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.

Conflict of interest statement

Competing interests: JG Fujimoto has declared associations with the following companies: Carl Zeiss Meditec, LightLab Imaging and Optovue. G Cutter has declared associations with the following companies and organizations: Accentia Biopharmaceuticals, Alexion Pharmaceuticals, Antisense Therapeutics, BaroFold, Bayhill Therapeutics, Biogen Idec, BioMS Medical, CIBA VISION, Consortium of Multiple Sclerosis Centers, Enzo, Genentech, Genmab, GlaxoSmithKline, Klein Buendel, MediciNova, the Multiple Sclerosis Association of America, MS-CORE, the NHLBI, NINDS, the National Multiple Sclerosis Society, Novartis, PTC Therapeutics, sanofi-aventis, Somnus Therapeutics, Teva, and Vivus. See the article online for full details of the relationships. The other authors declared no competing interests.

Figures

Figure 1

High-resolution images of the internal retinal structure taken with optical coherence tomography (OCT), demonstrating the processes involved in using this technology. (A) Low-coherence infrared light is transmitted into the eye through use of an interoferometer. (B) The infrared light is transmitted through the pupil and then penetrates through the transparent nine layers of the retina. Subsequently, the light backscatters and returns through the pupil, where detectors can analyze the interference of light returning from the layers of the retina compared with light traveling a reference path (mirror #2). An algorithm mathematically uses this information to construct a gray-scale or false-color image representing the anatomy of the retina (shown in the upper right portion of the figure). (C) A fundus image from the OCT device, showing the optic disc appropriately centered and surrounded by the target image circumference marker for analysis of the retinal nerve fiber layer.

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). On the upper left, retinal nerve fiber layer (RNFL) thickness is plotted (Y axis) with respect to a circumferential retinal map on the X axis (temporal-superior-nasal-inferior-temporal [TSNIT] quadrants of the RNFL). Note the normal ‘double-hump’ appearance of the topographic map of the right eye (OD), signifying the thicker RNFL measures derived from the superior and inferior retina compared with the nasal and temporal regions. Also note the quadrant and clockface sector measures of RNFL thickness (upper middle illustration). The table (lower middle) compiles the quantitative data, including the average RNFL thickness (bottom row). This patient experienced an episode of left optic neuritis 6 months before this study. Note the marked reduction in RNFL thickness across all quadrants (red region denoting values below 1% of what would be expected when compared with a reference population), multiple sectors, and with respect to the average RNFL thickness (bottom row of table). Abbreviations: OD, right eye; OS, left eye.

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. Note the volume reductions in the foveola (central macula) and the parafoveal quadrants on the left of the report. Whereas the reductions in retinal nerve fiber layer thickness implicate loss of ganglion cell axons, macular changes implicate losses of the ganglion cell neurons themselves. While the patient has had no history of optic neuritis in the right eye, there are some subtle macular changes on that side, suggesting occult involvement of this eye as well. Abbreviations: OD, right eye; OS, left eye.

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. (A) A Humphrey automated perimetry visual field analysis is shown, demonstrating a superior altitudinal field cut, best confirmed on the pattern deviation plot (bottom right). (B) The corresponding optical coherence tomography (OCT) report from the same patient. The OCT report reveals only a 6.58 μm difference in average retinal nerve fiber layer thickness between the two eyes. However, more-prominent discrepancy is demonstrated on quadrant and sector analysis in an inferior distribution. Abbreviations: OD, right eye; OS, left eye.

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. Note the reduction in retinal nerve fiber layer thickness in the inferior neural retinal rim in (A) the right eye compared with (B) the normal left eye, as shown in both the thickness map (less red) and deviation maps (increased colored pixels; arrow).

Figure 6

High-definition, ultra-high-resolution optical coherence tomography (OCT) scans. The high data acquisition speeds available with spectral domain detection enable the acquisition of high-definition images with large numbers of transverse pixels. (A) A 10,000 axial scans per second image of the papillomacular axis acquired in 0.6 s. The axial image resolution is approximately 3 μm. The image may be zoomed in the (B) foveal or (C) optic disc regions to visualize details of internal retinal morphology. OCT has been termed “optical biopsy”, and ultra-high-resolution OCT imaging can provide excellent visualization of retinal architecture. Abbreviations: ELM, external limiting membrane; IS/OS, junction between inner and outer photoreceptor segments; NFL, nerve fiber layer; ONL, outer nuclear layer; OPL, outer plexiform layer; RPE, retinal pigment epithelium.