Contributions
Abstract: P1038
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Neuro-ophthalmology
Background: Atrophy of the inner retinal layers (IRL) is an established biomarker of neurodegeneration in relapsing remitting multiple sclerosis (RRMS) and can be measured with optical coherence tomography (OCT). To date, it is unclear whether this degenerative process follows clear patterns or is random.
Objective: To investigate the randomness of IRL atrophy patterns, using structural covariance of layer regional thickness on OCT data in patients with RRMS, without evidence of optic neuritis (MS-NON) compared to healthy subjects, using a graph theoretical approach.
Method: 54 patients (mean age: 37.4 ± 10.7, mean EDSS: 1.9 ± 1.3) and 53 age and sex-matched healthy subjects were enrolled. Each eye was considered a statistical unit, eyes with history of optic neuritis (MS-ON) were excluded, selecting 97 cases and 106 controls. Posterior pole OCT scanning was used to measure thickness of retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) in 64 regions of interests (ROIs) with a 3° x 3° area. A network was derived based on Pearson correlations between ROIs and visualized in anatomical space by locating each layer ROIs according to their imaging acquisition coordinates. OCT network topologies were analysed using commonly used graph analysis measures, local and global mean clustering coefficients (C) and path lengths (L), using a minimum correlation threshold (T) from 0.3 to 0.5 to reduce noise.
Results: RNFL, GCL and IPL showed a significantly higher mean C in cases than controls for T from 0,3 to 0,5 (P< 0,05, Mann Whitney U Test), indicating an increased clustering of the network. RNFL mean L was significantly lower in cases than controls for T of 0.4 and 0.5 (P< 0.05, Mann Whitney U Test); GCL and IPL L were significantly lower in cases than controls for all T considered (P< 0.05, Mann Whitney U Test), indicating a reduction in network segregation.
Conclusions: IRL MS-NON eyes showed a global rearrangement in connectomic architecture compared to healthy controls. The combination of a higher local clustering (C) and lower remote segregation (L) indicate an increased connection density between regions close to each other and a specific change in long-distance connections. Together, these measures seem to indicate that the pattern of atrophy is non-random and features common network patterns. Whether such a network rearrangement has functional impact needs further research.
Disclosure: D. Landi received travel funding from Biogen, Merck Serono, Sanofi-Genzyme, Teva, honoraria for speaking from Sanofi-Genzyme, Teva, Biogen and consultation fees from Merck Serono, Teva, Roche. She is currently subinvestigator in clinical trials being conducted for Biogen, Novartis, Roche, Celgene.
E. Di Carlo has nothing to disclose.
G. Di Mauro has nothing to disclose.
M. Albanese received honoraria for traveling from Almirall, Biogen, Merck Serono, Novartis,and Teva. She is involved as sub-investigator in clinical trials for Bayer Schering, Biogen Idec, Novartis, Merck Serono, Sanofi-Genzyme, Teva, Roche.
M.M. Schoonheim serves on the editorial board of Frontiers of Neurology, receives research support from the Dutch MS Research Foundation and has received compensation for consulting services or speaker honoraria from Excemed, Genzyme and Biogen.
R. Sorge has nothing to disclose.
G. Mataluni received travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme; honoraria for speaking from Biogen. She is subinvestigator in clinical trials being conducted for Biogen, Merck Serono, Novartis, Roche and Teva.
F. Monteleone received funding for traveling from Almirall, Biogen and Sanofi-Genzyme and consultation fees from Almirall.
C.G. Nicoletti received funding for traveling from Almirall, Biogen, Merck and Sanofi-Genzyme.
L. Boffa received travel funding from Almirall, Merck Serono, Sanofi-Genzyme and Teva.
D. Centonze is an Advisory Board member of Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva. He is also the principal investigator in clinical trials for Bayer Schering, Biogen, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva. His preclinical and clinical research was supported by grants from Bayer Schering, Biogen Idec, Celgene, Merck Serono, Novartis, Roche, Sanofi- Genzyme e Teva.
R. Mancino has nothing to disclose.
G.A. Marfia is an Advisory Board member of Biogen Idec, Genzyme, Merck-Serono, Novartis, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, Teva. She is the principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva.
Abstract: P1038
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Neuro-ophthalmology
Background: Atrophy of the inner retinal layers (IRL) is an established biomarker of neurodegeneration in relapsing remitting multiple sclerosis (RRMS) and can be measured with optical coherence tomography (OCT). To date, it is unclear whether this degenerative process follows clear patterns or is random.
Objective: To investigate the randomness of IRL atrophy patterns, using structural covariance of layer regional thickness on OCT data in patients with RRMS, without evidence of optic neuritis (MS-NON) compared to healthy subjects, using a graph theoretical approach.
Method: 54 patients (mean age: 37.4 ± 10.7, mean EDSS: 1.9 ± 1.3) and 53 age and sex-matched healthy subjects were enrolled. Each eye was considered a statistical unit, eyes with history of optic neuritis (MS-ON) were excluded, selecting 97 cases and 106 controls. Posterior pole OCT scanning was used to measure thickness of retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) in 64 regions of interests (ROIs) with a 3° x 3° area. A network was derived based on Pearson correlations between ROIs and visualized in anatomical space by locating each layer ROIs according to their imaging acquisition coordinates. OCT network topologies were analysed using commonly used graph analysis measures, local and global mean clustering coefficients (C) and path lengths (L), using a minimum correlation threshold (T) from 0.3 to 0.5 to reduce noise.
Results: RNFL, GCL and IPL showed a significantly higher mean C in cases than controls for T from 0,3 to 0,5 (P< 0,05, Mann Whitney U Test), indicating an increased clustering of the network. RNFL mean L was significantly lower in cases than controls for T of 0.4 and 0.5 (P< 0.05, Mann Whitney U Test); GCL and IPL L were significantly lower in cases than controls for all T considered (P< 0.05, Mann Whitney U Test), indicating a reduction in network segregation.
Conclusions: IRL MS-NON eyes showed a global rearrangement in connectomic architecture compared to healthy controls. The combination of a higher local clustering (C) and lower remote segregation (L) indicate an increased connection density between regions close to each other and a specific change in long-distance connections. Together, these measures seem to indicate that the pattern of atrophy is non-random and features common network patterns. Whether such a network rearrangement has functional impact needs further research.
Disclosure: D. Landi received travel funding from Biogen, Merck Serono, Sanofi-Genzyme, Teva, honoraria for speaking from Sanofi-Genzyme, Teva, Biogen and consultation fees from Merck Serono, Teva, Roche. She is currently subinvestigator in clinical trials being conducted for Biogen, Novartis, Roche, Celgene.
E. Di Carlo has nothing to disclose.
G. Di Mauro has nothing to disclose.
M. Albanese received honoraria for traveling from Almirall, Biogen, Merck Serono, Novartis,and Teva. She is involved as sub-investigator in clinical trials for Bayer Schering, Biogen Idec, Novartis, Merck Serono, Sanofi-Genzyme, Teva, Roche.
M.M. Schoonheim serves on the editorial board of Frontiers of Neurology, receives research support from the Dutch MS Research Foundation and has received compensation for consulting services or speaker honoraria from Excemed, Genzyme and Biogen.
R. Sorge has nothing to disclose.
G. Mataluni received travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme; honoraria for speaking from Biogen. She is subinvestigator in clinical trials being conducted for Biogen, Merck Serono, Novartis, Roche and Teva.
F. Monteleone received funding for traveling from Almirall, Biogen and Sanofi-Genzyme and consultation fees from Almirall.
C.G. Nicoletti received funding for traveling from Almirall, Biogen, Merck and Sanofi-Genzyme.
L. Boffa received travel funding from Almirall, Merck Serono, Sanofi-Genzyme and Teva.
D. Centonze is an Advisory Board member of Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva. He is also the principal investigator in clinical trials for Bayer Schering, Biogen, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva. His preclinical and clinical research was supported by grants from Bayer Schering, Biogen Idec, Celgene, Merck Serono, Novartis, Roche, Sanofi- Genzyme e Teva.
R. Mancino has nothing to disclose.
G.A. Marfia is an Advisory Board member of Biogen Idec, Genzyme, Merck-Serono, Novartis, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, Teva. She is the principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva.