Development Of Diabetic Macular Edema Research Articles

Local ocular factors associated with the development of diabetic macular edema: an inter-eye study

To investigate local ocular factors associated with the development of diabetic macular edema (DME), we classified each eye of patients with unilateral DME as the DME eyes or the fellow eyes (without DME). We compared the clinical characteristics, optical coherence tomography (OCT), and OCT angiography (OCTA), ultra-wide field fundus photography, and angiography features of each eye. As a result, fifty-five patients with unilateral DME were enrolled. Although the diabetic retinopathy stage was not different between each group of eyes, DME eyes showed a higher prevalence of venous beading and a larger area of nonperfusion region than did fellow eyes (all P < 0.05). OCTA features of DME eyes also showed a larger foveal avascular zone in the deep capillary plexus and a lower vascular density in both the superficial and deep capillary plexuses (all P < 0.05). This study highlighted ocular features reflecting retinal ischemia, such as venous beading, area of nonperfusion region, and vascular density in the central retinal area, are associated with the development of DME. OCTA and ultra-wide field fluorescein angiography may be useful for evaluating the parameters of retinal ischemia and the risk of DME development.

Blood selectin levels as a predictive factor for diabetic retinopathy and diabetic macular edema in type 2 diabetes

Background: Diabetes mellitus (DM) is still a noninfectious global pandemic. Diabetic retinopathy (DR) is one of the most common and socially significant complications of both type 1 and type 2 diabetes. Predicting the probability of DR progression and potential diabetic macular edema (DME) development is still important. Currently available predictive models include a wide number of predictors, and such predictors as blood selectin levels seem to be promising. Purpose: To determine relationships between blood levels of selectins and DR progression and DME development in patients with T2DM, and to develop particular predictive models. Material and Methods: Of the 124 patients (124 eyes) involved into this study, 95 (95 eyes) had T2DM and retinopathy (group 1 of 29 eyes with mild non-proliferative DR (NPDR); group 2 of 35 eyes with moderate or severe non-proliferative NPDR; and group 3 of 31 eyes with proliferative DR (PDR)), and 29 (29 eyes) had no diabetes (controls). Patients underwent a routine eye examination and spectral domain optical coherence tomography (SD-OCT) to determine central retinal thickness (CRT). The presence of DME was based on an increased macular thickness in the Early Treatment Diabetic Retinopathy Study (ETDRS) subfields compared to the upper limit of normal for patient's age and gender. Enzyme-linked immunosorbent assay (ELISA) kits from Invitrogen Thermo Fisher Scientific (USA) were used to determine selectin levels in blood. Statistical analyses were conducted using MedStat and MedCalc v.15.1 (MedCalc Software bvba) software. Results: There was a statistically significant tendency for an increase in progression of DR to be accompanied by an increase in blood selectin levels. In the presence of DME, blood LS levels were statistically significantly increased in mild NPDR; blood PS levels, in PDR; and blood ES levels, in all stages of DR. A regression model for predicting the progression of DR was built. In the model developed, diabetes duration and blood selectin levels were positively correlated, while HbA1c level was inversely correlated with DR progression. The model was found to be adequate R2adjust = 0.84; F = 97.9, p less 0.001, demonstrating high correlation of the selected independent variables with the stage of DR. The calculated Y index may be considered a quantitative reflection of the severity of DR. A patient is predicted to have mild NPDR (with a prediction accuracy of 86.2%) if Y less 1.5, moderate of severe NPDR (with a prediction accuracy of 88.6%) if 1.5 less equal Y less 2.35, and PDR (with a prediction accuracy of 100%) if Y more equal 2.35. A regression model for predicting the development of DME was built, with CRT and blood ES level found to increase the risk of the development of DME. A high AUC value for the ROC curve (AUC = 0.97; 95% CI, 0.92-0.99) indicated a very strong correlation of the risk of DME development with the levels of selected independent variables. In addition, sensitivity and specificity values at the optimal cut-off point were 93.2% (95% CI, 83.5%-98.1%) and 92.3% (95% CI, 83.0%-97.5%), respectively. Conclusion: Our findings confirmed the current view that high blood selectin levels are important in the presence of T2DM and related to major pathogenetic mechanisms of microvascular complications, and blood selectin levels can be considered predictors of the progression of DR as well as the development of DME.

Accuracy of Artificial Intelligence in Estimating Best-Corrected Visual Acuity From Fundus Photographs in Eyes With Diabetic Macular Edema

Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely. To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information. Deidentified color fundus images taken after dilation were used post hoc to train AI systems to perform regression from image to BCVA and to evaluate resultant estimation errors. Participants were patients enrolled in the VISTA randomized clinical trial through 148 weeks wherein the study eye was treated with aflibercept or laser. The data from study participants included macular images, clinical information, and BCVA scores by trained examiners following protocol refraction and VA measurement on Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Primary outcome was regression evaluated by mean absolute error (MAE); the secondary outcome included percentage of predictions within 10 letters, computed over the entire cohort as well as over subsets categorized by baseline BCVA, determined from baseline through the 148-week visit. Analysis included 7185 macular color fundus images of the study and fellow eyes from 459 participants. Overall, the mean (SD) age was 62.2 (9.8) years, and 250 (54.5%) were male. The baseline BCVA score for the study eyes ranged from 73 to 24 letters (approximate Snellen equivalent 20/40 to 20/320). Using ResNet50 architecture, the MAE for the testing set (n = 641 images) was 9.66 (95% CI, 9.05-10.28); 33% of the values (95% CI, 30%-37%) were within 0 to 5 letters and 28% (95% CI, 25%-32%) within 6 to 10 letters. For BCVA of 100 letters or less but more than 80 letters (20/10 to 20/25, n = 161) and 80 letters or less but more than 55 letters (20/32 to 20/80, n = 309), the MAE was 8.84 letters (95% CI, 7.88-9.81) and 7.91 letters (95% CI, 7.28-8.53), respectively. This investigation suggests AI can estimate BCVA directly from fundus photographs in patients with DME, without refraction or subjective visual acuity measurements, often within 1 to 2 lines on an ETDRS chart, supporting this AI concept if additional improvements in estimates can be achieved.

Влияние пилинга внутренней пограничной мембраны на сосудистую плотность капиллярных сплетений сетчатки

Relevance. Diabetic macular edema (DME) in combination with epimacular fibrosis (EMF) is an indication for vitreoretinal surgical treatment. The necessity of the retinal internal limiting membrane (ILM) peeling is debatable. The question of assessing the anatomy and function of the eyes in the early and late postoperative period is relevant, in particular, the study of the retinal capillary plexuses (RCP) characteristics such that its vascular density. The perpose of the study was to evaluate the presence and nature of the various ILM peeling methods effect on the RCP vascular density in patients with proliferative diabetic retinopathy and DME in combination with EMF in the early and late periods after treatment. Material and methods. A randomized case-control study was conducted on three comparable groups of patients. Surgical treatment was performed – vitrectomy with ILM peeling. The groups differed in the ILM peeling methods. In the early (1 month) and late (1 year) postoperative period, the RCP vascular density CAS was assessed, as well as the development of complications: DME, EMF recurrence, and retinal atrophy. Results. Statistically significant intra- and intergroup differences in the values of indicators of RCP vascular density during the entire period of observation were not revealed. It has been established that the initially higher vascular density in the superficial and deep RCP tends to remain at this level in the early and late postoperative period. Statistically significant relationships between RCP vascular density and the development of postoperative DME, recurrence of EMF or retinal atrophy have not been established. Conclusion. According to the results of our study, ILM peeling does not have a significant effect on the RCP vascular in the early and late postoperative period. The pathogenesis of postoperative complications and their relationship with the state of the RCP require further study. Keywords: vitreoretinal surgery, vitreomacular interface, retinal internal limiting membrane, dosed fovea-sparing ILM peeling, optical coherence tomography, optical coherence tomographyangiography, vascular density, automatic image analysis

Assessment of Parafoveal Diabetic Macular Ischemia on Optical Coherence Tomography Angiography Images to Predict Diabetic Retinal Disease Progression and Visual Acuity Deterioration

The presence of diabetic macular ischemia (DMI) on optical coherence tomography angiography (OCTA) images predicts diabetic retinal disease progression and visual acuity (VA) deterioration, suggesting an OCTA-based DMI evaluation can further enhance diabetic retinopathy (DR) management. To investigate whether an automated binary DMI algorithm using OCTA images provides prognostic value on DR progression, diabetic macular edema (DME) development, and VA deterioration in a cohort of patients with diabetes. In this cohort study, DMI assessment of superficial capillary plexus and deep capillary plexus OCTA images was performed by a previously developed deep learning algorithm. The presence of DMI was defined as images exhibiting disruption of fovea avascular zone with or without additional areas of capillary loss, while absence of DMI was defined as images presented with intact fovea avascular zone outline and normal distribution of vasculature. Patients with diabetes were recruited starting in July 2015 and were followed up for at least 4 years. Cox proportional hazards models were used to evaluate the association of the presence of DMI with DR progression, DME development, and VA deterioration. Analysis took place between June and December 2022. DR progression, DME development, and VA deterioration. A total of 321 eyes from 178 patients were included for analysis (85 [47.75%] female; mean [SD] age, 63.39 [11.04] years). Over a median (IQR) follow-up of 50.41 (48.16-56.48) months, 105 eyes (32.71%) had DR progression, 33 eyes (10.28%) developed DME, and 68 eyes (21.18%) had VA deterioration. Presence of superficial capillary plexus-DMI (hazard ratio [HR], 2.69; 95% CI, 1.64-4.43; P < .001) and deep capillary plexus-DMI (HR, 3.21; 95% CI, 1.94-5.30; P < .001) at baseline were significantly associated with DR progression, whereas presence of deep capillary plexus-DMI was also associated with DME development (HR, 4.60; 95% CI, 1.15-8.20; P = .003) and VA deterioration (HR, 2.12; 95% CI, 1.01-5.22; P = .04) after adjusting for age, duration of diabetes, fasting glucose, glycated hemoglobin, mean arterial blood pressure, DR severity, ganglion cell-inner plexiform layer thickness, axial length, and smoking at baseline. In this study, the presence of DMI on OCTA images demonstrates prognostic value for DR progression, DME development, and VA deterioration.

Relationship between Diabetic Nephropathy and Development of Diabetic Macular Edema in Addition to Diabetic Retinopathy.

This study aimed to examine the relationship between diabetic retinopathy (DR) and systemic factors. We evaluated 261 patients (143 men, 118 women, aged 70.1 ± 10.1 years) with type 2 diabetes. All participants underwent a fundus examination, fundus photography using spectral domain optical coherence tomography (SD-OCT), and blood tests. For glycated hemoglobin (HbA1c) levels, the average and highest values in the past were used. We observed DR in 127 (70 men and 57 women) of 261 patients. Logistic regression analyses revealed a significant correlation between DR development and the duration of diabetes (OR = 2.40; 95% CI: 1.50), average HbA1c level (OR = 5.57; 95% CI: 1.27, 24.4), highest HbA1c level (OR = 2.46; 95% CI: 1.12, 5.38), and grade of diabetic nephropathy (DN) (OR = 6.23; 95% CI: 2.70, 14.4). Regression analyses revealed a significant correlation between the severity of DR and duration of diabetes (t = -6.66; 95% CI: 0.21, 0.39), average HbA1c level (t = 2.59; 95% CI: 0.14, 1.02), and severity of DN (t = 6.10; 95% CI: 0.49, 0.97). Logistic regression analyses revealed a significant correlation between diabetic macular edema (DME) development and DN grade (OR = 2.22; 95% CI: 1.33, 3.69). DN grade correlates with the development of DR and DME, and decreased renal function predicts the onset of DR.

Combined Treatment of Persistent Diabetic Macular Edema with Aflibercept and Triamcinolone Acetonide in Pseudophakic Eyes.

Background and Objectives: The main cause of the vision loss in diabetics is the development of diabetic macular edema, regardless of the stage of diabetic retinopathy. The paper aimed to examine whether the additional intravitreal application of triamcinolone acetonide to continuous anti-vascular endothelial growth factor therapy could improve therapeutic outcomes for pseudophakic eyes with persistent diabetic macular edema. Materials and Methods: twenty-four pseudophakic eyes with refractory diabetic macular edema, that had appeared despite three previously administered intravitreal injections of aflibercept, were divided into two groups (twelve eyes in each group). The first group continued to have aflibercept administered according to a fixed dosing regimen (once in two months). Triamcinolone acetonide 10 mg/0.1 mL (administered once per four months) was included for the second group, i.e., their treatment continued with a combination of aflibercept + triamcinolone acetonide. Results: The reduction in central macular thickness was higher in the eyes treated with combined therapy (aflibercept + triamcinolone acetonide) compared with the use of aflibercept alone during the entire 12-month follow-up period (3rd month p = 0.019; 6th month p = 0.023; 9th month p = 0.027; 12th month p = 0.031). As was evident from the p-values, the differences were statistically significant. No statistically significant difference was recorded for visual acuity: 3rd month p = 0.423; 6th month p = 0.392; 9th month p = 0.413; 12th month p = 0.418. Conclusions: Combined anti-vascular endothelial growth factor and steroid therapy leads to a better anatomical outcome of persistent diabetic macular edema in pseudophakic eyes, but does not lead to a more significant improvement in visual acuity than continuous anti-VEGF therapy alone.

The relationship between renal function and diabetic retinopathy in patients with type 2 diabetes: A three-year prospective study

ObjectiveTo explore the association of diabetic retinopathy (DR) and diabetic macular edema (DME) with renal function in patients with type 2 diabetes mellitus (T2DM). DesignA prospective cohort study. MethodsThis single-centre study included patients with no DR, mild non-proliferative DR (NPDR), and no DME at baseline. DR and DME were assessed using 7-field fundus photography and swept-source OCT (SS-OCT). The baseline renal function assessed included the estimated glomerular filtration rate (eGFR) and microalbuminuria (MAU). Cox regression analyses were used to assess the hazard ratio (HR) of renal function with the progression of DR and the development of DME. ResultsA total of 1409 patients with T2DM (1409 eyes) were included. During 3 years of follow-up,143 patients had DR progression, and 54 patients developed DME. Low eGFR levels at baseline were associated with the development of DR (HR, 1.044 per 1-SD decrease; 95% CI, 1.035–1.053; P < 0.001). Compared to the participants with eGFRs >90 mL/min/1.73 m2, the participants with eGFRs of 60–90 mL/min/1.73 m2 (HR, 1.649; 95% CI, 1.094–2.485; P = 0.017) or < 60 mL/min/1.73 m2 (HR, 2.106; 95% CI, 1.039–4.269; P = 0.039) had a higher risk of DR progression. Increasing MAU tertiles were associated with progression of DR (Tertile 2: HR, 2.577; 95% CI, 1.561–4.256; P < 0.001; Tertile 3: HR, 3.135; 95% CI, 1.892–5.194; P < 0.001). No significant relationship was found between renal function and the development of DME (P > 0.05). ConclusionsAbnormal renal profiles (i.e., low levels of eGFR and high levels of MAU) were associated with the progression of DR, but not with the development of DME.

Evaluation of microaneurysms as predictors of therapeutic response to anti-VEGF therapy in patients with DME.

Administration of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the first-line therapy for diabetic macular oedema (DME). However, some patients show no or insufficient response to repeated anti-VEGF injections. Therefore, it is necessary to identify factors that can predict this resistance against anti-VEGF treatment. Presence of microaneurysms (MAs) is a predictor of the development and progression of DME, but its relationship with the treatment response to the anti-VEGF agents is not well known. Therefore, we aimed to elucidate the relationship between the distribution of MAs and the response to anti-VEGF therapy in patients with DME. The number of MAs was measured before anti-VEGF therapy in each region using fluorescein angiography, indocyanine green angiography (IA), and optical coherence tomography angiography. Patients with DME were divided into the responder and non-responder groups after three loading phases. Differences in the distribution of MAs between the groups were investigated. Pre-treatment IA revealed more MAs in the nasal area in the non-responder group than in the responder group (10.7 ± 10.7 and 5.7 ± 5.7, respectively, in the nasal macula) (1.4 ± 2.1 and 0.4 ± 0.7, respectively, in the nasal fovea). Whereas, pre-treatment FA and OCTA could not reveal significantly difference between the groups. Detection of MAs in the nasal macula using pre-treatment IA may indicate resistance to anti-VEGF therapy. We recommend the clinicians confirm the presence of MAs in the nasal macula, as shown by IA, as a predictor of therapeutic response to anti-VEGF therapy in patients with treatment naive DME.

Choriocapillaris Flow Deficit as a Biomarker for Diabetic Retinopathy and Diabetic Macular Edema: 3-Year Longitudinal Cohort

To investigate the relationship between choriocapillaris flow deficit percentage (CC FD%) by swept-source optical coherence tomography angiography (SS-OCTA) and 3-year risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development. Prospective, observational cohort study. A total of 903 participants with type 2 diabetes mellitus (T2DM) without DR or with mild nonproliferative DR (NPDR) free of DME at baseline were followed up annually for 3 years. All participants underwent standard 7-field fundus photography and spectral-domain OCT. SS-OCTA was used for retinal and choriocapillaris imaging and 3×3-mm2 macular CC FD% was quantified. Univariate and multivariate logistic models were used to evaluate the association between CC FD% and 2 or more steps of DR progression and DME development. The additional predictive value of CC FD% for outcome events was assessed using C statistic, net reclassification index (NRI), and integrated discrimination improvement index (IDI). Over 3 years, 295 of 1805 eyes (16.34%) developed DR progression, and 118 eyes (6.54%) developed DME. A higher average CC FD% was correlated with DR progression (odds ratio [OR], 3.41 per SD increase, 95% CI: 2.65-4.39, P < .001) and DME development (OR, 1.37 per SD increase, 95% CI: 1.06-1.77, P=.016) after adjusting for confounders. In the ETDRS regions, increased CC FD% in all fields was associated with DR progression; however, increased CC FD% in the inferior field was associated with DME development. Compared with the models based on established risk factors, the addition of average CC FD% significantly improved the C statistics for DR progression (0.712 to 0.777, P < .001) and DME occurrence (0.743 to 0.773, P=.044). The estimated NRIs and IDIs (all >0) indicated that the addition of CC FD% led to a significant improvement in the discriminative performance for end points. CC FD% is independently associated with DR progression and DME development in the Chinese T2DM population and provides incremental predictive value beyond traditional risk factors and retinal microvascular parameters. Further inclusion of CC FD% in DR prediction models helps guide population-based screening and personalized management.

INCIDENCE OF NEW DIABETIC MACULAR EDEMA IN FELLOW EYES OF PATIENTS IN THE VISTA AND VIVID STUDIES.

To characterize diabetic macular edema (DME) incidence in fellow eyes of patients treated for DME in the study eye. This post hoc analysis of VISTA/VIVID data evaluated fellow eyes without DME at baseline through Week 100. Diabetic macular edema presence in the fellow eye was inferred by investigator-reported DME adverse events and use of DME treatments. Over 100 weeks, 44.9%, 44.2%, and 42.9% of fellow eyes developed DME in the intravitreal aflibercept injection 2 mg every 4 weeks (n = 245), intravitreal aflibercept injection 2 mg every 8 weeks (n = 258), and laser control (n = 252) groups, respectively. Mean time to DME development in combined treatment groups was ∼6 months. Multivariable regression analysis confirmed patients with shorter diabetes duration (hazard ratio per 10-year decrease, 1.16; 95% confidence interval, 1.03-1.30; P = 0.0160) and thicker baseline study eye central subfield thickness (hazard ratio per 10- µ m increase, 1.01; 95% confidence interval, 1.01-1.02; P = 0.0002) were at higher risk of developing DME in the fellow eye. Among patients with DME in one eye at baseline, almost half developed DME in the fellow eye over 2 years. Shorter duration of diabetes and thicker study eye central subfield thickness were predictors of DME development in the fellow eye.

Reduced serum magnesium is associated with the occurrence of diabetic macular edema in patients with diabetic retinopathy: A retrospective study.

Serum magnesium levels have been reported to reflect the risk of diabetic retinopathy (DR); however, the effect of serum magnesium level on diabetic macular edema (DME) remains unclear. Here, we investigated the association between the serum magnesium levels and DME in patients with DR. Patients with DR were recruited between January 2018 and June 2021. A total of 519 such patients were included in this study. All patients underwent a standardized clinical ophthalmic examination by an experienced ophthalmologist, and an assay was conducted to determine the serum magnesium concentration. Compared with the non-DME group, the DME group had a higher proportion of insulin use and a higher level of serum ischemia-modified albumin and fasting plasma glucose. The serum magnesium and calcium levels were lower in the DME group than in the non-DME group (P < 0.05). Higher magnesium levels were negatively associated with DME after adjustment for relevant covariates. Compared with the participants in the lowest magnesium quartile, those in the fourth quartile showed a significantly lower risk of DME after adjustment [odds ratio (OR), 0.294; 95% confidence interval, 0.153–0.566; P < 0.0001]. Considering the potentially different effects of serum magnesium on the development of DME in patients with DR based on age, DR staging and insulin use, stratified analysis was performed by considering these factors. Among insulin-using patients with non-proliferative DR who were < 66 years of age, those in the third and fourth quartile of serum magnesium were less likely to develop DME than those in the lowest quartile of serum magnesium [OR (95% CI), 0.095 (0.014–0.620), 0.057 (0.011–0.305); P = 0.014, 0.001]. Overall, a higher serum magnesium level was associated with a lower risk of DME in patients with DR. Furthermore, patients with DR who used insulin were more likely to develop DME. Long-term studies on oral magnesium supplements are needed to determine whether maintaining the serum magnesium levels in a higher physiological range can reduce the risk of DME in patients with DR.

Parapapillary Choroidal Microvasculature Predicts Diabetic Retinopathy Progression and Diabetic Macular Edema Development: A Three-Year Prospective Study

To determine the predictive value of the microcirculation of the optic nerve head by swept-source optical coherence tomography angiography for identifying individuals with high risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development. Prospective observational cohort study. A total of 946 patients (1879 eyes) with type 2 diabetes mellitus were recruited who had no DR or mild nonproliferative DR at baseline, and no DME. All subjects underwent 3×3 mm swept-source optical coherence tomography angiography centered on the optic nerve head to generate angiograms in 4 layers: radial peripapillary plexus, superficial retinal capillary plexus (SCP), deep retinal capillary plexus, and choriocapillaris (CC). The CC flow deficit percentage (CC FD%), vessel density (VD), and perfusion density (PD) were quantified. During the 3 consecutive years of follow-up, 312 eyes (16.60%) experienced DR progression and 115 eyes (6.12%) developed DME. The DR progression was related to a lower VD of the SCP (relative risk per standard deviation decrease, 95% confidence interval): 1.30, 1.14-1.48; P < .001), a lower PD of the SCP (1.41, 1.24-1.60; P < .001), a lower VD of the radial peripapillary plexus (1.23, 1.08-1.40; P=.002), and an elevated CC FD% (1.62, 1.40-1.88; P < .001). The DME occurrence was associated with a lower VD of SCP (1.35, 1.09-1.66; P=.005), a lower PD of SCP (1.29, 1.05-1.59; P=.016), and a higher CC FD% (1.29, 1.03-1.61; P < .001). The CC FD% significantly improved the predictive power, with the increase of the C-statistic for DR progression and DME occurrence by 3.83% (P=.002) and 5.24% (P < .001), respectively. This study provides the first longitudinal evidence suggesting that peripapillary CC FD% can improve the prediction of DR progression and DME development beyond traditional risk factors.

Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials

BackgroundThiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration...

Statin use and the risk of progression to vision threatening diabetic retinopathy.

This study aims to assess the effect of statins on progression from nonproliferative diabetic retinopathy (NPDR) to vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME). Two cohort studies using a U.S. medical claims database from 2002 to 2019 including NPDR patients 18 years or older. A risk factor analysis performed a time-updating cox regression model assessing statin usage. A second new-user active comparator design analysis replicating a previously published study. Main outcomes included a new diagnosis of VTDR (composite of either PDR or DME) or DME and PDR individually for the risk factor study and included additional outcomes of new DR, NPDR, vitreous hemorrhage (VH) and tractional retinal detachment (TRD) for the new user study. Risk factor analysis included 66 617 statin users with NPDR at baseline and 83 365 nonstatin users. Of these, 27 325 (18.2%) progressed to VTDR, 4086 (2.71%) progressed to PDR, and 22 750 (15.1%) progressed to DME. After multivariable analysis, no protective effect of statin use was found for progression to VTDR, PDR, or DME (HR=1.01-3, p >0.33 for all comparisons). Replicated new user design analysis also showed no protective effect for statins on risk of development of DR (HR=1.03, 95% CI: 0.99-1.07, p=0.13), PDR (HR=0.89, 95% CI: 0.79-1.02, p=0.09), DME (HR=0.94, 95% CI: 0.86-1.03, p=0.21), VH (HR=1.00, 95% CI: 0.86-1.16, p=0.99), and TRD (HR=1.11, 95% CI: 0.89-1.38, p=0.36). Statin use was found not to be protective for progression of DR regardless of study methodology. These results suggest that the specifics of the population studied rather than differing study methodology are important in assessing the effect of statins on DR progression.

The relationship between peripheral blood inflammatory markers and diabetic macular edema in patients with severe diabetic retinopathy.

Diabetic macular edema (DME) is a serious complication of diabetic retinopathy (DR). Recent studies have shown that inflammation is closely associated with the development of DME, and peripheral blood inflammatory markers [white blood cell (WBC) count and its subtypes] are relatively simple and easy to detect. Here, we investigated the relationship between peripheral blood inflammatory markers and macular edema in patients with severe DR (including both severe non-proliferative DR and proliferative DR). A total of 42 patients with severe DR were included in this study and divided into two groups: a severe DR with DME group (DME group, n=18) and a severe DR without DME group (non-DME group, n=24). Ophthalmologic findings and hematologic results were retrospectively retrieved from hospitalization records and databases. The neutrophil percentage was significantly higher in the DME group (62.52%±8.21%) than in the non-DME group (57.30%±8.17%) (P<0.05); in contrast, the lymphocyte percentage was significantly lower in the DME group (28.09%±7.45%) than in the non-DME group (33.54%±7.29%) (P<0.05). Logistic regression analysis showed a significant correlation between lymphocyte percentage and DME [odds ratio (OR) =0.654, 95% CI: 0.436-0.851; P=0.011]. Lymphocyte percentage can be used as an inflammatory marker for the development of DME in patients with severe DR.

The diagnostic value of systemic immune-inflammation index in diabetic macular oedema

ABSTRACT Clinical relevance Diabetic macular oedema (DME) is a significant cause of visual impairment and inflammation plays an important role in its pathophysiology. Background This study evaluates the diagnostic value of systemic immune-inflammation index (SII) in the occurrence of DME in patients with non-proliferative diabetic retinopathy. Methods In this prospective study, the SII was applied to 150 consecutive patients with non-proliferative diabetic retinopathy. The relationship between the SII and the occurrence of DME was examined. Patients with DME were also divided into two subgroups according to the presence of accompanying sub-retinal fluid. The SII value was calculated as follows: platelet count × (neutrophil/lymphocyte). The risk factors for DME were evaluated using multivariate logistic regression analysis. A receiver operating characteristic (ROC) curve analysis of SII for predicting DME was performed. Results Patients with DME had significantly higher levels of SII than those without DME (599.7 ± 279.2 and 464. 9 ± 172.2, respectively, p < 0.001). However, The SII values were similar between sub-retinal fluid subgroups. Multivariate regression analysis indicated that SII, together with duration of diabetes, was an independent factor for DME occurrence [Odds ratio (OR) = 1.005, 95% confidence interval = 1.001–1.009, p = 0.04, and OR = 1.146, 95% CI = 1.049–1.252, p = 0.003, respectively]. ROC curve analysis revealed that the best cut-off value of SII was 399 (area under the curve: 0.633; sensitivity: 70%; specificity: 60%). Conclusion An elevated SII value is strongly associated with the development of DME. The SII may be a diagnostic biomarker for identifying DME to improve the risk stratification and management of non-proliferative patients with diabetic retinopathy.

Expression of Long Non-Coding RNA (lncRNA) SNHG5 in Patients with Refractory Diabetic Macular Edema and Its Regulatory Mechanism.

BackgroundThe aim of this study was to assess use of lncRNAs as biomarkers in serum and aqueous humor of patients with diabetic macular edema (DME).Material/MethodsOptical coherence tomography and fundus photography were used to analyze the retinal features of the patients. RT-qPCR was used to analyze the differential expression of lncRNA snhg5 in patients who have idiopathic macular hole (MH), DME, or refractory DME. The relationship between SNHG5 and the clinical characteristics of the patients was analyzed. The effect of SNHG5 on the hyperplasia and apoptosis of human retino-microvascular endothelial cells (HRMECs) and its mechanism were analyzed in vitro.ResultsPatients with idiopathic MH developed retinal nerve epithelium rupture and retinal fundus thickening, and patients with DME or refractory DME showed significant macular edema with hemorrhaging. The refractory DME patients improved after treatment but still showed significant macular edema and multiple laser scarring. SNHG5 expression was not only low in the atrial fluid and plasma in DME patients, but also lower in the refractory DME group compared to the idiopathic MH patients. SNHG5 expression in the aqueous humor and plasma was negatively correlated with disease duration, body mass index, and levels of fasting blood glucose, glycated hemoglobin, proteinuria, and glycosuria. In the in vitro experiments, SNHG5 expression was significantly downregulated in high glucose-induced HMECs. After SNHG5 overexpression, cell proliferation, angiogenesis, and VEGF-A protein levels were distinctly downregulated.ConclusionsSNHG5 correlates with the development of DME and is a potential target for therapy.

Bradykinin and angiotensin-converting enzyme in serum of patients with diabetic retinopathy and the prognosis of diabetic macular edema development (pilot study)

Diabetic macular edema (DME) is a microvascular complication of diabetic retinopathy. One of the key roles in the pathogenesis of DME may belong to the components of rennin-angiotensin and kallikrein-kinin systems: bradykinin (Bk) and angiotensin-converting enzyme (ACE). To determine the Bk and ACE concentration and ACE activity in serum of patients with proliferative diabetic retinopathy (PDR) and to estimate the significance of these parameters for the early diagnostic and prognosis of DMO. Serum was collected from the 2 groups of patients with II type diabetes. Group I (n=9) had DME, group II (n=27) had PDR without DME. Control group (n=14) consisted of adult volonteers without diabetes and ophthalmic diseases. Concentration of Bk and ACE was measured using ELISA kits, ACE activity was determined enzymatically with specific fluorogenic substrate. Concentration of Bk in serum of patients without DME did not differ from one in controls (12,00 (9,70; 12,40) pg/ml) while all patients with DME had Bk level of 14,69 (13,68; 16,78) pg/ml that was significantly higher (p&lt;0,01). In patients without DME ACE concentration (88,60 (77,30; 97,45) ng/ml) and ACE activity (6,8 (5,1;7,1) nmol/min·ml) were higher than normal (p&lt;0,01) while in the case of DME concentration of ACE increased (77,36 (70,24; 86,29 ng/ml, p&lt;0,01) and activity remained normal. The Bk/ACE concentrations ratio decreased in patients without DME and increased in those having DME. Patients with DME have increased Bk concentration along with nearly normal ACE concentration that indicate predominance of Bk synthesis over its degradation that may lead to the DME development. The Bk/ACE ratio decrease in patients with uncomplicated PDR and increase significantly in ones with DME. It means that determination of Bk in serum of patients with PDR may be used for the prediction of DME development. The Bk/ACE concentrations ratio may be even more informative.

Comparison of Inflammatory and Angiogenic Factors in the Aqueous Humor of Vitrectomized and Non-Vitrectomized Eyes in Diabetic Macular Edema Patients.

Objectives: To compare the aqueous concentrations of inflammatory and angiogenetic factors in vitrectomized vs. non-vitrectomized eyes with diabetic macular edema (DME).Methods: Aqueous samples were obtained from 107 eyes with DME before intravitreal injection of anti-VEGF, 36 eyes with previous pars plana vitrectomy (PPV) combined with pan-retinal endolaser photocoagulation (PRP), and 71 treatment-naïve. Interleukin (IL)-6, IL-8, interferon-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF) were measured by cytometric bead array (CBA). Optical coherence tomography (OCT) was used for measuring central retinal thickness (CRT).Results: IL-6, IL-8, IP-10, and MCP-1 in aqueous humor of DME vitrectomized eyes were significantly higher than in non-vitrectomized DME eyes, while VEGF was lower than in non-vitrectomized DME eyes. VEGF in aqueous humor significantly correlated with CRT for DME in non-vitrectomized DME eyes. IL-6, IL-8, IP-10, and MCP-1 in aqueous humor were not significantly associated with VEGF for DME in vitrectomized eyes.Conclusions: Inflammation might play an important role in the pathogenesis of DME in vitrectomized eyes. Moreover, inflammation might play a central role in the development of DME via the VEGF-independent pathway. Thus, anti-inflammatory therapy might be a strategy for DME in vitrectomized eyes.