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Ronald Klein, Chelsea Myers, Sudha Iyengar, Theru Sivakumaran, Karen Cruickshanks, Kristine Lee, Ronald Gangnon, Barbara Klein; Inflammatory and Oxidative Stress Markers and the 20-Year Cumulative Incidence of Age-related Macular Degeneration: the Beaver Dam Eye Study. Invest. Ophthalmol. Vis. Sci. 2013;54(15):369.
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To determine whether inflammatory and oxidative stress markers are associated with the 20-year cumulative incidence of early and late age-related macular degeneration (AMD).
A randomized sample of the Beaver Dam Eye Study cohort of 1597 persons was identified for assessment of 4 inflammatory markers (serum high sensitivity C-reactive protein [CRP], tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and white blood cell [WBC] count) and 2 oxidative stress markers (serum isoprostane and total carbonyl content [TCC]) at baseline and were examined at 4 follow-up exams spaced 5 years apart. AMD was assessed from fundus photographs using the modified Wisconsin Age-Related Maculopathy Grading System. Genetic risk was defined by the number of risk alleles for variants of Complement Factor H (1061170) and Age-Related Maculopathy Susceptibility 2 (rs10490924) as low (0-1, n=1063), intermediate (2, n=416) and high (3-4, n=118).
The 20-year cumulative incidence of early AMD was 20.4% and for late AMD it was 3.8%. While adjusting for age, sex, smoking status, genetic risk status and other risk factors, only CRP (reported as odds ratio trend per quartile, P value for test of trend; 1.23, p=0.008) and IL-6 (1.18, p=0.04) were statistically significantly associated with the 20-year incidence of early AMD, and only CRP (1.44, P=0.04) was associated with the 20-year cumulative incidence of late AMD. Similar models were run stratifying by genetic risk. In the intermediate risk group, CRP (1.77, P=0.0001), TNF-α (1.54, P=0.006) and IL-6 (1.41, P=0.02) were associated with the risk of early AMD. CRP (2.13, p=0.01) and TNF-α (2.62, p=0.04) were also were associated with the 20-year cumulative incidence of late AMD. Among those in the high genetic risk group, isoprostane (2.13, P=0.04), TCC (2.03, P=0.04) and WBC count (2.07, P=0.03) were associated with the cumulative incidence of early AMD.
Our findings suggest a relation of inflammatory and oxidative stress markers to the 20-year cumulative incidence of early and late AMD in those with intermediate and high genetic risk.
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