Biomarkers of Vision Loss in Children with Optic Pathway Gliomas

项目摘要 低级别胶质瘤是儿童最常见的脑肿瘤，常累及视神经， 交叉和束-因此它们被称为视路胶质瘤(OPGs)。眼球过多会导致视力丧失，通常 1至8岁，导致终生残疾以及学业和职业能力下降 成就。这项研究计划的长期目标是改善视力和临床结果。 患有有机磷农药中毒的儿童的管理。这项提议的主要目标是确定光学相干性 视网膜乳头周围神经纤维层和神经节细胞内层的断层扫描(OCT)测量 丛状层(GCIPL)厚度是视力(视力和视野)的准确生物标志物。这个 基本假设是cpRNFL的大小和位置与GCIPL厚度密切相关 根据之前公布的数据，这两项OCT测量在 视觉功能下降，从而确定最佳治疗窗口。第二个假设是 在接受OPG治疗的同时恢复视力的儿童将表现出特定的趋光性阴性 反应(PhNR)、视觉诱发电位(VEP)、弥散张量成像(DTI)和容积MRI 与那些不能从治疗中恢复视力的人相比，他们的特点是。建议的理由是 研究表明，OCT测量提供了对视觉通路完整性的客观、可重复的评估， 将确保中心和临床试验的一致性，无论儿童的年龄和合作能力如何 通过标准的视力测试。主要和次要假设将在三个具体目标中进行检验：1) 使用OCT建立儿童OPG视力损失的结构-功能模型；2)确定最优 使用纵向OCT治疗OPGs的窗口；3)开发多模式生物标志物以预测 治疗反应，阐明视力丧失的机制。第一个目标建立在之前发布的基础上 数据，并将在一个足够强大的多中心队列中进行验证。目标2，得到初步数据的支持， 将利用传统和创新的统计技术开发即将到来的视力损失的预测模型 最终确定视力丧失前cpRNFL/GCIPL下降的最早和最准确的点 定义最佳治疗窗口。目标3将确定生物标志物(PhNR、VEP、DTI和容量 MRI)在整个视觉通路上的演变取决于儿童是否经历了视力恢复或 在接受OPG治疗后视力丧失。这一项目将立即对临床产生影响 儿童OPGs的护理、视觉结果和诊断性监测。该项目还将提供更多 需要深入了解OPG导致视力丧失的机制并强调未来的机会 NEI大胆目标倡议概述的神经保护和视觉恢复战略。

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.