Biomarkers of Vision Loss in Children with Optic Pathway Gliomas

视神经胶质瘤儿童视力丧失的生物标志物

• 批准号: 9883811
• 负责人: Robert Andrew Avery
• 金额: $ 61.17万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9883811
• 关键词: 8 year old; Achievement; Age; Axon; Biological Markers; Blindness; Brain Neoplasms; Cell physiology; Characteristics; Child; Clinical Management; Clinical Trials; Data; Diagnostic; Diffusion Magnetic Resonance Imaging; Early treatment; Electrophysiology (science); Electroretinography; Ensure; Event; Evolution; Excision; Future; Ganglion Cell Layer; Genetic; Genetic Engineering; Glioma; Goals; Human; Inner Plexiform Layer; Laboratories; Lead; Location; Magnetic Resonance Imaging; Measures; Modeling; Monitor; Mus; Operative Surgical Procedures; Optic Nerve; Optical Coherence Tomography; Optics; Outcome; Pathway interactions; Pediatric Neoplasm; Play; Prediction of Response to Therapy; Publishing; Quality of life; Recovery; Reproducibility; Research; Research Proposals; Role; Statistical Data Interpretation; Structure; Techniques; Testing; Thick; Time; Treatment outcome; Vision; Vision Tests; Visual; Visual Acuity; Visual Fields; Visual Pathways; Visual evoked cortical potential; area striata; axonal degeneration; base; chemotherapy; clinical care; cohort; disability; experience; ganglion cell; improved; innovation; insight; macula; markov model; multimodality; myelination; optimal treatments; predictive modeling; prevent; response; restoration; retinal nerve fiber layer; treatment response; tumor; tumor microenvironment

Project Summary Low-grade gliomas are the most common brain tumor in children and frequently involve the optic nerve, chiasm, and tract—so they are referred to as optic pathway gliomas (OPGs). OPGs cause vision loss, typically between 1 and 8 years of age, resulting in lifelong disability as well as reduced academic and vocational achievement. The long term goal of this research proposal is to improve the visual outcomes and clinical management of children with OPGs. The primary objective of this proposal is to determine if optical coherence tomography (OCT) measures of circumpapillary retinal nerve fiber layer (cpRNFL) and ganglion cell – inner plexiform layer (GCIPL) thickness are accurate biomarkers for vision (visual acuity and visual field). The primary hypothesis is that the magnitude and location of cpRNFL and GCIPL thickness will be tightly correlated to visual function and, based on previously published data, both of these OCT measures will decline before visual function declines, thereby identifying an optimal treatment window. The secondary hypothesis is that children who recover vision while being treated for their OPG will demonstrate specific photophic negative response (PhNR), visual evoked potential (VEP), diffusion tensor imaging (DTI) and volumetric MRI characteristics as compared to those that do not recover vision from treatment. The rationale for the proposed research is that OCT measures provide an objective, reproducible assessment of visual pathway integrity that will ensure consistency across centers and clinical trials regardless of the child’s age and ability to cooperate with standard vision testing. The primary and secondary hypotheses will be tested in three specific aims: 1) Create a structure-function model of vision loss for children with OPGs using OCT; 2) Identify the optimal treatment window for OPGs using longitudinal OCT; and 3) Develop multimodal biomarkers to predict treatment response and elucidate the mechanism of vision loss. The first aim builds on previously published data and will be validated in an adequately powered multicenter cohort. Aim 2, supported by preliminary data, will develop predictive models of impending vision loss by using traditional and innovative statistical techniques to identify the earliest and most precise point of cpRNFL/GCIPL decline preceding vision loss—ultimately defining the optimal treatment window. Aim 3 will determine how biomarkers (PhNR, VEP, DTI and volumetric MRI) across the entire visual pathway evolve depending on whether the child experiences visual recovery or visual loss after undergoing treatment for their OPG. This project will have an immediate impact on the clinical care, visual outcomes and diagnostic monitoring of children with OPGs. This project will also provide much needed insight into the mechanism of vision loss from OPGs and highlight future opportunities for neuroprotective and visual restoration strategies outlined by the NEI Audacious Goals Initiative.

项目摘要 低度神经胶质瘤是儿童中最常见的脑肿瘤，经常涉及视神经， chiasm和tract - 因此它们被称为光学途径神经胶质瘤（OPG）。 OPG会导致视力丧失，通常 在1至8岁之间，导致终身残疾以及学术和出版减少 该研究建议的长期目标是改善视觉结果和临床 OPG儿童的管理。该提议的主要目的是确定光学连贯性是否 层析成像（OCT）的电路视网膜神经纤维层（CPRNFL）和神经节细胞的测量 丛状层（GCIPL）厚度是视力（视敏度和视野）的准确生物标志物。这 主要假设是CPRNFL和GCIPL厚度的大小和位置将密切相关 视觉功能，并根据先前发布的数据，这两种OCT措施在 视觉功能降低，从而识别一个最佳的治疗窗口。第二个假设是 在接受OPG治疗时恢复视力的孩子将表现出特定的光照下阴性 响应（PHNR），视觉诱发电势（VEP），扩散张量成像（DTI）和体积MRI 与未从治疗中恢复视力的特征相比。提议的理由 研究是，OCT措施提供了对视觉途径完整性的客观，可重复的评估 无论孩子的年龄和协调能力如何 进行标准视觉测试。主要和次要假设将以三个特定目的进行测试：1） 使用OCT为患有OPG的儿童创建视力丧失的结构功能模型； 2）确定最佳 使用纵向OCT的OPG的治疗窗口； 3）开发多模式生物标志物以预测 治疗反应并阐明视力丧失的机制。第一个目的是基于先前发布的 数据并将在足够功能的多中心队列中进行验证。 AIM 2，受初步数据支持， 将通过使用传统和创新的统计技术来开发即将到来的视力丧失的预测模型 确定CPRNFL/GCIPL在视力丧失之前的最早，最精确的点 - 定义最佳治疗窗口。 AIM 3将确定生物标志物（PHNR，VEP，DTI和体积）如何 MRI）在整个视觉途径中，取决于孩子是否经历了视觉恢复还是 接受OPG治疗后的视觉损失。该项目将立即对临床产生影响 对OPG儿童的护理，视觉结果和诊断监测。该项目还将提供很多 需要深入了解OPG的视力丧失机制，并突出未来的机会 Nei Audacious目标倡议概述了神经保护和视觉恢复策略。