Optical coherence tomography: A quantitative tool to measure neurodegeneration and facilitate testing of novel treatments for tissue protection in multiple sclerosis

  • Eliza Gordon-Lipkin
    Affiliations
    Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD, USA

    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Search for articles by this author
  • Peter A. Calabresi
    Correspondence
    Corresponding author at: Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Pathology 627, Baltimore, MD 21287, USA.
    Affiliations
    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Search for articles by this author
Published:December 13, 2016DOI:https://doi.org/10.1016/j.jneuroim.2016.12.003

      Highlights

      • Optical coherence tomography (OCT) is a low cost, non-invasive imaging technique that has rapidly developed over the last two decades.
      • OCT is validated in multiple sclerosis and studies have demonstrated its potential for clinical use on both an individual and research level.
      • OCT has a unique ability to measure axons, and may be instrumental for clinical trials of neuroprotective and neurorestorative therapies.
      • OCT has the potential to improve the ways in which we understand, diagnosis, monitor and treat multiple sclerosis.

      Abstract

      Optical coherence tomography (OCT) is a relatively new imaging technology that has been introduced as a powerful biomarker in neurological disease, including multiple sclerosis. In this review, OCT as an imaging technique, its reproducibility and validation in multiple sclerosis, application to other neurodegenerative diseases and future technological directions are discussed.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Neuroimmunology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Balcer L.J.
        • Frohman E.M.
        Evaluating loss of visual function in multiple sclerosis as measured by low-contrast letter acuity.
        Neurology. 2010; 74: S16-S23
        • Bennett J.L.
        • de Seze J.
        • Lana-Peixoto M.
        • Palace J.
        • Waldman A.
        • Schippling S.
        • Tenembaum S.
        • Banwell B.
        • Greenberg B.
        • Levy M.
        • Fujihara K.
        • Chan K.H.
        • Kim H.J.
        • Asgari N.
        • Sato D.K.
        • Saiz A.
        • Wuerfel J.
        • Zimmermann H.
        • Green A.
        • Villoslada P.
        • Paul F.
        • GJCF-ICC&BR
        Neuromyelitis optica and multiple sclerosis: seeing differences through optical coherence tomography.
        Mult. Scler. 2015; 21: 678-688
        • Bouyon M.
        • Collongues N.
        • Zephir H.
        • Ballonzoli L.
        • Jeanjean L.
        • Lebrun C.
        • Chanson J.
        • Blanc F.
        • Fleury M.
        • Outteryck O.
        • Defoort S.
        • Labauge P.
        • Vermersch P.
        • Speeg C.
        • De Seze J.
        Longitudinal follow-up of vision in a neuromyelitis optica cohort.
        Mult. Scler. J. 2013; 19: 1320-1322
        • Calabresi P.A.
        • Balcer L.J.
        • Frohman E.M.
        Optical Coherence Tomography in Neurologic Diseases.
        Cambridge University Press, 2015
        • Cettomai D.
        • Pulicken M.
        • Gordon-Lipkin E.
        • Salter A.
        • Frohman T.C.
        • Conger A.
        • Zhang X.
        • Cutter G.
        • Balcer L.J.
        • Frohman E.M.
        • Calabresi P.A.
        Reproducibility of optical coherence tomography in multiple sclerosis.
        Arch. Neurol. 2008; 65: 1218-1222
        • Chahin S.
        • Salim C.
        • Deborah M.
        • Sakai R.E.
        • Wilson J.A.
        • Teresa F.
        • Clyde M.
        • Dina J.
        • Ari G.
        • Calabresi P.A.
        • Frohman E.M.
        • Galetta S.L.
        • Balcer L.J.
        Relation of quantitative visual and neurologic outcomes to fatigue in multiple sclerosis.
        Mult. Scler. Relat. Disord. 2015; 4: 304-310
        • Costello F.
        • Coupland S.
        • Hodge W.
        • Lorello G.R.
        • Koroluk J.
        • Pan Y.I.
        • Freedman M.S.
        • Zackon D.H.
        • Kardon R.H.
        Quantifying axonal loss after optic neuritis with optical coherence tomography.
        Ann. Neurol. 2006; 59: 963-969
        • Dörr J.
        • Wernecke K.D.
        • Bock M.
        • Gaede G.
        • Wuerfel J.T.
        • Pfueller C.F.
        • Bellmann-Strobl J.
        • Freing A.
        • Brandt A.U.
        • Friedemann P.
        Association of retinal and macular damage with brain atrophy in multiple sclerosis.
        PLoS One. 2011; 6e18132
        • Engell T.
        • Hvidberg A.
        • Uhrenholdt A.
        Multiple sclerosis: periphlebitis retinalis et cerebro-spinalis. A correlation between periphlebitis retinalis and abnormal technetium brain scintigraphy.
        Acta Neurol. Scand. 1984; 69: 293-297
        • Frisén L.
        • Hoyt W.F.
        Insidious atrophy of retinal nerve fibers in multiple sclerosis. Funduscopic identification in patients with and without visual complaints.
        Arch. Ophthalmol. 1974; 92: 91-97
        • Gao L.
        • Liu Y.
        • Li X.
        • Bai Q.
        • Liu P.
        Abnormal retinal nerve fiber layer thickness and macula lutea in patients with mild cognitive impairment and Alzheimer's disease.
        Arch. Gerontol. Geriatr. 2015; 60: 162-167
        • Gelfand J.M.
        • Goodin D.S.
        • Boscardin W.J.
        • Nolan R.
        • Cuneo A.
        • Green A.J.
        Retinal axonal loss begins early in the course of multiple sclerosis and is similar between progressive phenotypes.
        PLoS One. 2012; 7e36847
        • Gelfand J.M.
        • Nolan R.
        • Schwartz D.M.
        • Graves J.
        • Green A.J.
        Microcystic macular oedema in multiple sclerosis is associated with disease severity.
        Brain. 2012; 135: 1786-1793
        • Gordon-Lipkin E.
        • Chodkowski B.
        • Reich D.S.
        • Smith S.A.
        • Pulicken M.
        • Balcer L.J.
        • Frohman E.M.
        • Cutter G.
        • Calabresi P.A.
        Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis.
        Neurology. 2007; 69: 1603-1609
        • Grazioli E.
        • Zivadinov R.
        • Weinstock-Guttman B.
        • Lincoff N.
        • Baier M.
        • Wong J.R.
        • Hussein S.
        • Cox J.L.
        • Hojnacki D.
        • Ramanathan M.
        Retinal nerve fiber layer thickness is associated with brain MRI outcomes in multiple sclerosis.
        J. Neurol. Sci. 2008; 268: 12-17
        • Green A.J.
        • McQuaid S.
        • Hauser S.L.
        • Allen I.V.
        • Lyness R.
        Ocular pathology in multiple sclerosis: retinal atrophy and inflammation irrespective of disease duration.
        Brain. 2010; 133: 1591-1601
        • Henderson A.P.D.
        • Trip S.A.
        • Schlottmann P.G.
        • Altmann D.R.
        • Garway-Heath D.F.
        • Plant G.T.
        • Miller D.H.
        An investigation of the retinal nerve fibre layer in progressive multiple sclerosis using optical coherence tomography.
        Brain. 2008; 131: 277-287
        • Henderson A.P.D.
        • Trip S.A.
        • Schlottmann P.G.
        • Altmann D.R.
        • Garway-Heath D.F.
        • Plant G.T.
        • Miller D.H.
        A preliminary longitudinal study of the retinal nerve fiber layer in progressive multiple sclerosis.
        J. Neurol. 2010; 257: 1083-1091
        • Hu C.-R.
        • Zhang D.
        • Slipchenko M.N.
        • Cheng J.-X.
        • Hu B.
        Label-free real-time imaging of myelination in the Xenopus laevis tadpole by in vivo stimulated Raman scattering microscopy.
        J. Biomed. Opt. 2014; 19: 086005
        • Kerrison J.B.
        • Flynn T.
        • Green W.R.
        Retinal pathologic changes in multiple sclerosis.
        Retina. 1994; 14: 445-451
        • Lange A.P.
        • Sadjadi R.
        • Zhu F.
        • Alkabie S.
        • Costello F.
        • Traboulsee A.L.
        Spectral-domain optical coherence tomography of retinal nerve fiber layer thickness in NMO patients.
        J. Neuroophthalmol. 2013; 33: 213-219
        • Marro M.
        • Taubes A.
        • Abernathy A.
        • Balint S.
        • Moreno B.
        • Sanchez-Dalmau B.
        • Martínez-Lapiscina E.H.
        • Amat-Roldan I.
        • Petrov D.
        • Villoslada P.
        Dynamic molecular monitoring of retina inflammation by in vivo Raman spectroscopy coupled with multivariate analysis.
        J. Biophotonics. 2014; 7: 724-734
        • Pulicken M.
        • Gordon-Lipkin E.
        • Balcer L.J.
        • Frohman E.
        • Cutter G.
        • Calabresi P.A.
        Optical coherence tomography and disease subtype in multiple sclerosis.
        Neurology. 2007; 69: 2085-2092
        • Ratchford J.N.
        • Quigg M.E.
        • Conger A.
        • Frohman T.
        • Frohman E.
        • Balcer L.J.
        • Calabresi P.A.
        • Kerr D.A.
        Optical coherence tomography helps differentiate neuromyelitis optica and MS optic neuropathies.
        Neurology. 2009; 73: 302-308
        • Ratchford J.N.
        • Saidha S.
        • Sotirchos E.S.
        • Oh J.A.
        • Seigo M.A.
        • Eckstein C.
        • Durbin M.K.
        • Oakley J.D.
        • Meyer S.A.
        • Conger A.
        • Frohman T.C.
        • Newsome S.D.
        • Balcer L.J.
        • Frohman E.M.
        • Calabresi P.A.
        Active MS is associated with accelerated retinal ganglion cell/inner plexiform layer thinning.
        Neurology. 2013; 80: 47-54
        • Ringelstein M.
        • Marius R.
        • Philipp A.
        • Martin S.
        • Jens H.
        • Ann-Kristin M.
        • Nazmiye K.
        • David F.
        • Stefano F.
        • Rainer G.
        • Alfons S.
        • Hans-Peter H.
        • Axel M.
        • Orhan A.
        Subtle retinal pathology in amyotrophic lateral sclerosis.
        Ann. Clin. Transl. Neurol. 2014; 1: 290-297
        • Roth N.M.
        • Shiv S.
        • Hanna Z.
        • Brandt A.U.
        • Justine I.
        • Agnieszka B.-R.
        • Matthias D.
        • Kühn A.A.
        • Thomas M.
        • Calabresi P.A.
        • Friedemann P.
        Photoreceptor layer thinning in idiopathic Parkinson's disease.
        Mov. Disord. 2014; 29: 1163-1170
        • Saidha S.
        • Syc S.B.
        • Ibrahim M.A.
        • Eckstein C.
        • Warner C.V.
        • Farrell S.K.
        • Oakley J.D.
        • Durbin M.K.
        • Meyer S.A.
        • Balcer L.J.
        • Frohman E.M.
        • Rosenzweig J.M.
        • Newsome S.D.
        • Ratchford J.N.
        • Nguyen Q.D.
        • Calabresi P.A.
        Primary retinal pathology in multiple sclerosis as detected by optical coherence tomography.
        Brain. 2011; 134: 518-533
        • Saidha S.
        • Sotirchos E.S.
        • Ibrahim M.A.
        • Crainiceanu C.M.
        • Gelfand J.M.
        • Sepah Y.J.
        • Ratchford J.N.
        • Oh J.
        • Seigo M.A.
        • Newsome S.D.
        • Balcer L.J.
        • Frohman E.M.
        • Green A.J.
        • Nguyen Q.D.
        • Calabresi P.A.
        Microcystic macular oedema, thickness of the inner nuclear layer of the retina, and disease characteristics in multiple sclerosis: a retrospective study.
        Lancet Neurol. 2012; 11: 963-972
        • Saidha S.
        • Shiv S.
        • Sotirchos E.S.
        • Jiwon O.
        • Syc S.B.
        • Seigo M.A.
        • Navid S.
        • Chistopher E.
        • Durbin M.K.
        • Oakley J.D.
        • Meyer S.A.
        • Frohman T.C.
        • Scott N.
        • Ratchford J.N.
        • Balcer L.J.
        • Pham D.L.
        • Crainiceanu C.M.
        • Frohman E.M.
        • Reich D.S.
        • Calabresi P.A.
        Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis.
        JAMA Neurol. 2013; 70: 34
        • Saidha S.
        • Al-Louzi O.
        • Ratchford J.N.
        • Bhargava P.
        • Oh J.
        • Newsome S.D.
        • Prince J.L.
        • Pham D.
        • Roy S.
        • van Zijl P.
        • Balcer L.J.
        • Frohman E.M.
        • Reich D.S.
        • Crainiceanu C.
        • Calabresi P.A.
        Optical coherence tomography reflects brain atrophy in MS: a four year study.
        Ann. Neurol. 2015; https://doi.org/10.1002/ana.24487
        • Sepulcre J.
        • Murie-Fernandez M.
        • Salinas-Alaman A.
        • García-Layana A.
        • Bejarano B.
        • Villoslada P.
        Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS.
        Neurology. 2007; 68: 1488-1494
        • Siger M.
        • Dziegielewski K.
        • Jasek L.
        • Bieniek M.
        • Nicpan A.
        • Nawrocki J.
        • Selmaj K.
        Optical coherence tomography in multiple sclerosis: thickness of the retinal nerve fiber layer as a potential measure of axonal loss and brain atrophy.
        J. Neurol. 2008; 255: 1555-1560
        • Syc S.B.
        • Warner C.V.
        • Hiremath G.S.
        • Farrell S.K.
        • Ratchford J.N.
        • Conger A.
        • Frohman T.
        • Cutter G.
        • Balcer L.J.
        • Frohman E.M.
        • Calabresi P.A.
        Reproducibility of high-resolution optical coherence tomography in multiple sclerosis.
        Mult. Scler. 2010; 16: 829-839
        • Syc S.B.
        • Saidha S.
        • Newsome S.D.
        • Ratchford J.N.
        • Levy M.
        • Ford E.
        • Crainiceanu C.M.
        • Durbin M.K.
        • Oakley J.D.
        • Meyer S.A.
        • Frohman E.M.
        • Calabresi P.A.
        Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis.
        Brain. 2012; 135: 521-533
        • Toledo J.
        • Sepulcre J.
        • Salinas-Alaman A.
        • García-Layana A.
        • Murie-Fernandez M.
        • Bejarano B.
        • Villoslada P.
        Retinal nerve fiber layer atrophy is associated with physical and cognitive disability in multiple sclerosis.
        Mult. Scler. 2008; 14: 906-912
        • Villoslada P.
        • Cuneo A.
        • Gelfand J.
        • Hauser S.L.
        • Green A.
        Color vision is strongly associated with retinal thinning in multiple sclerosis.
        Mult. Scler. 2012; 18: 991-999
        • Walter S.D.
        • Ishikawa H.
        • Galetta K.M.
        • Sakai R.E.
        • Feller D.J.
        • Henderson S.B.
        • Wilson J.A.
        • Maguire M.G.
        • Galetta S.L.
        • Frohman E.
        • Calabresi P.A.
        • Schuman J.S.
        • Balcer L.J.
        Ganglion cell loss in relation to visual disability in multiple sclerosis.
        Ophthalmology. 2012; 119: 1250-1257
        • Young K.L.
        • Brandt A.U.
        • Petzold A.
        • Reitz L.Y.
        • Lintze F.
        • Paul F.
        • Martin R.
        • Schippling S.
        Loss of retinal nerve fibre layer axons indicates white but not grey matter damage in early multiple sclerosis.
        Eur. J. Neurol. 2013; 20: 803-811
        • Zivadinov R.
        • Bergsland N.
        • Cappellani R.
        • Hagemeier J.
        • Melia R.
        • Carl E.
        • Dwyer M.G.
        • Lincoff N.
        • Weinstock-Guttman B.
        • Ramanathan M.
        Retinal nerve fiber layer thickness and thalamus pathology in multiple sclerosis patients.
        Eur. J. Neurol. 2014; 21 (1137–e61)