Objective: To assess whether optic nerve head component testing can reveal sub-clinical damage not detected by optical coherence tomography and visual acuity testing in otherwise healthy MS eyes. Background Optical coherence tomography has long been used to determine thinning of the retinal nerve fiber layer, and its corresponding relationship to vision loss; in particular, abnormalities of low contrast letter acuity or sensitivity. A modification in the stimulus characteristics of multifocal electroretinography generates the optic nerve head component potential; a physiologic signature that signifies the integrity of ganglion cell axonal transmission and the transformation of membrane to saltatory conduction as these axons traverse the lamina cribrosa and acquires oligodendrocyte derived myelin. Design/Methods: Patients with multiple sclerosis were recruited to participate in the study. Subjects underwent retinal nerve fiber layer testing by optical coherence tomography (Spectralis), GDx, high and low contrast visual acuity, and blue optic nerve head component testing. The optic nerve head component testing was performed using the Veris FMS3 stimulator with a Grass amplifier and Burrian-Allan bipolar corneal electrode. Infra-red fundus and optic nerve head monitoring were performed throughout the 9 minute recording to ensure fixation and proper nerve head placement. Results: Preliminary data shows a large number of multiple sclerosis patients who have normal visual acuity, visual fields, oct and fundus exams exhibit a higher number of lost optic nerve component waveforms when compared to patients without multiple sclerosis and/or patients with no known history of ophthalmic or neurologic disease. Conclusions: Testing the optic nerve head component can detect damage to previously considered healthy eyes. This method could be used to assess previous damage for upcoming trials of neuro-protective and neuro-regenerative drugs. Supported by: DADS Foundation, Viragh Family Foundation. Disclosure: Dr. Conger has nothing to disclose. Dr. Conger has nothing to disclose. Dr. Frohman has received personal compensation for activities with Biogen Idec and Teva Pharmaceuticals. Dr. Beh has nothing to disclose. Dr. Greenberg has received personal compensation for activities with DioGenix, Greater Good Foundation, Biogen Idec, Serono, Inc., Sanofi-Aventis Pharmaceuticals, Inc., the Multiple Sclerosis Association of America and Teva Neuroscience as a consultant and/or speaker. Dr. Greenberg holds stock and/or stock options in Diogeix. Dr. Greenberg has received research support from Guthy-Jackson Charitable Foundation, Amplimmune, Inc. and the Accelerated Cure Project. 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.