Objective: To characterize a high precision and clinically useful paradigm for multifocal, digitally generated, visual evoked potential responses. Background Conventional visual evoked potential techniques are performed with sophisticated, multi-focal stimulators, coupled with digital amplifiers that generate a heterogeneity of cortical responses, with wide variability when compared to the traditional black and white CRT stimulators. While contemporary stimulators represent a technical refinement capable of yielding multi-focal data, with high spatial resolution using m-sequence patterns, no paradigm has been validated to produce a physiologic signature commensurate with the p-100 metric. Design/Methods: Patients with a history of unilateral optic neuritis, along with a control group of healthy patients with no known ophthalmic or neurologic disease, were scanned using the Veris FMS3 Stimulator with a Grass Digital Amplifier. Patients were tested using a 7 minute 120 sector m-sequence multi-focal visual evoked potential test. A standard template was used for each patient. Each electrode was monitored for impedance. The Veris Scientific software was used to formulate an analysis paradigm that would yield valid and reproducible signatures reflecting visual cortical responses. Various combinations of analysis patterns were tested. Results: ROC curves were utilized to assess sensitivity and specificity of data. By dividing the central 20 degrees into three rings, and deriving a single wave form for each of the corresponding geometries, a simulated and reproducible metric was derived, the application of which was confirmed as a highly sensitive and specific discriminator for differentiating normal vs abnormal cortical responses. Conclusions: While multi-focal VEP techniques have impressive spatial resolution, and appear to have utility for confirming pathophysiologic evidence for unilateral visual system dysfunction, the results are not yet comparable to the conventional gold standard p-100 metric. Our proposed technique was effective in segregating geometric ring ratios into a single codified waveform metric, from which normative values can be established. 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. 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. 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. Frohman has received personal compensation for activities with Biogen Idec, Teva Neuroscience, Acorda Therapeutics, Novartis, Astellas, and Abbott Laboratories, Inc.