Phenotypic heterogeneity in families with age-related macular degeneration

To evaluate the ophthalmic phenotype in families with three or more individuals who have age-related maculopathy.

Eight families were identified at academic centers in Massachusetts and North Carolina. Macular findings were graded based on a modification of the grading system used in the Age-Related Eye Disease Study (AREDS).

All families had at least three members with stage 3 (extensive drusen change) or higher maculopathy in at least one eye, and six families had at least two members with advanced maculopathy (stage 4, geographic atrophy of the retinal pigment epithelium, or stage 5, exudative maculopathy). Both stages 4 and 5 maculopathy were observed among different individuals in four families. Individuals with stage 3 maculopathy were members of families with more advanced maculopathy (six families) and were of similar age as more severely affected family members but tended to be older than those with stage 2.

The phenotypic appearance of the macula in families with multiple affected individuals is heterogeneous and representative of the spectrum of macular findings typically associated with age-related maculopathy.