Markers of Inflammation, Oxidative Stress, Endothelial Dysfunction and 20-Year Cumulative Incidence of Early AMD
Modifying levels of factors associated with age-related macular degeneration (AMD) may decrease the risk for visual impairment in older persons. This longitudinal population-based cohort study examined the relationships of markers of inflammation, oxidative stress and endothelial dysfunction to the 20-year cumulative incidence of early AMD. It involved a random sample of 975 persons in the Beaver Dam Eye Study without signs of AMD who participated in the baseline examination in 1988 to 1990 and up to four follow-up examinations in 1993 to 1995, 1998 to 2000, 2003 to 2005, and 2008 to 2010.
Serum markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor [TNF]–α receptor 2, interleukin-6, and white blood cell count), oxidative stress (8-isoprostane and total carbonyl content), and endothelial dysfunction (soluble vascular cell adhesion molecule [VCAM] ]–1 and soluble intercellular adhesion molecule]–1) were measured. Interactions with complement factor H (rs1061170), age-related maculopathy susceptibility 2 (rs10490924), complement component 3 (rs2230199), and complement component 2/complement factor B (rs4151667) were examined using multiplicative models. AMD was assessed from fundus photographs. The main outcome measure was early AMD defined by the presence of any size drusen and the presence of pigmentary abnormalities or by the presence of large-sized drusen (≥125-µm diameter) in the absence of late AMD.
It was determined that the 20-year cumulative incidence of early AMD was 23.0%. Adjusting for age, sex, and other risk factors, high-sensitivity C-reactive protein (odds ratio [OR] comparing fourth with first quartile, 2.18; p=0.005), TNF–α receptor 2 (OR, 1.78; p=0.04), and interleukin-6 (OR, 1.78; p=0.03) were associated with the incidence of early AMD. Additionally, increased incidence of early AMD was associated with soluble VCAM–1 (OR per SD on the logarithmic scale, 1.21; p=0.04).
Modest evidence of relationships of serum high-sensitivity C-reactive protein, TNF–α receptor 2, interleukin-6, and soluble VCAM–1 to the 20-year cumulative incidence of early AMD independent of age, smoking status, and other factors was found. It is not known whether these associations represent a cause-and-effect relationship or whether other unknown confounders accounted for the findings. Even if inflammatory processes are a cause of early AMD, it is not known whether interventions that reduce systemic inflammatory processes will reduce the incidence of early AMD.