Contributions
Abstract: P405
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Neuro-ophthalmology
Background: Development of markers for therapy response is a priority for therapeutic optimization in multiple sclerosis (MS). The retina represents an ideal model to investigate effects of DMTs using non-invasive technologies as multifocal electroretinography (mfERG) and optical coherence tomography (OCT), since it may mirror the inflammatory and neurodegenerative processes of MS. After DMT administration, functional changes may precede structural ones so neurophysiological retinal response deserves further evaluation.
Aim: To evaluate repeatability of first-kernel mfERG response and relationships between functional and structural retinal measures in relapsing remitting MS (RRMS).
Methods: RRMS patients who agreed to two visits before and 12 months after starting teriflunomide were evaluated using monocular 2.5% low contrast letter acuity (LCLA), OCT, mfERG, and EDSS. We performed baseline intra-session test-retest for mfERG. Analyses were done using a mixed linear effect models, with prior history of optic neuritis (ON) and age as covariates.
Results: 18 subjects (78% women; median 45 years), mildly disabled (median EDSS=2) were available for baseline analyses. Median (P25-P75) for average first-kernel responses: 5.8 (4.3-8.5) nV/deg2 for N1 amplitude; 25.6 (24.6-26.6) ms for N1 peak time; 15.9 (13.1-21.3) nV/deg2 for P1 amplitude; 45.2 (44.3-46.2) ms for P1 peak time. Intra-session changes were higher for amplitudes (N1: 34.7%; P1: 23.7%) than for peak times (N1: 2.3%; P1:3.8%). We did not find any association between ganglion cell plus inner plexiform layer (GCIPL) and thicknesses or first-kernel responses for bipolar cells (BP) and photoreceptors (PRL). We found a linear association between outer plexiform layer (OPL) thickness (synapsis between BP and PRL) and N1 amplitude (beta=0.846; p-value=0.004) but not N1 peak time (beta=-0.196 p-value=0.195). We did not find other associations between structural and mfERG markers of BP and PRL. GCIPL thickness (beta=0.828) was the only significant predictor for 2.5% LCLA.
Conclusion: Analysis of peak times, rather than amplitudes, is more reliable for mfERG longitudinal assessments. Absence of association between inner and outer retinal structures suggest that there is either an absence or a negligible retrograde trans-synaptic degeneration after ON. The significant structural-functional relationship between synapsis of bipolar cells and photoreceptors and N1 deserves further evaluation.
Disclosure: Funding: This study has been funded by Sanofi.
S Alba-Arbalat: nothing to disclose
N Vidal-Fernandez: expert testimony for Novartis and Roche and received speaking fees from Biogen.
M Andorra: nothing to disclose
A Camos-Carreras: nothing to disclose
I Pulido-Valdeolivas: travel reimbursement from Roche and Genzyme, and she holds stock in Aura Innovative Robotics.
I Zubizarreta: Compensation for consulting services from Bayer and travel reimbursement from Genzyme, Biogen and Novartis
N Sola-Valls: compensation for consulting services and speaker honoraria from Sanofi, Bayer-Schering.A Guerrero-Zamora: nothing to disclose
S Llufriu: speaker honoraria from Biogen Idec, Novartis, Teva, Genzyme and Merck.
M Sepulveda: speaker honoraria from Sanofi and Biogen
A Saiz: compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd and Novartis.
B Sanchez-Dalmau: nothing to disclose
L Querol: expert testimony for Grifols and CSL Behring, received speaking fees from CSL Behring, Grifols, Roche and Biogen and research funds from Novartis Spain and Grifols (Spin Award).
EH Martinez-Lapiscina: researcher in the OCTIMS study, an observational study (that involves no specific drugs) to validate SD-OCT as a biomarker for MS, sponsored by Novartis. She has received honoraria from Biogen, Roche, Novartis and Sanofi for speaking, and a travel reimbursement for international and national meetings over the last 3 years. She has received honoraria for services in boards for Sanofi and Roche. She is a member of the working committee of International Multiple Sclerosis Visual System (IMSVISUAL) Consortium.
Abstract: P405
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Neuro-ophthalmology
Background: Development of markers for therapy response is a priority for therapeutic optimization in multiple sclerosis (MS). The retina represents an ideal model to investigate effects of DMTs using non-invasive technologies as multifocal electroretinography (mfERG) and optical coherence tomography (OCT), since it may mirror the inflammatory and neurodegenerative processes of MS. After DMT administration, functional changes may precede structural ones so neurophysiological retinal response deserves further evaluation.
Aim: To evaluate repeatability of first-kernel mfERG response and relationships between functional and structural retinal measures in relapsing remitting MS (RRMS).
Methods: RRMS patients who agreed to two visits before and 12 months after starting teriflunomide were evaluated using monocular 2.5% low contrast letter acuity (LCLA), OCT, mfERG, and EDSS. We performed baseline intra-session test-retest for mfERG. Analyses were done using a mixed linear effect models, with prior history of optic neuritis (ON) and age as covariates.
Results: 18 subjects (78% women; median 45 years), mildly disabled (median EDSS=2) were available for baseline analyses. Median (P25-P75) for average first-kernel responses: 5.8 (4.3-8.5) nV/deg2 for N1 amplitude; 25.6 (24.6-26.6) ms for N1 peak time; 15.9 (13.1-21.3) nV/deg2 for P1 amplitude; 45.2 (44.3-46.2) ms for P1 peak time. Intra-session changes were higher for amplitudes (N1: 34.7%; P1: 23.7%) than for peak times (N1: 2.3%; P1:3.8%). We did not find any association between ganglion cell plus inner plexiform layer (GCIPL) and thicknesses or first-kernel responses for bipolar cells (BP) and photoreceptors (PRL). We found a linear association between outer plexiform layer (OPL) thickness (synapsis between BP and PRL) and N1 amplitude (beta=0.846; p-value=0.004) but not N1 peak time (beta=-0.196 p-value=0.195). We did not find other associations between structural and mfERG markers of BP and PRL. GCIPL thickness (beta=0.828) was the only significant predictor for 2.5% LCLA.
Conclusion: Analysis of peak times, rather than amplitudes, is more reliable for mfERG longitudinal assessments. Absence of association between inner and outer retinal structures suggest that there is either an absence or a negligible retrograde trans-synaptic degeneration after ON. The significant structural-functional relationship between synapsis of bipolar cells and photoreceptors and N1 deserves further evaluation.
Disclosure: Funding: This study has been funded by Sanofi.
S Alba-Arbalat: nothing to disclose
N Vidal-Fernandez: expert testimony for Novartis and Roche and received speaking fees from Biogen.
M Andorra: nothing to disclose
A Camos-Carreras: nothing to disclose
I Pulido-Valdeolivas: travel reimbursement from Roche and Genzyme, and she holds stock in Aura Innovative Robotics.
I Zubizarreta: Compensation for consulting services from Bayer and travel reimbursement from Genzyme, Biogen and Novartis
N Sola-Valls: compensation for consulting services and speaker honoraria from Sanofi, Bayer-Schering.A Guerrero-Zamora: nothing to disclose
S Llufriu: speaker honoraria from Biogen Idec, Novartis, Teva, Genzyme and Merck.
M Sepulveda: speaker honoraria from Sanofi and Biogen
A Saiz: compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd and Novartis.
B Sanchez-Dalmau: nothing to disclose
L Querol: expert testimony for Grifols and CSL Behring, received speaking fees from CSL Behring, Grifols, Roche and Biogen and research funds from Novartis Spain and Grifols (Spin Award).
EH Martinez-Lapiscina: researcher in the OCTIMS study, an observational study (that involves no specific drugs) to validate SD-OCT as a biomarker for MS, sponsored by Novartis. She has received honoraria from Biogen, Roche, Novartis and Sanofi for speaking, and a travel reimbursement for international and national meetings over the last 3 years. She has received honoraria for services in boards for Sanofi and Roche. She is a member of the working committee of International Multiple Sclerosis Visual System (IMSVISUAL) Consortium.