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Nichole D. Joachim, Paul Mitchell, Annette Kifley, Thomas H. Hong, Jie J. Wang; Risk Characteristics Associated with Development of Geographic Atrophy: The Blue Mountains Eye Study Cohort. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1327.
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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.
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.
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.
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).
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