Can Optical Coherence Tomography Be Used to Guide Treatment Decisions in Adult or Pediatric Multiple Sclerosis?
Abstract
Purpose of review
With the recognition that neurodegeneration represents the principal substrate of disability in multiple sclerosis (MS), there has been increased strives towards identifying biomarkers for accurately quantifying and tracking neurodegeneration during the disease course. The retina provides an opportune “window” into the central nervous system (CNS) in MS, with retinal changes in MS reflecting not only local, but also global aspects of neurodegeneration and inflammation operative in the disease. Optical coherence tomography (OCT) is a rapid, inexpensive, reproducible, high-resolution imaging technique allowing accurate quantification of discrete retinal layers. OCT determined thinning of inner retinal layers such as the retinal nerve fiber layer (RNFL) and in particular the composite of the ganglion cell and inner plexiform (GCIP) layers, predominantly related to optic neuropathy, have been shown to not only correlate with high and low contrast visual function in MS, but also global MS disability scores, as well as whole brain and particularly gray matter volumes. Rates of GCIP thinning have been shown to be accelerated among MS patients exhibiting inflammatory activity outside of the visual pathways, as well as disability progression during follow-up. Moreover, baseline RNFL thickness in MS has been shown to have utility for predicting future disability accumulation. On the other hand, thickening of the inner nuclear layer (INL) in MS, the pathophysiologic basis of which remains to be elucidated, has been found to predict the development of clinical and radiological inflammatory activity, as well as subsequent disability progression in MS. Given the potential for OCT to provide insight into neurodegeneration and inflammation occurring in MS, this review focuses on the potential utility of OCT within the clinical setting to influence treatment decisions for MS patients.
Recent findings
The evolution of spectral domain-OCT technology, with improved resolution and reproducibility allowing intra-retinal layer segmentation, has facilitated the determination that the OCT derived measure GCIP thickness is a highly accurate measure for quantifying and tracking neurodegeneration, and conversely neuroprotection, in MS. The strong relationships between rates of GCIP and brain atrophy across MS subtypes over time underpin the insight derived regarding the global MS disease process from OCT and highlight OCT as an excellent complementary tool to magnetic resonance imaging (MRI) for tracking MS patients. More recently, longitudinal studies are emerging which support the utility of OCT for monitoring the differential effects of disease-modifying therapies (DMTs) in MS.
Summary
Although further work is required, there is mounting evidence supporting the utility of OCT in the clinical setting to monitor disease course in individual patients with MS and to aid in the prediction of disease course. As pharmacological treatment options in MS expand to also include potentially neuroprotective and/or remyelinating or neurorestorative drugs, OCT as a biomarker of neurodegeneration and neuroprotection (and neuroinflammation to a lesser degree) may become an invaluable tool in both the research and clinical settings.
Keywords
Multiple sclerosis Optical coherence tomography Disease modifying therapiesNotes
Compliance with Ethical Standards
Conflict of Interest
Jeffrey Lambe and Olwen Murphy declare no conflict of interest.
Shiv Saidha has received consulting fees from Medical Logix for the development of CME programs in neurology and served on scientific advisory boards for Biogen-Idec, Genzyme, Genentech Corporation, and EMD Serono & Novartis. He has received equity compensation for consulting from JuneBrain LLC, a retinal imaging device developer. He receives research support from Genentech Corporation and the National MS Society and received support from the Race to Erase MS foundation. He is a member of the working committee of the International Multiple Sclerosis Visual System (IMSVISUAL) Consortium.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372:1502–17.CrossRefPubMedGoogle Scholar
- 2.Fisniku LK, Chard DT, Jackson JS, Anderson VM, Altmann DR, Miszkiel KA, et al. Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol. 2008;64(3):247–54.CrossRefPubMedGoogle Scholar
- 3.•• Saidha S, Al-Louzi O, Ratchford JN, Bhargava P, Oh J, Newsome SD, et al. Optical coherence tomography reflects brain atrophy in multiple sclerosis: a four-year study. Ann Neurol. 2015;78(5):801–13. This study offers the strongest evidence of correlation between retinal and brain atrophy in multiple sclerosis (MS) patientsCrossRefPubMedPubMedCentralGoogle Scholar
- 4.Frohman EM, Fujimoto JG, Frohman TC, Calabresi PA, Cutter G, Balcer LJ. Optical coherence tomography: a window into the mechanisms of multiple sclerosis. Nat Clin Pract Neurol. 2008;4(12):664–75.CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Hrynchak P, Simpson T. Optical coherence tomography: an introduction to the technique and it use. Optom Vis Sci. 2000;77:347–56.CrossRefPubMedGoogle Scholar
- 6.Parisi V, Manni G, Spadaro M, Colacino G, Restuccia R, Marchi S, et al. Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest Ophthalmol Vis Sci. 1999;40:2520–7.PubMedGoogle Scholar
- 7.Saidha S, Syc SB, Ibrahim MA, Eckstein C, Warner CV, Farrell SK, et al. Primary retinal pathology in multiple sclerosis as detected by optical coherence tomography. Brain. 2011;134(Pt 2):518–33.CrossRefPubMedGoogle Scholar
- 8.Kale N. Optic neuritis as an early sign of multiple sclerosis. Eye Brain. 2016;8:195–202.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Toussaint D, Perier O, Verstappen A, Bervoets S. Clinicopathological study of the visual pathways, eyes, and cerebral hemispheres in 32 cases of disseminated sclerosis. J Clin Neuroophthalmol. 1983;3:211–20.CrossRefPubMedGoogle Scholar
- 10.Ikuta F, Zimmerman HM. Distribution of plaques in seventy autopsy cases of multiple sclerosis in the United States. Neurology. 1976;26(6 pt. 2):26–8.CrossRefPubMedGoogle Scholar
- 11.Shindler KS, Ventura E, Dutt M, Rostami A. Inflammatory demyelination induces axonal injury and retinal ganglion cell apoptosis in experimental optic neuritis. Exp Eye Res. 2008;87:208–13.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Green A, McQuaid S, Hauser SL, Allen IV, Lyness R. Ocular pathology in multiple sclerosis: retinal atrophy and inflammation irrespective of disease duration. Brain. 2010;133:1591–601.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Kerrison JB, Flynn T, Green WR. Retinal pathologic changes in multiple sclerosis. Retina. 1994;14:445–51.CrossRefPubMedGoogle Scholar
- 14.Ratchford JN, Saidha S, Sotirchos ES, Oh J, Seigo MA, Eckstein C, et al. Active MS is associated with accelerated retinal ganglion cell/inner plexiform layer thinning. Neurology. 2013;80:47–54.CrossRefPubMedPubMedCentralGoogle Scholar
- 15.• Talman LS, Bisker ER, Sackel DJ, Long DA, Galetta KM, Ratchford JN, et al. Longitudinal study of vision and retinal nerve fiber layer thickness in MS. Ann Neurol. 2010;67:749–60. This study provided evidence for the correlation between retinal nerve fiber layer (RNFL) reduction and visual loss over time in multiple sclerosisPubMedPubMedCentralGoogle Scholar
- 16.Syc SB, Saidha S, Newsome SD, Ratchford JN, Levy M, Ford E, et al. Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis. Brain. 2012;135(pt 2):521–33.CrossRefPubMedGoogle Scholar
- 17.• Saidha S, Syc SB, Durbin MK, Eckstein C, Oakley JD, Meyer SA, et al. Visual dysfunction in multiple sclerosis correlates better with optical coherence tomography derived estimates of macular ganglion cell layer thickness than peripapillary retinal nerve fiber layer thickness. Mult Scler. 2011;17:1449–63. This study was among the first to suggest superiority of ganglion cell and inner plexiform layer (GCIP) over RNFL with regard to structure-function relationships with visual function and disability in MSCrossRefPubMedGoogle Scholar
- 18.Syc SB, Warner CV, Hiremath GS, Farrell SK, Ratchford JN, Conger A, et al. Reproducibility of high-resolution optical coherence tomography in multiple sclerosis. Mult Scler. 2010;16:829–39.CrossRefPubMedGoogle Scholar
- 19.Toledo J, Sepulcre J, Salinas-Alaman A, García-Layana A, Murie-Fernandez M, Bejarano B, et al. Retinal nerve fiber layer atrophy is associated with physical and cognitive disability in multiple sclerosis. Mult Scler. 2008;14:906–12.CrossRefPubMedGoogle Scholar
- 20.Gordon-Lipkin E, Chodkowski B, Reich DS, Smith SA, Pulicken M, Balcer LJ, et al. Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology. 2007;69:1603–9.CrossRefPubMedGoogle Scholar
- 21.•• Martinez-Lapiscina EH, Arnow S, Wilson JA, Saidha S, Preiningerova JL, Oberwahrenbrock T, et al. Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study. Lancet Neurol. 2016;15:574–84. This study provides the strongest evidence to date to support the utility of OCT in predicting disability progression in MSCrossRefPubMedGoogle Scholar
- 22.Bhargava P, Calabresi PA. The expanding spectrum of aetiologies causing retinal microcystic macular change. Brain. 2013;136(11):3212–4.CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Al-Louzi OA, Bhargava P, Newsome SD, Balcer LJ, Frohman EM, Crainiceanu C, et al. Outer retinal changes following acute optic neuritis. Mult Scler. 2016;22:362–72.CrossRefPubMedGoogle Scholar
- 24.• Gelfand JM, Nolan R, Schwartz DM, Graves J, Green AJ. Microcystic macular oedema in multiple sclerosis is associated with disease severity. Brain. 2012;135:1786–93. This study was the first to demonstrate microcystic macular changes in multiple sclerosis, as well as identify a correlation between these changes and increased risk of disability progressionCrossRefPubMedPubMedCentralGoogle Scholar
- 25.• Saidha S, Sotirchos ES, Ibrahim MA, Crainiceanu CM, Gelfand JM, Sepah YJ, et al. Relationship of the inner nuclear layer of the retina with clinicoradiologic disease characteristics in multiple sclerosis: a retrospective study. Lancet Neurol. 2012;11(11):963–72. This study demonstrates high correlation between inner nuclear layer thickness/volume and inflammatory activity in MSCrossRefPubMedPubMedCentralGoogle Scholar
- 26.• Gabilondo I, Martinez-Lapiscina EH, Fraga-Pumar E, Ortiz-Perez S, Torres-Torres R, Andorra M, et al. Dynamics of retinal injury after acute optic neuritis. Ann Neurol. 2015;77:517–28. Evidence from this study supports the potential role of trans-synaptic neurodegeneration in MSCrossRefPubMedGoogle Scholar
- 27.Kaushik M, Wang CY, Barnett MH, Garrick R, Parratt J, Graham SL, et al. Inner nuclear layer thickening is inversely proportional to retinal ganglion cell loss in optic neuritis. PLoS One. 2013;8(10):e78341.CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Costello F, Van Stavern GP. Should optical coherence tomography be used to manage patients with multiple sclerosis? J Neuro-Ophthalmol. 2012;32:363–71.CrossRefGoogle Scholar
- 29.Saidha S, Calabresi PA. Optical coherence tomography should be part of the routine monitoring of patients with multiple sclerosis: yes. Mult Scler. 2014;20(10):1296–8.CrossRefPubMedGoogle Scholar
- 30.Jenkins TM, Toosy AT. Optical coherence tomography should be part of the routine monitoring of patients with multiple sclerosis: no. Mult Scler. 2014;20(10):1299–301.CrossRefPubMedGoogle Scholar
- 31.Sakai RE, Feller DJ, Galetta SL, Balcer LJ. Vision in multiple sclerosis: the story, structure-functional correlations, and models for neuroprotection. J Neuroophthalmol. 2011;31:362–73.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.• Costello F, Coupland S, Hodge W, Lorello GR, Koroluk J, Pan YI, et al. Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol. 2006;59(6):963–9. This study is the first to demonstrate a threshold of RNFL thickness, below which measurements predicted residual visual dysfunction following an episode of acute optic neuritisCrossRefPubMedGoogle Scholar
- 33.Serbecic N, Aboul-Enein F, Beutelspacher SC, et al. High-resolution spectral domain-optical coherence tomography in multiple sclerosis, part II—the total macular volume. The first follow-up study over 2 years. Frontiers in Neurology. 2014;5:20.CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Balk LJ, Cruz-Herranz A, Albrecht P, Arnow S, Gelfand JM, Tewarie P, et al. Timing of retinal neuronal and axonal loss in MS: a longitudinal OCT study. J Neurol. 2016 Jul;263(7):1323–31.Google Scholar
- 35.Galetta KM, Graves J, Talman LS, Lile DJ, Frohman EM, Calabresi PA, et al. Visual pathway axonal loss in benign multiple sclerosis: a longitudinal study. J Neuroophthalmol. 2012;32(2):116–23.CrossRefPubMedPubMedCentralGoogle Scholar
- 36.Balk LJ, Tewarie P, Killestein J, Polman CH, Uitdehaag BMJ, Petzold A. Disease course heterogeneity and OCT in multiple sclerosis. Mult Scler. 2014;20(9):1198–206.CrossRefPubMedGoogle Scholar
- 37.Huang-Link YM, Fredrikson M, Link H. Benign multiple sclerosis is associated with reduced thinning of the retinal nerve fiber and ganglion cell layers in non-optic-neuritis eyes. J Clin Neurol. 2015;11(3):241–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 38.Knier B, Berthele A, Buck D, Schmidt P, Zimmer C, Mühlau M, et al. Optical coherence tomography indicates disease activity prior to clinical onset of central nervous system demyelination. Mult Scler. 2016;22(7):893–900.CrossRefPubMedGoogle Scholar
- 39.Gelfand JM, Goodin DS, Boscardin WJ, Nolan R, Cuneo A, Green AJ. Retinal axonal loss begins early in the course of multiple sclerosis and is similar between progressive phenotypes. PLoS One. 2012;7(5):e36847.CrossRefPubMedPubMedCentralGoogle Scholar
- 40.• Oberwahrenbrock T, Ringelstein M, Jentschke S, Deuschle K, Klumbies K, Bellmann-Strobl J, et al. Retinal ganglion cell and inner plexiform layer thinning in clinically isolated syndrome. Mult Scler. 2013;19(14):1887–95. This study supports the utility of GCIP measures in detecting retinal pathology in non-optic neuritis clinically isolated syndromeCrossRefPubMedGoogle Scholar
- 41.Outteryck O, Zephir H, Defoort S, Bouyon M, Debruyne P, Bouacha I, et al. Optical coherence tomography in clinically isolated syndrome: no evidence of subclinical retinal axonal loss. Arch Neurol. 2009;66:1373–7.CrossRefPubMedGoogle Scholar
- 42.Britze J, Pihl-Jensen G, Frederiksen JL. Retinal ganglion cell analysis in multiple sclerosis and optic neuritis: a systematic review and meta-analysis. J Neurology. 2017; [epub ahead of print]Google Scholar
- 43.Ratchford JN, Quigg ME, Conger A, Frohman T, Frohman E, Balcor LJ. Optical coherence tomography helps differentiate neuromyelitis optica and MS optic neuropathies. Neurology. 2009;73:302–8.CrossRefPubMedPubMedCentralGoogle Scholar
- 44.• Gabilondo I, Martínez-Lapiscina EH, Martínez-Heras E, Fraga-Pumar E, Llufriu S, Ortiz S, et al. Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. Ann Neurol. 2014;75:98–107. Evidence from this study supports the potential role of trans-synaptic neurodegeneration in MSCrossRefPubMedGoogle Scholar
- 45.Oh J, Sotirchos ES, Saidha S, Whetstone A, Chen M, Newsome SD, et al. Relationships between quantitative spinal cord MRI and retinal layers in multiple sclerosis. Neurology. 2015;84(7):720–8.CrossRefPubMedPubMedCentralGoogle Scholar
- 46.Saidha S, Sotirchos ES, Oh J, Syc SB, Seigo MA, Shiee N, et al. Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis. JAMA Neurol. 2013;70:34–43.CrossRefPubMedPubMedCentralGoogle Scholar
- 47.• Zimmermann H, Freing A, Kaufhold F, Gaede G, Bohn E, Bock M, et al. Optic neuritis interferes with optical coherence tomography and magnetic resonance imaging correlations. Mult Scler. 2013;19:443–50. This study suggests disproportionate localized retinal tissue damage following acute optic neuritis in MS as evidenced by altered correlations between retinal measures and global relationshipsCrossRefPubMedGoogle Scholar
- 48.Chilińska A, Ejma M, Turno-Kręcicka A, Guranski K, Misiuk-Hojlo M. Analysis of retinal nerve fibre layer, visual evoked potentials and relative afferent pupillary defect in multiple sclerosis patients. Clin Neurophysiol. 2016;127(1):821–6.CrossRefPubMedGoogle Scholar
- 49.Pul R, Saadat M, Morbiducci F, Skripuletz T, Pul Ü, Brockmann D, et al. Longitudinal time-domain optic coherence study of retinal nerve fiber layer in IFNβ-treated and untreated multiple sclerosis patients. Exp Ther Med. 2016;12(1):190–200.CrossRefPubMedPubMedCentralGoogle Scholar
- 50.Garcia-Martin E, Pueyo V, Fernandez J, Martin J, Ara JR, Almarcegui C, et al. Effect of treatment in loss of retinal nerve fiber layer in multiple sclerosis patients. Arch Soc Esp Oftalmol. 2010;85(6):209–14.CrossRefPubMedGoogle Scholar
- 51.Knier B, Schmidt P, Aly L, Buck D, Berthele A, Muhlau M, et al. Retinal inner nuclear layer volume reflects response to immunotherapy in multiple sclerosis. Brain. 2016;139(11):2855–63.CrossRefPubMedGoogle Scholar
- 52.•• Button J, Al-Louzi O, Lang A, Bhargava P, Newsome SD, Frohman T, et al. Disease-modifying therapies modulate retinal atrophy in multiple sclerosis: a retrospective study. Neurology. 2017;88(6):525–32. This study is among the first to longitudinally demonstrate the potential role of OCT in monitoring response to disease modifying therapies in multiple sclerosisCrossRefPubMedPubMedCentralGoogle Scholar
- 53.Raza A, Mittal S, Sood GK. Interferon-associated retinopathy during the treatment of chronic hepatitis C: a systematic review. J Viral Hepat. 2013 Sep;20(9):593–9.Google Scholar
- 54.Gaetani L, Menduno PS, Cometa F, Di Gregorio M, Sarchielli P, Cagini C, et al. Retinopathy during interferon-β treatment for multiple sclerosis: case report and review of the literature. J Neurol. 2016;263(3):422–7.CrossRefPubMedGoogle Scholar
- 55.Talmage GD, Coppes OJM, Javed A, Bernard J. Natalizumab stabilizes physical, cognitive, MRI, and OCT markers of disease activity: a prospective, non-randomized pilot study. PLoS One 2017:12(4):e0173299.Google Scholar
- 56.Kal A, Oğuz Ulusoy M, Horasanlı B, Cezairlioğlu Ş, Kal Ö. Effect of fingolimod (FTY720) on choroidal thickness in patients with multiple sclerosis. Mult Scler Relat Disord. 2017;14:4–7.CrossRefPubMedGoogle Scholar
- 57.• Nolan R, Gelfand JM, Green AJ. Fingolimod treatment in multiple sclerosis leads to increased macular volume. Neurology. 2013;80(2):139–44. This study demonstrates a correlation between macular volume and initiation of fingolimod therapy in MSCrossRefPubMedPubMedCentralGoogle Scholar
- 58.Zarbin MA, Jampol LM, Jager RD, Reder TR, Francis G, Collins W, et al. Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis. Ophthalmology. 2013;120(7):1432–9.CrossRefPubMedGoogle Scholar
- 59.Kappos L, Radue EW, O’Connor P, Polman C, Hohlfeld R, Calabresi P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387–401.CrossRefPubMedGoogle Scholar
- 60.Nguyen AL, Lam J, White R, Carruthers R, Traboulsee A. Prospective study of retinal nerve fibre layer thickness in alemtuzumab treated multiple sclerosis patients. Neurology. 2016;86:16. supp P3.083Google Scholar
- 61.Cruz-Herranz A, Balk LJ, Oberwahrenbrock T, Saidha S, Martínez-Lapiscina EH, Lagreze WA, et al. The APOSTEL recommendations for reporting quantitative optical coherence tomography studies. Neurology. 2016;86(24):2303–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 62.Costello F. Evaluating the use of optical coherence tomography in optic neuritis. Mult Scler Int. 2011;2011:148394.PubMedPubMedCentralGoogle Scholar
- 63.Lange AP, Sadjadi R, Saeedi J, Lindley J, Costello F, Traboulsee AL. Time-domain and spectral-domain optical coherence tomography of retinal nerve fiber layer in MS patients and healthy controls. J Ophthalmol. 2012;2012:564627.PubMedPubMedCentralGoogle Scholar
- 64.Watson GM, Keltner JL, Chin EK, Harvey D, Nguyen A, Park SS. Comparison of retinal nerve fiber layer and central macular thickness measurements among five different optical coherence tomography instruments in patients with multiple sclerosis and optic neuritis. J Neuroophthalmol. 2011;31(2):111–6.CrossRefGoogle Scholar
- 65.• Warner CV, Syc SB, Stankiewicz AM, Hiremath G, Farrell SK, Crainiceanu CM, et al. The impact of utilizing different optical coherence tomography devices for clinical purposes and in multiple sclerosis trials. PLoS One. 2011;6(8):e22947. This study demonstrated poor levels of agreement between different OCT machines at an individual level, limiting their interchangeability in a clinical settingCrossRefPubMedPubMedCentralGoogle Scholar
- 66.Rebolleda G, González-López JJ, Muñoz-Negrete FJ, Oblanca N, Costa-Frossard L, Álvarez-Cermeño JC. Color-code agreement among stratus, cirrus, and spectralis optical coherence tomography in relapsing-remitting multiple sclerosis with and without prior optic neuritis. Am J Ophthalmol. 2013;155:890–7.CrossRefPubMedGoogle Scholar
- 67.Oliveira C, Cestari DM, Rizzo JF 3rd. The use of fourth generation optical coherence tomography in multiple sclerosis: a review. Semin Ophthalmol. 2012;27(5–6):187–91.CrossRefPubMedGoogle Scholar
- 68.Seigo MA, Sotirchos ES, Newsome S, Babiarz A, Eckstein C, Ford E, et al. In vivo assessment of retinal neuronal layers in multiple sclerosis with manual and automated optical coherence tomography segmentation techniques. J Neurol. 2012;259(10):2119–30.CrossRefPubMedGoogle Scholar
- 69.Lang A, Carass A, Hauser M, et al. Retinal layer segmentation of macular OCT images using boundary classification. Biomedical Optics Express. 2013;4(7):1133–52.CrossRefPubMedPubMedCentralGoogle Scholar
- 70.Bhargava P, Lang A, Al-Louzi O, Carass A, Prince J, Calabresi PA, et al. Applying an open-source segmentation algorithm to different OCT devices in multiple sclerosis patients and healthy controls: implications for clinical trials. Mult Scler Int. 2015;136295Google Scholar
- 71.Lang A, Carass A, Al-Louzi O, Bhargava P, Ying HS, Calabresi PA, et al. Longitudinal graph-based segmentation of macular OCT using fundus alignment. Proc SPIE Int Soc Opt Eng. 2015;9413:94130 M.Google Scholar
- 72.Schippling S, Balk LJ, Costello F, Albrecht P, Balcer L, Calabresi PA, et al. Quality control for retinal OCT in multiple sclerosis: validation of the OSCAR-IB criteria. Mult Scler. 2015;21(2):163–70.CrossRefPubMedGoogle Scholar
- 73.Lang A, Carass A, Al-Louzi O, Bhargava P, Solomon SD, Calabresi PA, et al. Combined registration and motion correction of longitudinal retinal OCT data. Proc SPIE Int Soc Opt Eng. 2016;9784Google Scholar
- 74.Chauhan DS, Marshall J. The interpretation of optic coherence tomography images of the retina. Invest Ophthalmol Vis Sci. 1999;40:2332–42.PubMedGoogle Scholar
- 75.Balk LJ, Cruz-Herranz A, Albrecht P, Arnow S, Gelfand JM, Tewarie P, et al. Timing of retinal neuronal and axonal loss in MS: a longitudinal OCT study. J Neurol. 2016;263:1323–31.CrossRefPubMedPubMedCentralGoogle Scholar
- 76.Antony BJ, Chen M, Carass A, Jedynak BM, Al-Louzi O, Solomon SD, et al. Voxel based morphometry in optical coherence tomography: validation & core findings. Proc SPIE Int Soc Opt Eng. 2016;27:9788.Google Scholar
- 77.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(1):162–7.CrossRefPubMedGoogle Scholar
- 78.Roth NM, Saidha S, Zimmermann H, Brandt AU, Isensee J, Benkhellouf-Rutkowska A, et al. Photoreceptor layer thinning in idiopathic Parkinson’s disease. Mov Disord 2014:29(9):1163–1170.Google Scholar
- 79.Ringelstein M, Albrecht P, Südmeyer M, Harmel J, Müller AK, Keser N. Subtle retinal pathology in amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2014;1(4):290–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 80.•• Huhn K, Lammer R, Oberwahrenbrock T, Lammer A, Waschbisch A, Gosar D, et al. Optical coherence tomography in patients with a history of juvenile multiple sclerosis reveals early retinal damage. Eur J Neurol. 2015;22(1):86–92. This study demonstrates retinal layer thinning in early stages of pediatric MS.CrossRefPubMedGoogle Scholar
- 81.Renoux C, Vukusic S, Mikaeloff M, Edan G, Clanet M, Dubois B, et al. Natural history of multiple sclerosis with childhood onset. N Engl J Med. 2007;356:2603–13.CrossRefPubMedGoogle Scholar
- 82.Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol. 2009;66:54–9.CrossRefPubMedGoogle Scholar
- 83.Chou IJ, Whitehouse WP, Wang HS, Tanasescu R, Constantinescu CS. Diagnostic modalities in multiple sclerosis: perspectives in children. Biomed J. 2014;37(2):50–9.CrossRefPubMedGoogle Scholar
- 84.Fay AJ, Mowry EM, Strober J, Waubant E. Relapse severity and recovery in early pediatric multiple sclerosis. Mult Scler. 2012;18(7):1008–12.CrossRefPubMedGoogle Scholar
- 85.Huppke B, Ellenberger D, Rosewich H, Friede T, Gärtner J, Huppke P. Clinical presentation of pediatric multiple sclerosis before puberty. Eur J Neurol. 2014;21(3):441–6.CrossRefPubMedGoogle Scholar
- 86.O’Mahony J, Marrie RA, Laporte A, Yeh EA, Bar-Or A, Phan C, et al. Recovery from central nervous system acute demyelination in children. Pediatrics. 2015;136(1):e115–23.CrossRefPubMedGoogle Scholar
- 87.Ghezzi A. Randomized control trials (RCTs) in pediatric multiple sclerosis: are they really necessary? Mult Scler 2017:23(7):1042–1043.Google Scholar
- 88.Rose K, Muller T. Children with multiple sclerosis should not become therapeutic hostages. Ther Adv Neurol Disord. 2016;9(5):389–95.CrossRefPubMedPubMedCentralGoogle Scholar
- 89.Avery RA, Rajjoub RD, Trimboli-Heidler C, Waldman AT. Applications of optical coherence tomography in pediatric clinical neuroscience. Neuropediatrics. 2015;46(2):88–97.CrossRefPubMedPubMedCentralGoogle Scholar
- 90.Pena JA, Lotze TE. Pediatric multiple sclerosis: current concepts and consensus definitions. Autoimmune Dis. 2013;2013:673947.PubMedPubMedCentralGoogle Scholar
- 91.Yeh EA, Weinstock-Guttman B, Lincoff N, Reynolds J, Weinstock A, Madurai N, et al. Retinal nerve fiber thickness in inflammatory demyelinating diseases of childhood onset. Mult Scler. 2009;15(7):802–10.CrossRefPubMedGoogle Scholar
- 92.Yilmaz U, Gucuyener K, Erin DM, Yazar Z, Gurkas E, Serdaroglu A, et al. Reduced retinal nerve fiber layer thickness and macular volume in pediatric multiple sclerosis. J Child Neurol. 2012;27:1517–23.CrossRefPubMedGoogle Scholar
- 93.• Graves JS, Chohan H, Cedars B, Arnow S, Yiu H, Waubant E, et al. Sex differences and subclinical retinal injury in pediatric-onset MS. Mult Scler. 2017;23(3):447–55. This study demonstrated higher retinal layer atrophy in the eyes of pediatric MS patients with a prior history of optic neuritis than those without a history of optic neuritisCrossRefPubMedGoogle Scholar
- 94.Kerbrat A, Aubert-Broche B, Fonov V, Narayanan S, Sled JG, Arnold DA, et al. Reduced head and brain size for age and disproportionately smaller thalami in child-onset MS. Neurology. 2012;78:194–201.CrossRefPubMedGoogle Scholar
- 95.Calabrese M, Seppi D, Romualdi C, Rinaldi F, Alessio S, Perini P, et al. Gray matter pathology in MS: a 3-year longitudinal study in a pediatric population. AJNR Am J Neuroradiol. 2012;33(8):1507–11.CrossRefPubMedGoogle Scholar
- 96.Rauscher FM, Sekhon N, Feuer WJ, Budenz DL. Myopia affects retinal nerve fiber layer measurements as determined by optical coherence tomography. J Glaucoma. 2009;18(7):501–5.CrossRefPubMedPubMedCentralGoogle Scholar
- 97.Zha Y, Zhuang J, Lin D, Feng W, Zheng H, Cai J. Evaluation of myopia on retinal nerve fiber layer thickness measured by Spectralis optical coherence tomography. Exp Ther Med. 2017;14(3):2716–20.CrossRefPubMedPubMedCentralGoogle Scholar