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 sight-threatening 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 sight-threatening 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 3-fold 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):1519-26 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

  7. ^ 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):465-71 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 long-term 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 cross-sectional 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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