Assoc Cataract and Amd 3 Studies

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Is There an Association Between CataractSurgery and Age-related MacularDegeneration? Data From Three

Population-based Studies

ELLEN E. FREEMAN, MSc, BEATRIZ MUNOZ, MSC, SHEILA K. WEST, PHD,

JAMES M. TIELSCH, PHD, AND OLIVER D. SCHEIN, MD, MPH

●

PURPOSE: To determine whether cataract surgery isassociated with an increased prevalence of age-related

macular degeneration (AMD) in three independent pop-

ulation-based data sets.● DESIGN: Cross-sectional study.● METHODS: Data were used from the Salisbury Eye

Evaluation (2,520 subjects from Salisbury, Maryland,

aged 65 to 84 years), the Proyecto VER (4,774 Hispanic

subjects from Arizona aged 40 years and older), and the

Baltimore Eye Survey (4,396 subjects from Baltimore,

Maryland, aged 40 and older). The main outcome mea-

sure was AMD as determined by retinal photographs or

clinical examination.● RESULTS: A history of cataract surgery was associated

with an increased prevalence of late AMD in all three

data sets after adjusting for age, race, sex, and smoking,

but odds ratios (OR) were not individually statistically

significant. The OR for the combined analysis was 1.7

(95% confidence interval: 1.1–2.6). Having a severe

cataract in the eye was also associated with a slightly

higher prevalence of late AMD, although the combined

OR was not statistically significant (OR 1.4; 95%

confidence interval, 0.8%–2.4). Overall, increasing time

since cataract surgery was not associated with late AMD.

●

CONCLUSIONS: A history of cataract surgery may beassociated with an increased prevalence of late AMD.However, having a severe cataract in the eye may also be

associated with a higher prevalence of late AMD. Addi-tional research is needed to investigate whether a

causal relationship exists between cataract surgery andAMD or whether this relationship is due to residual

confounding or bias. (Am J Ophthalmol 2003;135:849–856. © 2003 by Elsevier Inc. All rights reserved.)

T

HE MOST COMMON CAUSE OF VISION LOSS IN THE

elderly in the United States is age-related cata-

ract,1,2

whereas the most common cause of blindnessin this group is age-related macular degeneration

(AMD).3,4 The visual prognosis for patients with cataractis very good. In fact, 96% have improved vision 4 months

after surgery.5 In contrast, the prognosis for patients withAMD is less optimistic, as there is only proven treatment

for the less common neovascular form.Cataract surgery is the most common procedure per-

formed in the Medicare population, with more than 1million cataract surgeries performed each year in the

United States.6 Several large epidemiologic studies haveassessed the question of a possible association between

cataract surgery and late AMD.7–10 The Beaver Dam EyeStudy, a population-based prospective study of 3,684 adults

aged 40 years and older, found that persons who hadprevious cataract surgery had a higher 10-year risk of

developing incident late age-related maculopathy (oddsratio [OR] 3.8; 95% confidence interval [CI], 1.9– 7.7).8

However, the Blue Mountain Eye Study, a population-based survey of 3,654 adults aged 49 years and older, did

not find an association.9 In addition, the Visual Impair-ment Project did not find an association between cataract

surgery and late AMD after adjusting for other variables.10

Some studies have found an association between the

presence of a lens opacity in the eye and late AMD,

Accepted for publication Dec 10, 2002.InternetAdvance publication at ajo.com Dec 12, 2002.From the Dana Center for Preventive Ophthalmology (E.E.F., B.M.,

S.K.W., J.M.T., O.D.S.), Wilmer Eye Institute, Johns Hopkins UniversitySchool of Medicine, and the International Health Department (J.M.T.),

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.This research was supported in part by an unrestricted grant from

Alcon Laboratories, Inc, Fort Worth, Texas; NEI Grants K24EY00395,EY11283; and NIA Grant AG16294. Doctor West is a Research toPrevent Blindness Senior Scientific Investigator. Doctor Schein is aconsultant to Alcon Research, Ltd.

Inquiries to Oliver Schein, MD, 116 Wilmer Bldg, Johns HopkinsHospital, 600 N Wolfe St, Baltimore, MD 21287-9019; fax: (410)614-9651; e-mail: [email protected]

© 2003 BY ELSEVIER INC. ALL RIGHTS RESERVED.0002-9394/03/$30.00 849doi:10.1016/S0002-9394(02)02253-5


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suggesting that cataract and late AMD may share one ormore common risk factors.7,11 Why cataract surgery and

late AMD may be associated is still unknown, althoughsome have suggested that surgery may increase the risk of

late AMD in susceptible eyes.11,12 Therefore, to evaluatewhether cataract surgery and late AMD are associated, we

examined existing data from three independent popula-

tion-based studies to maximize the number of subjects withlate AMD.

DESIGN

THE THREE POPULATION-BASED STUDIES TO BE USED FOR

this cross-sectional analysis, the Salisbury Eye Evaluation(SEE), Proyecto VER (PVER), and the Baltimore Eye

Survey (BES), were conducted according to the guidelinesestablished in the Declaration of Helsinki. In addition, the

projects were approved by the appropriate Internal Review

Boards of The Johns Hopkins University. All subjectsprovided written informed consent.

METHODS

THE SEE PROJECT IDENTIFIED A POPULATION-BASED RAN-

dom sample of elderly persons between the ages of 65 and84 years living in Salisbury, Maryland, in 1993. Details

about sample recruitment and methods are describedelsewhere.13 A total of 65% of those invited to participate

completed both the home questionnaire and the medical

examination, resulting in 2,520 participants. Data werecollected on history of previous cataract surgery by clinical

examination. At the clinical examination, photographs of the retina were taken and then assessed in a masked

fashion by trained graders for signs of AMD such aschoroidal neovascularization, geographic atrophy, hyper-

pigmentation, nongeographic atrophy, and drusen. Infor-mation on age, sex, race, and smoking habits were also

collected by interviewer-administered questionnaire.There were 471 participants who had cataract surgery on

718 eyes. Information on when cataract surgery occurredwas obtained after the initial examination by review of

medical records (232 subjects, or 49%) or by telephonecalls to participants (98 subjects, or 21%). Date of cataract

surgery could not be obtained for 141 participants (123eyes, 17%) because of inability to obtain medical records,

lack of information in records of cataract surgery date, orinability to reach the participant by telephone.

Late AMD was defined for this study as the presence of signs of choroidal neovascularization or geographic atro-

phy. Two definitions of early AMD were used: definition 1(AMD 1), drusen 64 m or greater, hyperpigmentation, or

nongeographic atrophy in the central macular zone; anddefinition 2 (AMD 2), drusen 125 m or greater, hyper-

pigmentation, or nongeographic atrophy in the central

macular zone. Subjects who had late AMD were excludedfrom analyses of early AMD. Presence of severe cataract

was defined as nuclear sclerosis grade 4 (highest grade),cortical opacification of 8/16 or greater, or any posterior

subcapsular opacification as graded by lens photographsusing the Wilmer grading scheme.14,15 Persons excluded

from the analyses were those who did not have photo-

graphs taken owing to camera failure, inability to dilate thepupil, refusal of the participant, significant corneal opacity,inability to maintain fixation, or photographs that were

not of gradable quality for the specific outcome understudy. Of 5,040 eyes, there were 4,641 eyes with gradable

photographs for late AMD, 4,022 for early AMD 1, and4,489 for early AMD 2.

The PVER is a population-based study of 4,774 Hispanicpersons over age 40 years living in either Pima County or

Santa Cruz County in Arizona. Of those subjects identifiedas eligible, 4,774 of 6,668 (72%) completed both the home

questionnaire and the clinical examination. Further details

about the sample and recruitment have been previouslydescribed.16 Data were collected on history of previouscataract surgery by clinical examination. Date of cataract

surgery was not collected. Subjects were identified in aclinical examination as having choroidal neovasculariza-

tion or geographic atrophy. In addition, data were col-lected on whether late AMD was a cause of blindness

(vision 20/200 or worse). Early AMD was not assessed.Information was also collected on age, sex, and smoking

habits through an interviewer-administered questionnaire.For this analysis, late AMD was defined as choriodal

neovascularization or geographic atrophy present as assessed

by clinical examination, or if late AMD was determined to bea cause of blindness (20/200 or worse). Presence of severe

cataract was defined as nuclear sclerosis grade 4, corticalopacification 8/16 or greater, or any PSC opacification as

graded clinically.14 Late AMD was clinically assessed in 9,478of 9,548 eyes. Reasons for not being able to assess late AMD

included inability to dilate the pupil, refusal of the partici-pant, and significant corneal opacity.

The Baltimore Eye Survey (BES), also population-based,is a study of ocular disease and vision loss among 5,308

African American and Caucasian residents of Baltimore,Maryland, aged 40 years or older. Of subjects selected to

participate, 5,308 of 7,265 (73%) completed the screeningexamination. All were then offered stereoscopic fundus

photography, and 4,396 persons who agreed to havephotography had at least one gradable photograph that was

included in this analysis. Further details have been previ-ously described.17 History of cataract surgery was obtained

by clinical examination. Those who had previous cataractsurgery (n 138) were asked to report their age at cataract

surgery. Because we knew their age at the baseline exam-ination, the difference in the two ages provided us with the

time since cataract surgery. Photographs of the retina werereviewed in a masked fashion and graded for signs of

choroidal neovascularization, geographic atrophy, and

AMERICAN JOURNAL OF OPHTHALMOLOGY850 JUNE 2003


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signs of early AMD such as drusen, hyperpigmentation, ornongeographic atrophy. Also, during the clinical exami-

nation, AMD was assessed as a cause of blindness. Duringthe personal interview, information was collected on age,

race, sex, and smoking habits.The definition of late AMD for this study was choroidal

neovascularization, geographic atrophy, or if AMD was

diagnosed by an ophthalmologist as a cause of blindness(20/200 or worse). The two definitions of early AMD wereused (AMD 1: drusen 64 m or greater, hyperpigmenta-

tion, or nongeographic atrophy; AMD 2: drusen 125 m orgreater, hyperpigmentation, or nongeographic atrophy in

the macular zone). Those who had late AMD wereexcluded from analyses of early AMD. Presence of a severe

cataract was defined if visual impairment or blindness wasattributed to cataract in the clinical examination. Eyes

excluded from the analyses were those whose photographswere not of gradable quality for the specific outcome under

study. Of 8,792 eyes, 7,428 were gradable for late AMD,

8,734 eyes were gradable for early AMD 1, and 8,717 eyeswere gradable for early AMD 2.

The general characteristics of the three study popula-

tions were examined and compared. Next, the character-istics of those who had cataract surgery in at least 1 eye were

compared with those who did not for the three populations.Age- specific and race-specific prevalence rates of having late

AMD in at least 1 eye were calculated. Next, regressionanalyses were performed for each of the individual study

populations and then for all the data sets combined.The primary outcome for this study was late AMD.

Associations with early AMD were also assessed in SEE

and BES. Indicator variables were created for the variouscataract exposures with neither cataract surgery nor severe

cataract at the time of the clinical examination as thereference level, presence of a severe cataract as the next

level, and previous cataract surgery or time since cataractsurgery as the final level. Regression analyses were done at

the eye level because cataract surgery and AMD status maydiffer by eye. The standard errors were adjusted using

generalized estimating equations to account for the corre-lation between eyes.18

Age-adjusted analyses were done using logistic regres-sion to determine the association of cataract surgery and

AMD for all eyes. Next, multiple logistic regression wasused to determine the association of cataract surgery and

AMD adjusting for the following other covariates besidesage: race (SEE and BES only), sex, smoking (never, past,

current), and study (combined analyses only). In the com-bined analyses, race was coded as Caucasian vs non-Cauca-

sian to avoid colinearity between Hispanic race and studypopulation, as all the PVER participants were Hispanic.

A fixed effects model that assumed no heterogeneity inthe true odds ratios across studies was assumed. With only

three studies, it was not possible to reliably estimate theacross-study component of variance for the log odds ratios

as would be done in a random-effects model.19 However,

the combined odds ratios under different assumptions aboutthe among-study variance were estimated. The moment

estimate of the among-study variance was 0.0, because thevariance among the three estimated log odds ratios was

smaller than the average statistical variance across the studies.Hence, the best indication available from the data was that

the fixed effects model was appropriate.

Interactions were assessed by stratification and by theaddition of interaction terms into the regression models.All analyses were done using the SAS statistical software

(SAS Institute, Cary, North Carolina, USA).

RESULTS

THE GENERAL CHARACTERISTICS OF THE THREE STUDY POP-

ulations are presented in Table 1. The SEE population wasmore likely to be Caucasian, to have had more formal

education, to be current smokers, and because they were older

(selected to be aged 65 to 84 years), they were more likely tohave had previous cataract surgery and late AMD comparedwith the PVER and BES populations. The proportion of

African Americans in BES was high (42%) owing to thesampling strategy. Baltimore Eye Survey participants had the

highest proportion of current smokers, at 39%. Late AMDwas rare in the three studies with 73 cases in SEE, 53 in

PVER, and 48 in BES.The characteristics of those who had cataract surgery in

at least one eye compared with those who did not for thethree studies are shown in Table 2. Subjects who had

undergone cataract surgery were older and were more likely to

be Caucasian. In addition, those who did not have cataractsurgery in SEE were more likely to have never smoked.

The age-specific and race-specific late AMD prevalencerates for the study populations are presented in Table 3.

The prevalence of late AMD tended to increase with agein the Caucasian population. This was not obviously so in

the African-American population, although there werevery small numbers of cases in the older age groups.

African-Americans were less likely to have late AMDcompared with Caucasians and Hispanics.

The three datasets for cataract surgery, severe cataract, andAMD consistently showed that previous cataract surgery was

associated with an increased prevalence of late AMD, al-though they differed in the magnitude of the point estimates

and none of them were individually statistically significant(Table 4). An analysis of the three data sets combined

together revealed an odds ratio (OR) for previous cataractsurgery of 1.7, which was statistically significant (95% confi-

dence interval [CI], 1.1– 2.6; Table 4). In addition, having asevere cataract in the eye at the time of the clinic examina-

tion was also associated with a higher odds of AMD in allthree studies, although these estimates were not statistically

significant (combined OR 1.4; 95% CI, 0.8– 2.4; Table 4).In the two datasets (SEE and BES) that had information

on time since cataract surgery (Table 5), the prevalence of

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late AMD increased as time since surgery increased.

Results from the combined analysis showed that those whoreported surgery 5 or more years earlier had 2.1 times the

odds of late AMD (95% CI, 1.0 – 4.6; Table 5). Those whoreported surgery less than 5 years earlier had modestly

elevated odds of late AMD, although it was not statisti-cally significant (OR 1.4; 95% CI, 0.7–2.6; Table 5).

Sensitivity analyses were done to see how the eyes in SEEthat were missing dates of cataract surgery might bias the

results. Those eyes that were missing date of cataractsurgery were less likely to have AMD (0.8% vs 2.2%). A

minimum odds ratio was estimated by assuming thatthose eyes that had cataract surgery but were missing the

date of cataract surgery were in the group that hadsurgery 5 or more years earlier. The odds ratio was

dramatically reduced and was no longer statisticallysignificant, suggesting that surgery 5 or more years

earlier was likely not associated with late AMD in theSEE data set (OR 1.2; 95% CI, 0.5–2.8). The

combined odds ratio for surgery 5 or more years earlier

was also attenuated and no longer statistically signifi-

cant (OR 1.5; 95% CI, 0.8 –2.6). Therefore, it doesnot appear that the prevalence of late AMD increases

with time since cataract surgery.A higher prevalence of early AMD 1 (the definition that

includes drusen of smaller size) was found in those who hadcataract surgery 5 or more years ago in SEE (OR 1.7;

95% CI, 1.1–2.4; Table 6). The prevalence of early AMD1 was no different in those who were missing dates of

cataract surgery compared with those who had informationon date of cataract surgery (46% vs 44%). Thus, it is

unlikely that the missing data would have changed theseresults. In the BES study and in the combined analysis,

though, previous cataract surgery was not associated withearly AMD 1. Severe cataract was also not associated with

early AMD 1 in SEE or in BES. Neither cataract surgery nor severe cataract was associ-

ated with the odds of early AMD 2 in either SEE or BES(Table 7), as none of the estimates were statistically

significant and no consistent trends were apparent.

TABLE 1. General Characteristics of the Study Populations

Characteristic

Salisbury Eye

Evaluation Proyecto VER

Baltimore Eye

Survey

Sample size 2,520 4,774 4,396

Age, mean 73.5 56.9 58.9

Sex, %Male 42.1 38.8 40.4

Female 57.9 61.2 59.6

Race, %

Caucasian 73.6 0.0 57.3

African American 26.4 0.0 41.9

Hispanic 0.0 100.0 0.7

Education, %

12 years 51.5 65.1 69.6

Smoking, %

Never 38.8 52.0 34.6

Past 46.2 27.6 26.5

Current 15.0 20.4 38.9

Severe cataract,* at least 1 eye, % 9.0 8.0 1.0Previous cataract surgery, at least

1 eye, %

18.8 8.2 3.1

Late AMD†

in at least 1 eye, %

40–49 years NA 0.2 0.1

50–59 years NA 0.5 0.6

60–64 years NA 0.2 0.7

65–69 years 1.8 1.5 0.9

70 years 3.4 4.1 4.1

Overall 2.9 1.1 1.1

*Severe cataract defined as grade 4 or higher on photographs in SEE and PVER, and by the clinical

determination of cataract as a cause of visual impairment or blindness in BES.†Late age-related macular degeneration (AMD) defined as choroidal neovascularization, geographic

atrophy, or as a cause of blindness as determined by photographs in the Salisbury Eye Evaluation

(SEE) and Baltimore Eye Survey (BES), and by clinical examination in Proyecto VER (PVER).



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DISCUSSION

THESE ANALYSES BASED ON DATA FROM THREE INDEPEN-

dent, population-based studies provide some evidence that

previous cataract surgery may be associated with a higher

prevalence of late AMD. In all studies, the odds ratios for

previous cataract surgery and late AMD were greater than

1, although they varied in magnitude from 1.3 to 2.6. The

reasons for this variation are not clear, but they may be due

to differences in the population that could not be con-

trolled for. They could also be due to the small number of

cases of late AMD, which can lead to unstable measures of

association. In addition, the assessment of AMD differed in

PVER, compared with BES and SEE. When data from the

three populations were pooled, the combined odds ratio

was 1.7, which was statistically significant.

TABLE 2. Characteristics of Subjects Who Had Cataract Surgery in at Least One Eye Compared With Those Who Did Not Have

Cataract Surgery

Characteristics

SEE

Cataract Surgery

n 471

SEE

No Cataract Surgery

n 2,037

PVER

Cataract Surgery

n 390

PVER

No Cataract Surgery

n 4,362

BES

Cataract Surgery

n 138

BES

No Cataract Surgery

n 4,256

Age category, %40–49 years NA NA 4 36 4 25

50–59 years NA NA 8 30 7 27

60–64 years NA NA 7 11 11 15

65–69 years 15 35 13 9 19 14

70–79 years 59 54 41 11 45 15

80 years 26 11* 27 2* 14 3*

Sex, %

Male 36 57 37 39 39 40

Female 64 43 63 61 61 60

Race, %

White 85 71 NA NA 76 57

Black 15 29†

NA NA 24 43†

Education, %

12 years 48 52 83 64 76 69

Smoking, %

Never 35 40†

54 52 46 34

Past 50 45 36 27 28 26

Current 15 15 10 21 26 40

BES Baltimore Eye Survey; NA not applicable; PVER Proyecto VER; SEE Salisbury Eye Evaluation.

*P .05 chi-square test.†P .05 after age adjustment using multiple logistic regression.

TABLE 3. Age- and Race-specific Prevalence Rates for Late AMD* in at Least One Eye for

Study Populations

Age Strata

SEE Whites

N (%)

BES Whites

N (%)

PVER Hispanics

N (%)

SEE Blacks

N (%)

BES Blacks

N (%)

40–49 years NA 0/478 (0.0) 3/1,587 (0.2) NA 1/536 (0.2)

50–59 years NA 4/539 (0.7) 7/1,357 (0.5) NA 2/544 (0.4)

60–64 years NA 2/373 (0.5) 1/518 (0.2) NA 2/244 (0.8)

65–69 years 9/521 (1.7) 4/377 (1.1) 7/463 (1.5) 4/214 (1.9) 1/204 (0.5)

70 ye ars 50/1 ,254 (4.0) 2 9/508 (5 .7) 34/82 7 (4.1) 5/4 00 (1.4) 1/ 218 (0.5 )

Overall 59/1,775 (3.3%) 39/2,275 (1.7%) 52/4,752 (1.1%) 9/614 (1.5%) 7/1,746 (0.4%)

AMD age-related macular degeneration; BES Baltimore Eye Survey; N number; NA not

applicable; PVER Proyecto VER; SEE Salisbury Eye Evaluation.

*Late age-related macular degeneration (AMD) defined as choroidal neovascularization, geographic

atrophy, or as a cause of blindness as determined by photographs in SEE and BES and by clinical

examination in PVER.



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In addition, at first glance it appeared that increasing

time since cataract surgery was associated with a higherprevalence of late AMD. In the BES study, those who had

cataract surgery 5 or more years earlier had an increasedprevalence of late AMD, although this was not statistically

significant. The SEE study showed a similar trend, al-though sensitivity analyses showed that this trend was due

to a bias caused by the missing dates of surgery.Our overall findings are in agreement with the prospec-

tive Beaver Dam results, which found previous cataractsurgery to be associated with a higher 10-year incidence of

late AMD (RR 3.8; 95% CI, 1.9 – 7.7).8 They also found

previous cataract surgery to be associated with a greater

progression of early AMD (OR 2.0; 95% CI, 1.3– 3.0),but not with the incidence of early AMD.8

There are several possible reasons that might explain,either individually or in concert, the association between

cataract surgery and late AMD that we and others haveobserved. One possibility is that cataract and AMD simply

share one or more common risk factors. In our analyses, thefinding that severe cataract was also associated with a

modestly increased prevalence of late AMD indicates thatit may not be the cataract surgery but perhaps factors

leading to cataract that potentially have a causal relation-

TABLE 4. Analysis of Late AMD* Associated With Previous Cataract Surgery or Presence of Severe Cataract at Time of Clinical

Examination for SEE, BES, PVER†

Variable

SEE n 4,627 eyes BES n 7,364 eyes PVER n 9,477 eyes Combined n 21,460

Late AMD Late AMD Late AMD Late AMD

OR 95% CI OR 95% CI OR 95% CI OR 95% CI

Neither cataract nor surgery 1.0 Reference 1.0 Reference 1.0 Reference 1.0 Reference

Severe cataract present‡

1.3 0.6–2.8 2.1 0.3–17.8 1.3 0.5–2.9 1.4 0.8–2.4

Previous cataract surgery 1.3 0.7–2.4 2.6 0.9–7.5 1.9 0.9–4.1 1.7 1.1–2.6

AMD age-related macular degeneration; BES Baltimore Eye Survey; CI confidence interval; OR odds ratio; PSC posterior

subcapsular; PVER Proyecto VER; SEE Salisbury Eye Evaluation.

*Late AMD defined as choroidal neovascularization, geographic atrophy, or as a cause of blindness as determined by photographs in SEE

and by clinical examination in PVER.†Individual studies adjusted for age, sex, smoking, race (SEE and BES only). Combined analyses adjusted for age, sex, smoking, race

(Caucasian, non-Caucasian), and study.‡Severe cataract: nuclear 4, cortical 8/16, or any PSC opacity as determined from photographs for SEE and PVER and by visual

impairment or blindness attributed to cataract as determined by clinical examination in BES.

TABLE 5. Analysis of Late AMD* Associated With Time Since Cataract Surgery or Presence of Severe Cataract at Clinical

Examination for SEE, BES†

Variable

SEE n 4,504 eyes‡

BES n 7,363 eyes SEE and BES n 11,867

Late AMD Late AMD Late AMD

OR 95% CI OR 95% CI OR 95% CI

Neither severe cataract nor surgery 1.0 Reference 1.0 Reference 1.0 Reference

Presence of severe cataract§

1.3 0.6–2.8 2.1 0.3–17.8 1.3 0.6–2.6

Surgery 5 years ago 1.4 0.7–2.9 1.8 0.4–7.5 1.4 0.7–2.6


AMD age-related macular degeneration; BES Baltimore Eye Survey; CI confidence interval; OR odds ratio; SEE Salisbury EyeEvaluation.

*Late AMD defined as choroidal neovascularization, geographic atrophy, or as a cause of blindness as determined by photographs in SEE

and BES.† Adjusted for age, sex, smoking, race, and study (SEE and BES combined). Generalized estimating equations were used to estimate the

standard errors to account for the correlation between eyes.‡Missing data for 123 eyes on time of cataract surgery. Sensitivity analyses showed that the association disappears when all eyes missing

date of cataract surgery are placed in surgery 5 years ago (SEE results: OR 1.2, 95% CI, 0.5–2.8; (combined results: OR 1.5, 95% CI,

0.8 –2.6).§Severe cataract defined as grade 4 or higher on photographs in SEE and PVER and by the clinical determination of cataract as a cause

of visual impairment or blindness in BES.



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ship with late AMD. The association between cataract

surgery and late AMD persists after controlling for theknown common risk factors of age and smoking. There

may be other risk factors (environmental or genetic) thathave not been identified, however, or cataract and late

AMD may both be markers for accelerated aging.A second possibility that could explain the association

between cataract surgery and AMD is that we are lesslikely to detect late AMD in persons who may still have a

lens opacity in the eye. That should not be an issue in ourstudy, however, because persons with severe cataract are

not included in the reference population. Therefore, thereshould not have been a problem in detecting retinal

pathology in the reference population. Likewise, an oph-

thalmologist may look more carefully for signs of AMD in

an eye that has had cataract surgery in the past. Never-theless, retinal photographs were used for two of the

studies and the graders had no knowledge of whether theperson had cataract surgery or not.

A third possibility is that cataract surgery in some wayphysically predisposes an eye to develop AMD, perhaps

through inflammatory mechanisms.12 The epidemiologicdata cannot directly address this possibility. Our data

indicate that the prevalence of late AMD does notincrease with time from cataract surgery, suggesting that

such an effect (if it exists) likely occurs soon after surgery.A fourth explanation for the observed association be-

tween cataract surgery and late AMD is the “light hypoth-

TABLE 6. Analysis of Early AMD 1 Associated With Time Since Cataract Surgery or

Presence of Severe Cataract at Clinical Examination for SEE, BES*

Variable

SEE BES SEE and BES

Early AMD 1†

n 3,912

Early AMD 1†

n 8,656

Early AMD 1†

n 12,568


Neither severe cataract n or surgery 1 .0 Reference 1 .0 Referen ce 1 .0 Referen ce

Presence of severe cataract‡

1.2 0.9–1.7 0.5 0.2–1.4 1.1 0.8–1.5



AMD age-related macular degeneration; BES Baltimore Eye Survey; CI confidence interval;

OR odds ratio; SEE Salisbury Eye Evaluation.

*Adjusted for age, sex, smoking, race, and study (SEE and BES combined). Generalized estimating

equations were used to estimate the standard errors to account for the correlation between eyes.†Early AMD 1: drusen 64 mm, hyperpigmention, or nongeographic atrophy.‡Severe cataract defined as grade 4 or higher on photographs in SEE and PVER and by the clinical

determination of cataract as a cause of visual impairment or blindness in BES.

TABLE 7. Analysis of Early AMD 2 Associated With Time Since Cataract Surgery or

Presence of Severe Cataract at Clinical Examination for SEE, BES*

Variable

SEE BES SEE and BES

Early AMD 2†

n 4,356

Early AMD 2†

n 8,639

Early AMD 2†

n 12,995


Neither severe cataract n or surgery 1 .0 Reference 1 .0 Referen ce 1 .0 Referen ce

Presence of severe cataract‡ 0.6 0.3–1.1 — —

Surgery 5 years ago 0.9 0.6–1.5 1.0 0.5–2.0 1.0 0.7–1.4Surgery 5 years ago 1.4 0.8–2.5 0.9 0.4–1.9 1.2 0.8–1.8

AMD age-related macular degeneration; BES Baltimore Eye Survey; CI confidence interval;

OR odds ratio; SEE Salisbury Eye Evaluation.

*Adjusted for age, sex, smoking, race, and study (SEE and BES combined). Generalized estimating

equations were used to estimate the standard errors to account for the correlation between eyes.†Early AMD 2: drusen 125 m, hyperpigmention, or nongeographic atrophy.

‡Severe cataract defined as grade 4 or higher on photographs in SEE and PVER and by the clinical

determination of cataract as a cause of visual impairment or blindness in BES.



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esis.”7,11 In this hypothesis, removal of the cataract newlyexposes the retina to certain wavelengths of light (or at

greater intensity), damaging the retina and increasing the

risk of AMD.20 As most of the intraocular lenses currently

in use have ultraviolet-B blockers, the critical wavelengths

are likely to be in the blue light region. Further investiga-

tions of this hypothesis would best be assessed by a

randomized controlled clinical trial in which critical orputative wavelengths are blocked.

Some eyes (1,803/23,380) could not be evaluated for

AMD status, which could cause concern for selection bias.

When we examined the characteristics, however, eyes

without information on AMD status were from older

subjects (66 vs 61 years old) and the eyes were more likely

to have had cataract surgery (8.1% vs 6.6%). Given the

older age, it is likely that the AMD rates of those eyes missingAMD status information would have been higher than the

rates seen in this study. As we suspect the AMD rates to be

higher and we know the rates of cataract surgery were higher

in eyes missing AMD status, including these eyes in theanalyses would have likely only strengthened the results.

These analyses are cross-sectional in nature. Therefore,

we are limited to identifying an association betweencataract surgery and AMD. Because we are unable to

determine the temporal relationship of cataract surgery

and signs of AMD, we cannot declare that cataract surgery

increases the risk of AMD. Another limit to our analyses is

the small number of cases of AMD, particularly in the

younger populations. For this reason, it is important to

examine the overall results and not just focus on the resultsthat were statistically significant. Finally, the PVER study

assessed AMD using a clinical examination whereas theother two studies assessed AMD with photographs. We

attempted to control for this by adjusting for study in thecombined analyses.

Using three large population-based studies, we found

modest evidence that cataract surgery may be associated

with a greater prevalence of late AMD. We also saw that

having a severe cataract in the eye was associated with aslightly higher prevalence of late AMD. Thus, it is dif ficult

to determine from this type of study design whether the

higher rates of late AMD are due to the cataract surgery, to

the cataract itself, or to a shared risk factor. It would be

helpful if additional studies could clarify the nature of thisassociation.

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Assoc Cataract and Amd 3 Studies