Non-proliferative Diabetic Retinopathy Group Research Articles

Association of Resolved Paracentral Acute Middle Maculopathy Lesions with Diabetic Retinopathy.

To evaluate the association between paracentral acute middle maculopathy (PAMM) lesions and diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). Thirteen diabetic patients without DR, 13 patients with mild nonproliferative DR (NPDR), 18 patients with moderate-to-severe NPDR, and 20 patients with proliferative DR (PDR) were included in this retrospective study. For each patient, 6 mm × 6 mm macular OCTA scans of both eyes were reviewed for the presence of acute and resolved PAMM lesions. Among diabetic patients with and without DR, 49 (94.9%) and 7 (53.8%) patients demonstrated small resolved PAMM lesions, respectively. The odds ratio for the presence of resolved PAMM lesions in the eye with DR compared to the eye of diabetic patient without DR was 21.8 (P < 0.001, 95% confidence interval 7.0-67.8). In the mild NPDR group, moderate-to-severe NPDR group, and the PDR group, 11 (84.6%), 18 (100.0%), and 20 (100.0%) patients demonstrated resolved PAMM lesions, respectively. There was a statistically significant increasing prevalence of PAMM lesions as the severity of DR increased (P < 0.001). Small resolved PAMM lesions are a common form of ischemic retinal lesions in DR.

Aqueous Humor Analyses in Patients with Diabetic Retinopathy Who Had Undergone Panretinal Photocoagulation

Purpose To determine the associations between aqueous humor cytokine levels and the severity of diabetic retinopathy and the prior panretinal photocoagulation (PRP) status of patients with diabetic macular edema (DME). Methods We divided 98 DME patients into those with nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and PRP patients. We compared the concentrations of interleukin- (IL-) 1β, IL-6, IL-8, IL-10, and IL-17; placental growth factor (PlGF); and vascular endothelial growth factor (VEGF) in the aqueous humors. We subclassified PRP patients by the interval between PRP and aqueous sampling and analyzed the associations between aqueous cytokine levels and this interval. Results The aqueous humor levels of IL-6, IL-8, VEGF, and PlGF were significantly higher in the PDR group than in the NPDR group. The PlGF and VEGF levels in the PDR group were significantly higher than those in the PRP group. On PRP subgroup analyses, patients who had undergone PRP within 6 months prior exhibited higher levels of VEGF, PlGF, and TNF-α than did those who had undergone PRP more than 12 months prior. The TNF-α level of the PRP subgroup treated within 6 months prior was significantly higher than that of the PDR group. Regression analyses showed that the levels of VEGF, PlGF, and TNF-α decreased significantly as the interval between PRP and aqueous sampling became longer. Conclusions PDR patients exhibited higher concentrations of VEGF and certain inflammatory cytokines than did NPDR and PRP patients. In the latter patients, the intraocular VEGF and inflammatory cytokine levels fell gradually over time.

Association of advanced chronic kidney disease with diabetic retinopathy severity in older patients with diabetes: a retrospective cross-sectional study.

Despite the recent increasing trend in the prevalence of type 2 diabetes among older individuals, the relationship between diabetic retinopathy (DR) and chronic kidney disease (CKD) in these patients remains unclear. This study investigated the severity of renal dysfunction according to the degree of DR in older patients with type 2 diabetes. A total of 116 patients with diabetes and CKD stage ≥3 who visited both the nephrology and ophthalmology outpatient departments between July 2021 and January 2022 were screened. There were 53 patients in the no DR group, 20 in the nonproliferative DR (NPDR) group, and 43 in the proliferative DR (PDR) group. DR severity was related to the deterioration of renal function. The proportion of patients with advanced CKD significantly increased with DR severity (p for trend <0.001). In the multivariate regression model adjusted for age of ≥80 years, male sex, poorly controlled diabetes, macroalbuminuria, insulin use, diabetes duration of ≥10 years, cerebrovascular accident, hypertension, hyperlipidemia, and cardiovascular disease history, the odds ratio compared with the no DR group was approximately 4.6 for the NPDR group and approximately 11.8 for the PDR group, which were both statistically significant (p=0.025 and p<0.001, respectively). DR severity in older patients with diabetes may be associated with deterioration of renal function and high prevalence of advanced CKD. Therefore, periodic examination for DR in older patients with diabetes is important for predicting renal function deterioration and CKD progression.

Choroidal structural alterations in diabetic patients in association with disease duration, HbA1c level, and presence of retinopathy.

To assess choroidal structural changes in diabetic patients in association with disease duration, HbA1c level, and presence of retinopathy. This retrospective cross-sectional study included treatment-naive patients with non-proliferative DR (NPDR) (group 1), diabetic patients without DR (group 2), and healthy subjects (group 3). Patients were also grouped according to the duration of diabetes: long-term group (> 15years, n = 32) and short-term group (˂ 15years, n = 28). The choroidal thickness was measured at three points; subfoveal, 1500μm nasal, and 1500μm temporal to the fovea. The choroidal area, stromal area, luminal area (LA), and choroidal vascularity index (CVI) were quantified using ImageJ. Partial correlation analysis and one-way analysis of covariance test were performed for statistical analysis. The study included 30 eyes of 30 treatment-naive patients with NPDR (group 1), 30 eyes of 30 diabetic patients without DR (group 2), and 30 eyes of 30 healthy persons (group 3). The mean subfoveal, nasal, and temporal choroidal thicknesses were decreased in group 1 in comparison with controls (p < 0.001, p = 0.035, and p = 0.005, respectively). The mean LA in group 1 and group 2 were both significantly lower compared to group 3 (group 1 vs. group 3, p = 0.004; group 2 vs. group 3, p = 0.020). CVI was significantly lower in group 1 and group 2 than in controls (group 1 vs. group 3, p = 0.019; group 2 vs. group 3, p = 0.025). CVI was significantly lower in the long-duration group than in the short-duration group (p < 0.001). A moderate negative correlation was found between the duration of diabetes and CVI (r = - 0.467, p < 0.001). A moderate negative correlation was found between HbA1c level and luminal area and CVI (r = - 0.466, p < 0.001, and r = - 0.425, p < 0.001, respectively). Choroidal structure and CVI are altered even in the absence of clinically confirmed retinopathy and these alterations are related to the duration of diabetes.

Proteome Changes Associated with the VEGFR Pathway and Immune System in Diabetic Macular Edema Patients at Different Diabetic Retinopathy Stages

Purpose Diabetic macular edema (DME) is a major cause of vision loss in all stages of diabetic retinopathy (DR). However, there is limited recognition of aqueous humor (AH) proteome profiles of DME patients at different DR stages. In this study, we aimed to investigate the AH proteome changes between DME patients at the nonproliferative diabetic retinopathy (NPDR) stage and those at the proliferative diabetic retinopathy (PDR) stage. Methods A label-free data-independent acquisition based liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis was performed to profile the abundances of AH proteins in 73 eyes from DME patients at different DR stages. Enzyme-linked immunosorbent assay (ELISA) was used to confirm the proteomics results with AH samples from non-diabetic patients and DME patients at the NPDR or PDR stage. Results LC-MS/MS results showed significantly changed expression of 308 proteins between DME patients in the NPDR and PDR groups. Compared to the NPDR group, the proteins relatively up-regulated in the PDR group are involved in the immune system and/or negative regulation of the cell cycle, while proteins relatively down-regulated in the PDR group are associated with the vascular endothelial growth factor receptor (VEGFR) pathway and/or metabolism. ELISA results further verified the proteomic result of down-regulated expression of the immune-associated protein cystatin C (CST3) in the PDR group compared to that in the NPDR and non-diabetic groups. Conclusions In this study, we reported for the first time the decreased abundances of AH proteins associated with the VEGFR pathway and both down- and up-regulated expression of AH proteins associated with the immune system in the PDR group compared to that in the NPDR group. Furthermore, we found negative correlations of immune-associated protein, CST3 concentration in AH with DR severity and central retinal thickness, suggesting CST3 as a promising target independent of the VEGFR pathway in DME-involved DR treatment.

Evaluation of the relationship between diabetic retinopathy and left atrial deformation parameters

BackgroundLeft ventricular systolic dysfunction (LVSD) may develop without coronary artery disease, hypertension (HT), or valvular pathologies in patients with diabetes mellitus (DM), which is defined as diabetic cardiomyopathy (DCM) and its pathophysiology is still unclear. Diabetic retinopathy (DR) is a microvascular complication of DM, and patients with DR have increased risk for the development of heart failure (HF). Two-dimensional speckle tracking echocardiography (2D-STE) evaluates longitudinal deformation in left atrium (LA) myocardium and previous studies utilizing 2D-STE have revealed the detrimental effects of DM on LA functions. Although some studies have shown the association between DR and left ventricle (LV) systolic functions, as far as the researchers of this study investigated, there is no study evaluating the relationship between LA deformation parameters and DR. Hence, we aimed to investigate the relationship between the presence and the degree of DR and LA deformation parameters.ResultsLA deformation parameters were analyzed in terms of LA reservoir, conduit, and contractile functions according to the degree of DR. LA reservoir strain value was 14.2 ± 3.6 in normal retina group, 12.2 ± 4.1 in non-proliferative diabetic retinopathy (NPDR) group, and 13 ± 3.7 in proliferative diabetic retinopathy (PDR) group (P = 0.04). LA contractile strain was 15.9 ± 6.8 in normal retina group, 13.1 ± 47.4 in NPDR group, and 9.9 ± 4.7 in PDR group (P < 0.001). LA conduit strain was 30.1 ± 6.6 in normal retina group, 25.3 ± 6.5 in NPDR group, and 22.9 ± 4.9 in PDR group (P < 0.001). Proportional odds regression for association between clinical data, echocardiographic parameters, and LA contractile strain function showed that increasing creatinine (from 0.7 to 1.0; OR 0.71; 95% CI 0.51–0.99; P = 0.04), DR presence (OR 0.24; 95% CI 0.11–0.50; P = 0.001), and increasing left atrial volume index (LAVI) (from 33.5 to 52.6; OR 0.62; 95% CI 0.43–0.89; P = 0.01) were associated with decreasing LA function; however, other variables indicated no association.ConclusionsOur results showed the relationship between LA deformation parameters and DR, although microvascular involvement is not a certainly defined cardiovascular risk factor. Further prospective studies are needed to determine the clinical importance of DR presence and its degree for deformation parameters.

Nonperfusion Area and Other Vascular Metrics by Wider Field Swept-Source OCT Angiography as Biomarkers of Diabetic Retinopathy Severity.

PurposeTo study the wider field (WF) swept-source OCT angiography (SS-OCTA) metrics, especially the nonperfusion area (NPA), in the diagnosing and staging of diabetic retinopathy (DR).DesignCross-sectional observational study (November 2018 to September 2020).ParticipantsA total of 473 eyes of 286 patients (69 eyes of 49 control patients and 404 eyes of 237 diabetic patients).MethodsWe imaged using 6 × 6 mm and 12 × 12 mm angiograms on WF SS-OCTA. Images were analyzed using the ARI Network and FIJI ImageJ. Mixed effects multiple regression models and receiver operating characteristic (ROC) analysis were used for statistical analyses.Main Outcome MeasuresQuantitative metrics such as vessel density (VD); vessel skeletonized density (VSD); foveal avascular zone (FAZ) area, circularity, and perimeter; and NPA in DR and their relative performance for its diagnosis and grading.ResultsAmong patients with diabetes (median age, 59 years), 51 eyes had no DR, 185 eyes (88 mild, 97 moderate-severe) had nonproliferative DR (NPDR), and 168 eyes had proliferative DR (PDR). Trend analysis revealed a progressive decline in superficial capillary plexus (SCP) VD and VSD, and increased NPA with increasing DR severity. Additionally, there was a significant reduction in deep capillary plexus (DCP) VD and VSD in early DR (mild NPDR), but the progressive reduction in advanced DR stages was not significant. The NPA was the best parameter to diagnose DR (area under the curve [AUC], 0.96), whereas all parameters combined on both angiograms efficiently diagnosed (AUC, 0.97) and differentiated between DR stages (AUC range, 0.83–0.97). The presence of diabetic macular edema was associated with reduced SCP and DCP VD and VSD within mild NPDR eyes, whereas increased VD and VSD in SCP were observed in the moderate-severe NPDR group.ConclusionsOur work highlights the importance of NPA, which can be measured more readily and easily with WF SS-OCTA compared with fluorescein angiography. It is quick and noninvasive, and thus can be an important adjunct for DR diagnosis and management. In our study, a combination of all OCTA metrics on both 6 × 6 mm and 12 × 12 mm angiograms had the best diagnostic accuracy for DR and its severity. Further longitudinal studies are needed to assess NPA as a biomarker for progression or regression of DR severity.

Choroidal Vascularity Index Assessment: A Potential Noninvasive Technique for Diagnosing Diabetic Nephropathy.

Aims This study aimed to compare the accuracy of the choroidal vascularity index (CVI) and diabetic retinopathy (DR) in the diagnosis of diabetic nephropathy (DN). Methods We performed a cross-sectional study of 117 patients with proteinuria and diabetes mellitus (DM) in which 45 patients were diagnosed with DN by renal pathology. Demographic information, clinical features, and laboratory data were collected. A total of 234 eyes underwent evaluation of DR and the CVI using enhanced depth imaging-optical coherence tomography scans. We analyzed the association between the CVI and DN and compared the CVI and DR for diagnosing DN using area under receiver operating characteristic curves (AUROCs). Results The severe nonproliferative DR and proliferative DR groups showed a lower CVI than the no DR and mild/moderate nonproliferative DR groups (P < 0.01 or P < 0.001). There was a significantly lower CVI in patients with DN stage III (63.01% ± 1.47%) compared with those in DN stages IIa (62.1% ± 1.41%, P < 0.001) and IIb (59.85% ± 1.98%, P < 0.01). The sensitivity and specificity of the CVI for diagnosing DN were 84% (71%–94%) and 95% (88%–99%), respectively, which were preferable to those of DR. The AUROCs for the CVI and DR for diagnosing DN were 0.932 and 0.831, respectively. The CVI outperformed DR for diagnosing DN (P < 0.05). The cutoff value of the CVI was 63.13%. Conclusion The CVI might be a reliable noninvasive technique for predicting the pathological stage of DN and is superior to DR in diagnosing DN.

Evaluation of TNF-α and IL-6 in saliva among diabetic retinopathy patients in East Coast Malaysia.

To compare tumour necrosis factor-alpha (TNF) and interleukin (IL)-6 levels in saliva between different stages of diabetic retinopathy (DR). This comparative cross-sectional study was conducted between January 2018 and November 2020. This study included diabetes mellitus (DM) patients with no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). None of the patients with DM were included in the control group. Unstimulated saliva samples were then collected. TNF-α and IL-6 levels were measured. Altogether, 120 patients were included in the study (DM without DR, 33 patients; DM with NPDR, 30 patients; DM with PDR, 32 patients; non-DM, 25 patients). The mean IL-6 level in saliva was significantly higher in the DM group (0.033±0.005pg/ml) than in the non-DM group (0.027±0.001pg/ml) (p<0.001 after adjusting for covariates). There was no significant difference in the mean salivary TNF-α between patients with DM and those without DM after adjusting for covariates. The mean IL-6 in saliva was significantly higher in the NPDR (0.036±0.003pg/ml) and PDR (0.093±0.023pg/ml) groups than in the no DR group (0.027±0.001pg/ml) (p<0.001 and p<0.001, respectively). Mean TNF-α in saliva was significantly higher in the NPDR (0.086±0.022pg/ml) and PDR (0.093±0.023pg/ml) groups than in the no DR group (0.049±0.011pg/ml) (p=0.015 and p=0.003, respectively). There is an association between inflammatory biomarkers in saliva (IL-6 and TNF-α) and severity of DR among patients with DM, suggesting that these salivary biomarkers are potential biomarkers for screening, monitoring, and predicting the progression of DR.

Correlation of anterior ocular-segment biometry with glycated hemoglobin level in type-2 diabetic patients

BackgroundDiabetic retinopathy (DR), nephropathy, and peripheral neuropathy are the common complications of diabetes mellitus. DR is one of the causes of blindness worldwide. Although diabetic-eye disease is often thought to refer merely to the retina, the anterior segment of the eye has also been shown to be affected in diabetes.ObjectiveTo compare the anterior ocular-segment biometry among type-2 diabetes mellitus with no DR, nonproliferative diabetic retinopathy (NPDR), and evaluate the correlation of anterior ocular-segment biometry with glycosylated hemoglobin (HbA1c) level.Patients and methodsA cross-sectional study was conducted on 48 patients. The patients were randomly selected from the Ophthalmology Outpatient Clinic of Menoufia University Hospital. Also, they were divided into group I that included 16 diabetic patients with no DR group, group II included 16 diabetic patients with NPDR group, and group III included 16 healthy participants of comparable age and sex. The results were collected, tabulated, and statistically analyzed. Descriptive statistics included percentage (%), mean, SD, range, and median, and analytic statistics included χ2 test, Student's t test, Spearman correlation, Mann–Whitney test, and analysis of variance (F).ResultsNumbers of angle-opening distance and anterior-chamber angle were significantly increased among diabetic patients with no DR group (524.69 ± 41.92, 29.75 ± 3.28) than diabetic patients with NPDR group (491.06 ± 40.80, 27.50 ± 2.53) and control group (479.00 ± 49.55, 26.94 ± 2.08). Also, central corneal thickness (CCT) was significantly increased among diabetic patients with the NPDR group (561.50 ± 14.93) than diabetic patients with no DR group (505.31 ± 46.15) and control groups (452.06 ± 32.14) (P > 0.05). There were significant positive correlations between HbA1c with age, HbA1c%, CCT, and number of angle-opening distance.ConclusionDiabetic patients appear to have significantly thicker CCT, regardless of retinopathy status, whereas anterior-chamber width was significantly narrower in diabetics with the NPDR group compared with a diabetic with no DR. Development of new noninvasive diagnostic technologies has provided a better understanding of corneal-tissue changes related to diabetes.

Correlation between foveal microvasculature and inner retinal layer thickness in type 2 diabetes: an optical coherence tomography angiography study

Aim The aim of this study was to evaluate the correlation between foveal microvasculature and inner retinal layer (IRL) thinning in patients with type 2 diabetes using optical coherence tomography angiography (OCTA).Patients and methods This is a prospective comparative study that included 100 eyes of 100 subjects: 50 eyes of diabetic patients with type 2 diabetes having mild to moderate nonproliferative diabetic retinopathy (NPDR) and 50 eyes of normal subjects. Foveal avascular zone (FAZ) area and vessel density of parafoveal and perifoveal areas were calculated using OCTA. The IRL thickness was measured using optical coherence tomography (OCT). The correlation between the IRL thickness and both FAZ area and macular vessel density was measured.Results The mean FAZ area was significantly larger in the NPDR group (0.69±0.01 mm2) than in the normal eyes group (0.45±0.02 mm2), (P=0.01). The mean parafoveal and perifoveal vessel density in the superficial capillary layer were significantly decreased in eyes with NPDR (46.7±6.5% and 43.8±7.1%, respectively) than in normal eyes (69.5±4.2% and 66.2±4.3%, respectively) (P=0.001). The mean parafoveal and perifoveal vessel density in the deep capillary layer had significantly lower values in eyes with NPDR (51.3±2.3% and 49.5±4.2%, respectively) than in normal eyes (70.1±5.4% and 68.3±3.73%, respectively), (P=0.001). The mean IRL thickness was significantly less in the NPDR eyes (54.7±6.8 μm) than in normal eyes (79.3±6.9 μm), (P=0.001). A statistically significant correlation was found between the IRL thickness and both FAZ area and macular vessel density in eyes with NPDR (P<0.001).Conclusion OCTA revealed that foveal microcirculatory alterations (FAZ area and macular vessel density) in diabetic eyes were related to the IRL thickness.

Application of iris angiography combined with ultra-wide-field fundus fluorescein angiography in diabetic retinopathy

Objective: To explore the application and value of iris angiography combined with ultra-wide-field fundus fluorescein angiography (UWFA) in diabetic retinopathy (DR). Methods: This was a cross-sectional study. From May 2016 to December 2019, 60 consecutive DR patients (120 eyes) including 30 patients (60 eyes) with severe non-proliferative DR (NPDR) and proliferative DR (PDR), respectively, who underwent iris angiography combined with UWFA in Tianjin Medical University Eye Hospital were enrolled in the study. There were 25 males and 35 females, with an average age of (53.5±10.7) years. All of the patients underwent ophthalmologic examination including visual acuity, intraocular pressure, slit-lamp microscopy, slit-lamp funduscopy, ultra-wide-field fundus photography, and iris angiography combined with UWFA. Iris angiography included iris fluorescein angiography (IFA) and iris indocyanine green angiography. The onset time of the iris vascular fluorescein leakage was recorded, and the circumference range of the pupil margin fluorescein leakage was measured by a self-developed software. Wilcoxon rank sum test was used to compare and analyze the difference in the onset time and the range of the iris vascular fluorescein leakage between the severe NPDR and PDR groups. Results: IFA showed that the onset time of the iris vascular fluorescein leakage was 31.00 (25.75, 34.00) s and 27.00 (21.75, 29.50) s in the severe NPDR group and the PDR group, respectively. The difference between two groups was statistically significant (Z=-2.13, P=0.033). The range of the iris vascular fluorescein leakage was 20.00(10.75, 75.00)° and 135.00(60.00, 182.50)° in the severe NPDR group and the PDR group, respectively. There was significant difference between two groups (Z=-4.23, P<0.001). Neovascularization of the iris was not found in all patients with PDR by slit-lamp microscope examination, but was found in 8 eyes by IFA and iris indocyanine green angiography. UWFA findings demonstrated that there was no strong fluorescence in retinal neovascularization elsewhere and/or neovascularization of the optic disc in severe NPDR patients. However, that could be seen in all PDR patients. Among them, 10 eyes had terminally petaloid or focal fluorescein leakage in macular area. Conclusions: Iris angiography combined with UWFA and quantitative analysis method could not only accurately assess the degree of fundus lesions, but also obtain more accurate and comprehensive iris vascular information, which provided help for comprehensive and personalized treatment of DR. (Chin J Ophthalmol, 2021, 57: 916-921).

Mean platelet component in nonproliferative and proliferative diabetic retinopathy

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.

Association Among Lipid Accumulation Product, Chinese Visceral Obesity Index and Diabetic Retinopathy in Patients with Type 2 Diabetes: A Cross-Sectional Study

Background and AimObesity often coexists with diabetes, especially abdominal obesity, recognized as a risk factor for diabetic complications. Diabetic retinopathy (DR), as one of the most common microvascular complications of diabetes, may be associated with these indices. Lipid accumulation product (LAP) and Chinese visceral obesity index (CVAI) are novel visceral obesity indicators, which have been proven to be an influential factor predicting type 2 diabetes (T2DM). However, the correlation among LAP, CVAI, and DR still lacks systematic research in T2DM. The study aimed to explore the relationship among LAP, CVAI levels in different DR stages of T2DM patients and the diagnostic efficacy of LAP and CVAI for DR.MethodsA total of 263 participants were recruited in this cross-sectional study. We enrolled 169 patients with T2DM, divided into the non-DR group (NDR, n = 61), non-proliferative DR group (NPDR, n = 55), and proliferative DR group (PDR, n = 53). And we also enrolled 94 healthy control participants. We collected demographic, anthropometric, and biochemical data on each subject. LAP and CVAI are calculated according to different formulas for men and women.ResultsCompared with the control group, LAP and CVAI were significantly higher (P < 0.05). After adjusting for confounding factors, LAP (OR: 1.029, 95CI%: 1.010–1.049, P < 0.05), WC (OR: 1.073, 95CI%: 1.009–1.141, P < 0.05) and CVAI (OR: 1.017, 95CI%: 1.000–1.033, P < 0.05) were all associated with an increased risk of DR. Furthermore, increased LAP (OR: 1.020, 95% CI: 0.100–0.290) is associated with DR severity (P < 0.001). Moreover, the LAP had the most significant area under the receiver operating characteristics (ROC) curve (AUC) (AUC = 0.728, 95% CI: 0.653–0.804).ConclusionA high LAP is associated with an increased risk of DR in T2DM patients, and the LAP index appears to be a good predictor of DR risk and severity in patients with T2DM, compared with BMI, WC, and CVAI.

Dysregulated Serum Lipid Metabolism Promotes the Occurrence and Development of Diabetic Retinopathy Associated With Upregulated Circulating Levels of VEGF-A, VEGF-D, and PlGF.

Purpose: This study aims to explore the correlations of arteriosclerosis-associated plasma indices with various severity levels of diabetic retinopathy (DR) and to test the hypothesis that elevated circulating level of known angiogenic cytokines induced by hyperglycemia is associated with dyslipidemia on DR.Methods: This cross-sectional study consists of 131 patients with type 2 diabetes. The patients were categorized based on their DR status into those with no DR (diabetes mellitus, DM), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) groups. The biochemical profile including fasting glucose, glycated hemoglobin (HbA1c), lipid profile were estimated, plasma angiogenic cytokines (vascular endothelial growth factor, VEGF-A, -C, -D) and placental growth factor (PlGF) were analyzed by protein microarrays. The atherogenic plasma index (API) was defined as low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C); atherogenic index (AI) was calculated as (TC-(HDL-C))/HDL-C and atherogenic index of plasma (AIP) was defined as log (TG/HDL-C).Results: No significant differences were detected in the duration of hypertension, age, and gender between the three groups. Serum TC and LDL-C, AI, and API in the NPDR group and PDR group were significantly higher than those in the DM group. The circulating level of PlGF, VEGF-A, and VEGF-C were significantly correlated with the severity of DR. VEGF-D is a risk factor independent of API (Z = −2.61, P = 0.009) and AI (Z = −2.40, P = 0.016). Multivariate logistic regression showed that AI and API are strong risk factors for the occurrence and severity of DR. Associated with AI and API, VEGF-D and PlGF contribute to DR: VEGF-D [AI: P = 0.038, odd ratio (OR) = 1.38; VEGF-D: P = 0.002, OR = 1.00. API: P = 0.027, OR = 1.56, VEGF-D:P = 0.002, OR = 1.00] and PlGF [AI: P = 0.021, OR = 1.43; VEGF-D: P = 0.004, OR = 1.50. API: P = 0.011, OR = 1.66; VEGF-D: P = 0.005, OR = 1.49].Conclusions: Total cholesterol (TC) and LDL-C are risk factors for presence of any DR. Atherogenic index and API are novel and better predictive indicators for the occurrence and severity of DR in comparion with the traditional lipid profiles. Abnormal lipid metabolism are associated with the upregulation of circulating cytokines that are linked to the severity of DR.

Zone-wise examination of optical coherence tomography features and their correspondence to multifocal electroretinography in eyes with nonproliferative diabetic retinopathy.

To examine (1) the retinal structure by optical coherence tomography (OCT) and function by means of multifocal electroretinography (mfERG) in eyes with and without nonproliferative diabetic retinopathy (NPDR) (2) for correspondence between local retinal function and OCT zones with retinal lesions. One hundred and thirty-two eligible participants (30 with nonproliferative DR (NPDR) and 102 with diabetes with no DR) underwent comprehensive ophthalmic examination, optical coherence tomography for retinal thickness measures, mfERG, and ultra-wide field fundus photography. OCT Early Treatment Diabetic Retinopathy Study (ETDRS) grid was overlaid on to mfERG plots. Those with NPDR had significantly thicker full retinal measures in the nine (ETDRS) zones compared to no DR. mfERG P1 latencies in rings 1-6 were significantly delayed, while the response densities in rings 4-6 were lower in the NPDR group. Significant negative correlation was noted between OCT thickness and mfERG P1 response densities in many ETDRS zones. Significant positive correlation was noted between P1 latencies and OCT thickness in a few zones. The combination of cystic spaces, microaneurysms, and hard exudates were present in all zones and were associated with a decrease in P1 response densities compared to no lesions. Reduced P1 response densities were associated with a sporadic delay in the mfERG latencies and vice versa. The number of lesions did not show correspondence to the mfERG measures. In eyes with NPDR, retinal function is differentially correlated with the DR lesions on OCT and can be assessed using multimodal imaging modalities.

Correlation between optical coherence tomography angiography and multifocal electroretinogram findings in patients with diabetes mellitus

BackgroundDiabetic retinopathy is characterized by microvascular, neural and glial cell damage. Optical coherence tomography angiography (OCTA) can detect subclinical microvasculopathy while multifocal electroretinography (mfERG) can detect subclinical local retinal dysfunction before onset of clinically observable retinopathy. Here, we investigated the relationship between retinal dysfunction in multifocal electroretinography and vascular changes in optical coherence tomography angiography. MethodsThe study included 63 eyes of 63 diabetic patients without retinopathy (DM+DR-) and 68 eyes of 68 patients with non-proliferative diabetic retinopathy (NPDR). In addition, 64 eyes of 64 age and sex-matched subjects were included as the control group (CG). All subjects were evaluated using OCTA and mfERG. ResultsThe vascular density in the superficial and deep capillary plexus was significantly decreased in the DM+DR-group and the NPDR group compared with the CG group (except for the superficial foveal area, NPDR group vs. CG group) (p < 0.05). The vascular density of the superficial and deep parafoveal region was significantly decreased in the NPDR group compared to the DM+DR-group (p < 0.05). In circles of 2-, 5- and 10°, the amplitudes of the N1 and P1 waves were statistically significantly decreased in both the DM+DR- group and the NPDR group compared with the CG (p < 0.05). When the NPDR group was compared with the DM+DR- group, there was a statistically significant decrease in the amplitude of the N1 and P1 waves in the circles of 2- and 5° (p < 0.05). According to the correlation analysis, the amplitude and implicit times of the N1 and P1 waves showed weak-to-moderate correlation with vascular density (p < 0.05). ConclusionsThe decreased peaks of mfERG wave provides evidence regarding neurodegenerative effect of DM-associated hyperglycaemia. The decreased vascular density caused by hyperglycaemia was topographically associated with the retinal dysfunction and neurodegeneration.

Association between cystatin C and diabetic retinopathy among type 2 diabetic patients in China: a Meta-analysis.

To explore the correlation between cystatin C (Cys-C) and diabetic retinopathy (DR) in those patients with type 2 diabetes mellitus (DM) in China. Articles were collected from China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and Google Scholar. Quality and risk of bias within included studies was assessed using the Newcastle-Ottawa scale (NOS). Heterogeneity was determined by using Cochran's Q-test and Higgins I 2 statistics. Mean differences (MDs) and 95% confidence intervals (CIs) of Cys-C within the diabetes without retinopathy (DWR) and DR, DWR and non-proliferative diabetic retinopathy (NPDR), NPDR and proliferative diabetic retinopathy (PDR) were collected by using random-effects model because of high heterogeneity. Meta-analysis was conducted based on 23 articles of 2331 DR including NPDR and PDR patients and 2023 DWR patients through Review Manager 5.3. Subgroup analyses were also performed according to DM duration, body mass index (BMI), total cholesterol (TC), total triglycerides (TG), low-density lipoprotein C (LDL-C), and high-density lipoprotein C (HDL-C), sample origins and methods. Publication bias was assessed by the funnel plot. Cys-C level in DR patients was increased compared with that of DWR (total MD: 0.69, 95%CI: 0.41 to 0.97, Z=4.79, P<0.01). Besides, the synthesized results of the studies showed the similar findings in the DWR vs NPDR group (total MD: 0.29, 95%CI 0.20 to 0.39, Z=6.02, P<0.01) and the NPDR vs PDR group (total MD: 0.63, 95%CI 0.43 to 0.82, Z=6.33, P<0.01). Heterogeneity of most of the subgroup analyses was still obvious (I 2≥50%, P<0.1). Forest plots of different subgroups indicated that there was a slight increase of Cys-C during the period between DWR and DR, DWR and NPDR, NPDR and PDR. Funnel plot showed that there was no significant publication bias. The elevated Cys-C is closely related with DR and probably plays a critical role in its progression.

Retinal structure-function correlation in type 2 diabetes.

To examine the relationship of visual function as assessed by visual acuity, contrast sensitivity, and multifocal electroretinography (mfERG) to macular structural and microvascular measures on optical coherence tomography (OCT) and angiography (OCTA) in individuals with diabetes. This is a prospective observational study conducted at a tertiary eye care centre in India. Right eyes of 121 adults with type 2 diabetes with no diabetic retinopathy (DR), mild or moderate nonproliferative DR (NPDR) were examined. Severe NPDR, proliferative DR and diabetic macular oedema were excluded. Participants underwent assessment of glycated haemoglobin (HbA1C), blood pressure, best corrected visual acuity (LogMAR), contrast sensitivity (CS), mfERG, ultrawide field fundus photography, OCT and OCTA. Correlations were assessed by Spearman's rank correlation (rho). Of the total of 121 eyes, 89 had No DR, 32 had mild to moderate NPDR. In the No DR group, the LogMAR acuity was significantly and negatively correlated to central subfoveal thickness (CST) (rho = -0.420), macular vessel density (rho = -0.270) and perfusion (rho = -0.270). (ii) Contrast sensitivity correlated to foveal avascular zone circularity (rho = 0.297); (iii) mfERG P1 response densities were better with higher macular perfusion index (rho = 0.240). In the NPDR group, the LogMAR acuity also showed a significant negative correlation to CST (rho = -0.379). Other correlations were not significant. Retinal and visual functional changes are evident in diabetic patients with No DR and are correlated to subclinical retinal structural changes detectable using multimodal imaging.

English

BACKGROUND Diabetes mellitus is a heterogeneous group of diseases, characterized by a state of chronic hyperglycemia, resulting from varied aetiologies. Diabetic retinopathy (DR) is the most common ocular complication of diabetes with 5 % of diabetics, progressing to severe visual loss of 5/200 or less. 3 Very few studies have been conducted on optical coherence tomography (OCT) changes in diabetic retinopathy in Indian scenario. We wanted to evaluate the association of retinal nerve fibre layer (RNFL) thickness with diabetic retinopathy and assess the possibility of RNFL thickness changes being a precursor to diabetic retinal changes. METHODS A cross sectional study was conducted at the Department of Ophthalmology, Acharya Vinobha Bhave Rural Hospital. A total of 120 patients were enrolled for the study and divided into four groups of equal population as controls / non-diabetics (NDM), diabetics without retinopathy (NDR), diabetics with non-proliferative diabetic retinopathy (NPDR) and diabetics with proliferative retinopathy (PDR). Patients were evaluated for visual acuity, RNFL thickness, intraocular pressure(IOP), cup disc ratio in each case and data was statistically analysed. RESULTS Mean temporal RNFL thickness in PDR group was 73.72 ± 15.22 and was statistically significant (P = 0.0001) than temporal RNFL thickness in controls (60.41 ± 7.56), NDR (61.06 ± 6.51) and NPDR (59.01 ± 5.51). Mean cup-disc disc ratio was 0.26 ± 0.08 in controls, was 0.28 ± 0.11 in NDR group, 0.32 ± 0.08 in NPDR group and 0.36 ± 0.11 in PDR group and was statistically significant (P = 0.026). However no statistically significant difference was seen in global average RNFL thickness across groups though it was more in NPDR and PDR when compared to NDM group, and was least in NDR group. CONCLUSIONS There was statistically significant increase in temporal RNFL thickness in diabetic group which worsens with the disease. Hence temporal RNFL thickness may be estimated in diabetic patients to predict transformation to diabetic retinopathy and intervene at an early stage. KEY WORDS Diabetes Mellitus, Retinal Nerve Fibre Layer, Proliferative Diabetic Retinopathy, Non Proliferative Diabetic Retinopathy