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Association Between Retinal Layer Atrophy With Clinical and Radiologic Progression in People With Relapsing Multiple
Gabriel Bsteh1,2, Harald Hegen3, Nik Krajnc1,2
1Department of Neurology, Medical University of Vienna, Austria.
Neurology
|September 29, 2025
Summary
Progression independent of relapse activity (PIRA) in multiple sclerosis (MS) is linked to retinal atrophy. This study shows retinal layer thinning correlates with progression independent of relapse and MRI activity (PIRMA), suggesting it reflects neuroaxonal damage beyond inflammation.
Area of Science:
- Neuroscience
- Ophthalmology
- Clinical Neurology
Background:
- Progression independent of relapse activity (PIRA) drives disability in relapsing multiple sclerosis (RMS).
- Retinal layer atrophy via optical coherence tomography (OCT) indicates neuroaxonal damage and correlates with PIRA.
- The link between retinal atrophy and PIRA's inflammatory drivers versus true progression remains unclear.
Purpose of the Study:
- To investigate the association between retinal layer atrophy and progression independent of relapse and MRI activity (PIRMA) in RMS.
- To clarify if retinal atrophy reflects subclinical inflammation or true progression in MS.
- To assess retinal layer thinning as a potential biomarker for neuroaxonal degeneration in MS.
Main Methods:
- Prospective observational study of 210 RMS patients with serial OCT scans after disease-modifying treatment (DMT) initiation.
- Disability accrual defined by composite measures, with PIRA and PIRMA identified based on relapse and MRI activity.
- Multivariable mixed-effects models assessed associations between PIRMA and peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) thinning.
Main Results:
- PIRMA was identified in 13.3% of patients, accounting for 54.1% of PIRA cases.
- PIRMA was significantly associated with accelerated thinning of both GCIPL (0.72% per year) and pRNFL (1.05% per year).
- These associations remained significant after adjusting for age, sex, disease duration, baseline retinal thickness, and DMT efficacy.
Conclusions:
- Retinal atrophy is significantly associated with PIRMA in RMS patients.
- These findings support retinal layer thinning as a biomarker for neuroaxonal degeneration in MS that is independent of acute focal inflammation.
- OCT-measured retinal atrophy may help differentiate inflammatory from non-inflammatory progression in MS.
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