PAI-1 is a vascular cell-specific HIF-2-dependent angiogenic factor that promotes retinal neovascularization in diabetic patients. Science advances For patients with proliferative diabetic retinopathy (PDR) who do not respond adequately to pan-retinal laser photocoagulation (PRP) or anti-vascular endothelial growth factor (VEGF) therapies, we hypothesized that vascular cells within neovascular tissue secrete autocrine/paracrine angiogenic factors that promote disease progression. To identify these factors, we performed multiplex ELISA angiogenesis arrays on aqueous fluid from PDR patients who responded inadequately to anti-VEGF therapy and/or PRP and identified plasminogen activator inhibitor-1 (PAI-1). PAI-1 expression was increased in vitreous biopsies and neovascular tissue from PDR eyes, limited to retinal vascular cells, regulated by the transcription factor hypoxia-inducible factor (HIF)-2α, and necessary and sufficient to stimulate angiogenesis. Using a pharmacologic inhibitor of HIF-2α (PT-2385) or nanoparticle-mediated RNA interference targeting , we demonstrate that the HIF-2α/PAI-1 axis is necessary for the development of retinal neovascularization in mice. These results suggest that targeting HIF-2α/PAI-1 will be an effective adjunct therapy for the treatment of PDR patients. 10.1126/sciadv.abm1896

Photoreceptor cells and RPE contribute to the development of diabetic retinopathy. Progress in retinal and eye research Diabetic retinopathy (DR) is a leading cause of blindness. It has long been regarded as vascular disease, but work in the past years has shown abnormalities also in the neural retina. Unfortunately, research on the vascular and neural abnormalities have remained largely separate, instead of being integrated into a comprehensive view of DR that includes both the neural and vascular components. Recent evidence suggests that the most predominant neural cell in the retina (photoreceptors) and the adjacent retinal pigment epithelium (RPE) play an important role in the development of vascular lesions characteristic of DR. This review summarizes evidence that the outer retina is altered in diabetes, and that photoreceptors and RPE contribute to retinal vascular alterations in the early stages of the retinopathy. The possible molecular mechanisms by which cells of the outer retina might contribute to retinal vascular damage in diabetes also are discussed. Diabetes-induced alterations in the outer retina represent a novel therapeutic target to inhibit DR. 10.1016/j.preteyeres.2020.100919

Optical coherence tomography angiography in diabetic retinopathy. Progress in retinal and eye research There remain many unanswered questions on how to assess and treat the pathology and complications that arise from diabetic retinopathy (DR). Optical coherence tomography angiography (OCTA) is a novel and non-invasive three-dimensional imaging method that can visualize capillaries in all retinal layers. Numerous studies have confirmed that OCTA can identify early evidence of microvascular changes and provide quantitative assessment of the extent of diseases such as DR and its complications. A number of informative OCTA metrics could be used to assess DR in clinical trials, including measurements of the foveal avascular zone (FAZ; area, acircularity, 3D para-FAZ vessel density), vessel density, extrafoveal avascular zones, and neovascularization. Assessing patients with DR using a full-retinal slab OCTA image can limit segmentation errors and confounding factors such as those related to center-involved diabetic macular edema. Given emerging data suggesting the importance of the peripheral retinal vasculature in assessing and predicting DR progression, wide-field OCTA imaging should also be used. Finally, the use of automated methods and algorithms for OCTA image analysis, such as those that can distinguish between areas of true and false signals, reconstruct images, and produce quantitative metrics, such as FAZ area, will greatly improve the efficiency and standardization of results between studies. Most importantly, clinical trial protocols should account for the relatively high frequency of poor-quality data related to sub-optimal imaging conditions in DR and should incorporate time for assessing OCTA image quality and re-imaging patients where necessary. 10.1016/j.preteyeres.2023.101206

Optical coherence angiography: A review. Medicine BACKGROUND:Retinal vascular diseases are one of the most common causes of blindness in the developed world. Optical Coherence Tomography Angiography (OCT-A) is a new noninvasive method that uses several algorithms to detect blood movement. This enables the creation of high-resolution vascular images with contrast depicting motionless tissue. METHODS:This review presents the results of articles relevant to age-related macular degeneration (AMD), diabetic retinopathy (DR), and OCT-A. The OCT-A technique can successfully be used in the diagnosis of neovascularization, retinal vein occlusion (RVO) and retinal artery occlusion (RAO), vessel abnormalities and even anterior segment neovascularization. OCT-A can also be applied to compute data such as vessel density, and flow index in both superficial and deep plexuses. RESULTS:Many studies have compared fluorescein angiography with OCT-A. Other studies have reported differences in vascular density in AMD patients and have compared them with people having healthy eyes. Although OCT-A offers rapid picture acquisition, high repeatability and resolution, it also has many drawbacks. The most common are: motion artifacts, projections from overlying vessels and limited field of view.An interesting new application is the possibility to assess changes during antivascular endothelial growth factor (anti-VEGF) therapy. Another function of OCT-A is the possible application in the study of choriocapillaries in many fields of ocular pathology. CONCLUSION:OCT-A is a new promising method that allows the visualization of the retinal vascular network and the counting of blood flow parameters. This technique provides reliable images useful in clinical routines. 10.1097/MD.0000000000004907