Retinal Layer Thinning Can Predict Treatment Failure in Relapsing Multiple Sclerosis

The study found worsening disease in those with thinning in the ganglion cell layer plus inner plexiform layer plus peripapillary retinal nerve fibre layer.

Macular ganglion cell layer plus inner plexiform layer (GCL-IPL) and peripapillary retinal nerve fibre layer (pRNFL) thinning predicts disability progression after disease-modifying treatment (DMT) initiation in relapsing multiple sclerosis (RMS), according to a study published in European Journal of Neurology.

The researchers sought to investigate the potential of retinal layer thinning as a predictor of treatment failure in RMS since retinal thinning, a marker of neuroaxonal damage in MS, has not yet been studied prospectively.

Both retinal layer thinning forms were measured at DMT initiation and after 12 months and 24 months (M12, M24) in 113 patients between the ages of 18 and 65 years who were diagnosed with RMS. Optical coherence tomography (OCT) was performed at these points as well.

During the observation period, 36 patients had disability worsening, 52 had a relapse, and 68 had clinical disease activity.

Patients with disability worsening displayed significantly more marked annualized retinal thinning of both forms compared with patients without disability worsening at both M12 and M24. Disease duration was weakly inversely correlated with annual loss of both GCL-IPL and pRNFL. Both baseline GCL-IPL  and pRNFL were weakly correlated with annualized loss of GCL-IPL and annualized loss of pRNFL (P <.001 for all).

The best possible cut-off values for identifying patients with disability worsening were greater than 0.5 µm for annualized loss of GCL-IPL (P <.001) and at least 2.0 µm for annualized loss of pRNFL (P <.001).

At M24,  annualized loss of GCL-IPL above the cut-off of 0.5 µm provided discrimination with 81% sensitivity and 86% specificity with a positive predictive value (PPV) of 71% and a negative predictive value (NPV) of 97%. Diagnostic accuracy of annualized loss of pRNFL greater than 0.5 µm at M24 was slightly superior to nnualized loss of GCL-IPL greater than 0.5 µm at M12 (sensitivity: 78%; specificity: 86%; PPV: 66%; NPV: 95%) and significantly superior to annualized loss of pRNFL that was at least 2.0 µm at M24 (sensitivity: 69%; specificity: 69%; PPV: 56%; NPV: 90%) and at M12.

In multivariate models, annualized loss of  GCL-IPL greater than 0.5 µm at M24 was the strongest predictor of disability worsening (P <.001) followed by aannualized loss of  GCL-IPL greater than 0.5 µm at M12 (P <.001). Annualized loss of RNFL that was greater than 2.0 µm at 24 months showed a weaker, but still significant, association with disability worsening (P <.001).

Annualized loss of GCL-IPL greater than 0.5 µm at M12 and M24 were also significant predictors of clinical disease activity and relapse. Annualized loss of pRNFL ≥2.0µm at M24 was significantly associated with clinical disease activity (HR 2.4, P =.025).

The researchers recommended that OCT measuring both retinal layer thinning forms be performed within 3 months after initiating DMT and repeated annually in monitoring.

Limitations of the study include the exclusion of patients with primary or secondary progressive MS from the study. In addition, prognostic accuracy of the cut-off values might have been higher since they were from the same cohort.

Disclosure: Several study authors declared affiliations with the biotech and pharmaceutical industries. Please see the original reference for a full list of authors’ disclosures.


Bsteh G, Hegen H, Altmann P, et al. Retinal layer thinning predicts treatment failure in relapsing multiple sclerosis. European J of Neurol. Published online March 17, 2021. doi:10.1111/ene.14829