Retinal thinning is a biomarker of neuroaxonal degeneration in multiple sclerosis (MS) and is associated with disability progression. Recently, the term PIRA, or progression independent of relapse, has emerged purporting to quantify the proportion of disability worsening due to non-inflammatory neurodegenerative processes.
The objective of this study was to determine the association of retinal thinning with PIRA in comparison to traditional physical disability worsening and relapse.
In a 4-year prospective observational study including 171 relapsing MS (RMS) patients, retinal thinning was determined by annual spectral-domain optical coherence tomography measuring macular-ganglion-cell-and-inner-plexiform-layer(mGCIPL). Physical disability was assessed by expanded disability status scale (EDSS), cognitive disability by the symbol digit modalities test (SDMT). PIRA was defined as either an EDSS or SDMT worsening during the observation period confirmed after 24 weeks with no relapse in the 30 days before or after the disability worsening. Multivariate linear regression models adjusted for sex, age, disease duration and disease-modifying treatment regarding retinal thinning were calculated.
Each PIRA event was associated with a mean additional loss of GCIPL (1.8µm) and pRNFL (1.9µm), similar to the impact of EDSS and SDMT worsening. Overall relapse and relapse without subsequent EDSS worsening did not influence retinal thinning, while a relapse with EDSS worsening was associated with an additional loss of GCIPL (1.3µm) and pRNFL (1.4µm).
PIRA is associated with retinal thinning, likely reflecting non-inflammatory neurodegenerative processes. It might be a clinical measure to identify MS patients with ongoing MS-associated neurodegeneration.