Cataract is the first of the five immediate priority areas for the global
initiative to eliminate avoidable blindness by the year 2020, Vision
2020.
1 Cataract was chosen because it is the leading cause
of vision impairment in the world
2 and because safe,
effective surgical intervention is available that leads to a dramatic
improvement in visual function. However, the results of cataract
surgery depend on surgical experience, the type of surgery performed,
the presence of ocular comorbidities, and environmental and social
conditions. For example, a recent population-based study in Australia
showed that 85% of eyes had best corrected visual acuity of 6/12
(20/40) or better after cataract surgery.
3 In contrast, a
study in India revealed that 32% of eyes had a poor visual outcome
(distance visual acuity, <20/60) and 20% of eyes were legally blind
after cataract surgery.
4
Cataract surgery has been estimated to cost $3.4 billion per year in
the United States and is the most commonly performed ophthalmic
procedure.
5 The incidence of cataract and the total cost
associated with cataract will increase as the percentage of older
people increases in most countries. For example, by applying
age-specific rates of cataract to the estimated Australian
population,
3 we find that although the total Australian
population is expected to increase by 22% between 1996 and 2021, the
number of people with age-related cataract is likely to increase by
76% during that same period
(Fig. 1) , because of the aging of the population alone.
From age-specific prevalence data, it can be estimated that if exposure
to risk factors for cataract could be modified to delay the onset of
cataract by just 10 years, the need for cataract surgery would decrease
by nearly 50%.
6 Because the median age for the
development of cataract is 70 years, a 10-year delay represents only a
modest, and not unrealistic, 14% decrease in the rate of development
of cataract.
Successful prevention programs require a good understanding of the risk
factors for age-related cataract. Numerous papers have been written
about the epidemiology of age-related cataract. Two review papers
published in 1995 summarized the known risk factors for
cataract,
6 7 which could be categorized as demographic,
environmental, lifestyle-associated, disease-related, and
miscellaneous. More recent studies have confirmed and extended these
findings, but have not identified new categories of risk factors, and
several prospective clinical trials are in progress to assess the
effect of supplementary antioxidants. Cross-sectional studies have
suggested that antioxidants protect against the development of
cataract. The most obvious demographic factor is increasing age, but
most studies have also shown that women have an increased risk of
cataract. Cataract is also generally more common in people of lower
socioeconomic status. The primary environmental risk factor is the link
between ocular exposure to UV-B and cortical cataract.
Lifestyle-associated risk factors include the increased risk of nuclear
cataract due to cigarette smoking and the potential increased risk of
cataract associated with high alcohol intake. Disease-related risk
factors include diabetes, hypertension and antihypertensive
medications, and the use of antipsychotic medications or steroids.
At the time that the review articles were published, family history
also had been shown to have some association with cataract, but recall
bias was suggested as a potential reason for the observed
associations.
7 Others had suggested that families that
lived a long time were more likely to need cataract surgery, just
because of their older age.
More sophisticated analyses of the potential role of genetics in the
development of cataract were reported subsequently. In the Framingham
Eye Study, strong associations were found between siblings for nuclear
and posterior subcapsular cataract.
8 Segregation analyses
on the Beaver Dam Eye Study cohort suggested that a single major gene
may account for 58% of the variable risk of development of cortical
cataract
9 and that another single major gene may account
for 35% of nuclear cataract.
10 Neither of these studies
measured the relative contribution of genetics versus environmental
effects on the development of age-related cataract. Twin studies
provide an excellent opportunity to address this question of nature
versus nurture.
Despite the extensive research that had been conducted into defining
the risk factors for cataract, a large percentage of the disease in the
population was still unaccounted for by known risk factors. Then,
Hammond et al.
11 published their findings from the Twin
Eye Study related to nuclear cataract. They found that the relative
contributions of genetics and environment to the development of nuclear
cataract were 48% and 14%, respectively, whereas age accounted for
the risk in their study group of older female twins.
11 In
the March 2001 issue of
IOVS, Hammond et al.
12 reported their findings on cortical cataract. They estimate that
genetics may account for between 37% and 58% of cortical cataract and
that environment accounts for between 11% and 37%. These findings
related to the genetic influence on cortical cataract are similar to
those of the Beaver Dam Eye Study.
9
Genetics had been known to explain a number of congenital eye
conditions, including congenital cataract,
13 but it was a
real surprise to discover that genetics explains such a large part of
the variation in age-related cataract after controlling for the other
known environmental and demographic risk factors. These new data from
investigation of both the nature and nurture elements are a great help
in filling the gap in our knowledge about the range of factors
associated with the development of age-related cataract. Results from
all published studies to date suggest that perhaps 50% of age-related
cataract can be explained by genetics, with the remainder due to aging
and to systemic and environmental factors.
The challenge now is to use the new genetic information to design
studies to decrease the incidence of age-related cataract in the
population. Obviously, the race is on to identify genes associated with
an increased risk of cataract. However, direct gene therapy in relation
to preventing the onset of cataract may not be possible in the near
future, because further research would be needed first, including
identification of the gene product and targets for intervention and
methods of delivery to the lens.
The next logical step may be to determine the impact of different risk
factors for cataract in those who have a known genetic susceptibility.
This information should allow an intervention to be designed for
families who have an increased risk of cataract. For example, families
with an increased risk of cortical cataract could be involved in a
study to specifically reduce ocular exposure to ocular UV-B. On the
other hand, families with an increased risk of nuclear cataract could
be enrolled in a specific program to stop cigarette smoking to
determine whether their risk of development of nuclear cataract is
decreased. Clinical trials to quantify the effect of antioxidants in
preventing the incidence and progression of cataracts may be better
targeted at families at higher risk.
The results of the two Twin Eye Studies of nuclear and cortical
cataract are exciting, because they provide us with more information
about the cause of age-related cataract and potentially allow us to
tailor our interventions. They provide the first really new
epidemiologic information about cataract that has been published in
some time and suddenly fill in a large gap in the knowledge about
factors associated with cataract.