Does Renin-angiotensin System Blockade have a Role in Preventing Diabetic Retinopathy? A Clinical Review

A. K. Sjølie; P. Dodson; F. R. R. Hobbs


Int J Clin Pract. 2011;65(2):148-153. 

In This Article

Abstract and Introduction


Diabetes management has increasingly focused on the prevention of macrovascular disease, in particular for type 2 diabetes. Diabetic retinopathy, one of the main microvascular complications of diabetes, is also an important public health problem. Much of the care invested in retinopathy relates to treatment rather than prevention of disease. Tight glycaemic and blood pressure control helps to reduce the risk of retinopathy, but this is not easy to achieve in practice and additional treatments are needed for both primary and secondary prevention of retinopathy. A renin-angiotensin system (RAS) has been identified in the eye and found to be upregulated in retinopathy. This has led to specific interest in the role of RAS blockade in retinopathy prevention. The recent DIRECT programme assessed use of the angiotensin receptor blocker (ARB) candesartan in type 1 and type 2 diabetes. Although the primary trial end-points were not met, there was a clear trend to less severe retinopathy with RAS blockade. A smaller trial, RASS, reported reduced retinopathy progression in type 1 diabetes from RAS blockade with both the ARB losartan and the angiotensin converting enzyme (ACE) inhibitor enalapril. The clinical implications of these new data are discussed.


Diabetic retinopathy is the most common long-term complication of diabetes and the most common cause of blindness in working-age people in developed countries. It is one of the most feared complications in people with diabetes[1] and has marked effects on patients' quality of life.[2] Quality of life can be affected in people with diabetic retinopathy before they have visual loss, because of anxiety about the future.[3]

At the time of the diagnosis of diabetes, up to 40% of patients with type 2 disease already have some degree of diabetic retinopathy.[4] In data from the Wisconsin Epidemiological Study of Diabetic Retinopathy (WESDR) collected about 30 years ago, more than 60% of patients with type 2 diabetes and almost all those with type 1 diabetes had some retinopathy after 20 years.[5]

There is evidence from the Diabetes Control and Complications Trial (DCCT) and UK Prospective Diabetes Study (UKPDS) and other studies that recent improvements in the treatment of diabetes have led to lower incidence of retinopathy; however, this is offset by the current increase in prevalence of diabetes.[6] In the UK, diabetes prevalence increased from 2.8% in 1996 to 4.3% in 2005. The marked increase in type 2 diabetes is probably related to changes in lifestyle, including increased obesity prevalence.[7]

If untreated, a large proportion of people who develop proliferative diabetic retinopathy (PDR) will experience severe loss of vision within 5 years.[8] Panretinal laser photocoagulation (PRP) is the only proven treatment with long-term beneficial effect in preventing severe visual loss once PDR is present. It can induce regression of retinal new vessels, but PRP is not always effective and can itself produce side effects on visual function such as loss of visual field and, in rare cases, accidental scars in the macula.[9] This treatment is usually used for patients in whom sight-threatening retinopathy has developed.

By the time visual symptoms occur, severe and irreversible damage to the retina has already occurred and laser treatment is less effective. Therefore, regular screening for retinal new vessels is recommended, the aim being to detect retinopathy at an asymptomatic stage when treatment is more likely to be successful.

Specific drug treatments for retinopathy are being investigated, but these are mostly used in advanced disease when damage to the retina and visual function has already occurred. The aim of this review was to evaluate the data on prevention of diabetic retinopathy development and progression, specifically considering new clinical trial data on the possible effect of drugs that inhibit the renin-angiotensin system.