Macular Pigment and Retinal Reflectance in a Feasibility Study of Multiple Sclerosis: Toward Novel Biomarkers of Hidden Disease Processes.

PURPOSE: To evaluate the feasibility and characteristics of macular pigment optical density (MPOD) and retinal reflectance (RR) measurements using two-wavelength autofluorescence (AF) and multicolor imaging, respectively, in multiple sclerosis (MS), and explore differences compared with healthy controls. Sixteen MS participants and 25 age-matched healthy controls were included in this prospective, observational, single-center, cross-sectional, feasibility study. METHODS: After pupil dilation, blue- and green-light fundus autofluorescence and multicolor imaging were performed using the Heidelberg Spectralis. Custom-built ImageJ plugins extracted MPOD, spatial profiles, macular pigment optical volume (MPOV), and hyperspectral indexes (HSI) from RR. Linear mixed-effects models compared outcomes between MS eyes with optic neuritis (MSON), without optic neuritis (MSnON), and controls. A post hoc power analysis characterized detectable effect sizes given the available sample size. RESULTS: MPOD and RR were successfully measured in all participants. Macular pigment spatial profiles differed between MS and controls (P = 0.010). Ring-like MPOD patterns were observed in 43% of MS eyes and were most pronounced in MSON (67%). HSI varied regionally (P < 0.001) but was not associated with MS status. MPOV did not differ significantly between groups. MPOD demonstrated inter-individual variability within both groups. Exploratory analyses showed that higher peripheral MPOD (3°-6°) was associated with greater inner/full retinal thickness, whereas higher HSI was associated with thinner outer retina and smaller foveal avascular zone volume (all P ≤ 0.05). CONCLUSIONS: AF-based MPOD measurement is feasible in MS, providing spatially resolved, objective macular pigment quantification. AF-derived MPOD showed limited sensitivity to MS-related changes in isolation. Larger cohort studies with multimodal retinal imaging are required to determine MPOD's role as a biomarker in MS.