OCT Offers Insights That Used To Require an Autopsy

Christoph Guetter suggests in “The eye is a window to the brain; but who’s looking?” that the micron scale resolution of optical coherence tomography (OCT) for in vivo cross-sectional imaging of the human retina may allow earlier and more accurate diagnoses of several common neurodegenerative disorders: Multiple Sclerosis (MS), Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).

Many of these diseases can only be definitively established by autopsy and rely on the detection of ambiguous symptoms that may only start years after the actual onset of the disease. If OCT lives up to its promise it will not only allow for earlier detection but more accurate assessments of potential new treatments earlier in their administration.

As an extension of the central nervous system, the eye offers a window to the brain. Since the advent of optical coherence tomography (OCT) imaging, in vivo cross-sectional imaging of the human retina has become commonplace, facilitating quantitative measurements of neuronal layer thicknesses at the micron scale.

Pioneering work by the group led by Professor Calabresi at the Johns Hopkins University School of Medicine has shown that intra-cranial volumes are associated with OCT-derived parameters in Multiple Sclerosis (MS) patients and healthy controls[1]. In particular:

  • Retinal nerve fiber layer (RNFL) and ganglion cell complex (GC-IPL) thicknesses correlate with whole-brain volume.
  • Inner nuclear layer (INL) thickness correlates with T2 lesion volume.
  • Outer nuclear layer (ONL) thickness “may reflect the global nature of neurodegeneration in MS”.
  • These findings create direct associations between brain and retinal structures that may be used clinically.

But what of other neurodegenerative diseases as seen using retinal OCT imaging? The associations there are more than compelling:

  • In Alzheimer’s disease, the correlates are measures of the RNFL, GC-IPL and INL [2,3].
  • In Parkinson’s, its the GC-IPL, ONL and OPL [4,5].
  • In amyotrophic lateral sclerosis (ALS), the RNFL and the INL are used [6].

[1] Saidha S, Sotirchos ES, Oh J et al. JAMA Neurol. 2013 Jan;70(1):34-43.
[2] Marziani et al., IOVS September 2013 54:5953-5958.
[3] Chang et al., Program No. 710.13, Society for Neuroscience, San Diego, 2013.
[4] Bayhan et al., Current Eye Research, 2014.
[5] Schneider et al., Journal of Neural Transmission, January 2014, Volume 121, Issue 1, pp 41-47.
[6] Ringelstein et al., Annals of Clinical and Translational Neurology, Volume 1, Issue 4, pp 290-7, April 2014.

In 2007 I attended a talk by Scott Johnson of the Myelin Repair Foundation on progress to date in developing new treatments for MS:  he indicated that one of the major challenges was that it was very difficult to access and assess the affected brain tissue.

Obviously Guetter’s informed speculation only points to the possibility of a breakthrough, but he cites research from the last two years that is certainly suggestive OCT may prove to be a useful new diagnostic modality not only for disorders of the eye but several other neurodegenerative conditions.

Imagine trying to manage high blood pressure or diabetes without low cost and accurate diagnostics; that’s where we are today with many of the neurodegenerative disorders. The deeper implication is that there are likely many other opportunities to apply complex algorithms to increasingly higher resolution sensor data for analyses that a decade or two ago would have been not just impossible but unthinkable. This in turn enables more rapid experimentation with new treatments that today are evaluated by gross measures of ongoing deterioration.

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