Diabetes Care. 2012 March; 35(3): 556–564.
© 2012 by the American Diabetes Association.
Global Prevalence and Major Risk Factors of Diabetic Retinopathy
1Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia
2Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
3Global Health Outcomes Strategy and Research, Allergan Inc., Irvine, California
4Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark
5Department of Ophthalmology, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
6Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands
7Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, U.K.
8Department of Ophthalmology, Odense University Hospital, Odense, Denmark
9Shavano Park, Texas
10Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado
11Departments of Epidemiology and Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands
12National Cancer Center/Department of Neurosurgery, Advanced Molecular Epidemiology Research Institute, Faculty of Medicine, Yamagata University, Yamagata, Japan
13Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin
14Center for Clinical Epidemiology and Biostatistics, L V Prasad Eye Institute, Hyderabad, India
15Department of Social Medicine, Samutsakhon General Hospital, Samutsakhon, Thailand
16Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, U.K.
17Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
18Department of Internal Medicine, University of Turin, Turin, Italy
19Department of Ophthalmology, Madras Diabetes Research Foundation, Chennai, India
20Institute of Ophthalmology and Visual Science, University of New Jersey, Newark, New Jersey
21Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, India
22Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
23Melbourne School of Population Health, University of Melbourne, Melbourne, Victoria, Australia
24Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
25Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California
26Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia
27Beijing Tongren Hospital, Capital Medical University, Beijing, China
28Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland
29Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
30Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
31Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia
32Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Received October 25, 2011; Accepted December 5, 2011.
This study provides a global estimate of the prevalence of DR and the severe stages of DR (PDR, DME) using individual-level data from population-based studies worldwide. On the basis of the data from all 35 studies on more than 20,000 participants with diabetes, we estimated that among individuals with diabetes, the overall prevalence of any DR was 34.6%, PDR was 7.0%, DME was 6.8%, and VTDR was 10.2%. Analyses confined only to studies with similar methodologies and ophthalmologic definitions showed that the age-standardized prevalence of any DR was 35.4%, PDR was 7.2%, DME was 7.4%, and VTDR was 11.7%, among individuals with diabetes. The prevalence estimates of any DR and VTDR were similar in men and women and were highest in African Americans and lowest in Asians. Prevalence rates were substantially higher in those with type 1 diabetes and increased with duration of diabetes, and values for HbA1c, blood pressure, and cholesterol. Extrapolated to the world diabetes population in 2010, we estimate that approximately 93 million may have some DR, and 28 million may have sight-threatening stages of DR.
The prevalence of DR has been previously reported in a number of population-based samples (11
). However, prevalence estimates varied considerably across some studies, depending on the population and study methodology. For example, variable prevalence rates were reported between populations of different ethnicities (e.g., 32.4% in an Australian Caucasian cohort (14
) vs. 48.0% in a Mexican American cohort (15
)) as well as between different populations of the same ethnicity (e.g., 35% in a U.S. Caucasian cohort (13
) and 15.3% in a more recent Australian Caucasian cohort). More important, prevalence estimates for the more severe and vision-threatening end points, such as PDR and DME, are scarce, due to the small numbers of these cases from individual population-based studies. Published estimates for VTDR prevalence (17
), for example, ranges widely, from 1.2 (17
) to 32.2% (18
). Our study provides the first precise estimates for these important clinical subgroups of DR.
The most comparable study to ours is the pooled analysis for prevalence of DR in the U.S. (6
). On the basis of eight population studies derived from the U.S. and Australia, an overall prevalence of 40% for any DR and 8% for VTDR was reported (6
). These estimates, however, represented findings limited to individuals aged older than 40 years and only with type 2 diabetes, were largely derived from individuals of Caucasian background, did not evaluate PDR and DME separately, and did not include studies from Asia. Ours is the first synthesis of individual-level data from all eligible population-based studies worldwide with a sufficiently large sample to allow a more precise estimation of the prevalence of PDR and DME.
Some of the differences in DR prevalence between individual studies may be partly attributed to the differing periods of the studies ( and Supplementary Table 3
). Improvements in the management of DR and diabetes, and increased screening for diabetes, may have led to lower DR incidence and prevalence over time (21
). Furthermore, DR susceptibility may also vary among ethnic groups. In support of the latter hypothesis, a number of multiethnic cohort studies have reported a higher DR prevalence among Mexican Americans than in non-Hispanic whites (5
). Others, however, showed a similar or lower prevalence of DR in African Americans (18
) and Mexican Americans (24
) than in non-Hispanic whites. In some studies (5
), after adjusting for putative DR risk factors, racial differences in the prevalence of DR was attributed to differing levels of risk factors for DR, but in others, the excess risk was unexplained (22
). Differences in socioeconomic factors, including access to and the level of diabetes care, and possibly genetic susceptibility (26
), may also possibly explain some of the disparities in rates and severity of DR in the different ethnic groups. In addition, racial differences in the effect of DR risk factors could also have accounted for some of these variations (23
). Population-based studies incorporating host and environmental data are needed to further clarify the effect of race and ethnicity on DR prevalence.
We highlight several key points regarding the major risk factors for DR: First, we confirm the importance of the three major risk factors for DR—diabetes duration (17
), and blood pressure (17
)—and suggest that they apply broadly across the mild to vision-threatening stages of DR.
Second, we establish that higher total serum cholesterol was associated with a higher prevalence of DME, bringing clarity to previously conflicting reports about this risk factor (19
). This is particularly relevant to recent reports from trials suggesting that fenofibrate, a lipid-altering agent, may slow the development and progression of DR (34
). Fenofibrate, however, acts mostly on triglycerides, and its effects on retinopathy in those trials were independent of lipid levels achieved. Statins, however, did not affect DR severity in the few studies in which this was evaluated, although not as a primary outcome (35
Third, we provide estimates of risk of DR by diabetes type, in which studies in individuals with type 1 diabetes are currently scarce. We showed that the prevalence of DR is substantially higher in type 1 than in type 2 diabetes (11
), an outcome independent of diabetes duration. However, because we classified type of diabetes by age of onset (younger or older than age 30 years), in some studies there may be potential misclassification (e.g., some people with type 2 diabetes will be younger than 30 years).
The strengths of our study include a large sample size to determine prevalence and risk factor associations for sight-threatening end points (PDR, DME), the inclusion of diverse ethnic population samples from around the world, and studies that had used photographic documentation of DR.
Our study has limitations. Pooling of data from various sources introduces many potential sources of heterogeneity that could influence accuracy; thus, although our estimates are highly precise, their accuracy is unknown. Samples of different study designs could have considerably different inclusion criteria, sample selection, and study protocols. For example, population samples could have varied considerably between a cardiovascular disease study and an eye survey, or a study on diabetes complications.
There was also a range of methods used in ascertaining diabetes status. Studies in which diagnosis of diabetes was based on self-report, without confirmation from blood tests, could have resulted in an overestimate of DR prevalence rates because those with undiagnosed diabetes might have been erroneously excluded from the sample denominator.
Furthermore, there were differences in the methodologies used to detect and diagnose DR, such as the number of eyes photographed per subject, number of retinal fields examined per eye, and the grading protocols and definitions used. In studies that did not collect data on diabetes type, this information was defined on the basis of age of diagnosis, with a cutoff at age 30 years to use as many studies with detailed information other than types of diabetes. Misclassification could have occurred as a result of this assumption. This, however, would not have affected the overall prevalence estimates but could have had a small effect of attenuating the comparative estimates between the type 1 and type 2 diabetes groups. A few studies with large numbers of participants could have influenced our results. Finally, the absence of studies from the Middle East, Africa, or South America could also affect the accuracy of our findings.
In conclusion, our current study provides the first global estimate of DR and, more important, the two sight-threatening end points (PDR and DME), based on a pooled individual participant analysis of more than 20,000 participants from 35 studies around the world. Our study shows that 35% of people with diabetes had some form of DR, and that 7% had PDR, 7% had DME, and 10% were affected by these vision-threatening stages. We estimate that in 2010, approximately 93 million were affected by DR, and 28 million by VTDR. This suggests that DR has the potential to be the leading cause of visual impairment and blindness worldwide. We confirmed the importance and impact of three major modifiable risk factors—hyperglycemia, hypertension, and dyslipidemia—on the risk of all DR end points, including for the first time, PDR and DME. These results highlight the substantial public health effect of diabetes, and thus, the need for effective screening and management of DR risk factors.