545144
research-article2014
MSJ0010.1177/1352458514545144Multiple Sclerosis JournalHutchinson
MULTIPLE SCLEROSIS MSJ JOURNAL
Controversies in Multiple Sclerosis
Optical coherence tomography should be part of the routine monitoring of patients with multiple sclerosis: Commentary
Multiple Sclerosis Journal 2014, Vol. 20(10) 1302–1303 DOI: 10.1177/ 1352458514545144 © The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Michael Hutchinson
There is no doubt that optical coherence tomography (OCT) has been an extremely exciting development for medicine and for multiple sclerosis (MS). The value of OCT as a diagnostic tool has been demonstrated and it has been to shown to identify patients with highly active disease (but magnetic resonance imaging (MRI) does both better). Its possible use as an instrument to measure neurodegeneration over time is perhaps the application most welcome to MS neurologists. Readers are directed to a systematic review of OCT1 and a discussion of the potential and the problems associated with OCT by Green.2 An important publication by the latter author was his work with Ingrid Allen (Multiple Sclerosis Journal’s first editor) and Stephen Hauser on the MS retinae from the Belfast MS brain bank; a detailed exploration of eye pathology in MS which is essential reading for understanding this disease.3 In this debate the antagonists, Jenkins and Toosy, among other criticisms, take the view that because there is no treatment available for the MS neurodegenerative process, there is no point in using OCT as a routine measure in the clinic. The protagonists, Saidha and Calabresi, have published widely on the subject and are highly enthusiastic about the application of OCT. It was surprising to learn that measures of retinal nerve fibre layer (RNFL) thinning correlated so widely with atrophy in both white matter and deep grey matter structures as assessed by MRI.4 However, the variation in reported OCT abnormalities in patients with primary progressive multiple sclerosis (PPMS) is worrying. Groups in California5 and Baltimore, USA6 reported that the degree of RNFL thinning was severe and indistinguishable between PPMS and secondary progressive MS (SPMS), whereas a Dutch group7 found less thinning in patients with PPMS than in patients with SPMS or relapsing–remitting MS. The problem is that we need more longitudinal studies over some years of the
retinal–brain atrophy relationship; before OCT is applied routinely in every MS centre as a surrogate measure of brain atrophy, we need more data. OCT illuminates a mechanism of neurodegeneration in MS The surprising finding, that RNFL thinning correlates so widely with atrophy in such disparate structures as the cerebellum and deep grey matter has, as yet, to be definitely explained. Using OCT as a research tool, recent studies from three separate laboratories have demonstrated that the phenomenon of trans-synaptic degeneration in the visual pathway (both anterograde and retrograde) is a significant degenerative process in MS.8–10 RNFL thinning was found to relate to the demyelinating lesion load in the optic radiation and to reduced diffusivity in the geniculate-cortical visual pathway (illustrating retrograde trans-synaptic degeneration).8–10 Anterograde trans-synaptic degeneration was demonstrated by finding that patients with a severe prior optic neuritis had reduced visual cortical volume.8 While one accepts that in one functional system (visual), this is an important mechanism of neurodegeneration, it is likely that the reported relationship between RNFL thinning and atrophy in nonanatomically related structures, such as the caudate,4 is simply that the severity of disease affecting the optic radiation is mirrored by disease severity elsewhere in the cerebral hemispheres.
Correspondence to: Michael Hutchinson St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. [email protected] Michael Hutchinson St Vincent’s University Hospital, Dublin, Ireland
To conclude I side with Jenkins and Toosy; before we can promote OCT in the clinic as a tool to assess cerebral atrophy we need more evidence. In particular, we need more longitudinal studies demonstrating correlations with MRI measures over a number of years. We also need to determine uniform methods of assessment and reporting OCT; recent papers from a consensus group,
1302 http://msj.sagepub.com
Hutchinson validating such criteria, is a step in this direction.11,12 The report from Peter Calabresi’s lab that OCT measures need to be corrected for intracranial volume4 (and also for eye length?2) indicates that this technique is still in research development; it would be premature to suggest that MS clinical centres should take it up routinely as a surrogate measure of cerebral atrophy. Conflict of interest Michael Hutchinson served on a medical advisory board for the CONFIRM study [BG00012] for Biogen Idec, serves on the editorial board of the Multiple Sclerosis Journal, has received speaker’s honoraria from Merck-Serono, Novartis, Biogen Idec and Bayer-Schering and receives research support from Dystonia Ireland, the Health Research Board of Ireland and the Foundation for Dystonia Research.
References 1. Petzold A, de Boer JF, Schippling S, et al. Optical coherence tomography in multiple sclerosis: A systematic review and meta-analysis. Lancet Neurol 2010; 9: 921–932. 2. Green AJ. Getting beyond the ganglion cell: Morphometric adjustments for retinal optical coherence tomography in multiple sclerosis. JAMA Neurol 2013; 70: 13–15. 3. Green AJ, McQuaid S, Hauser SL, et al. Ocular pathology in multiple sclerosis: Retinal atrophy and inflammation irrespective of disease duration. Brain 2010; 133: 1591–1601. 4. Saidha S, Sotirchos ES, Oh J, et al. Relationships between retinal axonal and neuronal measures and
global central nervous system pathology in multiple sclerosis. JAMA Neurol 2013; 70: 34–43. 5. Gelfand JM, Goodin DS, Boscardin WJ, et al. Retinal axonal loss begins early in the course of multiple sclerosis and is similar between progressive phenotypes. PLoS One 2012; 7: e36847. 6. Pulicken M, Gordon-Lipkin E, Balcer LJ, et al. Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 2007; 69: 2085–2092. 7. Balk L, Tewarie P, Killestein J, et al. Disease course heterogeneity and OCT in multiple sclerosis. Mult Scler J 2014 Jan 8. [Epub ahead of print]. 8. Gabilondo I, Martínez-Lapiscina EH, Martínez-Heras E, et al. Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. Ann Neurol 2014; 75: 98–107. 9. Klistorner A, Sriram P, Vootakuru N, et al. Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions. Neurology 2014; 82: 2165–2172. 10. Balk LJ, Steenwijk MD, Tewarie P, et al. Bidirectional trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. J Neurol Neurosurg Psychiatry 2014; Jun 27. pii: jnnp-2014308189. doi: 10.1136/jnnp-2014-308189. [Epub ahead of print]. 11. Tewarie P, Balk L, Costello F, et al. The OSCAR-IB consensus criteria for retinal OCT quality assessment. PLoS One 2012; 7: e34823. 12. Schippling S, Balk L, Costello F, et al. Quality control for retinal OCT in multiple sclerosis: Validation of the OSCAR-IB criteria. Mult Scler J 2014; Jun 16. pii: 1352458514538110. [Epub ahead of print].
Visit SAGE journals online http://msj.sagepub.com
SAGE journals
http://msj.sagepub.com 1303
research-article2014
MSJ0010.1177/1352458514545144Multiple Sclerosis JournalHutchinson
MULTIPLE SCLEROSIS MSJ JOURNAL
Controversies in Multiple Sclerosis
Optical coherence tomography should be part of the routine monitoring of patients with multiple sclerosis: Commentary
Multiple Sclerosis Journal 2014, Vol. 20(10) 1302–1303 DOI: 10.1177/ 1352458514545144 © The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Michael Hutchinson
There is no doubt that optical coherence tomography (OCT) has been an extremely exciting development for medicine and for multiple sclerosis (MS). The value of OCT as a diagnostic tool has been demonstrated and it has been to shown to identify patients with highly active disease (but magnetic resonance imaging (MRI) does both better). Its possible use as an instrument to measure neurodegeneration over time is perhaps the application most welcome to MS neurologists. Readers are directed to a systematic review of OCT1 and a discussion of the potential and the problems associated with OCT by Green.2 An important publication by the latter author was his work with Ingrid Allen (Multiple Sclerosis Journal’s first editor) and Stephen Hauser on the MS retinae from the Belfast MS brain bank; a detailed exploration of eye pathology in MS which is essential reading for understanding this disease.3 In this debate the antagonists, Jenkins and Toosy, among other criticisms, take the view that because there is no treatment available for the MS neurodegenerative process, there is no point in using OCT as a routine measure in the clinic. The protagonists, Saidha and Calabresi, have published widely on the subject and are highly enthusiastic about the application of OCT. It was surprising to learn that measures of retinal nerve fibre layer (RNFL) thinning correlated so widely with atrophy in both white matter and deep grey matter structures as assessed by MRI.4 However, the variation in reported OCT abnormalities in patients with primary progressive multiple sclerosis (PPMS) is worrying. Groups in California5 and Baltimore, USA6 reported that the degree of RNFL thinning was severe and indistinguishable between PPMS and secondary progressive MS (SPMS), whereas a Dutch group7 found less thinning in patients with PPMS than in patients with SPMS or relapsing–remitting MS. The problem is that we need more longitudinal studies over some years of the
retinal–brain atrophy relationship; before OCT is applied routinely in every MS centre as a surrogate measure of brain atrophy, we need more data. OCT illuminates a mechanism of neurodegeneration in MS The surprising finding, that RNFL thinning correlates so widely with atrophy in such disparate structures as the cerebellum and deep grey matter has, as yet, to be definitely explained. Using OCT as a research tool, recent studies from three separate laboratories have demonstrated that the phenomenon of trans-synaptic degeneration in the visual pathway (both anterograde and retrograde) is a significant degenerative process in MS.8–10 RNFL thinning was found to relate to the demyelinating lesion load in the optic radiation and to reduced diffusivity in the geniculate-cortical visual pathway (illustrating retrograde trans-synaptic degeneration).8–10 Anterograde trans-synaptic degeneration was demonstrated by finding that patients with a severe prior optic neuritis had reduced visual cortical volume.8 While one accepts that in one functional system (visual), this is an important mechanism of neurodegeneration, it is likely that the reported relationship between RNFL thinning and atrophy in nonanatomically related structures, such as the caudate,4 is simply that the severity of disease affecting the optic radiation is mirrored by disease severity elsewhere in the cerebral hemispheres.
Correspondence to: Michael Hutchinson St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. [email protected] Michael Hutchinson St Vincent’s University Hospital, Dublin, Ireland
To conclude I side with Jenkins and Toosy; before we can promote OCT in the clinic as a tool to assess cerebral atrophy we need more evidence. In particular, we need more longitudinal studies demonstrating correlations with MRI measures over a number of years. We also need to determine uniform methods of assessment and reporting OCT; recent papers from a consensus group,
1302 http://msj.sagepub.com
Hutchinson validating such criteria, is a step in this direction.11,12 The report from Peter Calabresi’s lab that OCT measures need to be corrected for intracranial volume4 (and also for eye length?2) indicates that this technique is still in research development; it would be premature to suggest that MS clinical centres should take it up routinely as a surrogate measure of cerebral atrophy. Conflict of interest Michael Hutchinson served on a medical advisory board for the CONFIRM study [BG00012] for Biogen Idec, serves on the editorial board of the Multiple Sclerosis Journal, has received speaker’s honoraria from Merck-Serono, Novartis, Biogen Idec and Bayer-Schering and receives research support from Dystonia Ireland, the Health Research Board of Ireland and the Foundation for Dystonia Research.
References 1. Petzold A, de Boer JF, Schippling S, et al. Optical coherence tomography in multiple sclerosis: A systematic review and meta-analysis. Lancet Neurol 2010; 9: 921–932. 2. Green AJ. Getting beyond the ganglion cell: Morphometric adjustments for retinal optical coherence tomography in multiple sclerosis. JAMA Neurol 2013; 70: 13–15. 3. Green AJ, McQuaid S, Hauser SL, et al. Ocular pathology in multiple sclerosis: Retinal atrophy and inflammation irrespective of disease duration. Brain 2010; 133: 1591–1601. 4. Saidha S, Sotirchos ES, Oh J, et al. Relationships between retinal axonal and neuronal measures and
global central nervous system pathology in multiple sclerosis. JAMA Neurol 2013; 70: 34–43. 5. Gelfand JM, Goodin DS, Boscardin WJ, et al. Retinal axonal loss begins early in the course of multiple sclerosis and is similar between progressive phenotypes. PLoS One 2012; 7: e36847. 6. Pulicken M, Gordon-Lipkin E, Balcer LJ, et al. Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 2007; 69: 2085–2092. 7. Balk L, Tewarie P, Killestein J, et al. Disease course heterogeneity and OCT in multiple sclerosis. Mult Scler J 2014 Jan 8. [Epub ahead of print]. 8. Gabilondo I, Martínez-Lapiscina EH, Martínez-Heras E, et al. Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. Ann Neurol 2014; 75: 98–107. 9. Klistorner A, Sriram P, Vootakuru N, et al. Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions. Neurology 2014; 82: 2165–2172. 10. Balk LJ, Steenwijk MD, Tewarie P, et al. Bidirectional trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. J Neurol Neurosurg Psychiatry 2014; Jun 27. pii: jnnp-2014308189. doi: 10.1136/jnnp-2014-308189. [Epub ahead of print]. 11. Tewarie P, Balk L, Costello F, et al. The OSCAR-IB consensus criteria for retinal OCT quality assessment. PLoS One 2012; 7: e34823. 12. Schippling S, Balk L, Costello F, et al. Quality control for retinal OCT in multiple sclerosis: Validation of the OSCAR-IB criteria. Mult Scler J 2014; Jun 16. pii: 1352458514538110. [Epub ahead of print].
Visit SAGE journals online http://msj.sagepub.com
SAGE journals
http://msj.sagepub.com 1303
