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

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.

Structure‐function relationships in the visual system in multiple sclerosis: an MEG and OCT study

“…Importantly, retrograde transsynaptic atrophy in the retina stops at the level of the INL 8, 9, 10, 11. The preservation of the INL following MSON is understood to be due to multiple afferent inputs through a network of horizontal and amacrine cells 8, 12, 13. Another less well understood, but consistent, observation in the retina is the thickening of the ORL following MSON 8, 12.…”

Time to steroid treatment in severe acute optic neuritis

“…The fact that the thickness of the peripapillar and macular retinal nerve fiber layer (pRNFL and mRNFL) and ganglion cell layer combined with the inner plexiform layer (GCIP) were reduced in the affected eye after 6 months, confirms that these cells are the primary cellular site of the disease (Al‐Louzi et al., 2015; Gabilondo et al., 2015; Henderson et al., 2010). The GCIP layer was the preferred outcome measure over the pRNFL and mRFNL, since the GCIP layer is unaffected by optic disc edema and therefore provides more precise information on the structural retinal changes caused by ON (Syc et al., 2012). The increased thickness of outer retinal layers after 6 months, followed by a slight thickness reduction of all retinal layers at 12 months may be due to involvement of the dentritical part of the retinal ganglion cells and a transitory reaction in the outer retina triggered by the inflammatory activity in the inner retina (Al‐Louzi et al., 2015; Gabilondo et al., 2015).…”

“…The prognosis for visual recovery is generally good but contrast sensitivity and color vision are rarely normal, especially in patients with MS (Beck et al., 2004; Cole, Beck, Moke, Gal, & Long, 2000; Fleishman, Beck, Linares, & Klein, 1987). ON can cause axonal loss in the optic nerve, which can be visualized using optical coherence tomography (OCT) scanning and is seen as reduced thickness of the retinal nerve fiber (RNFL) and ganglion cell layer (GCL) (Costello et al., 2006, 2008; Syc et al., 2012). …”

Retinal ganglion cell and axonal loss in optic neuritis: risk factors and visual functions

“…Significant axonal loss occurs following the acute inflammatory process that eventually results in retinal ganglion cell neuronal loss through retrograde degeneration. [1][2][3][4][5] The macular ganglion cell layer (GCL) gives rise to the retinal nerve fiber layer (RNFL) and can be affected by axonal inflammation. 6 Previously, the RNFL around the optic disc, which is composed of axons originating from retinal ganglion cell neurons, was used to assess eye damage instead of the GCL, because the GCL could not be analyzed separately in vivo.…”

“…7 SD-OCT can demonstrate both peripapillary retinal nerve fiber layer (pRNFL) and retinal GCL thinning in optic nerve injuries. 5,8 The RNFL contains the retinal ganglion cell axons that comprise the optic nerve. It represents a unique region of the central nervous system because it lacks myelin.…”