It was originally hypothesized that S1P3 modulation at the orbital vascular endothelial junctions was directly responsible, although macular edema has been reported as an adverse event with ponesimod, a highly selective S1P1 modulator.47,48 In addition, MME has been encountered in S1P modulation in other non-neurological conditions, such as ulcerative colitis, which argues against a direct neuroinflammatory effect underlying its pathogenesis. Here, MBTPS1 is linked to macular retinal edema.