Retinal Vessel Density Loss Without Structural Thinning in Early Multiple Sclerosis: An Optical Coherence Tomography Angiography Study

Abstract Retinal microvascular and structural changes both occur in multiple sclerosis (MS), but their relationship in early disease remains unclear. We conducted a prospective observational study of 15 participants with early relapsing-remitting MS (RRMS; mean disease duration 1.1 years) and 30 age- and sex-matched healthy controls (HC), using optical coherence tomography angiography (OCTA) to compare retinal vessel density and structural thickness. MS eyes were stratified by optic neuritis (ON) history. MS eyes without ON history (MS-NON) showed a significant (all standardized β < −1, p < 0.001) reduction in vessel density as compared to HC in macular superficial vascular complex (SVC) and ganglion cell layer plexus (GCLP), as well as peripapillary nerve fiber layer plexus (NFLP), despite relatively preserved macular ganglion cell inner plexiform layer (GCIPL β = −0.26) and ganglion cell complex thickness (GCC β = −0.17; both non-significant). In contrast, MS eyes with ON history (MS-ON) showed tightly coupled structural thinning and reduced vessel density. Structure-vascular correlations in MS-NON eyes were weak for superficial compartments (GCLP, SVC) but strong for NFLP. These findings indicate that microvascular dysfunction can occur in the absence of detectable structural loss in early MS, and raise the possibility that, in eyes without optic neuritis, vascular changes may precede detectable neuronal loss. OCTA-derived vascular biomarkers may complement structural OCT in early MS monitoring.