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  • Review Article
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Optical coherence tomography: a window into the mechanisms of multiple sclerosis

Abstract

The pathophysiology of multiple sclerosis (MS) is characterized by demyelination, which culminates in a reduction in axonal transmission. Axonal and neuronal degeneration seem to be concomitant features of MS and are probably the pathological processes responsible for permanent disability in this disease. The retina is unique within the CNS in that it contains axons and glia but no myelin, and it is, therefore, an ideal structure within which to visualize the processes of neurodegeneration, neuroprotection, and potentially even neurorestoration. In particular, the retina enables us to investigate a specific compartment of the CNS that is targeted by the disease process. Optical coherence tomography (OCT) can provide high-resolution reconstructions of retinal anatomy in a rapid and reproducible fashion and, we believe, is ideal for precisely modeling the disease process in MS. In this Review, we provide a broad overview of the physics of OCT, the unique properties of this method with respect to imaging retinal architecture, and the applications that are being developed for OCT to understand mechanisms of tissue injury within the brain.

Key Points

  • Multiple sclerosis (MS) is characterized by axonal and neuronal degeneration in both the white and the gray matter pathways of the CNS

  • The retina is devoid of myelin but contains ganglion cell neurons and their associated axons, and it thereby represents an ideal nervous tissue with which to model processes of axonal and neuronal degeneration in MS

  • Optical coherence tomography (OCT) is a noninvasive retinal imaging technology that can sensitively and rapidly measure changes in structural architecture that are a consequence of the disease process in MS

  • OCT metrics (retinal nerve fiber layer thickness and macular volumes) have been shown to correlate with clinical measures of vision loss (e.g. low-contrast letter acuity and visual field analyses)

  • OCT, and perhaps other retinal imaging technologies, may facilitate visualization of the disease process in MS and may be useful in detecting and monitoring the process of neuroprotection in response to therapeutic agents

  • More-advanced retinal imaging techniques are now available with the advantages of high definition, high speed, automatic optic disc centering, co-registration capability, and eye movement correction analysis, and they will ultimately bring us closer to more directly interrogating CNS tissues to understand the mechanisms of tissue damage and what can be done to prevent it

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Figure 1: High-resolution images of the internal retinal structure taken with optical coherence tomography (OCT), demonstrating the processes involved in using this technology.
Figure 2: A typical optical coherence tomography (OCT) report from a patient with multiple sclerosis (MS), generated by Zeiss Stratus OCT3™ with software 4.0 (Carl Zeiss Meditec, Inc).
Figure 3: An optical coherence tomography (OCT) report for the macular region of the retina from the same patient with multiple sclerosis as is shown in Figure 2.
Figure 4: Data are presented from a patient with multiple sclerosis with a remote episode of right optic neuritis resulting in superior visual field loss.
Figure 5: Fundus (left), nerve fiber layer maps (middle), and deviation maps (right; compared with normal individuals) derived from laser polarimetry (GDx) imaging of the same patient as is shown in Figure 4.
Figure 6: High-definition, ultra-high-resolution optical coherence tomography (OCT) scans.

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Acknowledgements

This project was supported by the Once Upon A Time Foundation, the Cain/Denius Comprehensive Center for Mobility Research, the Irene Wadel and Robert Atha fund, the Kenney Marie Dixon Pickens fund, and the Jean Ann and Steve Brock Fund for Medical Sciences (EM Frohman). We acknowledge support from the National Institutes of Health R01-EY11289-21, and from the Air Force Office of Scientific Research, Medical Free Electron Laser Program contract FA9550-07-1-0101 (J Fujimoto). The article is supported by National Multiple Sclerosis Society Grants PP115, RG 3208-A-1, RG 3428-A/2 (LJ Balcer), National Multiple Sclerosis Society Translational Research Partnership TR 3760-A-3 (PA Calabresi and LJ Balcer), and National Eye Institute/NIH grant K24 EY 018136 (LJ Balcer).

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Correspondence to Elliot M Frohman.

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Competing interests

JG Fujimoto is a director of Optovue and a patent holder or applicant with Carl Zeiss Meditec and LightLab Imaging. G Cutter has received funding for participation in data and safety monitoring committees from Antisense Therapeutics, Bayhill Therapeutics, BioMS Medical, Genmab, GlaxoSmithKline, the NHLBI, NINDS, the National Multiple Sclerosis Society, PTC Therapeutics, sanofi-aventis, Teva, and Vivus, and he has also received funding in the form of consulting, speaking or Advisory Board fees from Accentia Biopharmaceuticals, Alexion Pharmacueticals, BaroFold, Biogen Idec, CIBA VISION, Consortium of Multiple Sclerosis Centers, Enzo, Genentech, Klein Buendel, MediciNova, the Multiple Sclerosis Association of America, MS-CORE, the NMSS, Novartis, and Somnus Therapeutics.

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Frohman, E., Fujimoto, J., Frohman, T. et al. Optical coherence tomography: a window into the mechanisms of multiple sclerosis. Nat Rev Neurol 4, 664–675 (2008). https://doi.org/10.1038/ncpneuro0950

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