Optimal Inter-Eye Difference Thresholds in Retinal Nerve Fiber Layer and Ganglion Cell Layer Thickness for Predicting a Unilateral Optic Nerve Lesion in Multiple Sclerosis

Friday, June 1, 2018: 2:15 PM
104 C-E (Nashville Music City Center)
Rachel Nolan, BA , NYU Langone Medical Center, New York, NY
Omar Akhand, BS , NYU School of Medicine, New York, NY
Peter A Calabresi, MD , Neurology, Johns Hopkins University, Baltimore, MD
Friedemann Paul, MD , Charité-Universitätsmedizin Berlin, Berlin, Germany
Elena Hernandez Martinez de Lapiscina, MD, PhD , Hospital Clínic de Barcelona, Barcelona, Spain
Axel Petzold, MD, PhD , UCL Institute of Neurology, London, United Kingdom
Alexander Brandt, MD , Charité - Universitätsmedizin Berlin, Berlin, Germany
Shiv Saidha, MBBCh , Neurology, Johns Hopkins University, Baltimore, MD
Pablo Villoslada, MD , Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Abdullah Abu Al-Hassan, MD , Dasman Institute, Kuwait City, Kuwait
Raed Behbehani, MD , Dasman Institute, Kuwait City, Kuwait
Elliot Frohman, MD, PhD, FAAN , Neurology & Neurotherapeutics - MS Clinic, UT Southwestern Medical Center, Dallas, TX
Teresa Frohman, MPAS, PA-C , University of Texas Southwestern, Dallas, TX
Joachim Havla, MD , Ludwig-Maximilians-University of Munich, Munich, Germany
Bernhard Hemmer, MD, PhD , Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
Hong Jiang, MD, PhD , Bascom Palmer Institute, Miami, FL
Benjamin Knier, MD , Technische Universität München, Munich, Germany
Thomas Korn, MD , Technische Universität München, Munich, Germany
Letizia Leocani, MD , Ospedale San Raffaele, Milano, Italy
Athina Papadopoulou, MD , University of Basel, Basel, Switzerland
Marco Pisa, MD , Ospedale San Raffaele, Milan, Italy
Hanna Zimmermann, M.Eng , Charité - Universitätsmedizin Berlin, Berlin, Germany
Steven Galetta, MD , New York University Langone Medical Center, New York, NY
Laura J Balcer, MD, MSCE , New York University Langone Medical Center, New York, NY


The optic nerve is a frequent site for involvement in MS.  Current international diagnostic criteria for MS do not include the optic nerve as a lesion site despite the high prevalence of acute optic neuritis (ON).  Spectral-domain optical coherence tomography (SD-OCT) detects thinning of retinal nerve fiber layer (RNFL) and ganglion cell+inner plexiform (GCIP) layer in MS.  



To determine optimal thresholds for inter-eye differences in RNFL and GCIP layer thicknesses that are predictive of a unilateral optic nerve lesion in multiple sclerosis (MS).


In this multi-center international study at 9 sites, SD-OCT, high-contrast visual acuity (VA), low-contrast letter acuity (LCLA), and vision-specific quality of life (QOL) were measured for MS patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium (IMSVISUAL).  QOL was measured using the NEI-VFQ-25 and 10-item Neuro-Ophthalmic Supplement (NOS).  Presence of an optic nerve lesion was defined as history of acute unilateral ON.


Among healthy controls (n=348), the 95th percentile value for inter-eye difference (upper boundary of expected) was 7.0 microns; for GCIP, the 95th percentile was 3.0 microns.  These values were applied to the MS cohort (n=1,346), and were associated with worse vision-specific QOL for inter-eye differences above the threshold values (P≤0.04, linear regression, accounting for age).  Greater inter-eye differences in VA and LCLA were associated with greater inter-eye RNFL differences (P<0.001) and GCIP (P≤0.002).  Receiver operating characteristic (ROC) curve analysis demonstrated an optimal RNFL inter-eye difference threshold of 5 microns for identifying patients with unilateral ON (n=404) in the MS cohort (point on ROC curve where sensitivity and specificity are both optimized).  For GCIP, the threshold was 4 microns.



Optimal inter-eye differences of 5 microns for peripapillary RNFL and 4 microns for macular GCIP thickness are robust thresholds for identifying unilateral optic nerve lesions based on analyses of an international MS cohort.