You are on page 1of 9

The Association of Dietary Lutein plus

Zeaxanthin and B Vitamins with Cataracts in


the Age-Related Eye Disease Study
AREDS Report No. 37
Tanya S. Glaser, MD,1 Lauren E. Doss, MD,1 Grace Shih, MD,1 Divya Nigam, BA,1 Robert D. Sperduto, MD,2
Frederick L. Ferris III, MD,1 Elvira Agrón, MA,1 Traci E. Clemons, PhD,2 Emily Y. Chew, MD,1 for the
Age-Related Eye Disease Study Research Group*

Purpose: To evaluate whether dietary intake of luteiin/zeaxanthin and B vitamins is associated with cataract
prevalence and incidence.
Design: Clinic-based, baseline cross-sectional and prospective cohort study designs.
Participants: Three thousand one hundred fifteen patients (6129 eyes) enrolled in the Age-Related Eye
Disease Study 55 to 80 years of age followed up for mean of 9.6 years.
Methods: Participants completed baseline food frequency questionnaires. Baseline and annual lens photo-
graphs were graded centrally. Multivariate models controlling for previously identified risk factors for cataracts
tested for the association of cataracts with reported dietary intake, using the lowest quintile as reference.
Main Outcome Measures: Cataract surgery, cataract status (type and severity) at baseline, and develop-
ment of cataracts.
Results: At baseline, increased dietary riboflavin and B12 were associated inversely with nuclear and cortical
lens opacities. In comparisons of persons with and without cataract, persons with the highest riboflavin intake
versus those with the lowest intake had the following associations: mild nuclear cataract: odds ratio (OR), 0.78;
95% confidence interval (CI), 0.63e0.97; moderate nuclear cataract: OR, 0.62; 95% CI, 0.43e0.90; and mild
cortical cataract: OR, 0.80; 95% CI, 0.65e0.99. For B12, the results were: mild nuclear cataract: OR, 0.78; 95%
CI, 0.63e0.96; moderate nuclear cataract: OR, 0.62; 95% CI, 0.43e0.88; and mild cortical cataract: OR, 0.77;
95% CI, 0.63e0.95. Highest dietary B6 intake was associated with a decreased risk of moderate nuclear lens
opacity developing compared with the lowest quintile (OR, 0.67; 95% CI, 0.45e0.99). Highest dietary intake levels
of niacin and B12 were associated with a decreased risk of development of mild nuclear or mild cortical cataracts
in participants not taking Centrum (Pfizer, New York, NY) multivitamins. For participants taking multivitamins
during the study, the highest intake of dietary folate was associated with an increased risk of mild posterior
subcapsular lens opacity development. No statistically significant associations were found between lutein plus
zeaxanthin intake and presence at baseline or development of nuclear or cortical lens opacity outcomes.
Conclusions: These findings are consistent with earlier studies suggesting that dietary intake of B vitamins may
affect the occurrence of age-related lens opacities. Further investigations are warranted. Ophthalmology 2015;122:1471-
1479 ª 2015 by the American Academy of Ophthalmology.

*Supplemental material is available at www.aaojournal.org.

Cataract is the leading cause of blindness worldwide; the approaches to reduce visual impairment and healthcare
World Health Organization has estimated 20 million people costs.
are affected with vision loss resulting from cataract.1 In the Risk factors for cataract development include increasing
United States, age-related cataracts remain the leading cause age, diabetes,4,5 smoking,6 alcohol use, trauma, and
of vision loss, with Medicare spending more than $2 billion prolonged exposure to ultraviolet light.7e9 A greater un-
annually on cataract surgery.2,3 Because the total number of derstanding of the underlying processes involved in cataract
people with cataracts in the United States is expected to formation, particularly the role of oxidative stress,10,11 led to
increase to 30 million by 2020 in an aging population,3 numerous observational studies12e19 with a focus on vita-
identification of factors associated with the development mins and small molecules with antioxidant properties. Many
of age-related cataracts is an important step in developing of these studies reported inverse relationships between the

 2015 by the American Academy of Ophthalmology http://dx.doi.org/10.1016/j.ophtha.2015.04.007 1471


Published by Elsevier Inc. ISSN 0161-6420/15

Downloaded for Perpustakaan1 RSUD Ciawi (perpus1rsudciawi@gmail.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on November 05, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Ophthalmology Volume 122, Number 7, July 2015

development of age-related cataract or the occurrence of age-related type. For the cataract incidence analyses of cataract
cataract surgery and dietary intake or serum levels of development, eyes with moderate (type-specific) cataracts at
micronutrients with antioxidant properties. Micronutrients baseline were excluded from the progression to moderate cataract
of interest included vitamins A, C, and E; niacin; thiamin; analyses, and eyes with mild or moderate (type-specific) cataracts
at baseline were excluded from the development of at least mild
riboflavin; and carotenoids. However, results from the
cataract analyses.
observational studies have not been consistent, and in the
absence of any consensus about the importance of specific Participant Screening and Data Collection
micronutrients, several controlled clinical trials20e23 tested
high doses of what were thought to be the most promising of Baseline data and information regarding risk factors for the
the antioxidants (vitamins C and E, b-carotene, and lutein development of age-related cataract were obtained by examination
plus zeaxanthin), but found no statistically significant effects and interview. Because 55% of enrolled participants already were
users of multivitamin supplements or at least 1 ingredient in the
on cataract development.20,24 A randomized trial of vitamins AREDS formulation at the time of screening, a standard daily
C and E in 2 simultaneous trials in the United States and in multivitamin and mineral supplement, Centrum, was offered to all
the United Kingdom showed mixed results.25 participants to standardize the use of nonstudy supplements. Sixty-
The Age-Related Eye Disease Study (AREDS) was a ran- six percent of study participants opted to take Centrum. We eval-
domized controlled clinical trial of vitamins C and E, b-caro- uated baseline dietary intake calculated from a self-administered,
tene, and zinc for the treatment of age-related macular 90-item, semiquantitative food frequency questionnaire that
degeneration (AMD) and age-related cataracts.20 Although the assessed dietary intake (nutrients, vitamins, and minerals) during
AREDS found no statistically significant effect of vitamins C the year before randomization. Details of the food frequency
and E and b-carotene on the progression of lens opacities in questionnaire and its validation have been described previously.38
the controlled randomized trial,20 observational data from Standard lens photographs, obtained at baseline and annually
beginning 2 years after enrollment, were graded centrally and were
AREDS suggest that daily use of Centrum, (Pfizer, New used to assess the presence and progression of lens opacities. The
York, NY), a multivitamin and mineral supplement, may AREDS cataract grading scale is a modified version of the Wis-
decrease the progression of nuclear opacities.26 In the consin Cataract Grading System.39 Nuclear opacities were graded
AREDS, a food frequency questionnaire was administered at on a decimal scale using a series of 7 standard photographs with
baseline and lens photographs were obtained at baseline, year increasingly severe nuclear opacification. A grid overlay on
2, and annually thereafter. We examined the relationships of retroillumination lens photographs was used to estimate the area
baseline lutein plus zeaxanthin and B vitamin intake with of lens involvement for posterior subcapsular cataract (PSC) and
cataract prevalence, cataract incidence, and cataract surgery. cortical lens opacities. History of cataract surgery was
We chose these nutrients on the basis of antioxidant determined by patient report, slit-lamp examination during study
potential,10,27e29 presence in the lens,30e32 and reported pro- visits, and evidence of aphakia or pseudophakia on lens
photographs.
tective associations with cataracts in observational33e35 and
interventional36 studies. Outcome Measures
A standardized and validated grading system was used to establish
Methods a 3-step severity scale for each type of opacity.39,40 The controls
and the severity of the 3 types of cataract using the AREDS
The AREDS, a long-term multicenter, prospective study of in- standard for lens classification are described in Table 1A. The
dividuals 55 to 80 years of age, was designed to evaluate the risk baseline cross-sectional analyses compared controls with persons
factors, clinical course, and prognosis of AMD and cataract. The with mild and moderate nuclear or cortical opacities. Posterior
project included a randomized controlled clinical trial of the subcapsular cataract opacities were not included in the baseline
AREDS formulation (vitamins C and E, b-carotene, zinc, and cross-sectional analyses because they were uncommon in the
copper). Details of the study design have been published else- cohort at baseline (only 2.5% of persons had PSC of >5% of the
where37 and are summarized briefly here. Eleven retinal specialty central 5 mm in at least 1 eye). The outcomes examined in the
clinics enrolled 4757 individuals who were followed up at incidence analyses included development of moderate lens opaci-
6-month intervals in the clinical trial between 1992 and 2001. ties of all 3 types or cataract surgery.
Participants were followed up annually for an additional 5 years in
an observational study until 2005. Institutional review board Statistical Analyses
approval was obtained at each clinical site, and participants signed
informed consent forms for the study. Nutrient intake values were adjusted for total energy intake by
Based on fundus photographs graded at a central reading center, computing nutrient densities (nutrient intake/total energy intake).
best-corrected visual acuity, and ophthalmologic evaluations, par- For cataract prevalence, gender-adjusted quintiles then were
ticipants were enrolled in 1 of several AMD categories.38 However, calculated. For the analysis of cataract progression and advance-
there were no specific eligibility criteria for lens opacities except ment to cataract surgery, the vitamin intake amounts for partici-
that the lens had to be sufficiently clear to allow for adequate pants taking Centrum during the study (n ¼ 3143 [66%]) were
fundus photographs and visual acuity had to be 20/30 or better calculated by combining the contributions from multivitamins
in at least 1 eye. Participants who had advanced AMD in 1 eye (Table 2, available at www.aaojournal.org) with the vitamin intake
were excluded from these analyses because more advanced from food only. Because Centrum use was found to be associated
severity of lens opacities was allowed in these eyes, creating the significantly with nuclear opacities in our modeling, participants
possibility of an ascertainment bias. Excluded from the current then were stratified into Centrum users and nonusers and gender-
study were eyes that were aphakic or pseudophakic at baseline. adjusted quintiles were calculated separately. Because Centrum
Participants younger than 60 years were excluded from the ingredient amounts were added to the nutrient intake values,
prevalence analyses to ensure that the cataract was the stratification of Centrum users and nonusers allowed for more

1472

Downloaded for Perpustakaan1 RSUD Ciawi (perpus1rsudciawi@gmail.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on November 05, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Glaser et al 
Cataracts and Nutrition

Table 1. Definition of Cataract and Number of Participants and Eyes in Analyses

A. Definition of Controls and Cataract Types Evaluated in the Age-Related Eye Disease Study
Cataract Type Mild Moderate Controls
Nuclear AREDS nuclear grade, >2 and <4 AREDS nuclear grade, 4 AREDS nuclear grade, 2
Cortical Cortical, >0% and <10% Cortical, 10% Cortical, 0%
Posterior subcapsular PSC, >0% and <5% PSC, 5% PSC, 0%

B. No. of Participants and Eyes Included in the Prevalence Analyses of the Lutein plus Zeaxanthin and Vitamin B and Cataracts Analyses
Nuclear Cortical
No. of No. Eyes with No. of No. Eyes with
Cataract Severity Participants No. of Eyes Event (%) No. of Eyes Participants Event (%)
Mild 2939 5582 2279 (40.8) 2788 5296 3294 (62.2)
Moderate 2358 3840 537 (14.0) 1852 2618 616 (23.5)

C. No. of Participants and Eyes Included in the Incidence Analyses of the Lutein plus Zeaxanthin and Vitamin B and Cataracts Analyses
Taking Centrum Not Taking Centrum
No. of No. Eyes with No. of No. Eyes with
Cataract Severity Opacity Participants No. of Eyes Event (%) No. of Eyes Participants Event (%)
Mild Nuclear 639 1045 734 (70.2) 1190 1963 1279 (65.2)
Cortical 470 658 312 (47.4) 903 1245 619 (49.7)
PSC 939 1727 185 (10.7) 1807 3315 347 (10.5)
Moderate Nuclear 505 674 326 (48.4) 966 1354 617 (45.6)
Cortical 583 825 293 (35.5) 1132 1597 590 (36.9)
PSC 951 1716 161 (9.4) 1842 3326 313 (9.4)
Cataract surgery 1043 2047 558 (27.3) 2025 3985 1009 (25.3)

AREDS ¼ Age-Related Eye Disease Study; PSC ¼ posterior subcapsular cataract.

accurate quintile comparisons. The AREDS participants who proportional hazards regression (PHREG) procedures were used
completed a food frequency questionnaire at baseline (n ¼ 4751) in the cross-sectional and incidence analyses, respectively. All
were included in the quintile comparisons. The analyses exclude analyses were performed with the SAS software version 9.3 (SAS,
participants at the extremes of caloric intake, less than the first Inc., Cary, NC).
percentile and more than the ninety-ninth percentile (<677 or
>1995 kcal/day for women and <794 or >2771 kcal/day for men),
because these participants were less likely to have submitted ac- Results
curate dietary intake estimates.
Multivariate analyses, controlling for risk factors previously A total of 5582 and 3840 eyes of 2939 and 2358 participants,
identified in AREDS,41 were performed to assess the associations respectively, were included in the baseline cross-sectional analysis of
between B vitamins and lutein plus zeaxanthin intake and the mild and moderate nuclear cataract, and 5296 and 2681 eyes of 2788
cataract outcomes. Repeated-measures logistic regression using and 1852 participants, respectively, were included in the baseline
generalized estimating equations was performed to analyze the cross-sectional analysis of mild and moderate cortical cataracts.
baseline cross-sectional data.42 The unit of analysis was an eye, Table 1B, C also display the number of participants and eyes that
and each participant could contribute either one or both eyes. We
have progressed to the outcome. In this study, approximately 40%
accounted for the correlation between eyes using an
exchangeable covariance structure. Regression models were of the participants were older than 70 years, more than 50% were
applied separately for nuclear and cortical opacities, controlling women, approximately 95% were white, approximately 40% were
for risk factors found to be significant in AREDS report number college graduates, and approximately 40% had intermediate AMD
5.41 Goodness of fit was determined with the quasilikelihood (Tables 3 and 4, available at www.aaojournal.org). Tables 5 and 6
under the independence model criterion statistic for the purpose (available at www.aaojournal.org) display demographic
of selecting a nutrient-free final model. Each nutrient then was characteristics of participants included in the incident analyses for
included separately in each best-fit model to evaluate association nuclear cataract, cortical cataract, and PSC.
with our end points. Proportional hazards regression was used to Table 7 contains the odds ratios (ORs) for the baseline cross-
analyze the opacity-specific progression and cataract surgery out- sectional outcomes of nuclear and cortical cataracts adjusted for
comes. The Wei-Lin-Weissfeld method was implemented to
nonenutrient-based predictors and correlates, which had been
take into account the correlation of the 2 eyes per participant,43 and
regression models used were derived from AREDS report number determined previously.44 An OR of more than 1 indicated an
32.44 Mortality analysis of AREDS participants comparing the increased likelihood of having the outcome among participants
highest and lowest intake groups of each nutrient was performed reporting nutrient intake within the highest quintile of nutrient
using life table analyses. We did not adjust for multiplicity of intake compared with those reporting within the lowest quintile,
analyses. The generalized linear models (GENMOD) and whereas an OR of less than 1 indicated a decreased likelihood.

1473

Downloaded for Perpustakaan1 RSUD Ciawi (perpus1rsudciawi@gmail.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on November 05, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Ophthalmology Volume 122, Number 7, July 2015

Table 7B. Odds Ratios for Prevalence of Nuclear and Cortical Cataracts Adjusted for Risk Factors for Cataract Prevalence by Highest
versus Lowest Energy-Adjusted Intake Quintiles of Dietary Lutein plus Zeaxanthin and B Vitamins

Quintile 5 vs. Quintile 1, Odds Ratio (95% Confidence Interval)


Mild Nuclear* Mild Corticaly Moderate Nuclear* Moderate Corticaly
Lutein plus zeaxanthin 0.89 (0.71e1.11) 0.89 (0.72e1.11) 0.81 (0.55e1.20) 0.79 (0.55e1.16)
Vitamin B1 0.98 (0.79e1.23) 0.89 (0.72e1.09) 0.73 (0.49e1.09) 1.44 (0.98e2.13)
Riboflavin 0.78 (0.63e0.97)z 0.80 (0.65e0.99)z 0.62 (0.43e0.90)z 1.06 (0.73e1.53)
Niacin 0.95 (0.76e1.18) 0.92 (0.75e1.13) 0.83 (0.58e1.20) 1.16 (0.80e1.68)
Vitamin B6 0.87 (0.70e1.08) 0.90 (0.73e1.10) 0.67 (0.45e0.99)z 1.00 (0.69e1.44)
Folate 0.89 (0.71e1.11) 0.86 (0.70e1.07) 0.85 (0.57e1.27) 1.14 (0.78e1.67)
Vitamin B12 0.78 (0.63e0.96)z 0.77 (0.63e0.95)z 0.62 (0.43e0.88)z 0.86 (0.60e1.24)

*Covariates included in this model were age, gender, race, level of education, smoking status, eye color, refractive error, and anti-inflammatory use.
y
Covariates included in this model were age, race, gender, level of education, and beta-blocker use.
z
P  0.05.

Individuals reporting highest dietary intake of riboflavin had a 22% individual OR for each of the comparison of quintiles with
and 38% lower likelihood of mild and moderate nuclear cataracts at quintile 1 in those nutrients found to be statistically significant.
baseline, respectively, compared with participants reporting the There was no statistically significant association between B
lowest dietary intake (OR, 0.78; 95% CI, 0.63e0.97; P ¼ 0.02; vitamin intake and the risk of having moderate cortical cataract at
and OR, 0.62; 95% CI, 0.43e0.90; P ¼ 0.01). A similar reduction baseline. Findings for lutein plus zeaxanthin were in a protective
in likelihood of having mild and moderate nuclear cataracts was direction for both mild and moderate prevalent nuclear and
seen for individuals reporting the highest intake of vitamin B12 cortical opacities, but were not statistically significant.
(OR, 0.78; 95% CI, 0.63e0.96; P ¼ 0.02; and OR, 0.62; 95% CI, Tables 8 and 9 contain the hazards ratios, comparing the highest
0.43e0.88; P ¼ 0.01, respectively). Additionally, people with the lowest quintiles of reported dietary intake, for development
reporting intake in the highest quintile of vitamin B6 showed a of the 3 cataract types, cataract surgery, or both adjusted for possible
33% reduction in the odds of having moderate nuclear cataract at risk factors as described in AREDS report number 32 and stratified
baseline (OR, 0.67; 95% CI, 0.45e0.99). Participants reporting by Centrum use.44 For Centrum nonusers, niacin was associated
the highest intake of riboflavin and vitamin B12 were 20% and with a 31% reduction in the risk of mild nuclear cataract
23%, respectively, less likely to have mild cortical cataract at developing and vitamin B12 was associated with a 44% reduction
baseline (OR, 0.80; 95% CI, 0.65e0.99; P ¼ 0.04; and OR, 0.77; in the risk of mild cortical cataract developing (OR, 0.69; 95% CI,
95% CI, 0.63e0.95; P ¼ 0.01, respectively). In addition to 0.52e0.92; P ¼ 0.01; and OR, 0.56; 95% CI, 0.37e0.83; P <
statistically significant findings in comparisons of the highest 0.01, respectively). In Centrum users, those reporting the highest
versus the lowest quintile of dietary intake of these B vitamins, intake of folate had a 61% increased risk of at least mild PSC
statistically significant results were demonstrated in comparisons cataract compared with those with the lowest folate intake (OR,
of other quintiles versus the lowest quintile of dietary intake 1.61; 95% CI, 1.08e2.41; P ¼ 0.02). Aside from folate, there
(Fig 1). Table 7A (available at www.aaojournal.org) provides the were no statistically significant harmful associations between the

Figure 1. Heat map depicting protective nutrients for prevalence of nuclear and cortical cataracts by comparing highest versus lowest energy-adjusted intake
quintiles. Odds ratios (95% confidence intervals) for fifth vs. first quintile represented. All quintiles compared with the first quintile.

1474

Downloaded for Perpustakaan1 RSUD Ciawi (perpus1rsudciawi@gmail.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on November 05, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Table 8. Hazard Ratios for Incidence of Different Cataract Types and Cataract Surgery in Centrum Nonusers Adjusted for Cataract Risk Factors for Cataract Incidence* by Highest
versus Lowest Energy-Adjusted Intake Quintiles of Dietary Lutein plus Zeaxanthin and B Vitamins
Downloaded for Perpustakaan1 RSUD Ciawi (perpus1rsudciawi@gmail.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on November 05, 2018.

Quintile 5 vs. Quintile 1, Hazard Ratio (95% Confidence Interval)


Mild Posterior Moderate Posterior Cataract
Nutrient Mild Nuclear* Mild Corticaly Subcapsularz Moderate Nuclear* Moderate Corticaly Subcapsularz Surgeryx
Lutein plus zeaxanthin 0.94 (0.69e1.28) 0.88 (0.57e1.37) 0.97 (0.55e1.69) 1.01 (0.69e1.47) 1.11 (0.73e1.72) 0.93 (0.49e1.78) 1.08 (0.74e1.57)
Vitamin B1 0.88 (0.67e1.17) 1.05 (0.69e1.59) 1.09 (0.66e1.79) 0.98 (0.65e1.48) 0.87 (0.54e1.41) 1.29 (0.62e2.68) 1.14 (0.78e1.67)
Riboflavin 1.02 (0.79e1.33) 0.72 (0.49e1.07) 1.17 (0.71e1.90) 0.88 (0.60e1.30) 1.03 (0.65e1.62) 0.81 (0.46e1.43) 0.96 (0.68e1.36)
(0.52e0.92)jj
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.

Niacin 0.69 1.26 (0.81e1.98) 1.05 (0.60e1.84) 0.79 (0.51e1.20) 1.13 (0.72e1.80) 1.10 (0.56e2.14) 1.06 (0.75e1.49)
Vitamin B6 0.93 (0.70e1.24) 1.09 (0.72e1.66) 0.99 (0.57e1.71) 1.00 (0.66e1.51) 1.02 (0.65e1.62) 1.22 (0.64e2.32) 1.35 (0.93e1.97)
Folate 0.88 (0.67e1.16) 0.85 (0.55e1.33) 1.35 (0.78e2.31) 0.74 (0.48e1.13) 1.10 (0.69e1.75) 1.01 (0.57e1.79) 0.92 (0.64e1.32)
Vitamin B12 1.02 (0.77e1.34) 0.56 (0.37e0.83)jj 1.06 (0.64e1.76) 1.13 (0.75e1.69) 1.14 (0.73e1.80) 0.66 (0.38e1.16) 1.17 (0.81e1.68)

*Covariates included in this model are age, gender, refractive error, nuclear cataract at baseline (for moderate only), cortical and posterior subcapsular cataract at time of event, total energy intake, and body
mass index (for moderate only).

Glaser et al
y
Covariates included in this model are age, gender, race, education, smoking status, diabetes, weight change, cortical cataract at baseline (for moderate only), nuclear and posterior subcapsular cataract at time
of event, total energy intake, and body mass index (for moderate only).
z
Covariates included in this model are age, gender, diabetes, weight change since age 20 yrs, refractive error, thyroid hormone use, total energy intake, posterior subcapsular cataract at baseline (for moderate
only), and nuclear and cortical cataract at time of event.
x
Covariates included in this model are age, gender, race, smoking status, diabetes, refractive error, anti-inflammatory use, age-related macular degeneration category, total energy intake, and nuclear, cortical,
and posterior subcapsular cataract at baseline (for moderate only).
jj


P  0.05.

Cataracts and Nutrition


Table 9. Hazard Ratios for Incidence of Different Cataract Types and Cataract Surgery in Centrum Users Adjusted for Cataract Risk Factors for Cataract Incidence* by Highest versus
Lowest Energy-Adjusted Intake Quintiles of Dietary Lutein plus Zeaxanthin and B Vitamins

Quintile 5 vs. Quintile 1, Hazard Ratio (95% Confidence Interval)


Mild Posterior Moderate Posterior
Nutrient Mild Nuclear* Mild Corticaly Subcapsularz Moderate Nuclear* Moderate Corticaly Subcapsularz Cataract Surgeryx
Lutein/zea-xanthin 1.06 (0.86e1.31) 1.08 (0.80e1.47) 1.19 (0.81e1.75) 1.16 (0.88e1.52) 0.79 (0.57e1.10) 1.17 (0.75e1.81) 0.94 (0.72e1.23)
Vitamin B1 0.89 (0.72e1.09) 1.19 (0.89e1.60) 1.35 (0.92e2.00) 0.90 (0.67e1.21) 1.02 (0.74e1.40) 0.95 (0.63e1.45) 1.08 (0.83e1.41)
Riboflavin 0.83 (0.68e1.01) 1.00 (0.75e1.33) 1.20 (0.83e1.75) 0.78 (0.59e1.04) 0.74 (0.54e1.02) 1.28 (0.82e2.00) 0.99 (0.76e1.30)
Niacin 0.94 (0.75e1.17) 1.08 (0.80e1.44) 0.97 (0.66e1.43) 0.88 (0.64e1.19) 0.88 (0.65e1.19) 0.71 (0.46e1.11) 1.00 (0.77e1.30)
Vitamin B6 0.93 (0.75e1.16) 0.95 (0.71e1.27) 1.22 (0.83e1.79) 1.07 (0.78e1.47) 0.90 (0.65e1.23) 1.07 (0.69e1.66) 1.13 (0.85e1.49)
Folate 1.01 (0.82e1.24) 1.22 (0.90e1.66) 1.61 (1.08e2.41)jj 1.04 (0.78e1.39) 1.05 (0.76e1.44) 1.12 (0.73e1.74) 1.00 (0.76e1.32)
Vitamin B12 0.86 (0.69e1.06) 0.99 (0.75e1.30) 1.29 (0.87e1.91) 0.98 (0.73e1.32) 1.00 (0.72e1.38) 1.28 (0.82e2.00) 1.22 (0.92e1.60)

*Covariates included in this model are age, gender, refractive error, nuclear cataract at baseline (for moderate only), cortical and posterior subcapsular cataract at time of event, total energy intake, and body
mass index (for moderate only).
y
Covariates included in this model are age, gender, race, education, smoking status, diabetes, weight change, cortical cataract at baseline (for moderate only), nuclear and posterior subcapsular cataract at time
of event, total energy intake, and body mass index (for moderate only).
z
Covariates included in this model are age, gender, diabetes, weight change since age 20 yrs, refractive error, thyroid hormone use, total energy intake, posterior subcapsular cataract at baseline (for moderate
only), and nuclear and cortical cataract at time of event.
x
Covariates included in this model are age, gender, race, smoking status, diabetes, refractive error, anti-inflammatory use, age-related macular degeneration category, total energy intake, and nuclear, cortical,
and posterior subcapsular cataract at baseline (for moderate only).
1475

jj
P  0.05.
Ophthalmology Volume 122, Number 7, July 2015

highest dietary intake of any vitamin examined and development of derivatives, and mitochondrial dysfunction.47,48 The accu-
nuclear cataract, cortical cataract, or PSC. Again, the various ORs mulation of reactive oxygen species results in lipid peroxi-
for each of the quintiles of the nutrients that were found to be dation, protein denaturation, and crosslinking, which
statistically significantly associated with the cataract development aggregate within the lens and lead to cataract formation. B
are also displayed in Table 7A (sections B and C, available at vitamins may help to maintain the cellular response to
www.aaojournal.org). There was no excess mortality risk oxidative stress by functioning as cofactors in the enzymatic
associated with the highest versus the lowest level of intake for activation of antioxidants. Riboflavin (vitamin B2) and
any of the nutrients investigated (P > 0.05; Table 10, available at niacin (vitamin B3), once converted to their biologically
www.aaojournal.org). active forms as flavin adenine dinucleotide and nicotinamide
adenine dinucleotide phosphate, contribute to the reduction
of glutathione by acting as the cofactor and reducing
Discussion equivalent, respectively, for the enzyme glutathione reduc-
tase.11,31 The possible role of vitamins B6 and B12 in the
Our findings add to previous literature on the possible role prevention of oxidative damage is less clear. It is biologi-
of nutritional factors in the development of lens opacities. cally plausible that their importance may be attributed to
The clinical trial component of the AREDS found that high their function in the metabolic pathway that eliminates ho-
doses of vitamins C and E, b-carotene, zinc, or a combi- mocysteine, wherein vitamins B12 and B6 act as enzymatic
nation thereof had no apparent effect on the development or cofactors.
progression of lens opacities.20 The AREDS 2, a The Linxian Cataract Studies, 2 randomized, double-
randomized controlled clinical trial, also found no masked trials conducted in rural China in an undernourished
beneficial or harmful effect of treatment with lutein and population, found a protective effect of supplementation with
zeaxanthin on the occurrence of cataract surgery or riboflavin and niacin vitamins on the occurrence of nuclear
progression of lens opacities.24 Theoretical considerations, cataracts.36 Observational studies also have reported a
observational studies, and a few clinical trials suggest that decrease in the prevalence and progression of nuclear13,16
micronutrients other than those studied in the AREDS and cortical18 lens opacities in participants with the highest
clinical trials may affect cataract development. Testing the dietary intake of niacin, thiamin, and riboflavin.
many potential candidates in clinical trials requires large, Although most studies suggest no effect or a beneficial
long-term, and prohibitively expensive studies, so that effect on cataract development of vitamin supplementation,
observational studies are the most common source of in- some studies have raised the possibility of a possible
formation on this association. harmful effect of supplementation, particularly for PSC
In this report, cross-sectional and prospective data from cataract. The Linxian Cataract Studies found that riboflavin
the AREDS were used to examine associations between age- and niacin supplementation were associated with a slowing
related lens opacities and dietary intake of B vitamins and in the progression of nuclear lens opacities, but also were
lutein plus zeaxanthin, micronutrients for whom protective associated with an increase in the progression of PSC
associations have been reported.13,14,16,33,35,36,45 We found cataract and had no effect on cortical cataract.36 In our
that increased dietary intake of riboflavin and vitamin B12 study, we found that in Centrum users, among whom
were associated inversely in the cross-sectional baseline there was a thousand-fold increase in the highest quintile
comparison for both nuclear and cortical cataracts. The as- range for folate compared with non-Centrum users, the
sociation with vitamin B12 intake was seen when highest level of folate intake was associated with an
comparing several of the higher quintiles with the lowest increased risk of mild PSC cataract, possibly the result of
quintile of intake levels (Table 8). Vitamin B6 intake also chance or uncontrolled confounding in the high dietary
was associated with a decreased risk of moderate nuclear folate group. Two other studies of dietary and serum levels
lens opacities in the baseline cross-sectional analyses. of folate showed conflicting results.49,50 A randomized
Highest intake levels of niacin and vitamin B12 were placebo-controlled trial of Centrum found that those taking
associated with a decreased risk of development of nuclear the multivitamin had a 2-fold increased risk in PSC events.51
and mild cortical lens opacities, but only in participants not No increased mortality risk was associated with any B
taking Centrum multivitamins. In agreement with recently vitamin or lutein plus zeaxanthin intake levels.
published results from the AREDS 2 cohort,24 no Theoretical considerations and some observational
statistically significant associations were found between studies have suggested that carotenoids, in particular lutein
highest lutein plus zeaxanthin intake level and the nuclear plus zeaxanthin, may play a role in cataract prevention.
or cortical cataract outcomes. Lutein, and its structural isomer zeaxanthin, are the only
A large body of evidence suggests that micronutrients carotenoids found within the human lens.32 They have the
with antioxidant potential may affect cataract development. ability to filter and absorb potentially damaging short-
Aging lenses are thought to lose their capacity to neutralize wavelength light and to reduce oxidative stress.29 Their
free radicals and minimize oxidative damage as the efficacy unique structure, with an ionone ring and conjugated
of protective enzymes, such as superoxide dismutase, and polyene chain, allows for several types of reactions that
levels of compounds with antioxidant capabilities, such as can neutralize reactive oxygen species.29 Incubation of
glutathione and ascorbic acid decrease.46,47 Radical oxygen human lens epithelial cells with lutein and zeaxanthin
species increase within the lens secondary to environmental before exposure to hydrogen peroxide or ultraviolet B
ultraviolet exposure, the formation of cholesterol oxide light irradiation protects lens cells from protein oxidation,

1476

Downloaded for Perpustakaan1 RSUD Ciawi (perpus1rsudciawi@gmail.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on November 05, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Glaser et al 
Cataracts and Nutrition

lipid peroxidation, and DNA damage and also results in measurements of nutritional intake are limited in that they
increased levels of glutathione in response to oxidative are unable to account for changes in nutritional intake over
stress.27,28 Clinical studies have reported that high dietary time and instead make an averaged approximation of
intake of lutein plus zeaxanthin is protective against the dietary habits. Although we adjusted for known risk fac-
development and progression of nuclear cataract,34,35 as tors in the logistic and proportional hazards regression
well as all cataracts,33 and reduces the risk of cataract models, there is the possibility of unadjusted confounding
extraction.12,52 High levels of plasma lutein also have from other factors. Participants with higher self-reported
been associated with a reduced risk of nuclear cataract.45 levels of micronutrient intake may be healthier overall
However, other studies and our study found no rela- compared with those with the least nutrient intake, or the
tionship between lutein plus zeaxanthin intake and cataracts. accuracy of diet recall may have differed in individuals
Analysis of a small cohort from the Nurse’s Health Study, with and without more significant cataracts and worse
which incorporated 15 years of food frequency question- vision. Previous analysis of AREDS data has shown that
naire data, found that the protective association between PSC is associated with increased risk of nuclear and
high lutein plus zeaxanthin intake and nuclear cataract dis- cortical cataracts, suggesting that one cataract type may be
appeared after adjusting for vitamin C intake.53 In the associated with the development of other lens opacity
population-based Pathologies Oculaires Liées à l’Age types.44 We attempted to adjust for this in our lens opacity
study, which had fewer than 100 eyes with any cataract progression modeling, but it is unlikely that we could
type, only serum levels of zeaxanthin, but not lutein, were account fully for this possible effect, because we did not
associated with a reduced risk of nuclear cataract, and separate eyes with multiple types of cataracts from those
neither lutein nor zeaxanthin were associated with a reduced with only 1 type of cataract. Finally, because of the
risk of cortical cataract, PSC, mixed cataracts, or cataract multiple comparisons made between nutrient intake and
surgery.14 Most recently, analysis of data from the AREDS lens opacity outcomes, it is possible that some of our
2 clinical trial showed that lutein plus zeaxanthin findings are the result of chance. This is less likely for
supplementation did not reduce progression to cataract those vitamins that demonstrated a dose-response effect
surgery significantly.24 on cataract risk with increasing intake level and for those
It is unclear why riboflavin, vitamin B6, and vitamin B12 that had similar findings in both the cross-sectional and
are associated with a protective effect in the baseline cross- prospective analyses.
sectional analysis for nuclear and cortical lens opacities, but The totality of evidence from our study and other studies
only vitamin B12 intake had a statistically significant as- suggests that B vitamins may have a role in slowing cataract
sociation on the development of cortical lens opacities. One development. However, additional evidence would be
possibility for this discrepancy is that the power to detect an needed to make definitive clinical recommendations. Iden-
association was much larger in the cross-sectional baseline tification of micronutrients that retard cataract progression
data compared with the incidence data, where the duration would serve as a cost-effective way to reduce the disease
of difference in vitamin intake, although unknown, may burden of age-related cataracts.
have been present for decades, and likely for much longer
than the duration of AREDS. Additionally, our population
represents a relatively healthy and well-nourished cohort
References
with baseline levels of nutrient intake that are higher than
the general population. For all of the nutrients studied, the 1. Pascolini D, Mariotti SP. Global estimates of visual impair-
lowest intake quintile for the AREDS patient population was ment: 2010. Br J Ophthalmol 2012;96:614–8.
greater than the lowest intake quintile calculated from the 2. CMS Data Compendium: Table V.6a Medicare Leading Part
National Health and Nutrition Examination Survey data B Procedure Codes Ranked by Allowed Charges Calendar
acquired during the same period (Table 11, available at Year 2010. In: Services CfMaM. Available at: http://www.cms.
gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-
www.aaojournal.org).
Reports/DataCompendium/2011_Data_Compendium.html; Acc-
For lutein and zeaxanthin, the difference between the essed March 1, 2013.
lowest intake quintile and the highest intake quintile was 3. Congdon N, O’Colmain B, Klaver CC, et al. Causes and
less than the corresponding National Health and Nutrition prevalence of visual impairment among adults in the United
Examination Survey quintiles, making the identification of States. Arch Ophthalmol 2004;122:477–85.
differences in the risk of cataract progression more difficult 4. Hennis A, Wu SY, Nemesure B, Leske MC. Risk factors for
than if comparisons were being made across more widely incident cortical and posterior subcapsular lens opacities in
divergent populations. the Barbados Eye Studies. Arch Ophthalmol 2004;122:
Our observational study had strengths and some 525–30.
potential weaknesses. The strengths of the study include 5. Klein BE, Klein R, Lee KE. Diabetes, cardiovascular disease,
selected cardiovascular disease risk factors, and the 5-year
its size, with large numbers of each cataract type included,
incidence of age-related cataract and progression of lens
the use of standardized evaluation of lens photographs opacities: the Beaver Dam Eye Study. Am J Ophthalmol
longitudinally, and the long duration of follow-up. Self- 1998;126:782–90.
reported dietary intake is subject to recall bias, which we 6. Hiller R, Sperduto RD, Podgor MJ, et al. Cigarette smoking
attempted to minimize by comparing only the highest and and the risk of development of lens opacities. The Framingham
lowest quintiles of nutrient intake. However, self-reported studies. Arch Ophthalmol 1997;115:1113–8.

1477

Downloaded for Perpustakaan1 RSUD Ciawi (perpus1rsudciawi@gmail.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on November 05, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Ophthalmology Volume 122, Number 7, July 2015

7. Bochow TW, West SK, Azar A, et al. Ultraviolet light expo- 27. Chitchumroonchokchai C, Bomser JA, Glamm JE, Failla ML.
sure and risk of posterior subcapsular cataracts. Arch Oph- Xanthophylls and alpha-tocopherol decrease UVB-induced
thalmol 1989;107:369–72. lipid peroxidation and stress signaling in human lens epithe-
8. Cruickshanks KJ, Klein BE, Klein R. Ultraviolet light expo- lial cells. J Nutr 2004;134:3225–32.
sure and lens opacities: the Beaver Dam Eye Study. Am J 28. Gao S, Qin T, Liu Z, et al. Lutein and zeaxanthin supple-
Public Health 1992;82:1658–62. mentation reduces H2O2-induced oxidative damage in human
9. West SK, Duncan DD, Munoz B, et al. Sunlight exposure and lens epithelial cells. Mol Vis 2011;17:3180–90.
risk of lens opacities in a population-based study: the Salisbury 29. Krinsky NI, Landrum JT, Bone RA. Biologic mechanisms of
Eye Evaluation project. JAMA 1998;280:714–8. the protective role of lutein and zeaxanthin in the eye. Annu
10. Bunce GE, Kinoshita J, Horwitz J. Nutritional factors in Rev Nutr 2003;23:171–201.
cataract. Annu Rev Nutr 1990;10:233–54. 30. Batey DW, Eckhert CD. Analysis of flavins in ocular tissues of
11. Vinson JA. Oxidative stress in cataracts. Pathophysiology the rabbit. Invest Ophthalmol Vis Sci 1991;32:1981–5.
2006;13:151–62. 31. Gropper SAS, Smith JL. Advanced nutrition and human
12. Chasan-Taber L, Willett WC, Seddon JM, et al. A prospec- metabolism. 6th ed. Belmont, CA: Wadsworth/Cengage
tive study of carotenoid and vitamin A intakes and risk of Learning; 2013.
cataract extraction in US women. Am J Clin Nutr1999;70: 32. Yeum KJ, Taylor A, Tang G, Russell RM. Measurement of
509e516. carotenoids, retinoids, and tocopherols in human lenses. Invest
13. Cumming RG, Mitchell P, Smith W. Diet and cataract: the Ophthalmol Vis Sci 1995;36:2756–61.
Blue Mountains Eye Study. Ophthalmology 2000;107:450–6. 33. Christen WG, Liu S, Glynn RJ, et al. Dietary carotenoids,
14. Delcourt C, Carriere I, Delage M, et al. Plasma lutein and vitamins C and E, and risk of cataract in women: a prospective
zeaxanthin and other carotenoids as modifiable risk factors for study. Arch Ophthalmol 2008;126:102–9.
age-related maculopathy and cataract: the POLA Study. Invest 34. Lyle BJ, Mares-Perlman JA, Klein BE, et al. Antioxidant
Ophthalmol Vis Sci 2006;47:2329–35. intake and risk of incident age-related nuclear cataracts in the
15. Hankinson SE, Stampfer MJ, Seddon JM, et al. Nutrient intake Beaver Dam Eye Study. Am J Epidemiol 1999;149:801–9.
and cataract extraction in women: a prospective study. BMJ 35. Moeller SM, Voland R, Tinker L, et al. Associations between
1992;305:335–9. age-related nuclear cataract and lutein and zeaxanthin in the
16. Jacques PF, Taylor A, Moeller S, et al. Long-term nutrient diet and serum in the Carotenoids in the Age-Related Eye
intake and 5-year change in nuclear lens opacities. Arch Disease Study, an Ancillary Study of the Women’s Health
Ophthalmol 2005;123:517–26. Initiative. Arch Ophthalmol 2008;126:354–64.
17. Leske MC, Chylack LT Jr, He Q, et al. Antioxidant vitamins 36. Sperduto RD, Hu TS, Milton RC, et al. The Linxian cataract
and nuclear opacities: the longitudinal study of cataract. studies. Two nutrition intervention trials. Arch Ophthalmol
Ophthalmology 1998;105:831–6. 1993;111:1246–53.
18. Leske MC, Chylack LT Jr, Wu SY. The Lens Opacities Case- 37. The Age-Related Eye Disease Study (AREDS): design im-
Control Study. Risk factors for cataract. Arch Ophthalmol plications. AREDS report no. 1. Control Clin Trials 1999;20:
1991;109:244–51. 573–600.
19. Leske MC, Wu SY, Hyman L, et al. Biochemical factors in 38. SanGiovanni JP, Chew EY, Clemons TE, et al. The relation-
the lens opacities. Case-control study. The Lens Opacities ship of dietary carotenoid and vitamin A, E, and C intake with
Case-Control Study Group. Arch Ophthalmol 1995;113: age-related macular degeneration in a case-control study:
1113–9. AREDS report no. 22. Arch Ophthalmol 2007;125:1225–32.
20. A randomized, placebo-controlled, clinical trial of high-dose 39. Klein BE, Magli Y, Neider MW, Klein R. Wisconsin system
supplementation with vitamins C and E and beta carotene for classification of cataracts from photographs. Madison, WI:
for age-related cataract and vision loss: AREDS report no. 9. University of Wisconsin; 1989.
Arch Ophthalmol 2001;119:1439–52. 40. The Age-Related Eye Disease Study (AREDS) system for
21. Christen WG, Glynn RJ, Sesso HD, et al. Age-related cataract classifying cataracts from photographs: AREDS report no. 4.
in a randomized trial of vitamins E and C in men. Arch Am J Ophthalmol 2001;131:167–75.
Ophthalmol 2010;128:1397–405. 41. Risk factors associated with age-related nuclear and cortical
22. Christen WG, Manson JE, Glynn RJ, et al. A randomized trial cataract. a case-control study in the Age-Related Eye Disease
of beta carotene and age-related cataract in US physicians. Study. AREDS report no. 5. Ophthalmology 2001;108:1400–8.
Arch Ophthalmol 2003;121:372–8. 42. Diggle P, Liang K-Y, Zeger SL. Analysis of longitudinal data.
23. McNeil JJ, Robman L, Tikellis G, et al. Vitamin E supple- Oxford: Clarendon Press; 1994.
mentation and cataract: randomized controlled trial. Ophthal- 43. Wei LJ, Lin DY, Weissfeld L. Regression-analysis of multi-
mology 2004;111:75–84. variate incomplete failure time data by modeling marginal
24. Chew EY, SanGiovanni JP, Ferris FL, et al. Lutein/zeaxanthin distributions. J Am Stat Assoc 1989;84:1065–73.
for the treatment of age-related cataract: AREDS2 randomized 44. Chang JR, Koo E, Agron E, et al. Risk factors associated with
trial report no. 4. JAMA Ophthalmol 2013;131:843–50. incident cataracts and cataract surgery in the Age-related Eye
25. Chylack LT Jr, Brown NP, Bron A, et al. The Roche European Disease Study (AREDS): AREDS report number 32.
American Cataract Trial (REACT): a randomized clinical trial Ophthalmology 2011;118:2113–9.
to investigate the efficacy of an oral antioxidant micronutrient 45. Karppi J, Laukkanen JA, Kurl S. Plasma lutein and zeaxanthin
mixture to slow progression of age-related cataract. and the risk of age-related nuclear cataract among the elderly
Ophthalmic Epidemiol 2002;9:49–80. Finnish population. Br J Nutr 20111–7.
26. Milton RC, Sperduto RD, Clemons TE, Ferris FL 3rd. 46. Lou MF. Redox regulation in the lens. Prog Retin Eye Res
Centrum use and progression of age-related cataract in the 2003;22:657–82.
Age-Related Eye Disease Study: a propensity score approach. 47. Vejux A, Samadi M, Lizard G. Contribution of cholesterol and
AREDS report No. 21. Ophthalmology 2006;113:1264–70. oxysterols in the physiopathology of cataract: implication for

1478

Downloaded for Perpustakaan1 RSUD Ciawi (perpus1rsudciawi@gmail.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on November 05, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Glaser et al 
Cataracts and Nutrition

the development of pharmacological treatments. J Ophthalmol posterior subcapsular cataract. Invest Ophthalmol Vis Sci
2011;2011:471947. 2015;56:216–20.
48. Babizhayev MA. Mitochondria induce oxidative stress, gen- 51. Maraini G, Sperduto RD, Ferris F, et al. A random-
eration of reactive oxygen species and redox state unbalance of ized, double-masked, placebo-controlled clinical trial of
the eye lens leading to human cataract formation: disruption of multivitamin supplementation for age-related lens opaci-
redox lens organization by phospholipid hydroperoxides as a ties. Clinical Trial of Nutritional Supplements and Age-
common basis for cataract disease. Cell Biochem Funct Related Cataract report no. 3. Ophthalmology 2008;115:
2011;29:183–206. 599–607e1.
49. Taylor A, Jacques PF, Chylack LT Jr, et al. Long-term intake 52. Brown L, Rimm EB, Seddon JM, et al. A prospective study of
of vitamins and carotenoids and odds of early age-related carotenoid intake and risk of cataract extraction in US men.
cortical and posterior subcapsular lens opacities. Am J Clin Am J Clin Nutr 1999;70:517–24.
Nutr 2002;75:540–9. 53. Jacques PF, Chylack LT Jr, Hankinson SE, et al. Long-term
50. Tan AG, Mitchell P, Rochtchina E, et al. Serum homocysteine, nutrient intake and early age-related nuclear lens opacities.
vitamin B12, and folate, and the prevalence and incidence of Arch Ophthalmol 2001;119:1009–19.

Footnotes and Financial Disclosures


Originally received: January 20, 2015. medical-research-scholars-program); and the Howard Hughes Medical
Final revision: March 27, 2015. Institute (HHMI-NIH scholars program; G.S.).
Accepted: April 6, 2015. *Members of the Appendix AREDS directory available online
Available online: May 9, 2015. Manuscript no. 2015-61. (www.aaojournal.org).
1
National Eye Institute, National Institutes of Health, Bethesda, Maryland. Author Contributions:
2
EMMES Corporation, Rockville, Maryland. Conception and design: Glaser, Shih, Sperduto, Agrón, Chew
Presented at: American Academy of Ophthalmology Annual Meeting, Analysis and interpretation: Glaser, Shih, Sperduto, Agrón, Clemons, Chew
November 2012, Chicago, IL. Data collection: Shih, Nigam, Sperduto, Agrón, Clemons, Chew
Financial Disclosure(s): Obtained funding: Chew
The author(s) have no proprietary or commercial interest in any materials
discussed in this article. Overall responsibility: Glaser, Shih, Sperduto, Agrón, Clemons, Chew
Supported by the National Eye Institute, National Institutes of Health, Abbreviations and Acronyms:
Bethesda, Maryland (contract no.: NOI-EY-0-2127); the National Institutes AMD ¼ age-related macular degeneration; AREDS ¼ Age-Related Eye
of Health (NIH) Medical Research Scholars Program (T.S.G., L.E.D.), a Disease Study; CI ¼ confidence interval; OR ¼ odds ratio;
public-private partnership supported jointly by the NIH and contributions to PSC ¼ posterior subcapsular cataract.
the Foundation for the NIH from Pfizer, Inc., The Leona M. and Harry B. Correspondence:
Helmsley Charitable Trust, and the Howard Hughes Medical Institute, Emily Y. Chew, MD, National Eye Institute, National Institutes of Health,
as well as other private donors (for a complete list, please visit the 10 Center Drive, MSC 1204, BG 10-CRC Room 3-2531, Bethesda, MD
Foundation website at http://www.fnih.org/work/programs-development/ 20814-1204. E-mail: echew@nei.nih.gov.

1479

Downloaded for Perpustakaan1 RSUD Ciawi (perpus1rsudciawi@gmail.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on November 05, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.

You might also like