Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study

Elena H Martinez-Lapiscina; Sam Arnow; James A Wilson; Shiv Saidha; Jana Lizrova Preiningerova; Timm Oberwahrenbrock; Alexander U Brandt; Luis E Pablo; Simone Guerrieri; Ines Gonzalez; Olivier Outteryck; Ann-Kristin Mueller; Phillip Albrecht; Wesley Chan; Manuel Sebastian Lukas; Lisanne J Balk; Clare Fraser; Jette Lautrup Fredriksen; Jennifer Resto; Teresa Frohman; Christian Cordano; Irati Zubizarreta; Magi Andorra; Bernardo Sanchez-Dalmau; Albert Saiz; Robert Bermel; Alexander Klistorner; Axel Petzold; Sven Schippling; Fiona Costello; Orhan Aktas; Patrick Vermersch; Celia Oreja-Guevara; Giancarlo Comi; Letizia Leocani; Elena Garcia-Martin; Friedemann Paul; Eva Havrdová; Elliot Frohman; Laura J Balcer; Ari J Green; Peter A Calabresi; Pablo Villoslada; IMSVISUAL consortium

doi:10.1016/S1474-4422(16)00068-5

Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study

Elena H Martinez-Lapiscina, Sam Arnow, James A Wilson, Shiv Saidha, Jana Lizrova Preiningerova, Timm Oberwahrenbrock, Alexander U Brandt, Luis E Pablo, Simone Guerrieri, Ines Gonzalez, Olivier Outteryck, Ann-Kristin Mueller, Phillip Albrecht, Wesley Chan, Manuel Sebastian Lukas, Lisanne J Balk, Clare Fraser, Jette Lautrup Fredriksen, Jennifer Resto, Teresa FrohmanChristian Cordano, Irati Zubizarreta, Magi Andorra, Bernardo Sanchez-Dalmau, Albert Saiz, Robert Bermel, Alexander Klistorner, Axel Petzold, Sven Schippling, Fiona Costello, Orhan Aktas, Patrick Vermersch, Celia Oreja-Guevara, Giancarlo Comi, Letizia Leocani, Elena Garcia-Martin, Friedemann Paul, Eva Havrdová, Elliot Frohman, Laura J Balcer, Ari J Green, Peter A Calabresi, Pablo Villoslada, IMSVISUAL consortium

Department of Clinical Medicine

149 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Lancet Neurology
Volume	15
Issue number	6
Pages (from-to)	574-584
Number of pages	11
ISSN	1474-4422
DOIs	https://doi.org/10.1016/S1474-4422(16)00068-5
Publication status	Published - 1 May 2016

Keywords

Adult
Cohort Studies
Disease Progression
Female
Follow-Up Studies
Humans
Macula Lutea
Male
Middle Aged
Multiple Sclerosis
Prognosis
Retinal Diseases
Retinal Neurons
Severity of Illness Index
Tomography, Optical Coherence
Journal Article
Multicenter Study

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Martinez-Lapiscina, E. H., Arnow, S., Wilson, J. A., Saidha, S., Preiningerova, J. L., Oberwahrenbrock, T., Brandt, A. U., Pablo, L. E., Guerrieri, S., Gonzalez, I., Outteryck, O., Mueller, A-K., Albrecht, P., Chan, W., Lukas, M. S., Balk, L. J., Fraser, C., Fredriksen, J. L., Resto, J., ... IMSVISUAL consortium (2016). Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study. Lancet Neurology, 15(6), 574-584. https://doi.org/10.1016/S1474-4422(16)00068-5

Martinez-Lapiscina, EH, Arnow, S, Wilson, JA, Saidha, S, Preiningerova, JL, Oberwahrenbrock, T, Brandt, AU, Pablo, LE, Guerrieri, S, Gonzalez, I, Outteryck, O, Mueller, A-K, Albrecht, P, Chan, W, Lukas, MS, Balk, LJ, Fraser, C, Fredriksen, JL, Resto, J, Frohman, T, Cordano, C, Zubizarreta, I, Andorra, M, Sanchez-Dalmau, B, Saiz, A, Bermel, R, Klistorner, A, Petzold, A, Schippling, S, Costello, F, Aktas, O, Vermersch, P, Oreja-Guevara, C, Comi, G, Leocani, L, Garcia-Martin, E, Paul, F, Havrdová, E, Frohman, E, Balcer, LJ, Green, AJ, Calabresi, PA, Villoslada, P & IMSVISUAL consortium 2016, 'Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study', Lancet Neurology, vol. 15, no. 6, pp. 574-584. https://doi.org/10.1016/S1474-4422(16)00068-5

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abstract = "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.",

keywords = "Adult, Cohort Studies, Disease Progression, Female, Follow-Up Studies, Humans, Macula Lutea, Male, Middle Aged, Multiple Sclerosis, Prognosis, Retinal Diseases, Retinal Neurons, Severity of Illness Index, Tomography, Optical Coherence, Journal Article, Multicenter Study",

author = "Martinez-Lapiscina, {Elena H} and Sam Arnow and Wilson, {James A} and Shiv Saidha and Preiningerova, {Jana Lizrova} and Timm Oberwahrenbrock and Brandt, {Alexander U} and Pablo, {Luis E} and Simone Guerrieri and Ines Gonzalez and Olivier Outteryck and Ann-Kristin Mueller and Phillip Albrecht and Wesley Chan and Lukas, {Manuel Sebastian} and Balk, {Lisanne J} and Clare Fraser and Fredriksen, {Jette Lautrup} and Jennifer Resto and Teresa Frohman and Christian Cordano and Irati Zubizarreta and Magi Andorra and Bernardo Sanchez-Dalmau and Albert Saiz and Robert Bermel and Alexander Klistorner and Axel Petzold and Sven Schippling and Fiona Costello and Orhan Aktas and Patrick Vermersch and Celia Oreja-Guevara and Giancarlo Comi and Letizia Leocani and Elena Garcia-Martin and Friedemann Paul and Eva Havrdov{\'a} and Elliot Frohman and Balcer, {Laura J} and Green, {Ari J} and Calabresi, {Peter A} and Pablo Villoslada and {IMSVISUAL consortium}",

year = "2016",

month = may,

day = "1",

doi = "10.1016/S1474-4422(16)00068-5",

language = "English",

volume = "15",

pages = "574--584",

journal = "The Lancet Neurology",

issn = "1474-4422",

publisher = "TheLancet Publishing Group",

number = "6",

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TY - JOUR

T1 - Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis

T2 - a cohort study

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, Manuel Sebastian

AU - Balk, Lisanne J

AU - Fraser, Clare

AU - Fredriksen, Jette Lautrup

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 - Havrdová, Eva

AU - Frohman, Elliot

AU - Balcer, Laura J

AU - Green, Ari J

AU - Calabresi, Peter A

AU - Villoslada, Pablo

AU - IMSVISUAL consortium

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.

KW - Adult

KW - Cohort Studies

KW - Disease Progression

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Macula Lutea

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis

KW - Prognosis

KW - Retinal Diseases

KW - Retinal Neurons

KW - Severity of Illness Index

KW - Tomography, Optical Coherence

KW - Journal Article

KW - Multicenter Study

U2 - 10.1016/S1474-4422(16)00068-5

DO - 10.1016/S1474-4422(16)00068-5

M3 - Journal article

C2 - 27011339

SN - 1474-4422

VL - 15

SP - 574

EP - 584

JO - The Lancet Neurology

JF - The Lancet Neurology

IS - 6

ER -

Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study

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Keywords

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