Preclinical Diabetic Retinopathy Research Articles

Commentary: Is preclinical diabetic retinopathy in diabetic nephropathy individuals more severe?

Commentary: Is preclinical diabetic retinopathy in diabetic nephropathy individuals more severe?

Improved Melatonin Delivery by a Size-Controlled Polydopamine Nanoformulation Attenuates Preclinical Diabetic Retinopathy.

Oxidative stress, reactive oxygen species generation, and overexpression of VEGF are signatory events in diabetic retinopathy. The downregulation of VEGF and anti-inflammatory action pave the way for diabetic retinopathy (DR) therapy. In that, lower absorption kinetics of melatonin limits its immense therapeutic potential. Hence, we have demonstrated a reverse microemulsion method to synthesize melatonin-loaded polydopamine nanoparticles to replenish both at a single platform with an improved melatonin delivery profile. The study has evaluated in vitro and in vivo protection efficiency of biocompatible melatonin-loaded polydopamine nanoparticles (MPDANPs). The protection mechanism was explained by downregulation of VEGF, CASPASE3, and PKCδ against high-glucose/streptozotocin (STZ)-induced insults, in vitro and in vivo. The anti-inflammatory and antiangiogenic effect and potential of MPDANPs to enhance melatonin in vivo stability with prolonged circulation time have proved MPDANPs as a potential therapeutic candidate in DR management. The DR therapeutic potential of MPDANPs has been arbitrated by improving the bioavailability of melatonin and inhibition of VEGF-PKCδ crosstalk in vivo.

Is preclinical diabetic retinopathy in diabetic nephropathy individuals more severe?

To analyse the retinal vessel density and thickness characteristics of diabetic nephropathy (DN) individuals with preclinical diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). This retrospective case-control study included 88 eyes of 88 type 2 DM patients with preclinical DR [44 non-DN (NDN) and 44 DN]. OCTA images and data were acquired using AngioVue 2.0 of the spectral domain OCT device. The foveal avascular zone (FAZ) area, superficial capillary plexus (SCP) and deep capillary plexus vessel densities, ganglion cell complex (GCC) and full retinal thicknesses, peripapillary capillary density and nerve fibre layer (RNFL) thickness were compared between the NDN and DN groups. The relationship between each renal function parameter and each OCTA parameter was analysed. SCP vessel density, GCC thickness and full retinal thickness were significantly reduced in DN individuals compared to NDN individuals [(NDN versus DN) SCP vessel density: 46.65 ± 3.84% versus 44.35 ± 5.25%, p=0.030; GCC thickness: 100.79 ± 5.92 μm versus 93.28 ± 8.66 μm, p<0.001; full retinal thickness: whole area: 287.04 ± 13.62 μm versus 277.71 ± 15.10 μm, p=0.005). Within the peripapillary area, capillary density was also significantly reduced in the whole area (50.19 ± 3.10% versus 47.46 ± 5.93%, p=0.016) and some sectors in the DN group, though RNFL thickness was only decreased in some sectors. For all individuals, estimated glomerular filtration rate (eGFR) correlated significantly with most OCTA parameters and then showed a significantly negative correlation with FAZ area (β=-16.43, p=0.039) in multivariate linear regression analysis. In the NDN group, eGFR showed a significantly negative correlation with FAZ area (β=-18.746, p=0.048) and a significantly positive correlation with SCP vessel density (β=0.580, p=0.036). Preclinical DR may be more severe in DN individuals than in NDN individuals with regard to microvascular and microstructural impairment. Moreover, eGFR may be a good indicator for retinal microvascular impairment.

Neutrophil–lymphocyte ratio as a reliable marker to predict pre-clinical retinopathy among type 2 diabetic patients

BackgroundDiabetic retinopathy is now recognized as a neurovascular in lieu of a microvascular complication. Visual evoked potentials (VEPs) are greatly valuable in detecting early diabetic retinal functional changes before the occurrence of structural damage. Low-grade inflammation plays a fundamental part in the development and progression of retinopathy in diabetics. Detecting diabetic patients with early retinopathy before the occurrence of clinical symptoms provides a window of opportunity to ensure the best prognosis for these eyes. Neutrophil–lymphocyte ratio (NLR) has recently been introduced as a novel marker of inflammation in various diseases. Indeed, the presence of a cheap, available, and reliable marker of inflammation that is capable to detect pre-clinical diabetic retinopathy (P-DR) is crucial for early intervention to retard the progression of ocular damage. As far as we know no previous studies investigated the role of NLR in the detection of P-DR. The aim of this study was to investigate the quality of prediction of NLR in detecting pre-clinical retinopathy in type 2 diabetic patients.ResultsIn this case–control study, VEPs results showed a significant delay in P100 latencies of the patients’ group compared to the control group. According to the VEPs results, the patient group was further subdivided into two: diabetic with VEPs changes (a group with P-DR) and diabetic without VEPs changes. NLR was significantly elevated in patients with P-DR (p < 0.001). NLR cut-off point ≥ 1.97 is able to predict P-DR with 89.29% sensitivity and 84.37% specificity. Linear regression model revealed that NLR is the only independent factor that predicts P-DR. (odds ratio 3.312; 95% confidence interval 1.262–8.696, p = 0.015*.ConclusionsVisual evoked potentials have an important role to evaluate the visual pathway in diabetics and to diagnose pre-clinical diabetic retinopathy before the occurrence of structural damage. Neutrophil–lymphocyte ratio is a reliable marker for the detection of pre-clinical diabetic retinopathy with good sensitivity (89.29%) and specificity (84.37%). Finding a reliable available laboratory test to predict P-DR could be of help to save diabetic patients from serious ocular complications.

Retinal Capillary Nonperfusion in Preclinical Diabetic Retinopathy

Introduction: The aim of the study was to identify retinal microvascular changes using optical coherence tomography angiography (OCTA) in type 2 diabetes (T2D) patients with preclinical retinopathy identified by ultra-widefield fundus photography (UWF-FP). Methods: This is a cross-sectional observational study. All patients underwent UWF-FP 200° examinations with OPTOS California (Optos, Dunfermline, UK) and Cirrus AngioPlex® spectral-domain (SD)-OCTA 3 × 3 mm acquisitions (ZEISS, Dublin, CA, USA). The absence of visible lesions was identified using UWF-FP. Results: One hundred and ninety three eyes of individuals with T2D with no visible lesions in the fundus and identified in a screening setting were included in the study. Skeletonized vessel density (SVD), perfusion density (PD), and areas of capillary nonperfusion (CNP) values on SD-OCTA were significantly decreased when compared with healthy population (p Conclusions: Retinal capillary nonperfusion detected by OCTA metrics of SVD and CNP can be identified in the central retina in eyes with T2D before development of visible lesions in the retina. Our findings confirm the relevance of OCTA to identify macular microvascular changes in the initial stages of diabetic retinopathy, allowing the identification of its ischemic phenotype very early in the disease process.

OCT-Angiography in Detecting Preclinical Diabetic Retinopathy

The introduction of OCT-angiography was a milestone in studying the early stages of diabetic retinopathy (DR). The latest findings show significant changes in foveal avascular zone (FAZ) parameters (FAZ area, FAZ perimeter, acirculatory index, axis ratio, FAZ angle) in diabetes mellitus (DM) patients with no ophthalmoscopic signs of DR. Many research groups evaluate vessel density (VD) in superficial and deep plexuses in these patients using different methods of image postprocessing, different qualitative and quantitative parameters. Nonperfusion areas (NA) are very important findings at the preclinical stage of DR, which can be detected in superficial and deep layers. With OCT-A it is possible not only to reveal them but also to calculate their area. Vascular tortuosity (VT) was described earlier using fundus photography. Nowadays VT can be assessed at the microcirculation level in OCT-A scans. Microaneurysms are the earliest clinical sign of DR. They can be missed in fundus photos, but easily detected with OCT-A. The aim of the current review is to analyze the latest OCT-A findings at the preclinical stage of DR and to discuss the future diagnostic value of OCT-A in DR.

Structural and functional retinal changes in patients with type 2 diabetes without diabetic retinopathy

Objective The 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). Methods This 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). Results A 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). Conclusion The 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 messages Decreased 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.

Alpha-Smooth Muscle Actin Expression and Parafoveal Blood Flow Pathways Are Altered in Preclinical Diabetic Retinopathy.

PurposeTo investigate differences in alpha smooth muscle actin (αSMA) expression and parafoveal blood flow pathways in diabetic retinopathy (DR).MethodsHuman donor eyes from healthy subjects (n = 8), patients with diabetes but no DR (DR–; n = 7), and patients with clinical DR (DR+; n = 13) were perfusion labeled with antibodies targeting αSMA, lectin, collagen IV, and filamentous actin. High-resolution confocal scanning laser microscopy was used to quantify αSMA staining and capillary density in the parafoveal circulation. Quantitative analyses of connections between retinal arteries and veins within the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were performed.ResultsMean age between the groups was not different (P = 0.979). αSMA staining was seen in the SVP and ICP of all groups. The DCP was predominantly devoid of αSMA staining in control eyes but increased in a disease stage–specific manner in the DR– and DR+ groups. The increase in αSMA staining was localized to pericytes and endothelia of terminal arterioles and adjacent capillary segments. Capillary density was less in the DCP in the DR+ group (P < 0.001). ICP of the DR– and DR+ groups received more direct arteriole supplies than the control group (P < 0.001). Venous outflow pathways were not altered (all P > 0.284).ConclusionsAlterations in αSMA and vascular inflow pathways in preclinical DR suggest that perfusion abnormalities precede structural vascular changes such as capillary loss. Preclinical DR may be characterized by a “steal” phenomenon where blood flow is preferentially diverted from the SVP to the ICP and DCP.

Сосудистая плотность в поверхностном сплетении как окт-а маркер прогрессирования доклинической диабетической ретинопатии

Purpose. To evaluate time-related OCT-A changes in patients with preclinical diabetic retinopathy and to identify OCT-A biomarkers of progression. Methods. A total of 42 diabetes mellitus (DM) patients (73 eyes) were recruited in the study. All patients underwent 7-field fundus photography, optical coherence tomography (OCT) and OCT-angiography (OCT-A). The examination was repeated in one and two years. Assessed OCT-A parameters included foveal avascular zone (FAZ) area, acircularity index (AI), vessel density (VD0-300 and VD300-600), skeletonized density. Results. FAZ area was significantly enlarged after two years of observation (0.25 ± 0.05 mm² and 0.28 ± 0.06 mm² , respectively, р&lt; 0,0001). After a year of observation AI was significantly higher (1.37 ± 0.18 and 1.47 ± 0.20, respectively, р= 0.01) and VD0-300 was decreased in SVP and DCP. Logistic regression and ROC-analysis were used to identify biomarker of DR progression – VD0-300 in SVP, AUC = 0.821. Conclusions. To conclude, FAZ area and AI were significantly increased in follow-up visits. According to logistic regression analysis, VD0-300 in SVP can be the most appropriate OCT-A biomarker of preclinical DR progression. Keyword: diabetic retinopathy, vessel density, OCT-angiography.

Tissue Inhibitor of Metalloproteinase-3 Ameliorates Diabetes-Induced Retinal Inflammation.

Purpose: Endogenous tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) has powerful regulatory effects on inflammation and angiogenesis. In this study, we investigated the role of TIMP-3 in regulating inflammation in the diabetic retina.Methods: Vitreous samples from patients with proliferative diabetic retinopathy (PDR) and non-diabetic patients were subjected to Western blot analysis. Streptozotocin-treated rats were used as a preclinical diabetic retinopathy (DR) model. Blood-retinal barrier (BRB) breakdown was assessed with fluorescein isothiocyanate (FITC)-conjugated dextran. Rat retinas, human retinal microvascular endothelial cells (HRMECs) and human retinal Müller glial cells were studied by Western blot analysis and ELISA. Adherence of human monocytes to HRMECs was assessed and in vitro angiogenesis assays were performed.Results: Tissue inhibitor of matrix metalloproteinase-3 in vitreous samples was largely glycosylated. Intravitreal injection of TIMP-3 attenuated diabetes-induced BRB breakdown. This effect was associated with downregulation of diabetes-induced upregulation of the p65 subunit of NF-κB, intercellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF), whereas phospho-ERK1/2 levels were not altered. In Müller cell cultures, TIMP-3 significantly attenuated VEGF upregulation induced by high-glucose (HG), the hypoxia mimetic agent cobalt chloride (CoCl2) and TNF-α and attenuated MCP-1 upregulation induced by CoCl2 and TNF-α, but not by HG. TIMP-3 attenuated HG-induced upregulation of phospho-ERK1/2, caspase-3 and the mature form of ADAM17, but not the levels of the p65 subunit of NF-κB and the proform of ADAM17 in Müller cells. TIMP-3 significantly downregulated TNF-α-induced upregulation of ICAM-1 and VCAM-1 in HRMECs. Accordingly, TIMP-3 significantly decreased spontaneous and TNF-α- and VEGF-induced adherence of monocytes to HRMECs. Finally, TIMP-3 significantly attenuated VEGF-induced migration, chemotaxis and proliferation of HRMECs.Conclusion: In vitro and in vivo data point to anti-inflammatory and anti-angiogenic effects of TIMP-3 and support further studies for its applications in the treatment of DR.

The role of Optical Coherence Tomography Angiography to detect early microvascular changes in Diabetic Retinopathy: a systematic review.

To evaluate quantitative parafoveal microvascular changes using Optical Coherence Tomography Angiography (OCTA) by comparing the area of foveal avascular zone (FAZ) and vessel density (VD) between nondiabetic controls and patients with different levels of Diabetic Retinopathy (DR). A systematic review was performed according to the recommendations of the "Cochrane Handbook for Systematic Reviews of Interventions" and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Three electronic databases including PubMed, Web of Science and Cochrane Library were systematically retrieved by using key terms with Boolean operators. The data extracted from each study included: first author, year of publication, study design, sample size and participant characteristics (mean age, type of diabetes mellitus and mean duration of diabetic disease). Outcome variables included: VD and area of FAZ, in superficial and deep capillary plexuses of parafovea. 355 articles were identified from our search of databases and 10 studies were included in this systematic review. Patients with diabetes with or without clinical signs of DR have a significantly enlarged area of FAZ and decreased parafoveal VD compared to healthy controls, as well as an association between these microvascular changes and worsening DR. OCTA can provide valuable information about early and subtle microvascular changes of parafoveal capillary plexuses in patients with diabetes and can identify preclinical DR before the manifestation of clinically apparent retinopathy. The non-invasive nature of OCTA allows routine imaging of the retinal vasculature, so this approach may be a promising tool for screening programmes of DR.

OCT angiography in detecting preclinical diabetic retinopathy

The invention of OCT angiography (OCTA) was a milestone in studying the early stages of diabetic retinopathy (DR). The latest findings show significant changes in foveal avascular zone (FAZ) parameters (FAZ area, FAZ perimeter, acirculatory index, axis ratio, FAZ angle) in diabetes mellitus patients with no ophthalmoscopic signs of DR. Many studies evaluate vessel density in superficial and deep plexuses in these patients using different methods of image processing and different qualitative and quantitative parameters. Nonperfusion areas (NA) are very important findings at the preclinical stage of DR, which can be detected in superficial and deep layers. With OCT-A it is possible not only to reveal them but also to calculate their area. Vascular tortuosity (VT) was described earlier using fundus photography. Nowadays VT can be assessed at the microcirculation level in OCT-A scans. Microaneurysms are the earliest clinical sign of DR. They can be missed in fundus photos, but easily detected with OCT-A. The aim of the current review is to analyze the latest OCT-A findings at the preclinical stage of DR and to discuss the future diagnostic value of OCT-A in DR.

Do SGLT2 inhibitors prevent preclinical diabetic retinopathy? A Prospective Pilot Optical Coherence Tomography Angiography Study

To evaluate the effects of metformin alone and combined treatment with metformin and an SGLT2 inhibitor on retinal microvascular morphology using optical coherence tomography angiography (OCTA) in isolated type 2 diabetes mellitus (DM) patients with HbA1c above the expected target (> 7%). Fifty patients with isolated DM, 7% < HbA1c < 8%, without diabetic retinopathy (DR) using 500 mg metformin ×2 for glycemic control were included in the study. OCTA and BMI measurements were obtained at the first evaluation. Treatment was changed to metformin 1000 mg ×2. Patients who did not develop side effects due to the metformin were defined as the metformin-tolerant group (group-1). Patients who developed side effects were defined as the metformin-intolerant group (group-2), and their treatment was changed to metformin 500 mg ×2 and empagliflozin 10 mg. The second evaluation was performed three months after the last treatment change. HbA1c was lower on the second evaluation in both groups ( P < 0.001, in both). On the second evaluation in group-1, a decrease was found in superficial perifoveal and deep parafoveal macular vascular plexus densities ( P : 0.040 and P : 0.020, respectively). No statistically significant difference was observed in group-2. SGLT2 inhibitors may contribute to preventing the development of preclinical DR. In patients with metformin intolerance, adding SGLT2 inhibitors may be a reasonable choice to protect the retina. Évaluer les effets de la metformine seule et du traitement combiné de la metformine et de l’inhibiteur du SGLT2 sur la morphologie microvasculaire rétinienne en utilisant une angiographie par tomographie par cohérence optique (OCTA) chez des patients diabétiques de type 2 isolés (DM) avec un taux d’HbA1c supérieur à la cible attendue (> 7 %). Cinquante patients atteints de diabète isolé, 7 % < HbA1c < 8 %, sans rétinopathie diabétique (DRP) et utilisant 500 mg de metformine ×2 pour le contrôle glycémique ont été inclus dans l’étude. Les mesures OCTA et IMC ont été effectuées lors de la première évaluation. Le traitement a été changé en metformine 1000 mg ×2. Les patients qui n’ont pas développé d’effets secondaires dus à la metformine ont été acceptés dans le groupe tolérant la metformine (groupe 1). Les patients qui ont développé des effets indésirables ont été acceptés dans le groupe intolérant à la metformine (groupe 2) et leur traitement a été changé en metformine 500 mg ×2 et empagliflozine 10 mg. La deuxième évaluation a été faite trois mois après le dernier changement de traitement. L’HbA1c était plus faible dans la seconde évaluation dans les deux groupes ( p < 0,001, dans les deux). Dans la deuxième évaluation du groupe 1, une diminution a été observée dans les densités de plexus vasculaires maculaires superficielles périfovéales et parafovéales profondes ( p : 0,040 et p : 0,020, respectivement). Aucune différence statistiquement significative n’a été observée dans le groupe 2. Les inhibiteurs du SGLT2 peuvent contribuer à prévenir le développement de la DRP préclinique. Chez les patients présentant une intolérance à la metformine, l’ajout d’inhibiteurs du SGLT2 au traitement peut être un choix raisonnable pour protéger la rétine.

Early neurovascular changes in the retina in preclinical diabetic retinopathy and its relation with blood glucose

BackgroundTo investigate the changes in retinal nerve fiber layer thickness and macular blood flow density during the preclinical stage of diabetic retinopathy and their relationship with blood glucose.MethodsIn this cross-sectional study, 97 diabetic patients (total of 188 eyes; 144 eyes in no diabetic retinopathy group, 44 eyes in mild diabetic non-proliferative retinopathy group) and 35 healthy people (70 eyes) were enrolled, All the subjects were divided into different groups based on their HbA1c levels, and they underwent optical coherence tomography angiography. We compared the optical coherence tomography angiography parameters and retinal nerve fiber layer thickness among the different glucose groups.ResultsThe parafoveal vessel density and the temporal retinal nerve fiber layer thickness were lower (p < 0.05) in the diabetic group than in the normal group. The diabetic group showed a higher acircularity index than the normal group. The normal group had the highest vessel density and the lowest acircularity index, followed by the no-diabetic retinopathy group and the mild non-proliferative retinopathy group, (p < 0.001). Foveal vascular density and parafoveal vessel density decreased with an increase in HbA1c. There was a negative correlation between parafoveal vessel density in the deep retinal vascular layer and fasting blood glucose (p < 0.01). The temporal retinal nerve fiber layer thickness decreased across the HbA1c level groups, and was positively correlated with the parafoveal vessel density in the superficial retinal vascular layer (p < 0.05).ConclusionsThis study shows that retinal microvasculopathy and neuropathy can be present in the absence of retinopathy. The vessel density of the deep retinal vascular layer was negatively correlated with fasting blood glucose, and the temporal retinal nerve fiber layer thickness was positively correlated with the vessel density of the superficial retinal vascular layer. These indicators are helpful for endocrinologists and ophthalmologists in detecting early diabetic retinal pathological lesions.

Ultra-wide field swept-source optical coherence tomography angiography in patients with diabetes without clinically detectable retinopathy

BackgroundTo investigate alterations in retinal microvasculature in eyes with preclinical diabetic retinopathy (DR) using ultra-wide field swept-source optical coherence tomography angiography (UWF SS OCTA).MethodsProspective cross-sectional study. Fifty-five eyes of 30 diabetic patients without clinical retinal signs were included. All subjects underwent OCTA examination with a 12 × 12 mm2 field of view of 5 visual fixations (1 central fixation and 4 peripheral fixations) to compose a UWF OCTA image. In the UWF images, the central area corresponded to the original central image obtained using central fixation, and the peripheral area was the remaining area. Lesions, including nonperfusion areas (NPAs), microvascular dilation and tortuosity, and neovascularization (NV), were recorded in different areas. Diabetes history was also recorded.ResultsPeripheral areas presented significantly more microvascular dilation and tortuosity than central areas (P = 0.024) and more NPAs than central areas, with borderline significance (P = 0.085). The number of lesion types was associated with HbA1c levels in the peripheral and overall areas (all P values < 0.001).ConclusionsUWF SS OCTA is a promising imaging method for detecting vascular alterations in diabetic eyes without clinical signs to reveal retinal microvascular alterations. These alterations were correlated with systemic conditions.

Optical coherence tomography angiography in patients with type 2 diabetes without clinical diabetic retinopathy

Background and objectives To investigate changes in retinal vascular plexuses, choriocapillaris, along with microcirculation of optic nerve head (ONH), in patients with type 2 diabetes mellitus without clinically evident retinopathy and healthy controls using optical coherence tomography angiography (OCTA).Patients and methods This is a prospective, cross-sectional observational study that included 20 eyes of normal healthy controls (group 1) and 20 eyes of diabetic patients without clinically evident retinopathy (group 2). All participants underwent OCTA examination (RTVue-XR Avanti; Optovue). Average and parafoveal vessel density in superficial capillary plexus (SCP), deep capillary plexus, choriocapillaris vessel density, foveal avascular zone area and perimeter, and vessel density inside ONH and in peripapillary region were compared between groups. Microaneurysms and capillary nonperfusion were taken into analysis. glycated hemoglobin and serum creatinine were assessed for diabetic patients.Results Group 2 showed statistically significant lower average vessel densities of SCP and deep capillary plexus (P<0.01) and parafoveal vessel density of SCP (P<0.01) compared with group 1. Moreover, there was statistically significant and highly significant difference between group 2 and group 1 regarding tempo-inferior and tempo-superior sectors of peripapillary area (P=0.016 and 0.001, respectively). A statistically significant increase in foveal avascular zone area and perimeter was found in group 2 compared with group 1 (P<0.01). Average vessel density of choriocapillaris had a negative correlation with serum creatinine in group 2 (P<0.05). Microaneurysms and capillary nonperfusion were detected by OCTA in diabetic patients.Conclusion OCTA can identify preclinical diabetic retinopathy before the clinical manifestations appear. It is a promising noninvasive tool for assessing retinal vascular plexuses, choriocapillaris, and ONH microcirculation.

Correlation Analysis between Nerve Fiber Layer Thickness and Peripapillary Vessel Density and Influencing Factors of Peripapillary Vessel Density in Preclinical Diabetic Retinopathy

Purpose To observe the changes of the retinal nerve fiber layer (RNFL) thickness and the optic disc vessel density (VD) in preclinical diabetic retinopathy (DR) and the relationship between RNFL changes and VD, as well as to investigate the influencing factors on peripapillary vessel density. Methods This was a cross-sectional study. Thirty-four eyes of 34 type 2 diabetes mellitus (T2DM) patients diagnosed with preclinical diabetic retinopathy (DR) were included in our study, with twenty-three eyes of 23 healthy subjects set up as normal controls. History of diabetes, hypertension, and dyslipidemia was recorded in detail. All participants underwent color fundus photography (CFP), RNFL around the optic disc, and OCT angiography (OCTA) over the optic disc. The 4.5 mm × 4.5 mm Angio Disc scan mode was performed with all participants by using the OCTA instrument. The relationship between changes of RNFL in the four quadrants (superior, inferior, temporal, and nasal) and VD changes was analyzed. Results Vessel density was significantly lower in the superior (t = −2.27) and temporal (t = −2.02) peripapillary sectors of diabetic eyes compared to normal eyes (P < 0.05). The retinal nerve fiber layer (RNFL) was significantly thinner in the temporal quadrant (P < 0.001) of diabetic eyes compared to normal eyes. Pearson correlation coefficient analysis showed a significant positive correlation between vessel density and RNFL thickness in the peripapillary region in the temporal (r = 0.468, P < 0.01) and superior (r = 0.612, P < 0.01) sectors. Multiple linear regression analysis showed that glycated hemoglobin (HbA1c) (β = −1.50, P < 0.01) and the duration of diabetes (β = −0.33, P=0.03) were associated with peripapillary vessel density. Conclusions Preclinical DR presented optic disc microcirculation changes. Temporal RNFL thinning is an early sign of retinal neurodegeneration and is associated with temporal peripapillary vessel density reduction. The duration of diabetes and HbA1c are risk factors for peripapillary vessel density reduction in patients with preclinical DR.

Vessel Density around Foveal Avascular Zone as a Potential Imaging Biomarker for Detecting Preclinical Diabetic Retinopathy: An Optical Coherence Tomography Angiography Study

ABSTRACT Purpose: The purpose of this study was to investigate the changes of optical coherence tomography angiography (OCTA) parameters in diabetic retinopathy (DR) using an updated software with 3D projection artifact removal. Methods: In this cross-sectional observational study, 192 eyes of 111 patients with diabetes mellitus (DM) and 55 eyes of 34 age-matched healthy subjects were included. Diabetic patients were divided into three subgroups: without DR, with mild non-proliferative DR, and with moderate-to-severe non-proliferative DR. All eyes underwent dilated fundoscopy along with 3x3mm and 6x6mm OCTA image acquisition. Vessel density (VD), retinal thickness and foveal avascular zone (FAZ) parameters were analyzed. Correlation analyses between OCTA parameters and DR severity were also performed. Results: There was a statistically significant difference in all OCTA parameters among groups, except for superficial foveal VD in 6x6mm scan and whole image retinal thickness in both 3x3mm and 6x6mm scans, while 3x3mm scan parameters were found to be diagnostically superior to the corresponding ones of 6x6mm scan. As the DR stage progressed, the mean VD values decreased. FD-300, which is the VD of a 300-μm width annulus surrounding FAZ, demonstrated the strongest inverse correlation with DR severity (r = −0.590/rs = −0.562, p < .001) and showed the highest area under the ROC curve (AUROC = 0.833 ± 0.030, p < .001) in scan 3 × 3. Conclusion: OCTA shows progressive decrease of VD parameters with increasing DR severity. Foveal VD, FAZ area, and perimeter are not very useful indexes due to the high interindividual variability of FAZ size. OCTA and specifically FD-300 may serve as a promising DR screening tool for detecting preclinical microvascular alterations.

Diabetic Retinopathy Vascular Density Maps Using Optical Coherence Topography Angiography

Abstract Background Diabetic retinopathy (DR) is one of the most common diabetic complications, which has become a leading cause for vision loss, mainly because of macular edema and vitreous hemorrhage. Objective Using Optical Coherence Tomography(OCT) and Optical Coherence Tomography Angiography (OCT-A) for qualitative and quantitative assessment of retinal vascular density in superficial capillary plexus, quantitative assessment of foveal avascular zone, choroidal vascular density map, assessment of retinal thickness and choroidal thickness in normal individuals and diabetic patients with and without diabetic retinopathy (DR). Patients and Methods This study included 64 eyes. Diabetics and control group were recruited from internal medicine clinic in Misr University for science and Technology Hospital and asked to participate in this study. This study was designed as an observational and cross sectional study in the period from 8/2018 to 2/2019. Results There is decrease in Choroidal vascular density in diabetic patients. There is decrease in retinal thickness in diabetic patients and there is no significant differences in the retinal thickness between control subjects and patients with NDR. Conclusion Our study suggested that OCTA can identify preclinical DR before the manifestation of clinically apparent retinopathy. Our findings highlight the potential role of OCT-A in monitoring and quantifying retinal vascular alterations in diabetes

Novel Detection and Restorative Levodopa Treatment for Preclinical Diabetic Retinopathy.

Diabetic retinopathy (DR) is diagnosed clinically by directly viewing retinal vascular changes during ophthalmoscopy or through fundus photographs. However, electroretinography (ERG) studies in humans and rodents have revealed that retinal dysfunction is demonstrable prior to the development of visible vascular defects. Specifically, delays in dark-adapted ERG oscillatory potential (OP) implicit times in response to dim-flash stimuli (<−1.8 log cd · s/m2) occur prior to clinically recognized DR. Animal studies suggest that retinal dopamine deficiency underlies these early functional deficits. In this study, we randomized individuals with diabetes, without clinically detectable retinopathy, to treatment with either low- or high-dose Sinemet (levodopa plus carbidopa) for 2 weeks and compared their ERG findings with those of control subjects (no diabetes). We assessed dim-flash–stimulated OP delays using a novel handheld ERG system (RETeval) at baseline and 2 and 4 weeks. RETeval recordings identified significant OP implicit time delays in individuals with diabetes without retinopathy compared with age-matched control subjects (P < 0.001). After 2 weeks of Sinemet treatment, OP implicit times were restored to control values, and these improvements persisted even after a 2-week washout. We conclude that detection of dim-flash OP delays could provide early detection of DR and that Sinemet treatment may reverse retinal dysfunction.