Peripapillary retinal nerve fibre layer thinning rate as a biomarker discriminating stable and progressing relapsing–remitting multiple sclerosis

Abstract

Background and purpose Peripapillary retinal nerve fibre layer (pRNFL) thickness is a strong candidate as a biomarker of axonal degeneration in multiple sclerosis (MS). The aim was to determine a cut‐off value of pRNFL thinning rates in relapsing–remitting MS (RRMS) to discriminate between stable and progressing patients. Methods In this 3‐year prospective longitudinal study on 141 RRMS patients, annual pRNFL thinning rates (aLpRNFL) were determined by individual linear regression models. The best possible cut‐off value discriminating clinically progressing (physical progression or cognitive decline) and stable patients was defined by receiver operating characteristic analysis. Cut‐off values were validated using a multivariate logistic regression model. Results Average aLpRNFL in progressing patients (2.4 μm, SD 2.1) was significantly higher compared to stable patients (0.5 μm, SD 1.2, P < 0.001). At a predefined specificity of 90%, aLpRNFL >1.5 μm was able to distinguish between stable and progressing RRMS with a sensitivity of 76.1%. aLpRNFL >1.5 μm was associated with a 15‐fold increased risk of clinically progressing MS (P < 0.001). Conclusions A cut‐off of aLpRNFL discriminating clinically progressing and stable RRMS was identified. After validation in independent cohorts, this cut‐off could be used as a biomarker of axonal degeneration supporting disease monitoring in daily clinical routine.

Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis

“…We included 171 patients diagnosed with RMS according to the 2010 McDonald criteria aged between 18 and 65 years from a prospective, observational study on OCT in RMS. 8 – 10 …”

“…DMT was grouped as following: 1) “no DMT” (N-DMT) defined as patients receiving no DMT at least 6 months prior to baseline visit and during the whole observation period, 2) “moderate efficacious DMT” (M-DMT) defined as patients receiving one or more DMT of either interferon beta preparations, glatiramer acetate, dimethylfumarate, or teriflunomide during the whole observation period, 3) “highly efficacious DMT” (H-DMT) defined as patients receiving one or more DMT of either natalizumab, fingolimod, alemtuzumab, ocrelizumab or cladribine during the whole observation period, and 4) “ESC-DMT” defined as patients in whom DMT was escalated either from no DMT to moderate or from moderate to highly efficacious DMT during the observation period. 9 , 10 …”

“…In MS, atrophy of the macular ganglion cell layer plus the adjacent inner plexiform layer (GCIPL) and the peripapillary retinal nerve fibre layer (pRNFL) are established markers of neurodegeneration in MS. GCIPL and pRNFL thickness correlate with and also predict physical and cognitive disability progression. 7 – 10 …”

Validation of inter-eye difference thresholds in optical coherence tomography for identification of optic neuritis in multiple sclerosis

“…We included 340 patients with clinically isolated syndrome (CIS) and MS diagnosed according to the 2010 version of McDonald criteria aged between 18 and 65 years from a prospective-observational study in two centres (Medical Universities of Innsbruck and Vienna) (Bsteh et al, 2017(Bsteh et al, , 2019. Patients were grouped according to optic neuritis status into patients with (ON) and without (NON) a history of unilateral ON.…”

Retinal thinning and brain atrophy in early MS and CIS

“…Thinning of GCIPL, and their axons in the peripapillary RNFL are assumed to be associated with clinical disability 15 and brain atrophy 7,16 . However, the usefulness of OCT in diagnosing and monitoring MS remains somewhat controversial and is still under evaluation 17‐19 …”