Retinal imaging with optical coherence tomography: a biomarker in multiple sclerosis?

Abstract

Multiple sclerosis (MS) is a progressive neurological disorder characterized by both inflammatory and degenerative components that affect genetically susceptible individuals. Currently, the cause of MS remains unclear, and there is no known cure. Commonly used therapies tend to target inflammatory aspects of MS, but may not halt disease progression, which may be governed by the slow, subclinical accumulation of injury to neuroaxonal structures in the central nervous system (CNS). A recognized challenge in the field of MS relates to the need for better methods of detecting, quantifying, and ameliorating the effects of subclinical disease. Simply stated, better biomarkers are required. To this end, optical coherence tomography (OCT) provides highly reliable, reproducible measures of axonal damage and neuronal loss in MS patients. OCT-detected decrements in retinal nerve fiber layer thickness and ganglion-cell layer-inner plexiform layer thickness, which represent markers of axonal damage and neuronal injury, respectively, have been shown to correlate with worse visual outcomes, increased clinical disability, and magnetic resonance imaging-measured burden of disease in MS patients. Recent reports have also suggested that OCT-measured microcystic macular edema and associated thickening of the retinal inner nuclear layer represent markers of active CNS inflammatory activity. Using the visual system as a putative clinical model in MS, OCT measures of neuroaxonal structure can be correlated with functional outcomes to help us elucidate mechanisms of CNS injury and repair. In this review, we evaluate evidence from the published literature and ongoing clinical trials that support the emerging role of OCT in diagnosing, staging, and determining response to therapy in MS patients.

Keywords: axonal degeneration; biomarker; central nervous system inflammation; multiple sclerosis; neuronal loss; optical coherence tomography.

Figure 1

Macular OCT with intraretinal layers. Notes: Reproduced from Schematic Figure – Macular OCT with Intraretinal Layers by Neurodiagnostics Laboratory @ Charité – Universitätsmedizin Berlin, Germany. Available from: http://neurodial.de/2017/08/25/schematic-figure-macular-oct-with-intraretinal-layers/. Creative Commons Attribution 4.0 International License. Abbreviations: OCT, optical coherence tomography; ILM, internal limiting membrane; RNFL, retinal nerve fiber layer; GCIP, ganglion cell–internal plexiform; GCL, ganglion cell layer; IPL, internal plexiform layer; INL, inner nuclear layer; BM, Bruch membrane; RPE, retinal pigment epithelium; ISOS, inner segment–outer segment (junction); ELM, external limiting membrane; ONL, outer nuclear layer; OPL, outer plexiform layer; OPT, outer photoreceptor tip.

Figure 2

OCT-measured peripapillary RNFL thickness measures obtained from May 2011 to September 2017 in a patient with acute optic neuritis in the left eye (2011), and subclinical optic neuritis in the right eye (2012). Note there is mild test–retest variability in the RNFL measures of both eyes over time. The clinical and subclinical optic neuritis events were heralded by marked increases in the RNFL thickness of the affected eye(s), relative to the baseline RNFL values. Abbreviations: OCT, optical coherence tomography; RNFL, retinal nerve fiber layer.

Figure 3

GCL analysis showing right hemiretinal thinning and left homonymous visual field loss caused by a lesion in the right optic tract. Notes: This 30-year old woman with RRMS presented with difficulty seeing the beginning of words caused by a left quandrantanopic visual field defect. She had a left relative afferent visual field defect. GCL analysis shows a pattern of right hemiretinal loss (arrows) correlating with a right optic tract lesion. Abbreviations: GCL, ganglion-cell layer; RRMS, relapsing–remitting multiple sclerosis; IPL, internal plexiform layer.

Figure 4

Optical coherence tomography showing evidence of cystoid macular edema (arrow) in a patient with fingolimod-associated macular edema.