Balancing Data through Data Augmentation Improves the Generality of Transfer Learning for Diabetic Retinopathy Classification

Objective To investigate the distribution patterns of diabetic macular edema (DME) based on optical coherence tomography (OCT), and explore its correlation with diabetic retinopathy (DR) stages and systemic factors. Methods A total of 135 patients (242 eyes) with type 2 diabetes were included in this retrospective study. There were 75 males (138 eyes) and 60 females (104 eyes), the ages were from 29 to 83 years, with an average age of (58.8±11.1) years. The general information such as height, weight, smoking history and blood glucose [such as glycosylated hemoglobin (HbA1c)], blood pressure, blood lipid, 24 hours urine protein and other examinations were collected. The diagnosis of DR and DME were made, and the staging of DR and typing of DME were performed based on fundus color imaging and OCT. DR were divided into mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR and proliferative DR (PDR). DME were categorized into 4 types including sponge-like retinal swelling (SME), cystoid macular edema (CME), serous retinal detachment (SRD) and posterior hyaloid traction (PHT). The correlation between DME types and DR staging were analyzed by χ2 test and Fisher exact test. Multivariate logistic regression analysis was used to analyze the correlation between DME types and systemic factors. Results In 242 DR eyes the proportions of mild, moderate, severe NPDR and PDR were 30.99%, 32.64%, 23.14% and 13.23%, respectively. There were 199 eyes (82.23%) with DME. There were statistically significant differences in the proportion of DME in different stages of DR (χ2=21.077, P<0.01). In the 199 eyes with DME, There were 165 eyes (68.18%) of SME, 22 eyes (9.09%) of CME, 7 eyes (2.89%) of SRD and 5 eyes (2.07%) of PHT. The distribution of DME patterns in different stages of DR was statistically significant (χ2=156.273, P<0.01). Logistic regression analysis showed that the duration of diabetes, HbA1c and macroalbuminuria were independent risk factors for DME [odds ratio (OR)= 1.090, 1.510, 4.123; P<0.05], and were also independent for SME (OR=1.092, 1.445, 3.942; P<0.05); HbA1c was an independent risk factor for SRD (OR=2.337, P<0.05). Conclusions There are differences in the distribution of different DME types in each stage of DR. The duration of diabetes, HbA1c and macroalbuminuria were independent risk factors for DME and SME, and macroalbuminuria and HbA1c for CME and SRD. Key words: Macular edema/diagnosis; Risk factors; Diabetic retinopathy/diagnosis; Tomography, optical coherence

BackgroundWith the diabetes mellitus (DM) prevalence increasing annually, the human grading of retinal images to evaluate DR has posed a substantial burden worldwide. SmartEye is a recently developed fundus image processing and analysis system with lesion quantification function for DR screening. It is sensitive to the lesion area and can automatically identify the lesion position and size. We reported the diabetic retinopathy (DR) grading results of SmartEye versus ophthalmologists in analyzing images captured with non-mydriatic fundus cameras in community healthcare centers, as well as DR lesion quantitative analysis results on different disease stages.MethodsThis is a cross-sectional study. All the fundus images were collected from the Shanghai Diabetic Eye Study in Diabetics (SDES) program from Apr 2016 to Aug 2017. 19,904 fundus images were acquired from 6013 diabetic patients. The grading results of ophthalmologists and SmartEye are compared. Lesion quantification of several images at different DR stages is also presented.ResultsThe sensitivity for diagnosing no DR, mild NPDR (non-proliferative diabetic retinopathy), moderate NPDR, severe NPDR, PDR (proliferative diabetic retinopathy) are 86.19, 83.18, 88.64, 89.59, and 85.02%. The specificity are 63.07, 70.96, 64.16, 70.38, and 74.79%, respectively. The AUC are PDR, 0.80 (0.79, 0.81); severe NPDR, 0.80 (0.79, 0.80); moderate NPDR, 0.77 (0.76, 0.77); and mild NPDR, 0.78 (0.77, 0.79). Lesion quantification results showed that the total hemorrhage area, maximum hemorrhage area, total exudation area, and maximum exudation area increase with DR severity.ConclusionsSmartEye has a high diagnostic accuracy in DR screening program using non-mydriatic fundus cameras. SmartEye quantitative analysis may be an innovative and promising method of DR diagnosis and grading.

To investigate the clinical value of epiretinal macrophage-like cells (eMLCs) in different stages of diabetic retinopathy (DR), including diabetic macular edema (DME). One hundred and seventy-six eyes of 176 patients, including 31 diabetes eyes without retinopathy, 24 with mild nonproliferative DR (NPDR), 37 with moderate NPDR, 32 with severe NPDR, and 52 with proliferative DR, were compared with 30 healthy controls. The optic nerve head and macular region were examined using en face optical coherence tomography and optical coherence tomography angiography. A previously described technique was employed to measure the eMLCs on the inner limiting membrane. The optic nerve head and macular eMLC densities increased with worsening DR stage and were higher in moderate, severe NPDR, and proliferative DR, especially in eyes with DME (all adjusted P < 0.01). The optic nerve head and macular eMLC densities in the DME groups were higher than those in their corresponding non-DME groups at the same DR stage (all P < 0.05). The average macular thickness was correlated with macular eMLC density (standardized β = 0.661, P < 0.001) in patients with diabetes. The proportion of eyes with larger and plumper eMLCs increased with worsening DR and was higher in moderate, severe NPDR, proliferative DR, and eyes with DME ( P = 0.018, P < 0.001, P < 0.001, and P < 0.001, respectively). Increased density along with morphological changes of eMLCs is observed beginning with moderate NPDR and correlates with the progression of DR, including DME.

PurposeTo characterize the natural course of diabetic retinopathy (DR) in contemporary clinical practice.Patients and MethodsThis was a retrospective analysis of US claims data collected between January 1, 2006, and April 30, 2017. Patients aged ≥18 years with continuous medical and prescription insurance coverage for 18 months before DR diagnosis (index date) and for a follow-up period of 5 years were included (N=14,490). The time and risk of progressing to severe nonproliferative DR (NPDR) or proliferative DR (PDR) and of developing diabetic macular edema (DME) were evaluated over 5 years in patients stratified by DR severity at initial diagnosis.ResultsThe estimated probability of progressing to severe NPDR or PDR within 5 years of diagnosis was 17.6% for patients with moderate NPDR versus 5.8% for mild NPDR. The probability of developing DME within 5 years was 62.6%, 44.6%, and 28.4% for patients diagnosed with severe NPDR, moderate NPDR, and PDR, respectively, versus 15.6% for mild NPDR. Among those observed to progress, median time to severe NPDR or PDR was approximately 2.0 years in patients with moderate NPDR, whereas median time to DME was approximately 0.5 years in patients with severe NPDR, 1.3 years in moderate NPDR, and 1.6 years in PDR. Relative to mild NPDR, adjusted hazard ratios (95% confidence interval) for progression to severe NPDR or PDR within 5 years were 3.12 (2.61–3.72) in patients with moderate NPDR, and for incident DME were 5.92 (5.13–6.82), 3.54 (3.22–3.91), and 1.96 (1.80–2.14) in patients with severe NPDR, moderate NPDR, and PDR, respectively.ConclusionThe risk of DR progression and DME over 5 years was highest among patients diagnosed with moderate and severe NPDR, respectively. Our findings reinforce the importance of close monitoring for these patients to avoid unobserved disease progression toward PDR and/or DME.

Introduction: This study aimed to evaluate the association between macular optical coherence tomography angiography (OCT-A) metrics, characteristics of ultrawide field (UWF) imaging, and cerebrovascular disease in patients with diabetes mellitus (DM) with different stages of diabetic retinopathy (DR). Methods: 516 eyes of 258 DM patients were enrolled in two centers (Milan and Belfast). UWF color fundus photos (CFPs) were obtained with Optos California (Optos, PLC) and graded for both DR severity and predominantly peripheral lesions presence (>50% of CFP lesions) by two independent graders. OCT-A (3 × 3 mm), available in 252 eyes of 136 patients, was used to determine perimeter, area, and circularity index of the foveal avascular zone and vessel density (VD); perfusion density (PD); fractal dimension on superficial, intermediate (ICP), and deep capillary plexuses; flow voids (FVs) in the choriocapillaris. Results: Out of 516 eyes, 108 eyes (20.9%) had no DR, and 6 eyes were not gradable. The remaining 402 eyes were as follows: 10.3% (53) had mild nonproliferative DR (NPDR), 38.2% (197) had moderate NPDR, 11.8% (61) had severe NPDR, and 17.6% (91) had proliferative DR. A worse DR stage was associated with a history of stroke (p = 0.044). Logistic regression analysis after taking into account sex, type of DM, age, DM duration, and OCT-A variables found that PD and VD on ICP were significantly associated with presence of stroke and DR severity. Conclusion: OCT-A metrics show an association with the presence of cerebrovascular complications, providing potentially useful parameters to estimate vascular risk in patients with DM.

PurposeThe purpose of this study was to evaluate differences in optical coherence tomography angiography (OCTA) metrics in the superficial (SCP), intermediate (ICP), and deep (DCP) vascular plexuses across diabetic retinopathy (DR) severity levels.MethodsThis was a cross sectional observational retrospective chart review study. Eligible patients with diabetes who underwent same day RTVue XR Avanti OCTA, spectral-domain optical coherence tomography (SD-OCT), and 200-degree Optos ultrawide field color imaging. SCP, ICP, and DCP vessel density (VD) and vessel length density (VLD) were assessed using 3-D projection artifact removal software (PAROCTA) software.ResultsOf 396 eyes (237 patients), 16.1% had no DR, 26.9% mild nonproliferative DR (NPDR), 21.1% moderate NPDR, 12.1% severe NPDR, 10.1% proliferative DR (PDR) without panretinal photocoagulation (PRP), and 13.4% PDR with PRP. When comparing mild NPDR to no DR eyes, ICP and DCP VD and VLD were significantly lower, but there was no difference for SCP metrics. In eyes with more severe DR, there were significant differences in SCP VD and VLD between DR severity levels (mild versus moderate NPDR: VD 35.45 ± 3.31 vs. 34.14 ± 3.38, P = 0.008 and VLD 17.59 ± 1.83 vs. 16.80 ± 1.83, P = 0.003; moderate versus severe NPDR: VLD 16.80 ± 1.83 vs. 15.79 ± 1.84, P = 0.019), but no significant differences in ICP or DCP.ConclusionsAlthough VD of each of the three individual layers decreases with increasing DR severity, DR severity has a substantially different effect on OCTA parameters within each layer. Vascular changes in eyes with no to early DR were present primarily in the deeper vascular layers, whereas in eyes with advanced DR the opposite was observed. This study highlights the effects of ICP and the importance of assessing SCP and DCP changes independently across each DR severity level.

Inadequacies and inaccuracies in grading non proliferative diabetic retinopathy without fluorescein fundus angiography in Chinese patients.

Introduction: Diabetic retinopathy (DR) remains a visually debilitating disease and is commonly classified according to its severity as non-proliferative DR (NPDR) or proliferative DR (PDR). Those suffering from PDR tend to have worse vascular complications and prognosis. Platelets exposed by vasculopathy caused by DR maybe activated to try to maintain haemostasis. This activity can be illustrated by the mean platelet component (MPC). Therefore, by MPC monitoring we may be able to predict the progression from NPDR into PDR.Purpose: To investigate the difference of MPC in patients with NPDR and PDR.Study design: Cross-sectional.Materials and methods: This study involved 71 DR patients. Preliminary data regarding the patients’ demographic characteristics, diabetes history, related diseases, medication history, and general eye examination were recorded. Fundus photographs were taken after dilating eyedrops and DR was graded by an ophthalmologist. The patients were grouped into NPDR and PDR. Mean platelet component was analyzed using the automatic hematology analyzer ADVIA 120.Results: Mean platelet component (MPC) was 26.69 g/dl (± 1.79) and 25.52 g/dl (± 1.20) in the NPDR and PDR group, respectively (p = 0.002), but was not clinically significant. In depth analysis into the DR grades differed significantly between mild NPDR and high-risk PDR (p = 0.015), and moderate NPDR and high-risk PDR (p = 0.024). Using our definition of mild DR (mild and moderate NPDR) and severe DR (high-risk and advanced PDR), there was a significant difference with mean MPC of 27.01 g/dl (± 1.64) and 25.31 g/dl (± 1.22), respectively (p = 0.001). The proportion of activated platelets was also higher in severe DR. Negative correlations were found between MPC with duration of DM (r = -0.333; p = 0.004) and MPC with systolic blood pressure (r = -0.241; p = 0.043).Conclusion: There was a significant difference in MPC between NPDR and PDR, but the results should be interpreted carefully. Further analysis between the mild and severe form of DR strengthened this finding.

Our aim is to study the dynamics of pupillary abnormalities in varying severity of diabetic retinopathy. A non-interventional case-control study with 405 eyes of 244 subjects with diabetes, and 41 eyes of 26 subjects with no history of diabetes was done. Diabetes group was classified according to retinopathy severity: no retinopathy, mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR and proliferative diabetic retinopathy (PDR). After dark adaptation, pupil size and flashlight response were captured with an infrared camera. Baseline Pupil Diameter (BPD), Amplitude of Pupillary Constriction (APC), Velocity of Pupillary Constriction (VPC) and Velocity of Pupillary Dilatation (VPD). Compared to controls, mean BPD decreased with increasing severity of diabetic retinopathy. Mean APC in control group was 1.73 ± 0.37 mm and reduced in mild NPDR (1.57 ± 0.39, p = 1.000), moderate NPDR (1.51 ± 0.44, p = 0.152) and found to be significant reduced in severe NPDR (1.43 ± 0.48, p = 0.001) and PDR (1.29 ± 0.43, p = 0.008). Compared to controls, mean VPC decreased progressively with increasing severity of retinopathy, with a maximal difference in the PDR group. Mean VPD as compared to the control group was significantly reduced in the no DR (p = 0.03), mild NPDR (p = 0.038), moderate NPDR (p = 0.05), PDR group (p = 0.02). We found pupillary dynamics are abnormal in early stages of diabetic retinopathy and progress with increasing retinopathy severity.

目的 探讨尿白蛋白在糖尿病性视网膜病变(diabetic retinopathy,DR)不同临床分型阶段中的应用价值,了解尿白蛋白与DR病程的相关性,探讨它在DR中的临床应用价值,以期用于DR病情监测.方法 前瞻性调查研究.散瞳眼底检查在糖尿病人群中测定96例存在视网膜病变患者(病例组)及144例尚未出现视网膜病变患者(对照组)的尿白蛋白水平.计量资料采用u检验,进行相关性分析,并应用受试者工作特征(receiver operating characteristic,ROC)曲线进行比较和分析.结果 尿白蛋白水平在DR不同临床分型的组间差异有统计学意义(F=10.683,P=0.000).DR不同临床分型的ROC曲线分析:在轻度非增殖性糖尿病性视网膜病变(nonproliferative diabetic retinopathy,NPDR)时期,尿白蛋白ROC曲线位于机会对角线以下,曲线下面积(area under curve,AUC)仅为0.441;而在中、重度NPDR时期,当诊断界值为12.7 mg/L(约登指数=0.440)时,尿白蛋白的AUC为0.742,特异度(specificity,SPE)为56.10%,灵敏度(sensitivity,SEN)为87.88%;在增殖性糖尿病性视网膜病变(proliferative diabetic retinopathy,PDR)时期,当诊断界值为45 mg/L时(约登指数=0.503),其AUC为0.761,SPE为87.80%,SEN为62.50%.结论 尿白蛋白的表达水平与DR程度相关,可以反映DR的发展情况,辅助临床对糖尿病性视网膜病变进行监测。

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Diabetes-related retinal disease (DR) is the subject of the investigation. One of the main reasons why diabetic individuals become blind is diabetic retinopathy syndrome. DR is classified into two major types, first Non-Proliferative Diabetic Retinopathy (NPDR) and the second Proliferative Diabetic Retinopathy (PDR). The treatment can be given to the patients based on the neovascularization (Abnormal Blood Vessel Growth) in the retina. Early findings of neovascularization are much important. Based on this report only an optometrist can identify, whether if the patient comes under NPDR or PDR. NPDR is further classified into three stages, Mild NPDR, Moderate NPDR and Severe NPDR. The main causes of vision impairment in this group of patients are of concern. Early diagnosis, careful observation, and appropriate evidence-based management—which frequently involves several different health care disciplines and professions—are necessary for diabetes and diabetic retinopathy (DR). The one area of the body where physical damage to blood vessels brought on by systemic disorders can be seen noninvasively is treated and observed by an optometrist. This highlights how crucial it is to keep an eye on all diabetic patients and collaborate with endocrinologists or primary care physicians (PCPs) to properly manage these individuals. In the past, skilled professionals would treat patients by hand. However, with the rapid advancement of technology, diabetic retinopathy may now be treated digitally. A specialist can identify the more intricate characteristics of the eye and treat patients appropriately.

Wide-field optical coherence tomographic angiography (OCTA) may provide insights to peripheral capillary dropout in eyes with diabetic retinopathy (DR). To describe the diagnostic performance of wide-field OCTA with and without large vessel removal for assessment of DR in persons with diabetes. This case-control study was performed from April 26, 2018, to April 8, 2019, at a single tertiary eye center in Singapore. Case patients were those with type 2 diabetes for more than 5 years and bilateral DR diagnosed by fundus imaging; control participants included those with no self-reported history of diabetes, a fasting glucose level within the normal range in the past year, and no ocular pathologic findings. A wide-field (12 × 12-mm2) fovea-centered scan was performed using a prototype swept source OCTA system. Retinal microvasculature was examined by separating the angiograms into large vessels, capillaries, and capillary dropout regions. Area under the receiver operating characteristic curve (AUC) for DR severity discrimination using wide-field vascular metrics. Retinal perfusion density (RPD), capillary perfusion density (CPD), large vessel density (LVD), and capillary dropout density (CDD) were calculated. Low-contrast regions were excluded from the calculation. A total of 49 eyes in 27 control participants (17 male [63.0%]; mean [SD] age, 59.96 [7.63] years; age range, 44-79 years) and 76 eyes in 47 patients with diabetes (29 male [61.7%]; mean [SD] age, 64.36 [8.08] years; range, 41-79 years) were included. Among eyes in patients with diabetes, 23 were in those with diabetes but no DR, 25 in those with mild nonproliferative DR, and 28 in those with moderate to severe nonproliferative DR. There was no difference in RPD, CPD, LVD, and CDD between the control group and the group with diabetes and no DR. There was a stepwise decrease in RPD, CPD, and CDD in the diabetes with no DR, mild nonproliferative DR, and moderate to severe nonproliferative DR groups, whereas LVD was not associated with DR staging. The nonproliferative DR group had decreased RPD, CPD, and CDD compared with the control group. The CPD had higher AUCs than RPD for discriminating diabetes with nonproliferative DR (combined mild and moderate to severe nonproliferative DR) vs no DM (AUC, 0.92 [95% CI, 0.87-0.98] vs 0.89 [95% CI, 0.83-0.95], P = .01), diabetes with no DR vs mild nonproliferative DR (AUC, 0.81 [95% CI, 0.68-0.94] vs 0.77 [95% CI, 0.64-0.91], P = .18), and mild nonproliferative DR vs moderate to severe nonproliferative DR (AUC, 0.82 [95% CI, 0.71-0.94] vs 0.78 [95% CI, 0.65-0.91], P = .01) but similar AUCs for no DM vs diabetes with no DR. The total perfusion density and CPD in wide-field OCTA had better discriminative power than the central 6 × 6-mm2 field (CPD, 0.89 [95% CI, 0.83-0.95] vs 0.84 [95% CI, 0.77-0.92], P = .06; total perfusion density, 0.93 [95% CI, 0.87-0.98] vs 0.90 [95% CI, 0.83-0.96], P = .06). The findings suggest that wide-field OCTA provides information on microvascular perfusion and may be useful for detecting predominant peripheral capillary dropout in eyes with nonproliferative DR. A vascular selectivity approach excluding the large vessels may improve the discriminative power for different stages of DR.

Introduction: Diabetes Mellitus (DM) causes high blood sugar, leading to complications such as cerebrovascular events, chronic kidney disease, cardiovascular issues and retinopathy. Diabetic Retinopathy (DR) is a key microvascular complication and may indicate other diabetic issues. Studies suggest a link between DR and Cerebrovascular Accidents (CVAs) (strokes), particularly in low and middle-income countries where stroke rates are increasing. Aim: To assess the prevalence of DR among individuals who have experienced CVAs and to explore the relationship between DR and CVAs within the Indian population. Materials and Methods: The present cross-sectional study was conducted in the Department of Ophthalmology, Dr. D. Y. Patil Medical College and Research Centre (tertiary care hospital), Pimpri, Pune, Western Maharashtra, India, from November 2022 to June 2024. The study included 100 patients (200 eyes) aged 40-70 years with CVAs and diabetes. Details regarding age, gender and, detailed ocular and systemic information were recorded. Diagnosis of DM and CVA is done according to standard methods. Intraocular pressure was measured using the Goldmann Applanation Tonometer (GAT) and Optical Coherence Tomography (OCT). DR was classified based on severity into mild, moderate and severe groups. Data were analysed using Statistical Package for Social Sciences (SPSS) software version 26.0. Statistical significance was set at 5%. Results: In the present study, patients with DR had a mean±Standard Deviation (SD) age of 57.13±7.63 years. Among the CVA patients, 79% had DR. A total of 44 (44%) patients had moderate Non Proliferative Diabetic Retinopathy (NPDR), 20 (20%) had mild NPDR and 15 (15%) had severe NPDR. The average age of DR patients was 57.13±7.63 years, compared to 51.48±6.36 years for non DR patients. Haemorrhagic strokes were more common, occurring in 59 (59%) patients. Patients with both DR and CVAs were older and had higher blood sugar and HbA1c levels than those without DR. No association was found between DR and the type of stroke (p-value 0.761). Conclusion: Diabetic retinopathy was present in 79% of stroke patients, with moderate NPDR being the most common type. DR patients were older and had higher blood sugar and HbA1c levels. Haemorrhagic stroke was more prevalent in this group. However, no significant association was found between the types of stroke and DR.

The aim of this study was to analyze the correlation between serum levels of inflammatory cytokines IL-1beta, IL-6, TNF-alpha and VEGF and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). In this prospective study we included 38 healthy volunteers (group 1) and 39 patients with type 2 DM (group 2). All participants underwent routine ophthalmological examination and laboratory analysis of the serum cytokines IL-1beta, IL-6, TNF-alpha and VEGF. Group 2 patients were additionally examined by colour fundus photography and fluorescein angiography to determine the DR stage. We studied the correlation of IL-1beta, IL-6, TNF-alpha and VEGF with the presence of DM, the presence and severity of DR, the duration of DM and DR, the serum levels of glycosylated haemoglobin, as well as with hyperlipidemia and the general indicators of inflammation - erythrocyte sedimentation rate (ESR) and fibrinogen. The group 2 patients had statistically significantly higher levels of IL-1beta (p = 0.01) and IL-6 (p = 0.029) and elevated TNF-alpha and VEGF levels in comparison with group 1 patients. Group 2 patients were divided into 5 subgroups depending on the severity of DR: patients without DR (n = 11), patients with mild non-proliferative DR (n = 10), patients with moderate non-proliferative DR (n = 5), and patients with severe non-proliferative DR (n = 2) (total number of non-proliferative DR (n = 17)) and patients with proliferative DR (n = 11). The comparative analysis showed statistically significant differences in the serum levels of IL-1beta (p = 0.003), TNF-alpha (p = 0.002) and VEGF (p = 0.005) between the different subgroups. Patients with proliferative DR showed significantly higher values of serum IL-1beta (p < 0.0001), IL-6 (p = 0.007), TNF-alpha (p = 0.002) and VEGF (p < 0.0001) compared with the patients with non-proliferative DR. The cytokine serum levels did not correlate with the duration of DM, the duration of DR (except for IL-1beta, p = 0.045), and hyperlipidemia (except for TNF-alpha, p = 0.05). TNF-alpha(p = 0.05) and VEGF (p = 0.047) serum levels correlated with the levels of glycosylated hemoglobin, and IL-1beta, TNF-alpha and VEGF correlated with the general indicators of inflammation (ESR and fibrinogen). Serum concentrations of IL-1beta, TNF-alpha and VEGF have an effect on the development and progression of DR. They correlate with the presence and severity of the disease. Whether serum cytokines can play the role of a prognostic factor or serve as a means to choose a proper therapeutic agent for the treatment of diabetic retinopathy should be analyzed by further more extensive prospective longitudinal studies in future.