In the absence of a mutation, it is possible that modifications due to aging, cigarette smoking, or oxidative, thermal, or other stress cause overexpression of EFEMP1 (Giasson et al., 2000; Stanton et al., 2017) in RPE cells and vascular endothelial cells in the retina of AMD eyes. This evidence concerns the gene EFEMP1 and age-related macular degeneration.