Epidemiology of Diabetic Retinopathy

Diabetic retinopathy (DR) is the leading cause of visual loss and blindness in working
age populations in the developed world. Although everyone with a diagnosis of
diabetes is at risk of developing retinopathy, only a minority progress to sightthreatening complications. These are for the most part preventable. Since the
prevalence of diabetes is rising rapidly, particularly in Asian countries, and people
are living longer following diagnosis, diabetic retinopathy has emerged as a major
public health concern. Despite this, accurate data on its prevalence and outcome
worldwide are still lacking.

Introduction
Almost all patients with diabetes show evidence of retinal changes over the course of time,
if investigated with sufficiently sensitive techniques, and that a large minority - up to half in
some populations - progress to sight-threatening variants of the condition. This proportion
has fallen over time, most likely because of improved glucose control, and techniques of
ophthalmic management have improved in parallel.
Epidemiology has played an essential role in monitoring the impact of diabetic retinopathy
at a population level, and the success or failure of public health measures designed to
influence the course of this largely preventable condition.

Worldwide Prevalence of Diabetic Retinopathy

A recent pooled analysis from 35 population-based studies estimated that 93 million people
worldwide have diabetic retinopathy, of whom 17 million (~18%) have proliferative DR, 21
million (~23%) have diabetic macular edema (DME), and 28 million (~20%) have sightthreatening DR [1].
Among people with diabetes, this translates to an overall prevalence of 34.6% for any DR,
7.0% for proliferative DR, 6.8% for DME, and 10.2% for sight-threatening DR [1]. Pooled
analyses showed no difference in prevalence between men and women. Asians had the
lowest prevalence and African Americans the highest.
The prevalence of retinopathy is higher in people with long duration of diabetes, those with
type 1 diabetes, and those with increased levels of HBA1c, blood pressure, or cholesterol [1].
Historically, DR was considered to be relatively infrequent in developing countries such as
India and China; however changes in economies, diet, and longevity mean these nations
now have as much, or more, DR than fully developed countries [2]. A recent study from rural
China reported disturbingly high rates of DR among people with diabetes: 43% for any DR
and 3.5% for DME [3]. These levels are significantly higher than those for urban Chinese:
37% for DR and 2.6% for DME[4].

Incidence of Diabetic Retinopathy

Given the public health significance of diabetes complications, relatively few studies have
prospective data to define the incidence and rates of progression of DR and DME. One of

the longest duration prospective studies is the Wisconsin Epidemiologic Study of Diabetic
Retinopathy (WESDR).
WESDR investigators reported a 10-year incidence of retinopathy of 74%. Of those with DR
at baseline, 64% developed more severe DR and 17% progressed to proliferative DR [5].
Information from the 25-year follow-up of this cohort showed that virtually everyone
eventually developed DR (97%), with up to half progressing to sight-threatening disease [6][7].
Long term modelling based on the WESDR data predicts that of the 515,000-1.3 million
Americans with known type 1 diabetes, 185,000-466,000 will develop proliferative DR and
377,000 will develop DME[6][7].
The Blue Mountains Eye Study in Australia reported a cumulative 5-year incidence of DR of
22.2% in those diagnosed with diabetes at baseline, while progression to proliferative DR
occurred in 4.1% of those who had DR at baseline [8].
The DR screening program in the UK has reported the 5-year cumulative incidence of any
DR as 36%, proliferative DR as 0.7% and DME as 0.6%, rising to 66%, 1.5%, and 1.2%
respectively after 10-years follow-up[9].

Risk factors for Diabetic Retinopathy

Established risk factors from both cross-sectional and longitudinal studies include
hyperglycaemia, hypertension, dyslipidemia, duration of diabetes, pregnancy, puberty, and
cataract surgery[10], highlighting a substantial modifiable component to the risk factor profile.
Clinical trials have demonstrated the efficacy of intensive control of both hypertension and
hyperglycaemia in the reducing the incidence and progression of DR [11][12]. However, caution
is required when lowering blood gucose in those deemed at high risk of cardiovascular
disease, since the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial
reported that intensive glycaemic control was associated with increased mortality [13].
Unlike age-related macular degeneration, whose prevalence increases rapidly with age, the
prevalence rates are similar for DR in those aged 40-64years (28%) and in those over 65
years(30%) [14]. For a recent overview of risk factors of DR, see Ding et al, 2012 [14].
Genetic Risk factors
A genetic predisposition to the development and progression of DR is suggested by the
difference in risk between ethnic groups observed after controlling for demographic and
environmental factors [15]. Family studies have also shown that there is an approximately 3fold increased risk of severe DR in siblings of affected individuals, and heritability studies
showing a moderate effect of genetic factors (0.52).
Despite this, identifying genes consistently associated with DR has proven difficult, partially
due to significant differences in assessment and documentation of retinopathy across
studies [15]. Despite this, candidate gene studies have reported links between DR status and
the following genes: Aldose Reductase Gene (ALR2) [16], Vascular Endothelial Growth Factor
Gene (VEGF)[17]and Receptor for Advanced Glycation End Products Gene (RAGE) [18].
Although several genome-wide association studies have highlighted potential loci, none

have reached genome-wide significance (P-values <1 x 10-8). It is likely that larger
consortia with standardised grading may be required to reveal significant findings.

References
1.

^ Yau JW, Rogers SL, Kawasaki R, et al. Global Prevalence and Major Risk Factors of
Diabetic Retinopathy. Diabetes care 2012 10.2337/dc11-1909

2.

^ Zheng Y, He M, Congdon N. The worldwide epidemic of diabetic retinopathy. Indian journal

of ophthalmology 2012;60(5):428-31 10.4103/0301-4738.100542.

3.

^ Wang FH, Liang YB, Zhang F, et al. Prevalence of diabetic retinopathy in rural Cthe Handan
Eye Study. Ophthalmology 2009;116(3):461-7 10.1016/j.ophtha.2008.10.003.

4.

^ Xie XW, Xu L, Wang YX, et al. Prevalence and associated factors of diabetic retinopathy.
The Beijing Eye Study 2006. Graefe's archive for clinical and experimental ophthalmology =
Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 2008;246(11):151926 10.1007/s00417-008-0884-6.

5.

^ Klein R, Klein BE, Moss SE, et al. The Wisconsin Epidemiologic Study of diabetic
retinopathy. XIV. Ten-year incidence and progression of diabetic retinopathy. Archives of
ophthalmology 1994;112(9):1217-28

6.

^ Klein R, Knudtson MD, Lee KE, et al. The Wisconsin Epidemiologic Study of Diabetic RXXII
the twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology
2008;115(11):1859-68 10.1016/j.ophtha.2008.08.023

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^ Klein R, Knudtson MD, Lee KE, et al. The Wisconsin Epidemiologic Study of Diabetic
Retinopathy XXIII: the twenty-five-year incidence of macular edema in persons with type 1
diabetes. Ophthalmology 2009;116(3):497-503 10.1016/j.ophtha.2008.10.016

8.

^ Cikamatana L, Mitchell P, Rochtchina E, et al. Five-year incidence and progression of

diabetic retinopathy in a defined older the Blue Mountains Eye Study. Eye (Lond) 2007;21(4):46571 10.1038/sj.eye.6702771.

9.

^ Jones CD, Greenwood RH, Misra A, et al. Incidence and progression of diabetic retinopathy
during 17 years of a population-based screening program in England. Diabetes care
2012;35(3):592-6 10.2337/dc11-0943.

10.

^ Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet 2010;376(9735):124-36

10.1016/S0140-6736(09)62124-3.

11.

^ The effect of intensive treatment of diabetes on the development and progression of longterm complications in insulin-dependent diabetes mellitus. The Diabetes Control and
Complications Trial Research Group. The New England journal of medicine 1993;329(14):977-86
10.1056/NEJM199309303291401.

12.

^ Tight blood pressure control and risk of macrovascular and microvascular complications in
type 2 UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317(7160):703-13

13.

^ Group AS, Group AES, Chew EY, et al. Effects of medical therapies on retinopathy
progression in type 2 diabetes. The New England journal of medicine 2010;363(3):233-44
10.1056/NEJMoa1001288.

14.

^ Ding J, Wong TY. Current epidemiology of diabetic retinopathy and diabetic macular edema.
Current diabetes reports 2012;12(4):346-54 10.1007/s11892-012-0283-6.

15.

^ Liew G, Klein R, Wong TY. The role of genetics in susceptibility to diabetic retinopathy.
International ophthalmology clinics 2009;49(2):35-52 10.1097/IIO.0b013e31819fd5d7.

16.

^ Katakami N, Kaneto H, Takahara M, et al. Aldose reductase C-106T gene polymorphism is

associated with diabetic retinopathy in Japanese patients with type 2 diabetes. Diabetes research
and clinical practice 2011;92(3):e57-60 10.1016/j.diabres.2011.02.017.

17.

^ Fan X, Wu Q, Li Y, et al. Association of polymorphisms in the vascular endothelial growth

factor gene and its serum levels with diabetic retinopathy in Chinese patients with type 2 A crosssectional study. Chinese medical journal 2014;127(4):651-7

18.

^ Yang L, Wu Q, Li Y, et al. Association of the receptor for advanced glycation end products
gene polymorphisms and circulating RAGE levels with diabetic retinopathy in the Chinese
population. Journal of diabetes research 2013;264579 10.1155/2013/264579.

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