C3 and age-related macular degeneration: This supports the theory that densely affected families may harbor rare, more penetrant genetic variants for AMD.[34,39,40] Even though no statistically significant difference was observed between familial and sporadic subjects concerning the association of the C3d/C3 ratio with AMD, the very high ORs that we reported for the patients from densely affected families can point towards a more important role for systemic complement activation in families with AMD compared to sporadic AMD patients.