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Ronald Klein, Chelsea E Myers, Kristine E Lee, Ronald Gangnon, Theru A Sivakumaran, Sudha K Iyengar, Barbara E K Klein; Small drusen and age-related macular degeneration (AMD): the Beaver Dam Eye Study. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2571.
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Small hard drusen (<63 μm diameter) have been considered a result of normal aging. Their relationship to the development of AMD is unclear. We tested the hypothesis that the presence of a large area of small hard drusen and the presence of intermediate size drusen are associated with the incidence of AMD.
Both eyes of 3630 persons aged 43-86 years at baseline in 1988-1990 with gradable color film 30° stereoscopic fundus photographs from at least 2-4 consecutive visits between baseline and 2008-2010 were included in analyses. Area of involvement of drusen was assessed by grading fundus photographs. A 6-step severity scale with levels varying from no drusen, 4 levels of increasing area of small hard drusen only (from minimal area [<2596 µm²] to large area [>9086 µm²]) and intermediate sized drusen (64-125 μm diameter) was used. The outcomes included incidence of large area of small hard drusen or worse and the incidence of AMD.
The 5-year incidence of a large area of small drusen or worse was 8%, 11%, 19% and 25% in eyes with no, minimal, small and moderate area at the start of the interval, respectively (Figure). The odds ratio (OR) for incidence of large area of small drusen from one severity level to the next varied from 1.4 to 1.7, with an OR per step progression of 1.5 (95% confidence interval [CI] 1.5-1.6, P<.001). The 5-year incidence of AMD was 3% in eyes with no, minimal, small and moderate small drusen area at the start of the interval, and 5% and 25% for eyes with large area and intermediate drusen, respectively (Figure). Compared to eyes with moderate area of small drusen, the OR for eyes developing AMD with large area of small drusen was 1.8 (95% CI 1.3-2.4, P<.001) and compared to eyes with large small drusen area, eyes with intermediate drusen had an OR of 5.5 (95% CI 4.5-6.8, P<.001). Older age and the presence of 1 or 2 risk alleles of Complement Factor H rs1061170 and Age Related Maculopathy Susceptibility 2 rs10490924 but not sex were associated with increased risk of larger area of small hard drusen or worse and incidence of AMD.
Our results suggest that the presence of a large area of small hard drusen and presence of intermediate drusen may define an earlier clinical stage of AMD than currently defined by large soft drusen.
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