TABLE 2.

Ten-Year Incidence of Age-related Macular Degeneration in the Blue Mountains Eye Study, Classified by Statin Use

AMD Stage/Lesion Statin Use* No. of Incident Cases Adjusted HR (95% CI)† P value Adjusted HR (95% CI)‡ P value

Early AMD sublesions

Indistinct soft drusen No (n ⫽ 2,015) 202 1.00 1.00
Yes (n ⫽ 145) 5 0.32 (0.13–0.80) .015 0.33 (0.13–0.84) .020
Large distinct soft drusen No (n ⫽ 1,861) 143 1.00 1.00
Yes (n ⫽ 139) 8 0.75 (0.35–1.60) .46 0.82 (0.38–1.78) .62
Pigmentary abnormality No (n ⫽ 1,883) 360 1.00 1.00
Yes (n ⫽ 133) 22 0.80 (0.49–1.29) .35 0.81 (0.49–1.36) .44
Early AMD No (n ⫽ 2,001) 235 1.00 1.00
Yes (n ⫽ 144) 9 0.50 (0.25–1.02) .057 0.54 (0.26–1.11) .094
Any (late ⫹ early) AMD No (n ⫽ 2,033) 267 1.00 1.00
Yes (n ⫽ 145) 10 0.48 (0.25–0.95) .036 0.52 (0.26–1.04) .064

AMD ⫽ age-related macular degeneration; CI ⫽ confidence interval; HR ⫽ hazard ratio.

*Statin use was defined according to use at the examination five years before the incident case/censoring.
†
Hazard ratio (95% confidence interval); adjusted for age, gender, smoking, job prestige, and history of cardiovascular disease.
‡
Hazard ratio (95% confidence interval); additionally adjusted for serum total cholesterol, high-density lipoprotein cholesterol, fibrinogen,
and white cell count.

REFERENCES DESIGN: Population-based cohort study.

1. Guymer RH, Chiu AW, Lim L, Baird PN. HMG CoA reductase
inhibitors (statins): do they have a role in age-related macular
degeneration? Surv Ophthalmol 2005;50:194 –206.
2. Hall NF, Gale CR, Syddall H, et al. Risk of macular degen-
eration in users of statins: Cross-Sectional Study. Br Med J
2001;323:375–376.
3. Mitchell P, Smith W, Attebo K, Wang JJ. Prevalence of
age-related maculopathy in Australia: the Blue Mountains Eye
Study. Ophthalmology 1995;102:1450 –1460.
4. Klein R, Davis MD, Magli YL, et al. The Wisconsin age-related
maculopathy grading system. Ophthalmology 1991;98:1128–1134.
5. Van Leeuwen R, Tomany SC, Wang JJ, et al. Is medication
use associated with the incidence of early age-related macu-
lopathy? Pooled findings from 3 continents. Ophthalmology
2004;111:1169 –1175.
6. Van Leeuwen R, Vingerling JR, Hofman A, et al. Cholesterol
lowering drugs and risk of age-related maculopathy: prospec-
tive cohort study with cumulative exposure measurement. Br
Med J 2003;326:255–256.
7. Anderson DH, Mullins RF, Hageman GS, Johnson LV. A role
for local inflammation in the formation of drusen in the aging
eye. Am J Ophthalmol 2002;134:411– 431.
METHODS: Of 3,654 baseline (1992 to 1994) elderly
participants in the Blue Mountains Eye Study (BMES),
2,335 (75% of survivors) were reexamined after five
years (1997 to 1999) and 1,952 (76% of survivors) after
10 years (2002 to 2004). Lens photographs were taken
and graded using the Wisconsin Cataract Grading Sys-
tem. History, physical examination, and fasting blood sam-
ples provided data on possible risk factors. Discrete linear
logistic models were used to assess the risk of cataract.
RESULTS: After controlling for age, gender, and other
factors, statin use was protective for any cataract (hazard
ratio [HR] 0.52; 95% confidence interval [CI] 0.29-
0.93), but was not significantly associated with incident
nuclear (HR 0.66; CI 0.35 to 1.25), cortical (HR 0.76;
CI 0.44 to 1.33), or posterior subcapsular (PSC) cataract
(HR 1.47; CI 0.70 to 3.08).
CONCLUSIONS: Statin use was found to reduce by 50%
the risk of cataract development, principally nuclear or
cortical cataract subtypes. (Am J Ophthalmol 2007;143:
687– 689. © 2007 by Elsevier Inc. All rights reserved.)

Statin Use and the Long-term Risk of

I T IS HYPOTHESIZED THAT STATIN USE COULD INFLUENCE
cataract development. Data recently reported from the
Beaver Dam Eye Study1 suggest statin use protects against
five-year incident nuclear cataract (odds ratio 0.60; 95%
Incident Cataract: The Blue confidence interval [CI] 0.39 to 0.93). We aimed to
Mountains Eye Study explore this association in another population-based study,
Jennifer S. L. Tan, Paul Mitchell, the Blue Mountains Eye Study (BMES).
Elena Rochtchina, and Jie Jin Wang
From the Centre for Vision Research, Department of Ophthalmology,
Westmead Millennium Institute, University of Sydney, Australia.
PURPOSE: To assess the association between statin use and Inquiries to Jie Jin Wang, Centre for Vision Research, Department of
long-term incident cataract. Ophthalmology, University of Sydney, Westmead Hospital, Hawkesbury
Rd, Westmead, NSW Australia, 2145; e-mail: jiejin_wang@wmi.usyd.
Accepted for publication Nov 14, 2006. edu.au

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 TABLE 1. Comparison of Baseline (1992 to 1994) Characteristics (%) Between Participants Followed and Not Followed Over
10 Years (Excluding Those Who Died): the Blue Mountains Eye Study

Not Followed or Without

Baseline Characteristics Followed (n ⫽ 2406) Gradable Photos (n ⫽ 462) P value†

Mean age in years (95% CI) 64.3 (64.0-64.6) 62.2 (61.4-62.9) ⬍.0001
Women 57.5 62.5 .044
Statin use 2.9 3.5 .49
Ever use of inhaled steroids 10.6 10.0 .66
Presence of obesity (body mass index ⱖ 30) 17.6 20.1 .20
History of diabetes 6.1 9.5 .0079
History of cardiovascular disease (angina, myocardial infarction, or stroke) 16.4 12.5 .037
Presence of hypertension 43.4 45.7 .36
Presence of any myopia 21.3 24.7 .11
Mean fasting blood results
High-density lipoprotein cholesterol (mmol/l) 1.44 1.43 .75
Total cholesterol (mmol/l) 6.05 6.15 .11
White cell count (109 cells/l) 6.38 6.58 .047
Smoking status
Never 51.5 45.9
Past 35.4 35.1 .90
Current 13.1 19.0 .0007
High job prestige 62.5 58.4 .096

CI ⫽ confidence interval.
†
Chi-square test used for discrete risk factors; t test used for continuous risk factors (Satterthwaite for unequal variances, otherwise pooled
t test).

The BMES is a cohort study of an elderly Australian
population.2 Of 3,654 baseline (1992 to 1994) partici-
pants, 2,335 (75% of survivors) were reexamined after five
years and 1,952 (76% of survivors) after 10 years. Of those
followed, 2,406 had photographs available for cataract
assessment. Lens photographs were taken at each exami-
nation and graded using the Wisconsin Cataract Grading
System.2 Questionnaires ascertained relevant history, and
fasting blood samples were taken.
Incident cataract was defined as the appearance of nuclear,
cortical, or posterior subcapsular (PSC) cataract in either eye
in bilaterally phakic participants without corresponding cat-
aract type in either eye at baseline. Incident any cataract was
defined as cataract surgery performed or any cataract type
developed in bilaterally phakic participants without any
cataract at baseline. Statistical Analysis System (SAS Insti-
tute, Cary, North Carolina, USA) was used for analyses.
Discrete logistic models estimated hazard ratio (HR) and CI
for the association between statin use and cataract. Except for
age and gender, all other variables were represented as
time-dependent covariates indexed at the examination pre-
ceding incident cataract or censoring. Incident cases from
both follow-up examinations were combined in a single
model. The study obtained Institutional Ethics Committee
approval and written consent.
At the baseline and five-year examinations, there were 70
and 195 statin users, respectively. Table 1 compares baseline
characteristics of those followed and not followed. After
controlling for risk factors associated with each cataract type,
we found no significant association between statin use and
the incidence of each cataract subtype (Table 2). Results were
similar for cataract subtypes when referencing to those with-
out any baseline cataract. However, statin use was protective
for the incidence of any cataract.
At both the baseline3 and 10-year examinations, we
could not confirm the significant protective effect of statins
on nuclear cataract reported by Klein and associates,1
although our finding of a 35% reduction in the risk point
estimate is generally consistent with their report. We did
find statin use protective for any cataract, consistent with
the 25% risk reduction in the equivalent point estimate
reported by Klein and associates1 However, because par-
ticipants without gradable photographs for all cataract
types were excluded, the analyses of any cataract were
based on a reduced number of participants and should be
interpreted cautiously. Previous epidemiologic studies have
reported no significant association between statin use and
cataract,4 and some animal models highlighted a poten-
tially increased risk of PSC cataract with excessive statin
doses.5 Our results show a nonsignificant increased risk of
PSC cataract with statin use. Hence our result for any
cataract is likely driven by the protective but nonsignifi-
cant associations between statin use and cortical or nuclear
cataract. Each cataract subtype on its own did not reach
statistical significance, likely because of either insufficient
power or misclassification in each specific control group

688 AMERICAN JOURNAL OF OPHTHALMOLOGY APRIL 2007

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 TABLE 2. Ten-Year Incidence of Cataract in the Blue Mountains Eye Study, Classified by Use of Statins

Age-Adjusted Hazard Ratio Multivariate Hazard Ratio

No. in Each Group No. of Incident Cases (95% Confidence Interval) P value (95% Confidence Interval) P value

Nuclear cataract
No statin use 1,152 365 1.00 1.00
Statin use 72 17 0.75 (0.42–1.35) 0.34 0.64 (0.33–1.23)* .18
Cortical cataract
No statin use 1,604 359 1.00 1.00
Statin use 115 21 0.84 (0.51–1.36) 0.47 0.76 (0.44–1.33)† .34
Posterior subcapsular cataract
No statin use 1,825 123 1.00 1.00
Statin use 126 11 1.38 (0.72–2.65) 0.33 1.47 (0.70–3.08)‡ .30
Any cataract储
No statin use 981 473 1.00 1.00
Statin use 63 22 0.55 (0.30–0.94) 0.030 0.52 (0.29–0.93)§ .028

*Additionally adjusted for gender, total cholesterol, high-density lipoprotein cholesterol, smoking, skin damage, and diabetes.
†
Additionally adjusted for gender, total cholesterol, high-density lipoprotein cholesterol, and obesity.
‡
Additionally adjusted for gender, total cholesterol, high-density lipoprotein cholesterol, obesity, ever use of inhaled steroids, hypertension,
and myopia.
§
Additionally adjusted for gender, total cholesterol, high-density lipoprotein cholesterol, smoking, obesity, and diabetes.
储
Includes cases of incident cataract surgery and each specific cataract type.

(subjects without incident cortical cataract likely have
incident nuclear cataract). A protective influence of statin
therapy on these two cataract types is biologically plausi-
ble. Oxidative stress has been associated with both cataract
types,1,6 and inflammation linked with any cataract.7
Statins may counter both effects.1
Strengths of our study include prospective observation
from a population-based sample with reasonable follow-up.
However, our findings could be attributable to chance or
affected by indication bias. Our negative findings could
have resulted from insufficient study power, because our
study can detect a minimum HR of 0.4 for nuclear cataract
with 80% power at .05 significance.
In summary, statin use was significantly protective for
the incidence of cataract in the BMES cohort, principally
for nuclear or cortical cataract. Because a protective
influence from statins on cataract could have potentially
important health care implications, this relationship needs
confirmation and exploration.
THIS STUDY WAS SUPPORTED IN PART BY THE AUSTRALIAN
National Health and Medical Research Council, Canberra, Australia
(NHMRC Project Grants 974159 and 211069). The authors indicate no
financial conflict of interest. Involved in design and conduct of study
(P.M., J.J.W., J.T.); collection and management of the data (P.M.,
J.J.W.); analysis (E.R., J.T.); and interpretation of the data (P.M., J.J.W.,
E.R., J.T.); and preparation of the first draft manuscript (J.T.); review and
approval of the manuscript (P.M., J.J.W., E.R., J.T.).
REFERENCES
1. Klein BEK, Klein R, Lee KE, Grady LM. Statin use and
incident nuclear cataract. JAMA 2006;295:2752–2758.
2. Mitchell P, Cumming RG, Attebo K, Panchapakesan J.
Prevalence of cataract in Australia: the Blue Mountains Eye
Study. Ophthalmology 1997;104:581–588.
3. Cumming RG, Mitchell P. Medications and cataract: the Blue
Mountains Eye Study. Ophthalmology 1998;105:1751–1758.
4. Smeeth L, Hubbard R, Fletcher AE. Cataract and the use of
statins: a Case-Control Study. QJM 2003;96:337–343.
5. Gerson RJ, MacDonald JS, Alberts AW, et al. On the etiology of
subcapsular lenticular opacities produced in dogs receiving
HMG-CoA reductase inhibitors. Exp Eye Res 1990;50:65–78.
6. Sobol RW, Foley JF, Nyska A, et al. Regulated over-expres-
sion of DNA polymerase B mediates early onset cataract in
mice. DNA Repair 2003;2:609 – 622.
7. Schaumberg DA, Ridker PM, Glynn RJ, et al. High levels of
plasma C-reactive protein and future risk of age-related
cataract. Ann Epidemiol 1999;9:166 –171.
“Top Hat”–Shaped Penetrating
Keratoplasty Using the
Femtosecond Laser
Roger F. Steinert, Teresa S. Ignacio, and
Melvin A. Sarayba
Accepted for publication Nov 3, 2006.
From the Department of Ophthalmology, University of California
Irvine, California (R.F.S., T.S.I.); and IntraLase Corp, Irvine, California
(M.A.S.).
Inquiries to Roger F. Steinert, Department of Ophthalmology, Univer-
sity of California Irvine, 118 Med Surge I, Irvine, CA 92697; e-mail:
steinert@uci.edu

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