Cellular-Level Visualization of Retinal Pathology in Multiple Sclerosis With Adaptive Optics

PURPOSE: To apply adaptive optics–optical coherence tomography (AO-OCT) to quantify multiple sclerosis (MS)–induced changes in axonal bundles in the macular nerve fiber layer, ganglion cell somas, and macrophage-like cells at the vitreomacular interface. METHODS: We used AO-OCT imaging in a pilot study of MS participants (n = 10), including those without and with a history of optic neuritis (ON, n = 4), and healthy volunteers (HV, n = 9) to reveal pathologic changes to inner retinal cells and structures affected by MS. RESULTS: We found that nerve fiber layer axonal bundles had 38% lower volume in MS participants (1.5 × 10(−3) mm(3)) compared to HVs (2.4 × 10(−3) mm(3); P < 0.001). Retinal ganglion cell (RGC) density was 51% lower in MS participants (12.3 cells/mm(2) × 1000) compared to HVs (25.0 cells/mm(2) × 1000; P < 0.001). Spatial differences across the macula were observed in RGC density. RGC diameter was 15% higher in MS participants (11.7 µm) compared to HVs (10.1 µm; P < 0.001). A nonsignificant trend of higher density of macrophage-like cells in MS eyes was also observed. For all AO-OCT measures, outcomes were worse for MS participants with a history of ON compared to MS participants without a history of ON. AO-OCT measures were associated with key visual and physical disabilities in the MS cohort. CONCLUSIONS: Our findings demonstrate the utility of AO-OCT for highly sensitive and specific detection of neurodegenerative changes in MS. Moreover, the results shed light on the mechanisms that underpin specific neuronal pathology that occurs when MS attacks the retina. The new findings support the further development of AO-based biomarkers for MS.