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: 8532907
• 负责人: Robert Andrew Avery
• 金额: $ 22.96万
• 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/8532907
• 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.

描述（由申请人提供）：这项以患者为导向的研究职业发展奖将为一名儿科神经眼科医生做好学术生涯的准备，成为一名独立的多学科临床研究人员，重点关注患有视觉通路脑肿瘤（称为视神经胶质瘤）的儿童的视力结果（OPG）。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 OPG 儿童视力 (VA) 的替代标志。候选人提议由儿科眼科医生首席导师、生物统计学家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提供多学科指导。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“开发和验证可用于诊断和分层患者、测量疾病进展和衡量治疗结果的生物标志物。” OPG 可导致儿童（通常为 1 至 8 岁）的 VA 严重永久性丧失。只有在检测到新的或进行性的 VA 丧失以试图保留或改善视力时，才开始用化疗治疗 OPG。然而，准确测量儿童 VA 高度依赖于他们的合作，许多患有 OPG 的幼儿由于相关的行为问题经常无法配合 VA 测试。因此，患有 OPG 的儿童迫切需要一种不依赖患者合作的可靠的 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，先前的研究表明 VA 与 RNFL 厚度密​​切相关。具体来说，随着 RNFL 厚度的减小，VA 也会减小。光学相干断层扫描 (OCT) 是超声成像的光学模拟，可以安全地测量 RNFL 厚度，但也需要患者的配合。该提案通过在镇静剂进行 MRI 扫描时使用手持式谱域 OCT (HH-OCT)，解决了无法配合 OCT 的婴儿/幼儿获取 RNFL 测量的困难。 HH-OCT 成像协议专门针对非常年轻的人（他们因 OPG 导致 VA 损失的风险最高），将建立 RNFL 厚度作为 VA 的定量生物标志物。对使用和未使用 OPG 的儿童进行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（通过 HH-OCT 测量）。第三项研究将分析患有 OPG 的儿童 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，并提高我们对 OPG 儿童做出关键治疗决策的能力。检测即将发生的视力丧失的能力将 让我们能够提供早期治疗，以期防止视力丧失。