Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study - 13/04/16

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

Elena H Martinez-Lapiscina, MD ^a, Sam Arnow, BS ^b, James A Wilson, BS ^c, Shiv Saidha, MD ^d, Jana Lizrova Preiningerova, MD ^e, Timm Oberwahrenbrock, MD ^f, Alexander U Brandt, MD ^f, Luis E Pablo, MD ^g, Simone Guerrieri, MD ^h, Ines Gonzalez, MD ⁱ, Olivier Outteryck, MD ^j, Ann-Kristin Mueller, BS ^k, Phillip Albrecht, MD ^k, Wesley Chan, BS ^l, Sebastian Lukas, BS ^m, Lisanne J Balk, PhD ⁿ, Clare Fraser, MD ^p, Jette L Frederiksen, ProfMD ^q, Jennifer Resto, BS ^r, Teresa Frohman, MD ^s, Christian Cordano, MD ^b, Irati Zubizarreta, MD ^a, Magi Andorra, BSc ^a, Bernardo Sanchez-Dalmau, MD ^a, Albert Saiz, MD ^a, Robert Bermel, MD ^r, Alexander Klistorner, PhD ^p, Axel Petzold, MD ^n,^o, Sven Schippling, MD ^m, Fiona Costello, MD ^l, Orhan Aktas, ProfMD ^k, Patrick Vermersch, ProfMD ^j, Celia Oreja-Guevara, MD ⁱ, Giancarlo Comi, ProfMD ^h, Letizia Leocani, MD ^h, Elena Garcia-Martin, MD ^g, Friedemann Paul, ProfMD ^f, Eva Havrdova, MD ^e, Elliot Frohman, ProfMD ^s, Laura J Balcer, ProfMD ^c,^t, Ari J Green, MD ^b, Peter A Calabresi, ProfMD ^d, Pablo Villoslada, ProfMD ^a,^b,^⁎
the
IMSVISUAL consortium

^a Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain

^b University of California, San Francisco, CA, USA

^c University of Pennsylvania, Philadelphia, PA, USA

^d Johns Hopkins University, Baltimore, MD, USA

^e Charles University, Prague, Czech Republic

^f Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité University Medicine and Max Delbrueck Center for Molecular Medicine, Berlin, Germany

^g Hospital Miguel Servet, Zaragoza, Spain

^h San Raffaele Hospital, Milan, Italy

ⁱ Hospital Clinico San Carlos, Madrid, Spain

^j University of Lille, Lille, France

^k University of Düsseldorf, Düsseldorf, Germany

^l University of Calgary, Calgary, AB, Canada

^m University of Zurich, Zurich, Switzerland

ⁿ VU Medical Center, Amsterdam, Netherlands

^o Moorfields Eye Hospital, London, UK

^p Save Sight Institute, University of Sydney, NSW, Australia

^q Glostrup Hospital, University of Copenhagen, Denmark

^r Cleveland Clinic Foundation, Cleveland, OH, USA

^s University of Texas Southwestern Medical Center, Dallas, TX, USA

^t New York University, New York, NY, USA

^* Correspondence to: Prof Pablo Villoslada, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona 08036, Spain Correspondence to: Prof Pablo Villoslada Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS) Barcelona 08036 Spain

Summary

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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Vol 15 - N° 6

P. 574-584 - mai 2016 Retour au numéro

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Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study - 13/04/16

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