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）：这个以患者为导向的指导研究职业发展奖将为一名儿科神经眼科医生的学术生涯做好准备，使其成为一名独立的多学科临床研究人员，专注于视觉通路中称为视神经胶质瘤（OPGs）的脑肿瘤儿童的视力结果。候选人的申请提供了建立临床研究职业所需的培训，致力于使用新型眼科成像方法作为OPGs儿童视力（VA）的替代标记。候选人建议由一名儿科眼科医生担任首席评论员，生物统计学家担任首席联合导师，以及神经肿瘤学、青光眼和眼科成像领域的杰出专家顾问小组担任多学科指导。该应用程序解决了NEI视觉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，用于诊断和分层患者，测量疾病进展和测量治疗结果。”OPGs可导致儿童（通常在1至8岁之间）显著的永久性VA丧失。为了保护或改善视力，只有在检测到新的或进行性VA丧失时，才开始用化疗治疗OPGs。然而，准确测量儿童的VA高度依赖于他们的合作，许多患有OPGs的幼儿由于相关的行为问题而经常无法配合VA测试。因此，迫切需要一种可靠的、不依赖于患者合作的VA定量生物标志物。视网膜神经纤维层（RNFL）是视觉通路的最近端区域，已有研究表明VA与RNFL厚度密切相关。具体来说，随着RNFL厚度的下降，VA也会减少。光学相干断层扫描（OCT）是一种光学模拟超声成像技术，可以安全地测量RNFL的厚度，但也需要患者的配合。该建议通过在镇静下进行MRI扫描时使用手持式光谱域OCT (HH-OCT)，解决了无法合作进行OCT的婴儿/幼儿获得RNFL测量的困难。HH-OCT成像方案专门针对非常年轻的患者，他们因opg导致VA损失的风险最高，将RNFL厚度作为VA的定量生物标志物。两项针对有和没有opg的儿童的横断面研究将建立VA和RNFL厚度之间的结构-功能关系，通过HH-OCT测量。第三项研究将分析OPGs患儿VA和RNFL厚度的纵向变化。这些研究将确立RNFL厚度作为VA的定量生物标志物，并提高我们对OPGs患儿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会