1. ¹Departments of Diabetes and Ophthalmology, Heart of England NHS Foundation Trust, Heart of England Diabetic Retinopathy Screening Unit and the University Hospitals, Birmingham NHS Foundation Trust, Birmingham, West Midlands, UK
2. ²Department of Life and Health Sciences, Aston University Birmingham, Birmingham, West Midlands, UK

Correspondence: PM Dodson, Departments of Diabetes and Ophthalmology, Birmingham Heartlands Hospital, Bordesley Green, Birmingham, West Midlands B9 5SS, UK. Tel: +0121 424 2104; Fax: +0121 424 0593; E-mail: paul.dodson@heartofengland.nhs.uk

³AD Wright was an investigator in UKPDS

⁴PM Dodson has received honoraria for advisory board membership from Pfizer, AstraZeneca, Takeda and Solvay, and research grants from Eli Lilly. The author is on advisory boards concerning the DIRECT, CARDS, and FIELD studies and principal investigator for the Ruboxistaurin trials in the UK

Received 24 June 2009; Accepted 24 June 2009; Published online 24 July 2009.

Abstract

The pathogenesis and medical management of diabetic retinopathy is reviewed. The importance of good control of blood glucose and blood pressure remain key elements in the prevention and treatment of diabetic retinopathy, and a number of specific metabolic pathways have been identified that may be useful additional targets for therapeutic intervention. Trial data, however, aimed specifically to answer the questions of optimum medical management are limited, so the DIRECT study of renin–angiotensin blockade using oral candesartan 32 mg daily is a welcome addition to our knowledge. This arose from the promising improvement of retinopathy outcomes in the EUCLID study of lisinopril in type I diabetes. In DIRECT, 5 years of candesartan treatment in type I diabetes reduced the incidence of retinopathy by two or more steps (EDTRS) in severity by 18% (P=0.0508) and, in a post hoc analysis, reduced the incidence of retinopathy by three-step progression by 35% (P=0.034). In type I diabetes patients there was no effect on progression of established retinopathy. In contrast, in type II diabetes, 5 years of candesartan treatment resulted in 34% regression of retinopathy (P=0.009). Importantly, an overall significant change towards less-severe retinopathy was noted in both type I and II diabetes (P0.03). Although there is still no absolute proof that these effects were specific to RAS blockade, or just an effect of lower blood pressure, it is reasonable to conclude that candesartan has earned a place in the medical management of diabetic retinopathy, to prevent the problem in type I diabetes and to treat the early stages in type II diabetes.