Incidence and progression of reticular drusen in age-related macular degeneration: findings from an older Australian cohort

Ophthalmology. 2014 Apr;121(4):917-25. doi: 10.1016/j.ophtha.2013.10.043. Epub 2013 Dec 12.


Purpose: To assess the 15-year incidence and progression of reticular drusen and associations of this lesion with age-related macular degeneration (AMD) risk factors.

Design: Population-based cohort.

Participants: Blue Mountains Eye Study participants (n = 3654) 49 years of age and older attended baseline examinations; of these, 75.8%, 76.7%, and 56.1% of survivors attended 5-year, 10-year, and 15-year follow-up examinations, respectively.

Methods: Color retinal photographs were obtained and comprehensive questionnaires were administered at each visit, and DNA samples were genotyped. Fundus autofluorescence images were not available. Reticular drusen identified from photographs were confirmed with side-by-side grading using the Wisconsin AMD grading protocol. Incidence was assessed using Kaplan-Meier product limit survival methods, controlling for competing risk of death. Associations between smoking, fish consumption, serum lipids, systemic and dietary factors, the CFH single nucleotide polymorphism (SNP) rs1061170 and ARMS2 SNP rs10490924, and the 15-year incidence of reticular drusen were analyzed in discrete logistic regression models. Generalized estimating equation models were used to analyze eye-specific relationships between these risk factors and 5-year progression from reticular drusen to late AMD.

Main outcome measures: Incidence and progression of reticular drusen.

Results: The 15-year cumulative incidence of reticular drusen was 4.0% (n = 95). Increasing age (per decade increase; odds ratio [OR], 3.4; 95% confidence interval [CI], 2.6-4.4), female sex (OR, 2.0; 95% CI, 1.3-3.2), and presence of risk alleles of CFH-rs1061170 (OR, 1.8; 95% CI, 1.3-2.4) or ARMS2-rs10490924 (OR, 3.0; 95% CI, 2.1-4.4) were associated with higher reticular drusen incidence. Current smoking at baseline predicted higher reticular drusen incidence (OR 2.1, 95% CI 1.0-4.5) after adjusting for age, sex, CFH-rs1061170 and ARMS2-rs10490924 polymorphisms. Of 118 eyes with reticular drusen, 40 (33.9%) developed late AMD over 5 years. A higher proportion of eyes with reticular drusen located outside versus within the macular area progressed to late AMD (50.0% vs. 37.8%). Dietary lutein-zeaxanthin intake was associated with decreased likelihood of progression from reticular drusen to late AMD (adjusted OR, 0.5; 95% CI, 0.3-1.0).

Conclusions: Known AMD risk factors were associated with greater long-term risk of reticular drusen. Neither total area nor central location of reticular drusen predicted 5-year progression to late AMD. Increased consumption of lutein-zeaxanthin predicted a lower risk of progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Complement Factor H / genetics
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Genotyping Techniques
  • Humans
  • Incidence
  • Macular Degeneration / diagnosis
  • Macular Degeneration / epidemiology*
  • Macular Degeneration / genetics
  • Male
  • Middle Aged
  • New South Wales / epidemiology
  • Photography
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Proteins / genetics
  • Retinal Drusen / diagnosis
  • Retinal Drusen / epidemiology*
  • Retinal Drusen / genetics
  • Risk Factors


  • ARMS2 protein, human
  • CFH protein, human
  • Proteins
  • Complement Factor H