Development Of Diabetic Macular Edema Research Articles

Comparison of the cytokines levels in aqueous humor in vitrectomized eyes versus non-vitrectomized eyes with diabetic macular edema.

This study was conducted to compare concentrations of VEGF family growth factors, inflammation-related factors, and adhesion molecules in the aqueous humor of eyes with diabetic macular edema (DME), with and without prior vitrectomy. A total of 31 eyes were included, 11 with DME that had undergone vitrectomy, 9 with DME but without vitrectomy, and 11 from age-related cataract patients as controls. The concentrations of cytokines including TNF-α, IL-6, IL-8, IP-10, MCP-1, IFN-γ, MIP-1 α, MIP-1 β, PECAM-1, MIF, VCAM-1, ICAM-1, PIGF were quantified using Luminex Human Discovery Assay. Central macular thickness (CMT) values of all eyes were measured using optical coherence tomography (OCT). (1) Vitrectomized DME eyes exhibited significantly higher levels of IL-6 and IL-8 compared to non-vitrectomized eyes (P < 0.05). (2) In vitrectomized group, after Benjamini-Hochberg correction, there was a significant positive correlation between the levels of VEGF and PlGF (rs = 0.855, P < 0.05), as well as the levels of TNF-α and IFN-γ (rs = 0.858, P < 0.05). In non-vitrectomized group, significant positive correlations were found between VEGF and PlGF levels after correcting for multiple comparisons (rs = 0.9, P < 0.05). (3) In non-vitrectomized group, the concentrations of VEGF and PlGF in aqueous humor were significantly positively correlated with CMT values (rs = 0.95, P < 0.05; rs = 0.9, P < 0.05, respectively). The concentrations of IL-6 and IL-8 in the aqueous humor were significantly higher in vitrectomized DME eyes compared to nonvitrectomized DME eyes and the levels of VEGF were similar in the two groups, suggesting that inflammation after vitrectomy may be a key factor in the occurrence and development of DME.

Impact of GLP-1 Agonists and SGLT-2 Inhibitors on Diabetic Retinopathy Progression: An Aggregated Electronic Health Record Data Study

PurposeTo examine the effects of GLP-1 agonists compared to SGLT-2 inhibitors on diabetic retinopathy. DesignRetrospective clinical cohort study using TriNetX (Cambridge, MA, USA), a federated electronic health records network comprising multiple healthcare organizations. MethodsPatients with an International Classification of Diseases, Tenth Revision (ICD-10) code of non-proliferative diabetic retinopathy and monotherapy treatment, excluding insulin, with GLP-1 agonists or SGLT-2 inhibitors. Patients with history of proliferative diabetic retinopathy prior to initiation of treatment were excluded. Rate of progression to proliferative diabetic retinopathy and rate of development of diabetic macular edema were compared between patients on GLP-1 agonists compared to those on SGLT-2 inhibitors. The groups were propensity score matched for age, gender, ethnicity, race, type of diabetes, and severity of non-proliferative diabetic retinopathy. Main outcomes included rate and relative risk of progression to proliferative diabetic retinopathy and risk of diabetic macular edema in the GLP-1 agonist group versus the SGLT-2 inhibitor group. ResultsA total of 6481 patients were identified in the GLP-1 cohort and the SGLT-2 inhibitor cohort after propensity score matching. At 1 year and 3 years after initiation of therapy, a higher rate of progression of proliferative diabetic retinopathy was noted (RR: 1.26, CI 1.04-1.51, p=0.017 at 1 year, RR: 1.284, CI 1.1-1.499, p=0.002 at 3 years) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. There was a higher rate of diabetic macular edema noted at 3 months (RR: 1.192, CI 1.059-1.276, p=0.002), 6 months (RR: 1.22, CI 1.13-1.32, p<0.001), 1 year (RR: 1.24, CI 1.15-1.33, p<0.001), and at 3 years (RR: 1.29, CI 1.21-1.38, p<0.001) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. ConclusionsA higher rate of progression of proliferative diabetic retinopathy and risk of new-onset diabetic macular edema was observed in patients on monotherapy with GLP-1 agonists compared to those on SGLT-2 inhibitors. It is important for clinicians to be aware of these potential effects and to consider the current retinopathy status when initiating treatment with newer hypoglycemic agents to ensure these patients are appropriately monitored for developing potential vision threatening complications.

The Treatment of Diabetic Retinal Edema with Intravitreal Steroids: How and When.

Diabetic macular edema (DME) is a common complication of diabetes mellitus and a leading cause of visual impairment worldwide. It is defined as the diabetes-related accumulation of fluid, proteins, and lipids, with retinal thickening, within the macular area. DME affects a significant proportion of individuals with diabetes, with the prevalence increasing with disease duration and severity. It is estimated that approximately 25-30% of diabetic patients will develop DME during their lifetime. Poor glycemic control, hypertension, hyperlipidemia, diabetes duration, and genetic predisposition are recognized as risk factors for the development and progression of DME. Although the exact pathophysiology is still not completely understood, it has been demonstrated that chronic hyperglycemia triggers a cascade of biochemical processes, including increased oxidative stress, inflammation, activation of vascular endothelial growth factor (VEGF), cellular dysfunction, and apoptosis, with breakdown of the blood-retinal barriers and fluid accumulation within the macular area. Early diagnosis and appropriate management of DME are crucial for improving visual outcomes. Although the control of systemic risk factors still remains the most important strategy in DME treatment, intravitreal pharmacotherapy with anti-VEGF molecules or steroids is currently considered the first-line approach in DME patients, whereas macular laser photocoagulation and pars plana vitrectomy may be useful in selected cases. Available intravitreal steroids, including triamcinolone acetonide injections and dexamethasone and fluocinolone acetonide implants, exert their therapeutic effect by reducing inflammation, inhibiting VEGF expression, stabilizing the blood-retinal barrier and thus reducing vascular permeability. They have been demonstrated to be effective in reducing macular edema and improving visual outcomes in DME patients but are associated with a high risk of intraocular pressure elevation and cataract development, so their use requires an accurate patient selection. This manuscript aims to provide a comprehensive overview of the pathology, epidemiology, risk factors, physiopathology, clinical features, treatment mechanisms of actions, treatment options, prognosis, and ongoing clinical studies related to the treatment of DME, with particular consideration of intravitreal steroids therapy.

OCT angiography 2023 update: focus on diabetic retinopathy.

Optical coherence tomography angiography (OCTA) has become part of the clinical practice and its growing applications are in continuous development. Coherently with the growing concern about the human and economic cost of diabetes, diabetic retinopathy (DR) was the most popular topic for OCTA studies in the past year. The analysis of the literature reveals that applications of OCTA in DR are in continuous growth. In particular, ultrawide field (UWF) OCTA and artificial intelligence (AI) based on OCTA images are affirming as the new frontiers of scientific research in the field. Diagnostic accuracy of AI methods based on OCTA is equal or superior to the one based on OCT methods and also bears potential to detect systemic associations. UWF OCTA is noninvasive method that is reaching similar accuracy of FA in detection of neovascularization and intraretinal microvascular abnormalities (IRMAs) and has allowed better characterization of microvascular peripherical changes in DR. Lastly, deep capillary plexus (DCP) characteristics seem to play a pivotal role in the development of diabetic macular edema (DME) and refinement of biomarkers for different phenotypes of DME and diabetic macular ischemia (DMI) is currently on its way.

Incidence of Central Involving Macular Oedema After Cataract Surgery in Diabetic Retinopathy Patients – A Prospective Study

Aim: To study the incidence of central macular oedema at 4, 8 and 12 weeks following cataract surgery in diabetic retinopathy eyes. Materials and Methods: A prospective observational study was conducted over a period of 3 months to investigate the presence of centrally involved macular oedema following cataract surgery in diabetic retinopathy patients. Preoperative OCT scans were performed and patients without centrally involved macular oedema were enrolled. Subfield thickness (central, outer and inner) was measured preoperatively and at 4, 8 and 12 weeks postoperatively. The correlation between diabetic macular oedema (DME) and HbA1c, as well as random blood sugar (RBS) levels at the time of surgery, was analysed. Best.corrected visual acuity (BCVA) was assessed preoperatively and postoperatively, and fundus examinations were conducted each visit to evaluate diabetic retinopathy progression. Results: This study included 80 eyes from 44 patients. Postoperatively, central subfield thickness (CSF) increased significantly at first (14.7 μm), second (26.7 μm) and third (30.3 μm) compared to baseline. Inner subfield thickness (ISF) also increased at first (13.3 μm), second (20.6 μm) and third (24.3 μm) months, while the outer subfield thickness (OSF) showed progression from 6.7 μm to 16.6 μm from the first to third month. A statistically significant shift in DME was observed three months post.cataract surgery. There was a significant association between HbA1c levels and the development of DME, but no correlation with RBS levels. BCVA improved remarkably from preoperative mean log MAR of 0.75 to a mean log MAR of 0.1 at 3 months postoperatively. About 30% had mild non-proliferative diabetic retinopathy (NPDR) preoperatively, and in that group, 60% progressed to moderate NPDR. The status of moderate and severe NPDR remained the same postoperatively at 3 months. Of all patients who progressed to moderate NPDR, 3 cases developed non-central macular oedema, and three cases developed both central and non.central macular oedema postoperatively at 3 months. All eyes with severe NPDR resulted in DME, except for one (9.1%) eye. Conclusion: Preoperatively, 57.5% had no macular oedema, while 42.5% had non.central macular oedema. Postoperatively, 4.4% had central oedema, and 10.9% had both central and non.central oedema among those who initially had no macular oedema. Additionally, 38.2% developed oedema in both central and non.central regions among patients initially presenting with non-central macular oedema. There was also a significant statistical difference with longer duration of diabetes mellitus, severity of diabetic retinopathy and elevated HbA1c values with the development of diabetic macular oedema postoperatively. However, larger sample sizes and longer-term follow-up are essential for assessing retinopathy progression and the incidence of DME.

MATHEMATICAL MODELING OF ASSESSMENT OF THE PROBABILITY OF THE DEVELOPMENT AND PROGRESSING OF DIABETIC MACULAR EDEMA IN PATIENTS WITH TYPE 2 DIABETES

Background. The participation of fractalkine, clusterin and sICAM in the pathogenesis of diabetic complications of the fundus was established. The development of methods of mathematical assessment of the prognosis of the development and course of diabetic macular edema (DME) with the participation of these cytokines is an actual problem of modern ophthalmology and endocrinology.&#x0D; Aim: To develop the prognostic mathematical models for assessing the probability of development and progression of DME in patients with diabetes mellitus (DM) type 2 based on the study of the content of blood serum fractalkine, clusterin and sICAM-1.&#x0D; Material and methods. A single-center selective one-moment open observational study of 82 patients (145 eyes) with DME in type 2 diabetes, divided into 4 groups according to the severity of DME, was conducted. The average age of the patients was 65.25±10.85 years, the average duration of diabetes was 14.0±7.05 years (±SD). The concentration of blood serum fractalkine (Frl), clusterin (Cls) and sICAM-1 was determined by the ELISA, and an instrumental examination of the fundus was performed. Multivariate discriminant analysis was used with the “SPSS 9.0” program. Differences at p&lt;0.05 were considered statistically significant. 3 models with linear combinations of the investigated indicators were developed and corresponding formulas of classification functions (FC) were obtained.&#x0D; Results. Models for assessing the risk of DME development and progression in patients with type 2 DM characterize by the fact that, at the first stage, fix the duration of diabetes mellitus (DD), and measure the concentration of blood serum fractalkine, clusterin, and sICAM-1. Further, with the helpness of ophthalmoscopy, determine the presence and severity of DMN, assigning the code 1 - the presence of concomitant diabetic retinopathy (DRP), the code 2 - the absence of DRP. At the final stage, calculate the classification functions FK1 and FK2 or FK2 and FK3 (depending on the model), compare FK1 with FK2 or FK2 with FK3, and determine which of them is larger according to the appropriate formulas. Moreover, the prognostic decision takes as the choice of the FC that is more important. So, if FK1&gt;FK2, the prognosis is possible the stabilization of the pathological process, and if FK2&gt;FK1 or FK3&gt;FK2, then the prognosis is the probability of progression of the DME.&#x0D; The main model is presented below:&#x0D; FK1DME(0) = -111,278 + 8,57411*Frl + 0,562616*Cls + 0,257994*sICAM -0,139202*DD +7,72433*DRP&#x0D; FK2DME(1) = -101,108 + 8,5887* Frl + 0,544401* Cls + 0,235155*sICAM + +0,0261057*DD + 10,1873*DRP&#x0D; FK3DME(2+3) = -105,68 + 9,06663* Frl + 0,552074* Cls + 0,241348*sICAM -0,102963*DD + 11,8493*DRP&#x0D; Conclusion. The informativeness of mathematical models for assessing the prognostic significance of serum cytokines fractalkine, clusterin and sICAM-1 in the development and progression of DME in patients with type 2 diabetes is 62.5-77.5%, depending on the type of model.

Патогенез, ангиогенез диабетического макулярного отека и общая характеристика его лечения (Обзор литературы. Часть I)

Currently, the increase in the prevalence of diabetes mellitus is in the nature of a pandemic. Diabetic macular edema is a vision-threatening complication of diabetic retinopathy, the pathogenesis of which is multifactorial and includes hyperglycemia, endothelial dysfunction, leukostasis and inflammation, vasoconstriction and occlusion, oxidative stress and ischemia, neovascularization, which leads to the accumulation of exudative fluid, thickening of the central zone of the retina and irreversible processes of photoreceptors neurodegeneration with a significant decrease in visual functions. The article presents up-to-date information on the epidemiology, patho- and angiogenesis of this condition as well as the general characteristics of the DMO therapy. It consists of primary treatment of diabetes, laser photocoagulation and anti-angiogenic therapy. Intravitreal drug therapy based on VEGF inhibitors is currently the standard first-line treatment for DMO. The authors emphasize the necessity for further study of trigger points in the pathogenesis of diabetic retinopathy and the development of diabetic macular edema in order to find new drugs and work out a more individualized approach to patients. Key words:: diabetic retinopathy, diabetic macular edema, vascular endothelial growth factor, VEGF-therapy

Association of a Bioimpedance Profile with Optical Coherence Tomography Features in Diabetic Macular Edema.

We examined the association between bioimpedance profiles and optical coherence tomography (OCT) features in patients with diabetic macular edema (DME). This cross-sectional study included 100 eyes of 100 patients with type 2 diabetes mellitus. The systemic fluid status was assessed using extracellular water-to-total body water ratio (ECW/TBW) and phase angle (PhA), which was measured using bioimpedance equipment. ECW/TBW was higher in the DR (diabetic retinopathy) with DME group than in the no DR and DR without DME groups (p = 0.007 and p = 0.047, respectively); however, no significant difference was observed between the no DR and DR without DME groups. The PhA values were significantly lower in the DR with DME group (5.45 ± 0.84) than in the no DR (6.69 ± 0.69) and DR without DME groups (6.05 ± 1.15) (p < 0.001, p = 0.032, respectively). The presence of multiple HRF (hyper-reflective foci) was associated with a significantly higher ECW/TBW (p = 0.001). In the group with the most significant HRF, PhA was lower than in those with none or moderate amounts of HRF (p < 0.05). Bioimpedance fluid profiles of patients with OCT features of DME suggest a connection between the overall systemic state, including fluid status and DME development. Further research is required to fully understand and utilize this information for effective clinical assessment and treatment planning.

Biomarkers determining treatment interval of diabetic macular edema after initial resolution by anti-vascular endothelial growth factor.

To identify predictive factors that help determine the interval of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection after the initial resolution of diabetic macular edema (DME). This retrospective case-control study enrolled treatment-naïve DME patients who had achieved DME resolution after intravitreal anti-VEGF injections. Patients were classified into the recurrence and no-recurrence groups, depending on the development of recurrent DME after deferring intravitreal anti-VEGF injection. The demographics and clinical features, including optical coherence tomography findings, were compared between the two groups. We enrolled 105 eyes. Sixty eyes (57.1%) belonged to the no-recurrence group, and 45 (42.9%), belonged to the recurrence group. The severity of diabetic retinopathy at baseline was related to early DME recurrence (P = 0.009). At the treatment deferring point, the non-recurrence group had both thinner central subfield thickness (289.5 ± 27.2μm vs. 307.0 ± 38.2μm, P = 0.011) and thinner central retinal thickness (214.9 ± 41.4μm vs. 231.8 ± 41.2μm, P = 0.043) compared to the recurrence group. Intraretinal cyst was observed in 34 eyes (56.7%) in the no-recurrence group and 42 eyes (93.3%) in the recurrence group at the deferring point (P < 0.001). A low risk of early DME recurrence is anticipated in the eyes with foveal thinning and no intraretinal cyst when anti-VEGF injection is deferred. These predictive biomarkers can be useful for patient monitoring and determining treatment strategies for DME patients.

Development of diabetic macular oedema shows associations with systemic medication - An epidemiological study.

To identify associations between systemic drugs and the incidence of diabetic macular oedema (DME). Of interest was to find beneficial and/or deleterious associations of used drugs. A historic cohort design based on administrative data. Study population consisted of 150 353 individuals with diabetes. Endpoint event was the development of DME (ICD-10 H36.01), censoring events were death or study end December 2017. The follow-up started between 1997 and 2010. The systemic medication consisted of 95 substances. We constructed a nested case-control study design comparing 2630 cases with DME to 13 144 age- and sex-matched controls without DME. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs) based on conditional logistic regression models. Incidence rate for DME was 1.80 per 1000 person-years (95% CI 1.73-1.87). In all, we observed a lower incidence rate of DME in females (IRR 0.57; 95% CI 0.52-0.62) compared to males. Exposure to hormone replacement therapy estradiol (OR 0.42; 0.25-0.68), temazepam (0.23; 0.08-0.62) and allopurinol (0.61; 0.43-0.86) were associated with lower risk of DME, while use of insulin or insulin analogue (3.30; 2.99-3.64), sulfonylureas (1.21; 1.05-1.40), diuretic furosemide (1.90; 1.61-2.24), calcium channel blocker amlodipine (1.53; 1.34-1.75), ACE inhibitors ramipril (1.66; 1.46-1.89) and enalapril (1.38; 1.16-1.64) were associated with an increased risk of DME. Large-scale studies examining the incidence of DME are lacking. Our findings suggest that associations of systemic medications with the incidence of DME may shed light on the pathogenesis of complex DME, encouraging further studies.

Surgical Treatment for Diabetic Macular Edema

Diabetic macular edema (DME) is defined as excess fluid accumulation within the retina in the macular area, and when it is centered on the fovea it is the most common cause of decreased visual acuity in patients with diabetic retinopathy. The development of diabetic macular edema is closely related to the duration of diabetes, poor glycemic control, and type 2 diabetes on insulin therapy. The first-line therapy in diabetic macular edema has been the intravitreal injection of anti-vascular endothelial growth factors (VEGF). Other treatment modalities are intravitreal corticosteroid injection and focal laser photocoagulation. However, the efficacy of intravitreal therapy may decrease significantly over time, especially in the presence of vitreomacular traction, tight posterior hyaloid, or epiretinal membrane (ERM). At this stage, pars plana vitrectomy (PPV) is preferred as an alternative treatment method in eyes with chronic DME resistant to intravitreal injections. The vitreous of diabetic patients contains high amounts of VEGF and Angiotensin 2, which cause DME, and cytokines such as interleukin-6 and ICAM-1. In addition, due to the enzymes, it contains, the vitreous causes cross-linking and thickening of the collagen fibers in its structure, causing tight adhesion and traction on the macula. The mechanism of action of pars plana vitrectomy in macular edema can be explained by removing the vitreous and vitreomacular tractions. Vitrectomy may also increase retinal oxygenation. Selection of the appropriate case is important. The undisturbed integrity of the outer retinal layers including the external limiting membrane(ELM) and the ellipsoid zone, no preoperative foveal ischemia, and performing surgery early before ELM is damaged, have been found to be related to better postoperative visual acuity gain. Further, prospective, randomized, controlled studies with large series including detailed parameters and long follow-up evaluating the efficacy of surgical treatment in diabetic macular edema are warranted.

THE ROLE OF E-SELECTIN IN THE DEVELOPMENT OF MACULAR EDEMA IN DIABETIC RETINOPATHY DURING TYPE 2 DIABETES

Background. Diabetic retinopathy (DR) and diabetic macular edema (DME) are frequent complications of type 2 diabetes (T2D). Implementation of their effective diagnosis and prognosis by identifying new biomarkers is an important task of modern ophthalmology.&#x0D; Aim: is to establish the role of E-selectin in the development of DME in DR of various degrees in patients with T2D.&#x0D; Materials and methods. The study included 124 patients (124 eyes) with T2D who had mild (29 eyes, group 1), moderate or severe (35 eyes, group 2) non-proliferative DR and proliferative DR (31 eyes, 3rd group); the control group consisted of 29 eyes without diabetes. All patients underwent standard ophthalmological examinations, spectral domain optical coherence tomography (OCT) with determination of central retinal thickness (CRT, μm). The DME set more values of the regulatory database on the ETDRS fields of the spectral-domain OKT software when the CRT is increased. The content of E-selectin in the blood was determined by the immunoenzymatic method (Invitrogen ThermoFisher Scientific, USA). MedStat and MedCalc v.15.1 software packages (MedCalc Software bvba) were used for statistical research.&#x0D; Results. The content of E-selectin in the blood in DR and T2D was significantly increased in all stages of DR (1.2-1.3 times; p&lt;0.01), with a maximum in proliferative DR, which directly correlated with indicators that reflected glycemic control (HbA1c), retinal edema (CRT) and visual acuity deterioration. The content of E-selectin when dividing patients according to the presence of DMN was higher than without it (1.3 times; p&lt;0.001), which was preserved for all stages of DR. The existence of a pathogenetic connection between an increase in the content of E-selectin and the development of DME and the possibility of its use as a biomarker of DME was confirmed in a univariate regression analysis: an increase in the DME risk with an increase in the content of E-selectin was found (OR=1.19; 95% CI 1.12-1.26). The model had satisfactory performance criteria - AUC=0.89 (95% CI 0.83-0.94) with a sensitivity of 89.8% and a specificity of 80.0%.&#x0D; Conclusion. The results of the study confirmed the concept of the significant importance of increasing the content of E-selectin in the blood for the development of DME in DM and T2D.

TLR4 GENE POLYMORPHISM rs2149356 IN TYPE 2 DIABETES - POSSIBLE RELATIONSHIP WITH DIABETIC MACULAR EDEMA

Background. Polymorphisms in the non-coding regions of the TLR4 gene are known to be associated with the risk of ocular complications of type 2 diabetes (T2DM), with some polymorphisms having no association, others increasing the risk, and some reducing the risk of complications.&#x0D; Aim: to establish the association of the TLR4 gene polymorphism rs2149356 with diabetic retinopathy (DR) and diabetic macular edema (DME) in T2DM.&#x0D; Materials and methods. The study included 81 patients (81 eyes) with T2DM, in whom, according to the guidelines of the American Academy of Ophthalmology (2002), DR and DME were detected, the control group consisted of 50 patients (50 eyes) with T2DM, normalized carbohydrate metabolism, DR 0 (no retinopathy) and absent DME. Genotypes of rs2149356 were determined by real-time polymerase chain reaction using the Gene Amp® PCR System 7500 amplifier (Applied Biosystems, USA) and TaqMan Mutation Detection Assays Life-Technology (USA). MedStat and MedCalc v.15.1 software packages (MedCalc Software bvba) were used for statistical research.&#x0D; Results. In this study, no association of the genetic polymorphism rs2149356 of the TLR4 gene with the development of DR and DME in T2DM was found (p=0.326). Stratification by stages of DR showed no dependence of the distribution of genotypes, while according to the degree of DME, the distribution of genotypes was definitely different in DME 3. Thus, among the carriers of the ancestral genotype G/G, none of DME 3 was found, the borderline level of the total retinal volume (TRV) was 6.7 mm3, above which DME 1 or DME 2 was determined. All carriers of the heterozygote G/T had DME 3, and for carriers of the minor homozygote T/T, two threshold values of TRV were determined: above 6.7 mm3, DME 1 or DME 2 was determined, and higher than 8.7 mm3 – DME 3. Analysis of the relationship between the rs2149356 TLR4 and the phenotype of patients showed greater central retinal thickness and TRV in heterozygous and minor homozygous T/T carriers, which corresponded to greater retinal damage compared to ancestral homozygous G/G carriers (p&lt;0.001).&#x0D; Conclusion. Data were obtained on the association of diabetic retinal damage with the rs2149356 TLR4 – retinal edema was more pronounced in carriers of the T allele.

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.