Evidence of CC impairment in AMD emerged from several studies with different approaches, including prolonged choroidal filling on both indocyanine green and fluorescein angiography in early AMD, Doppler flow studies, a proteomic analysis that found the loss of CC protein (CA4 and HLA-A) with the preservation of RPE proteins (CRALBP and RPE 65), histopathological studies, and more recently, with the advancements in multimodal imaging [43,44,45,46,47,48,49]. Here, CA4 is linked to age-related macular degeneration.