Elsevier

The Lancet

Volume 376, Issue 9735, 10–16 July 2010, Pages 124-136
The Lancet

Seminar
Diabetic retinopathy

https://doi.org/10.1016/S0140-6736(09)62124-3Get rights and content

Summary

Diabetic retinopathy is a common and specific microvascular complication of diabetes, and remains the leading cause of preventable blindness in working-aged people. It is identified in a third of people with diabetes and associated with increased risk of life-threatening systemic vascular complications, including stroke, coronary heart disease, and heart failure. Optimum control of blood glucose, blood pressure, and possibly blood lipids remains the foundation for reduction of risk of retinopathy development and progression. Timely laser therapy is effective for preservation of sight in proliferative retinopathy and macular oedema, but its ability to reverse visual loss is poor. Vitrectomy surgery might occasionally be needed for advanced retinopathy. New therapies, such as intraocular injection of steroids and antivascular endothelial growth-factor agents, are less destructive to the retina than are older therapies, and could be useful in patients who respond poorly to conventional therapy. The outlook for future treatment modalities, such as inhibition of other angiogenic factors, regenerative therapy, and topical therapy, is promising.

Introduction

As the worldwide prevalence of diabetes mellitus continues to increase, diabetic retinopathy remains a leading cause of vision loss in many developed countries.1, 2 Although diabetes affects the eye in many ways (eg, heightened risk of cataract),3 diabetic retinopathy is the most common and serious ocular complication. Of the 246 million people with diabetes,4 about a third have signs of diabetic retinopathy, and a third of these might have vision-threatening retinopathy, defined as severe retinopathy or macular oedema.5 Apart from its effects on vision, the presence of diabetic retinopathy also signifies a heightened risk of life-threatening systemic vascular complications.6

Epidemiological, genetic, and experimental studies have furthered our understanding of the pathophysiology underlying diabetic retinopathy. Moreover, new clinical trials have provided contemporary data for evidence-based treatment strategies for diabetic retinopathy. This Seminar summarises the present state of knowledge of diabetic retinopathy, from epidemiological, pathophysiological, and clinical perspectives.

Section snippets

Prevalence

In many countries, diabetic retinopathy is the most frequent cause of preventable blindness in working-aged adults (20–74 years).7 In the USA, an estimated 40% (8% for vision-threatening retinopathy) of people with type 2 diabetes and 86% (42%) with type 1 diabetes have diabetic retinopathy.8, 9 Similarly, high prevalence estimates have been reported in other countries (figure 1).12 The low prevalence rates reported in some developing countries (eg, India16, 17) will probably change with

Risk factors

The panel shows several important risk factors for diabetic retinopathy. Ethnic origin differences in the prevalence of diabetic retinopathy have been a focal point of interest in research. Findings from population-based studies suggest that the prevalence and severity of diabetic retinopathy are higher in African Americans, Hispanics, and south Asians than in white people, and are not fully accounted for by differences in the distribution of retinopathy risk factors.12, 25, 29 For example, in

Pathophysiology

Our understanding of the pathophysiological mechanisms underlying the development of diabetic retinopathy is constantly evolving with new research.48, 49, 50 Chronic exposure to hyperglycaemia and other causal risk factors (eg, hypertension) is believed to initiate a cascade of biochemical and physiological changes that ultimately lead to microvascular damage and retinal dysfunction (figure 2).

Clinical features and classifications

Clinically, diabetic retinopathy is defined as the presence of typical retinal microvascular signs in an individual with diabetes mellitus. Vision loss develops from the sequelae of maculopathy (macular oedema and ischaemia) and neovascularisation of the retina (vitreous haemorrhage and retinal detachment) and iris (neovascular glaucoma). Clinical assessment should therefore aim to detect these serious ocular manifestations, and in their absence assess the risk of progression to

Treatment considerations

Present guidelines for the optimum eye care of patients with diabetes are tight glycaemic and blood pressure control in conjunction with timely laser therapy as needed.7 However, several key questions remain. For example, what are the target glycaemia and blood pressure levels for effective prevention of retinopathy development and progression? Are some hypoglycaemic and blood pressure-lowering agents more effective than are others for retinopathy? What is the role of lipid-lowering agents?

Laser photocoagulation

Laser photocoagulation remains the mainstay of ophthalmic therapy for vision-threatening diabetic retinopathy. However, despite its remarkable efficacy in prevention of visual loss when undertaken in a timely and appropriate manner, the destructive nature of laser is associated with significant ocular side-effects. Additionally, even with adequate laser therapy, reversal of visual loss is uncommon. Therefore, researchers continue to search for new and increasingly effective therapeutic

Future directions

Despite good control of systemic risk factors, a significant proportion of patients will still progress to develop vision-threatening diabetic retinopathy (either macular oedema or proliferative retinopathy). The present standard of care for management of these disorders relies mainly on laser therapy, which is inherently destructive, associated with unavoidable side-effects, and not universally effective in reversal of visual loss. Thus, new approaches have also emerged, such as use of

Search strategy and selection criteria

We searched the Cochrane Library (1980–2009), Medline (1980–2009), and Embase (1980–2009). We used the search terms “diabetic retinopathy” in combination with the following terms: “prevalence”, “incidence”, “risk factors”, “pathogenesis”, “gene”, “diagnosis”, “screening”, “imaging”, “treatment”, and “therapy”. We largely selected publications in the past 5 years, but did not exclude commonly referenced and highly regarded older publications. We also searched the reference lists of

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