To apply adaptive optics-optical coherence tomography (AO-OCT) to investigate multiple sclerosis (MS)-induced changes in retinal macrophage-like cell (MLC) morphology and density.

We previously reported use of AO-OCT to visualize MLCs, which are presumed to be retinal microglia, at the vitreomacular interface in MS. Since microglia take on various morphologies in response to environmental conditions, including ramified, rod-like, and ameboid shapes, visualization of cell morphology with AO-OCT may enable direct quantification of the inflammatory and neurodegenerative state of retinal tissue in MS.

Six macular regions in one eye each from nine healthy volunteers (HV) and ten patients with MS (four with a history of optic neuritis (MS-ON) in the imaged eye, six without (MS-no-ON)) were imaged using AO-OCT on a custom-built multi-modal AO device. MLCs were examined directly above the inner limiting membrane (ILM) and labelled based on morphology.

Total MLC counts in the macular regions were higher in MS (median: MS=32.5, HV=6; p=0.033), preferentially in the temporal macula (median: MS=24.5, HV=4; p=0.007). Subtype analysis revealed higher rod-like (median: MS=3.5, HV=1; p=0.010) and ameboid (median: MS=18.5, HV=2; p=0.005) morphologies temporally in MS, along with higher ameboid (median: MS=9.5, HV=0; p=0.046) morphology nasally. There was no significant difference in ramified MLC count in any retinal location between MS and HV (median: MS=6, HV=1; p=0.322). The only difference between MS-ON and MS-no-ON was a higher rod-like appearance (median 12 vs 5, respectively, p=0.009).

Retinal MLCs in activated states are higher in MS as visualized by AO-OCT, particularly in the temporal macula. Our findings add further in vivo evidence of neurodegenerative changes in MS.