Graefes Arch Clin Exp Ophthalmol (2011) 249:981985

DOI 10.1007/s00417-010-1571-y

RETINAL DISORDERS

Association between asymmetry in cataract and asymmetry

in age-related macular degeneration. The Beijing Eye Study
Liang Xu & Qi Sheng You & Tongtong Cui & Jost B. Jonas

Received: 17 June 2010 / Revised: 16 October 2010 / Accepted: 3 November 2010 / Published online: 21 December 2010
# Springer-Verlag 2010

Abstract
Background To examine in an intra-individual comparison
whether cataract is associated with age-related macular
degeneration (AMD).
Methods The population-based Beijing Eye Study included
4,439 subjects (age: 40+ years) out of 5,324 subjects
invited to be examined. Using lens and fundus photographs,
the amount of AMD was graded according to the
Wisconsin Age-Related Maculopathy Grading system and
the degree of cataract was graded using the system of the
Age-Related Eye Disease Study.
Results Photographs with sufficient quality for bilateral
examination of the lens and macula were available for
3,826 (86.2%) participants with a mean age of 55.3
10.0 years (range: 4090 years) and a mean refractive error
of 0.382.18 diopters (range: 20.13 diopters to +7.50
diopters). The side difference in presence of early AMD
and late AMD respectively was not significantly associated
with the inter-eye difference in the amount of nuclear
cataract [P= 0.27 and P= 0.28 (r= 0.02) respectively),
amount of cortical cataract (P=0.12 and P=0.05 respecProprietary interest none
L. Xu (*) : Q. Sheng You : T. Cui : J. B. Jonas (*)
Beijing Institute of Ophthalmology, Beijing Tongren Hospital,
Capital University of Medical Science,
17 Hougou Lane, Chong Wen Men,
100005, Beijing, China
e-mail: xlbio@yahoo.cn
J. B. Jonas
e-mail: Jost.Jonas@umm.de
J. B. Jonas
Department of Ophthalmology, Medical Faculty Mannheim
of the Ruprecht-Karls-University Heidelberg,
Heidelberg, Germany

tively), and amount of subcapsular posterior cataract

(P=0.91 and P=0.85 respectively). In a similar manner,
the side difference in the presence of early AMD and late
AMD was not significantly associated with the inter-eye
difference in the presence of nuclear cataract (P=0.99 and
P=0.99 respectively), cortical cataract (P=0.25 and P=1.00
respectively), and subcapsular posterior cataract (P=0.59
and P=0.05 respectively). The side difference in the
number of macular drusen was not significantly associated
with the inter-eye difference in the amount of nuclear
cataract (P=0.74), amount of cortical cataract (P=0.19) and
amount of subcapsular posterior cataract (P=0.88). As a
corollary, unilateral pseudophakia or aphakia was not
significantly associated with inter-eye differences in the
count (P=0.59) of drusen, and overall presence of early
AMD (P=0.99) or late AMD (P=0.99).
Conclusions In an intra-individual, inter-eye comparison,
avoiding interdependencies of systemic parameters, intereye difference was not significantly associated with any
characteristics of age-related macular degeneration in either
any type of cataract or in pseudophakia. This suggests that
the development of cataract or cataract surgery did not
markedly influence the development of age-related macular
degeneration.
Keywords Cataract . Age-related macular degeneration .
Beijing Eye Study

Introduction
Population-based studies performed in the last 20 years
have revealed that age-related macular degeneration (AMD)
is one of the most common causes for visual impairment in
elderly populations [15]. The list of risk factors for the

982

development and progression of AMD includes smoking,

genetic factors such as an association with the complement
factor H gene complex, family history, and ethnic background [619]. There has been controversy whether
cataract, cataract progression, and cataract surgery are
related to AMD [2029]. Since interdependencies of ocular
parameters with systemic parameters can lead to a bias in
the results, it was the purpose of our study to examine
whether, in an intra-individual inter-eye comparison, intereye differences in cataract are correlated with inter-eye
differences in the amount of AMD. Such a study design
excludes the possibility of a bias by systemic parameters,
since systemic parameters supposedly influence both eyes
of the same individual to a similar degree.

Methods
The Beijing Eye Study, a population-based cross-sectional
study in Northern China, was carried out in seven
communities. Four communities were selected from the
Haidian urban district of the Northern part of Central
Beijing, and three communities were selected from the rural
village area of Yufa in the county of Daxing District south
of Beijing. In the rural areas, eye care services and a referral
system to ophthalmologists were not available, and the cost
for medical care was not covered by the government. In the
urban areas included in the Beijing Eye Study, eye care was
at a relatively high standard, with some communities
supplying free ophthalmic examinations, and in these areas,
the cost for medical care was covered by the government.
The Medical Ethics Committee of the Beijing Tongren
Hospital had approved the study protocol, and all participants had given informed consent. The study has been
described in detail previously [30, 31].
At the time of the survey in the year 2001, there were a
total of 5,324 individuals aged 40 years or older residing in
the seven communities and who were eligible for the study.
In total, 4,439 individuals (2,505 women) participated in
the eye examination, corresponding to an overall response
rate of 83.4%. From the 8,878 eyes, data on the lens were
available for 8,724 eyes (4,378 subjects). For 4,346
subjects, lens data were available for both eyes. The study
was divided into a rural part [1,918 (43.8%) subjects; 3,814
eyes] and an urban part [2,460 (56.2%) subjects; 4,910
eyes]. Mean age was 56.110.5 years (median, 56 years;
range, 40101 years).
All examinations were carried out in the communities,
either in schoolhouses or in community houses. Visual
acuity was measured as uncorrected visual acuity (Snellen
charts) in a distance of 5 m, and as near vision in a distance
2530 cm using Jaeger charts, uncorrected and then
corrected using an addition for near vision. Automatic

Graefes Arch Clin Exp Ophthalmol (2011) 249:981985

refractometry (Auto Refractometer AR-610, Nidek Co.,

Ltd, Tokyo, Japan) was performed if uncorrected visual
acuity was lower than 1.0 . The values obtained by
automatic refractometry were verified and refined by
subjective refractometry. Intraocular pressure was measured
using a non-contact pneumotonometer (CT-60 computerized tonometer, Topcon Ltd., Japan) by an experienced
technician. The pupil was dilated using tropicamide once or
twice, until the pupil diameter was at last 6 mm. Using the
slit lamp, digital photographs of the cornea and lens were
taken. For the lens photographs, the slit-lamp beam had a
width of 0.3 mm and a height of 9.0 mm. The angle
between the slit-lamp beam and the sagittal axis was at 45.
The slit-lamp beam bisected the central lens from of its
superior pole at the 12 o'clock position to its inferior pole at
the 6 o'clock position. It was focused onto the center of the
lens nucleus. Additionally, retro-illuminated photographs of
the lens were taken. The degree of nuclear cataract was
graded in six grades according to the lens photographs
using the classifying scheme for cataract of the Age-Related
Eye Disease Study [32, 33]. We combined standard
photograph 6 and 7 into one grade, i.e., grade 6 . Grade
1 was no nuclear opacity in the lens, and grade 6 was
very dense nuclear lens opacity. The degree of cortical lens
opacification and posterior subcapsular lens opacification
was graded using two photographs taken by retroillumination with the Neitz CT-R camera (Neitz Instruments
Co., Tokyo, Japan). Cortical and posterior subcapsular
opacities appeared as darkly shaded areas on the white
background through the computer screen. The per cent area
of opacity was measured using a grid. In addition to the
grading of the amount of nuclear cataract, we defined the
presence of nuclear cataract as a degree of nuclear cataract
of 4 or higher, the presence of cortical cataract as any
cortical cataract, and the presence of subcapsular posterior
cataract as any subcapsular posterior cataract.
For the assessment of AMD, the Wisconsin Age-Related
Maculopathy Grading system was used [34, 35]. In a first
step, a measurement scale was prepared using three circular
fields which were centered around the foveola. The first
field, with a diameter of 1 mm, outlined the fovea centralis.
The second field with a diameter of 3 mm diameter covered
the parafovea, and the field with a diameter of 6 mm
included the perifoveal area. For drusen, three features were
considered: size, area, and type. The predominant drusen
size was graded with one of the following categories: none,
less than 63 m in diameter, between 63 and 125 m in
diameter, between 126 and 175 m in diameter, between
175 m and 250 m, and 250 m or greater in diameter.
The area covered by drusen was estimated using the area of
circles with a projected diameter on the fundus of 63 m,
125 m, 175 m, 250 m, and 500 m respectively. The
ratio of the estimated affected area to the total area of the

Graefes Arch Clin Exp Ophthalmol (2011) 249:981985

grid was calculated to obtain the percentage of area covered

by drusen. We graded the maximum drusen type, addressing the most severe drusen type present, as none, hard
distinct drusen (<125 m), intermediate soft distinct drusen
(63 m to 125 m), large soft distinct drusen (>125 m),
and large soft indistinct semisolid drusen (>125 m). In
gauging retinal pigment epithelial (RPE) abnormalities, we
considered two aspects: increased RPE pigmentation and
RPE depigmentation. Increased RPE pigment was graded
as absent, questionable, total area of hyperpigmentation
occupying an area of a circle with a diameter of less than
63 m, between 63 and 125 m in diameter, and greater
than 125 m. Retinal pigment epithelial depigmentation
was graded as absent, questionable, total area of RPE
depigmentation occupying a circle with a diameter of less
than 125 m, and greater than 125 m. Five types of late
AMD lesions were considered: geographic atrophy, RPE
detachment, detachment of sensory retina, subretinal hemorrhage, and subretinal disciform scar. Exudative AMD was
considered present if any of the following lesions were
present: RPE detachment, detachment of sensory retina,
subretinal hemorrhage, or subretinal disciform scar. Late
AMD was present if there were signs of exudative AMD or
pure geographic atrophy. Early AMD was present if late
AMD was absent and there were signs of soft indistinct or
any drusen (except hard indistinct drusen) combined with
RPE changes in the macular area. Senior investigators (LX,
JBJ) adjudicated all photos graded as early or late AMD.
Statistical analysis was performed by using a commercially
available statistical software package (SPSS for Windows,
version 17.0, SPSS, Chicago, IL, USA). The data were given
as meanstandard deviation. In a first step of the statistical
analysis, we calculated the inter-eye difference of right eye
minus left eye for the presence and amount of nuclear cataract,
cortical cataract and subcapsular posterior cataract, and the
inter-eye difference of right eye minus left eye for the presence
of early and late AMD, and the number and size of macular
drusen. In a second step of the analysis, we tried to find
significant correlations between the inter-eye differences of
the lens parameters with the inter-eye differences of the
parameters describing the presence and amount of AMD. We
applied a linear regression analysis to assess the relationship
between the side difference in the amount of cataract and the
side difference in the number of drusen. We performed the
Chi-square test to examine the relationship in the side
difference in the presence of cataract and the side difference
in the presence of AMD.

Results
Photographs with sufficient quality for bilateral examination of the lens and macula were available for 3,826

983

participants (86.2% of the original sample). The mean age

was 55.310.0 years, ranging from 40 to 90 years. The
mean refractive error was 0.382.18 diopters, ranging
from 20.13 diopters to +7.50 diopters.
The mean side difference in the amount of nuclear lens
opacity was 0.060.29, with 227 (5.4%) subjects showing
an inter-eye difference of at least one grade in the nuclear
opacity assessment. The mean side difference in the amount
of cortical lens opacity was 0.010.05, with 388 (9.5%)
subjects showing an inter-eye difference in the cortical
nuclear opacity assessment. The mean side difference in the
amount of subcapsular posterior lens opacity was 0.01
0.04, with 144 (3.5%) subjects showing an inter-eye
difference in the subcapsular posterior opacity assessment.
Correspondingly, a side difference in the presence of
nuclear cataract (defined as grade 4 or higher of nuclear
lens opacity) was found in 53 (1.2%) subjects, a side
difference in cortical cataract in 194 (4.8%), and a side
difference in subcapsular posterior cataract in 106 (2.4%)
subjects. A side difference in the presence of early AMD
was detected in 196 (4.7%) subjects, and a side difference
in the presence of late AMD in 12 (0.2%) subjects.
The side difference in presence of early AMD and late
AMD respectively was not significantly associated with the
inter-eye difference in the amount of nuclear cataract [P=0.27
(correlation coefficient r=0.02) and P=0.28 (r=0.02) respectively], the inter-eye difference in the amount of cortical
cataract [P=0.12 (r=0.03) and P=0.05 (r=0.03) respectively], and the inter-eye difference in the amount of subcapsular
posterior cataract [P=0.91 (r=0.002) and P=0.85 (r=0.003)
respectively]. In a similar manner, the side difference in the
presence of early AMD and late AMD, respectively was not
significantly associated with the inter-eye difference in the
presence of nuclear cataract (P=0.99 and P=0.99 respectively), the inter-eye difference in the presence of cortical cataract
(P=0.25 and P=1.00 respectively), and the inter-eye difference in the presence of subcapsular posterior cataract
(P=0.59 and P=0.05 respectively.).
The side difference in the number of macular drusen was
not significantly associated with the inter-eye difference in the
amount of nuclear cataract (P=0.74; r=0.005), the inter-eye
difference in the amount of cortical cataract (P=0.19; r=
0.02) and the inter-eye difference in the amount of
subcapsular posterior cataract (P=0.88; r=0.002).
As a corollary, unilateral pseudophakia or aphakia was
not significantly associated with inter-eye differences in the
count (P=0.59) of drusen, and overall presence of early
AMD (P=0.99) or late AMD (P=0.99).
In contrast, the inter-eye difference in best-corrected visual
acuity was significantly associated with the inter-eye difference
in cortical cataract (P=0.001), nuclear cataract (P<0.001),
total drusen area (P=0.003), and drusen size (P=0.01), and
presence of late AMD (P=0.007).

984

Discussion
In our study, with an intra-individual, inter-eye comparison
and thus avoiding interdependencies of systemic parameters, inter-eye differences were not significantly associated
with the prevalence of early AMD nor late AMD in either
any type of cataract or in pseudophakia. In a parallel
manner, unilateral pseudophakia or aphakia was not
significantly associated with inter-eye differences in the
presence of either early AMD nor late AMD. These results
suggest that the development and the presence of cataract as
well as cataract surgery was not markedly associated with
the development or presence of AMD.
These findings agree with, but partially are in contrast to,
previous studies. Our study confirms a recent large-scale
hospital-based study in which cataract surgery was not
related with the development of AMD [29]. It suggests that
the development of cataract or cataract surgery did not
markedly influence the development of age-related macular
degeneration. Both these studies, however, are contradictory to a number of studies, including an investigation of
autopsy eyes [36], several case series [3739], and
population-based epidemiologic studies [23, 24, 4042],
in which concerns were raised with regard to the potential
of cataract surgery to accelerate progression to advanced,
vision-threatening forms of AMD.
In a similar manner, the presence and amount of neither
nuclear cataract, cortical cataract nor subcapsular posterior
cataract was not significantly associated with the presence of
either early AMD or late AMD. The reports published so far in
the literature have been inconsistent [21, 22, 36, 43, 44]. In
the Beaver Dam Eye Study, a positive cross-sectional
relationship was found between cataract and early AMD, as
well as an association between cataract and the subsequent
risk for early AMD [23]. This association was consistent
with findings in the Chesapeake Bay Watermen Study [44],
but not with findings in the Framingham Study or the Blue
Mountains Eye Study [22, 45]. One of the reasons for the
diversity in the findings between the studies mentioned may
be the effect of confounding factors such as age, gender,
socioeconomic background, nutrition, etc. The advantage of
our study design was that as an intra-individual inter-eye
comparison, the confounding effect of systemic factors was
avoided. This includes the potentially confounding effect of
non-participation in a population-based study.
In conclusion, in an intra-individual, inter-eye comparison, avoiding interdependencies of systemic parameters,
inter-eye differences were not significantly associated with
any characteristics of age-related macular degeneration
either in any type of cataract or in pseudophakia. This
suggests that the development of cataract or cataract
surgery did not markedly influence the development of
age-related macular degeneration.

Graefes Arch Clin Exp Ophthalmol (2011) 249:981985

Acknowledgment Supported by Beijing Municipal Natural Science
Foundation and Bureau of International Cooperation, Beijing Municipal Science & Technology Commission

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