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: 10594904
• 负责人: Robert Andrew Avery
• 金额: $ 68.57万
• 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 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594904
• 关键词: 8 year old; Achievement; Age; Axon; Biological Markers; Blindness; Brain Neoplasms; Cell physiology; Cells; Characteristics; Child; Clinical Management; Clinical Trials; Data; Diagnostic; Diffusion Magnetic Resonance Imaging; Early identification; Early treatment; Electrophysiology (science); Electroretinography; Ensure; Event; Evolution; Excision; Future; Genetic; Genetic Engineering; Glioma; Goals; Human; Inner Plexiform Layer; Institution; 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; Visualization; Vocation; area striata; axonal degeneration; chemotherapy; clinical care; cohort; disability; experience; ganglion cell; improved; innovation; insight; macula; markov model; multimodality; myelination; neuroprotection; 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.

项目概要 低度恶性胶质瘤是儿童中最常见的脑肿瘤，经常累及视神经， 视交叉和视束，因此它们被称为视神经胶质瘤 (OPG)，通常会导致视力丧失。 1至8岁之间，导致终身残疾以及学业和职业能力下降 该研究计划的长期目标是改善视力结果和临床。 患有 OPG 的儿童的管理 该提案的主要目标是确定光学相干性。 环视乳头视网膜神经纤维层 (cpRNFL) 和神经节细胞的断层扫描 (OCT) 测量 – 内部 丛状层 (GCIPL) 厚度是准确的视力生物标志物（视敏度和视野）。 主要假设是 cpRNFL 和 GCIPL 厚度的大小和位置紧密相关 视功能，并且根据之前发布的数据，这两项 OCT 测量值在之前都会下降 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 治疗期间恢复视力的儿童将表现出特定的适光负性 反应 (PhNR)、视觉诱发电位 (VEP)、扩散张量成像 (DTI) 和体积 MRI 与那些未从治疗中恢复视力的患者相比的特征。 研究表明，OCT 测量可对视觉通路完整性提供客观、可重复的评估， 无论孩子的年龄和合作能力如何，都将确保各中心和临床试验的一致性 通过标准视力测试，主要和次要假设将在三个具体目标中进行测试：1) 使用 OCT 创建 OPG 儿童视力丧失的结构功能模型 2) 确定最佳模型； 使用纵向 OCT 确定 OPG 的治疗窗口；3) 开发多模式生物标志物进行预测 第一个目标建立在之前发表的文章的基础上。 数据，并将在充分有力的多中心队列中进行验证，并得到初步数据的支持， 将使用传统和创新的统计技术开发即将发生的视力丧失的预测模型 确定 cpRNFL/GCIPL 在视力丧失之前最早和最精确的下降点——最终 目标 3 将确定生物标志物（PhNR、VEP、DTI 和体积）的定义。 整个视觉通路的 MRI）的演变取决于孩子是否经历视力恢复或 接受 OPG 治疗后视力丧失 该项目将对临床产生直接影响。 该项目还将为患有 OPG 的儿童提供很多护理、视力结果和诊断监测。 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 大胆目标计划概述的神经保护和视觉恢复策略。

项目成果

Current treatment of optic nerve gliomas.

目前视神经胶质瘤的治疗。

• 发表时间: 2019-09
• 影响因子: 3.7
• 作者: Farazdaghi, Marybeth K;Katowitz, William R;Avery, Robert A
• 通讯作者: Avery, Robert A

The Relationship Between Choroidal Abnormalities and Visual Outcomes in Pediatric Patients With NF1-Associated Optic Pathway Gliomas.

NF1 相关视神经胶质瘤儿科患者脉络膜异常与视力结果之间的关系。

• 发表时间: 2024-03-01
• 作者: Estrela, Tais;Truong, Saprina;Garcia, Arielle;He, Jocelyn;Ying, Gui;Devakandan, Keshini;Reginald, Y Arun;Fisher, Michael J;Liu, Grant T;Ullrich, Nicole J;Avery, Robert A;Heidary, Gena
• 通讯作者: Heidary, Gena