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Published in final edited form as:

Curr Opin Ophthalmol. 2023 January 01; 34(1): 27–31. doi:10.1097/ICU.0000000000000909.

Cataract surgery and the risk of progression of macular

degeneration
Sanjeeb Bhandari, MD, PhD,
Emily Y. Chew, MD*
Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of
Health, Bethesda, MD
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Abstract
Purpose of review—Cataract surgery improves vision loss due to cataracts in eyes with co-
existing age-related macular degeneration (AMD), but whether surgery itself pose an increased
risk for the progression of AMD has been of concern to both physicians and their patients. This
review describes evidence on cataract surgery and its impact on the progression of AMD.

Recent findings—Recent evidence suggests that cataract surgery does not increase the risk for
progression of AMD.

Summary—Cataract surgery should be discussed in patients with both AMD and visually
significant cataract. Patients should be reassured that the cataract surgery will not increase the risk
of AMD progression. In patients with AMD, especially those with the more severe intermediate
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stage and those with advanced AMD in the fellow eye, the natural course of progression
to late AMD is high. The importance of vigilant follow-up needs to be emphasized for the
detection of natural progression of the disease and early initiation of treatment should signs of
neovascularization develop.

Keywords
Age-related macular degeneration; cataract surgery; Age-Related Eye Disease Study; Age-Related
Eye Disease Study 2

Introduction
Vision impairment from cataracts and AMD is expected to increase with the global rise
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in the aging population.(1) Cataract often co-exists in eyes with age-related macular
degeneration (AMD) as both share common risk factors.(2, 3) Cataract surgery improves
vision loss due to lens opacities in eyes with co-existent AMD. The surgical procedure,
however, can cause intraocular inflammation which could theoretically contribute to AMD
progression.(4) The risk of AMD progression after cataract surgery, if any, is of concern
to both patients and their physicians. This review analyzes current evidence that will help

*
Corresponding author: Emily Y. Chew, MD, Division of Epidemiology and Clinical Applications, National Eye Institute, National
Institutes of Health, Building 10, CRC-Room 3-2531, 10 Center Drive, Bethesda, MD, 20892-1204, USA; echew@nei.nih.gov.
Conflicts of interest: None
 Bhandari and Chew Page 2

counsel patients with AMD for potential cataract surgery often seen in day-to-day clinical
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practice.

Evidence from epidemiological studies

Evidence on the risk of AMD progression after cataract surgery stems from the earlier
population-based longitudinal studies.(5–10) The Beaver Dam Eye Study (BDES) and the
Blue Mountains Eye Study (BMES) found that eyes with a history of cataract surgery at
baseline had an increased risk of late AMD, Odd’s ratio (OR) of 5.5 (95% Confidence
Interval [CI]: 2.4 – 13.6), relative to their phakic cohort.(6) The risk of late AMD in eyes
that had cataract surgery before the baseline visit persisted at 10 years with a risk ratio of
3.81 (95% CI: 1.89 – 7.69) for BDES and 3.3 (1.1 – 9.9) for BMES (Table 1).(5, 8) The
risk of late AMD was not increased in the BMES cohort when cataract surgery occurred
within five years after the baseline visit (OR of 0.82, 95%CI: 0.26 – 2.59).(8) The BDES,
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however, found that of the 39% of their original cohort assessed at 20 years, eyes that
received cataract surgery after the baseline visit had an increased risk of late AMD (OR
of 1.93, 95%CI: 1.28 – 2.90, Table 1) and the OR was higher ≥ 5 years after the surgery
than < 5 years.(11) The Rotterdam Eye Study reported an association of incident subtype of
late AMD, geographic atrophy, in eyes that had a history of cataract surgery (OR of 3.43,
95%CI: 1.82 – 6.49, Table 1).(9)

Recent epidemiological studies, in contrast, did not find AMD progression following
cataract surgery. The Korean National Health and Nutrition Examination Survey found that
there was no association between cataract surgery and late AMD (OR of 1.42, 95%CI: 0.88
– 2.29, Table 1).(12) The Beijing Study found that neither cataract nor cataract surgery was
associated with early or late AMD (p = 0.99).(13)
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Evidence from Clinic-based studies

Clinic-based studies have consistently found that eyes with early or moderate AMD that
received cataract surgery did not have an accelerated progression to late AMD in the 12
months following the surgery (Table 1).(14, 15). A study found that there was no difference
in the lens status in eyes with late AMD and their fellow eyes without advanced AMD
(OR of 1.42, 95%CI: 0.88 – 2.29).(16) The Australian Cataract Surgery and Age-Related
Macular Degeneration Study that prospectively evaluated the rates of late AMD at 5 years
in eyes receiving cataract surgery with their fellow phakic eyes provides compelling data
on the risk of AMD progression after cataract surgery. This study found that there were no
statistically significant differences in the rate of late AMD between the pseudophakic eyes
and their fellow eyes at 3 and 5 years of follow-up (Table 1).(17, 18)
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Evidence from Age-Related Eye Disease Study (AREDS) and AREDS2

The association between cataract surgery and progression to late AMD has been of
considerable interest to the investigators of the Age-Related Eye Disease Study (AREDS)
and Age-Related Eye Disease Study 2 (AREDS2) research groups. AREDS was a
randomized placebo-controlled clinical trial in participants 55 – 59 years that assessed

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the role of vitamins and mineral supplementation on the development of late AMD and
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cataract.(19) An analysis from AREDS evaluated the risk of developing late AMD after
incident cataract surgery in 8050 eyes (4557 participants) without cataract and late AMD at
baseline.(20) The Cox proportional hazards model showed a hazards ratio for neovascular
AMD of 1.20 (95%CI: 0.82 – 1.75) for right and 1.07 (95%CI: 0.72 – 1.58) for left eyes,
for geographic atrophy of 0.80 (95%CI: 0.61 – 1.06) for right and 0.94 (95%CI: 0.71 –
1.25) for left eyes and for central geographic atrophy of 0.87 (95%CI: 0.64 – 1.18) for right
and 0.86 (95%CI: 0.63 – 1.19) for left eyes. The two other models used for data analyses,
logistic regression and matched-pair analysis, did not suggest an increased risk for late
AMD progression following cataract surgery either (Table 1). The AREDS results showed
no increased risk of late AMD over a median follow-up of 10 years after cataract surgery
(Table 2).

A recent study from AREDS2 prospectively evaluated the incidence of late AMD following
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cataract surgery.(21) The AREDS 2 enrolled 4203 participants 50 – 85 years with bilateral
large drusen or unilateral AMD in a randomized controlled clinical trial between 2006
– 2008 to evaluate the potential benefits of a modified nutritional supplement on the
development of late AMD and were followed until 2012.(22) An additional follow-up of
5 years (2013 – 2018) was conducted on the surviving AREDS2 participants after the end
of the clinical trial in 2012. Telephone interviews at 6-monthly intervals collected data on
adverse events, AMD treatment and cataract surgery between the study visits for this cohort
during the clinical trial.

In the final 5 years of follow-up, only telephone interviews were conducted to obtain
information regarding cataract surgery. A subset of the AREDS2 participants (n=709)
underwent a comprehensive eye exam, and stereoscopic fundus and red reflex lens
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photographs at the year 10 study visit. Late AMD was defined as the presence of
neovascularization or the presence of geographic atrophy on color fundus photos and/or
a history of nAMD treatment during the clinical trial period supplemented by telephone
calls and medical records at follow-up. Of the 2754 participants (4553 eyes) available for
analysis in the Cox proportional hazards model, 1767 eyes (1195 participants) had cataract
surgery while 1981 eyes (1524 participants) developed late AMD. The hazard ratio for the
development of late AMD after cataract surgery was not statistically significant, 0.96 (95%
CI: 0.81 – 1.13) for right eyes and 1.05 (95%CI: 0.89 – 1.25) for left eyes. Neither the
logistic regression model (OR of 0.92, 95% CI: 0.56 – 1.49) nor the matched-pair analysis
(OR of 0.92, 95% I: 0.77 – 1.10) showed an increased risk of AMD progression among
AREDS2 participants with up to 10 years of follow-up (Table 1). This study from AREDS2
is consistent with the results of the AREDS study and provides further evidence that cataract
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surgery does not increase the risk of developing late AMD.

Reasons for the differences in the results

One of the reasons for the differing results between the Age-Related Eye Disease studies
and the prior population-based longitudinal studies that reported an increased risk of AMD
progression after cataract surgery may be the difference in the study participants. The
AREDS and AREDS 2 clinical trials enrolled a highly selective group of healthy volunteers

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who are more health conscious and may have healthier lifestyles than the general population
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with the disease. The volunteers selected in the previous epidemiological studies were at
higher risk of developing late AMD. More than two-fifths of their cohort had high-risk
characteristics for late AMD such as at least one large drusen, extensive intermediate drusen,
or geographic atrophy not involving the center of the macula. The inclusion of a higher
proportion of participants who had a demonstrable propensity for AMD progression in these
studies might have reduced the likelihood of detecting additional risk factors, such as the
impact of cataract surgery.

The other reason for the contradicting risks on AMD progression following cataract surgery
could have resulted from unadjusted confounding. Cataract and AMD share common risk
factors and aging is an important risk factor for both.(2, 3) Eyes that had cataract at baseline
in the previous population-based studies had signs of early AMD.(3, 7) These eyes were
more susceptible to developing late AMD.(5) In contrast, eyes that had incident cataract
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surgery and those that did not in AREDS and AREDS2 studies had an equal propensity for
developing late AMD.

The presence of unrecognized, subtle maculopathy before cataract surgery in the previous
population-based studies could have led to the discrepancy in the results from those of
the recent epidemiological studies, clinic-based studies, and AREDS and AREDS2.(2, 7–9)
Cataract surgery could have facilitated better visualization of the fundus and identification
of the maculopathy persisting before the surgery. Both cataract and AMD decrease visual
acuity making it difficult to predict whether a decreased vision requiring cataract surgery in
the earlier epidemiological studies had contributions from one or the other.(2, 3) Eyes that
had cataract and early AMD at baseline in the earlier population-based studies were more
likely to receive cataract surgery than those with cataract in the absence of early AMD at
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baseline.(5) Moreover, the decision for cataract surgery in the clinic-based studies and the
AREDS studies were highly adjudicated by physicians who had examined the participants at
regular intervals, thus participants in these studies were less likely to receive the surgery for
subtle macular changes.

The earlier epidemiological studies that found an increased risk of AMD progression
following cataract surgery date to the mid- or late 1990s.(3, 7, 23) Significant advances
have occurred in surgical techniques and diagnostic tools since then. The cataract surgical
technique evolved from extracapsular/intracapsular during these studies to less traumatic
phacoemulsification cataract surgery - the standard of care in the later epidemiological
studies, clinic-based studies, and AREDS and AREDS2 studies. The increased use of
ultraviolet blocking or blue filtering intraocular lenses might have addressed the potential
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macular toxicity and eventual degeneration after cataract surgery. Evaluation of the retina
using optical coherence tomography provides a better assessment of the macula before
contemplating cataract surgery.

Visual acuity and quality of life after cataract surgery

The AREDS and AREDS2 studies reported significant visual gains after cataract surgery in
all the subgroups that were stratified by pre-operative AMD severity.(24, 25) A significant

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proportion of eyes achieved a visual acuity (VA) ≥ 20/40 after the surgery. A post-hoc
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analysis of landmark clinical trials of anti-vascular endothelial growth factor (VEGF)

antibody for the treatment of neovascular AMD (Minimally Classic/Occult Trial of the anti-
VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD [MARINA] and Anti-
VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization
in AMD [ANCHOR]) reported an improvement in VA by 2 lines in eyes that received
cataract surgery.(26) Functional vision improvement, however, is dependent on the pre-
operative VA.(27) The improvement in eyes with pre-operative VA ≥ 20/40 is similar to
those without retinal pathology while for those ≤ 20/40, improvement is significantly less
and is decreased with a decreasing pre-operative VA.(27) Cataract surgery may not reliably
improve VA in fovea-involving geographic atrophy. However, it improves other critical
aspects of visual function such as contrast sensitivity, color vision, peripheral vision, glare
and also the quality of life indices.(28)
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Conclusion
Recent evidence suggests that cataract surgery does not increase the risk of AMD
progression. Patient with AMD who have visually significant cataracts should be counseled
that cataract surgery improves vision and quality of life without imposing a significant risk
for disease progression. The patient should also be made aware about the natural progression
of the disease irrespective of cataract surgery. Patient should be encouraged to vigilant
follow-up visits for the detection of signs of neovascular changes for which early initiation
of treatment leads to good outcomes.

Acknowledgments
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This work has been supported by the intramural research program funds of the National Eye Institute, National
Institutes of Health, Bethesda, MD

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Key points
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• A recent prospective study that evaluated the association of cataract surgery

with incident late age-related macular degeneration (AMD) found that the risk
of AMD progression was not increased after cataract surgery.

• Data from the Age-Related Eye Disease Studies, clinic-based studies, and
recent epidemiological studies show that cataract surgery does not worsen
AMD.

• Emphasis on follow-up visits should be made after cataract surgery in patients

with AMD for the detection of the natural progression of AMD and early
initiation of treatment should there be signs of neovascular AMD.
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Table 1.

Characteristics of the studies included in the review

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Participants
Study/ Published Adjusted/ AMD Follow- OR/RR/H
cases/ 95% CI Remarks
Author year matched factors classification up R
controls

Population-based studies
Age, smoking,
alcohol
BDES/Klein consumption, 1.03 –
1998 3684 Late AMD 5 years OR – 2.80
R, et al.,(2) pulse pressure, 7.63
hypertension and
vitamin use

Age, gender,
smoking, alcohol
BDES/Klein consumption, 1.89 –
2002 2764 Late AMD 10 years RR – 3.81
R, et al.,(5) systolic blood 7.69
pressure, vitamin
use
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Age, gender,
education,
smoking, alcohol
BDES/Klein consumption, 1.28 –
2012 1913 Late AMD 20 years OR – 1.93
R, et al.,(11) cardiovascular 2.90
disease, diabetes
and diastolic
pressure

Age, gender,
smoking and
BMES/Cugati presence of early 1.11 –
2006 1952 Late AMD 10 years OR – 3.31
S, et al.,(8) age-related 9.87
maculopathy
lesions

Age, gender,
RES/ Ho, L et follow-up duration Late AMD - 1.82 –
2008 6032 5.7 years OR – 3.43
al.,(9) and co-relation GA 6.49
between eyes

Clinic-based studies
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BEI/Xu L, et Early AMD P = 0.99

2011 3826 - -
al.,(13) Late AMD P = 0.99

Age, gender,
smoking status,
gross income,
education,
KNHNES/ occupation,
Both early and 0.87 –
Park SJ, et 2016 34863 diabetes, - OR – 1.02
Late AMD 1.21
al.,(12) dyslipidemia,
body mass index,
hepatitis B surface
antigens and
anemia

Armbrecht 0.06 –
α
AM, et al., 2003 40/43 - Late AMD 1 year RR – 0.58 α
(14) 6.17

Sutter FKP, et 0.77 –

2007 499 - Late AMD - OR – 1.04
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al.,(16) 1.39

Baatz H, et Age, baseline 0.52 –

2008 696 Late AMD 1 year OR – 1.30
al.,(15) visual acuity 3.24

0.23 –
CSAMD/
2012 3 years 0.74 2.36
Wang JJ, et 1760 - Late AMD
2016 5 years 0.70 0.40 –
al.,(17, 18)
1.20

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Participants
Study/ Published Adjusted/ AMD Follow- OR/RR/H
cases/ 95% CI Remarks
Author year matched factors classification up R
controls
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Age-Related Eye Disease Study

2009 Age, AMD status, HR – 0.82 –
gender, smoking, 1.20/1.07 1.75 /
nAMD
(Right/left 0.61 –
eyes) 1.06

HR – 0.61 –
0.80/0.94 1.06 /
GA
(Right/left 0.71 –
eyes) 1.25

HR – 0.64 –
0.87/0.86 1.18 /
CGA
(Right/left 0.64 –
AREDS/ eyes) 1.49
Chew E, et 4577 10 years
al.,(20) Age, AMD status,
0.44 –
gender, smoking,
1.30
AMD status of the nAMD OR – 0.76 Matched-
0.31 –
fellow eye, GA OR – 0.55 pair
0.99
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AREDS treatment, CGA OR – 0.68 analysis

0.33 –
duration of follow-
1.41
up after surgery

1.07 –
Age, gender, 2.10
nAMD OR – 1.49 Logistic
AMD status, 0.42 –
GA OR – 0.58 regression
duration of follow- 0.80
CGA OR – 0.90 model
up after surgery 0.62 –
1.29

2022 Age, AMD HR – 0.89 –

9 years
severity score, 1.1/0.96 1.25 /
2754 Late AMD range(1
smoking gender, (Right/left 0.81 –
– 12)
education eyes) 1.13

Age, AMD score,

duration of follow-
up, gender,
AREDS2/ education, Matched-
0.77 –
Bhandari S, et 1061/1061 AREDS2 Late AMD 6 years OR – 0.92 pair
1.10
al.,(21) treatment group, analysis
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smoking, diabetes,
aspirin and statin
use

Age, AMD
9 years Logistic
severity score, 0.56 –
1702 Late AMD range(1 OR – 0.92 regression
smoking gender, 1.49
– 12) model
education

BDES – Beaver Dam Eye Study; BMES – Blue Mountain Eye Study; RES – Rotterdam Eye Study; BEI – Beijing Eye Study; KNHES –
Korean National Health and Nutrition Examination Survey; CSAMD – Cataract Surgery and Age-Related Macular Degeneration Study; AREDS –
Age-Related Eye Disease Study; AREDS2 – Age-Related Eye Disease Study 2; AMD – Age-related macular degeneration, nAMD – Neovascular
Age-related macular degeneration; GA – Geographic atrophy, CGA – Central geographic atrophy; OR – Odd’s ratio; RR – Relative risk; HR –
Hazards ratio
α
- Estimated
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