1. Children's Hospital of Philadelphia Receives NIH Grant for Biomarkers of Vision Loss in Children with Optic Pathway Gliomas

    Children's Hospital of Philadelphia Receives NIH Grant for Biomarkers of Vision Loss in Children with Optic Pathway Gliomas

    Children's Hospital of Philadelphia Receives a 2020 NIH Grant for $611,652 for Biomarkers of Vision Loss in Children with Optic Pathway Gliomas. The principal investigator is Rogbert Avery. Below is a summary of the proposed work.

    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.

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