Abstract
Purpose:
The natural course and prognosis of intermediate drusen and risk factors associated with the incidence and progression of this lesion type is not well understood. We aimed to assess the 15-year incidence and progression of intermediate drusen and their associations with known risk factors of age-related macular degeneration (AMD).
Methods:
Of 3654 Blue Mountains Eye Study baseline participants aged 49+ years (1992-1994), 75.8%, 76.7% and 56.1% of survivors attended the 5-, 10- and 15-year follow-up examinations, respectively. Incidence of intermediate drusen (with maximum diameter ≥63µm but <125µm) were assessed using Kaplan-Meier product limit survival methods controlling for the competing risk of death. Associations between known AMD risk factors and the 15-year incidence of intermediate drusen were assessed using discrete logistic regression models after adjusting for age, sex, smoking, serum lipids, systemic and dietary factors, CFH-rs1061170 and ARMS2-rs10490924 polymorphisms. Associations between lesion characteristics and progression to late AMD were assessed using generalized estimating equation models and eye-specific data.
Results:
The 15-year cumulative incidence of intermediate drusen was 13.9% (n=281). Increasing age (per decade older, odds ratio, OR 1.43) and the presence of ≥3 risk alleles of the CFH-rs1061170 or ARMS2-rs10490924 genes (OR 2.14) were associated with a higher incidence of intermediate drusen. There was no association between past or current smoking and development of intermediate drusen (OR’s 0.80 and 0.62, respectively). The progression rate to late AMD in eyes that had both intermediate drusen and retinal pigmentary abnormalities was 4-fold higher than the progression rate of eyes with intermediate drusen alone. Larger total area and central location of intermediate drusen were also associated with a greater likelihood of progression to advanced stage lesions of early and late AMD.
Conclusions:
Increasing age and the presence of AMD genetic susceptibility, indicated by the presence of CFH and ARMS2 risk alleles, were associated with greater risk of developing intermediate drusen. The co-presence of intermediate drusen and retinal pigmentary abnormalities signals a much greater risk of progression to late AMD than the presence of intermediate drusen alone.