Optical coherence tomography as a potential readout in clinical trials

Abstract

Optical coherence tomography (OCT) is a noninvasive tool used for measuring tissue at micrometer resolution. It has been extensively applied to ocular pathologies and is now being studied as a biomarker in various neurologic conditions. The retina represents a unique environment for study, with unmyelinated axons that directly synapse into the central nervous system. When trying to quantify axonal degradation in neurologic disease, the currently used imaging modalities are limited in sensitivity and specificity. Early data suggest that several neurologic conditions have pathologic changes in the retinal nerve fiber layer of the eye, creating a potential surrogate marker for neurodegeneration. OCT has the potential to become a noninvasive, reproducible test for axonal degeneration that could become an invaluable tool for measuring the efficacy of potential neuroprotective agents. If the natural history of neurodegeneration, as measured by OCT, can be documented in diseases such as Alzheimer's, Parkinson's and multiple sclerosis, then OCT can be used to measure alterations in the rate of degeneration when treatment is applied. Thus, OCT represents a new, promising technology for documenting outcomes in neuroprotection trials.

Keywords: macula; multiple sclerosis; neurodegeneration; optical coherence tomography; retinal nerve fiber layer.

Figures

Figure 1.

Diagram of optical coherence tomography.

Figure 2.

(a) Optic nerve head pictured on fundus photography. (b) Representative report from a time domain optical coherence tomography (OCT) device acquired on a Zeiss Cirrus™ model 4000 OCT device. (c) Representative report from a GDx polarimetry device acquired on a Zeiss GDx™ scanner.

Figure 3.

Findings in a multiple sclerosis patient with previous right eye optic neuritis.

Figure 4.

Evidence of a saccadic eye movement occurring during optical coherence tomography (OCT) acquisition. The arrow denotes the point where the saccade occurred. If this had happened at the point of the optic nerve, the retinal nerve fiber layer (RNFL) measurement would be affected.