Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy

Aims/hypothesis. Vascular endothelial growth factor (VEGF) is thought to be instrumental in the progression of diabetic retinopathy. Indications exist that the renin-angiotensin system is involved in VEOF overexpression. We assessed the vitreous VEGF concentrations in patients and related them to anti-hypertensive treatment, with special interest in the use of ACE-inhibitors. Methods. Samples of vitreous fluid (10-80 mul) were obtained from 39 patients both with Type I (insulin-dependent) and Type It (non-insulin-dependent) diabetes mellitus and 11 non-diabetic patients undergoing intra-ocular surgery. The VEGF-A concentrations were assessed by immunoassay. Results. Control patients and patients without proliferative diabetic retinopathy (n = 8) had low and comparable VEGF concentrations (medians < 50 pg/ml). In contrast, patients with proliferative diabetic retinopathy (n = 31) had high vitreous VEGF concentrations (median 1134 pg/ml), which showed a negative correlation with the use of ACE inhibiting medication (Spearman rank-R = -0.54; p = 0.002, n = 13). Diastolic and systolic blood pressure did not differ significantly between the two subgroups with proliferative diabetic retinopathy, i.e. those patients receiving ACE-inhibition (medians 88/160 mm Hg, respectively) and the others (90/160). For the mostly used ACE-inhibitor in the proliferative diabetic retinopathy group, i.e. enalapril (n = 8), a linear dose-effect relation was observed (-20 +/- 4 pg . ml(-1) mg(-1) . day(-1); p = 0.024; coefficient +/- SEM). Conclusion/interpretation. Treatment with ACE-inhibitors attenuates retinal overexpression of VEGF-A in patients with proliferative diabetic retinopathy, probably by interference with a local effect of angiotensin II.