The Relationship between Changes in Body Mass Index and

Retinal Vascular Caliber in Children

Emil D. Kurniawan, MD1, Carol Y. Cheung, PhD2,3, Wan Ting Tay, BSc2, Paul Mitchell, MD, PhD4, Seang-Mei Saw, MD, PhD2,3,
Tien Yin Wong, MD, PhD2,3, and Ning Cheung, MD2,5

Objective To examine the longitudinal relationship between changes in childhood body mass index (BMI) and
retinal vascular caliber.
Study design A prospective study of 421 healthy children aged 7-9 years in 2001 who returned for follow-up in
2006. At both visits, retinal photographs and anthropometric measurements were taken following standardized pro-
tocols. Retinal arteriolar and venular calibers were measured using a computer-based program and summarized as
central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE).
Results At follow-up, mean weight, height, and BMI increased significantly (P < .001). Mean CRVE increased by
3.4 mm (P < .001) but mean CRAE did not alter significantly (P = .340). On multivariate analysis, greater BMI was
cross-sectionally associated with narrower CRAE (P < .01) and wider CRVE (P < .01). On longitudinal analysis,
increasing BMI was associated with increasing CRVE (P = .04) over the 5-year period. Baseline BMI was associated
with increased venular caliber and decreased arteriolar caliber at follow-up, and vice versa (P < .05).
Conclusions Increasing BMI is associated with increasing retinal venular caliber over time in children, and baseline
retinal vascular caliber changes increase the risk of higher BMI at follow-up. As both widened retinal venular caliber
and greater BMI are associated with risk of cardiovascular events in adults, progressive retinal venular widening
could be a manifestation of an adverse microvascular effect of obesity early in life. (J Pediatr 2014;165:1166-71).

C
hildhood overweight and obesity have become a major public health concern worldwide. Epidemiologic studies suggest that
close to 50% of children are overweight in some developed countries.1,2 More importantly, childhood obesity is associated
with early-onset diabetes, dyslipidemia, and hypertension,3 and future risk of cardiovascular disease and mortality.4 Although
studies have linked childhood obesity or its measures with large-vessel disease, the effect of obesity on the microvasculature is less well
documented. This is, at least in part, because of the difficulty in noninvasively studying subtle changes in the microcirculation.
Recent technological advances have allowed precise and reliable quantitative measurements of retinal vascular caliber from
retinal photographs. Wider retinal veins and narrower retinal arteries have been associated with measures of obesity in a wide
range of studies in children5-9 and adults.10,11 Similar associations have been observed between these variations in retinal
vascular caliber and other cardiovascular risk factors (diabetes, hypertension).11-13 In addition, narrowed retinal arterioles
and widened retinal venules have also been linked to future cardiovascular events (stroke, coronary heart disease), independent
of traditional risk factors.14-16 Therefore, variations in retinal vascular caliber may represent a useful marker of microvascular
changes that precede development of overt cardiovascular disease.15
A few cross-sectional studies have shown associations between retinal vascular caliber and measures of obesity in children.5-9
Although it has been proposed that these findings may reflect early adverse microvascular effects of obesity in early life, there is a
lack of longitudinal data. The purpose of this study was to examine the relationship between changes in body mass index (BMI)
and changes in retinal vascular caliber over time in young children and adolescents.

Methods
The Singapore Cohort Study of Risk Factors for Myopia is a school-based study of children aged 7-9 years at baseline in
Singapore. Details of the study population have been described elsewhere.17 In brief, permission to conduct the study was
obtained from the Ministry of Education of Singapore. The study was supported
by the principals and teachers of the 2 schools. To sample children from schools 1
From the Center for Eye Research Australia, University
with different overall academic performance, 2 elementary schools were selected of Melbourne, Melbourne, Australia; Singapore Eye 2

Research Institute, Singapore National Eye Center,

based on prior National Examination results of their students. One school in the 3
Singapore; Department of Ophthalmology, Yong Loo
Eastern part of Singapore ranked among the top 20 schools in the country, and Lin School of Medicine, National University of Singapore,
Singapore; 4Center for Vision Research, Department of
Ophthalmology and Westmead Millennium Institute,
University of Sydney, Sydney, Australia; and
5
Department of Ophthalmology, University of Hong
Kong, Hong Kong SAR, China
BMI Body mass index
The authors declare no conflicts of interest.
CRAE Central retinal artery equivalent
CRVE Central retinal vein equivalent 0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc.
WHO World Health Organization All rights reserved.
http://dx.doi.org/10.1016/j.jpeds.2014.08.033

1166

the other school in the Northern part of Singapore ranked
among the bottom 20 schools. A third school (Western prov-
ince) was enrolled in 2001. Initially, 2913 children were re-
cruited for the study with a participation rate of 67.9%
(1979 participants). Children from grades 1 and 2 from an
eastern school (n = 660) and children from grades 1, 2, and
3 from a northern school (n = 1023) were invited to partici-
pate in November 1999, and children from grades 1, 2, and 3
from a western school (n = 1230) were enrolled in May 2001.
Children with medical conditions (n = 94), such as heart dis-
orders, syndrome-associated myopia, or eye disorders, such
as cataracts, were excluded from the study. In 2006, 1251 par-
ticipants attended a follow-up examination. After excluding
participants with missing BMI measurements or without
gradable retinal photographs at either visit (n = 65), a total
of 421 participants were left for analysis.
The Ethics Committee of the Singapore Eye Research Insti-
tute approved the study, and the conduct of the study fol-
lowed the tenets of the Declaration of Helsinki. Written
informed consent was obtained from all parents after the
nature of the study was explained.
All participants were examined on the school premises by a
team of ophthalmologists, optometrists, and research assis-
tants on both visits. After pupil dilatation with cyclopentolate
1%, digital retinal photographs centered on the optic disc
were taken of both eyes using a Canon CR6-45NM non-
mydriatic camera (Tochigiken, Japan).
The methods used to measure and summarize retinal
vascular caliber from digitized photographs after standard-
ized protocols have been described.18,19 Briefly, a
computer-based program was used to measure the caliber
of all retinal vessels located 0.5-1 disc diameter from the optic
disc margin in the digitized retinal photographs. Before mea-
surement, an image conversion factor was derived from 50
randomly selected images, calculated as a standard vertical
optic disc diameter (assumed to be 1800 mm) divided by
optic disc diameter in pixels. The conversion factor in this
study was 7.67 mm per pixel. Individual retinal vascular
caliber measurements from an eye were summarized as an
average index according to formulae described elsewhere.20
These indices, the central retinal artery and vein equivalents
(CRAE and CRVE), represent the average arteriolar and ven-
ular caliber of that eye.
Trained graders, masked to participant identity and char-
acteristics, performed the retinal vascular caliber measure-
ments for both visits. Retinal vascular caliber in the right
eye was measured. Left eye measurements were performed
when photographs of the right eye were ungradable. Re-
measurement of 50 retinal images 2 weeks apart showed
high reproducibility, with intraclass correlation coefficients
of 0.873 for CRAE and 0.928 for CRVE.
Height, weight, and blood pressure measurements were
performed on school premises using standardized proto-
cols.21 Height was measured with students standing and
without shoes. Weight was measured using a standard
portable weighing machine calibrated before the beginning
of the study. BMI was calculated as the weight divided by
Vol. 165, No. 6  December 2014
the square of the height (kg/m2). Sex- and age-specific BMI
SDS or Z-scores were calculated using the World Health Or-
ganization (WHO) AnthroPlus software (2009), which used
the 2007 WHO reference growth charts for ages 5-19 years.22
Blood pressure was measured in the seated position after
5 minutes of rest using an automated sphygmomanometer
(Omron HEM 705 LP; Omron Healthcare, Inc, Bannock-
burn, Illinois) with the appropriate cuff size. The cuff size
was selected to ensure that the bladder spanned the circum-
ference of the arm and covered at least 75% of the upper arm
without obscuring the antecubital fossa. The average of
3 separate measurements of systolic blood pressure and dia-
stolic blood pressure was used for analysis. Mean arterial
blood pressure was calculated as one-third of the systolic
blood pressure plus two-thirds of the diastolic blood pres-
sure. Blood pressure measurement methods did not differ be-
tween the 2 visits.
Cycloplegic refraction was obtained using calibrated au-
torefractometers (RK5; Canon, Inc Ltd, Tochigiken, Japan).
Axial length was obtained using a biometry ultrasound unit
(probe frequency, 10 mHz; Echoscan US-800; Nidek Co.
Ltd, Tokyo, Japan). One drop of 0.5% proparacaine was
instilled into each eye before ultrasound biometry measure-
ments were made. The average of 6 values was taken with
the SD of the 6 measurements <0.12 mm.
Statistical Analyses
We compared characteristics of included and excluded par-
ticipants using the Student t test. Participant characteristics
at the 2001 and the 2006 visits had their means and SD
compared for differences using paired t tests. Linear regres-
sion models were used to analyze the association between
BMI and retinal vessel caliber, initially adjusted for age
and sex (model 1), and then additionally adjusted for race,
spherical equivalent, birth weight, and fellow retinal vessel
caliber (model 2). Beta coefficients and 95% CIs are re-
ported. The associations between changes in retinal vascular
caliber and BMI across the 5-year interval were compared
using ANOVA across 3 ordinal categories of BMI change.
All statistical analyses used SPSS v 17 (SPSS Inc, Chicago,
Illinois).
Results
Out of 421 participants, 49.2% were male and 50.8% were fe-
male; 81.9% were Chinese, 12.6% Malay, 5.0% Indian, and
0.5% of other ethnicities. Compared with participants
excluded from the analysis because of incomplete BMI data
or ungradable images (n = 65), included participants were
slightly older (7.93 vs 7.76; P = .001) and had more myopic
spherical equivalent refraction ( 1.59 D vs 0.34 D;
P < .001) but were similar in other characteristics.
The changes in characteristics between the 2 visits are out-
lined in Table I. Weight, height, BMI, and BMI Z-score
significantly increased between the 2001 and 2006 visits.
BMI increased from an average of 17.0-19.3 kg/m2
(P < .001), and BMI Z-score from 0.35-0.44 (P = .048).
1167
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Table I. Changes in participant characteristics between 2001 and 2006 visits

2001 visit 2006 visit Difference between visits
Characteristics N Mean SD Mean SD Mean SD P*
Age (y) 421 7.9 0.86 11.9 0.86
Weight (kg) 421 31.4 8.97 50.2 11.54 18.79 7.38 <.001
Height (cm) 421 134.7 9.97 160.9 8.50 26.24 7.64 <.001
BMI (kg/m2) 421 17.0 3.03 19.3 3.57 2.25 2.26 <.001
BMI Z-score 421 0.35 1.31 0.44 1.43 0.09 0.98 .048
Spherical equivalent (diopters) 418 1.1 2.15 3.9 2.88 2.23 1.45 <.001
Mean arterial blood pressure (mm Hg) 208 79.5 9.70 80.1 10.46 0.66 11.73 .415
Systolic blood pressure (mm Hg) 208 110.4 14.27 111.3 14.59 0.88 15.56 .418
Diastolic blood pressure (mm Hg) 208 64.0 9.36 64.5 9.60 0.56 12.08 .506
CRAE (mm) 421 147.01 11.13 147.47 12.04 0.46 9.78 .340
CRVE (mm) 421 216.99 16.81 220.40 17.13 3.41 13.24 <.001

Blood pressure data for both visits were only available for 208 subjects.
Data presented are mean and SD.
*Paired t test was used to assess differences between 2001 and 2006 visits.

Blood pressure measurements were similar between the
2 visits. Mean CRVE increased by 3.4 mm, from 217.0 mm
in 2001 to 220.4 mm in 2006 (P < .001). In contrast, mean
CRAE remained similar over the 5-year period (P = .340).
Table II shows that in multivariate analysis adjusted for
potential confounders (model 2), BMI was cross-sectionally
associated with narrower CRAE and wider CRVE at both
2001 and 2006 visits. Over the 5-year interval (Table III),
each 1 kg/m2 increase in BMI was associated with a
significant increase in CRVE (0.597 mm; P = .044), but not
with CRAE. The associations were similar for BMI Z-score
and retinal vascular caliber (P = .047). The Figure
(available at www.jpeds.com) illustrates the 5-year change
in CRVE with increased BMI in one of the subjects.
Incident BMI at the initial visit is associated with a wider
follow-up CRVE (0.760 mm increase for every 1 kg/m2 of
BMI, P = .003) and narrower follow-up CRAE ( 0.472 for
every 1 kg/m2 of BMI, P = .010; Table IV). Conversely,
wider initial CRVE and narrower initial CRAE are
associated with higher BMI and BMI Z-scores in the
follow-up visit (P < .05; Table V).
Discussion
We showed that BMI is related to retinal vascular caliber over
time. The association between BMI and retinal arteriolar
caliber has not been consistently reported. For example, the
Multi-Ethnic Study of Atherosclerosis,11 the Rotterdam
Study,10 and the Sydney Childhood Eye Study5 have all
shown a significant association between higher BMI and nar-
rower retinal arteriolar caliber, though such finding was not
observed in some other studies.8,9,23,24 Our cross-sectional
data similarly suggest an inverse relationship between BMI
and retinal arteriolar caliber. However, for model 1, this as-
sociation was significant only at the 2006, but not 2001, visit.
The exact reason for such disparity is not apparent, but it
could be due to the age of the study sample. As children
grow older, overweight and obesity might have a more pro-
found effect on the microvasculature. This theory needs to
be verified in future studies.
Our findings may have several clinical and research impli-
cations. Retinal vessel analysis is potentially useful as a nonin-
vasive clinical tool to predict or monitor the development
and progression of cardiovascular diseases and risk factors.25
This study showed that narrower arteriolar caliber and wider
venular caliber at baseline increases the risk of higher BMI at
5 years. Consistent with our findings, 2 recent studies have
shown that adults with wider retinal venular caliber at base-
line had an increased risk of incident obesity at 5 and
15 years.23,24 Other prospective studies have shown that
measuring retinal vascular caliber might provide clinically
meaningful information on the risk of stroke, coronary heart

Table II. Cross-sectional relationships between retinal vascular caliber and BMI
Model 1 Model 2
Difference in retinal vascular caliber per Difference in retinal vascular caliber
n unit increase in BMI (kg/m2) P value n per unit increase in BMI (kg/m2) P value
Arteriolar caliber
CRAE (2001 visit) BMI (2001 visit) 412 0.242 ( 0.593 to 0.110) .178 412 0.462 ( 0.778 to 0.145) .004
CRAE (2006 visit) BMI (2006 visit) 412 0.392 ( 0.710 to 0.074) .016 412 0.574 ( 0.843 to 0.306) <.001
Venular caliber
CRVE (2001 visit) BMI (2001 visit) 412 0.660 (0.127 to 1.194) .015 412 0.808 (0.325 to 1.290) .001
CRVE (2006 visit) BMI (2006 visit) 412 0.459 (0.000 to 0.919) .050 412 0.748 (0.370 to 1.126) <.001

Statistically significant P values are in bold.

Model 1 adjusted for age and sex.
Model 2 adjusted for age, sex, race, spherical equivalent, birth weight, and fellow retinal vessel.

1168 Kurniawan et al
December 2014 ORIGINAL ARTICLES

Table III. Longitudinal relationships between retinal vascular caliber and BMI
Model 1 Model 2
Difference in retinal vascular caliber Difference in retinal vascular caliber
per unit increase in BMI (kg/m2) or BMI per unit increase in BMI (kg/m2) or BMI
n Z-score P value n Z-score P value
Arteriolar caliber
Change in CRAE Change in BMI 412 0.284 ( 0.704 to 0.137) .185 412 0.355 ( 0.753 to 0.043) .081
Change in CRAE Change in BMI Z-score 412 0.459 ( 1.558 to 0.641) .413 412 0.707 ( 1.751 to 0.337) .184
Venular caliber
Change in CRVE Change in BMI 412 0.580 (0.009 to 1.152) .047 412 0.597 (0.016 to 1.179) .044
Change in CRVE Change in BMI Z-score 412 1.600 (0.109 to 3.092) .036 412 1.544 (0.023 to 3.065) .047

Change in values calculated between 2001 (baseline) and 2006 (follow-up) visits.
Statistically significant P values are in bold.
Model 1 adjusted for age, sex, baseline BMI, and baseline retinal vessel calibers (2001 visit).
Model 2 adjusted for age, gender, race, spherical equivalent, birth weight, baseline BMI, and baseline retinal vessel calibers (2001 visit).

disease, and microvascular complications of diabetes (eg,
diabetic retinopathy), above and beyond the conventional
risk factors.14,15,26,27 However, all of these studies focused
on a single “snap-shot” measurement of retinal vascular
caliber. Therefore, the value of serial monitoring of retinal
vascular caliber over time remained uncertain. Recently,
the Wisconsin Epidemiologic Study of Diabetic Retinopathy
demonstrated that increasing retinal venular caliber over
time was associated with subsequent risk of retinopathy
development and progression among patients with dia-
betes.27-29 This study, along with the findings of our current
study, offers further evidence of potential clinical value in se-
rial measurements of retinal vessel diameter.
Moreover, our findings might have several pathophysiolog-
ical implications on the link between obesity and microvas-
cular disease. The association between obesity and large-
vessel atherosclerotic disease has been well documented.30-32
Our study contributes to an increasing body of evidence that
obesity might also be related to small-vessel disease.7,9,33,34
Although the underlying causative mechanisms for our find-
ings remain unclear, reverse causation appears unlikely, and
several pathways have been proposed. First, obesity is a proin-
flammatory state.35 Various inflammatory markers have been
associated with retinal venular widening,36-38 and the role of
substances such as nitric oxide have been demonstrated in
experimental studies.39 Leptin, expressed in excess by adipose
cells, could increase nitric oxide synthesis leading to venular
dilatation.40 Second, an increase in body mass may exert an ef-
fect on the microvasculature independent of inflammation,24
as part of a wider metabolic derangement similar to the alter-
ation in microvascular perfusion seen in diabetes.41 Third, the
venous system is a major reservoir for blood volume, which
may increase in persons with greater body mass because of
growth. Thus, venular widening could be a normal physiolog-
ical response to raise total body capacitance, in order to
accommodate the increased blood volume associated with
growth in children.42
Strengths of our study include its unique longitudinal
design, standardized measurements of systemic and ocular
variables, use of age- and sex-specific standardized WHO
BMI Z-scores, and a sample of generally healthy young
schoolchildren. Generally, healthy schoolchildren are likely
to have fewer confounding effects from chronic diseases
and other factors (eg, hypertension, diabetes, smoking,
lipids) on retinal vascular caliber as expected among older
adult populations. However, our study did not collect these
data, so we could not determine any potential confounding
effects of these factors.
Several limitations should also be noted. First, the possibil-
ity of selection bias cannot be totally excluded as a significant
proportion of participants were excluded due to incomplete
data or ungradable retinal images. However, there was no sig-
nificant difference in BMI and blood pressure measurements
between the excluded and included participants. Second,
BMI might not be the most precise representation of body
fat distribution.43 Although it is a practical and commonly
used clinical measure of obesity, it may be less accurate
than skinfold measurements and give erroneous estimation
of adiposity across different body shapes and athleticity.44
Pubertal status may also influence body fat distribution,
however, these data were not available. Third, in our gener-
ally healthy sample of children, there were too few clinically

Table IV. Relationships between BMI and follow-up retinal vascular caliber
CRAE (2006 visit) CRVE (2006 visit)
Difference in retinal vascular caliber per Difference in retinal vascular caliber
BMI n unit increase in BMI (kg/m2) or BMI Z-score P value n per unit increase in BMI (kg/m2) or BMI Z-score P value
BMI (2001 visit) 412 0.472 ( 0.829 to 0.115) .010 412 0.760 (0.261 to 1.258) .003
Change in BMI* 412 0.352 ( 0.834 to 0.130) .152 412 0.357 ( 0.318 to 1.032) .299
Change in BMI Z-score* 412 0.569 ( 1.833 to 0.695) .377 412 0.577 ( 1.189 to 2.343) .521

Adjusted for age, sex, race, spherical equivalent, birth weight, and fellow retinal vessel. Change models adjusted additionally for baseline BMI and retinal vessel calibers (2001 visit).
Statistically significant P values are in bold.
*Between 2001 and 2006 visits.

The Relationship between Changes in Body Mass Index and Retinal Vascular Caliber in Children 1169
THE JOURNAL OF PEDIATRICS  www.jpeds.com
Table V. Relationships between retinal vascular caliber and follow-up BMI
BMI (2006 visit)
Difference in BMI per unit increase in
Retinal vascular caliber n retinal vascular caliber (mm)
Arteriolar caliber
CRAE (2001 visit) 412 0.042 ( 0.078 to 0.006)
Change in CRAE* 412 0.018 ( 0.055 to 0.018)
Venular caliber
CRVE (2001 visit) 412 0.025 (0.002 to 0.048)
Change in CRVE* 412 0.015 ( 0.012 to 0.041)
Adjusted for age, sex, race, spherical equivalent, birth weight, and fellow retinal vessel. Change models adjusted additionally for baseline BMI and retinal vessel calibers (2001 visit).
Statistically significant P values are in bold.
*Between 2001 and 2006 visits.
obese children for categorical analysis by clinical weight sta-
tus. Finally, our study had a relatively short duration of
follow-up. A longer follow-up study may help to determine
whether the relationship between changes in BMI and in
retinal venular caliber persists into adulthood.
Progressive widening of retinal venules could be a manifes-
tation of adverse microvascular effects of obesity early in life.
Additional research is warranted to further elucidate the po-
tential value of monitoring retinal vascular caliber over time,
as a surrogate marker of microvascular damage from obesity
and other cardiovascular risk factors. n
Submitted for publication Dec 11, 2013; last revision received Jun 30, 2014;
accepted Aug 18, 2014.
Reprint requests: Ning Cheung, MD, Singapore Eye Research Institute, 11
Third Hospital Ave, Singapore 168751. E-mail: dannycheung@hotmail.com
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Figure. Change in venular diameter over a 5-year period in subject 366. Retinal vascular caliber is measured between 2-3 disc
diameters from the optic disc. Areas highlighted in red indicate retinal arteriolar caliber, and areas in blue indicate retinal venular
caliber. The average retinal venular caliber, CRVE, has increased between visits 1 and 2.

1171.e1 Kurniawan et al