Retinal layer thinning predicts treatment failure in relapsing multiple sclerosis

Abstract

Background and purpose: Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) thinning are markers of neuroaxonal degeneration in multiple sclerosis (MS), which is reduced by disease-modifying treatment (DMT). We aimed to investigate the potential of pRNFL and GCIPL thinning for prediction of DMT failure in relapsing MS (RMS).

Methods: In this 4-year prospective observational study on 113 RMS patients, pRNFL and GCIPL were measured at DMT initiation and after 12 months (M12) and 24 months (M24). Treatment failure was defined as 6-month confirmed Expanded Disability Status Scale (EDSS) progression and/or Symbol Digit Modalities Test (SDMT) worsening. Optimal cutoff values for predicting treatment failure were determined by receiver operating characteristic analyses and hazard ratios (HRs) by multivariable Cox regression adjusting for age, sex, disease duration, EDSS/SDMT, and DMT class.

Results: Thinning of GCIPL >0.5 μm/year at M24 showed superior value for treatment failure prediction (HR: 4.5, 95% confidence interval [CI]: 1.8-7.6, p < 0.001; specificity 91%, sensitivity 81%), followed by GCIPL >0.5 μm at M12 (odds ratio [OR]: 3.9, 95% CI: 1.4-6.9, p < 0.001; specificity 85%, sensitivity 78%), and pRNFL ≥2 μm/year at M24 (OR: 3.7, 95% CI: 1.1-6.5, p = 0.023; specificity 84%, sensitivity 69%), whereas pRNFL at M12 was not predictive.

Conclusions: GCIPL, and to a lesser degree pRNFL, thinning predicts disability progression after DMT initiation and may be a useful and accessible biomarker of treatment failure in RMS.

Keywords: GCIPL; OCT; disease-modifying treatment; multiple sclerosis; retinal thinning.

FIGURE 1

Schematic overview of study design. Small circles: relapse, Expanded Disability Status Scale/Symbol Digit Modalities Test rating. Big circles: Relapse, Expanded Disability Status Scale/Symbol Digit Modalities Test rating, and optical coherence tomography. DMT, disease‐modifying treatment; M, month. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Inclusion flowchart. DMT, disease‐modifying treatment; M0, baseline; M12, month 12; M24, month 24; MS, multiple sclerosis; ON, optic neuritis.

FIGURE 3

Accuracy of disease‐modifying treatment failure prediction by annualized retinal layer thinning and as determined by receiver operating characteristic analyses of aLGCIPL measured after 12 and 24 months (a, b) and aLpRNFL after 12 and 24 months (c, d). aLGCIPL, annualized loss of macular ganglion cell and inner plexiform layer; aLpRNFL, annualized loss of peripapillary retinal nerve fiber layer; AUC, area under the curve; CI, confidence interval; M12, measured between baseline and 12 months after DMT initiation; M24, measured between baseline and 24 months after DMT initiation.

FIGURE 4

Annualized retinal layer thinning predicts DMT failure. Probability of DMT failure regarding disability worsening (a), relapse (b), and clinical disease activity (c) as predicted by annualized loss of GCIPL and pRNFL measured 12 and 24 months after DMT initiation. aLGCIPL, annualized loss of macular ganglion cell and inner plexiform layer; aLpRNFL, annualized loss of peripapillary retinal nerve fiber layer; CI, confidence interval; DMT, disease‐modifying treatment; HR, hazard ratio; M12, measured between baseline and 12 months after DMT initiation; M24, measured between baseline and 24 months after DMT initiation; ns, not significant.