Retinal Capillary Plexus Pattern and Density from Fovea to Periphery Measured in Healthy Eyes with Swept-Source Optical Coherence Tomography Angiography.

Optical coherence tomography angiography is evolving towards wider fields of view. As single widefield acquisitions have a lower resolution, preventing an accurate segmentation of vascular plexuses in the periphery, we examined the retinal vascularisation from the macula to the periphery in all retinal quadrants, using 3 × 3-mm volume scans, to obtain montages with sufficient image resolution up to 11 mm from the foveal centre. Images were qualitatively and quantitatively analysed, using C- and B-scan approaches to calculate the capillary density (CD) and the interplexus distance (IPD). Three vascular plexuses (i.e., superficial vascular plexus: SVP, intermediate capillary plexus: ICP, and deep capillary plexus: DCP) were observed up to the mid-periphery in all sectors. The CD of the SVP decreased from about 5 mm of eccentricity, along with ganglion cell density decrease. The CD of the ICP progressively decreased from the fovea towards the periphery, along with the retinal thinning and then vanished from 8 to 9 mm of eccentricity, becoming undetectable beyond. This ICP disappearance resulted in an increased IPD between the SVP and the DCP in an area known to be frequently affected by capillary drop-out in diabetic retinopathy. The DCP only showed a slightly decreased CD towards the retinal periphery.

Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study.

AIMS: Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. METHODS: We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs.We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. RESULTS: In the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1.139 [0.800-1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. CONCLUSIONS: The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.