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Optical coherence tomography emerging as a promising biomarker for MS



– Optical coherence tomography (OCT) has emerged as a promising biomarker in multiple sclerosis.

Dr. Shiv Saidha of Johns Hopkins University, Baltimore Doug Brunk/MDedge News

Dr. Shiv Saidha

Thanks to OCT, clinicians are gaining an improved understanding of how MS affects certain eye structures. An optical analogue of ultrasound B mode imaging, OCT achieves a resolution of about 3-6 microns with commercially available devices. “That allows us to quantify the layers of the retina with quite a degree of accuracy,” Shiv Saidha, MD, said at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

At postmortem, up to 99% of MS patients have demyelinated plaques in their optic nerves. “This implies that optic neuropathy is an ubiquitous phenomenon as part of the MS disease process,” said Dr. Saidha, a neurologist at Johns Hopkins University, Baltimore. “The prevailing hypothesis is that there is demyelination or axonal transection related to acute inflammation that occurs within the optic nerve. There’s a retrograde degeneration of its constituent axons, and that results in thinning of the inner retinal nerve fiber layer as well as the neuronal derivative of this layer called the ganglion cell layer. In addition to neurodegenerative mechanisms in the retina, there is also perivascular inflammation, called retinal periphlebitis, which we know occurs in about 20% of MS patients. At postmortem, there are also activate microglia present within the retina of MS patients.”

One of the principal findings of OCT in MS to date is that the retinal nerve fiber layer (RNFL) and ganglion cell plus inner plexiform layer (GCIP) thinning reflects MS-related optic nerve neurodegeneration. In addition, RNFL and GCIP thinning occur after optic neuritis and also as part of the MS disease course in eyes without a history of optic neuritis. “RNFL and GCIP thinning in MS are clinically relevant and correlate with visual function, global disability, and brain atrophy,” Dr. Saidha said. Researchers have also found that rates of GCIP thinning are accelerated in MS patients exhibiting clinical and/or radiological disease activity and are altered by disease-modifying therapies, and that increased inner nuclear layer (INL) thickness correlates with T2 lesion volume and predicts clinical and radiological disease activity. “In numerous trials of putatively neuroprotective and restorative treatments, we see OCT incorporated more and more, either as a secondary or a primary outcome,” he said.

Predicting disability and brain atrophy

In a study expected to be appear in a forthcoming issue of the Annals of Translational and Clinical Neurology, colleagues of Dr. Saidha found that OCT derived retinal layer measurements and visual function predict disability at 10 years in patients with MS. The researchers used an earlier generation, lower quality OCT device to examine tertiles of total macular volume, “an old, nonspecific composite measure of all of the retinal components,” he explained. “Even with inferior technology, a single measurement at a point in time not only could predict the change in EDSS [Expanded Disability Status Scale] scores from baseline to 10 years, but the accumulation of meaningful disability.”

In an earlier study, Dr. Saidha and his colleagues conducted a 4-year study of OCT and MRI in MS (Ann Neurol 2015; 78[5]:801-13). It consisted of six monthly spectral domain OCT scans (including automated intra-retinal segmentation) and baseline and annual 3 T brain MRI (including substructure volumetrics). Patients with ocular relapses (optic neuritis) during the study were excluded. The researchers correlated individual-specific rates of change in retinal and brain measurements, adjusting for age, sex, disease duration, and optic neuritis history. They found that cerebral volume fraction (analogous to whole brain volume) “had a decent correlation between rates of GCIP atrophy and rates of whole brain volume loss,” he said. “That was predominately driven by cortical gray matter atrophy.”

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