Visual improvement following Nerve Growth Factor eye-drop administration in patients with optic pathway glioma-associated visual impairment; prelimary results of a double blind trial

Background: To date, no specific therapy is available for optic pathway glioma (OPG)-associated visual impairment. The aim of this study was to evaluate the effects on visual function of murine nerve growth factor (NGF) eye drop administration in patients with visual impairment due to OPGs. Methods: A prospective randomized double-blind controlled study was conducted in patients younger than 24 years with OPG-induced visual impairment, without or with NF1. All patients were off-therapy and with stable disease at 2 brain magnetic resonance imaging (MRI) controls, performed at least 6 months apart. NGF eye-drop was prepared by Policlinico Gemelli University Pharmacy according to standard required for human use. The patients were assessed by clinical evaluation and ophthalmological examinations including visual acuity, visual field, photopic negative response (PhNR), visual evoked potentials (PEV), Ganzfeld electroretinograms and optic coherence tomography. All patients were recorded at baseline and 15, 30, and 90 days post treatment. A further evaluation at 180 days is planned but no data are available at this time. Brain MRI was performed at baseline and is planned at 180 days after NGF treatment. All the evaluations were performed by considering the change of parameters values from baseline. Results: Ten and 8 patients received a single 10-day course of 1mg murine NGF topical administration and placebo, respectively. Preliminary results (up to 90 days) showed a 40% (p=0.02) and a 50% (p=0.09) improvement of visual field in at least one eye from the baseline evaluations with a better quality of life in the NGF group at 30 and at 90 days post treatment, respectively, compared to a 14% increase in the placebo group. An increase of the mean PhNR amplitude till 90 days was observed in the treated eyes but this was not statistically significant compared to the placebo group; mean PhNR latency increased significantly compared to the placebo group (1.3 vs -1.8 p=0.03) at 15 days but then the difference disappeared. Mean PEV amplitude increase was borderline significant compared to placebo group (p=0.06) at 30 days. No changes in the visual acuity were observed in both groups and no other significant differences were observed for the other ophthalmological examinations. Conclusions: Preliminary results suggest a visual rescuing mechanism exerted by murine NGF on the residual viable optic pathways. NGF administration appears an effective and safe adjunct therapy in patients with OPG-associated visual impairment. No conflict of interest.