Multiple Sclerosis Progression: Retinal Layer Thickness May Act as Biomarker

The change in retinal thickness may be a biomarker for multiple sclerosis (MS) progression, according study findings published in Neurology Neuroimmunology & Neuroinflammation.

Previous studies have postulated that optical coherence tomography (OCT)-based biomarkers may predict relapse and/or progression in MS. However, no standardized definitions or robust pathologic thresholds have been proposed.

Researchers sourced data for this study from the IMSVISUAL cohort, Berlin CIS cohort, and 552 healthy control participants (mean age, 38.8; women, 61.2%) in 4 MS studies conducted in Europe. Overall, data from 910 healthy eyes for peripheral retinal nerve fiber layer (pRNFL) thickness and 423 healthy eyes for ganglion cell-inner plexiform layer (GCIP) thickness were used to determine age-adjusted healthy z scores. These distributions were compared with data from 863 (mean age, 40.9; women, 66.0%) and 78 (mean age, 33.7; women, 64.1%) patients with MS to predict worsening disability using pRNFL and GCIP as biomarkers, respectively, defined using the Expanded Disability Status Scale (EDSS) the no evidence of disease activity (NEDA-3) criteria.

In the pRNFL analysis, most patients (n=722) underwent OCT on a Spectralis SD-OCT device. Of those with Spectralis SD-OCT data, 23.8% had a confirmed EDSS increase during a median follow-up of 2.0 years.

Worsening disability was associated with lower pRNFL z score (pRNFL-z). The optimal pRNFL-z cutoff using Spectralis SD-OCT data was -2.04 or lower (hazard ratio [HR], 2.08; 95% CI, 1.47-2.95; P =3.82e^-5) and using Cirrus HD-OCT data was -0.8 or lower (HR, 1.76; 95% CI, 1.02-3.07; P =.044).

In the GCIP analysis, 59.0% did not maintain their NEDA-3 status. Failure to maintain NEDA-3 was due to new clinical relapse (29.5%), new magnetic resonance imaging (MRI) brain activity (48.7%), and EDSS score increase (11.5%). All GCIP data were collected using the Spectralis SD-OCT.

Increased disease activity was associated with lower GCIP z score (GCIP-z). The optimal GCIP-z cutoff was -1.03 or lower (adjusted hazard ratio [aHR], 2.14; 95% CI, 1.03-4.43; P =.042). Stratified by outcome, the optimal GCIP-z cutoffs were -1.3 or lower for new relapse, -0.17 for new brain MRI activity, and 0.56 or lower for confirmed EDSS score increase. However, the GCIP-z cutoff only significantly predicted new relapse (aHR, 2.81; 95% CI, 1.19-6.66; P =.019).

The major limitation of this study was that the normative healthy control data were derived from a homogeneous population of mostly White individuals.

“[O]ur results support the potential of both pRNFL-z and GCIP-z as promising biomarkers with prognostic value for future disease progression in MS. Generating retinal layer thickness z scores that control for age and other confounding factors may be a robust approach for individual prognostication,” the researchers concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.