Diabetic Retinopathy Management Guidelines

Rahul Chakrabarti; C Alex Harper; Jill Elizabeth Keeffe


Expert Rev Ophthalmol. 2012;7(5):417-439. 

In This Article

Risk Factors for DR

The principal risk factors for the development and progression of DR were covered well across the international guidelines. All published guidelines acknowledged that the established risk factors for DR were duration of diabetes, glycemic control,[31,32] hypertension,[33,34] dyslipidemia,[35,36] nephropathy[37,38] and pregnancy.[39] In particular, the importance of diabetes duration, glycemic control and optimization of blood pressure (BP) was consistently covered.

The significance of glycemic control as a major risk factor for DR was emphasized in all guidelines through the acknowledgement of the landmark studies, the Diabetes Control and Complications Trial (PCCT) and the United Kingdom Prospective Diabetes Study (UKPDS). The DCCT was a multicenter randomized control study that examined the effect of glycemic control on the frequency of microvascular complications in patients with Type 1 diabetes mellitus (DM).[31] The investigators randomized 1441 patients with Type 1 DM to receive intensive glycemic control (median HbA1c: 7.3%) compared with conventional levels of control (median HbA1c: 9.1%). The results demonstrated that over a 6.5-year follow-up, intensive glycemic control compared with conventional treatment was associated with reduction in any DR by 76% (95% CI: 62–85),[40] and progression of DR by 54% (95% CI: 39–66).[41] Similarly, in the UKPDS, the investigators randomized 3867 patients with newly diagnosed Type 2 DM to receive intensive treatment (oral hypoglycemic medication or insulin) or conventional glycemic control (diet control) over a period of 10 years.[32] The results demonstrated that intensive treatment reduced the development of any DR by 25% (95% CI: 7–40). Furthermore, this was associated with a 29% reduction (relative risk: 0.71; 95% CI: 0.53–0.96; p = 0.003) in progression to requirement of laser photocoagulation in the intensive group compared with conventional treatment.

The rationale for tight BP control has similarly been explored in landmark studies. In the UKPDS, 1048 patients with Type 2 DM were randomized to receive intensive BP control of patients with Type 2 DM (target BP; <150/<85 mmHg) versus <180/<105 mmHg, with observation over a period of 9 years. The study demonstrated that intensive control of hypertension was associated with reduction in progression of DR (34 vs 51%; p < 0.05), reduction in moderate vision loss (10 vs 19%; p < 0.05), and reduction in need for photocoagulation (relative risk: 0.65, 95% CI: 0.39–1.06; p = 0.023).[33] However, there is conflicting evidence regarding whether aggressive treatment of normotensive patients is beneficial in DR. The EUCLID demonstrated over a 2-year follow-up that lisinopril (antihypertensive agent) reduced the progression of any DR by 50% (95% CI: 0.28–0.89; p = 0.02), and progression to proliferative DR (PDR) by 80% (95% CI: 0.04–0.91; p = 0.04) in patients with Type 1 DM with normal BP and renal function.[36] Recently, a 4-year follow-up from the ACCORD Eye study 'blood pressure' trial demonstrated that there was no significant difference in the progression of DR with intensive (target systolic BP: <120 mmHg) versus standard BP control (target systolic BP: <140 mmHg) in patients with Type 2 DM.[42] The authors reported no statistically significant difference in any progression of DR (odds ratio: 1.23; 95% CI: 0.84–1.79); or rate of moderate vision loss (hazard ratio: 1.17; 95% CI: 0.96–1.42). Nevertheless, it is clear that optimization of BP in patients with hypertension is a major factor in attenuating the progression of DR.

Guidelines also consistently emphazised the role of early examination in reducing the risk of DR progression. Guidelines from developing regions used data from WESDR and the ETDRS, which demonstrated that after 15 years, retinopathy is noted in almost all people with Type 1 DM and 75% of people with Type 2 DM; 2% become blind and 10% develop severe vision impairment.[8,43,44] The role of puberty as a risk factor for DR among patients with Type 1 DM was acknowledged by all guidelines except South Africa and Aravind. This was consistent with findings from several studies that demonstrated that physiological changes post puberty accelerated the development of microvascular complications including DR.[45,46] Consequently, puberty is now accepted as a risk factor for onset of DR.

The significance of ethnic background upon risk of DR is well established. Many of the guidelines identified high-risk ethnic groups within their population. The American Academy of Ophthalmology (AAO) identified African–Americans and Mexicans as having a greater risk of developing any DR compared with Americans of European descent.[47] The NHMRC in Australia estimated that 31% of indigenous people with DM had evidence of retinopathy, compared with 20% in the nonindigenous population. Recent meta-analysis of population-based studies from around the world demonstrated that the age-standardized prevalence of any DR at 49.6% among African–Americans, 34.6% among Hispanic populations, 19.9% in Asians, compared with 45.8% in Caucasians.[30] While this was the first meta-analysis to incorporate risk factor data from Asia, the authors acknowledged the deficiency of good quality population studies from the Middle East, Africa and South America. The guidelines for the Pacific Islands, although based on the New Zealand Ministry of Health recommendation, stated that the proportion of any DR among the diabetic population exceeded 50% in some Pacific countries. This is consistent with trends from a recent systematic review that demonstrated that Oceania had the largest DM prevalence (15%) and highest average fasting plasma glucose level of any region in the world.[48] The South African and Malaysian guidelines each acknowledged that people of Indian background were at elevated risk of DR compared with the locals (African and Malay, respectively). This was supported by findings from several cross-sectional studies in India that demonstrated up to 25% prevalence of DR among patients with DM.[11,22] More recently, the UK Asian Diabetes Study also identified people with south Asian ethnicity as possessing an elevated risk of DR after controlling for other risk factors.[49] However, none of the published guidelines mentioned Indians or south Asians as a high-risk ethnic group. The Australian guideline was the only one to offer insight into factors contributing to ethnic differences. They acknowledged the role of westernization and change from traditional diets and lifestyle of indigenous people as a significant contributor to the higher prevalence rate of DM.