Zane S Schnurman1, Teresa C Frohman1, Shin C Beh1, Darrel Conger1, Amy Conger1, Shiv Saidha1, Steven Galetta1, Peter A Calabresi1, Ari J Green1, Laura J Balcer2, Elliot M Frohman2. 1. From the Departments of Neurology (Z.S.S., T.C.F., S.C.B., D.C., A.C., E.M.F.) and Ophthalmology (E.M.F.), University of Texas Southwestern Medical Center at Dallas; Department of Neurology (S.S., P.A.C.), Johns Hopkins Hospital, Baltimore, MD; Department of Neurology (S.S.), Beaumont University Hospital, Dublin, Ireland; Department of Neurology (S.G., L.J.B.), New York University Langone Medical Center; and Departments of Neurology (A.J.G.) and Ophthalmology (A.J.G.), University of California at San Francisco. 2. From the Departments of Neurology (Z.S.S., T.C.F., S.C.B., D.C., A.C., E.M.F.) and Ophthalmology (E.M.F.), University of Texas Southwestern Medical Center at Dallas; Department of Neurology (S.S., P.A.C.), Johns Hopkins Hospital, Baltimore, MD; Department of Neurology (S.S.), Beaumont University Hospital, Dublin, Ireland; Department of Neurology (S.G., L.J.B.), New York University Langone Medical Center; and Departments of Neurology (A.J.G.) and Ophthalmology (A.J.G.), University of California at San Francisco. elliot.frohman@utsouthwestern.edu laura.balcer@nyumc.org.
Abstract
OBJECTIVE: To describe a novel neurophysiologic signature of the retinal ganglion cell and to elucidate its relationship to abnormalities in validated structural and functional measures of the visual system. METHODS: We used multifocal electroretinogram-generated optic nerve head component (ONHC) responses from normal subjects (n = 18), patients with multiple sclerosis (MS) (n = 18), and those with glaucoma (n = 3). We then characterized the relationship between ONHC response abnormalities and performance on low-contrast visual acuity, multifocal visual-evoked potential-induced cortical responses, and average and quadrant retinal nerve fiber layer (RNFL) thicknesses, as measured by spectral-domain optical coherence tomography. RESULTS: Compared with the eyes of normal subjects, the eyes of patients with MS exhibited an increased number of abnormal or absent ONHC responses (p < 0.0001). For every 7-letter reduction in low-contrast letter acuity, there were corresponding 4.6 abnormal ONHC responses at 2.5% contrast (p < 0.0001) and 6.6 abnormalities at the 1.25% contrast level (p < 0.0001). Regarding average RNFL thickness, for each 10-μm thickness reduction, we correspondingly observed 6.8 abnormal ONHC responses (p = 0.0002). The most robust association was between RNFL thinning in the temporal quadrant and ONHC response abnormalities (p < 0.0001). CONCLUSION: Further characterization of ONHC abnormalities (those that are reversible and irreversible) may contribute to the development of novel neurotherapeutic strategies aimed at achieving neuroprotective, and perhaps even neurorestorative, effects in disorders that target the CNS in general, and MS in particular.
OBJECTIVE: To describe a novel neurophysiologic signature of the retinal ganglion cell and to elucidate its relationship to abnormalities in validated structural and functional measures of the visual system. METHODS: We used multifocal electroretinogram-generated optic nerve head component (ONHC) responses from normal subjects (n = 18), patients with multiple sclerosis (MS) (n = 18), and those with glaucoma (n = 3). We then characterized the relationship between ONHC response abnormalities and performance on low-contrast visual acuity, multifocal visual-evoked potential-induced cortical responses, and average and quadrant retinal nerve fiber layer (RNFL) thicknesses, as measured by spectral-domain optical coherence tomography. RESULTS: Compared with the eyes of normal subjects, the eyes of patients with MS exhibited an increased number of abnormal or absent ONHC responses (p < 0.0001). For every 7-letter reduction in low-contrast letter acuity, there were corresponding 4.6 abnormal ONHC responses at 2.5% contrast (p < 0.0001) and 6.6 abnormalities at the 1.25% contrast level (p < 0.0001). Regarding average RNFL thickness, for each 10-μm thickness reduction, we correspondingly observed 6.8 abnormal ONHC responses (p = 0.0002). The most robust association was between RNFL thinning in the temporal quadrant and ONHC response abnormalities (p < 0.0001). CONCLUSION: Further characterization of ONHC abnormalities (those that are reversible and irreversible) may contribute to the development of novel neurotherapeutic strategies aimed at achieving neuroprotective, and perhaps even neurorestorative, effects in disorders that target the CNS in general, and MS in particular.
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