21 Diabetic Retinopathy and Systemic

Complications

Ning Cheung and Tien Y. Wong

CONTENTS

INTRODUCTION

DIABETIC RETINOPATHY AND MORTALITY

DIABETIC RETINOPATHY AND CEREBROVASCULAR DISEASE

DIABETIC RETINOPATHY AND HEART DISEASE

DIABETIC RETINOPATHY, NEPHROPATHY, AND NEUROPATHY

PATHOGENIC BASIS BETWEEN DIABETIC RETINOPATHY AND

SYSTEMETIC DISEASE

CLINICAL SIGNIFICANCE OF RETINOPATHY IN SYSTEMIC DISEASE

SCREENING

CONCLUSION

REFERENCES

Key Words: Retinopathy, stroke, heart failure, coronary heart disease, nephropathy, complications, microvascular disease, macrovascular disease, cardiovascular disease prediction, mortality.

INTRODUCTION

Diabetic retinopathy is the most common and specific complication of diabetes (1). Its adverse impact on vision is well known. The clinical significance of retinopathy signs beyond the eyes of diabetic individuals, however, is less clear. The routine ophthalmic examination to detect retinopathy signs presents ophthalmologists and physicians with the unique opportunity to directly visualize and assess actual pathology of diabetic microvascular damage. New studies now show that early signs of retinopathy are associated with a wide range of systemic complications in persons with diabetes, including the development of stroke, coronary heart disease, heart failure, nephropathy, and peripheral vascular disease (2–8). Diabetic retinopathy signs therefore not only reflect microvascular dysfunction in the retina, but also may be markers of more widespread

From: Diabetic Retinopathy

Edited by: MD Elia Duh © Humana Press, Totowa, NJ

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deleterious effects of abnormal glucose metabolism on the systemic vasculature. This chapter will discuss the relationships of diabetic retinopathy with mortality and various systemic microand macrovascular morbidities.

DIABETIC RETINOPATHY AND MORTALITY

It has long been known that in persons with diabetes, the presence of retinopathy is associated with an increased risk of mortality (Table 1). Studies suggest this association is more consistently seen in patients with type 2 as compared to type 1 diabetes, reflecting older age and possibly the higher prevalence of cardiovascular risk factors in type 2 diabetes.

In the Wisconsin Epidemiological Study of Diabetic Retinopathy (WESDR), a large population-based study in the United States, both nonproliferative (NPDR) and proliferative (PDR) diabetic retinopathy were associated with a 34–89% excess risk of death in participants with type 2 diabetes after 16 years of follow-up (9). Importantly, this association was independent of age, sex, diabetes duration, glycemic control, and other survival-related risk factors. Consistent with this finding are data from other studies in Caucasians (10–14), Asians (15), and Mexicans (16).

While retinopathy also predicts poorer survival in persons with type 1 diabetes, some studies suggest that the association is largely explained by coexisting cardiovascular risk factors (9, 17, 18). Not all studies have found this association consistently. In the Early Treatment Diabetic Retinopathy Study, a large clinical trial with a relatively short follow-up, retinopathy was shown to have no association with mortality in type 1 diabetes (14). Some (19, 20), but not all (13), investigators believe that, besides the traditional cardiovascular risk factors, coexisting nephropathy (e.g., end-stage renal disease) is a major determinant for the poorer survival in patients with diabetic retinopathy.

The association of diabetic retinopathy with mortality is largely related to the increased risk of cardiovascular mortality in persons with retinopathy (Table 2). The World Health Organization Multinational Study of Vascular Disease in Diabetes (WHOMSVDD) consists of a large cohort of type 1 and 2 diabetic persons who were followed up for 12 years for incidence of fatal and nonfatal cardiovascular outcomes (21). In the WHO-MSVDD, the presence of diabetic retinopathy predicted higher risk of cardiovascular disease and mortality (21). This association was seen in persons with type 2, but not type 1, diabetes and was stronger in women than in men, and remained significant even after adjusting for traditional cardiovascular risk factors (21). In addition, some studies show a “dose-dependent” association between diabetic retinopathy and cardiovascular disease risk, with increasing risk in eyes with more severe retinopathy (11, 12). These associations are supported by other studies, such as prospective data from the EURODIAB Study and cross-sectional data from the Cardiovascular Health Study (10, 13, 18, 22–24).

DIABETIC RETINOPATHY AND CEREBROVASCULAR DISEASE

Stroke and other cerebrovascular diseases (e.g., vascular dementia) are major sources of morbidity and mortality in people with diabetes. Over the past decade, despite the significant progress made in stroke prevention and treatment, most advances have been