Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis

Stephanie B. Syc, Shiv Saidha, Scott D. Newsome, John N. Ratchford, Michael Levy, E'Tona Ford, Ciprian M. Crainiceanu, Mary K. Durbin, Jonathan D. Oakley, Scott A. Meyer, Elliot Frohman, Peter A. Calabresi

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)521-533
Number of pages13
JournalBrain
Volume135
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

Optic Neuritis
Optical Coherence Tomography
Ganglia
Pathology
Neuromyelitis Optica
Multiple Sclerosis
Neuroprotective Agents
Nerve Fibers
Cells
Tomography
Segmentation
Optics
Optical
Layer
Retrograde Degeneration
Longitudinal Studies
Edema
Healthy Volunteers

Keywords

  • demyelinating disease
  • multiple sclerosis
  • neuro-ophthalmology
  • optic neuritis
  • optical coherence tomography
  • retinal segmentation

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Syc, S. B., Saidha, S., Newsome, S. D., Ratchford, J. N., Levy, M., Ford, ET., ... Calabresi, P. A. (2012). Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis. Brain, 135(2), 521-533. https://doi.org/10.1093/brain/awr264

Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis. / Syc, Stephanie B.; Saidha, Shiv; Newsome, Scott D.; Ratchford, John N.; Levy, Michael; Ford, E'Tona; Crainiceanu, Ciprian M.; Durbin, Mary K.; Oakley, Jonathan D.; Meyer, Scott A.; Frohman, Elliot; Calabresi, Peter A.

In: Brain, Vol. 135, No. 2, 02.2012, p. 521-533.

Research output: Contribution to journalArticle

Syc, SB, Saidha, S, Newsome, SD, Ratchford, JN, Levy, M, Ford, ET, Crainiceanu, CM, Durbin, MK, Oakley, JD, Meyer, SA, Frohman, E & Calabresi, PA 2012, 'Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis', Brain, vol. 135, no. 2, pp. 521-533. https://doi.org/10.1093/brain/awr264
Syc SB, Saidha S, Newsome SD, Ratchford JN, Levy M, Ford ET et al. Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis. Brain. 2012 Feb;135(2):521-533. https://doi.org/10.1093/brain/awr264
Syc, Stephanie B. ; Saidha, Shiv ; Newsome, Scott D. ; Ratchford, John N. ; Levy, Michael ; Ford, E'Tona ; Crainiceanu, Ciprian M. ; Durbin, Mary K. ; Oakley, Jonathan D. ; Meyer, Scott A. ; Frohman, Elliot ; Calabresi, Peter A. / Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis. In: Brain. 2012 ; Vol. 135, No. 2. pp. 521-533.
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abstract = "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.",
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