BOSTON — The thinning of the retina that occurs during the course of multiple sclerosis (MS) closely parallels brain atrophy and may be used to measure neurodegeneration, a new study has shown.

Presenting the data here at MSBoston 2014, the 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) meeting, Shiv Saidha, MD, Johns Hopkins Hospital, Baltimore, Maryland, explained that previous studies had correlated retinal thinning with global disability and brain atrophy, but these studies were primarily cross-sectional in design.

"Our study is groundbreaking in that it is the first ever longitudinal study to look at how retinal changes measured by optical coherence tomography (OCT) track with MRI measures of brain atrophy," he said. "These results could have far-reaching implications for the field of neurodegeneration."

"We showed clearly that the degree of retinal layer thinning predicts the loss of brain tissue. Patients who lost the most neurons in the retina had the highest amount of brain loss on MRI."

Dr. Shiv Saidha

He added: "It was particularly effective in patients with progressive MS, but it can be used from the very beginning to identify which patients are deteriorating the fastest."

The MS field has suffered from a lack of tools to track neurodegeneration, and much work is underway to identify such markers, Dr. Saidha added. "Our data shows that measuring changes in the retina with OCT is one of the most promising techniques for this purpose."

"It is easy to do — it takes just 5 minutes to assay the retina," he commented to Medscape Medical News. "It is cheap and easily reproducible. In my view, it is very encouraging."

Validation for Use in Clinical Trials

These opinions were echoed by the chair of the Young Investigators session at which Dr. Saidha presented the study, Patrick Vermersch, MD, Centre Hospitalier Régional Universitaire de Lille, France.

"This study is really interesting," he told Medscape Medical News. "This methodology adds complementary information to explain the neurodegenerative process in MS. Measuring retinal thinning with OCT is much easier than trying to assess brain atrophy with MRI. It is already being used as a marker of treatment response in therapeutic trials, but this study gives validation that this is an appropriate marker to measure."

Dr. Vermersch suggested that OCT may not be as sensitive as measuring brain atrophy with MRI, but it is far more convenient. "I would think MRI will be superior, but it is not widely available," he added. "It is not possible to measure brain atrophy in routine clinical practice — the specific software is only available in specialist centers for research use at present. But OCT is widely available and easy to use."

For the study, 108 MS patients underwent OCT every 6 months (average follow-up duration, 42 months) and annual MRI (3T) of the brain (average follow-up duration, 39 months). Patients with optic neuritis during the study were excluded. Individual-specific rates of change in retinal and brain measures were correlated after adjustment for age, sex, disease duration, and optic neuritis history.

Results showed that the thickness of the ganglion cell layer plus inner plexiform layer of the retina together (GCIP) had the best correlation to whole brain atrophy, with a correlation coefficient of 0.449. GCIP loss was also correlated to atrophy in gray matter (r = 0.371), white matter (r = 0.285), and thalamic (r = 0.379) regions of the brain over time.

Best in Secondary Progressive Disease

The correlation between GCIP and brain atrophy rates was stronger in secondary progressive MS (r = 0.730) and primary progressive MS (r = 0.542) than in relapsing-remitting MS (r = 0.328).

"Although the association between GCIP and brain atrophy in relapsing-remitting MS is impressive, the association in progressive MS, particularly secondary progressive MS, appears to be exceptional," Dr. Saidha stated.

The relationship between GCIP and brain atrophy was affected by history of optic neuritis, which reduced the strength of the correlation, especially in the relapsing-remitting population.

Dr. Saidha reported that for every yearly change of 1 micron in GCIP thickness there was a 0.45% yearly brain loss in eyes without a history of optic neuritis. GCIP atrophy also mirrored lesion accumulation in MS, although this was not as strong as the relationship with brain atrophy.

"Our findings confirm the utility of OCT for tracking subclinical as well as clinical disease progression in MS and establish a role for OCT in clinical trials for the objective investigation of neuroprotection," Dr. Saidha concluded.

MSBoston 2014: 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS). Abstract Y12.2. Presented September 10, 2014.

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