TY - JOUR
T1 - Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis
T2 - A cohort study
AU - IMSVISUAL consortium
AU - Martinez-Lapiscina, Elena H.
AU - Arnow, Sam
AU - Wilson, James A.
AU - Saidha, Shiv
AU - Preiningerova, Jana Lizrova
AU - Oberwahrenbrock, Timm
AU - Brandt, Alexander U.
AU - Pablo, Luis E.
AU - Guerrieri, Simone
AU - Gonzalez, Ines
AU - Outteryck, Olivier
AU - Mueller, Ann Kristin
AU - Albrecht, Phillip
AU - Chan, Wesley
AU - Lukas, Sebastian
AU - Balk, Lisanne J.
AU - Fraser, Clare
AU - Frederiksen, Jette L.
AU - Resto, Jennifer
AU - Frohman, Teresa
AU - Cordano, Christian
AU - Zubizarreta, Irati
AU - Andorra, Magi
AU - Sanchez-Dalmau, Bernardo
AU - Saiz, Albert
AU - Bermel, Robert
AU - Klistorner, Alexander
AU - Petzold, Axel
AU - Schippling, Sven
AU - Costello, Fiona
AU - Aktas, Orhan
AU - Vermersch, Patrick
AU - Oreja-Guevara, Celia
AU - Comi, Giancarlo
AU - Leocani, Letizia
AU - Garcia-Martin, Elena
AU - Paul, Friedemann
AU - Havrdova, Eva
AU - Frohman, Elliot
AU - Balcer, Laura J.
AU - Green, Ari J.
AU - Calabresi, Peter A.
AU - Villoslada, Pablo
N1 - Funding Information:
This study was supported by Instituto de Salud Carlos III, Spain ( PI15/00061 and RD012/0060/01 ) to PVi and RD12/0032/0002 to AS. EHM-L was supported by a fellowship from the Instituto de Salud Carlos III (Spain; Rio Hortega program: CM13/00150). FP is supported by Deutsche Forschungsgemeinschaft (DFG Exc 257), Bundesministerium für Bildung und Forschung (Competence Network Multiple Sclerosis KKNMS) and the Guthy Jackson Charitable Foundation. FC has received funding support from the MS Society of Canada. PAC is supported by NIH R01NS082347 and the National Multiple Sclerosis Society. LiJB and AP are supported by the Stichting MS Research (Netherlands). JLP and EH are supported by Czech Ministry of Health grant IGA NT13239–4 and by Czech Ministry of Education Project PRVOUK-P26/LF1/4. SG, LL, and GC are supported through INSPE-Institute of Experimental Neurology, Hospital San Raffaele, and by Merck Serono SA (Geneva, Switzerland). SSc is supported by the Clinical Research Priority Program of the University of Zurich and the Betty and David Koetser Foundation for Brain Research. AJG is supported by the National Multiple Sclerosis Society Harry Weaver Neuroscience Scholars programme ( JF2151-A-1 ). We thank Craig Smith for his valuable comments on the manuscript.
Funding Information:
Instituto de Salud Carlos III. This study was supported by Instituto de Salud Carlos III, Spain (PI15/00061 and RD012/0060/01) to PVi and RD12/0032/0002 to AS. EHM-L was supported by a fellowship from the Instituto de Salud Carlos III (Spain; Rio Hortega program: CM13/00150). FP is supported by Deutsche Forschungsgemeinschaft (DFG Exc 257), Bundesministerium für Bildung und Forschung (Competence Network Multiple Sclerosis KKNMS) and the Guthy Jackson Charitable Foundation. FC has received funding support from the MS Society of Canada. PAC is supported by NIH R01NS082347 and the National Multiple Sclerosis Society. LiJB and AP are supported by the Stichting MS Research (Netherlands). JLP and EH are supported by Czech Ministry of Health grant IGA NT13239–4 and by Czech Ministry of Education Project PRVOUK-P26/LF1/4. SG, LL, and GC are supported through INSPE-Institute of Experimental Neurology, Hospital San Raffaele, and by Merck Serono SA (Geneva, Switzerland). SSc is supported by the Clinical Research Priority Program of the University of Zurich and the Betty and David Koetser Foundation for Brain Research. AJG is supported by the National Multiple Sclerosis Society Harry Weaver Neuroscience Scholars programme (JF2151-A-1). We thank Craig Smith for his valuable comments on the manuscript.
Publisher Copyright:
© 2016 Elsevier Ltd.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Background: Most patients with multiple sclerosis without previous optic neuritis have thinner retinal layers than healthy controls. We assessed the role of peripapillary retinal nerve fibre layer (pRNFL) thickness and macular volume in eyes with no history of optic neuritis as a biomarker of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available. Methods: In this multicentre, cohort study, we collected data about patients (age ≥16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis, and progressive multiple sclerosis. Patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Netherlands, Canada, and the USA, with the first cohort starting in 2008 and the latest cohort starting in 2013. We assessed disability worsening using the Expanded Disability Status Scale (EDSS). The pRNFL thickness and macular volume were assessed once at study entry (baseline) by optical coherence tomography (OCT) and was calculated as the mean value of both eyes without optic neuritis for patients without a history of optic neuritis or the value of the non-optic neuritis eye for patients with previous unilateral optic neuritis. Researchers who did the OCT at baseline were masked to EDSS results and the researchers assessing disability with EDSS were masked to OCT results. We estimated the association of pRNFL thickness or macular volume at baseline in eyes without optic neuritis with the risk of subsequent disability worsening by use of proportional hazards models that included OCT metrics and age, disease duration, disability, presence of previous unilateral optic neuritis, and use of disease-modifying therapies as covariates. Findings: 879 patients with clinically isolated syndrome (n=74), relapsing-remitting multiple sclerosis (n=664), or progressive multiple sclerosis (n=141) were included in the primary analyses. Disability worsening occurred in 252 (29%) of 879 patients with multiple sclerosis after a median follow-up of 2·0 years (range 0·5-5 years). Patients with a pRNFL of less than or equal to 87 μm or less than or equal to 88 μm (measured with Spectralis or Cirrus OCT devices) had double the risk of disability worsening at any time after the first and up to the third years of follow-up (hazard ratio 2·06, 95% CI 1·36-3·11; p=0·001), and the risk was increased by nearly four times after the third and up to the fifth years of follow-up (3·81, 1·63-8·91; p=0·002). We did not identify meaningful associations for macular volume. Interpretation: Our results provide evidence of the usefulness of monitoring pRNFL thickness by OCT for prediction of the risk of disability worsening with time in patients with multiple sclerosis. Funding: Instituto de Salud Carlos III.
AB - Background: Most patients with multiple sclerosis without previous optic neuritis have thinner retinal layers than healthy controls. We assessed the role of peripapillary retinal nerve fibre layer (pRNFL) thickness and macular volume in eyes with no history of optic neuritis as a biomarker of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available. Methods: In this multicentre, cohort study, we collected data about patients (age ≥16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis, and progressive multiple sclerosis. Patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Netherlands, Canada, and the USA, with the first cohort starting in 2008 and the latest cohort starting in 2013. We assessed disability worsening using the Expanded Disability Status Scale (EDSS). The pRNFL thickness and macular volume were assessed once at study entry (baseline) by optical coherence tomography (OCT) and was calculated as the mean value of both eyes without optic neuritis for patients without a history of optic neuritis or the value of the non-optic neuritis eye for patients with previous unilateral optic neuritis. Researchers who did the OCT at baseline were masked to EDSS results and the researchers assessing disability with EDSS were masked to OCT results. We estimated the association of pRNFL thickness or macular volume at baseline in eyes without optic neuritis with the risk of subsequent disability worsening by use of proportional hazards models that included OCT metrics and age, disease duration, disability, presence of previous unilateral optic neuritis, and use of disease-modifying therapies as covariates. Findings: 879 patients with clinically isolated syndrome (n=74), relapsing-remitting multiple sclerosis (n=664), or progressive multiple sclerosis (n=141) were included in the primary analyses. Disability worsening occurred in 252 (29%) of 879 patients with multiple sclerosis after a median follow-up of 2·0 years (range 0·5-5 years). Patients with a pRNFL of less than or equal to 87 μm or less than or equal to 88 μm (measured with Spectralis or Cirrus OCT devices) had double the risk of disability worsening at any time after the first and up to the third years of follow-up (hazard ratio 2·06, 95% CI 1·36-3·11; p=0·001), and the risk was increased by nearly four times after the third and up to the fifth years of follow-up (3·81, 1·63-8·91; p=0·002). We did not identify meaningful associations for macular volume. Interpretation: Our results provide evidence of the usefulness of monitoring pRNFL thickness by OCT for prediction of the risk of disability worsening with time in patients with multiple sclerosis. Funding: Instituto de Salud Carlos III.
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U2 - 10.1016/S1474-4422(16)00068-5
DO - 10.1016/S1474-4422(16)00068-5
M3 - Article
C2 - 27011339
AN - SCOPUS:84962505981
SN - 1474-4422
VL - 15
SP - 574
EP - 584
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 6
ER -