title: Incidence, Progression, and Associated Risk Factors of Medium Drusen in Age-Related Macular Degeneration: Findings From the 15-Year Follow-up of an Australian Cohort.
abstract: OBJECTIVE
  The natural course and prognosis of medium drusen and risk factors associated with the incidence and progression of this lesion type in age-related macular degeneration (AMD) are not well understood.
  
  
  OBJECTIVE
  To assess the 15-year incidence and progression of medium drusen and associated risk factors.
  
  
  METHODS
  Population-based cohort in the Blue Mountains region, west of Sydney, Australia. Included in the study were 3654 participants 49 years or older who attended baseline examinations of the Blue Mountains Eye Study (1992-1994), and 75.8%, 76.7%, and 56.1% of survivors who attended the 5-year, 10-year, and 15-year follow-up examinations, respectively.
  
  
  METHODS
  Color retinal fundus photographs were obtained at each examination. The incidence and progression of medium drusen (maximum diameter, 63 to <125 µm) were assessed using Kaplan-Meier product-limit survival methods, controlling for competing risk of death. Factors associated with a 15-year incidence of medium drusen were assessed using discrete logistic regression models after adjusting for age, sex, smoking status, serum lipid levels, systemic and dietary factors, and CFH rs1061170 and ARMS2 rs10490924 polymorphisms. Associations between lesion characteristics and the progression to late AMD were assessed using generalized estimating equation models and eye-specific data.
  
  
  RESULTS
  Among 1317 participants at risk, the 15-year cumulative incidence of medium drusen was 13.9% (n = 281). Increasing age (per decade older) (odds ratio [OR], 1.4; 95% CI, 1.2-1.8) and the presence of at least 3 risk alleles of the CFH rs1061170 or ARMS2 rs10490924 genes (OR, 2.1; 95% CI, 1.1-4.1) were associated with a higher incidence. There was no association between past smoking (OR, 0.8; 95% CI, 0.6-1.1) or current smoking (OR, 0.6; 95% CI, 0.4-1.1) and the development of medium drusen. The progression rate to late AMD in eyes with both medium drusen and retinal pigmentary abnormalities was 4-fold higher than that in eyes with medium drusen alone. Larger total area and central location of medium drusen were associated with a greater likelihood of the progression to worse stages of AMD.
  
  
  CONCLUSIONS
  Older age and the presence of CFH and ARMS2 risk alleles are 2 main risk factors associated with the development of medium drusen. The copresence of medium drusen plus retinal pigment epithelium abnormalities signals a greater risk of the progression to late AMD than the presence of medium drusen alone.
authors.affiliation: Centre for Vision Research, Department of Ophthalmology, University of Sydney, Sydney, Australia2Westmead Millennium Institute, Westmead Hospital, Westmead, Australia.
authors.forename: Nichole D L
authors.initials: ND
authors.lastname: Joachim
authors.affiliation: Centre for Vision Research, Department of Ophthalmology, University of Sydney, Sydney, Australia2Westmead Millennium Institute, Westmead Hospital, Westmead, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.affiliation: Centre for Vision Research, Department of Ophthalmology, University of Sydney, Sydney, Australia2Westmead Millennium Institute, Westmead Hospital, Westmead, Australia.
authors.forename: Annette
authors.initials: A
authors.lastname: Kifley
authors.affiliation: Centre for Vision Research, Department of Ophthalmology, University of Sydney, Sydney, Australia2Westmead Millennium Institute, Westmead Hospital, Westmead, Australia.
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000453:epidemiology; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D060005:Genotyping Techniques; D006801:Humans; D015994:Incidence; D008268:Macular Degeneration / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D015593:Retinal Drusen / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D012307:Risk Factors
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; D011506:Proteins; D017242:Complement Factor H