title: Nerve growth factor improves visual loss in childhood optic gliomas: a randomized, double-blind, phase II clinical trial.
abstract: Paediatric optic pathway gliomas are low-grade brain tumours characterized by slow progression and invalidating visual loss. Presently there is no strategy to prevent visual loss in this kind of tumour. This study evaluated the effects of nerve growth factor administration in protecting visual function in patients with optic pathway glioma-related visual impairment. A prospective randomized double-blind phase II clinical trial was conducted in 18 optic pathway glioma patients, aged from 2 to 23 years, with stable disease and severe visual loss. Ten patients were randomly assigned to receive a single 10-day course of 0.5 mg murine nerve growth factor as eye drops, while eight patients received placebo. All patients were evaluated before and after treatment, testing visual acuity, visual field, visual-evoked potentials, optic coherence tomography, electroretinographic photopic negative response, and magnetic resonance imaging. Post-treatment evaluations were repeated at 15, 30, 90, and 180 days Brain magnetic resonance imaging was performed at baseline and at 180 days. Treatment with nerve growth factor led to statistically significant improvements in objective electrophysiological parameters (electroretinographic photopic negative response amplitude at 180 days and visual-evoked potentials at 30 days), which were not observed in placebo-treated patients. Furthermore, in patients in whom visual fields could still be measured, visual field worsening was only observed in placebo-treated cases, while three of four nerve growth factor-treated subjects showed significant visual field enlargement. This corresponded to improved visually guided behaviour, as reported by the patients and/or the caregivers. There was no evidence of side effects related to nerve growth factor treatment. Nerve growth factor eye drop administration appears a safe, easy and effective strategy for the treatment of visual loss associated with optic pathway gliomas.
authors.affiliation: 1 Institute of Ophthalmology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy achiaretti@yahoo.it.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Falsini
authors.affiliation: 2 Paediatric Oncology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Chiaretti
authors.affiliation: 2 Paediatric Oncology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rizzo
authors.affiliation: 1 Institute of Ophthalmology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Piccardi
authors.affiliation: 2 Paediatric Oncology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ruggiero
authors.affiliation: 3 Institute of Translational Pharmacology, CNR, 00142 Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Manni
authors.affiliation: 3 Institute of Translational Pharmacology, CNR, 00142 Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Soligo
authors.affiliation: 1 Institute of Ophthalmology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Dickmann
authors.affiliation: 1 Institute of Ophthalmology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Federici
authors.affiliation: 1 Institute of Ophthalmology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Annabella
authors.initials: A
authors.lastname: Salerni
authors.affiliation: 4 Informa Society, 00135 Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Timelli
authors.affiliation: 5 Pharmacy Gemelli Hospital, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Gaspare
authors.initials: G
authors.lastname: Guglielmi
authors.affiliation: 2 Paediatric Oncology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lazzareschi
authors.affiliation: 6 Paediatric Neurosurgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Caldarelli
authors.affiliation: 7 Institute of Neuroscience, CNR, 56121 Pisa, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Galli-Resta
authors.affiliation: 8 Institute of Radiology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Colosimo
authors.affiliation: 2 Paediatric Oncology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Riccardi
mesh_terms: D000293:Adolescent; D001766:Blindness / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D020932:Nerve Growth Factor / Q000008:administration & dosage*; D020339:Optic Nerve Glioma / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D011446:Prospective Studies; D014794:Visual Fields / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: C502240:NGF protein, human; D020932:Nerve Growth Factor
keywords: blindness; nerve growth factor; optic pathway gliomas; visual function rescue