Retinal thickness points to disability worsening in MS patients

By Lucy Piper

The thickness of the peripapillary retinal nerve fibre layer (pRNFL) may help to predict worsening disability in patients with multiple sclerosis (MS), optical coherence tomography (OCT) findings indicate.

The risk of disability worsening was about doubled among MS patients who had a pRNFL thickness below 88 µm in eyes unaffected by optic neuritis, compared with patients with thicker pRNFL.

"Our findings might help neurologists to monitor the disease in clinical settings and, more importantly, to help drive treatment decisions based on a marker of neuro-axonal damage", say Pablo Villoslada (Insitut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain) and co-researchers.

They used the Expanded Disability Status Scale (EDSS) to assess disability worsening over a period of 0.5 to 5 years in 879 patients with clinically isolated syndrome, relapsing-remitting MS or progressive MS.

The patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Canada, the Netherlands and the USA and were all older than 16 years.

Their pRNFL thickness was measured at baseline using Spectralis (Heidelberg Engineering, Germany) or Cirrus (Carl Zeiss, Dublin, California, USA) OCT and calculated as the average value of both eyes for patients without optic neuritis or just the one non-optic neuritis eye for those with unilateral optic neuritis.

During a median 2 years of follow-up, 252 (29%) patients experienced disability worsening. This was most likely to occur in patients who were older, had a longer disease duration, worse disability at baseline and progressive MS. Patients were less likely to have disability worsening if they had previous optic neuritis.

Adjusted analysis showed that patients in the lowest tertile of pRNFL (≤87 µm) at baseline were a significant 1.75 times more likely to experience disability worsening than those in the intermediate (>87-98 µm) and highest (>98 µm) tertiles. There was no significant difference among patients in the intermediate and highest tertiles and when this aggregate group was used as comparison, the risk of disability worsening for patients in the lowest tertile was increased 1.96 times.

Also further analysis indicated that the association between the risk of worsening disability and pRNFL thickness was not significant for the first year and was similar for years 2 and 3 and for 4 and 5.

Based on this, the team's exploratory analyses estimated that patients with pRNFL of or below 87 µm (Cirrus) or 88 µm (Spectralis) had a twofold increased risk of disability worsening any time after the first year and until the third year of follow-up compared with patients with thicker pRNFL.

This risk increased to nearly fourfold after 3 years and up to 5 years, the researchers report in The Lancet Neurology.

By contrast, there was no association between worsening disability and macular volume.

"Our finding that patients with a given level of axonal damage, as shown by pRNFL thickness, are more likely to have disability worsening lends supports to the notion of a threshold in CNS [central nervous system] damage, after which further damage translates to increasing clinical disability", observes the team.

Although the causes underlying disability worsening are not well understood, the researchers say they probably involve acute damage during relapses of chronic CNS inflammation and degenerative processes.

They also highlight the benefits of being able to use OCT as a complement to magnetic resonance imaging, being technically easier and more accessible and amenable to use in outpatient settings.

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