7.15 Treatments

7.15.1Metabolic Control and Effects of Drugs

Recognition of the risk factors for diabetic macular edema led to randomized clinical trials of better blood glucose and blood pressure control in attempts to reduce the prevalence of the condition. The Diabetes Control and Complications Trial (DCCT) showed that tight blood glucose control in patients with type 1 diabetes reduced the cumulative incidence of macular edema at 9 years followup by 29% and reduced the application of focal

laser treatment for diabetic macular edema by half.198,199 The effects of years of improved glycemic

control persist even if control later deteriorates. In the Epidemiology of Diabetes Interventions and Complications (EDIC) study, an extension study of the DCCT in which the level of glycemic control of the former intensive and conventional control groups converged, the former intensive control group continued to fare better than the former conventional control group. Four years after the end of the DCCT, the former intensive control group had a 2% incidence of CSME compared to 8% for the former conventional control group (P < 0.001).200 The UK Prospective Diabetes Study was an analogous randomized clinical trial of patients with type 2 diabetes. It showed that tighter blood glucose control reduced the requirement for laser treatment at 10 years follow-up by 29%, compared to looser control; 78% of the laser treatments were for DME.201 It also showed that a mean systolic blood pressure reduction of 10 mmHg and a diastolic blood pressure reduction of 5 mmHg over a median follow-up of 8.4 years led to a 35% reduction in retinal laser treatments, of which 78% were for DME.202 These clinical trial results make physiologic sense, as it has been shown that in eyes with retinopathy and a damaged blood–retina barrier, reduction of blood pressure not only reduces the driving force for egress of fluid to the extracellular space, but also decreases microvessel permeability, an effect documented before the appearance of microaneurysms and other morphologic stigmata of diabetic retinopathy.50,196 In studies of blood– retina barrier permeability in patients with NPDR

and hypertension, captopril with or without a diuretic has been shown to reduce permeability when used for 6 months. The effect was not immediate suggesting that a structural change in the blood–retinal barrier occurs that takes time to develop.50,203 Over longer periods in normotensive patients with NPDR, captopril delayed the increase in BRB permeability seen in untreated patients.194 There is suggestive evidence that level of glycemic control also influences responsiveness to therapy; higher glycosylated hemoglobin levels have been reported in patients with DME refractory to focal/ grid laser photocoagulation.148

Multiple studies suggest a causal link between a patient’s lipid profile and the presence of DME.204 Increased serum cholesterol levels are associated with increased severity of retinal hard exudates at baseline, increased risk of developing DME during follow-up, and increased risk of losing visual acuity

even after adjusting for presence or absence of macular edema (Fig. 7.31).12,205 Patients with

abnormally elevated triglycerides and HDL cholesterol had worse visual acuity outcomes after focal/ grid photocoagulation than did patients with normal levels in one small prospective study.206 Small studies have shown that 3-hydroxy-3-methylglu- taryl coenzyme A inhibitors can reduce serum cholesterol levels and retinal hard exudates by themselves, and may reduce subfoveal lipid migration

and improve regression rates of DME as adjunctive therapy to focal/grid laser.87,207 Small clinical trials

of clofibrate showed that macular exudates could be

Fig. 7.31 Diabetic macular edema in a patient with marked elevation of serum cholesterol and triglycerides can be associated with more pronounced lipid exudates as illustrated in this case