N E W D E V E L O P M E N T S
The Genetics of Cataract
Catherine A. McCarty and Hugh R. Taylor
C ataract 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 world2 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 Austra-
lian 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 understand-
ing of the risk factors for age-related cataract. Numerous papers
have been written about the epidemiology of age-related cata-
ract. 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 con-
firmed 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 anti-
oxidants 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
From the Centre for Eye Research Australia, University of Mel-
bourne.
Submitted for publication December 6, 2000; revised February 23,
2001; accepted March 8, 2001.
Commercial relationships policy: N.
Corresponding author: Hugh R. Taylor, Centre for Eye Research
Australia, University of Melbourne, 32 Gisborne Street, East Melbourne,
VIC 3002, Australia. h.taylor@unimelb.edu.au
Investigative Ophthalmology & Visual Science, July 2001, Vol. 42, No. 8
Copyright Association for Research in Vision and Ophthalmology
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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 sur-
gery, 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 cata-
ract.8 Segregation analyses on the Beaver Dam Eye Study co-
hort suggested that a single major gene may account for 58% of
the variable risk of development of cortical cataract9 and that
another single major gene may account for 35% of nuclear
cataract.10 Neither of these studies measured the relative con-
tribution of genetics versus environmental effects on the de-
velopment 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 environ-
ment 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 congen-
ital 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
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 1678 McCarty and Taylor IOVS, July 2001, Vol. 42, No. 8

more information about the cause of age-related cataract and

FIGURE 1. Percentage of increase in the total Australian population
and the number of people with age-related cataract from 2001 to 2021,
relative to 1996.
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 re-
search 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 inter-
vention 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 cata-
ract is decreased. Clinical trials to quantify the effect of anti-
oxidants in preventing the incidence and progression of cata-
racts 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
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 cat-
aract.
References
1. Pararajasegaram R. Vision 2020 the right to sight: from strategies
to action. Am J Ophthalmol. 1999;128:359 360.
2. Thylefors B, Negrel A-D, Pararajasegaram R, Dadzie KY. Available
data on blindness. WHO Programme for the Prevention of Blind-
ness. Geneva: World Health Organization; 1995.
3. McCarty CA, Nanjan MB, Taylor HR. Operated and unoperated
cataract in Australia. Clin Exp Ophthalmol. 2000;28:77 82.
4. Dandona L, Dandona R, Naduvilath TJ, et al. Population-based
assessment of the outcome of cataract surgery in an urban popu-
lation in southern India. Am J Ophthalmol. 1999;127:650 658.
5. Javitt JC, Steinberg EP, Sharkey P, et al. Cataract surgery in one eye
or both. Ophthalmol. 1995;102:15831593.
6. West SK, Valmadrid CT. Epidemiology of risk factors for age-
related cataract. Surv Ophthalmol. 1995;39:323334.
7. Hodge WG, Whitcher JP, Satariano W. Risk factors for age-related
cataracts. Epidemiol Rev. 1995;17:336 346.
8. The Framingham Offspring Eye Study Group. Familial aggregation
of lens opacities: the Framingham Eye Study and the Framingham
Offspring Eye Study. Am J Epidemiol. 1994;140:555564.
9. Heiba IM, Elston RC, Klein BEK, Klein R. Evidence for a major gene
for cortical cataract. Invest Ophthalmol Vis Sci. 1995;36:227235.
10. Heiba IM, Elston RC, Klein BEK, Klein R. Genetic etiology of
nuclear cataract: evidence for a major gene. Am J Med Gen.
1993;47:1208 1214.
11. Hammond CJ, Snieder H, Spector TD, Gilbert CE. Genetic and
environmental factors in age-related nuclear cataracts in monozy-
gotic and dizygotic twins. N Engl J Med. 2000;342:1786 1790.
12. Hammond CJ, Duncan DD, Snieder H, de Lange ME, West SK,
Spector TD, Gilbert CE. The heritability of age-related cortical
cataract: the Twin Eye Study. Invest Ophthalmol Vis Sci. 2001;42:
601 605.
13. Duke-Elder S. Congenital deformities. Part 2. Normal and Abnor-
mal Development. Vol III. System of Ophthalmology. St Louis: CV
Mosby; 1964.

New Developments in Vision Research

Written for a broad audience, the articles in this column succinctly and provoca-
tively review a rapidly changing area of visual science that shows progress and holds
potential. Authors and topics are chosen by the Editor-in-Chief in collaboration with
the Editorial Board.
To avoid bias, the Editor-in-Chief subjects these articles to the same rigorous
peer review process to which all other IOVS articles are subjected. Space and
reference limitations are imposed on the authors.
The purpose of this series is not the recognition of individual scientists, nor
exhaustive review of a subject, but the stimulation of interest in a new research
area.
Editor-in-Chief

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