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      Characterization of One-Year Progression of Risk Phenotypes of Diabetic Retinopathy

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          Abstract

          Introduction

          We characterized the progression of different diabetic retinopathy (DR) phenotypes in type 2 diabetes (T2D).

          Methods

          A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with three visits (baseline, 6 months, and 1 year). Demographic and systemic data included age, sex, diabetes duration, lipid profile, and hemoglobin A1c (HbA1c). Ophthalmological examinations included best-corrected visual acuity (BCVA), color fundus photography (CFP), and optical coherence tomography (OCT and OCTA). Phenotype classification was performed at the 6-month visit based on microaneurysm turnover (MAT, on CFP) and central retinal thickness (CRT, on OCT). Only risk phenotypes B (MAT < 6 and increased CRT) and C (MAT ≥ 6 with or without increased CRT) were included. ETDRS grading was performed at the baseline visit based on seven-field CFP.

          Results

          A total of 133 T2D individuals were included in the study; 81 (60%) eyes were classified as phenotype B and 52 (40%) eyes as phenotype C. Of these, 128 completed the 1-year follow-up. At baseline, eyes with phenotype C showed greater capillary closure (superior capillary plexus, deep capillary plexus, and full retina, p < 0.001) and increased foveal avascular zone (FAZ) area ( p < 0.001), indicating more advanced microvascular disease. Neurodegeneration represented by thinning of the ganglion cell layer + inner plexiform layer (GCL + IPL) was present in both phenotypes. When analyzing the 1-year progression of each phenotype, only phenotype C revealed a significant decrease in BCVA ( p = 0.02) and enlargement of the FAZ ( p = 0.03). A significant progressive decrease in the vessel density of the deep capillary layer and in MAT occurred in both phenotypes, but these changes were particularly relevant in phenotype C and ETDRS grades 43–47. During the 1-year period, both phenotypes B and C showed progression in GCL + IPL thinning ( p < 0.001).

          Conclusions

          In the 1-year period of follow-up, both phenotypes B and C showed progression in retinal neurodegeneration, whereas phenotype C showed more marked disease progression at the microvascular level.

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          Most cited references24

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          Diabetic retinopathy.

          Diabetic retinopathy is a common and specific microvascular complication of diabetes, and remains the leading cause of preventable blindness in working-aged people. It is identified in a third of people with diabetes and associated with increased risk of life-threatening systemic vascular complications, including stroke, coronary heart disease, and heart failure. Optimum control of blood glucose, blood pressure, and possibly blood lipids remains the foundation for reduction of risk of retinopathy development and progression. Timely laser therapy is effective for preservation of sight in proliferative retinopathy and macular oedema, but its ability to reverse visual loss is poor. Vitrectomy surgery might occasionally be needed for advanced retinopathy. New therapies, such as intraocular injection of steroids and antivascular endothelial growth-factor agents, are less destructive to the retina than are older therapies, and could be useful in patients who respond poorly to conventional therapy. The outlook for future treatment modalities, such as inhibition of other angiogenic factors, regenerative therapy, and topical therapy, is promising. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Neurodegeneration in diabetic retinopathy: does it really matter?

            The concept of diabetic retinopathy as a microvascular disease has evolved, in that it is now considered a more complex diabetic complication in which neurodegeneration plays a significant role. In this article we provide a critical overview of the role of microvascular abnormalities and neurodegeneration in the pathogenesis of diabetic retinopathy. A special emphasis is placed on the pathophysiology of the neurovascular unit (NVU), including the contributions of microvascular and neural elements. The potential mechanisms linking retinal neurodegeneration and early microvascular impairment, and the effects of neuroprotective drugs are summarised. Additionally, we discuss how the assessment of retinal neurodegeneration could be an important index of cognitive status, thus helping to identify individuals at risk of dementia, which will impact on current procedures for diabetes management. We conclude that glial, neural and microvascular dysfunction are interdependent and essential for the development of diabetic retinopathy. Despite this intricate relationship, retinal neurodegeneration is a critical endpoint and neuroprotection, itself, can be considered a therapeutic target, independently of its potential impact on microvascular disease. In addition, interventional studies targeting pathogenic pathways that impact the NVU are needed. Findings from these studies will be crucial, not only for increasing our understanding of diabetic retinopathy, but also to help to implement a timely and efficient personalised medicine approach for treating this diabetic complication. Electronic supplementary material The online version of this article (10.1007/s00125-018-4692-1) contains a slideset of the figures for download, which is available to authorised users.
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              Impact of recent increase in incidence on future diabetes burden: U.S., 2005-2050.

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                Author and article information

                Contributors
                mlribeiro@aibili.pt
                cunhavaz@aibili.pt
                Journal
                Ophthalmol Ther
                Ophthalmol Ther
                Ophthalmology and Therapy
                Springer Healthcare (Cheshire )
                2193-8245
                2193-6528
                5 December 2021
                5 December 2021
                February 2022
                : 11
                : 1
                : 333-345
                Affiliations
                [1 ]GRID grid.422199.5, ISNI 0000 0004 6364 7450, AIBILI-Association for Innovation and Biomedical Research on Light and Image, ; Coimbra, Portugal
                [2 ]GRID grid.8051.c, ISNI 0000 0000 9511 4342, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, , University of Coimbra, ; Coimbra, Portugal
                [3 ]GRID grid.8051.c, ISNI 0000 0000 9511 4342, Center for Innovative Biomedicine and Biotechnology (CIBB), , University of Coimbra, ; 3000-548 Coimbra, Portugal
                [4 ]GRID grid.28911.33, ISNI 0000000106861985, Department of Ophthalmology, , Centro Hospitalar e Universitário de Coimbra (CHUC), ; Coimbra, Portugal
                [5 ]GRID grid.410926.8, ISNI 0000 0001 2191 8636, Department of Orthoptics, School of Health, , Polytechnic of Porto, ; Porto, Portugal
                Article
                437
                10.1007/s40123-021-00437-z
                8770718
                34865186
                a07ca3fd-b25f-4339-be8d-22a4237f5e67
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 18 October 2021
                : 18 November 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001871, Fundação para a Ciência e a Tecnologia;
                Award ID: 02/SAICT/2017 – 032412
                Award Recipient :
                Funded by: COMPETE Portugal2020
                Funded by: Fundo de inovação, tecnologia e economia circular - FITEC
                Award ID: Programa Interface (FITEC/CIT/2018/2)
                Categories
                Original Research
                Custom metadata
                © The Author(s) 2022

                diabetes,retinopathy,capillary closure,neurodegeneration

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