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, Sebastian Lukas, Lisanne J. Balk, Clare Fraser, Jette L. Frederiksen, 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 Havrdova, Elliot Frohman, Laura J. Balcer, Ari J. Green, Peter A. Calabresi, Pablo Villoslada*, IMSVISUAL consortium

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

213 Citations (Scopus)


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 languageEnglish
Pages (from-to)574-584
Number of pages11
JournalThe Lancet Neurology
Issue number6
Publication statusPublished - 1 May 2016
Externally publishedYes


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