moderately abnormal vascular dilation and tortuosity of central, posterior retinal blood vessels) are more likely to develop sight-threatening ROP. The specific aims are (1) to investigate whether pre-plus predicts progression to severe ROP (threshold disease), (2) to determine if pre-plus adds predictive value beyond that already provided by established ROP descriptors of location (zone) and severity (stage), and (3) to study the natural history of pre-plus disease. To address these aims, 2 masked experts in ROP will grade the degree of vascular dilation and tortuosity in digital retinal images generated from video indirect ophthalmoscopy in a cohort of 150 infants. Eyes with pre-plus will be compared to normal eyes in regard to the proportion that progress to threshold. There are important clinical implications if pre-plus accurately predicts progression to threshold. These include improved ability to identify high-risk infants who may benefit from earlier than usual laser treatment, more effective screening protocols for some infants, and more accurate counseling of parents regarding the risk of disease progression.