Abstract: Examination of 956 age-related macular degeneration cases showed that the complement factor H variant (Y402H, C allele at rs1061170) increases risk for the development of peripheral reticular pigmentary change. AMD phenotypes of 796 carriers of the CFH Y402H variant were compared to the AMD phenotypes of 160 non-carriers. Of 34 phenotypic features analyzed, only peripheral reticular pigmentary change (PRPC) was associated with this CFH variant (P-value 0.0006). The proportion of AMD cases with PRPC correlated with the number of CFH risk C alleles in a dose-response fashion. The association of CFH Y402H polymorphism with PRPC suggests that AMD changes are not limited to the macula. Current AMD grading methods assess only the macula; peripheral retinal changes should also be included in grading methods. PRPC may be used as a surrogate of a high-risk genotype and may be used for diagnostic, therapeutic, and research purposes.