Pathophysiological basis of low contrast visual acuity loss in multiple sclerosis

James D. Triplett, Con Yiannikas, Michael H. Barnett, John Parratt, Joshua Barton, Stuart L. Graham, Yuyi You, Alexander Klistorner

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective: There is currently an urgent need for reliable clinical biomarkers of remyelination to be used in Phase 2 and Phase 3 clinical trials. Low contrast visual acuity (LCVA) has been suggested as a functional measure of the integrity of the visual pathway. Therefore, the aim of this study was to elucidate the potential contribution of axonal loss and demyelination to LCVA loss in MS patients. Method: In this study, 50 consecutive relapsing remitting MS patients with a previous history of unilateral optic neuritis were enrolled. Using the linear regression model, we assessed the relative contribution of multifocal Visual Evoked Potentials (mfVEP) latency and Retinal Nerve Fiber Layer (RNFL) thickness to LCVA deficit. Results: Intereye asymmetry of mfVEP latency and RNFL thickness correlated significantly with intereye asymmetry of LCVA (P < 0.001). A linear regression model demonstrated increased predictive power of LCVA when mfVEP latency and RNFL thinning were combined (reaching R2 = 0.67) and confirmed a higher predictive value of RNFL thinning compared to mfVEP latency delay for both contrast levels. However, elimination of subjects with severe axonal loss dramatically increased the relative contribution of mfVEP latency, with contribution of RNFL thickness losing significance for both 1.25% and 2.5% LCVA. Interpretation: While retinal ganglion cell axonal loss is a superior predictor of LCVA, the degree of demyelination contributes significantly to worsening of LCVA, particularly when patients with severe axonal loss are excluded. These results support the feasibility of using LCVA as a functional biomarker in remyelination therapy trials, providing appropriate patient's selection criteria are implemented.

LanguageEnglish
Pages1505-1512
Number of pages8
JournalAnnals of Clinical and Translational Neurology
Volume5
Issue number12
Early online date24 Oct 2018
DOIs
Publication statusPublished - Dec 2018

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Visual Acuity
Multiple Sclerosis
Visual Evoked Potentials
Nerve Fibers
Linear Models
Demyelinating Diseases
Patient Selection
Biomarkers
Optic Neuritis
Phase III Clinical Trials
Visual Pathways
Retinal Ganglion Cells

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Cite this

Triplett, James D. ; Yiannikas, Con ; Barnett, Michael H. ; Parratt, John ; Barton, Joshua ; Graham, Stuart L. ; You, Yuyi ; Klistorner, Alexander. / Pathophysiological basis of low contrast visual acuity loss in multiple sclerosis. In: Annals of Clinical and Translational Neurology. 2018 ; Vol. 5, No. 12. pp. 1505-1512.
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abstract = "Objective: There is currently an urgent need for reliable clinical biomarkers of remyelination to be used in Phase 2 and Phase 3 clinical trials. Low contrast visual acuity (LCVA) has been suggested as a functional measure of the integrity of the visual pathway. Therefore, the aim of this study was to elucidate the potential contribution of axonal loss and demyelination to LCVA loss in MS patients. Method: In this study, 50 consecutive relapsing remitting MS patients with a previous history of unilateral optic neuritis were enrolled. Using the linear regression model, we assessed the relative contribution of multifocal Visual Evoked Potentials (mfVEP) latency and Retinal Nerve Fiber Layer (RNFL) thickness to LCVA deficit. Results: Intereye asymmetry of mfVEP latency and RNFL thickness correlated significantly with intereye asymmetry of LCVA (P < 0.001). A linear regression model demonstrated increased predictive power of LCVA when mfVEP latency and RNFL thinning were combined (reaching R2 = 0.67) and confirmed a higher predictive value of RNFL thinning compared to mfVEP latency delay for both contrast levels. However, elimination of subjects with severe axonal loss dramatically increased the relative contribution of mfVEP latency, with contribution of RNFL thickness losing significance for both 1.25{\%} and 2.5{\%} LCVA. Interpretation: While retinal ganglion cell axonal loss is a superior predictor of LCVA, the degree of demyelination contributes significantly to worsening of LCVA, particularly when patients with severe axonal loss are excluded. These results support the feasibility of using LCVA as a functional biomarker in remyelination therapy trials, providing appropriate patient's selection criteria are implemented.",
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Pathophysiological basis of low contrast visual acuity loss in multiple sclerosis. / Triplett, James D.; Yiannikas, Con; Barnett, Michael H.; Parratt, John; Barton, Joshua; Graham, Stuart L.; You, Yuyi; Klistorner, Alexander.

In: Annals of Clinical and Translational Neurology, Vol. 5, No. 12, 12.2018, p. 1505-1512.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Pathophysiological basis of low contrast visual acuity loss in multiple sclerosis

AU - Triplett, James D.

AU - Yiannikas, Con

AU - Barnett, Michael H.

AU - Parratt, John

AU - Barton, Joshua

AU - Graham, Stuart L.

AU - You, Yuyi

AU - Klistorner, Alexander

N1 - Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2018/12

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