Visual outcome measures in children with optic pathway gliomas

视神经胶质瘤儿童的视力结果测量

• 批准号: 8353177
• 负责人: Robert Andrew Avery
• 金额: $ 23.01万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8353177
• 关键词: 10 year old; 6 year old; 8 year old; Address; Adult; Affect; Age; Anterior; Axon; Biological Markers; Blindness; Brain Neoplasms; Child; Child Care; Childhood; Clinical; Clinical Research; Commit; Complex; Cross-Sectional Studies; Diagnosis; Disease Progression; Early Diagnosis; Early treatment; Excision; Glaucoma; Glioma; Goals; Hand; Image; Impairment; Infant; Lead; Location; MRI Scans; Magnetic Resonance Imaging; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Modeling; Modification; Morbidity - disease rate; Multiple Sclerosis; Normal Statistical Distribution; Operative Surgical Procedures; Ophthalmologist; Optic Nerve; Optical Coherence Tomography; Optics; Outcome; Outcome Measure; Pathway interactions; Patients; Problem behavior; Protocols documentation; Radiation; Reference Values; Refractive Errors; Research Personnel; Retina; Risk; Schedule; Structure-Activity Relationship; Surrogate Markers; Testing; Therapeutic; Thick; Training; Ultrasonography; Vision; Vision Tests; Vision research; Visual; Visual Acuity; Visual Pathways; Work; age group; age related; analog; axonal degeneration; career; chemotherapy; clinically significant; compliance behavior; experience; high risk; imaging modality; improved; mortality; multidisciplinary; neuro-oncology; novel; prevent; retinal nerve fiber layer; tumor

DESCRIPTION (provided by applicant): This Mentored Patient-Oriented Research Career Development Award will prepare a pediatric neuroophthalmologist for an academic career as an independent multidisciplinary clinical researcher with a focus on vision outcomes in children with brain tumors of the visual pathway called optic pathway gliomas (OPGs). The candidate's application provides training needed to establish a clinical research career committed to using novel ophthalmologic imaging methods that serve as a surrogate marker of visual acuity (VA) for children with OPGs. The candidate is proposing multidisciplinary mentorship from a pediatric ophthalmologist lead comentor, biostatistician lead co-mentor, and distinguished panel of expert consultants in neuro-oncology, glaucoma and ophthalmologic imaging. This application addresses goals outlined in the NEI's Framework for Vision Research, specifically goal 3.2 "Develop and validate biomarkers that are useful in diagnosing and stratifying patients, measuring disease progression and gauging therapeutic outcomes." OPGs can cause significant permanent VA loss in children, typically between the ages of 1 and 8 years of age. Treatment of OPGs with chemotherapy is only initiated once new or progressive VA loss has been detected in an attempt to preserve or improve vision. However, accurately measuring VA in children is highly dependent upon their cooperation and many young children with OPGs are frequently unable to cooperate with VA testing due to associated behavioral problems. Therefore, a reliable quantitative biomarker of VA that does not rely on patient cooperation is desperately needed in children with OPGs. The retinal nerve fiber layer (RNFL) is the most proximal region of the visual pathway and prior studies have shown that VA is closely correlated to RNFL thickness. Specifically, as RNFL thickness declines, VA also diminishes. Optical coherence tomography (OCT), an optical analog of ultrasound imaging, can safely measure RNFL thickness, but also requires patient cooperation. This proposal remedies the difficulty in acquiring RNFL measures in infants/young children who cannot cooperate for OCT, by using a hand-held spectral domain OCT (HH-OCT) while sedated for a MRI scan. HH-OCT imaging protocols targeted specifically for the very young-who are at the highest risk for VA loss from their OPG-will establish RNFL thickness as a quantitative biomarker of VA. Two cross-sectional studies of children with and without OPGs will establish the structure-function relationship between VA and RNFL thickness, as measured by HH-OCT. A third study will analyze longitudinal changes in VA and RNFL thickness in children with OPGs. These studies will establish RNFL thickness as a quantitative biomarker of VA and improve our ability to make crucial treatment decisions in children with OPGs. The ability to detect impending vision loss will allow us to provide early treatment with the hope of preventing vision loss. PUBLIC HEALTH RELEVANCE: Low-grade gliomas, the most common type of brain tumor in children, can cause severe vision loss in some, but not all of the children with these tumors. Treatment with chemotherapy is only initiated after vision loss has occurred, but unfortunately young children with these tumors are frequently uncooperative with their vision testing. The goal of this project is to use novel ophthalmologic imaging methods that do not require patient cooperation as a surrogate marker of vision which may allow for early detection and treatment of impending vision loss.

描述（由申请人提供）：这项受过指导的以患者为导向的研究职业发展奖将为学术生涯做好准备，作为一名独立的多学科临床研究人员，为学术生涯做好了准备，并重点介绍了视觉途径儿童的视觉结果，称为Optic Pathway Gliomas（OPGS）。候选人的应用程序提供了建立临床研究职业所需的培训，该研究职业致力于使用新型的眼科成像方法，这些方法是为患有OPG的儿童的视力标记（VA）。该候选人正在提出来自儿科眼科医生的主要学者，生物统计学家首席同事的多学科指导，以及神经肿瘤学专家顾问的杰出专家小组。该应用程序解决了NEI视力研究框架中概述的目标，特别是目标3.2“开发和验证生物标志物，这些标志物可用于诊断和分层患者，测量疾病进展并测量治疗结果。” OPG通常会在1至8岁之间造成儿童的重大永久性VA损失。只有在发现新的或进行性VA损失以维护或改善视力的过程中，就开始使用化学疗法的OPG治疗。但是，准确地衡量儿童的VA高度取决于他们的合作，许多OPG的幼儿由于相关的行为问题而经常无法与VA测试进行合作。因此，在患有OPG的儿童中，迫切需要VA的可靠定量生物标志物。视网膜神经纤维层（RNFL）是视觉途径的最近端区域，先前的研究表明，VA与RNFL厚度密切相关。具体而言，随着RNFL厚度的下降，VA也会减少。光学相干断层扫描（OCT）是超声成像的光学类似物，可以安全地测量RNFL厚度，但也需要患者合作。该提案补救了难以通过使用手持光谱域OCT（HH-OCT）在镇静下进行MRI扫描时使用手持频谱域（HH-OCT）获得无法合作的婴儿/幼儿的RNFL措施的困难。专门针对非常年轻的HH-OCT成像方案，其OPG损失的风险最高，其opg-Will将RNFL厚度确定为VA的定量生物标志物。通过HH-OCT测量，对患有和没有OPG的儿童的两项横断面研究将建立VA和RNFL厚度之间的结构功能关系。第三项研究将分析OPG儿童的VA和RNFL厚度的纵向变化。这些研究将建立RNFL厚度作为VA的定量生物标志物，并提高我们在OPG儿童中做出关键治疗决策的能力。检测即将到来的视力丧失的能力将 允许我们提供早期治疗，希望预防视力丧失。 公共卫生相关性：低度神经胶质瘤是儿童中最常见的脑肿瘤类型，可能会导致某些患有这些肿瘤的儿童，但并非所有患有这些肿瘤的儿童。仅在视力丧失发生后才开始使用化学疗法的治疗，但不幸的是，患有这些肿瘤的幼儿经常对其视力测试不合作。该项目的目的是使用新型的眼科成像方法，这些方法不需要患者合作作为视力的替代标记，这可能可以及早发现和治疗即将来临的视力丧失。