Contributions
Abstract: 162
Type: Scientific Session
Abstract Category: Clinical aspects of MS - Neuro-ophthalmology
Objective: To determine optimal thresholds for inter-eye differences in retinal nerve fiber (RNFL) and ganglion cell+inner plexiform (GCIP) layer thicknesses that are predictive of a unilateral optic nerve lesion in multiple sclerosis (MS).
Background: 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 RNFL and GCIP in MS.
Methods: 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.
Results: 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.
Conclusions: 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.
Disclosure: L. Leocani received honoraria for consulting services or speaking activities from Roche, Novartis, Merck KGaA, Biogen, and Almirall
Dr. Havla has received consultancy fees from Novartis, Genzyme, Santhera and Merck. He has received reimbursements of congress attendance and travel costs from Novartis, Merck, and Bayer.
Dr. Pablo Villoslada hold stocks in Bionure Inc, Spire Bioventures, Mint-Labs and Health Engineering and is an employee of Genentech Inc at present.
Elliot Frohman: speaker/consultant for Acorda, Genzyme, NovartisTeresa Frohman: speaker/consultant Acorda, Genzyme, Novartis
Bernhard Hemmer has served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Novartis, Bayer AG, and Genentech; he has served as DMSC member for AllergyCare and TG Therapeutics; he or his institution have received speaker honoraria from Biogen Idec, Teva Neuroscience, Merck Serono, Medimmune, Novartis, Desitin, and F. Hoffmann-La Roche Ltd; his institution has received research support from Chugai Pharmaceuticals and Hoffmann-La-Roche; holds part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon β
F. Paul serves on the scientific advisoryboard for Novartis; received speaker honoraria and travel funding fromBayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, MerckSerono, Alexion, Chugai, MedImmune, and Shire; is an academic editorfor PLoS ONE; is an associate editor for Neurology® Neuroimmunology &Neuroinflammation; consulted for SanofiGenzyme, Biogen Idec, MedImmune,Shire, and Alexion; and received research support from Bayer,Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, MerckSerono, German Research Council, Werth Stiftung of the City ofCologne, German Ministry of Education and Research, Arthur ArnsteinStiftung Berlin, EU FP7 Framework Program, Arthur Arnstein FoundationBerlin, Guthy Jackson Charitable Foundation, and National MultipleSclerosis of the USA.
PAC has received consulting fees from Disarm Therapeutics, and is PI on research grants to JHU from Annexon, MedImmune, Sanofi, Biogen and Novartis.
Dr. Balcer has received investigator-initiated research grant funding from Biogen.
The remaining authors have nothing to disclose.
Abstract: 162
Type: Scientific Session
Abstract Category: Clinical aspects of MS - Neuro-ophthalmology
Objective: To determine optimal thresholds for inter-eye differences in retinal nerve fiber (RNFL) and ganglion cell+inner plexiform (GCIP) layer thicknesses that are predictive of a unilateral optic nerve lesion in multiple sclerosis (MS).
Background: 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 RNFL and GCIP in MS.
Methods: 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.
Results: 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.
Conclusions: 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.
Disclosure: L. Leocani received honoraria for consulting services or speaking activities from Roche, Novartis, Merck KGaA, Biogen, and Almirall
Dr. Havla has received consultancy fees from Novartis, Genzyme, Santhera and Merck. He has received reimbursements of congress attendance and travel costs from Novartis, Merck, and Bayer.
Dr. Pablo Villoslada hold stocks in Bionure Inc, Spire Bioventures, Mint-Labs and Health Engineering and is an employee of Genentech Inc at present.
Elliot Frohman: speaker/consultant for Acorda, Genzyme, NovartisTeresa Frohman: speaker/consultant Acorda, Genzyme, Novartis
Bernhard Hemmer has served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Novartis, Bayer AG, and Genentech; he has served as DMSC member for AllergyCare and TG Therapeutics; he or his institution have received speaker honoraria from Biogen Idec, Teva Neuroscience, Merck Serono, Medimmune, Novartis, Desitin, and F. Hoffmann-La Roche Ltd; his institution has received research support from Chugai Pharmaceuticals and Hoffmann-La-Roche; holds part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon β
F. Paul serves on the scientific advisoryboard for Novartis; received speaker honoraria and travel funding fromBayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, MerckSerono, Alexion, Chugai, MedImmune, and Shire; is an academic editorfor PLoS ONE; is an associate editor for Neurology® Neuroimmunology &Neuroinflammation; consulted for SanofiGenzyme, Biogen Idec, MedImmune,Shire, and Alexion; and received research support from Bayer,Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, MerckSerono, German Research Council, Werth Stiftung of the City ofCologne, German Ministry of Education and Research, Arthur ArnsteinStiftung Berlin, EU FP7 Framework Program, Arthur Arnstein FoundationBerlin, Guthy Jackson Charitable Foundation, and National MultipleSclerosis of the USA.
PAC has received consulting fees from Disarm Therapeutics, and is PI on research grants to JHU from Annexon, MedImmune, Sanofi, Biogen and Novartis.
Dr. Balcer has received investigator-initiated research grant funding from Biogen.
The remaining authors have nothing to disclose.