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.

Public Health Relevance

Low-grade gliomas, the most common type of brain tumor in children, can cause severe vision loss in some, but not all of the children with these tumors. Treatment with chemotherapy is only initiated after vision loss has occurred, but unfortunately young children with these tumors are frequently uncooperative with their vision testing. The goal of this project is to use novel ophthalmologic imaging methods that do not require patient cooperation as a surrogate marker of vision which may allow for early detection and treatment of impending vision loss.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23EY022673-01
Application #
8353177
Study Section
Special Emphasis Panel (ZEY1-VSN (10))
Program Officer
Agarwal, Neeraj
Project Start
2012-09-01
Project End
2017-07-31
Budget Start
2012-09-01
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$230,124
Indirect Cost
$17,046
Name
Children's Research Institute
Department
Type
DUNS #
143983562
City
Washington
State
DC
Country
United States
Zip Code
20010
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Avery, Robert A; Hardy, Kristina K (2014) Vision specific quality of life in children with optic pathway gliomas. J Neurooncol 116:341-7
Avery, Robert A; Cnaan, Avital; Schuman, Joel S et al. (2014) Intra- and inter-visit reproducibility of ganglion cell-inner plexiform layer measurements using handheld optical coherence tomography in children with optic pathway gliomas. Am J Ophthalmol 158:916-23
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