OCT is an alternative to MRI for monitoring MS – Commentary

Commentary

“How am I to get in?” asked Alice again in a louder tone.

“Are you to get in at all?” said the Footman. “That’s the first question, you know.” (Lewis Carroll)

“It is better to debate a question without settling it than to settle a question without debating it.” (Joseph Joubert)

A basic presumption about a useful tool for monitoring disease is not only that the metric measures some salient aspect of disease pathobiology but that responding to that metric would yield some tangible clinical benefit for patients. Since its introduction to the field 19 years ago, optical coherence tomography (OCT) has been suggested to hold promise as a biomarker for tracking disease progression in multiple sclerosis (MS). ¹ In this issue of Multiple Sclerosis, Sotirchos and Saidha take up the contentious position that OCT has now reached the mature state that it may be more valuable than magnetic resonance imaging (MRI) in monitoring MS. However, ultimately, the authors hedge in claiming that OCT’s singular advantage over MRI is its cost and ready availability, but yield that the technique is only complementary to MRI. ²

MRI has proven itself extraordinarily useful at aiding in the diagnosis of MS. So much so that MRI has assumed an increasingly central role in unfolding iterations of the diagnostic criteria used to confirm an MS diagnosis. ³ Furthermore, gadolinium-enhancing lesions and new T2 lesions on MRI have proven to be meaningfully associated with relapses and short-term progression of disability in MS. These measurements have become standardized as outcome measures in phase-II clinical trials assessing immunomodulatory disease-modifying therapies. Mounting evidence has also suggested that use of these immunomodulatory agents has been associated with a reduction in long-term disability in MS and a delay in reaching disability milestones and even mortality in MS.^4,5

This would naturally lead one to conclude that MRI is a useful tool for monitoring progression in MS—and as claimed by Djamshidian and Seberic ⁶ that it is a better tool than OCT because it measures damage to the whole neuroaxis rather than just the retina. However, the question tackled by the two opposing sides was loaded from the start—it is prefaced on the assumption that MRI (as it is currently utilized in routine clinical management of MS) is useful for tracking the disease. Still more than 30 years since its introduction, it is far from clear that MRI is truly useful for monitoring disease progression in MS. In fact, long-term data suggest that MRI fails as a monitoring tool—as changes in therapy brought about by MRI evidence of disease do not appear to result in benefits for patients when viewed over a longer time frame. ⁴ Similarly, although OCT metrics correlate with disease progression over time, it has not been shown that changes in existing treatments brought about by responding to changes on OCT yields any benefit to patients. For now, the evidence would seem to suggest that standard MRI sequences fail as monitoring tools and that OCT has not been adequately assessed. Newer, refined, or focused sequences on MRI may prove to be better and more useful ⁷ —although focusing on a single area of the central nervous system (CNS) such as the thalamus or spinal cord may suffer the same limitations attributed to OCT.

A loaded question must be handled with care. The truth is that none of our metrics have proven that they should be employed for useful clinical monitoring of patients over the medium to long term. Existing OCT metrics—as measures of atrophy rather than inflammation—may yet prove to be extraordinarily valuable for tracking patients—and at the very least continue to have the advantage over MRI of cost and a readily interpretable result. For now, the full resolution of the current debate is not at hand. Both MRI and OCT partisans need to marshal long-term longitudinal data to see if either yields truly actionable results. Until then, the debates—and all of us interested in their outcome—remain unsettled.