APOE and age-related macular degeneration: The protective role of the ApoE4 isoform against AMD was first reported in 1998 in a study with 88 AMD cases and 901 healthy controls, which showed low prevalence of AMD particularly with soft drusen in E4 carriers, they suggested two possible biological mechanisms for the observed protective effect of ApoE4 against AMD which were related to Bruch's membrane (BM) [42].