Visual outcome measures in children with optic pathway gliomas

描述(由申请者提供)：这个以患者为导向的研究职业发展奖将为儿科神经眼科医生的学术生涯做好准备，成为一名独立的多学科临床研究人员，重点关注患有视路胶质瘤(OPGs)视觉通路脑瘤的儿童的视力结果。候选人的申请提供了建立临床研究生涯所需的培训，致力于使用新的眼科成像方法，作为患有OPGs的儿童视力(VA)的替代标志。这位候选人建议由儿科眼科医生首席主持人、生物统计学家首席共同导师以及神经肿瘤学、青光眼和眼科成像方面的杰出专家顾问小组提供多学科指导。这一应用解决了NEI的视觉研究框架中概述的目标，特别是目标3.2“开发和验证在诊断和分层患者、测量疾病进展和衡量治疗结果方面有用的生物标记物。”OPGs可能会导致儿童永久性严重的VA丧失，通常在1至8岁之间。只有在检测到新的或进行性的视力丧失时，才开始对OPGs进行化疗，以试图保持或改善视力。然而，准确测量儿童的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，迫切需要一种不依赖于患者合作的可靠的VA定量生物标志物来治疗OPGs。视网膜神经纤维层(RNFL)是视觉通路最近端的区域，已有研究表明VA与RNFL厚度密切相关。具体地说，随着RNFL厚度的下降，VA也会减小。光学相干断层成像(OCT)是超声成像的光学模拟，可以安全地测量RNFL厚度，但也需要患者的合作。这项建议通过在注射镇静剂进行MRI扫描时使用手持光谱域OCT(HH-OCT)，解决了无法合作进行OCT的婴幼儿获得RNFL测量的困难。HH-OCT成像方案专门针对非常年轻的人-他们的OPG导致VA丢失的风险最高-将建立RNFL厚度作为VA的定量生物标记物。两项对患有和不患有OPGs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，如HH-OCT所测量的。第三项研究将分析患有OPGs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，并提高我们对患有OPGs的儿童做出关键治疗决定的能力。检测即将到来的视力丧失的能力将 允许我们提供早期治疗，希望能防止视力丧失。

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.