Jakob Grauslund1,2,3, Ulrik Frydkjaer-Olsen1,2, Tunde Peto2,4, Jimena Fernández-Carneado5, Berta Ponsati5, Cristina Hernández6, José Cunha-Vaz7, Rafael Simó6. 1. Department of Ophthalmology, Odense University Hospital, Odense, Denmark. 2. Department of Clinical Research, University of Southern Denmark, Odense, Denmark. 3. Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark. 4. Centre for Public Health, Institute of Clinical Sciences, Queen's University Belfast, Belfast, United Kingdom. 5. BCN Peptides, Barcelona, Spain. 6. Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d'Hebron (VHIR), Barcelona, Spain. 7. Association for Innovation and Biomedical Research on Light and Image (AIBILI), and University of Coimbra, Coimbra, Portugal.
Abstract
Purpose: Structural retinal microvascular changes have been identified as risk markers of diabetic retinopathy (DR). In order to estimate the retinal response of neuroprotective eye drops, we aimed to evaluate the effect of topical retinal neuroprotection on retinal microvascular changes in early DR. Methods:Patients with type 2 diabetes with no or early DR were randomized 1:1:1 to topical treatment with placebo, brimonidine, or somatostatin in a 96-week prospective, phase II to III, European multicenter trial. Retinal vascular calibers were measured semiautomatically in digital fundus images by certified graders at baseline and follow-up and summarized as central retinal arteriolar and venular equivalent (CRAE and CRVE). Results: Of 449 patients originally included, 297 completed the study with gradable retinal images. Median age and duration of diabetes was 64.5 and 9.9 years, and 65.7% were male. At baseline, Early Treatment Diabetic Retinopathy Study levels were 10 (no DR, 42.8%), 20 (minimal DR, 28.3%), and 35 (mild DR, 29.0%), and CRAE and CRVE did not differ between groups. As opposed to patients with no or minimal DR at baseline, patients with mild DR in the active groups developed a larger retinal arteriolar (brimonidine: +6.2 μm, P = 0.006; somatostatin: +7.2 μm, P = 0.006) and venular (brimonidine: +13.9 μm, P = 0.01; somatostatin: +14.3 μm, P = 0.0001) caliber in contrast to those in the placebo group. Conclusions: Topical treatment with brimonidine and somatostatin causes retinal arteriolar and venular dilation in patients with type 2 diabetes and preexisting early DR. Upcoming studies should elaborate on the potential of these findings in arresting early DR.
RCT Entities:
Purpose: Structural retinal microvascular changes have been identified as risk markers of diabetic retinopathy (DR). In order to estimate the retinal response of neuroprotective eye drops, we aimed to evaluate the effect of topical retinal neuroprotection on retinal microvascular changes in early DR. Methods:Patients with type 2 diabetes with no or early DR were randomized 1:1:1 to topical treatment with placebo, brimonidine, or somatostatin in a 96-week prospective, phase II to III, European multicenter trial. Retinal vascular calibers were measured semiautomatically in digital fundus images by certified graders at baseline and follow-up and summarized as central retinal arteriolar and venular equivalent (CRAE and CRVE). Results: Of 449 patients originally included, 297 completed the study with gradable retinal images. Median age and duration of diabetes was 64.5 and 9.9 years, and 65.7% were male. At baseline, Early Treatment Diabetic Retinopathy Study levels were 10 (no DR, 42.8%), 20 (minimal DR, 28.3%), and 35 (mild DR, 29.0%), and CRAE and CRVE did not differ between groups. As opposed to patients with no or minimal DR at baseline, patients with mild DR in the active groups developed a larger retinal arteriolar (brimonidine: +6.2 μm, P = 0.006; somatostatin: +7.2 μm, P = 0.006) and venular (brimonidine: +13.9 μm, P = 0.01; somatostatin: +14.3 μm, P = 0.0001) caliber in contrast to those in the placebo group. Conclusions: Topical treatment with brimonidine and somatostatin causes retinal arteriolar and venular dilation in patients with type 2 diabetes and preexisting early DR. Upcoming studies should elaborate on the potential of these findings in arresting early DR.
Authors: Ricardo Raúl Robles-Rivera; José Alberto Castellanos-González; Cecilia Olvera-Montaño; Raúl Alonso Flores-Martin; Ana Karen López-Contreras; Diana Esperanza Arevalo-Simental; Ernesto Germán Cardona-Muñoz; Luis Miguel Roman-Pintos; Adolfo Daniel Rodríguez-Carrizalez Journal: Oxid Med Cell Longev Date: 2020-03-11 Impact factor: 6.543