Clinical Signs Of Diabetic Retinopathy Research Articles

The possibilities of using adaptive optics in modern ophthalmology

Until recently, the assessment of individual retinal cells was possible only with the help of histological examination, since such retinal imaging methods as scanning laser ophthalmoscopy and optical coherence tomography had low resolution to obtain images of structures at the cellular level, which was mainly due to aberrations caused by the optics of the eye. Adaptive optics technology has improved the performance of optical systems by correcting optical wavefront aberrations. Adaptive optics allows noninvasively visualizing the retina at the microscopic level in vivo, providing the opportunity to analyze individual structures such as photoreceptors, blood vessels, nerve fibers, ganglion cells and a lattice plate. Adaptive optics imaging in patients with diabetic retinopathy makes it possible to accurately determine the spatial distribution of cones, a decrease in which is associated with the presence of diabetic retinopathy and an increase in the severity of the disease. The detection of differences in cone distribution density between the control group and patients with diabetes mellitus without clinical signs of diabetic retinopathy may contribute to its early diagnosis, as well as a deeper understanding of the consequences of changes in the photoreceptor apparatus. Adaptive optics imaging methods are able to identify disorders of photoreceptor cells and assess the degree of progression of age-related macular degeneration, which definitely expands diagnostic capabilities at the early stages of its detection. Assessment of the condition of nerve fiber bundles through the use of Adaptive optics helps to identify changes associated with glaucoma, and also provides the ability to visualize details that cannot be evaluated using optical coherence tomography. Adaptive optics imaging allows you to directly measure the wall of retinal vessels and the diameter of their lumen. The ratio of wall thickness to vessel lumen and the cross-sectional area of the vessel wall directly reflect the remodeling process and can be used for the purpose of early diagnosis and monitoring of hypertension.

Optical coherence tomography angiography evaluation of retinal and optic disc alterations in children with type 1 diabetes without retinopathy.

To determine the earliest characteristics of retinal and optic disc alterations in diabetic children without diabetic retinopathy (DR) changes by using optical coherence tomography angiography (OCTA). This was a prospective, non-interventional case-control study that involved 25 patients with type 1 diabetes mellitus (T1DM) without clinical signs of DR and a demographically similar group of 25 healthy children as the control. The retina and optic disc were examined using OCTA. Correlations between the OCTA parameters and clinical predictors were evaluated. Twenty-five patients (median age: 14 years, interquartile range [IQR]: 13-15.9 years; 12/25 [48%] girls) with T1DM and 25 age-matched controls were enrolled. The patients had a tendency toward thinner fovea (232.5 Symbolm) as compared to the controls (244.3 Symbolm) (P = 0.142). Superficial vascular density was significantly lower in the DM group compared to the controls (48.90 ± 2.3 vs. 50.91 ± 3.1, P = 0.015). However, no such differences were observed at deeper vascular densities. The patients also had lower whole-disc (48.65 vs. 50.21, P = 0.029), disc interior (49.14 vs. 52.11, P = 0.044), superior (50.67 vs. 53.45, P = 0.039), and peripapillary capillary densities (50.49 vs. 52.68, P = 0.033). There was no statistical correlation between retinal/optic disc angiography parameters and clinical predictors. In diabetic children without visual impairment or DR, signs of microvasculopathy were found in the superficial macular vascular density and inside the disc.

Structural and functional characterization of retinal impairment in T1DM patients without diabetic retinopathy: a 3-year longitudinal study.

To analyze the progression of structural and functional retinal impairment in type 1 diabetes mellitus (T1DM) patients with no clinical signs of diabetic retinopathy (DR) during a 3-year follow-up. This was an observational longitudinal study. Post-pediatric T1DM patients without clinical signs of DR, and sex- and age-matched healthy subjects were recruited at San Raffaele Hospital (Milan, Italy). Each patient underwent a comprehensive ophthalmological evaluation, including optical coherence tomography (OCT), OCT-angiography (OCT-A), retinal static and dynamic vessel analysis (DVA), and microperimetry. 21 eyes of 21 T1DM patients (10 females; 24 ± 2years old), and 21 age and sex-matched healthy subjects were enrolled. At baseline, T1DM eyes revealed a significantly decreased vessel length density using OCT-A (p < 0.001 and p = 0.046 in 3 × 3 and 6 × 6mm images) and a significantly increased vessel density index (p = 0.013 and p = 0.087 in 3 × 3 and 6 × 6mm images) of deep capillary plexus. DVA detected a significantly decreased vessel response to flicker light (p = 0.002). A significantly increased thickness of ganglion cellular layer 6-mm-diameter subfields in inferior and superior quadrants was found in diabetic patients (p < 0.001 in both subfields). At 3-years-follow-up no significant longitudinal changes were disclosed in all analyses. Concomitant subclinical microvascular and neurodegenerative damages could be early signs of DR onset that precede functional alterations and clinical signs of DR development. These alterations demonstrated a stable trend over time.

Early retinal neurovascular findings in post-transplant diabetes mellitus patients without clinical signs of diabetic retinopathy

BackgroundPost-transplant diabetes mellitus (PTDM) is a specific subtype of diabetes with an uncertain impact on mortality and morbidity in post-transplant patients. Diabetic retinopathy is the most common microvascular complication of diabetes mellitus, but the long-term clinical progression in PTDM is unknown. New technologies are being used to assess pre-clinical signs of retinal changes, such as swept-source optical coherence tomography (OCT) and OCT-angiography. The aim of this study was to detect pre-clinical structural and vascular changes in the retina using swept-source-OCT and OCT-angiography in patients with PTDM.MethodsIn this retrospective cohort study, post-kidney transplant patients were divided into PTDM and non-PTDM (control) groups. Both eyes of eligible PTDM patients and controls were included in this study. Inner retinal layer thickness was measured with swept-source-OCT. Retinal capillary density and the foveal avascular zone were measured with OCT-angiography.ResultsIn the PTDM group, reduced thickness was found in the inferior ganglion cell layer plus inner plexiform layer (95% CI -8.76 to -0.68; p = 0.022) and the temporal inferior segment (95% CI -10.23 to -0.76; p = 0.024) of the inner retina, as well as in the retinal nerve fiber layer in the temporal (95% CI -34.78 to -9.28 p = 0.001) and temporal inferior segments (95% CI -33.26 to -5.03 p = 0.008). No significant differences were found in the vascular capillary plexus between groups at all depths, segments, or foveal avascular zone (p = 0.088).ConclusionsAccording to OCT-angiography, PTDM patients had reduced inner neurosensory retinal layers but no significant change in vascular density, which suggests that early neuroretinal degeneration might occur prior to vascular changes secondary to PTDM. Prospective studies could help elucidate the clinical course of retinal neuropathy and microvascular pathology in PTDM and provide a better understanding of PTDM complications.

Retinal and choroidal microvascular characterization and density changes in different stages of diabetic retinopathy eyes.

The purpose of this study was to evaluate the changes in fundus vascular density and micromorphological structure of all vascular plexuses during the different stages of diabetic retinopathy (DR), and the correlation between fundus blood flow and the DR severity. This observational cross-sectional study was conducted of 50 eyes with different stages of DR, 25 diabetes mellitus (DM) patients without clinical signs of DR and 41 healthy eyes. The foveal avascular zone (FAZ), vessel density of superficial capillary plexus (SCP), and deep retinal capillary plexus (DCP) were acquired by RTVue XR Avanti OCTA device. The perfusion density (PD), skeleton vessel density (SVD) was manually calculated using ImageJ. The area under receiver operating characteristic (ROC) curve was used to determine the diagnostic value of OCTA parameters in distinguishing DR and healthy eyes. The choroidal VD were significantly higher in the healthy group than in the DM without DR, NPDR, and PDR groups (p < 0.001). The mean retinal parafovea VD, PD, and retinal SVD were higher in healthy and DM without DR eyes compared with NPDR and DR eyes in all vascular layers (p < 0.001). The parafoveal VD of SCP, and DCP decreased, and FAZ area increased with the exacerbation of DR. The OCTA parameters, including FAZ area, parafovea VD, PD, and SVD in all vascular layers showed significant correlation with DR severity (all p < 0.001). ROC curves of OCTA parameters (FAZ area, retinal parafovea VD, retinal PD, and SVD in all vascular layers) for had high sensitivity and specificity in distinguishing DR versus healthy eyes. The choroidal parafovea VD, retinal parafovea VD, retinal PD, and SVD in the two plexuses decreased, and retinal FAZ area increased significantly with worsening DR. VD, PD, and SVD might be potential early biomarkers indicating the progression of DR before appearance of clinically PDR in patients with DM. In this study, OCTA parameters had high sensitivity and specificity in distinguishing DR and healthy eyes.

Content of mediators of innate immunity in the tears of patients with vascular and neurodegenerative manifestations of diabetic retinopathy

According to the results of recent studies, diabetic retinopathy can be considered not only as a vascular disease, but also as a neurodegenerative process. Study of the composition of the tear fluid is used to assess the state of local immunity in the development of eye diseases. However, studies examining the effect of tear composition in diabetic retinopathy are few. The aim of the study is to determine the levels of IL-1β, IL-10, TGF-β3, MMP-7, TIMP-2, protein S100b, BDNF and NGF in the tear fluid ofpatients with vascular and neurodegenerative manifestations of diabetic retinopathy. The study included 80 patients diagnosed with type 2 diabetes which were divided into 2 groups: the 1st group included 40 patients who had no clinical signs of diabetic retinopathy on the fundus; the 2nd group included 40 patients with initial signs of non-proliferative diabetic retinopathy. All those included in the study were examined on an optical coherent tomograph RTVue-100 (USA); the volume of focal losses of retinal ganglion cells (FLV) was determined. An increase in FLV above the normative base of the device was regarded as an OCT-sign of retinal neurodegeneration. According to the results of OCT, the participants of the first and second groups were additionally divided into 4 subgroups: 1A — patients without vascular changes in the fundus and without OCT signs of retinal neurodegeneration (n = 12); 1B — patients without vascular changes in the fundus and with the presence of OCT signs of retinal neurodegeneration (n = 28); 2A — patients with initial non-proliferative DR and without OCT signs of retinal neurodegeneration (n = 10); and 2B — patients with initial non-proliferative DR and with OCT signs of retinal neurodegeneration (n = 30). The levels of IL-1β, IL-10, TGF-β3, MMP-7, TIMP-2, protein S100 b, BDNF, and NGF in tear fluid were determined by enzyme-linked immunosorbent assay. Levels of IL-1β and IL-10 in tear fluid in all subgroups were comparable to controls throughout the study. TGF-β3 content in the tear fluid of patients in the group with initial signs of non-proliferative DR (group 2) was significantly (p = 0.001) lower compared with control and group 2. However, there was no significant difference (p &gt; 0.05) between subgroups A and B within groups. The concentration of MMP-7 in the tear fluid in all subgroups was significantly lower than in the control (p &lt; 0.05). However, in the subgroups with OCT signs of retinal neurodegeneration (1B and 2B), the deficiency of this metalloproteinase was more pronounced (p = 0.0001). The levels of the neuropeptides under study NGF, BDNF and S100 B in tear fluid did not differ from controls in all subgroups.

Early Retinal Microvascular Alterations in Young Type 1 Diabetic Patients without Clinical Retinopathy.

The purpose of this study is to identify and quantify preclinical changes with the help of optical coherence tomography angiography (OCTA) within the retinal microcirculation of young type 1 diabetes (T1D) patients without clinical signs of diabetic retinopathy (DR) and to compare these results with those obtained from healthy age-matched subjects. OCTA is currently used for monitoring diabetic retinopathy; however, there is no current consensus on which OCTA parameter alterations predict the first clinical signs of diabetic retinopathy. The main challenge that young patients with T1D face during the course of the disease is that they can rapidly progress to the development of DR, especially during adolescence. Moreover, they also present an increased risk of rapid progression toward advanced stages of DR and vision loss compared to type 2 diabetes patients, indicating the importance of early diagnosis and intervention. The limitations of the currently used screening procedures that led to the conceptualization of our study are the difficulties in performing fluorescein angiography tests for diagnosing the clinical signs of DR on young patients, namely the invasive procedure of dye injection, the risk of allergic reactions and the long duration of the examination. Moreover, given the long life expectancy of young T1D patients, it is essential to identify the preclinical changes in retinal microvasculature before reaching the first clinical signs quantifiable by FFA. The clinical study enrolled 119 subjects aged between 4 and 30 years old with a mean age of 13 years old, comprising 61 T1D patients with a mean duration of the disease of 4 years and 8 months and 58 healthy age-matched subjects for the control group. OCTA scans were performed using the RevoNX 130 OCTA device (Optopol) to evaluate the following retinal parameters: foveal avascular zone (FAZ) area, perimeter and circularity, overall foveal thickness, and superficial and deep vessel densities. Statistically significant differences between the two groups were identified for the following parameters: the FAZ area in the T1D group (0.42 ± 0.17) was larger than the control group (0.26 ± 0.080), the FAZ circularity (0.41 ± 0.11) was decreased compared to the control group (0.61 ± 0.08) and the FAZ perimeter was larger (3.63 ± 0.97) compared to the control group (2.30 ± 0.50). The overall foveal thickness was decreased in the T1D group (222.98 ± 17.33) compared to the control group (230.64 ± 20.82). The total vessel density of the superficial capillary plexus (SCP) on an investigated area of 6 X 6 mm centered around the fovea was decreased in the T1D group (37.4164 ± 2.14) compared to the control group (38.0241 ± 2.44). Our data suggest that specific imaging biomarkers such as FAZ perimeter, area and circularity, decreased overall foveal thickness and decreased vessel density in the SCP precede the clinical diagnosis of DR in young T1D patients and represent useful parameters in quantifying capillary nonperfusion in T1D patients without clinical signs of DR.

CLC-Net: Contextual and local collaborative network for lesion segmentation in diabetic retinopathy images

Diabetic retinopathy (DR) is the leading cause of blindness among people of working age. Fundus lesions are clinical signs of DR, and their recognition and delineation are important for early screening, grading, and monitoring of the disease. We propose in this work a fully automatic deep convolutional neural network method for simultaneous segmentation of four different types of DR-related fundus lesions. To exploit multi-scale image information, we propose a collaborative architecture that comprises a contextual branch and a local branch. An attention mechanism is designed to fuse feature maps from all decoding layers in order to effectively and fully combine informative features from the two branches. Moreover, an auxiliary classification task with a novel supervision scheme is introduced to reduce model overfitting and further improve the accuracy of lesion segmentation. Extensive experiments are conducted using three public fundus datasets, and our method produces a mean AUC value of 0.677, 0.629, and 0.581 on them respectively. The results demonstrate the advantages of the proposed method, outperforming alternative strategies and other state-of-the-art methods in the literature.

Comparison of central macular thickness between diabetic patients without clinical retinopathy and non-diabetic patients.

Diabetic retinopathy (DR) is one of the leading causes of blindness in patients between 20 and 60 years of age which can be prevented by early detection of diabetic retinopathy. The duration of diabetes is probably the strongest predictor for development and progression of retinopathy. Optical Coherence Tomography (OCT) is a recent advance in imaging which is sensitive in early detection of small changes in macular thickness. This hospital based cross-sectional study was done at a tertiary referral center in Kathmandu, Nepal where 364 eyes of 182 patients (182 eyes in 91 patients in each group diabetes without retinopathy group and nondiabetic group) were evaluated. Thickness of the macula was determined by using Spectral Domain Optical Coherence Tomography (SD- OCT) and compared between diabetic patients without clinical retinopathy and nondiabetic patients. The mean CMT as measured by Spectral Domain Optical Coherence Tomography in diabetic patients was 236.29±40.31 µm whereas it was 244.25±30.51 µm in non-diabetic cases. The mean central macular thickness of diabetic patients with duration of diabetes less than 1 year, 1-5 years, 6-10 years, 11-15 years and more than 15 years were 217.19±42.22, 233.49±45.69, 248.5±31.37, 250.89±21.62 and 240.75±11.26 respectively. This study concluded that in diabetic patients there was an initial decrease in central macular thickness which gradually increased with increasing duration of diabetes mellitus. Examination of macular thickness could be a useful modality to evaluate progression of disease before appearance of other clinical signs of diabetic retinopathy.

Assessment of macular findings by OCT angiography in patients without clinical signs of diabetic retinopathy: radiomics features for early screening of diabetic retinopathy

This cross-sectional study aimed to quantitatively analyze the optical coherence tomography angiography (OCTA) images using MATLAB-based software and evaluate the initial changes in macular vascular density and the distortion of the foveal avascular zone (FAZ), before the clinical appearance of diabetic retinopathy. For this purpose, 21 diabetic patients without any clinical features indicating DR, and 21 healthy individuals matched with patients based on their demographic characteristics were included. Macular thickness, macular vascular density, and morphological changes of FAZ were assessed using OCTA. The diagnostic ability of morphological parameters was evaluated by receiver operating curve analysis. The intraclass correlation coefficient (ICCC) index was used to check the consistency of the extracted values. There was no significant difference in age, gender, LogMAR visual acuity, spherical equivalent, and intra-ocular pressure amongst patients and controls. No correlation was found between age and the FAZ area as well as vascular density. The vascular structure of the superficial layer showed FAZ enlargement, reduced vascular density in the macular area, and significant deviations of FAZ shape parameters (convexity and Frequency Domain Irregularity) in patients compared with healthy individuals. Measurements were highly correlated between separate imaging sessions with ICCC of over 0.85 for all parameters. The represented data suggests that radiomics parameters can be applied as both an early screening tool and guidance for better follow-up of diabetic patients who have not had any sign of DR in fundoscopic exams.

Quantitative Evaluation of Retinal Microvascular Abnormalities in Patients With Type 2 Diabetes Mellitus Without Clinical Sign of Diabetic Retinopathy.

PurposeTo evaluate microvascular abnormalities in the macula and peripapillary area in diabetic patients without clinical signs of diabetic retinopathy (DR) and compare them with healthy control eyes, using optical coherence tomography angiography (OCTA).MethodsA prospective study was performed of 49 eyes from 49 diabetic patients without clinical signs of DR and a control group of 52 eyes from 52 healthy normal individuals. The 3 × 3 mm macular scans and 4.5 × 4.5 mm optic disc scans were obtained with the OCTA RTVue-XR Avanti system. Angiograms from the superficial capillary plexus, the deep capillary plexus of the macula scans, and radial peripapillary capillary plexus of the optic disc scans were analyzed with MATLAB. Multivariate binary logistic regression and the least absolute shrinkage and selection operator (LASSO) regression were used to select ideal parameters that distinguish diabetic eyes without DR from normal eyes. A receiver operating characteristic (ROC) curve was generated, and sensitivity and specificity were calculated.ResultsOur final model identified FD-300 (foveal vessel density in a 300-µm-wide region around foveal avascular zone) as the only parameter selected by both the LASSO regression and the final multivariate logistic regression model that significantly differentiates diabetic eyes without clinical signs of DR from healthy normal eyes. The area under the ROC curve of FD-300 was 0.685, and sensitivity and specificity were 65.3% and 71.2%, respectively.ConclusionsQuantitative evaluation of retinal microvascular abnormalities using OCTA identified FD-300 as a useful biomarker versus the other macular and peripapillary OCTA metrics in the early detection of preclinical diabetic retinal abnormalities.Translational RelevanceOCTA may be useful in detecting early retinal microvascular abnormalities in diabetic patients before the clinical findings of DR become visible.

Detection of microaneurysms in color fundus images based on local Fourier transform

Retinal microaneurysm (MA) is one of the early clinical signs of diabetic retinopathy (DR), which is essential for the early diagnosis of DR. Its shape is often shown as a red dot, which makes detection of MA challenging because of its tiny size. There are many effective MA automatic detection methods having been proposed, but these methods are hard to describe the overall shape of Mas. This paper proposes an automatic MA detection method based on local Fourier transform which splits the original image into small independent images and calculates their local Fourier transforms in isolation. After that, the object is not the whole image but a series of independent small images. We also extract a statistical feature to check for normality and design a new feature to represent the difference among every direction. After that, a group of candidate points are extracted from the images. Finally, some features are extracted from the candidate points, and the confidence scores of the candidate points are obtained by using random forest algorithm for classification. The proposed method obtained a FROC curve score of 0.847 on the E-Ophtha MA database, which is better than most existing methods. In the ROC database, although the FROC curve score is only 0.283, the AUC can reach 0.961, which is better than most methods. It can be seen that the proposed method can achieve a better result with low noise and large sample size.

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.

EARLY RETINAL MICROVASCULAR ABNORMALITIES IN YOUNG ADULTS WITH TYPE 1 DIABETES MELLITUS WITHOUT CLINICALLY EVIDENT DIABETIC RETINOPATHY.

To characterize the early retinal microvascular changes in young adults (age: 22.69 ± 3.50 years) with Type 1 diabetes mellitus without clinically detectable diabetic retinopathy using optical coherence tomography angiography and investigate the associated factors. A total of 36 participants with Type 1 diabetes mellitus (70 eyes) and 34 healthy controls (57 eyes) were retrospectively reviewed. The analyzed optical coherence tomography angiography indices included capillary vessel density, foveal avascular zone area/perimeter/acircularity index, and foveal vascular density, acquired in the 6 × 6-mm2 area centered on the fovea. The generalized estimation equations model was applied to compare the mean values and to study the associated factors. In subjects with diabetes, statistically significant decreases were observed in parafoveal vessel density in both superficial and deep capillary plexuses, foveal avascular zone area/perimeter, and foveal vascular density when compared with controls (all P < 0.05). Higher glycated hemoglobin level was independently associated with the decrease of parafoveal vessel density as well as the increase of foveal avascular zone area/perimeter (all P < 0.05). Prepubescent onset of diabetes mellitus was also independently associated with the decrease of superficial parafoveal vessel density, foveal avascular zone area/perimeter, and foveal vascular density (P = 0.015, 0.011, 0.015, and 0.001, respectively). In young adults with Type 1 diabetes mellitus lacking clinical signs of diabetic retinopathy, optical coherence tomography angiography revealed alterations in retinal microvasculature that were associated with glycated hemoglobin level and onset of diabetes mellitus related to puberty.

Early Identification of Retinal Neuropathy in Subclinical Diabetic Eyes by Reduced Birefringence of the Peripapillary Retinal Nerve Fiber Layer.

PurposeTo study birefringence of the peripapillary retinal nerve fiber layer (RNFL) of diabetic eyes with no clinical signs of diabetic retinopathy (DR) or mild to moderate DR stages using spectral-domain polarization-sensitive (PS) optical coherence tomography (OCT).MethodsIn this observational pilot study, circular PS-OCT scans centered on the optic nerve head were recorded in prospectively recruited diabetic and age-matched healthy eyes. From averaged circumpapillary intensity and retardation tomograms plots of RNFL birefringence were obtained by a linear fit of retardation versus depth within the RNFL tissue for each A-scan position and mean birefringence values for RNFL calculated. Spectral-domain OCT imaging (Heidelberg Engineering) was performed to assess peripapillary RNFL thickness and macular ganglion cell complex (GCC).ResultsOut of 70 eyes of 43 diabetic patients (mean ± SD age: 50.86 ± 15.71) 36 showed no signs of DR, 17 mild and 17 moderate nonproliferative DR with no diabetic macular edema. Thirty-four eyes of 34 healthy subjects (53.21 ± 13.88 years) served as controls. Compared with healthy controls (0.143° ± 0.014°/µm) mean total birefringence of peripapillary RNFL was significantly reduced in subclinical diabetic eyes (0.131° ± 0.014°/µm; P = 0.0033), as well as in mild to moderate DR stages (0.125° ± 0.018°/µm, P < 0.0001) with borderline statistically significant differences between diabetic patients (P = 0.0049). Mean birefringence values were significantly lower in inferior compared with superior RNFL sectors (P < 0.0001) of diabetic eyes with no such difference detected in the healthy control group.ConclusionsWe identified evidence of early neuroretinal alteration in diabetic eyes through reduced peripapillary RNFL birefringence assessed by PS-OCT occurring before appearance of clinical microvascular lesions or GCC alterations.

The GG genotype of erythropoietin rs1617640 polymorphism affects the risk of proliferative diabetic retinopathy in Slovenian subjects with type 2 diabetes mellitus: enemy or ally?

The aim of this study was to investigate the relationship between erythropoietin rs1617640 polymorphism and proliferative diabetic retinopathy (PDR) in Slovenian subjects with type 2 diabetes mellitus. The second aim was to find whether erythropoietin expression in fibrovascular membranes varies among individuals carrying different genotypes of the rs1617640. This was a retrospective cross-sectional study based on 797 unrelated Slovenian (Caucasian) participants with type 2 diabetes mellitus. The study group consisted of 217 cases with PDR and 580 controls without clinical signs of diabetic retinopathy. Each subject was genotyped for rs1617640 polymorphism. Fibrovascular membranes from 27 subjects who underwent vitreoretinal surgery were analysed with immunohistochemistry. We searched for expression of erythropoietin, its cognate receptor and for a pan-endothelial marker CD-34. Our results show that subjects carrying a minor GG genotype had significantly higher risk for PDR in both unadjusted (p = 0.02) and adjusted (p = 0.04) recessive genetic models. Subjects with the GG genotype had a 1.6-fold increased risk of developing PDR compared to subjects carrying the major T allele. In fibrovascular membranes from subjects with PDR, the mean number of cells expressing EPO was significantly higher in G allele carriers compared to the homozygotes for the common T allele. In Slovenian subjects with type 2 diabetes mellitus, a significant increased risk of PDR was found in GG carriers of the erythropoietin gene rs1617640 polymorphism.

Retinal damage in a new model of hyperglycemia induced by high-sucrose diets

Loss of retinal neurons may precede clinical signs of diabetic retinopathy (DR). We studied for the first time the effects of hyperglycemia on the visual system of the fruit fly Drosophila melanogaster to characterize a model for glucose-induced retinal neurodegeneration, thus complementing more traditional vertebrate systems. Adult flies were fed with increased high-sucrose regimens which did not modify the locomotion ability, muscle phenotype and mobility after 10 days. The increased availability of dietary sucrose induced hyperglycemia and phosphorylation of Akt in fat tissue, without significant effects on adult growth and viability, consistent with the early phase of insulin signaling and a low impact on the overall metabolic profile of flies at short term. Noteworthy, high-sucrose diets significantly decreased Drosophila responsiveness to the light as a consequence of vision defects. Hyperglycemia did not alter the gross anatomical architecture of the external eye phenotype although a progressive damage of photosensitive units was observed. Appreciable levels of cleaved caspase 3 and nitrotyrosine were detected in the internal retina network as well as punctate staining of Light-Chain 3 and p62, and accumulated autophagosomes, indicating apoptotic features, peroxynitrite formation and autophagy turnover defects. In summary, our results in Drosophila support the view that hyperglycemia induced by high-sucrose diets lead to eye defects, apoptosis/autophagy dysregulation, oxidative stress, and visual dysfunctions which are evolutionarily conserved, thus offering a meaningful opportunity of using a simple in vivo model to study the pathophysiology of neuroretinal alterations that develop in patients at the early stages of DR.

Differential effects of high-intensity interval training (HIIT) on choriocapillaris perfusion in healthy adults and patients with type 1 diabetes mellitus (T1DM)

PurposeTo investigate the effects of a four-week high-intensity interval training (HIIT) on choriocapillaris (CC) perfusion in young healthy adults and type 1 diabetes mellitus (T1DM) patients. MethodsData of two HIIT studies with baseline to follow-up comparison were retrospectively analysed. Twenty healthy participants and twenty T1DM patients without clinical signs of diabetic retinopathy were included. All participants had performed a four-week all-out HIIT protocol with a total of 8 training sessions. Changes in physical fitness were assessed using power output at the individual aerobic lactate threshold (IANT). Optical coherence tomography angiography (OCTA) imaging was performed at baseline and follow-up. CC images were analysed for number, size and total area of flow deficits (FD), mean signal intensity, signal intensity standard deviation and kurtosis of signal intensity distribution. ResultsAt baseline, CC OCTA revealed a lower and more heterogeneous intensity signal in T1DM eyes (mean intensity signal and standard deviation of signal intensity, p < 0.001). Percent of CC FD area was greater in T1DM eyes (p < 0.001). While T1DM patients showed greater improvement of exercise capacity at IANT than healthy controls (group×time p = 0.0403), CC FD area and standard deviation of intensity increased in healthy controls but not in T1DM patients (group×time p ≤ 0.029). Moreover, linear regression slopes of FD region distribution differed significantly at baseline and follow-up (p = 0.0002) in healthy individuals but not in T1DM patients. ConclusionsEffects of regular physical exercise performed as HIIT on CC perfusion were only seen in healthy participants, not in T1DM patients suggesting impaired CC adaptation in T1DM.

Foveal avascular zone analysis by optical coherence tomography angiography in patients with type 1 and 2 diabetes and without clinical signs of diabetic retinopathy.

To analyze the early macular microvascular alterations in patients with type 1 and 2 diabetes mellitus (DM) without diabetic retinopathy (DR), using optical coherence tomography angiography (OCT-A), and compare these with nondiabetic patients. This prospective study involved 93 patients with type 1 diabetes (DM1), 104 patients with type 2 diabetes (DM2) without signs of DR, and 71 healthy subjects for the control group. The foveal avascular zone (FAZ) area and the vessel density (VD) at the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were evaluated. The SCP and DCP FAZ areas were significantly larger in the DM1 group in comparison with the controls (p = .001), while no significant differences were observed between the DM2 group and the healthy control group (p = .12). Additionally, no significant differences in FAZ area were found between the DM1 and DM2 groups (p = .26). The VD was significantly reduced in DM1 and DM2 groups compared to controls. A direct correlation was found between the duration of diabetes and SCP FAZ area (r = 0.44; R2 = 0.19; p = .0001). Statistically significant differences in the FAZ area at SCP and DCP were observed when comparing patients with a diabetes duration > 10years and < 10years in the DM2 group (p = .0001, respectively) and only in the FAZ area at the DCP in the DM1 group (p = .0001). Diabetic patients without DR demonstrate early microvascular alteration in the macular area on OCT-A, which is more pronounced in type I DM, and correlates with the duration of the disease.

Automatic microaneurysm detection in fundus image based on local cross-section transformation and multi-feature fusion

Background and objective: Retinal microaneurysm (MA) is one of the earliest clinical signs of diabetic retinopathy(DR). Its detection is essential for controlling DR and preventing vision loss. However, the spatial scale of MA is extremely small and the contrast to surrounding background is subtle, which make MA detection challenging. The purpose of this work is to automatically detect MAs from fundus images. Methods: Our MA detector involves two stages: MA candidate extraction and classification. In MA candidate extraction stage, local minimum region extraction and block filtering are used to exploit the regions where MA may exist. In this way, most of irrelavent background regions are discarded , which subsequently facilitates the training of MA classifier. In the second stage, multiple features are extracted to train the MA classifier. To distinguish MA from vascular regions, we propose a series of descriptors according to the cross-section profile of MA. Specially, as MAs are small and their contrast to surroundings is subtle, we propose local cross-section transformation (LCT) to amplify the difference between the MA and confusing structures. Finally, an under-sampling boosting-based classifier (RUSBoost) is trained to determine whether the candidate is an MA. Results: The proposed method is evaluated on three public available databases i.e. e-ophtha-MA, DiaretDB1 and ROC training set. It achieves high sensitivities for low false positive rates on the three databases. Using the FROC metric, the final scores are 0.516, 0.402 and 0.293 respectively, which are comparable to existing state-of-the-art methods. Conclusions: The proposed local cross-section transformation enhances the discrimination of descriptors by amplifying difference between MAs and confusing structures, which facilitates the classification and improves the detection performances. With the powerful descriptors, our method achieves state-of-the-art performances on three public datasets consistently.