TIMP3 and age-related macular degeneration: The presence of different variants in TIMP-3 makes SFD a condition that exhibits heterogeneity in the severity of different clinical phenotypes.[3] Although most mutations are located closer to the C-terminus of the protein, there are mutations affecting the N-terminus as well, and the severity of the disease cannot be easily correlated with the affected amino acid.[3,14–16,21,22,24,29] Some authors suggest that some additional risk factors may affect the severity of SFD, such as smoking or age-related macular degeneration (AMD) genetic factors.[3,17,30]