23
Modifiable risk factors for AMD
2
The epidemiological studies conducted in the past 25
years have helped identifying major modifiable risk
factors for AMD. In particular, smoking and nutrition
appear ever more important in determining the occur-
rence of AMD, and may, in the future, lead to preven-
tion strategies.
2. Smoking
Smoking is the best characterized risk factor for AMD
(1)
.
The initial observations performed in Caucasian popula-
tions fromWestern countries
(2)
, are now being confirmed
in other ethnic groups, such as African-Americans
(3)
,
Latino-American
(4)
, or Asian populations
(5-7)
. In most
studies, the risk for late AMD was multiplied by 2.5 to
4.5 in current smokers. In addition, the dose-response
relationship was explored in some studies
(6,8-12)
. Most of
these studies found that the risk for AMD increased with
increasing number of cigarettes smoked per day, and,
even more, with number of pack-years smoked, which
is an indicator of cumulative smoking over the lifetime
(mean number of packs smoked/day x duration of smok-
ing (years). Moreover, the risk for AMD appeared to
decrease with time from cessation of smoking. Former
smokers generally demonstrated a lower risk for AMD
than current smokers. Several studies have shown that
the risk for AMD in subjects having ceased smoking for
more than 20 years was similar to the risk in never smok-
ers
(8-10,13)
. One study suggested that passive smoking is
also associated with an increased risk for AMD
(9)
, while
this association did not reach statistical significance in
another study
(14)
. Finally, smoking appeared to be related
to similar risks for both types of late AMD (geographic
atrophy and neovascular AMD)
(9,13,15-16)
. By contrast,
associations with early AMD were weaker in the vast
majority of published studies, and often not statistically
significant
(8-9,13,15,17-18)
.
Overall, the strength of the association (about 3-fold
increased risk in current smokers), its consistency
across different populations, the observation of a
clear dose-response relationship in most studies, and
the decrease of the risk with stopping smoking are all
strong arguments in favour of a causal role of tobacco
smoking in the aetiology of late AMD.
The exact mechanisms by which smoking increases the
risk for AMD are unclear, and probably multiple, includ-
ing oxidative stress, inflammation and decreased macular
pigment. Finally, recent studies gave important insights
on the joint effects of smoking and genetic polymor-
phisms, showing that the risk for AMD is particularly
high in smokers bearing at-risk polymorphisms in the
CFH or LOC387715 genes
(19-21)
.
Other vascular risk factors, such as systemic hyperten-
sion, obesity, diabetes, plasma lipids or alcohol drinking
may be associated with an increased risk of AMD, but
epidemiological studies have been inconsistent in this
field
(22)
. At the time being, they remain putative, but not
clearly identified risk factors for AMD.
3. Nutritional factors
More recently, epidemiological studies have focused on
the potential association of AMD with nutritional fac-
tors. Mainly three types of nutritional factors have been
investigated for their potential protection against eye
ageing: antioxidants (mainly vitamins C and E, zinc), the
carotenoids lutein and zeaxanthin and omega 3 polyun-
saturated fatty acids (PUFA).
The retina is particularly susceptible to oxidative stress
because of the high level of in-site reactive oxygen spe-
cies production, due in particular to light exposure and
high metabolic activity
(23)
. Epidemiological studies are
1. Introduction
Author:
Cécile Delcourt, MD, PhD
Inserm, U897, Bordeaux, France
Université Bordeaux 2, Bordeaux, France
