Optic pathway glioma volume predicts retinal axon degeneration in neurofibromatosis type 1.
OBJECTIVE
To determine whether tumor size is associated with retinal nerve fiber layer (RNFL) thickness, a measure of axonal degeneration and an established biomarker of visual impairment in children with optic pathway gliomas (OPGs) secondary to neurofibromatosis type 1 (NF1).


METHODS
Children with NF1-OPGs involving the optic nerve (extension into the chiasm and tracts permitted) who underwent both volumetric MRI analysis and optical coherence tomography (OCT) within 2 weeks of each other were included. Volumetric measurement of the entire anterior visual pathway (AVP; optic nerve, chiasm, and tract) was performed using high-resolution T1-weighted MRI. OCT measured the average RNFL thickness around the optic nerve. Linear regression models evaluated the relationship between RNFL thickness and AVP dimensions and volume.


RESULTS
Thirty-eight participants contributed 55 study eyes. The mean age was 5.78 years. Twenty-two participants (58%) were female. RNFL thickness had a significant negative relationship to total AVP volume and total brain volume (p < 0.05, all comparisons). For every 1 mL increase in AVP volume, RNFL thickness declined by approximately 5 microns. A greater AVP volume of OPGs involving the optic nerve and chiasm, but not the tracts, was independently associated with a lower RNFL thickness (p < 0.05). All participants with an optic chiasm volume >1.3 mL demonstrated axonal damage (i.e., RNFL thickness <80 microns).


CONCLUSIONS
Greater OPG and AVP volume predicts axonal degeneration, a biomarker of vision loss, in children with NF1-OPGs. MRI volumetric measures may help stratify the risk of visual loss from NF1-OPGs.
From the Center for Neuroscience and Behavior (R.A.A., R.J.P.), The Gilbert Family Neurofibromatosis Institute (R.A.A., C.T.-H., R.J.P.), Sheikh Zayed Institute for Pediatric Surgical Innovation (A.M., M.G.L.), and The Brain Tumor Institute (R.J.P.), Children's National Health System; The George Washington University School of Medicine and Health Sciences (R.I., M.G.L.), Washington, DC; UPMC Eye Center, Eye and Ear Institute (H.I.), Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine; and Department of Bioengineering (H.I.), Swanson School of Engineering, University of Pittsburgh, PA. averyr@email.chop.edu.
Robert A
RA
Avery
From the Center for Neuroscience and Behavior (R.A.A., R.J.P.), The Gilbert Family Neurofibromatosis Institute (R.A.A., C.T.-H., R.J.P.), Sheikh Zayed Institute for Pediatric Surgical Innovation (A.M., M.G.L.), and The Brain Tumor Institute (R.J.P.), Children's National Health System; The George Washington University School of Medicine and Health Sciences (R.I., M.G.L.), Washington, DC; UPMC Eye Center, Eye and Ear Institute (H.I.), Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine; and Department of Bioengineering (H.I.), Swanson School of Engineering, University of Pittsburgh, PA.
Awais
A
Mansoor
From the Center for Neuroscience and Behavior (R.A.A., R.J.P.), The Gilbert Family Neurofibromatosis Institute (R.A.A., C.T.-H., R.J.P.), Sheikh Zayed Institute for Pediatric Surgical Innovation (A.M., M.G.L.), and The Brain Tumor Institute (R.J.P.), Children's National Health System; The George Washington University School of Medicine and Health Sciences (R.I., M.G.L.), Washington, DC; UPMC Eye Center, Eye and Ear Institute (H.I.), Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine; and Department of Bioengineering (H.I.), Swanson School of Engineering, University of Pittsburgh, PA.
Rabia
R
Idrees
From the Center for Neuroscience and Behavior (R.A.A., R.J.P.), The Gilbert Family Neurofibromatosis Institute (R.A.A., C.T.-H., R.J.P.), Sheikh Zayed Institute for Pediatric Surgical Innovation (A.M., M.G.L.), and The Brain Tumor Institute (R.J.P.), Children's National Health System; The George Washington University School of Medicine and Health Sciences (R.I., M.G.L.), Washington, DC; UPMC Eye Center, Eye and Ear Institute (H.I.), Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine; and Department of Bioengineering (H.I.), Swanson School of Engineering, University of Pittsburgh, PA.
Carmelina
C
Trimboli-Heidler
From the Center for Neuroscience and Behavior (R.A.A., R.J.P.), The Gilbert Family Neurofibromatosis Institute (R.A.A., C.T.-H., R.J.P.), Sheikh Zayed Institute for Pediatric Surgical Innovation (A.M., M.G.L.), and The Brain Tumor Institute (R.J.P.), Children's National Health System; The George Washington University School of Medicine and Health Sciences (R.I., M.G.L.), Washington, DC; UPMC Eye Center, Eye and Ear Institute (H.I.), Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine; and Department of Bioengineering (H.I.), Swanson School of Engineering, University of Pittsburgh, PA.
Hiroshi
H
Ishikawa
From the Center for Neuroscience and Behavior (R.A.A., R.J.P.), The Gilbert Family Neurofibromatosis Institute (R.A.A., C.T.-H., R.J.P.), Sheikh Zayed Institute for Pediatric Surgical Innovation (A.M., M.G.L.), and The Brain Tumor Institute (R.J.P.), Children's National Health System; The George Washington University School of Medicine and Health Sciences (R.I., M.G.L.), Washington, DC; UPMC Eye Center, Eye and Ear Institute (H.I.), Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine; and Department of Bioengineering (H.I.), Swanson School of Engineering, University of Pittsburgh, PA.
Roger J
RJ
Packer
From the Center for Neuroscience and Behavior (R.A.A., R.J.P.), The Gilbert Family Neurofibromatosis Institute (R.A.A., C.T.-H., R.J.P.), Sheikh Zayed Institute for Pediatric Surgical Innovation (A.M., M.G.L.), and The Brain Tumor Institute (R.J.P.), Children's National Health System; The George Washington University School of Medicine and Health Sciences (R.I., M.G.L.), Washington, DC; UPMC Eye Center, Eye and Ear Institute (H.I.), Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine; and Department of Bioengineering (H.I.), Swanson School of Engineering, University of Pittsburgh, PA.
Marius George
MG
Linguraru
D000293:Adolescent; D001369:Axons; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009456:Neurofibromatosis 1 / Q000150:complications / Q000000981:diagnostic imaging*; D009900:Optic Nerve / Q000000981:diagnostic imaging*; D020339:Optic Nerve Glioma / Q000000981:diagnostic imaging* / Q000209:etiology; D009929:Organ Size; D012162:Retinal Degeneration / Q000000981:diagnostic imaging* / Q000209:etiology; D041623:Tomography, Optical Coherence; D047368:Tumor Burden; D014795:Visual Pathways / Q000000981:diagnostic imaging*