Purpose:
To report factors and early age-related macular degeneration (AMD) lesion characteristics associated with the long-term development of geographic atrophy (GA) in an older Australian sample.
Methods:
Of 3654 Blue Mountains Eye Study participants at baseline, 75.8%, 76.7% and 56.1% of survivors were re-examined at the 5-, 10- and 15-year follow-ups, respectively. Retinal photographs and comprehensive questionnaires were taken at each visit and genotyping performed on DNA samples of 1854 participants. Incident GA was confirmed using a side-by-side grading method (Wisconsin AMD grading protocol). Development of GA was assessed based on the Age-Related Eye Disease Study (AREDS) severity scale and lesion type, location and area within the macula. Incident pure GA (excluding neovascular AMD cases) was estimated using Kaplan-Meier product-limit survival estimates. Generalized estimating equation models were used for analysis of eye-specific data. Odds ratios (ORs) are reported after adjusting for age, current smoking status, regular fish consumption and CFH and ARMS2 risk alleles.
Results:
Incident GA was confirmed in 61 participants with an overall 15-year incidence of 3.8%. Incidence rates (and 95% confidence intervals, CI) by steps 0, 1, 2, 3 and 4 of the AREDS scale were 1.3% (CI 0.8-2.3), 8.9% (CI 4.4-17.8), 38.8% (CI 25.2-56.7), 19.8% (CI 6.0-54.4) and 100.0%, respectively, over a 15-year period. Risk factors identified were baseline age (OR 1.2, CI 1.2-1.3 per year older), current smoking (OR 4.8, CI 2.0-11.6), the CFH (OR 1.6, CI 1.0-2.6 per risk allele) and ARMS2 genes (OR 2.6, CI 1.5-4.4 per risk allele). Baseline early AMD lesion characteristics that predicted higher GA risk included drusen type (soft indistinct: OR 46.0, CI 14.9-141.9; and reticular drusen: OR 13.3, CI 3.9-45.0); central drusen location within 500µm radius of the fovea (OR 9.8, CI 4.4-21.5); drusen area greater than 375µm in diameter (OR 8.0, CI 2.8-22.6), the presence of retinal pigment epithelial depigmentation (OR 6.9, CI 2.5-19.1) and hyperpigmentation (OR 11.9, CI 5.5-25.5), referenced to the group with none or hard drusen only.
Conclusions:
We confirm a substantial high risk of developing GA associated with early AMD lesion characteristics, independent of age, smoking and AMD genetic susceptibility from the two major AMD genes (CFH and ARMS2).
Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: prevalence/incidence • clinical (human) or epidemiologic studies: risk factor assessment