Modifying levels of factors associated with age-related macular
degeneration (AMD) may decrease risk of visual impairment in older
To examine the relationships of markers of inflammation, oxidative
stress, and endothelial dysfunction to the 20-year cumulative incidence of
Longitudinal population-based cohort study.
Beaver Dam, Wisconsin.
A random sample of 975 persons in the Beaver Dam Eye Study without
signs of AMD who participated in the baseline examination in 1988-1990 and
up to four follow-up examinations in 1993-1995, 1998-2000, 2003-2005, and
Serum markers of inflammation (high sensitivity C-reactive protein
[hsCRP], tumor necrosis factor-α receptor 2
[TNF-αR2], interleukin-6 [IL-6], and
white blood cell count), oxidative stress (8-isoprostane and total carbonyl
content), and endothelial dysfunction (soluble vascular cell adhesion
molecule-1 [sVCAM-1] and soluble intercellular adhesion
molecule-1) were measured. Interactions with Complement Factor
H (rs1061170) and Age-Related Maculopathy
Susceptibility 2 (rs10490924), C3 (rs2230199)
and C2/CFB (rs4151667) were examined using multiplicative
models. AMD was assessed from fundus photographs.
Main Outcome Measure
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.
The 20-year cumulative incidence of early AMD was 23.0%.
Adjusting for age, sex, and other risk factors, hsCRP (odds ratio
[OR] comparing 4th to 1st quartile
2.18, P=0.005), TNF-αR2 (1.78, P=0.04), and IL-6
(1.78, P=0.03) were associated with the incidence of early AMD.
Increased incidence of early AMD was associated with sVCAM-1 (OR per
standard deviation on the log ng/mL scale 1.21, P=0.04).
Conclusions and Relevance
We found modest evidence of relationships of serum hsCRP,
TNF-αR2, and IL-6 and sVCAM-1 to the 20-year cumulative incidence of
early AMD independent of age, smoking status, and other factors. It is not
known whether these associations represent a cause and effect relationship
or if 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.