Prevalence of Diabetic Retinopathy in The United States, 2005-2008

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ORIGINAL CONTRIBUTION

Prevalence of Diabetic Retinopathy


in the United States, 2005-2008
Xinzhi Zhang, MD, PhD
Jinan B. Saaddine, MD, MPH
Chiu-Fang Chou, DrPH
Mary Frances Cotch, PhD
Yiling J. Cheng, MD, PhD
Linda S. Geiss, MA
Edward W. Gregg, PhD
Ann L. Albright, PhD, RD
Barbara E. K. Klein, MD, MPH
Ronald Klein, MD, MPH

IABETIC RETINOPATHY IS THE

leading cause of new cases of


legal blindness among adults
aged 20 to 74 years in the
United States.1 Vision loss due to diabetic retinopathy occurs through a variety of mechanisms, including retinal
detachment, preretinal or vitreous hemorrhage, associated neovascular glaucoma, and macular edema or capillary
nonperfusion.2 The presence of diabetic retinopathy may indicate microcirculatory dysfunction in other organ
systems.3,4 Diabetes-related blindness is
a personal catastrophe to the individual and costs the United States approximately $500 million annually.5
However, risk of vision loss due to diabetic retinopathy can be reduced by effective control of serum glucose and
blood pressure and by its early detection and timely treatment.6-8 The efficacy and cost-effectiveness of early detection and treatment of diabetic
retinopathy is well established.9,10
Investigating the prevalence of diabetic retinopathy is important because it is a key indicator of systemic
diabetic microvascular complications,
and as such, a sentinel indicator of the
impact of diabetes. Despite the docu-

Context The prevalence of diabetes in the United States has increased. People with
diabetes are at risk for diabetic retinopathy. No recent national population-based estimate of the prevalence and severity of diabetic retinopathy exists.
Objectives To describe the prevalence and risk factors of diabetic retinopathy among
US adults with diabetes aged 40 years and older.
Design, Setting, and Participants Analysis of a cross-sectional, nationally representative sample of the National Health and Nutrition Examination Survey 2005-2008
(N=1006). Diabetes was defined as a self-report of a previous diagnosis of the disease
(excluding gestational diabetes mellitus) or glycated hemoglobin A1c of 6.5% or greater.
Two fundus photographs were taken of each eye with a digital nonmydriatic camera and
were graded using the Airlie House classification scheme and the Early Treatment Diabetic Retinopathy Study severity scale. Prevalence estimates were weighted to represent
the civilian, noninstitutionalized US population aged 40 years and older.
Main Outcome Measurements Diabetic retinopathy and vision-threatening diabetic retinopathy.
Results The estimated prevalence of diabetic retinopathy and vision-threatening
diabetic retinopathy was 28.5% (95% confidence interval [CI], 24.9%-32.5%) and
4.4% (95% CI, 3.5%-5.7%) among US adults with diabetes, respectively. Diabetic
retinopathy was slightly more prevalent among men than women with diabetes
(31.6%; 95% CI, 26.8%-36.8%; vs 25.7%; 95% CI, 21.7%-30.1%; P=.04). NonHispanic black individuals had a higher crude prevalence than non-Hispanic white
individuals of diabetic retinopathy (38.8%; 95% CI, 31.9%-46.1%; vs 26.4%; 95%
CI, 21.4%-32.2%; P=.01) and vision-threatening diabetic retinopathy (9.3%; 95%
CI, 5.9%-14.4%; vs 3.2%; 95% CI, 2.0%-5.1%; P = .01). Male sex was independently associated with the presence of diabetic retinopathy (odds ratio [OR], 2.07;
95% CI, 1.39-3.10), as well as higher hemoglobin A1c level (OR, 1.45; 95% CI, 1.201.75), longer duration of diabetes (OR, 1.06 per year duration; 95% CI, 1.03-1.10),
insulin use (OR, 3.23; 95% CI, 1.99-5.26), and higher systolic blood pressure (OR,
1.03 per mm Hg; 95% CI, 1.02-1.03).
Conclusion In a nationally representative sample of US adults with diabetes aged
40 years and older, the prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy was high, especially among Non-Hispanic black individuals.
www.jama.com

JAMA. 2010;304(6):649-656

mented increase in the prevalence of


diabetes in the US population,11 national population-based data on the
prevalence and severity of diabetic retinopathy remain scarce, with previous
nationwide prevalence estimates dating back to 1988-1994 (National Health
and Nutrition Examination Surveys III
[NHANES III]).12 In 2004, the Eye
Diseases Prevalence Research Group estimated the prevalence of diabetic retinopathy from the compilation of 8 sepa-

2010 American Medical Association. All rights reserved.

Author Affiliations: Division of Diabetes Translation,


National Center for Chronic Disease Prevention and
Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia (Drs Zhang, Saaddine, Chou,
Cheng, Geiss, Gregg, and Albright); Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD
(Dr Cotch); Department of Ophthalmology and Visual Sciences, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin (Drs B.
Klein and R. Klein).
Corresponding Author: Xinzhi Zhang MD, PhD, Division of Diabetes Translation, National Center for
Chronic Disease Prevention and Health Promotion,
Centers for Disease Control and Prevention, 4770 Buford Hwy, NE (K-10), Atlanta, GA 30341-3727
([email protected]).

(Reprinted) JAMA, August 11, 2010Vol 304, No. 6

649

DIABETIC RETINOPATHY IN THE UNITED STATES

rate population-based studies from the


United States and elsewhere conducted in the late 1980s or early
1990s.13 Their report recommended
that more recent estimates of diabetic
retinopathy prevalence be obtained
from the nationally representative
sample of NHANES.
Moreover, several other populationbased studies reported a decrease in the
prevalence and incidence of severe diabetic retinopathy and related visual impairment.14-16 However, these findings
were limited to regional cohorts and the
status of diabetic retinopathy at the national level remains unknown. Thus,
the principal aim of this study is to describe the most recent prevalence and
risk factors of diabetic retinopathy in
the US population aged 40 years and
older using NHANES 2005-2008.
METHODS
Study Population

NHANES are national representative


surveys conducted by the National Center for Health Statistics, part of the Centers for Disease Control and Prevention. The data consist of samples of the
US noninstitutionalized civilian population, which were obtained using a
stratified multistage probability design with planned oversampling of certain age and racial/ethnic groups.17
There were 6797 individuals aged 40
years and older interviewed for sociodemographic, medical, and family information and had a full medical examination at the medical examination
center in NHANES 2005-2008. The
NHANES 2005-2008 response rate for
the interview sample aged 40 years and
older was 71% and 69% for the examined sample.18 The NHANES protocol
was approved by a human subjects review board and written informed consent was obtained from all participants.
Fundus Photography

NHANES 2005-2008 used the Canon


CR6-45NM ophthalmic digital imaging
system and Canon EOS 10D digital
camera (Canon, Tokyo, Japan) to take
2 digital images per eye (total 4 im650

ages per participant) through a nonpharmacologically dilated pupil. Participants were seated in a windowless
room with the lights turned off to allow the pupils to dilate naturally in
preparation for the retinal imaging examination. One image was centered on
the macula and the second on the optic nerve. The digital images were
graded by masked photo graders at the
University of Wisconsin Ocular Epidemiologic Reading Center, Madison,
using a modification of the Airlie House
classification system.19-21 Capture and
grading of digital images and quality
control by the Wisconsin group have
been described in detail previously.22
Survey participants who had no light
perception or severe visual impairment in both eyes or had a severe infection in one or both eyes were excluded (n = 13). Complete data of
fundus photographs of both eyes were
obtained for 5371 (79%) participants
aged 40 years and older who had full
medical examinations.
Reasons for having incomplete data
(n = 1426, 21%) included insufficient
time to finish the examination (ie, arrived late or left early; n = 514; 42%),
physical limitation (n=238; 19%), eyespecific limitation (n=193; 16%), participants refusal (n=119; 10%), communication problems (n=40; 3%), and
others. Those individuals with incomplete data were more likely to be older,
non-Hispanic black, with less than a
high school education, higher systolic
blood pressure, higher glycated hemoglobin A1c level, and a history of using
insulin than participants with complete gradable photographs (all
P.001). We further examined the potential influence of nonresponse bias
due to the exclusion of participants
without complete gradable photographs by adjusting the original sampling weights using the standard
weightingclass method.23,24 Findings
using these adjusted weights led to only
minor differences in point and variance estimates (0%-0.5%), indicating
minimal impact of nonresponse; therefore, we present all estimates using the
original sampling weights.

JAMA, August 11, 2010Vol 304, No. 6 (Reprinted)

Diabetic retinopathy was defined as


the presence of 1 or more retinal microaneurysms or retinal blot hemorrhages with or without more severe lesions (hard exudates, soft exudates,
intraretinal microvascular abnormalities, venous beading, retinal new vessels, preretinal and vitreous hemorrhage, and fibroproliferans) using the
Early Treatment Diabetic Retinopathy
Study (ETDRS) grading standards.19
Diabetic retinopathy was further
categorized as nonproliferative and
proliferative determined by assessment of the presence of retinal neovascularization or abnormal growth of
new retinal blood vessels into the vitreous. Vision-threatening diabetic
retinopathy, a level that may soon
result in vision loss if left untreated,
was defined as the presence of severe
nonproliferative diabetic retinopathy,
proliferative diabetic retinopathy, or
clinically significant macular edema.
Clinically significant macular edema
was considered present when edema
involved the fovea or was within 500
microns of the fovea, or when a
1disc area of edema was present
with at least a portion of it within the
macula. Outcomes for this study were
defined on the basis of the worse of
the 2 eyes.
Other Measurements

Diabetes was defined as self-report of


a previous diagnosis of the disease by
a clinician (excluding gestational diabetes mellitus) or hemoglobin A1c of
6.5% or greater (American Diabetes Associations new diagnostic criterion for
undiagnosed diabetes).25 Although hemoglobin A1c does not capture completely the increased risk of microvascular complications due to diabetes,26
the diagnostic hemoglobin A1c cut point
of 6.5% was determined to be an inflection point for retinopathy prevalence, as is also true for the diagnostic
thresholds of the glucose-based
test.25,27,28 The final analytic sample consisted of 1006 individuals with diabetes aged 40 years and older (n=795 for
diagnosed diabetes; n=211 for undiagnosed diabetes).

2010 American Medical Association. All rights reserved.

DIABETIC RETINOPATHY IN THE UNITED STATES

All participants were asked about


their age, sex, race/ethnicity (nonHispanic white, non-Hispanic black,
Mexican American, and others [including those who selected multiple races
and non-Mexican American Hispanics]), educational attainment (less than
high school, high school education, or
higher), and health insurance status.
Consistent with previous epidemiologic studies,29-31 risk factors for diabetic retinopathy and vision-threatening diabetic retinopathy (hemoglobin
A1c, duration of diabetes, insulin use
[yes/no], systolic and diastolic blood
pressure, body mass index [BMI, calculated as weight in kilograms divided by height in meters squared], current smoking status [yes/no], and
history of cardiovascular diseases [CVD;
yes/no]) were examined. Hemoglobin
A1c, duration of diabetes, and systolic
and diastolic blood pressure were used
as continuous variables. Hemoglobin
A1c was used as the surrogate for blood
glucose level and measured by a highperformance liquid chromatographic
assay as used in the Diabetes Control
and Complications Trial. 7 Insulin
therapy indicated that the participant
had type 1 diabetes or their diabetes
could not otherwise be controlled without insulin. We used measured height
and weight to calculate BMI and divided respondents into 3 groups: normal/underweight (BMI25), overweight (BMI 25-30), and obese
(BMI 30). Prior history of CVD was
ascertained by self-report of coronary
heart disease, angina, myocardial
infarction, stroke, or congestive heart
failure.
Statistical Methods

Statistical analyses were conducted


using SAS version 9.2 (SAS Institute,
Cary, North Carolina) and SUDAAN
version 10.1 software (Research Triangle Institute, Research Triangle Park,
North Carolina) to calculate national
estimates and their standard errors
while accounting for the complex survey design of the survey. Taylor series
linearization was used for variance estimation.32 The NHANES 2005-2008

study has sufficient sample size to detect a relative difference of 6% (effective sample size = sample size/design
effect = 1006/1.7 = 591) at 85% power
and an level of .05.
Characteristics of the study population are described using means for continuous variables and percentages for
categorical variables. For continuous
variables, t tests were used and for categorical variables the 2 test. We estimated the crude prevalence of diabetic retinopathy and vision-threatening
diabetic retinopathy by age, sex, and
race/ethnicity in the diabetic and overall US population. Multiple logistic regressions were used to assess the association between diabetic retinopathy
and vision-threatening diabetic retinopathy, vs clinical potential risk factors for diabetic retinopathy and visionthreatening diabetic retinopathy after
controlling for age, sex, race/ethnicity,
and education attainment.
Predictive margins, odds ratios (OR),
and 95% confidence intervals (CI) for
each were calculated. Associations were
considered to be significant if the P
value was less than .05. Additionally,
we compared the prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy in NHANES
2005-2008 with NHANES III by using
the right eye if the last digit of the participant identification number was even
and the left eye if it was odd. The prevalence estimates were age standardized
to the 2000 US census population.
RESULTS
In 2005-2008, the estimated (weighted)
crude prevalence of diabetic retinopathy and vision-threatening diabetic
retinopathy was 28.5% (95% CI, 24.9%32.5%) and 4.4% (95% CI, 3.5%-5.7%),
respectively, among persons with diabetes aged 40 years and older (TABLE 1).
Extrapolating to the overall US population in the same period, the prevalence
nation wide would be 3.8% (95% CI,
3.2%-4.5%) and 0.6% (95% CI, 0.5%0.8%). Approximately 1.5% (95% CI,
1.1%-2.2%) of adults with diabetes
had proliferative diabetic retinopathy
and 2.7% (95% CI, 1.8%-4.0%) had

2010 American Medical Association. All rights reserved.

clinically significant macular edema. In


other words, approximately 0.2% (95%
CI, 0.1%-0.3%) of adults aged 40 years
or older had proliferative diabetic retinopathy and 0.4% (95% CI, 0.2%0.5%) had clinically significant macular edema.
Among individuals with diabetes, no
significant difference was found in the
prevalence of diabetic retinopathy
between those aged 40 to 64 years and
those aged 65 years and older (28.0%;
95% CI, 23.0%-33.6%; vs 29.5%; 95%
CI, 25.4%-33.9%; P = .64). Approximately 31.6% (95% CI, 26.8%-36.8%)
of men with diabetes had diabetic
retinopathy and approximately 25.7%
(95% CI, 21.7%-30.1%) of women with
diabetes had diabetic retinopathy
(P = .04). Approximately 26.4% (95%
CI, 21.4%-32.2%) of non-Hispanic
white individuals, 38.8% (95% CI,
31.9%-46.1%) of non-Hispanic black
individuals, and 34.0% (95% CI,
26.7%-42.1%) of Mexican American
individuals with diabetes had diabetic
retinopathy (P = .008). Prevalence of
vision-threatening diabetic retinopathy was not statistically different
between individuals aged 40 to 64 years
and those aged 65 years and older (4.1%;
95% CI, 2.8%-5.8%; vs 5.1%; 95% CI,
3.5%-7.3%; P =.41). There was no significant difference in the prevalence of
vision-threatening diabetic retinopathy between men and women (4.2%;
95% CI, 2.8%-6.1%; vs 4.7%, 95% CI,
3.2%-6.9%; P = .67). Approximately
3.2% (95% CI, 2.0%-5.1%) of nonHispanic white individuals, 9.3% (95%
CI, 5.9%-14.4%) of non-Hispanic black
individuals, and 7.3% (95% CI, 3.9%13.3%) of Mexican American individuals with diabetes had vision-threatening diabetic retinopathy (P=.006).
Extrapolating survey findings to the
entire US adult population in the same
period (without regard for diabetes status), the prevalence of diabetic retinopathy was significantly higher among
individuals who were aged 65 years or
older than those younger than 65 years
of age (6.1%; 95% CI, 5.1%-7.3%; vs
3.1%; 95% CI, 2.4%-3.9% P.001). Approximately 4.3% (95% CI, 3.5%-

(Reprinted) JAMA, August 11, 2010Vol 304, No. 6

651

DIABETIC RETINOPATHY IN THE UNITED STATES

5.3%) of adult men in the United States


had diabetic retinopathy compared with
3.3% (95% CI, 2.7%-4.1%) of adult
women (P=.046). Non-Hispanic black
individuals and Mexican American individuals had a higher prevalence of diabetic retinopathy than non-Hispanic
white individuals (9.6%; 95% CI, 7.7%11.9%; 6.7%; 95% CI, 5.4%-8.4%; vs
2.9%; 95% CI, 2.2%-3.9%; both
P .001).
Prevalence of vision-threatening diabetic retinopathy was higher among
people aged 65 years or older than those
aged 40 to 64 years (1.0%; 95% CI,
0.7%-1.5%; vs 0.4%; 95% CI, 0.3%0.7%; P=.009). There was no significant difference in the prevalence of vision-threatening diabetic retinopathy
between men and women observed
(0.6%; 95% CI, 0.4%-0.9%; vs 0.6%;

95% CI, 0.4%-0.9%; P =.81). Approximately 0.4% (95% CI, 0.2%-0.6%) of


non-Hispanic white individuals, 2.3%
(95% CI, 1.5%-3.6%) of non-Hispanic
black individuals, and 1.4% (95% CI,
0.8%-2.7%) of Mexican American individuals had vision-threatening diabetic retinopathy (P .001).
Among individuals with diabetes,
those with diabetic retinopathy were
more likely to be men (53.7%; 95% CI,
47.4%-59.9%; vs 46.5%; 95% CI, 41.5%51.6%; P=.04) than those without diabetic retinopathy (TABLE 2). Diabetic
individuals with diabetic retinopathy
had a longer duration of diabetes (15.0
years; 95% CI, 13.4-16.5; vs 7.3 years;
95% CI, 6.5-8.1; P .001), higher systolic blood pressure (134.2 mm Hg;
95% CI, 131.6-136.9; vs 130.1 mm Hg;
95% CI, 127.9-132.4; P = .04), and

higher hemoglobin A1c level (7.9%; 95%


CI, 7.6%-8.1%; vs 7.0%; 95% CI, 6.8%7.1%; P.001) than those without diabetic retinopathy. Diabetic individuals with diabetic retinopathy were more
likely to use insulin than those with diabetes but no diabetic retinopathy
(44.6%; 95% CI, 38.5%-50.9%; vs
10.2%; 95% CI, 8.1%-12.7%; P.001).
TABLE 3 shows the associations of
various risk factors with diabetic retinopathy and vision-threatening diabetic retinopathy among individuals
with diabetes. In multivariate analysis,
independent risk factors for diabetic
retinopathy include male sex (38.1%;
95% CI, 32.6%-43.6%; vs 27.1%; 95%
CI, 22.4%-31.8%; OR, 2.07; 95% CI,
1.39-3.10), higher hemoglobin A 1c
level (OR, 1.45; 95% CI, 1.20-1.75),
longer diabetes duration (OR, 1.06

Table 1. Estimated Prevalence of Diabetic Retinopathy and Vision-Threatening Diabetic Retinopathy in Individuals With Diabetes Aged 40
Years and Older and in the Adult US Population, by Age, Sex, and Race/Ethnicity: NHANES 2005-2008
Crude Prevalence of Diabetic Retinopathy

Characteristics
Total
Age, y
40-64
65
Sex
Male
Female
Race/ethnicity
Non-Hispanic white
Non-Hispanic black
Mexican American
Other
Total
Age, y
40-64
65
Sex
Male
Female
Race/ethnicity
Non-Hispanic white
Non-Hispanic black
Mexican American
Other

324

Weighted
Size, in
Thousands c
4202

% (95%CI)
28.5 (24.9-32.5)

575
431

189
135

2588
1613

28.0 (23.0-33.6)
29.5 (25.4-33.9)

.64

504
502

173
151

2257
1944

31.6 (26.8-36.8)
25.7 (21.7-30.1)

.04

396
306
197
107

107
119
70
28

2507
1006
401
286

26.4 (21.4-32.2)
38.8 (31.9-46.1)
34.0 (26.7-42.1)
19.7 (12.5-29.7)

1006

62

Crude Prevalence of Vision-Threatening Diabetic Retinopathy


655
4.4 (3.5-5.7)
0.6 (0.5-0.8)

575
431

36
26

376
278

4.1 (2.8-5.8)
5.1 (3.5-7.3)

.41

504
502

24
38

298
356

4.2 (2.8-6.1)
4.7 (3.2-6.9)

.67

396
306
197
107

13
28
16
5

304
241
85
22

3.2 (2.0-5.1)
9.3 (5.9-14.4)
7.3 (3.9-13.3)
1.6 (0.6-3.8) d

No. a

No. b

1006

Diabetes Population
P Value

.008

.006

US Population
% (95%CI)
3.8 (3.2-4.5)

P Value

3.1 (2.4-3.9)

.001

6.1 (5.1-7.3)
4.3 (3.5-5.3)
3.3 (2.7-4.1)
2.9 (2.2-3.9)
9.6 (7.7-11.9)
6.7 (5.4-8.4)
3.3 (2.3-4.7)

0.4 (0.3-0.7)
1.0 (0.7-1.5)
0.6 (0.4-0.9)
0.6 (0.4-0.9)
0.4 (0.2-0.6)
2.3 (1.5-3.6)
1.4 (0.8-2.7)
0.3 (0.1-0.6)

.046

.001

.009

.81

.001

Abbreviations: CI, confidence interval; NHANES, National Health and Nutrition Examination Surveys.
a Number of participants with diabetes in NHANES 2005-2008.
b Number of participants with diabetes who had diabetic retinopathy or vision-threatening diabetic retinopathy in NHANES 2005-2008.
c Weighted total number of US adult population who had diabetic retinopathy or vision-threatening diabetic retinopathy.
d Estimate is considered unreliable because relative standard error is greater than 30%.

652

JAMA, August 11, 2010Vol 304, No. 6 (Reprinted)

2010 American Medical Association. All rights reserved.

DIABETIC RETINOPATHY IN THE UNITED STATES

per year duration; 95% CI, 1.03-1.10),


use of insulin (47.4%; 95% CI, 39.1%55.8%; vs 26.7%; 95% CI, 21.9%31.5%; OR, 3.23; 95% CI, 1.99-5.26),
and higher systolic blood pressure
(OR, 1.03 per mm Hg; 95% CI, 1.021.03). Moreover, longer diabetes
duration (OR=1.03 per year duration;
95% CI, 1.01-1.05), use of insulin
(7.5%; 95% CI, 4.8%-10.1%; vs 3.3%;
95% CI, 1.9%-4.7%; OR = 2.63; 95%
CI, 1.34-5.15), and higher systolic
blood pressure (OR, 1.03 per mm Hg;
95%CI, 1.01-1.06) were also associated with increased odds of visionthreatening diabetic retinopathy. The
odds of vision-threatening diabetic
retinopathy were significantly higher
among non-Hispanic black individuals than in non-Hispanic white individuals, even after controlling for all
other factors considered (9.8%; 95%
CI, 5.7%-13.8%; vs 3.3%; 95% CI,
1.6%-5.0%; OR, 3.77; 95% CI, 1.479.69).
Additionally, we found that the agestandardized prevalence of diabetic retinopathy was statistically significantly
different between 2 periods (15.8%;
95% CI, 12.7%-19.6% in NHANES III
vs 22.1%; 95% CI, 18.4%-26.3% in
NHANES 2005-2008; P=.01). A statistically significant difference of visionthreatening diabetic retinopathy was
also observed; 1.3% (95% CI, 0.7%2.3%) had vision-threatening diabetic
retinopathy from the NHANES III data
and 3.3% (95% CI, 2.4%-4.4%) from
NHANES 2005-2008 (P = .002).
COMMENT
This study provides the latest nationally representative estimates on the
prevalence and risk factors for diabetic retinopathy in the United States.
Earlier population-based studies
showed that almost all individuals with
type 1 diabetes and more than 60% of
those with type 2 diabetes develop diabetic retinopathy during the first 2 decades of the disease. 2 With the expected increased prevalence of type 2
diabetes in the population, due in part
to increasing rates of obesity and decreasing physical activity, the burden

Table 2. Comparison of Characteristics of Individuals With Diabetes Aged 40 Years and


Older, by Diabetic Retinopathy Status: NHANES 2005-2008
Weighted Mean (95% CI)
Characteristics
Age at examination, y
Duration of diabetes, y
Systolic blood pressure,
mm Hg
Diastolic blood
pressure, mm Hg
Hemoglobin A1c, %
Male sex
Race/ethnicity
Non-Hispanic white
Non-Hispanic black
Mexican American
Other
Less than high school
education
With health insurance
Insulin use
BMI a
Normal 25
Overweight 25-30
Obese 30
Smoker
History of CVD (yes)

With Diabetic
Retinopathy
61.6 (60.2-62.9)

Without Diabetic
Retinopathy
60.0 (58.9-61.0)

P Value
.04

15.0 (13.4-16.5)
134.2 (131.6-136.9)

7.3 (6.5-8.1)
130.1 (127.9-132.4)

.001
.04

67.5 (66.0-69.0)

71.6 (70.2-73.0)

.001

7.9 (7.6-8.1)

7.0 (6.8-7.1)

.001

Weighted % (95% CI)


53.7 (47.4-59.9)
46.5 (41.5-51.6)

.04

59.7 (49.5-69.1)
24.0 (18.2-30.8)
9.6 (6.2-14.4)
6.8 (4.5-10.3)
31.8 (25.1-39.3)

66.4 (56.7-74.9)
15.1 (10.6-21.1)
7.4 (4.9-11.2)
11.1 (7.0-17.2)
25.4 (21.2-30.1)

.08

85.9 (80.3-90.1)
44.6 (38.5-50.9)

89.5 (85.5-92.5)
10.2 (8.1-12.7)

.26
.001

11.3 (8.1-15.5)
31.6 (23.0-41.7)
57.1 (48.5-65.2)
17.2 (12.3-23.5)
27.8 (22.6-33.8)

11.1 (8.5-14.4)
23.8 (20.2-27.9)
65.0 (60.4-69.4)
18.0 (14.2-22.6)
20.6 (16.8-25.1)

.008

.21
.78
.06

Abbreviations: BMI, body mass index; CI, confidence interval; CVD, cardiovascular diseases; NHANES, National Health
and Nutrition Examination Surveys.
a BMI was calculated as weight in kilograms divided by height in meters squared.

of diabetic retinopathy might be expected to increase as well.33 However,


improved access to screening for and
treatment of diabetic retinopathy may
reduce the burden of diabetes-related
vision loss.
Our prevalence estimates are somewhat lower than those from a previous meta-analysis that compiled data
from 8 population-based studies of nonHispanic white, non-Hispanic black,
and Hispanic people with diabetes from
the United States and elsewhere that reported an overall estimate of prevalence of diabetic retinopathy of 40% and
a prevalence of vision-threatening diabetic retinopathy of 8%.13 However, the
studies that were included in the metaanalysis were from regional cohorts,
many were from prior decades, and
most did not include individuals with
undiagnosed diabetes. If undiagnosed
diabetes were excluded from our
sample, our estimates for diabetic reti-

2010 American Medical Association. All rights reserved.

nopathy and vision-threatening diabetic retinopathy among self-reported


diagnosed diabetes would be 32.8%
(95% CI, 28.6-37.2) and 5.2% (95% CI,
4.0-6.7), respectively.
It is also possible that the lower
prevalence reported in this study reflects a true reduction in the prevalence of diabetic retinopathy. Rates of
other diabetic complications have declined during recent decades. For example, Geiss et al34 found that hospitalization rate for lower extremity
amputations among individuals with
diabetes began decreasing in 1997. Another recent study found that ageadjusted diabetes-related end-stage renal disease decreased between 1996 and
2006.35 Improved diabetes care, such as
effective management of blood glucose levels, blood pressure, and serum
lipid levels, is likely to reduce the incidence of diabetic retinopathy. Conversely, it might also lead to increased

(Reprinted) JAMA, August 11, 2010Vol 304, No. 6

653

DIABETIC RETINOPATHY IN THE UNITED STATES

survival resulting in higher prevalence of diabetic retinopathy. Moreover, a recent longitudinal cohort study
suggested that low vision and blindness could be substantially reduced
among individuals with diagnosed
diabetes who received guidelinerecommended levels of care.36
We found that the age-standardized
prevalences of diabetic retinopathy and
vision-threatening diabetic retinopathy were statistically significantly different between NHANES III and
NHANES 2005-2008. These differ-

ences between surveys may be real or


may be attributed to improved methods used to photograph the fundus in
the more recent NHANES 2005-2008
compared with NHANES III. Two digital 45 color images of both eyes were
taken in the NHANES 2005-2008 while
in NHANES III only one 45 color film
image from 1 eye was taken. Although
some studies have shown grading of
digital images to have similar sensitivity for detecting diabetic retinopathy as
grading of film images, it is possible that
the current method led to increased de-

Table 3. Multiple Logistic Regressions for Risk Factors of Diabetic Retinopathy and
Vision-Threatening Diabetic Retinopathy in Individuals With Diabetes Aged 40 Years and
Older: NHANES 2005-2008
Diabetic Retinopathy
Characteristics
Age per y
Sex
Male
Female
Race/ethnicity
Non-Hispanic white
Non-Hispanic black
Mexican American
Other
Education
High school
High school
Health insurance
Yes
No
Hemoglobin A1c per
percentage point
Duration of diabetes per y
Insulin use
Yes
No
Systolic blood pressure
per mm Hg
Diastolic blood pressure
per mm Hg
BMI a
Normal 25
Overweight 25-30
Obese 30
Smoking status
Yes
No
History of CVD
Yes
No

Vision-Threatening
Diabetic Retinopathy

PM (95%CI)
NA

OR (95%CI)
0.99 (0.95-1.02)

PM (95%CI)
NA

OR (95%CI)
1.00 (0.95-1.05)

38.1 (32.6-43.6)
27.1 (22.4-31.8)

2.07 (1.39-3.10)
1 [Reference]

6.1 (3.4-8.8)
3.8 (1.9-5.7)

1.79 (0.67-4.80)
1 [Reference]

31.2 (25.4-37.0)
38.9 (30.4-47.4)
31.7 (19.5-43.9)
29.3 (19.9-38.6)

1 [Reference]
1.62 (0.81-3.26)
1.03 (0.39-2.76)
0.88 (0.42-1.82)

3.3 (1.6-5.0)
9.8 (5.7-13.8)
9.5 (2.0-17.0)
2.9 (0-6.5)

1 [Reference]
3.77 (1.47-9.69)
3.63 (1.05-12.56)
0.86 (0.19-3.82)

33.8 (26.9-40.7)
31.8 (26.8-36.7)

1 [Reference]
0.87 (0.51-1.50)

6.3 (3.2-9.3)
4.0 (2.1-5.9)

1 [Reference]
0.59 (0.22-1.54)

31.8 (27.2-36.4)
36.5 (25.4-47.6)
NA

0.74 (0.34-1.59)
1 [Reference]
1.45 (1.20-1.75)

5.1 (3.6-6.6)
2.5 (0-5.5)
NA

2.27 (0.54-9.52)
1 [Reference]
1.21 (0.97-1.50)

NA

1.06 (1.03-1.10)

NA

1.03 (1.01-1.05)

47.4 (39.1-55.8)
26.7 (21.9-31.5)
NA

3.23 (1.99-5.26)
1 [Reference]
1.03 (1.02-1.03)

7.5 (4.8-10.1)
3.3 (1.9-4.7)
NA

2.63 (1.34-5.15)
1 [Reference]
1.03 (1.01-1.06)

NA

0.96 (0.93-0.98)

NA

0.96 (0.94-0.98)

30.9 (21.2-40.6)

1 [Reference]

37.0 (29.4-44.6)
30.3 (25.4-35.3)

1.49 (0.71-3.13)
0.96 (0.47-1.96)

4.8 (2.2-7.4)
5.0 (2.7-7.2)

4.0 (0-8.0)

1.25 (0.29-5.41)
1.31 (0.34-5.05)

1 [Reference]

36.8 (25.4-48.3)
31.6 (27.3-35.9)

1.40 (0.67-2.92)
1 [Reference]

3.3 (1.1-5.5)
5.0 (3.5-6.5)

0.61 (0.25-1.47)
1 [Reference]

33.5 (27.0-40.0)
32.0 (27.4-36.5)

1.10 (0.72-1.71)
1 [Reference]

6.4 (2.7-10.1)
4.2 (2.3-6.0)

1.69 (0.58-4.92)
1 [Reference]

Abbreviations: BMI, body mass index; CI, confidence interval; CVD, cardiovascular disease; NA, not applicable; NHANES,
National Health and Nutrition Examination Surveys; OR, odds ratio; PM, predictive margin.
a BMI was calculated as weight in kilograms divided by height in meters squared.

654

JAMA, August 11, 2010Vol 304, No. 6 (Reprinted)

tection of both diabetic retinopathy and


vision-threatening diabetic retinopathy because of more retina being assessed in 2 images compared with 1 and
higher-quality digital images compared with earlier film images used in
NHANES III, thus limiting our ability
to directly compare results from
NHANES III and current NHANES
2005-2008 study (R.K., unpublished
data, 2009).
A previous analysis of NHANES III
data by Harris et al12 suggests that the
prevalence of diabetic retinopathy was
46% higher in non-Hispanic black
individuals and 84% higher in Mexican American individuals than in
non-Hispanic white individuals.
Although not statistically significant
at a .05 level, we also found that
among individuals with diabetes, nonHispanic black individuals (47%
higher) and Mexican American individuals (29% higher) had a higher
crude prevalence of diabetic retinopathy than their non-Hispanic white
counterparts. Moreover, the prevalence of vision-threatening diabetic
retinopathy in individuals with diabetes was 190% higher in non-Hispanic
black individuals and 130% higher in
Mexican American individuals than in
non-Hispanic white individuals. This
may be due to individuals of nonHispanic black and Mexican American heritage being more likely to have
poorer glycemic control and being
less likely to be screened and treated
for diabetic retinopathy.37 Data from
National Health Interview Survey also
suggest that non-Hispanic black individuals and Hispanics are less likely to
use eye care services.38 These findings
lend further insight to inform national
efforts to reduce disparities in care
among racial/ethnic and socioeconomic groups and preserve sight for
all adults in the United States.
Consistent with previous research,
we found that higher levels of hemoglobin A1c, longer duration of diabetes, insulin use, and higher systolic
blood pressure were independently
associated with diabetic retinopathy
in the NHANES data. 29,39-41 This is

2010 American Medical Association. All rights reserved.

DIABETIC RETINOPATHY IN THE UNITED STATES

consistent with findings from randomized controlled clinical trials that


showed that modifying identified risk
factors such as glycemic control and
blood pressure control could reduce
the burden of diabetic retinopathy
and also prevent vision loss caused by
it.7,8 Prevention efforts may also need
to target individuals with longer duration of diabetes and those using insulin. The new availability of care for
vulnerable sections of the population
should have demonstrable effect on
risk of blindness in diabetes. Furthermore, primary prevention of diabetes,
including identifying and protecting
individuals at risk (ie, by reduced
body weight and increased physical
activity), may also help delay the
onset of type 2 diabetes and reduce
complications of diabetic retinopathy.
We also found an inverse relationship
between diastolic blood pressure and
the presence of diabetic retinopathy.
The underlying reason remains unexplained and requires further exploration. It could be due to selective participation bias. However, previous
studies from Singapore42 and Africa43
also suggested a possible association
between pulse pressure (difference
between systolic and diastolic blood
pressure) and diabetic retinopathy.
The strengths of this study include
its population-based national sample,
its inclusion of individuals with undiagnosed diabetes, and improved
detection of retinopathy due to use of
digital fundus images of both eyes.
This improved methodology results in
estimates that are less biased than
those obtained from NHANES III.
However, individuals without diabetes may have retinopathy because of
higher glucose level or hypertension,
which is not assessed in the current
study. Also, due to the infrequency of
proliferative diabetic retinopathy
(n = 23) and clinically significant
macular edema (n = 37), we were
unable to provide meaningful estimates by age, sex, and race/ethnicity.
Our study is subject to several limitations. First, individuals who were institutionalized (eg, nursing home resi-

dents) were not included in the


NHANES, which may have led to an underestimate of diabetic retinopathy
prevalence. Second, we could not distinguish between type 1 and type 2 diabetes and the specific risk of diabetic
retinopathy complications. Third, there
were substantial numbers of eligible individuals with diabetes who did not
have photographs that could be graded,
which may negatively bias estimates of
diabetic retinopathy prevalence. Survey participants who had no light perception or severe visual impairment in
both eyes, or a severe infection in 1 or
both eyes were excludedthis might
negatively bias the prevalence estimates. Small sample sizes might have
prevented us from detecting differences, if they existed, between and
among subgroups. Due to limitations
inherent with the NHANES sampling
frame, we were unable to estimate the
prevalence of diabetic retinopathy and
vision-threatening diabetic retinopathy among racial/ethnic groups other
than non-Hispanic white individuals,
non-Hispanic black individuals, and
Mexican American individuals.
CONCLUSIONS
Our data demonstrate that a high prevalence of diabetic retinopathy and visionthreatening diabetic retinopathy in the
United States exists, especially among
racial/ethnic minorities. Male sex,
higher hemoglobin A1c level, longer
duration of diabetes, insulin use, and
higher systolic blood pressure were
independently associated with the presence of diabetic retinopathy. These estimates provide policy makers updated
information for use in planning eye care
services and rehabilitation. With the
aging of the population and the increasing proportion of the population with
diverse racial/ethnic heritage, the number of cases of diabetic retinopathy and
vision-threatening diabetic retinopathy will likely increase. Furthermore,
the need for eye care and for culturally
appropriate interventions that can
reduce disparity and improve access to
eye care among diverse populations is
also likely to increase.

2010 American Medical Association. All rights reserved.

Author Contributions: Dr Zhang had full access to all


of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data
analysis.
Study concept and design: Zhang, Saaddine, Cotch,
Cheng, Albright.
Acquisition of data: Chou, Cotch, Cheng, Albright,
B. Klein, R. Klein.
Analysis and interpretation of data: Zhang, Saaddine,
Chou, Cotch, Cheng, Geiss, Gregg, Albright.
Drafting of the manuscript: Zhang, Cheng, R. Klein.
Critical revision of the manuscript for important intellectual content: Saaddine, Chou, Cotch, Cheng,
Geiss, Gregg, Albright, B. Klein, R. Klein.
Statistical analysis: Zhang, Chou, Cheng, R. Klein.
Administrative, technical, or material support: Zhang,
Saaddine, Cotch, Geiss, R. Klein.
Study supervision: Saaddine, Gregg, Albright, R. Klein.
Financial Disclosures: None reported.
Funding/Support: This study was supported by the
National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention (CDC).
Funding for the National Health and Nutrition
Examination Survey (NHANES) retinal component
was provided by the Intra Agency Agreement
05FED47304 from the Division of Diabetes Translation, CDC. Funding for the vision component was
provided by the National Eye Institute, National
Institutes of Health, Intramural Research Program
grant Z01EY000402.
Role of the Sponsor: The NCHS was involved in the
design and conduct of the NHANES study and in
data collection, but was not involved in the analysis
or interpretation of the study results or in the
preparation of the manuscript. The Division of Diabetes Translation provided funding support for the
retinal component and was involved in the design
and conduct of the study; in the collection, analysis,
and interpretation of the data; and in the preparation, review, and approval of this article before submission.
Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily
represent the official position of the CDC.
Additional Contributions: We gratefully acknowledge the important statistical contribution of Theodore J. Thompson, MS, Division of Diabetes Translation, National Center for Chronic Disease Prevention
and Health Promotion, Centers for Disease Control and
Prevention, Atlanta, Georgia. Mr Thompson did not
receive compensation in association with his contribution to this article. We also thank the NHANES participants without whom this study would not be possible.

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