The Effect of Topical Administration of ET-1 Inhibitor Unoprostone Isopropyl on Retinal Hemodynamics in Diabetic Patients: Study Design and Baseline Data

Abstract

Abstract: : Purpose: Early retinal hemodynamic changes in diabetic patients, which include alterations in mean circulation time (MCT) and retinal blood flow (RBF), are thought to contribute to the progression of diabetic retinopathy and to be partially mediated by endothelin-1 (ET-1)-induced vasoconstriction. Since ET-1 inhibition may normalize these effects, we conducted a single-center, prospective, double-masked, randomized, placebo-controlled crossover clinical trial to determine if a topically-administered ET-1 inhibitor, unoprostone isopropyl, could normalize retinal hemodynamics in diabetic patients. Methods: Of 59 patients screened, 19 were enrolled (age ≥ 18 years, diabetes duration ≤ 14 years, normotensive, 7.6<HbA1c<13.0%, no or minimal diabetic retinopathy [ETDRS retinopathy severity level 10 or 15]). Patients were randomized to 0.15% unoprostone isopropyl ophthalmic solution or placebo. At study entry, retinal hemodynamics were assessed by dye-dilution video fluorescein angiography both at baseline and after an initial dosing regimen lasting 2 hours, and HbA1c and ET-1 plasma level were assessed. Thereafter, patients administered gtts OU BID with treatment group crossover after one month. Assessment of retinal hemodynamics, HbA1c, and plasma ET-1 were performed at crossover and study completion. Results: Baseline demographic data on 19 patients recruited include mean age 48±8 years (range 35-66), diabetes duration 7±3 years (1-14), and hemoglobin A1c 9.0±1.2% (7.7-12.2%). Participants are 74% Caucasian, 32% female, 26% Type 1 diabetic, and 58% of ETDRS diabetic retinopathy level 10. Baseline results for the first 11 patients include MCT 3.9±0.9 sec (2.5-5.0), and RBF 27.6±9.4 arbitrary units (AU) (15.8-34.5). Conclusions: As expected, RBF is significantly lower than in historical non-diabetic controls (35.2±6.4 AU). These findings, good demographic distribution, and comparable randomized groups will permit valid comparison of MCT and RBF in diabetic patients following topical administration of an ET-1 inhibitor when data are unmasked in February, 2003. Complete data on all patients will be presented.

Keywords: diabetic retinopathy • clinical (human) or epidemiologic studies: tre • retina