OBJECTIVE: To compare phenotypes of 2 age-related macular degeneration (AMD) susceptibility genes: LOC387715 and complement factor H (CFH). METHODS: Phenotypes of 755 AMD cases were characterized. The number of LOC387715 (T allele at rs10490924, or A69S) and CFH (T1277C at rs1061170, or Y402H) risk alleles were determined in each case. Individuals were divided into 5 groups by genotype: group 1, LOC-/- CFH-/-; group 2, LOC+/- CFH-/- or LOC+/+ CFH-/-; group 3, LOC-/- CFH+/- or LOC-/- CFH+/+; group 4, LOC+/- CFH+/-, LOC+/+ CFH+/-, or LOC+/- CFH+/+; and group 5, LOC+/+ CFH+/+. RESULTS: Signs of neovascular AMD including grade (P = .002), pigment epithelial detachment (P = .001), and subretinal hemorrhage (P<.001) demonstrated significant association with groups 2, 4, and 5 vs groups 1 and 3. Group 5 had a significantly younger mean age (72.3 years) compared with other groups (P = .002). CONCLUSIONS: The AMD cases possessing the LOC387715 (rs10490924) variant may have a higher risk of neovascular AMD. Individuals with AMD who are homozygous for both variants might be at greater risk for earlier onset of neovascular AMD.