We compared HRF frequencies and their association with retinal neurodegeneration between people with clinically isolated syndrome (pwCIS), multiple sclerosis (pwMS), aquaporin 4‐IgG positive neuromyelitis optica spectrum disorder (pwNMOSD), and healthy controls (HC)—as well as between eyes with (ON+eyes) and without a history of optic neuritis (ON−eyes). This evidence concerns the gene AQP4 and multiple sclerosis.