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May 27, 2014; 82 (21) Article

Retinal architecture and mfERG

Optic nerve head component response characteristics in MS

Zane S. Schnurman, Teresa C. Frohman, Shin C. Beh, Darrel Conger, Amy Conger, Shiv Saidha, Steven Galetta, Peter A. Calabresi, Ari J. Green, Laura J. Balcer, Elliot M. Frohman
First published April 30, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000447
Zane S. Schnurman
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.
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Teresa C. Frohman
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.
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Shin C. Beh
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.
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Darrel Conger
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.
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Amy Conger
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.
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Shiv Saidha
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.
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Steven Galetta
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.
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Peter A. Calabresi
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.
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Ari J. Green
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.
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Laura J. Balcer
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.
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Elliot M. Frohman
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.
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Full PDF
Citation
Retinal architecture and mfERG
Optic nerve head component response characteristics in MS
Zane S. Schnurman, Teresa C. Frohman, Shin C. Beh, Darrel Conger, Amy Conger, Shiv Saidha, Steven Galetta, Peter A. Calabresi, Ari J. Green, Laura J. Balcer, Elliot M. Frohman
Neurology May 2014, 82 (21) 1888-1896; DOI: 10.1212/WNL.0000000000000447

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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.

GLOSSARY

AON=
acute optic neuritis;
CI=
confidence interval;
GEE=
generalized estimating equation;
ICC=
intraclass correlation coefficient;
mfERG=
multifocal electroretinography;
mfVEP=
multifocal visual-evoked potential;
MS=
multiple sclerosis;
OCT=
optical coherence tomography;
ONHC=
optic nerve head component;
RGC=
retinal ganglion cell;
RNFL=
retinal nerve fiber layer

Footnotes

  • ↵* These authors contributed equally to these investigations as senior authors.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received August 9, 2013.
  • Accepted in final form February 21, 2014.
  • © 2014 American Academy of Neurology
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