Peripheral retinal drusen and reticular pigment: association with CFHY402H and CFHrs1410996 genotypes in family and twin studies

Invest Ophthalmol Vis Sci. 2009 Feb;50(2):586-91. doi: 10.1167/iovs.08-2514. Epub 2008 Oct 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Aged
  • Complement C2 / genetics
  • Complement C3 / genetics
  • Complement Factor B / genetics
  • Complement Factor H / genetics
  • Diseases in Twins / genetics*
  • Exons
  • Female
  • Genotype
  • Humans
  • Introns
  • Macular Degeneration / diagnosis
  • Macular Degeneration / genetics*
  • Male
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics
  • Retinal Drusen / diagnosis
  • Retinal Drusen / genetics*
  • Retinal Pigment Epithelium / pathology*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • ARMS2 protein, human
  • CFH protein, human
  • Complement C2
  • Complement C3
  • Proteins
  • Complement Factor H
  • Complement Factor B