Retinal Nerve Fibre Layer Thinning in Patients with Clinically Isolated Optic Neuritis and Early Treatment with Interferon-Beta Kurt-Wolfram Su ¨ hs 1,2 , Katharina Hein 3 , Jens R. Pehlke 1,4 , Barbara Ka ¨ smann-Kellner 5 , Ricarda Diem 1,6 * 1 Department of Neurology, Saarland University, Homburg, Germany, 2 Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany, 3 Department of Neurology, Georg-August University, Go ¨ ttingen, Germany, 4 Department of Addiction Disorders, LWL Clinic Mu ¨ nster, Mu ¨ nster, Germany, 5 Department of Ophthalmology, Saarland University, Homburg, Germany, 6 Department of Neuro-oncology, University Clinic Heidelberg, Heidelberg, Germany Abstract Background: Optic neuritis is associated with neurodegeneration leading to chronic impairment of visual functions. Objective: This study investigated whether early treatment with interferon beta (IFN-b) slows retinal nerve fibre layer (RNFL) thinning in clinically isolated optic neuritis. Methods: Twenty patients with optic neuritis and visual acuity decreased to #0.5 (decimal system) were included into this prospective, open-label, parallel group 4-month observation. After methylprednisolone pulse therapy, 10 patients received IFN-b from week 2 onwards. This group was compared to 10 patients free of any disease modifying treatment (DMT). The parameter of interest was change in RNFL thickness assessed at baseline and at weeks 4, 8, and 16. Changes in visual acuity, visual field, and visual evoked potentials (VEPs) served as additional outcome parameters. Results: RNFL thinning did not differ between the groups with a mean reduction of 9.8062.80 mm in IFN-b-treated patients (6SD) vs. 12.4465.79 mm in patients who did not receive DMT (baseline non-affected eye minus affected eye at week 16; p = 0.67, t-test, 95% confidence interval: 215.77 to 10.48). Parameters of visual function did not show any differences between the groups either. Conclusions: In isolated optic neuritis, early IFN-b treatment did not influence RNFL thinning nor had it any effect on recovery of visual functions. Citation: Su ¨ hs K-W, Hein K, Pehlke JR, Ka ¨smann-Kellner B, Diem R (2012) Retinal Nerve Fibre Layer Thinning in Patients with Clinically Isolated Optic Neuritis and Early Treatment with Interferon-Beta. PLoS ONE 7(12): e51645. doi:10.1371/journal.pone.0051645 Editor: Ralf Andreas Linker, Friedrich-Alexander University Erlangen, Germany Received August 14, 2012; Accepted November 2, 2012; Published December 13, 2012 Copyright: ß 2012 Su ¨ hs et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported by research grants from Bayer Healthcare, Leverkusen, Germany, and Merck Serono GmbH, Darmstadt. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: RD has received travel expenses from Biogen Idec, and consultancy fees from Synthon BV, KWS and KH have received travel expenses from Biogen Idec, Bayer Healthcare, and TEVA. JRP and BKK have nothing to declare. This study was supported by research grants from Bayer Healthcare, Leverkusen, Germany, and Merck Serono GmbH, Darmstadt. Betaferon is marketed by Bayer, and Rebif is marketed by Merck Serono. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. * E-mail: ricarda.diem@med.uni-heidelberg.de Introduction Multiple sclerosis (MS) is a major cause of neurological disability in young adults and often manifests with optic neuritis as its earliest clinical presentation. In both MS and optic neuritis, neurodegenerative changes lead to persistent functional deficits. [1,2] Disease modifying therapy (DMT) with interferon-beta (IFN- b) belongs to the standard therapies of MS and has already been found to be beneficial in an early disease stage termed clinically isolated syndrome (CIS). [3–6] However, irrespective of the documented effects on immune responses, it still is a subject of discussion whether and to what extent DMT counteracts inflammation-associated neurodegeneration. [2] Although treat- ment with IFN-b has been shown to delay conversion of CIS into clinically definite MS, neurological disability was not reduced five years later [4] suggesting that neurodegeneration might not be influenced by early start of DMT. Direct monitoring of neurodegeneration in patients with CIS is challenging, particularly due to the heterogeneity of this patient group with different anatomical lesion localisation, variable numbers of initial lesions, and different dynamics of neurodegeneration. Amongst the spectrum of CIS, optic neuritis represents a homogenous disease condition with a predictable extent of retinal nerve fibre layer (RNFL) degeneration. By using optical coherence tomography (OCT), atrophy of the RNFL which contains the non- myelinated part of optic nerve axons can directly be assessed. [7] Moreover, changes in RNFL thickness during MS allow conclu- sions to be drawn about neurodegenerative changes on a global level due to their association with brain atrophy. [8–13] In previous work, it has been shown that RNFL thinning can be observed during the first six months following optic neuritis and that more than 90% of this fibre loss has occurred by the end of PLOS ONE | www.plosone.org 1 December 2012 | Volume 7 | Issue 12 | e51645