OBJECTIVES: This study investigated the longitudinal progression of retinal structure and microvasculature over 3 years in patients with relapsing-remitting multiple sclerosis (RRMS) using optical coherence tomography (OCT) and OCT angiography (OCTA). It also explored the correlation between these changes and the Expanded Disability Status Scale (EDSS) scores. METHODS: In this prospective, longitudinal study, we enrolled 66 patients with RRMS without history of optic neuritis and 124 healthy controls. All participants underwent full ophthalmological examination, OCT/OCTA scans, and disability scoring (EDSS) at baseline and after 12 and 24 months. OCT data were analyzed for retinal layer thickness, while OCTA assessed microvascular perfusion in the retinal capillary plexuses and choriocapillaris. Statistical models evaluated yearly rates of change and their association with EDSS scores. RESULTS: The patients with RRMS exhibited 3.6 times faster thinning of the inner plexiform layer (IPL
- 0.47 µm per year, P = 0.002) compared to controls over 3 years. Additionally, superficial retinal capillary layer perfusion density decreased more rapidly at - 0.44% per year (P = 0.006) in patients with MS. A strong correlation was found between worsening EDSS scores and accelerated ONL thinning (estimated coefficient: - 1.62 µm/per unit change of EDSS score, P = 0.004). DISCUSSION: This study demonstrates progressive retinal neurodegeneration and microvascular dysfunction in patients with RRMS without a history of optic neuritis. The association between ONL thinning and increased disability supports the potential of OCT/OCTA as valuable tools for monitoring disease progression and severity in RRMS.