TY - JOUR
T1 - Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis
AU - Syc, Stephanie B.
AU - Saidha, Shiv
AU - Newsome, Scott D.
AU - Ratchford, John N.
AU - Levy, Michael
AU - Ford, E'Tona
AU - Crainiceanu, Ciprian M.
AU - Durbin, Mary K.
AU - Oakley, Jonathan D.
AU - Meyer, Scott A.
AU - Frohman, Elliot
AU - Calabresi, Peter A.
N1 - Funding Information:
National Multiple Sclerosis Society (TR 3760-A-3 to P.A.C and RG 4212-A-4 to Laura J. Balcer subcontracted to P.A.C.); the National Eye Institute (R01 EY 014993 and R01 EY 019473 to Laura J. Balcer subcontracted to P.A.C.); the Braxton Debbie Angela Dillon and Skip (DADS) Donor Advisor Fund (to P.A.C., E.M.F.). S.B.S. reports no disclosures. S.S. has received consulting fees from MedicalLogix for the development of continuing medical education programs. S.D.N. has received speaker honoraria and consulting fees from Biogen Idec. J.N.R. receives research support for clinical trials from Novartis, Biogen-Idec and University of California-Los Angeles. M.L. and E.F. report no disclosures. C.M.C. has received consulting fees from On-X Life technologies and speaking and consulting fees from Merck. J.D.O., M.K.D. and S.A.M. are employed by Carl Zeiss Meditec Inc. E.M.F. has received speaking and consulting fees from Biogen Idec, TEVA Neuroscience, Acorda, Bayer and Novartis and consulting fees Abbott Laboratories. P.A.C. has provided consultation services to Novartis, EMD-Serono, Teva, Biogen-IDEC; and has received grant support from EMD-Serono, Teva, Biogen-IDEC, Genentech, Bayer, Abbott and Vertex.
PY - 2012/2
Y1 - 2012/2
N2 - Post-mortem ganglion cell dropout has been observed in multiple sclerosis; however, longitudinal in vivo assessment of retinal neuronal layers following acute optic neuritis remains largely unexplored. Peripapillary retinal nerve fibre layer thickness, measured by optical coherence tomography, has been proposed as an outcome measure in studies of neuroprotective agents in multiple sclerosis, yet potential swelling during the acute stages of optic neuritis may confound baseline measurements. The objective of this study was to ascertain whether patients with multiple sclerosis or neuromyelitis optica develop retinal neuronal layer pathology following acute optic neuritis, and to systematically characterize such changes in vivo over time. Spectral domain optical coherence tomography imaging, including automated retinal layer segmentation, was performed serially in 20 participants during the acute phase of optic neuritis, and again 3 and 6 months later. Imaging was performed cross-sectionally in 98 multiple sclerosis participants, 22 neuromyelitis optica participants and 72 healthy controls. Neuronal thinning was observed in the ganglion cell layer of eyes affected by acute optic neuritis 3 and 6 months after onset (P<0.001). Baseline ganglion cell layer thicknesses did not demonstrate swelling when compared with contralateral unaffected eyes, whereas peripapillary retinal nerve fibre layer oedema was observed in affected eyes (P=0.008) and subsequently thinned over the course of this study. Ganglion cell layer thickness was lower in both participants with multiple sclerosis and participants with neuromyelitis optica, with and without a history of optic neuritis, when compared with healthy controls (P<0.001) and correlated with visual function. Of all patient groups investigated, those with neuromyelitis optica and a history of optic neuritis exhibited the greatest reduction in ganglion cell layer thickness. Results from our in vivo longitudinal study demonstrate retinal neuronal layer thinning following acute optic neuritis, corroborating the hypothesis that axonal injury may cause neuronal pathology in multiple sclerosis. Further, these data provide evidence of subclinical disease activity, in both participants with multiple sclerosis and with neuromyelitis optica without a history of optic neuritis, a disease in which subclinical disease activity has not been widely appreciated. No pathology was seen in the inner or outer nuclear layers of eyes with optic neuritis, suggesting that retrograde degeneration after optic neuritis may not extend into the deeper retinal layers. The subsequent thinning of the ganglion cell layer following acute optic neuritis, in the absence of evidence of baseline swelling, suggests the potential utility of quantitative optical coherence tomography retinal layer segmentation to monitor neuroprotective effects of novel agents in therapeutic trials.
AB - Post-mortem ganglion cell dropout has been observed in multiple sclerosis; however, longitudinal in vivo assessment of retinal neuronal layers following acute optic neuritis remains largely unexplored. Peripapillary retinal nerve fibre layer thickness, measured by optical coherence tomography, has been proposed as an outcome measure in studies of neuroprotective agents in multiple sclerosis, yet potential swelling during the acute stages of optic neuritis may confound baseline measurements. The objective of this study was to ascertain whether patients with multiple sclerosis or neuromyelitis optica develop retinal neuronal layer pathology following acute optic neuritis, and to systematically characterize such changes in vivo over time. Spectral domain optical coherence tomography imaging, including automated retinal layer segmentation, was performed serially in 20 participants during the acute phase of optic neuritis, and again 3 and 6 months later. Imaging was performed cross-sectionally in 98 multiple sclerosis participants, 22 neuromyelitis optica participants and 72 healthy controls. Neuronal thinning was observed in the ganglion cell layer of eyes affected by acute optic neuritis 3 and 6 months after onset (P<0.001). Baseline ganglion cell layer thicknesses did not demonstrate swelling when compared with contralateral unaffected eyes, whereas peripapillary retinal nerve fibre layer oedema was observed in affected eyes (P=0.008) and subsequently thinned over the course of this study. Ganglion cell layer thickness was lower in both participants with multiple sclerosis and participants with neuromyelitis optica, with and without a history of optic neuritis, when compared with healthy controls (P<0.001) and correlated with visual function. Of all patient groups investigated, those with neuromyelitis optica and a history of optic neuritis exhibited the greatest reduction in ganglion cell layer thickness. Results from our in vivo longitudinal study demonstrate retinal neuronal layer thinning following acute optic neuritis, corroborating the hypothesis that axonal injury may cause neuronal pathology in multiple sclerosis. Further, these data provide evidence of subclinical disease activity, in both participants with multiple sclerosis and with neuromyelitis optica without a history of optic neuritis, a disease in which subclinical disease activity has not been widely appreciated. No pathology was seen in the inner or outer nuclear layers of eyes with optic neuritis, suggesting that retrograde degeneration after optic neuritis may not extend into the deeper retinal layers. The subsequent thinning of the ganglion cell layer following acute optic neuritis, in the absence of evidence of baseline swelling, suggests the potential utility of quantitative optical coherence tomography retinal layer segmentation to monitor neuroprotective effects of novel agents in therapeutic trials.
KW - demyelinating disease
KW - multiple sclerosis
KW - neuro-ophthalmology
KW - optic neuritis
KW - optical coherence tomography
KW - retinal segmentation
UR - http://www.scopus.com/inward/record.url?scp=84857223041&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857223041&partnerID=8YFLogxK
U2 - 10.1093/brain/awr264
DO - 10.1093/brain/awr264
M3 - Article
C2 - 22006982
AN - SCOPUS:84857223041
SN - 0006-8950
VL - 135
SP - 521
EP - 533
JO - Brain
JF - Brain
IS - 2
ER -