Retinal Layer Thickness May Predict MS Progression, Relapses

Measurements of the thickness of the eye’s retina — the layer of nerve cells lining the back of the eye — could be used to predict disability progression and relapses in people with multiple sclerosis (MS), a real-world study from Austria suggests.

“Our study shows that both crossectional and longitudinal measurement of [retinal] thinning is reliable as a biomarker of disability worsening in a real-world setting,” the researchers said.

The study, “Evaluation of Retinal Layer Thickness Parameters as Biomarkers in a Real-World Multiple Sclerosis Cohort,” was published in the journal Eye and Brain.

In MS, the thinning of the external and deeper retinal layers has been linked to a reduction in brain volume. Measurements of two specific layers of the retina, the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion-cell-and-inner-plexiform-layer (GCIPL), are considered biomarkers of neurodegeneration and disease progression.

Previous studies have established that patients with pRNFL thickness of 88 micrometers (mcm) or less, and GCIPL thickness of below 70–77 mcm, have an increased risk of experiencing disability worsening. Loss of GCIPL over 1.0 mcm and pRNFL over 1.5 mcm per year are associated with functional and cognitive worsening.

In contrast, thickening of the inner nuclear layer (INL) of the retina has been suggested as a marker of MS-related inflammation and is linked with the occurrence of relapses.

Interestingly, INL volume is decreased in those patients who are responsive to disease-modifying treatments (DMTs).

However, since these measurements are typically gathered from patients under controlled experimental settings, researchers at the Medical University of Vienna hypothesized that the thinning/thickening rates may not resemble those observed in the real world.

Thus, the team set out to determine the usefulness of retinal layer measurements in predicting disability progression and relapse in a real-world group of MS patients.

A total of 1,331 MS patients were initially screened by researchers. Their clinical data were obtained from the Vienna MS database (VMSD), which included several parameters such as demographics, disease course, diagnostic findings, and DMT history.

Patients diagnosed after the age of 18, with available optical coherence tomography (OCT) scans, and with one or more years of clinical follow-up were included in the final analysis. Of note, OCT is a non-invasive, high-resolution imaging technique that assesses the distinct layers of the retina.

In the final group were a total of 60 patients, who were followed for a mean of three years. pRNFL, GCIPL, and INL thicknesses were determined based on OCT scans. Measurements were carried out cross-sectionally, meaning they were determined at the baseline scan when the study started, and longitudinally, or over time.

“OCT has considerable advantages in this context as it is non-invasive, inexpensive, easy to perform and accessible, fast, and produces standardized, reliable quantitative measures,” the researchers wrote.

Among the participants, 41 (68.3%) had at least one relapse, and 24 (40.0%) experienced disability progression after a mean of 3.8 years. At the end of the study, the median expanded disability status scale (EDSS) score was 1.5, indicating minimal disability. The mean thicknesses for pRNFL were 92.0 mcm, GCIPL 74.8 mcm, and INL 34.9 mcm.

Patients experiencing disability progression had significantly reduced pRNFL and GCIPL thickness compared with those who were stable.

Using statistical analysis, the researchers found patients with a GCIPL thickness below 77 mcm, or a pRNFL equal to or below 88 mcm, measured at the start of the study, had a three to four times higher risk of disability progression.

The risk for such disability progression increased by almost six times if GCIPL thinning was of 1 mcm or more per year, and if pRNFL thinning was more than 1.5 mcm per year.

In patients with relapse, INL thickened by a mean 0.9 mcm and thinned by 0.3 mcm in patients without relapse. Statistically, the researchers found that INL thickening was associated with an increased probability of relapse. However, INL thickness measured at the start of the study could not predict disability progression.

“INL thickness might be a valuable parameter for capturing inflammatory disease activity and may be considered as an outcome measure for treatment trials, although its potential applicability as a biomarker in individual patients seems limited,” the researchers wrote.

“Our study shows that both crossectional and longitudinal measurement of GCIPL and pRNFL thinning is reliable as a biomarker of disability worsening in a real-world setting. Conversely, INL thickening is a promising marker of relapse,” they concluded.

The researchers said the study “provides an important new piece to the available body of evidence,” since it used real-life data collected within a regular clinical routine.

“Going forward, retinal layer thinning measured by OCT seems as one of the most promising biomarkers of MS-associated neurodegeneration in MS,” they wrote.