Retinopathy Group Research Articles

Genomic DNA Methylation in Diabetic Chronic Complications in Patients With Type 2 Diabetes Mellitus.

AimTo explore the relationship between genomic DNA methylation and diabetic chronic complications.Methods299 patients with type 2 diabetes mellitus (T2DM) hospitalized in the Second Affiliated Hospital of Soochow University were enrolled. We divided the patients into different complications groups and corresponding non-complication groups. Clinical and biochemical parameters were compared between the two groups. The level of genomic DNA methylation in leukocytes was determined by high-performance liquid chromatography-tandem mass spectrometry.Results(1) Age, duration of diabetes, creatinine (Cr), blood urea nitrogen (BUN), genomic DNA methylation, 24- hour urine total protein (24-hUTP), and intima-media thickness (IMT) were significantly higher in the carotid plaque (CP) group. Waist-to-hip ratio (WHR), body mass index (BMI), estimated glomerular- filtration rate (eGFR), and albumin (Alb) were significantly lower in the CP group. Gender, age and BMI were the influencing factors of CP. (2) Age, duration, Cr, BUN, urinary microalbumin creatinine ratio (UACR), systolic blood pressure (SBP), TCSS, and 24- hUTP were significantly higher in the diabetic retinopathy (DR) group. eGFR, 2h postprandial C- peptide, and Alb were lower in the DR group. Age, duration, Cr, Alb, SBP, and the presence of DN were the influencing factors of DR. (3) Age, duration, HbA1c, BUN, TCSS, SBP, and IMT(R) were significantly higher in the diabetic nephropathy (DN) group. 2h postprandial C-peptide, and Alb were lower in the DN group. HbA1c, BUN, DR, and HBP were the influencing factors of DN. (4) Age, duration, total cholesterol (TC), low-density lipoprotein (LDL-C), triglyceride (TG), Cr, BUN, uric acid (UA), and SBP were significantly higher in the diabetic peripheral neuropathy (DPN) group. The level of genomic DNA methylation and eGFR were significantly lower in the DPN group. Age, duration, LDL-C, UA, the presence of DR, and the genomic DNA methylation level were the influencing factors for DPN. Incorporating the level of genomic DNA methylation into the prediction model could improve the ability to predict DPN on the basis of conventional risk factors.ConclusionLow level of genomic DNA methylation is a relatively specific risk factor for DPN in patients with T2DM and not a contributing factor to the other chronic complications.

Fatty Acid-Binding Protein 4 in Patients with and without Diabetic Retinopathy.

BackgroundFatty acid-binding protein 4 (FABP4) has been demonstrated to be a predictor of early diabetic nephropathy. However, little is known about the relationship between FABP4 and diabetic retinopathy (DR). This study explored the value of FABP4 as a biomarker of DR in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 238 subjects were enrolled, including 20 healthy controls and 218 T2DM patients. Serum FABP4 levels were measured using a sandwich enzyme-linked immunosorbent assay. The grade of DR was determined using fundus fluorescence angiography. Based on the international classification of DR, all T2DM patients were classified into the following three subgroups: non-DR group, non-proliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Multivariate logistic regression analyses were employed to assess the correlation between FABP4 levels and DR severity.ResultsFABP4 correlated positively with DR severity (r=0.225, P=0.001). Receiver operating characteristic curve analysis was used to assess the diagnostic potential of FABP4 in identifying DR, with an area under the curve of 0.624 (37% sensitivity, 83.6% specificity) and an optimum cut-off value of 76.4 μg/L. Multivariate logistic regression model including FABP4 as a categorized binary variable using the cut-off value of 76.4 μg/L showed that the concentration of FABP4 above the cut-off value increased the risk of NPDR (odds ratio [OR], 3.231; 95% confidence interval [CI], 1.574 to 6.632; P=0.001) and PDR (OR, 3.689; 95% CI, 1.306 to 10.424; P=0.014).ConclusionFABP4 may be used as a serum biomarker for the diagnosis of DR.

Dry Eye Syndrome in Patients of Diabetes with and without Diabetic Retinopathy

Background: The present study was done to assess dry eye syndrome in patients with and without diabetic retinopathy. We compared symptoms and signs of dry eye syndrome in patients with and without retinopathy
 Methods: The study was conducted on cases of Type 2 diabetes mellitus with age ?35 years. The study participants were divided into two distinct groups. First group consists of diabetic patients with clinical evidence of diabetic retinopathy and second group with no evidence of diabetic retinopathy. 50 patients were enrolled in each of the above two groups after written informed consent.
 Results: All Signs of dry eye disorder were found more commonly in patients with diabetic retinopathy(42.00%) as compared to those without diabetic retinopathy(18.00%).
 Conclusion: Dry eye syndrome was positively correlated with the presence of diabetic retinopathy in this study. Any diabetic patient complaining of dry eye symptoms should be screened for diabetic retinopathy.
 Keywords: Dry eye, Diabetes, Retinopathy

Plasma and aqueous humor levels of adiponutrin and pannexin 1 in patients with and without diabetic retinopathy.

To evaluate plasma and aqueous levels of adiponutrin and pannexin 1 in patients with and without diabetic retinopathy. The study included three age and gender-matched groups of 20 cataract patients with no diabetes or additional disease (Group C), 20 cataract patients with diabetes and no retinopathy (Group DM+C), and 20 cataract patients with diabetic retinopathy (Group DR+C). All the patients were examined with respect to body mass index (BMI), fasting plasma glucose, hemoglobin A1c (HbA1c), and lipid profile. Phacoemulsification and intraocular lens (Phaco+IOL) implantation were performed to all patients in all the groups, and aqueous samples were taken during the operation. The plasma and aqueous adiponutrin and pannexin 1 levels were analyzed using enzyme-linked immunosorbent assays. A statistically significant difference was determined between the groups with respect to BMI, fasting plasma glucose, and HbA1c levels (P<0.05 for all parameters tested). The plasma adiponutrin levels of Group DR+C were statistically significantly lower than those of Group C and Group DM+C (P<0.001, P=0.004). No statistically significant difference was determined in the aqueous adiponutrin levels in three groups. The plasma pannexin 1 levels of Groups DM+C and DR+C were statistically significantly lower than those of Group C (both P=0.001). The aqueous pannexin 1 levels of Group DR+C were statistically significantly higher than those of Group C and Group DM+C (P=0.001, P<0.001). Adiponutrin and pannexin 1, which play an important role in the pathophysiology of diabetes and obesity, and have a regulatory role in hyperglycemia and insulin resistance. The measurement of adiponutrin and pannexin 1 levels may support clinicians in determining the risk of DR development.

Assessment of circulating fibrotic proteins (periostin and tenascin -C) In Type 2 diabetes mellitus patients with and without retinopathy.

Diabetic retinopathy is a leading cause of vision impairment. Surging diabetic population and poor visual care raises the need for better diagnostic tools. Hence, it is worthwhile to look for biomarkers associated with the disease pathogenesis. Periostin and tenascin-C are matricellular proteins mediating fibrillogenesis in retinopathy. Their serum levels and association with the presence and severity of retinopathy in diabetics is of importance to be explored. The study involved two groups of type 2 diabetes patients, 38 controls without retinopathy and 38 cases with retinopathy. We obtained serum sample and performed biochemical autoanalysis for routine parameters. Special parameters periostin, tenascin-C, and C-peptide were estimated by ELISA. Periostin and tenascin-C were significantly elevated in the retinopathy group. Periostin progressively increased among subgroups. C-peptide decreased significantly in retinopathy group and had a negative correlation with duration of DM, duration of retinopathy, HbA1c and tenascin-C. We observed a positive correlation for periostin and tenascin-C with duration of diabetes. The AUC for C-peptide was the highest (0.750) amongst our parameters. HOMA 2 (%B) index was significantly lower in retinopathy group. Serum Levels of PO and TnC increased in retinopathy. As the disease advances, periostin level increases, indicating continuing fibrosis and fibrovascular membrane formation. Periostin and tenascin-C increase with duration of retinopathy whereas levels of C-peptide decrease. C-peptide has a better differentiating potential for DR from DM. Reduced insulin production as indicated by declined HOMA 2-%BETA in retinopathy favors hyperglycemia and chronic inflammatory state for the disease progression.

The relationship of serum asprosin level with diabetic and non-diabetic retinopathy.

This study was aimed at investigating the role of serum asprosin level in diabetic retinopathy pathogenesis and differential diagnosis diabetic and non-diabetic retinopathy. The cross-sectional study was conducted between May 2021 and August 2021. A total of 21 subjects with diabetic retinopathy, 21 subjects with non-diabetic retinopathy, 21 subjects with type 2 diabetes mellitus (T2DM) without retinopathy and 21 healthy controls were included in the study. Biochemical parameters, serum asprosin, serum IL-6 and TNF-α levels were measured in all participants. Fasting blood glucose (FBG), HbA1c, HOMA-IR and LDL levels were higher in diabetic patients than non-diabetic. The blood asprosin levels were higher in the diabetic retinopathy group compared to the healthy control group (p=0.001), T2DM without diabetic retinopathy (p=0.010), and non-diabetic retinopathy group (p=0.043). There is a significant positive relationship between asprosin level and high FBG, HbA1c and HOMA-IR scores. Serum asprosin level is significantly increased in DRP group than others. A high asprosin level might be a risk factor for the development of diabetic complications, such as diabetic retinopathy. These findings suggest that the measurement of serum asprosin level may support clinicians in determining the risk of DRP development.

Sulforaphane Modulates the Inflammation and Delays Neurodegeneration on a Retinitis Pigmentosa Mice Model.

The term retinitis pigmentosa (RP) describes a large group of hereditary retinopathies. From a cellular view, retinal degeneration is prompted by an initial death of rods, followed later by cone degeneration. This cellular progressive degeneration is translated clinically in tunnel vision, which evolves to complete blindness. The mechanism underlying the photoreceptor degeneration is unknown, but several mechanisms have been pointed out as main co-stars, inflammation being one of the most relevant. Retinal inflammation is characterized by proliferation, migration, and morphological changes in glial cells, in both microglia and Müller cells, as well as the increase in the expression of inflammatory mediators. Retinal inflammation has been reported in several animal models and clinical cases of RP, but the specific role that inflammation plays in the pathology evolution remains uncertain. Sulforaphane (SFN) is an antioxidant natural compound that has shown anti-inflammatory properties, including the modulation of glial cells activation. The present work explores the effects of SFN on retinal degeneration and inflammation, analyzing the modulation of glial cells in the RP rd10 mice model. A daily dose of 20 mg/kg of sulforaphane was administered intraperitoneally to control (C57BL/6J wild type) and rd10 (Pde6brd10) mice, from postnatal day 14 to day 20. On postnatal day 21, euthanasia was performed. Histological retina samples were used to assess cellular degeneration, Müller cells, and microglia activation. SFN administration delayed the loss of photoreceptors. It also ameliorated the characteristic reactive gliosis, assessed by retinal GFAP expression. Moreover, sulforaphane treatment regulated the microglia activation state, inducing changes in the microglia morphology, migration, and expression through the retina. In addition, SFN modulated the expression of the interleukins 1β, 4, Ym1, and arginase inflammatory mediators. Surprisingly, M2 polarization marker expression was increased at P21 and was reduced by SFN treatment. To summarize, SFN administration reduced retinal neurodegeneration and modified the inflammatory profile of RP, which may contribute to the SFN neuroprotective effect.

Correlation of Asymmetric Dimethyl Arginine Level to Sickle Retinopathy in Children With Sickle Cell Disease.

Asymmetric dimethyl arginine (ADMA) is a competitive inhibitor of nitric oxide synthetase especially in L-arginine deficiency, which is the case in sickle cell disease (SCD). we aimed to assess the level of ADMA in children with sickle retinopathy and to correlate it to the degree of retinopathy. In this cross-sectional study 40 children with SCD were included, 20 of them with sickle cell retinopathy (SCR) (group I), 20 with normal fundus examination (group II), and another 20 healthy children served as controls (group III). We measured ADMA level by ELISA and performed fundus examination. Seventeen of the 20 children included in group I had Grade I retinopathy (85%), 2 children had Grade II retinopathy (10%), and 1 child had Grade III retinopathy (5%). ADMA was significantly higher in SCD than controls ( P -value <0.001), and it was even higher in patients with SCR compared those without retinopathy ( P -value <0.002), and there was positive linear correlation between ADMA and the grade of retinopathy. The type of retinopathy detect in the studied patients was the nonproliferative type. In conclusion, ADMA is elevated in children with SCD, and its level is even higher in those who develop SCR.

Do serum vitamin D levels correlate with Macular Edema or with Diabetic Retinopathy?

To compare serum vitamin D (25(OH)D) levels according to the presence of diabetic macular edema (DME) in Diabetes Mellitus (DM) patients with different retinopathy conditions. The files of all DM patients presenting for examination at the ophthalmology clinic between October 2018 and March 2020 were retrospectively examined. Data was collected from the files and included a comprehensive ophthalmological examination, laboratory results from fasting blood tests, and the internal medicine outpatient clinic examination. Patients were divided into two groups according to the presence of DME, they were divided into three groups in terms of retinopathy and DME, and in terms of retinopathy severity and presence of DME, they were divided into five groups. Ninety one (51.1%) of the age-sex matched participants were female and 87 (48.9%) were male. There was a statistically significant difference in vitamin D levels between the group with DME and the group without DME (p ≤ 0.001). In the comparison made according to the presence of retinopathy and DME; a significant difference was found between the DME group and the group with retinopathy but no DME (p ≤ 0.001). When the severity of retinopathy and the presence of DME were evaluated, a significant difference was found between the proliferative diabetic retinopathy (PDR) group with DME and the PDR group without DME in terms of vitamin D levels (p = 0.004). Our study shows that the presence of DME is associated with lower serum 25(OH)D levels.

Serum levels of vasohibin-1 in type 2 diabetes mellitus patients with diabetic retinopathy.

To determine whether Vasohibin-1 which is a potential clinical biomarker is an independent risk factor in patients with diabetic retinopathy. Diabetic retinopathy (DR) is a common chronic microangiopathy in type 2 diabetes mellitus (T2DM). Vasohibin-1 (VASH-1) is an angiogenesis regulator that is closely related to pathological vascularization in DM. This study aimed to determine whether the serum levels of VASH-1 were related to the occurrence of DR in T2DM patients. T2DM patients were divided into three groups: the nondiabetic retinopathy (NDR) group (n = 41), the nonproliferative diabetic retinopathy (NPRD) group (n = 40), and the proliferative diabetic retinopathy (PDR) group (n = 41). A control (CON) group consisting of 40 healthy subjects was also recruited. The serum levels of VASH-1 were measured by enzyme-linked immunosorbent assay kits. The concentration of VASH-1 in the CON groups was less significantly than that of the NDR, NPDR and PDR groups. (P < 0.05). Body mass index, fasting plasma glucose (FPG), hemoglobina1c (HbA1C), blood urea nitrogen (BUN) and diabetic durations were positively correlated with the serum concentration of VASH-1 (all P < 0.05). In univariate logistic regression analyses, the HbA1C, diabetic durations, HDL-c, eGFR and VASH1 were associated with the presence of diabetic retinopathy. Multivariate logistic regression analysis showed that duration of diabetes were significantly associated with diabetic retinopathy. We have shown that VASH-1 is associated with an increased risk of developing diabetic retinopathy. But the serum levels of VASH-1 are not independent risk factors for DR in T2DM.

Compensatory contribution of retinal larger vessels to perfusion density in diabetics without retinopathy

Vessel and perfusion densities may decrease before diabetic retinopathy appears; it is unknown whether these changes affect the contribution of vessel density to perfusion density. This was a non-experimental, comparative, prospective, cross-sectional study in non-diabetic subjects (group 1) and diabetics without retinopathy (group 2). Vessel and perfusion densities in the superficial capillary plexus were compared between groups at the center, inner, and full regions and by field (superior, temporal, inferior, nasal) using optical coherence tomography angiography. Coefficients of determination (R2) between vessel and perfusion densities were calculated to find the contribution of larger retinal vessels to perfusion density. Percent differences were used to evaluate the contribution of these vessels to perfusion density in a regression model. There were 62 participants, 31 eyes by group; vessel and perfusion densities as well as the coefficients of determination between them were lower in group 2, especially in the nasal field (R2 0.85 vs. 0.71), which showed a higher contribution of larger retinal vessels to perfusion density. The regression model adjusted to a quadratic equation. In diabetics without retinopathy the contribution of vessel density to perfusion density may decrease; a low vessel density may increase the contribution of larger retinal vessels to perfusion density.

The quantitative measurements of choroidal thickness and volume in diabetic retinopathy using optical coherence tomography and optical coherence tomography angiography; correlation with vision and foveal avascular zone

BackgroundTo represent choroidal thickness (CT) and choroidal volume (CV) databases in diabetic retinopathy (DR) patients and healthy control participants using optical coherence tomography (OCT) and enhanced depth imaging OCT (EDI-OCT). No study had evaluated CT at all main stages of diabetic retinopathy in a single study.MethodsThe study included 176 eyes from 93 patients (39–80 years old; 42% females) who were divided into three groups based on DR severity and normal control group: 39 eyes no DR, 64 eyes NPDR, 33 eyes PDR, and 40 eyes normal control. The CT and CV were measured and statistically analyzed. Intra-observer and inter-observer coefficients of repeatability were calculated.ResultsSubfoveal CT showed persistent thinning from normal group (322.50 ± 69.24) to no-diabetic retinopathy (NDR, 308.33 ± 74.45) to nonproliferative diabetic retinopathy (NPDR, 283.45 ± 56.50) group and then thickening as the patient progressed to proliferative diabetic retinopathy (PDR, 295.17 ± 95.69) (P = 0.087). A significant difference was found between the control group and the NDR, NPDR, and PDR groups in nearly all CT and CV of Early Treatment Diabetic Retinopathy Study macular subfields. Fasting blood sugar (FBS = 189.08 ± 51.3 mg/dl) and diabetes mellitus (DM) duration (13.6 ± 6.5 years) had no noticeable effect on CT. In patients with diabetes, the best-corrected visual acuity (BCVA), diabetic macular edema (DME), and foveal avascular zone (FAZ) were not affected by CT and CV.ConclusionsThe choroidal thickness decreases from the early stages of diabetic retinopathy up to the NPDR stage, with a subsequent modest rise in CT during the PDR stage. There was no correlation between FBS, diabetes duration, BCVA, DME, and FAZ, and CT.

Comparing the effects of serum GPER-1 and oxidant/antioxidant levels on retinopathy in patients with diabetes and healthy individuals: a pilot study.

This study aimed to determine the effect of serum G receptor-mediated protein-1 levels on the development of retinopathy in patients with diabetes in comparison with healthy individuals. The study enrolled patients with diabetic retinopathy (Group 1), patients without diabetic retinopathy (Group 2), and healthy individuals (Group 3). Levels of serum progesterone, serum G receptor-mediated protein-1, estradiol, oxidant/antioxidants, and thyroid-releasing hormones were analyzed and compared among the groups. Post-hoc analysis was performed to compare the subgroups in which significant differences were found. Groups 1, 2, and 3 each included 40 patients. A significant difference was found among all groups in terms of serum G receptor-mediated protein-1, oxidant/antioxidant, and estradiol levels (p<0.01), but no significant difference was found in terms of thyroid-releasing hormone or progesterone (p=0.496, p=0.220, respectively). In the post-hoc analysis of the groups with significant differences, another significant difference was found among all groups for serum G receptor-mediated protein-1 and oxidant/antioxidant levels (p<0.05). Serum G receptor-mediated protein-1 and oxidant levels were positively correlated, whereas serum G receptor-mediated protein-1 and antioxidant levels were negatively correlated (r=0.622/p<0.01, r=0.453/p<0.01, r=0.460/p<0.01, respectively). The multiple regression analysis showed that increased levels of serum G receptor-mediated protein-1 may help prevent diabetic retinopathy. Serum G receptor-mediated protein-1 levels, which were the highest in the diabetic retinopathy Group, increased as the oxidant/antioxidant balance changed in favor of oxidative stress. This appears to be a defense mechanism for preventing neuronal damage.

Predictive value of inflammatory and hematological data in diabetic and non-diabetic retinopathy.

The current study aimed at investigating the predictive role of inflammatory, hematological and biochemical parameters in diabetic and non-diabetic retinopathy. The cross-sectional study was conducted between June 2019 and September 2020. We included patients with diabetic retinopathy (proliferative DR=14, non-proliferative DR=16), patients with non-diabetic retinopathy (n=30), patients with Type 2 Diabetes Mellitus (T2DM) without retinopathy (n=30) and control group (n=30). Demographic, hematological, and biochemical parameters of the participants were examined. Participants' age and duration of diabetes mellitus were higher in proliferative and non-proliferative DR groups than patients with T2DM without retinopathy (p<0.001). There were significantly difference in terms of BMI (p<0.001), HbA1c (p<0.001), glucose (p<0.001), LDL (p<0.001), AST (p=0.001), hemoglobin (p<0.001), urea (p<0.001), creatinine (p<0.001), lymphocyte (p=0.001), and neutrophil (p=0.002) levels between groups. IL-6 levels were higher in proliferative DR, non-proliferative DR, and non-diabetic retinopathy groups than the control group. TNF-α levels were higher in proliferative DR and non-diabetic retinopathy groups than the control group. The NLR and PLR median values were significantly higher in the proliferative DR group than in other groups (p<0.001). The current study showed that IL-6 and TNF-α levels are elevated in diabetic and non-diabetic retinopathy. In addition, neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) median levels are higher in proliferative diabetic retinopathy than other groups. These findings support the inflammatory process may be accelerating the development of retinopathy.

Study of Biochemical Parameters in Diabetic Patients with and without Diabetic Retinopathy – A Hospital based study

Background: Diabetic Retinopathy (DR) is a common, potentially blinding and visually disabling complication of diabetes. Early detection of retinopathy and its progression to severity with routine referral for screening by Ophthalmologist can save vision by timely management. Methods: This was a hospital based cross-sectional study done to study the association of glycated hemoglobin (HbA1c), fasting and postprandial blood sugar, serum lipid profile, serum creatinine and urine albumin in diabetic patient with and without DR. A total of 50 patients with Diabetic retinopathy and 50 patients without diabetic retinopathy were enrolled in this study. All patients included were Type 2 DM aged 35 years and above. Results: The mean HbA1c was 8.62±1.5 and 5.54±1.2, total cholesterol was 228.9±63 and 184.9±39.8 mg/dl, serum triglyceride was 226.6±80.7 and 160.8±45.1 mg/dl, LDL-C was 152.3±49 and 127.2±37 mg/dl and serum creatinine was 1.15±0.45 and 0.66±0.27 mg/dl in diabetic retinopathy group and no diabetic retinopathy group respectively. There was significant association of elevated HbA1c, serum triglyceride, LDL- C and total cholesterol with diabetic retinopathy in patients with type 2 DM. The mean values of serum lipoproteins were higher in the diabetic retinopathy group. Conclusion: Elevated fasting and postprandial blood sugar, glycated hemoglobin, total cholesterol, serum triglyceride, LDL-C, serum creatinine and urine albumin were significantly associated with DR in our study. So, all patients with diabetes mellitus should be screened routinely for serum lipoproteins along with blood sugar profile, as it would help in early detection of diabetic retinopathy.

Aqueous angiopoietin-like levels correlate with optical coherence tomography angiography metrics in diabetic macular edema.

To quantitatively detect aqueous levels of angiopoietin-like (ANGPTL)3, ANGPTL4, and ANGPTL6 and investigate their correlation with optical coherence tomography angiography (OCTA) findings in patients with diabetic macular edema (DME). This cross-sectional study included 23 patients (27 eyes) with type 2 diabetes and 16 control subjects (20 eyes). All patients underwent OCTA imaging and ultra-wide field fundus photography. Diabetic patients were categorized into two groups according to the presence or absence of diabetic retinopathy (DME group, 14 patients, 16 eyes); and non-diabetic retinopathy (NDR) group, 9 patients, 11 eyes, respectively. Aqueous levels of ANGPTL3, ANGPTL4, and ANGPTL6 were assessed using suspension array technology, and foveal-centered 3×3 mm2 OCTA scans were automatically graded to determine the central, inner, and full vessel density (CVD, IVD, FVD); central, inner, and full perfusion density (CPD, IPD, FPD), foveal avascular zone (FAZ) area, FAZ perimeter, and FAZ circularity index (FAZ-CI) on superficial capillary plexuses. Additionally, central subfield thickness (CST), cube volume (CV), and cube average thickness (CAT) were measured in a model of macular cube 512×128. Aqueous ANGPTL3 levels were not significantly different among the three groups (P>0.05). ANGPTL4 levels were significantly higher in the DME group than the control and NDR groups (P<0.0001 and P<0.001), while ANGPTL6 levels were significantly higher in the DME group than the control group (P<0.05). In the whole cohort, the aqueous ANGPTL3 levels correlated negatively with the IVD, FVD, IPD, and FPD, and positively with the CV and CAT. The aqueous ANGPTL4 levels correlated negatively with the CVD, IVD, FVD, CPD, IPD, and FPD, and positively with the FAZ perimeter, CST, CV, and CAT. The aqueous ANGPTL6 levels correlated negatively with the IVD, FVD, IPD, FPD, FAZ-CI and positively with CST, CV, CAT. ANGPTL4 and ANGPTL6 may be associated with vascular leakage in DME and may represent good targets for DME therapy. In addition, OCTA metrics may be useful for evaluating macular ischemia in DME.

Effects of Intravitreal Aflibercept on the Systemic Insulin-like Growth Factor-I and Vascular Endothelial Growth Factor-A in Patients with Diabetic Retinopathy and Age-Related Macular Degeneration.

Purpose To analyze the effect of intravitreal aflibercept injections on systemic levels of insulin-like growth factor-1 and vascular endothelial growth factor-A in patients with diabetic retinopathy and age-related macular degeneration. Methods Vascular endothelial growth factor-A and insulin-like growth factor-1 levels were determined before and one week and four weeks after intravitreal injection of aflibercept (2.0 mg/50 μl) for 19 patients with age-related macular degeneration (mean age, 76 ± 11 years) and 18 patients with diabetic retinopathy (mean age, 64 ± 14 years). Twenty-two healthy individuals were enrolled as controls. Results A significant decline in systemic vascular endothelial growth factor-A level, from 43 (30–57) pg/ml at baseline to 8 (8–8) pg/ml (p < 0.001) at week one and 17 (8–25) pg/ml (p=0.0054) at week four, was observed in the age-related macular degeneration group. In the diabetic retinopathy group, vascular endothelial growth factor-A levels declined from 53 (35–117) pg/ml to 2 (1–5) pg/ml (p < 0.0001) one week after injection and 16 (13–22) pg/ml four weeks after injection (p=0.0327). At baseline, systemic insulin-like growth factor-1 concentration was higher in the diabetic retinopathy group (57 [37–99] pg/ml) than in the age-related macular degeneration group (35 [24–51] pg/ml) (p=0.0056). A subgroup analysis showed that patients in the proliferative diabetic retinopathy subgroup had significantly higher systemic insulin-like growth factor-1 concentrations (71 [44.7–243] pg/ml) than those in the nonproliferative diabetic retinopathy subgroup (43 [29–66] pg/ml) (p=0.0048). Conclusions The difference between the baseline systemic insulin-like growth factor-1 levels of the age-related macular degeneration and diabetic retinopathy groups and the higher insulin-like growth factor-1 levels in the proliferative diabetic retinopathy subgroup one week after aflibercept therapy suggest that insulin-like growth factor-1 may play a role in the pathomechanism of diabetic retinopathy.

Pentosan Polysulfate Sodium-Associated Pigmentary Retinopathy: Risk Factors and Fundus Findings.

PurposeTo evaluate the risk factors and fundus findings of patients with potential PPS-associated retinopathy.Patients and MethodsA retrospective chart review was performed of patients exposed to PPS who had a dilated fundus examination at a large retina-only practice from 2018–21. Multimodal images were evaluated by masked reviewers.ResultsA total of 148 patients were included, of whom 33 (22%) had PPS-associated retinopathy, and 115 (78%) did not. The mean age was 60.3 years old, and the mean follow-up was 11.8 months. The PPS-associated retinopathy group had higher mean cumulative doses of PPS (1600g±849 vs 864g±852, P < 0.0001, Mann–Whitney test) and longer duration of PPS use (13.6 years vs 7.48, P < 0.0001). There was no statistically significant difference based on a history of kidney or liver disease or the dosage per day for the weight, body mass index, body surface area, or lean body weight. Of the patients with PPS-associated retinopathy whose genetic results were available, 15 of 16 (93%) were heterozygous for variants of uncertain significance.ConclusionA longer duration of PPS use and higher cumulative dosage of PPS were associated with an increased risk of developing PPS-associated pigmentary retinopathy. The role of genetic mutations in patients exposed to PPS is still to be determined.

The Role of Biochemical Parameters in Prediction of Retinal Diseases and their Relationship to Cataract, Diabetes, and Hypertension, in Ibn Al Haytham Hospital, Baghdad, Iraq

This work summarize multiple protective roles serum Zeaxanthin, and Malondialdehyde, in association with metabolic profiles and as a risk of retinal disorder disease with cataract, diabetes, and hypertension, totally thirty healthy control group, and seventy-five patients group for both genders were studied. Retinal disorder disease subdivided after clinical diagnosis, into three major -subgroups, the first cohort was twenty-five patients suffers of cataract, the second twenty-five of diabetic patients, while the third group is twenty-five hypertensive patients. Lipid-profile, Fasting-insulin-levels, serum zeaxanthin and malondialdehyde, have been done to all groups. Important findings presented in the roles of serum zeaxanthin, and malondialdehyde, by similarities and differences, in retinal diseases with cataract, diabetes, and hypertension. The activity levels of serum zeaxanthin in hypertensive retinopathy patients (32.80±30.56 ng/mL), was non-significantly (P&gt;0.01) reduced compared to healthy control (88.85±139.31 ng/mL), in compression with the same patients for serum malondialdehyde MDA which expressed the highest level of MDA (2.456±2.149 μg/mL) among the rest groups, which was significantly higher (P&lt;0.05) than that in control (0.783±0.937 μg/mL), but the differences were non-significant (P&gt;0.05) compared to diabetic retinopathy group (1.839±1.515 μg/mL).The activity levels are negatively associated with malondialdehyde levels in retinal disease patients with cataract, diabetes, and hypertension. Retinal disease patients with cataract, diabetes, and hypertension pathogenesis aren’t legitimately ensured. But multiple protective roles may be adopted in clinical diagnosis of retina, also in response to higher levels of oxidative stress, including serum malondialdehyde, and zeaxanthin, by fasting at least eight hours pre sophisticated lens surgery.

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.