Retinal Microvascular and Neuronal Changes Are Also Present, Even If Differently, in Adolescents with Type 1 Diabetes without Clinical Diabetic Retinopathy
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SUBMITTER: Pilotto E
PROVIDER: S-EPMC9323684 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo determine the risk factors for retinal microvascular impairment on optical coherence tomography angiography (OCT-A) in type 2 diabetic patients without clinical diabetic retinopathy (DR).MethodsThis retrospective and cross-sectional study enrolled 74 diabetic patients without clinically evident DR for the study group and 34 healthy subjects for the control group. OCT-A parameters were measured to determine vascular density (VD) and the foveal avascular zone (FAZ) size in the superficial and deep capillary plexuses (SCP/DCP) of the retina. Clinical data were collected on sex, age, diabetes duration, hemoglobin A1c (HbA1c), hypertension, dyslipidemia, low-density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate (eGFR) and smoking status. Multiple linear regression analyses were performed to represent the associated clinical variables with OCT-A parameters in diabetic patients.ResultsIn comparison between the study and control groups, the VD in the SCP and DCP were significantly lower in diabetic patients compared to the controls (P = 0.022 and 0.003, respectively). The FAZ size in the SCP and DCP were significantly greater in diabetic patients compared to the controls (P = 0.035 and <0.001, respectively). In age- and sex-adjusted multiple regression analyses for the diabetic patients, dyslipidemia and hypertension were negatively associated with SCP-VD (β = -0.357, P = 0.002; β = -0.239, P = 0.039, respectively). Current smoking was correlated with lower DCP-VD (β = -0.255, P = 0.043). Greater SCP-FAZ size was associated with dyslipidemia and greater LDL-C (β = 0.254, P = 0.013; β = 0.232, P = 0.029, respectively), and greater DCP-FAZ size, with lower eGFR and greater LDL-C (β = -0.355, P = 0.004; β = 0.235, P = 0.037, respectively).ConclusionsDiabetic patients without clinical DR showed lower VD and greater FAZ size in the SCP and DCP compared to healthy controls. In diabetic patients without clinical DR, dyslipidemia and/or high LDL-C were important risk factors for retinal microvascular impairment. Hypertension, current smoking and lower eGFR also contributed to microvascular impairment.
| S-EPMC6084984 | biostudies-literature
Project description:We used a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) to image the retina of subjects with non-proliferative diabetic retinopathy (NPDR). To improve visualization of different retinal features, the size and alignment of the confocal aperture were varied. The inner retinal layers contained clearly visualized retinal vessels. In diabetic subjects there was extensive capillary remodeling despite the subjects having only mild or moderate NPDR. Details of the retinal microvasculature were readily imaged with a larger confocal aperture. Hard exudates were observed with the AOSLO in all imaging modes. Photoreceptor layer images showed regions of bright cones and dark areas, corresponding in location to overlying vascular abnormalities and retinal edema. Clinically undetected intraretinal vessel remodeling and varying blood flow patterns were found. Perifoveal capillary diameters were larger in the diabetic subjects (p<0.01), and small arteriolar walls were thickened, based on wall to lumen measurements (p<.05). The results suggest that existing clinical classifications based on lower magnification clinical assessment may not adequately measure key vascular differences among individuals with NPDR.
| S-EPMC3959854 | biostudies-other
Project description:ImportanceQuantitative measurements based on optical coherence tomographic angiography (OCTA) may have value in managing diabetic retinopathy (DR), but there is limited information on the ability of OCTA to distinguish eyes with DR.ObjectiveTo evaluate the ability of measurements of retinal microvasculature using OCTA to distinguish healthy eyes from eyes with DR.Design, setting, and participantsIn this prospective cross-sectional study, OCTA was used to examine the eyes of participants with type 2 diabetes with or without DR and the eyes of participants without diabetes from September 17, 2015, to April 6, 2016. Density maps based on superficial retinal layer (SRL) and deeper retinal layer (DRL) images were generated after a method to remove decorrelation tails was applied to the DRL images.ExposuresBoth eyes of each participant were examined by means of a 3-mm OCTA scan and 7-field fundus photography using the Diabetic Retinopathy Severity Scale.Main outcomes and measuresTwo measures were examined: perfusion density, based on the area of vessels, and vessel density, based on a map with vessels of 1-pixel width. The size of the foveal avascular zone was also calculated automatically, and so was the area under the receiver operating characteristic curve.ResultsA total of 50 eyes from 26 participants with diabetes (10 women and 16 men; mean [SD] age, 64.9 [7.5] years) and 50 healthy eyes from 25 participants without diabetes (14 women and 11 men; mean [SD] age, 64.0 [7.1] years) were imaged. All participants were white. Vessel density measured in the SRL had the highest area under the receiver operating characteristic curve (0.893 [95% CI, 0.827-0.959]), compared with perfusion density in the SRL (0.794 [95% CI, 0.707-0.881]), foveal avascular zone area (0.472 [95% CI, 0.356-0.588]), and vessel density in the DRL (0.703 [95% CI, 0.601-0.805]). Vessel density in the SRL negatively correlated with best-corrected visual acuity (r = -0.28; P = .05) and severity of DR (r = -0.46; P = .001). Density metrics correlated with age. No correlation was detected between vascular density or foveal avascular zone metrics and hemoglobin A1C or duration of diabetes.Conclusions and relevanceVessel density measured by OCTA provides a quantitative metric of capillary closure that correlates with severity of DR and may allow staging, diagnosis, and monitoring that do not require subjective evaluation of fundus images.
| S-EPMC5470403 | biostudies-literature
Project description:BackgroundDiabetic retinopathy (DR) is a main complication of diabetes mellitus (DM). Recent studies have implicated microRNAs in human retinal microvascular endothelial cell (HRMEC) dysfunction. In this study, we aim to investigate the apoptotic promotion of miR-29b-3p by blocking SIRT1 in HRMEC for DR situation.MethodBlood samples were obtained from DR patients and controls. Dual-luciferase reporter assay using HEK-293T cells was performed to show the direct interaction of miR-29b-3p and the 3'UTR of SIRT1. HRMECs were exposed to 5.5 mmol/L of glucose (normal control), 5.5 mmol/L of glucose and 24.5 mmol/L of mannitol (osmotic pressure control), 30 mmol/L of glucose [hyperglycemia (HG)], 150 μmol/L of CoCl2 (hypoxia), and 30 mmol/L of glucose plus 150 μmol/L of CoCl2 (HG-CoCl2). To identify the regulating relationship between miR-29b-3p and SIRT1, HRMECs were transfected with miR-29b-3p mimics/inhibitors or their negative controls. SRT1720 was used as a SIRT1 agonist. Cell viability was assessed with the cell counting kit-8 (CCK-8) assay, and apoptotic cells were stained by one-step terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay kit. Gene and protein expression were assayed by quantitative real-time reverse transcriptase-PCR (RT-qPCR) and western blotting separately.ResultMiR-29b-3p was upregulated to 3.2-fold, and SIRT1 protein was downregulated to 65% in DR patients. Dual-luciferase reporter assay showed the direct interaction of miR-29b-3p and SIRT1. HRMECs were identified as >95% positive for CD31 and von Willebrand factor (vWF). MiR-29b-3p and Bax/Bcl-2 ratio was upregulated, whereas SIRT1 was downregulated in HRMECs in the HG-CoCl2 condition. Decreased cell viability and upregulated apoptosis were also found in HRMECs of the HG-CoCl2 condition. Upregulated miR-29b-3p decreased the expression of SIRT1 and increased the ratio of Bax/Bcl-2, whereas downregulated miR-29b-3p increased the expression of SIRT1 protein and downregulated the ratio of Bax/Bcl-2. SRT1720 rescued miR-29b-3p-induced HRMEC apoptosis via upregulating the expression of SIRT1 protein.ConclusionThe dysregulation of miR-29b-3p/SIRT1 is a potential mechanism of HRMEC apoptosis in DR. MiR-29b-3p/SIRT1 may be a potential therapeutic target for DR.
| S-EPMC7000655 | biostudies-literature
Project description:Purpose:To investigate the microvascular changes in macular retina and choriocapillaris (CC) in diabetic eyes without retinopathy using swept-source optical coherence tomography angiography (SS-OCTA). Methods:A commercial SS-OCTA system was used to collect 6 × 6-mm macular scans from patients. Three depth-resolved retinal slabs and a CC slab were segmented by a validated semiautomated algorithm. Retinal vessel area density, vessel skeleton density, and nonperfusion area were calculated on segmented retinal slabs. Foveal avascular zone was automatically measured based on en face image of the whole retinal layer. For CC quantification, the percentage of flow deficits (FD%) and the flow deficit (FD) sizes were measured. Results:Sixteen eyes from 16 diabetic patients without clinically detectable retinopathy and 16 eyes from 16 age-matched nondiabetic controls were included. There was no significant difference between the two groups in all retinal vessel quantitative parameters (all P > 0.05). However, the mean FD% and mean FD sizes were significantly increased in CC in the central 1.0-mm disk (P = 0.011 and P = 0.017, respectively), the central 1.5-mm rim (P = 0.003 and P = 0.009, respectively), the central 2.5-mm rim (P = 0.018 and P = 0.020, respectively), and the entire 5.0-mm disk (P = 0.009 and P = 0.008, respectively) in diabetic eyes compared with controls. Conclusions:CC perfusion in the macula is decreased in diabetic patients without retinopathy as compared to age-matched normal controls. Decreased CC perfusion in the macula may be an early indicator of otherwise clinically undetectable diabetic vasculopathy.
| S-EPMC7401698 | biostudies-literature
Project description:ObjectiveThe characteristics of the early changes in preclinical diabetic retinopathy (DR) are poorly known. This study aimed to analyse the changes in the structure and function of the fundus in diabetic patients without diabetic retinopathy (NDR).MethodsThis prospective study enrolled patients with type 2 diabetes and healthy controls from April to December 2020. Retinal sensitivity was measured by microperimetry. The peripapillary retinal nerve fibre layer (p-RNFL) thickness, macular retinal thickness, and retinal volume were measured by optical coherence tomography (OCT). The vessel density (VD) and perfusion density (PD) of the peripapillary area, as well as the foveal avascular zone (FAZ) area, FAZ perimeter, and FAZ circularity, were measured by optical coherence tomographic angiography (OCTA).ResultsA total of 71 cases (100 eyes) were enrolled in the study, including 34 cases (51 eyes) in the NDR group and 37 cases (49 eyes) in the control group. The mean retinal sensitivity was lower in the NDR group than in the control group for all sectors (all p < .001). Compared with controls, the NDR group showed thinner p-RNFL in the T sector (76.24 ± 14.29 vs. 85.47 ± 19.66 µm, p = .035). The NDR group had a thinner retina in the N2 sector (304.55 ± 16.07 vs. 312.02 ± 12.30 µm, p = .010). The PD of DCP was lower in the N2 sector in the NDR group (44.92 ± 11.77 vs. 50.27 ± 6.37%, p = .044). The VD was higher in the NDR group in RPCP-S/N/I, and the PD was higher in the RPCP-S/N (all p < .05). The frequencies of perifoveal capillary drop-out, notched or punched out borders of the superficial FAZ, and loss of smooth contour were all higher in the NDR group (all p < .05).ConclusionThe structure (p-RNFL thickness, VD, and PD) and function (retinal sensitivity) display some changes in diabetic patients even if they had not been found to have DR.Key messagesDecreased retinal sensitivity was observed in diabetic patients before the onset of diabetic retinopathy.Compared with the control group, we found the changes in vessel density or perfusion density in a certain area, whether in SCP, DCP, or RPCP in the NDR group.Before the onset of diabetic retinopathy, the structure and function of the retina in diabetic patients had changed.
| S-EPMC9258434 | biostudies-literature
Project description:Diabetic retinopathy is a major cause of vision loss worldwide and areas of retinal non-perfusion (RNP) are a key pathologic feature of the vascular component of diabetic retinopathy. While there is a need for a more complete understanding of the natural history of RNP development and progression, overall, increasing RNP has been closely linked with worsening DR severity. Both traditional and novel approaches to quantitative image assessment are being explored to advance our understanding of the vascular, physiologic and functional changes associated with progressive RNP. Retinal ischemia secondary to RNP leads to tissue hypoxia and changes in the expression of a host of signalling molecules. Current anti-vascular endothelial growth factor and steroid pharmaceutical agents appear to be unable to reperuse areas of RNP, but may be able to slow the progressive longitudinal accumulation of RNP with regular retreatments. There remains a tremendous unmet need for pharmacotherapies that can slow RNP progression and ultimately reperfuse areas of the non-perfused retina. Towards this end, novel targets including the semaphorin family are being investigated.
| S-EPMC8807828 | biostudies-literature
Project description:Diabetic retinopathy (DR) is a leading cause of visual impairment and blindness worldwide. Since DR was first recognized as an important complication of diabetes, there have been many attempts to accurately classify the severity and stages of disease. These historical classification systems evolved as understanding of disease pathophysiology improved, methods of imaging and assessing DR changed, and effective treatments were developed. Current DR classification systems are effective, and have been the basis of major research trials and clinical management guidelines for decades. However, with further new developments such as recognition of diabetic retinal neurodegeneration, new imaging platforms such as optical coherence tomography and ultra wide-field retinal imaging, artificial intelligence and new treatments, our current classification systems have significant limitations that need to be addressed. In this paper, we provide a historical review of different classification systems for DR, and discuss the limitations of our current classification systems in the context of new developments. We also review the implications of new developments in the field, to see how they might feature in a future, updated classification.
| S-EPMC9800497 | biostudies-literature
Project description:BackgroundTo explore the characteristics of retina microvascular changes in patients with diabetic nephropathy (DN) and its risk factors.MethodsRetrospective, observational study. 145 patients with type 2 diabetic mellitus (DM) and DN were included in the study. Demographic and clinical parameters were obtained from medical records. Presence of diabetic retinopathy (DR), hard exudates (HEs) and diabetic macular edema (DME) were evaluated according to the color fundus images, optical coherence tomography (OCT) and fluorescence angiography (FFA).ResultsDR accounted for 61.4% in type 2 DM patients with DN, of which proliferative diabetic retinopathy (PDR) accounted for 23.6% and sight threatening DR accounted for 35.7%. DR group had significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p = 0.004), HbA1c (P = 0.037), Urine albumin creatine ratio (ACR) (p < 0.001) and lower level of estimated glomerular filtration rate (eGFR) (P = 0.013). Logistic regression analysis showed DR was significantly associated with ACR stage (p = 0.011). Subjects with ACR stage3 had higher incidence of DR compared with subjects with ACR stage1 (OR = 24.15, 95%CI: 2.06-282.95). 138 eyes of 138 patients were analyzed for HEs and DME, of which 23.2% had HEs in posterior pole and 9.4% had DME. Visual acuity was worse in HEs group than in non-HEs group. There was significant difference in the LDL-C cholesterol level, total cholesterol (CHOL) level and ACR between HEs group and non-HEs group.ConclusionsA relatively higher prevalence of DR was found in type 2 DM patients with DN. ACR stage could be recognized as a risk factor for DR in DN patients. Patients with DN needs ophthalmic examination more timely and more frequently.
| S-EPMC10161482 | biostudies-literature
Project description:Diabetic retinopathy is the major blinding disease among working-age populations, which is becoming more significant due to the growth of diabetes. The metabolic-induced oxidative and inflammatory stress leads to the insult of neovascular unit, resulting in the core pathophysiology of diabetic retinopathy. Existing therapies focus on the inflammation, oxidation, and angiogenesis phenomena of diabetic retinopathy, without effect to radically cure the disease. This review also summarizes novel therapeutic attempts for diabetic retinopathy along with their advantages and disadvantages, mainly focusing on those using cellular and genetic techniques to achieve remission on a fundamental level of disease.
| S-EPMC9267063 | biostudies-literature