Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report

Br J Ophthalmol. 2017 Sep;101(9):1185-1192. doi: 10.1136/bjophthalmol-2016-309729. Epub 2017 Jan 20.


Purpose: To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors.

Design: Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study.

Methods: Retinal photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors.

Results: In any 5-year duration, 19-28% of unilateral any AMD cases became bilateral and 27-68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye.

Conclusion: One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement.

Keywords: Degeneration; Epidemiology; Macula.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Age Factors
  • 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
  • Photography
  • Prospective Studies
  • Proteins / genetics
  • Risk Factors
  • Surveys and Questionnaires


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