Purpose: To evaluate the relationship between peripheral retinal drusen and reticular pigment changes and genotypes associated with age-related macular degeneration (AMD).
Methods: Using standard protocols, 2103 family members and twins were examined. Clinical and photographic data were graded according to the Clinical Age-Related Maculopathy Grading System (CARMS) as grade 1 (no AMD), grade 2 (small drusen and/or pigment irregularities), grade 3 (intermediate AMD), grade 4 (central or noncentral geographic atrophy), or grade 5 (neovascular disease). Peripheral drusen and reticular pigment were assessed with a standardized examination. Associations between six AMD genetic variants and retinal phenotypes were analyzed.
Results: AMD grade was associated with peripheral drusen and reticular pigment (odds ratio [OR] 1.9 for advanced AMD; P<0.001). Both peripheral retinal phenotypes were associated with AMD related genotypes. For CFHY402H, the OR was 2.8 for the CC genotype versus TT (P for trend<0.001, with increase in peripheral drusen with each additional risk [C] allele). Similar results were seen for CFHrs1410996. Reticular pigment was related to CFHY402H, with OR 2.0 for the CC genotype versus TT (P for trend<0.001, for increase in pigment with each risk allele) and to CFHrs1410996 (P for trend=0.006). These findings were not seen for the LOC387715 A69S gene region, CFB, C2, or C3. Among individuals with no or minimal maculopathy, CFH variants were associated with more than a twofold increased risk of drusen and reticular pigment.
Conclusions: Peripheral retinal drusen and reticular pigment are associated with AMD and with CFHY402H and CFHrs1410996 genotypes, adjusting for AMD grade. These phenotypes may be a marker of genetic susceptibility for patients with or without AMD.