Risk Of Diabetic Retinopathy Progression Research Articles

Effects of RAS inhibitors on diabetic retinopathy: a systematic review and meta-analysis

Results of several studies have shown a possible beneficial effect of renin-angiotensin system (RAS) inhibitors on diabetic retinopathy, but the findings were contradictory. We did a systematic review and meta-analysis to assess the effect of RAS inhibitors on diabetic retinopathy. We identified relevant publications in PubMed, Embase, Cochrane Library Central Register of Controlled Trials, and abstracts from main annual meetings. Only randomised controlled trials comparing angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) monotherapy with other antihypertensive drugs or placebo in type 1 or type 2 diabetes were eligible for inclusion in the analysis. The primary outcomes were progression and regression of diabetic retinopathy in all patients and several subgroups. Risk ratios (RRs) with corresponding 95% CIs were pooled. We also did a network meta-analysis to assess the effect of different antihypertensive drugs on diabetic retinopathy by ranking order. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42013004548. 21 randomised clinical trials with 13,823 participants were included in the meta-analysis. RAS inhibitors were associated with reduced risk of progression (absolute risk difference -3%, 95% CI -5 to -1; pooled RR 0.87, 95% CI 0.80-0.95; p=0.002) and increased possibility of regression of diabetic retinopathy (8%, 1-16; RR 1.39, 95% CI 1.19-1.61; p=0.00002). In normotensive patients, RAS inhibitors decreased risk of diabetic retinopathy progression (0.81, 0.69-0.94; p=0.007) and increased possibility of regression (1.43, 1.14-1.79; p=0.002). In hypertensive patients, RAS inhibitors were not associated with difference in risk of progression of diabetic retinopathy (0.93, 0.79-1.10; p=0.42) or possibility of diabetic retinopathy regression (2.21, 0.92-5.31; p=0.08). ACE inhibitors were associated with reduced risk of diabetic retinopathy progression (0.84, 0.75-0.94; p=0.002) and higher possibility of disease regression (1.50, 1.20-1.86; p=0.0003). ARBs were associated with a higher possibility of diabetic retinopathy regression (1.32, 1.07-1.61; p=0.008), but had no effect on disease progression (0.92, 0.80-1.06; p=0.25). Network meta-analysis showed the association of antihypertensive drugs with risk of diabetic retinopathy progression was lowest for ACE inhibitors, followed by ARBs, β blockers, calcium channel blockers, and placebo in rank order. The association of antihypertensive drugs with possibility of diabetic retinopathy regression was highest for ACE inhibitors, followed by ARBs, placebo, and calcium channel blockers in rank order. In patients with diabetes, RAS inhibitors reduce the risk of diabetic retinopathy, and increase the possibility of diabetic retinopathy regression. ACE inhibitors might be better than ARBs for treating diabetic retinopathy, and might exert the most beneficial effect on diabetic retinopathy of all widely used antihypertensive drug classes.

Predicting development of proliferative diabetic retinopathy.

OBJECTIVEIdentifying individuals most at risk for diabetic retinopathy progression and intervening early can limit vision loss and reduce the costs associated with managing more advanced disease. The purpose of this study was to identify factors associated with progression from nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR).RESEARCH DESIGN AND METHODSThis was a retrospective cohort analysis using a claims database of all eye care recipients age ≥30 years enrolled in a large managed-care network from 2001 to 2009. Individuals with newly diagnosed NPDR were followed longitudinally. Multivariable Cox regression analyses identified factors associated with progression to PDR. Three- and five-year probabilities of retinopathy progression were determined.RESULTSAmong the 4,617 enrollees with incident NPDR, 307 (6.6%) developed PDR. After adjustment for confounders, every 1-point increase in HbA1c was associated with a 14% (adjusted hazard ratio 1.14 [95% CI 1.07–1.21]) increased hazard of developing PDR. Those with nonhealing ulcers had a 54% (1.54 [1.15–2.07]) increased hazard of progressing to PDR, and enrollees with nephropathy had a marginally significant increased hazard of progressing to PDR (1.29 [0.99–1.67]) relative to those without these conditions. The 5-year probability of progression for low-risk individuals with NPDR was 5% (range 2–8) and for high-risk patients was 38% (14–55).CONCLUSIONSAlong with glycemic control, nonophthalmologic manifestations of diabetes mellitus (e.g., nephropathy and nonhealing ulcers) are associated with an increased risk of diabetic retinopathy progression. Our retinopathy progression risk score can help clinicians stratify patients who are most at risk for disease progression.

Direct Effects of PPARα Agonists on Retinal Inflammation and Angiogenesis May Explain How Fenofibrate Lowers Risk of Severe Proliferative Diabetic Retinopathy

In this issue of Diabetes , Chen et al. (1) used rodent models of type 1 diabetes and ischemia-induced retinal neovascularization to examine how the lipid-lowering drug fenofibrate may prevent progression of diabetic retinopathy. Diabetic retinopathy is the sight-threatening complication of diabetes that causes retinal microvascular dysfunction, which in turn leads to diabetic macular edema (DME), formation of exudate deposits, and microhemorrhages. In the advanced proliferative stage of diabetic retinopathy, neovascularization can result in retinal detachment and blindness. Therapeutic options for diabetic retinopathy have been limited. Until recently, intensive glycemic control, with its risks of hypoglycemic events and increased mortality, was the only known means of reducing the progression of diabetic retinopathy (2,3). Laser photocoagulation of the peripheral retinal tissue, intravitreal injection of steroids or vascular endothelial growth factor (VEGF) inhibitors, and vitrectomy can each stabilize or improve vision, but they are all invasive and are associated with various complications. Additional treatment options are needed. An orally available drug that reduces the risk of diabetic retinopathy progression without intensive glycemic control, retinal destruction, or repeated intravitreal injections would be ideal. Type 2 diabetes is often associated with dyslipidemia characterized by elevated triglycerides, reduced HDL cholesterol, and variable LDL cholesterol. Although statins are clearly beneficial, a residual atherogenic dyslipidemia often remains (4). Fibric acid derivatives, such as fenofibrate, stimulate the peroxisome proliferator–activated receptor type α (PPARα) and lead to increased fatty acid β-oxidation, thus decreasing plasma triglyceride and LDL cholesterol levels and increasing HDL cholesterol levels (5). This makes fibrates, in combination with statins, a logical treatment for diabetic dyslipidemia. Recent large-scale clinical studies, including the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and …

High Caloric and Sodium Intakes as Risk Factors for Progression of Retinopathy in Type 1 Diabetes Mellitus

To report the association of dietary nutrient intakes in relation to the 6-year progression of diabetic retinopathy (DR) in African American patients with type 1 diabetes mellitus. African American patients with type 1 diabetes who participated in the baseline and 6-year follow-up examinations as part of the New Jersey 725 study were included. At the baseline examination, a food frequency questionnaire was used to document average daily dietary nutrient intakes. Clinical evaluations at baseline and at the 6-year follow-up also included a structured clinical interview, ocular examination, grading of 7 standard field stereoscopic fundus photographs, and blood pressure measurements. Biological evaluations included blood and urine assays. Nutrient intake data were analyzed using DietSys software and nutrient databases developed by the National Cancer Institute. Among the 469 participants at risk for progression of DR, baseline total caloric intake was significantly associated with 6-year incidence of vision-threatening DR (either proliferative DR or macular edema) and of severe hard exudates--after adjusting for clinical risk factors for DR progression. Baseline high sodium intake was a significant and independent risk factor for 6-year incidence of macular edema. In African American patients with type 1 diabetes, high caloric and sodium intakes are significant and independent risk factors for progression to severe forms of DR. Dietary recommendations of low caloric and sodium intakes may be beneficial in relation to the development of DR.