The Optic Nerve Head Component: A Novel Eletrophysiologic Marker of Optic Neuropathy in Multiple Sclerosis and Neuromyelitis Optica (S48.001)

Objective: To characterize abnormalities of a novel multifocal electroretinographic (mfERG) late response potential, the optic nerve head component (ONHC), in patients with multiple sclerosis (MS)- and neuromyelitis optica (NMO)-associated optic neuropathy. Background The ONHC is generated from the geometric array of the ganglion cell axons in the vicinity of the optic nerve head. Its latency increases with distance of the stimulus from the nerve head, possibly due to the delay in the propagation of action potentials along the unmyelinated axons of the retinal nerve fiber layer (RNFL). At the level of lamina cribrosa, as the unmyelinated axons of the RNFL transition to myelinated axons of the optic nerve, the change from membrane to saltatory conduction is believed to also be responsible for the ONHC generation. Design/Methods: The following metrics were measured in a group of subjects with MS- and NMO-related optic neuropathy and compared to a group of healthy controls: reduced contrast visual acuity (2.5% and 1.25%), optical coherence tomography (OCT), GDx-VCC, multifocal visual evoked potentials (mfVEP) and mfERG. A pseudo-random m-sequence stimulation on an array of 103 hexagons tiling the central 50 degree of the visual field was used to elicit the ONHC. Results: In the group with MS- or NMO-related optic neuropathy, the absence or disorganization of the ONHC was found in the eye(s) previously affected by optic neuritis. Perturnation of this waveform was associated with disruption of other metrics i.e. loss of contrast sensitivity, abnormal mfVEP responses and RNFL thinning (as measured by OCT and GDx-VCC). Conclusions: Our findings validate a novel electrophysiologic method of evaluating MS- and NMO-related optic neuropathy which may serve as a unique marker of disease activity and neurorestorative therapy. The ONHC may represent a more sensitive and site-selective signature of chronic demyelination, and as such could be utilized as a reliable outcome in remyelination trials. Disclosure: Dr. Beh has nothing to disclose. Dr. Schnurman has nothing to disclose. Dr. Frohman has received personal compensation for activities with Biogen Idec and Teva Pharmaceuticals. Dr. Conger has nothing to disclose. Dr. Conger has nothing to disclose. Dr. Sutter has received personal compensation for activities with Electro-Diagnostics Imaging as an employee. Dr. Sutter holds stock and/or stock options in Electro-Diagnostics Imaging. Dr. Balcer has received personal compensation for activities with Biogen Idec, Vaccinex and Bayer as a consultant and has received honoraria from Biogen Idec and Novartis. Dr. Calabresi has received personal compensation for activities with Teva, Biogen Idec, Novartis, Genzyme, Johnson & Johnson, and Vertex. Dr. Calabresi has received research support from Biogen Idec, Teva, EMD Serono, Vertex, Genentech, Abbott, and Bayer. Dr. Frohman has received personal compensation for activities with Biogen Idec, Teva Neuroscience, Acorda Therapeutics, Novartis, Astellas, and Abbott Laboratories, Inc.