TY - JOUR
T1 - Timing of retinal neuronal and axonal loss in MS
T2 - a longitudinal OCT study
AU - Balk, Lisanne J.
AU - Cruz-Herranz, Andrés
AU - Albrecht, Philipp
AU - Arnow, Sam
AU - Gelfand, Jeffrey M.
AU - Tewarie, Prejaas
AU - Killestein, Joep
AU - Uitdehaag, Bernard M.J.
AU - Petzold, Axel
AU - Green, Ari J.
N1 - Funding Information:
LB reports grants from the Dutch MS Research Foundation, during the conduct of the study and the VUmc MS Centre reports grants for OCT projects from TEVA. AC, PT and SA report no disclosures. PA reports grants and personal fees from Biogen Idec, grants, personal fees and non-financial support from Novartis, grants from Merz Pharmaceuticals, personal fees and non-financial support from Teva, non-financial support from Ipsen, outside the submitted work. JG reports grants from NIH KL2TR000143, personal fees from MedImmune, support from Quest Diagnostics for work on a Dementia Care Pathway, personal fees from Medical-Legal Consulting, outside the submitted work. JK reports grants and personal fees from Biogen Idec, Novartis, Merck Serono, TEVA, Genzyme, Bayer Schering Pharma Glaxo Smith Kline, outside the submitted work. BU reports personal fees from Novartis, Merck Serono, Biogen Idec and Danone Research, outside the submitted work. AP reports grants from Dutch MS Society, grants from VKC foundation, during the conduct of the study; and is a member of the steering committee of the OCTiMS study by Novartis. AG reports personal fees from Roche, Accorda, Mylan Pharma, grants from Rachleff Family, NMSS, Novartis, UCSF CTSI, That Man May See, Robert Dale Family and Medimmune, outside the submitted work.
Publisher Copyright:
© 2016, The Author(s).
PY - 2016/7/1
Y1 - 2016/7/1
N2 - The objective of the study was to investigate the timing of central nervous system tissue atrophy in MS by evaluating longitudinal retinal volume changes in a broadly representative cohort with disease duration across the entire arc of disease. In this longitudinal study, 135 patients with MS and 16 healthy reference subjects underwent spectral-domain optical coherence tomography (OCT) at baseline and 2 years later. Following OCT quality control, automated segmentation of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell–inner plexiform layer (mGCIPL) and macular inner nuclear layer (mINL) was performed. Generalized estimation equations were used to analyze longitudinal changes and associations with disease duration and clinical measures. Participants had a median disease duration at baseline of 16.4 years (range 0.1–45.4). Nearly half (44 %) of the MS patients had previously experienced MS-related optic neuritis (MSON) more than 6 months prior. The MS patients demonstrated a significant decrease over 2 years of the pRNFL (−1.1 µm, 95 % CI 1.4–0.7, p < 0.001) and mGCIPL (−1.1 µm, 95 % CI −1.4 to −0.8, p < 0.001). This thinning was most pronounced early in the course of disease. These findings were irrespective of previous episodes of MSON. No consistent pattern of change was observed for the mINL (−0.03 µm, 95 % CI −0.2 to 0.2, p = 0.795). This longitudinal study demonstrated that injury of the innermost retinal layers is found in MS and that this damage occurs most rapidly during the early stages of disease. The attenuation of atrophy with longer disease duration is suggestive of a plateau effect. These findings emphasize the importance of early intervention to prevent such injury.
AB - The objective of the study was to investigate the timing of central nervous system tissue atrophy in MS by evaluating longitudinal retinal volume changes in a broadly representative cohort with disease duration across the entire arc of disease. In this longitudinal study, 135 patients with MS and 16 healthy reference subjects underwent spectral-domain optical coherence tomography (OCT) at baseline and 2 years later. Following OCT quality control, automated segmentation of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell–inner plexiform layer (mGCIPL) and macular inner nuclear layer (mINL) was performed. Generalized estimation equations were used to analyze longitudinal changes and associations with disease duration and clinical measures. Participants had a median disease duration at baseline of 16.4 years (range 0.1–45.4). Nearly half (44 %) of the MS patients had previously experienced MS-related optic neuritis (MSON) more than 6 months prior. The MS patients demonstrated a significant decrease over 2 years of the pRNFL (−1.1 µm, 95 % CI 1.4–0.7, p < 0.001) and mGCIPL (−1.1 µm, 95 % CI −1.4 to −0.8, p < 0.001). This thinning was most pronounced early in the course of disease. These findings were irrespective of previous episodes of MSON. No consistent pattern of change was observed for the mINL (−0.03 µm, 95 % CI −0.2 to 0.2, p = 0.795). This longitudinal study demonstrated that injury of the innermost retinal layers is found in MS and that this damage occurs most rapidly during the early stages of disease. The attenuation of atrophy with longer disease duration is suggestive of a plateau effect. These findings emphasize the importance of early intervention to prevent such injury.
KW - Multiple sclerosis
KW - Neurodegeneration
KW - Optical coherence tomography
KW - Retina
KW - RNFL
UR - http://www.scopus.com/inward/record.url?scp=84965078728&partnerID=8YFLogxK
U2 - 10.1007/s00415-016-8127-y
DO - 10.1007/s00415-016-8127-y
M3 - Article
C2 - 27142714
AN - SCOPUS:84965078728
SN - 0340-5354
VL - 263
SP - 1323
EP - 1331
JO - Journal of neurology
JF - Journal of neurology
IS - 7
ER -