Considering that SMAD4-dependent signaling is responsible for the collagen formation and the findings of the keratocytes attachments to Descemet’s membrane due to the ultra-pathological thinning of corneal stroma in Smad4kera-cko, the pathological changes in keratocytes and the elimination/absence of posterior keratocytes found in Tgfbr2kera-cko might serve as the fundamental background of ACH in advanced CE. Here, SMAD4 is linked to cholesteryl ester measurement.