Stages Of Retinopathy Research Articles

Elective high frequency oscillatory ventilation versus conventional mechanical ventilation on the chronic lung disease or death in preterm infants administered surfactant: a systematic review and meta-analysis.

Use of elective high frequency oscillatory ventilation (HFOV) compared with conventional mechanical ventilation (CMV) results in a small reduction in the risk of chronic lung disease (CLD) or death, but the evidence is weak. Our objective was to explore whether elective HFOV was associated with less CLD or death as compared with CMV in preterm infants administered surfactant. We conducted a systematic review and meta-analysis, including 1835 ventilated participants from 11 randomized controlled trials comparing elective HFOV with CMV between February 1993 and February 2014. The primary outcome was the incidence of CLD or death. Compared with CMV, elective HFOV was associated with less CLD or death (relative risk (RR) 0.76, 95% confidence interval (CI) 0.61-0.94, p = 0.01) (p = 0.01, I2 = 55%), CLD (RR 0.71, 95%CI 0.53-0.93, p = 0.01) (p = 0.03, I2 = 50%), and ≥2nd stages of retinopathy of prematurity (RR 0.77, 95%CI 0.62-0.94, p = 0.01) (p = 0.42, I2 = 0%). In the subgroup of > 1 dose of surfactant, compared with CMV, elective HFOV was also related to less CLD or death (RR 0.87, 95%CI 0.77-0.98, p = 0.02) (p = 0.10, I2 = 42%). No differences were found in the incidences of death, grade 3 or 4 of intraventricular hemorrhage, periventricular leukomalacia, airleak and necrotizing enterocolitis between the two groups. Elective HFOV is superior to CMV in reducing the incidence of CLD or death in ventilated preterm infants administered surfactant, especially in the subgroup of >1 dose of surfactant. International Prospective Register of Systematic Reviews: No.: CRD42022301033; URL: https://www.crd.york.ac.uk/PROSPERO/ .

IL-1β-induced pericyte dysfunction with a secretory phenotype exacerbates retinal microenvironment inflammation via Hes1/STAT3 signaling pathway

Retinal pericytes are mural cells surrounding capillaries to maintain the integrity of blood-retina barrier and regulate vascular behaviors. Pericyte loss has been considered as the hallmark of diabetic retinopathy (DR), which is a major complication of diabetes and the leading cause of blindness in adults. However, the precise function of pericytes in regulating the retinal microenvironment and the underlying mechanism remains largely unknown. In this study, we observed a secretory phenotype of pericytes with elevated inflammatory cytokines in response to Interleukin-1β (IL-1β), a canonical inflammatory cytokine which significantly increases during the initial stages of diabetic retinopathy. This phenotype is also accompanied by reduced expression of adherent junction proteins and contractile proteins. Paracrine cytokines derived from pericytes further induce the chemotaxis of microglia cells and trigger detrimental changes in endothelial cells, including reduced expression of tight junction protein Occludin and increased apoptosis. Mechanically, the secretion potential in pericytes is partially mediated by Hes1/STAT3 signaling pathway. Moreover, co-injection of stattic, an inhibitor targeting STAT3 activation, could effectively attenuate IL-1β-induced retinal inflammation and microglial activation in retina tissues. Collectively, these findings demonstrate the potential of retinal pericytes as an initial inflammatory sensor prior to their anatomical pathological loss, via undergoing phenotypic changes and secreting paracrine factors to amplify local inflammation and damage endothelial cells in vitro. Furthermore, inhibition of STAT3 activation by inhibitors significantly ameliorates IL-1β-induced retinal inflammation, suggesting STAT3 in retinal pericytes as a promising target for alleviating DR and other IL-1β-induced ocular diseases.

Effectiveness of treatment for different stages of diabetic retinopathy in type 2 diabetes

Effectiveness of treatment for different stages of diabetic retinopathy in type 2 diabetes

Ocular and Plasma Pharmacokinetics of Sitagliptin Eye Drops: Preclinical Data

Background/Objectives: Early stages of diabetic retinopathy are currently considered an unmet medical need due to the lack of effective treatments beyond proper monitoring and control of glycemia and blood pressure. Sitagliptin eye drops have emerged as a new therapeutic approach against early stages of the disease, as they can prevent its main hallmarks, including both neurodegeneration and microvascular impairment. Interestingly, all of these effects occur without any glycemic systemic improvement. In the present study, we aimed to investigate the pharmacokinetics and distribution of the drug within the eye and plasma. Methods: A total of 48 male New Zealand rabbits were treated with topical administration (eye drops) of sitagliptin at two concentrations: 5 mg/mL and 10 mg/mL. Blood, iris/ciliary body, retina/choroid, aqueous humor, and vitreous humor samples were collected at specific intervals post-administration (10 and 30 min and 1, 3, 6, 15, and 24 h), processed, and analyzed using an LC-MS/MS method. The pharmacokinetics of sitagliptin were then calculated, and statistical comparisons were performed. Results: Our findings indicate that sitagliptin reaches the retina prior to the aqueous and vitreous humors, suggesting that its absorption follows the transscleral route. Additionally, systemic absorption was minimal and below pharmacologically active concentrations. Conclusions: These results support the use of an eye drop formulation for the treatment of diabetic retinopathy and other retinal diseases.

OXIDANTS AND BLOOD-RETINAL BARRIER: PROGRESSION AND MOLECULAR MECHANISMS OF DIABETIC RETINOPATHY

Diabetic retinopathy is a microvascular complication of the eye that arises as a consequence of poor control of hyperglycemia in patients with diabetes mellitus. This condition is characterized by progressive damage to the blood vessels of the retina, leading to increased vascular permeability, microaneurysms, intraretinal hemorrhages and, in more advanced stages, neovascularization. Depending on its degree of progression, it can be classified into a non-proliferative form, more frequent in the initial stages, and a proliferative form, which appears in advanced stages and is associated with a higher risk of severe visual loss. Regarding its pathophysiology, chronic hyperglycemia triggers a series of harmful metabolic and molecular pathways, such as the accumulation of reactive oxygen species, which cause oxidative stress and jointly contribute to endothelial damage and dysfunction of the blood-retinal barrier. Patients with this complication require strict and continuous glycemic control using hypoglycemic drugs capable of reducing the osmolar disturbances characteristic of diabetes, combined with specific ocular therapies such as endothelial growth factor inhibitors, which slow down neovascularization and consequently reduce the likelihood of blindness. However, even with treatment protocols, diabetic retinopathy remains the leading cause of blindness in adults worldwide, underlining the importance of prevention and early diagnosis. This study was based on the bibliographic method, collecting scientific medical data from specialized journals such as PUBMED and Scielo published between 2018 and 2023. The results highlight the close relationship between hyperglycemic states and diabetic retinopathy. Thus, it is concluded that it is essential to develop new therapies that attack not only the advanced symptoms of the disease, but also the early molecular changes that occur during the early stages of diabetic retinopathy, effectively combating the cause and effect of the pathology.

Autophagy-dependent ferroptosis may play a critical role in early stages of diabetic retinopathy.

Diabetic retinopathy (DR), as one of the most common and significant microvascular complications of diabetes mellitus (DM), continues to elude effective targeted treatment for vision loss despite ongoing enrichment of the understanding of its pathogenic mechanisms from perspectives such as inflammation and oxidative stress. Recent studies have indicated that characteristic neuroglial degeneration induced by DM occurs before the onset of apparent microvascular lesions. In order to comprehensively grasp the early-stage pathological changes of DR, the retinal neurovascular unit (NVU) will become a crucial focal point for future research into the occurrence and progression of DR. Based on existing evidence, ferroptosis, a form of cell death regulated by processes like ferritinophagy and chaperone-mediated autophagy, mediates apoptosis in retinal NVU components, including pericytes and ganglion cells. Autophagy-dependent ferroptosis-related factors, including BECN1 and FABP4, may serve as both biomarkers for DR occurrence and development and potentially crucial targets for future effective DR treatments. The aforementioned findings present novel perspectives for comprehending the mechanisms underlying the early-stage pathological alterations in DR and open up innovative avenues for investigating supplementary therapeutic strategies.

ANTI-VEGF IN COMPLICATIONS OF PROLIFERATIVE DIABETIC RETHINOPATHY

This paper has the purpose to analyse the relevance of the use of angiogenesis inhibitors (anti-VEGF drugs) in the treatment of the proliferative stage of diabetic retinopathy. The literature review was carried out using the search engines PubMed, the Library, and the analysis of literature sources, 30 in number, published from 2000 to 2024. In patients with complicated cases of proliferative diabetic retinopathy, pre-intravitreal injection of angiogenesis inhibitors provides the most gentle approach to surgical treatment, which improves the anatomical and functional results of vitreoretinal surgery and helps reduce the number of intra- and postoperative complications.

Correlation of Central Corneal Thickness and Keratometry Findings With the Severity of Diabetic Retinopathy and Glycosylated Hemoglobin (HbA1c) Levels in Type II Diabetes Mellitus Patients.

Diabetes today is a global health issue, posing a risk to several organ systems. Besides complications like cataracts, diabetic retinopathy (DR), glaucoma and refractive errors, anatomical parameters like central corneal thickness (CCT), which is a crucial indicator of corneal endothelium function and keratometry parameters, have also been noticed to be altered in diabetes. Variations in these parameters may affect the accuracy of applanation tonometry in measuring intraocular pressure. This study aims to investigate variations in CCT and keratometry across different stages of DR, as prior research has yielded inconsistent results. The study also intends to explore the relationship between glycosylated hemoglobin (HbA1C) levels and changes in keratometry and CCT. This observational cross-sectional study was conducted from July 2022 to June 2024. A total of 204 subjects, aged 35-70 years, were included in the study. All participants were evaluated for DR, and those showing fundus findings were graded into five classes based on the Early Treatment Diabetic Retinopathy Study (ETDRS) classification. CCT, keratometry parameters (K1 and K2) and HbA1C levels were measured for all participants. The clinical parameters were correlated across different grades of diabetes mellitus and compared using StatisticalPackage for the Social Sciences (IBM SPSS Statistics for Windows, IBMCorp., Version 23.0, Armonk,NY) software. The patient population consisted of 130 males (63.7%) and 74 females (36.3%). It was found that there was a trend indicating that the presence of DR increased with age, which was statistically significant (p=0.036). However, the differences in the mean duration of diabetes across DR groups were not statistically significant. Findings suggested that individuals with DR generally possess a higher CCT compared to the control group, particularly in the earlier stages of the disease, i.e. noDRand mild non-proliferative diabetic retinopathy (NPDR). However, as the severity of DR increases, the CCT tends to decrease slightly in moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR) stages. The study notes that the variations in CCT across these groups were not statistically significant (p-value of 0.29). The study also found that changes in corneal curvature, as indicated by keratometry values, were more pronounced in the proliferative stage of DR, with a statistically significant increase in k2 values of the left eye (p-value = 0.025). The study concluded that there was no statistically significant relationship between CCT and keratometry values of both eyes with HbA1c levels. While there were some clear patterns, especially concerning age, most variations in ocular parameters were not statistically significant, suggesting that other factors might need an in-depth study in the development of DR and its correlation with ocular parameters. Similarly, while HbA1c has often been stated to be a prognostic factor in diabetes mellitus, significant correlations were neither noted with ocular parameters like CCT and keratometry, nor the stage of retinopathy.

Causal association between cystatin C and diabetic retinopathy: A two-sample Mendelian randomization study.

To explore the causal relationship between cystatin C levels and different stages of diabetic retinopathy through Mendelian randomization (MR). The MRC Integrative Epidemiology Unit provided the Genome-wide association studies (GWAS) data related to cystatin C (exposure). GWAS data for outcomes [DR, proliferative diabetic retinopathy (PDR), severe non-proliferative background diabetic retinopathy (SNPBDR)] were sourced from the FinnGen. Adopted Inverse Variance Weighting (IVW), MR-Egger regression MR-PRESSO, Weighted Median, Constrained Maximum Likelihood and Model Averaging (cML-MA), Weighted model, Radial MR, and MR-Lasso to estimate the causal relationship between cystatin C and diabetic retinopathy. We conducted multivariable MR analysis to evaluate the independent causal effects of cystatin C levels on diabetic retinopathy. Based on the IVW method, we observed a causal relationship between cystatin C and diabetic retinopathy [odds ratio (OR)random effect = 1.137, 95% confidence interval (CI): 1.035-1.250]/PDR (ORrandom effect = 1.123, 95%CI: 1.004-1.255)/SNPBDR (ORfixed effect = 2.002, 95%CI: 1.343-2.986). Consistent findings were obtained through the cML-MA method. Cochran's Q test suggested the presence of heterogeneity between the cystatin C level and instrumental variables in relation to diabetic retinopathy and proliferative diabetic retinopathy, respectively. After adjusting for outliers using MR-PRESSO and Radial MR, it was observed that the statistical significance of the association between cystatin C level and diabetic retinopathy persists. Reverse MR analysis indicated that genetically related SNPBDR may influence the cystatin C level. In multivariable MR analysis, there were indications suggesting a causal relationship of cystatin C with the risk of DR/PDR/SNPBDR adjusting for confounders. This study utilizes Mendelian randomization analyses to establish a causal relationship between cystatin C and diabetic retinopathy, and reveals the impact of cystatin C on the risk of diabetic retinopathy, thus providing new evidence for clinical intervention of diabetic retinopathy.

Correlation Between Photoreceptor and Vascular Parameters in Diabetic Retinopathy Using Adaptive Optics.

This study aimed to investigate correlations between photoreceptor and vascular parameters in varying stages of diabetic retinopathy (DR) using adaptive optics (AO) imaging. In this single-center, prospective cohort study, 29 participants (46 eyes) were classified into control/mild non-proliferative DR (NPDR), moderate/severe NPDR, and proliferative DR. AO images of photoreceptors and retinal vasculature were analyzed, and Spearman's correlation (ρ) was used to assess relationships between photoreceptor density and vascular parameters. Higher cone density was inversely associated with total vessel (ρ = 0.22, P = 0.03) and lumen diameters (ρ = -0.24, P = 0.01), while higher dispersion was associated with total vessel (ρ = 0.19, P = 0.06) and lumen diameters (ρ = 0.21, P = 0.04). These associations were primarily significant in mild NPDR. No significant correlations were found in advanced DR stages. This study underscores intricate neurovascular correlations in early-stage DR, suggesting these parameters may aid in early disease detection. Further research is needed to understand whether similar correlations exist in advanced DR. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Early expression of osteopontin glycoprotein on the ocular surface and in tear fluid contributes to ocular surface diseases in type 2 diabetic mice.

Osteopontin (OPN) is a glycosylated, secreted phosphoprotein known to be elevated in both human and mouse retinas during various stages of diabetic retinopathy. However, its specific roles in modulating ocular surface dynamics and immune responses in diabetes remain unexplored. This study aims to investigate the role of OPN in the development of ocular surface disease (OSD) in type 2 diabetic (T2D) mice. Three- to four-week-old C57BL/6 wild-type (WT) and OPN-knockout (OPN-/-) mice were fed a high-fat diet (HFD) and were rendered diabetic by streptozotocin (STZ; 40 mg/kg body weight) in citrate buffer (vehicle); non-diabetic controls were injected with vehicle alone. Diabetes was confirmed if blood glucose levels were >200 mg/dL, measured 1-2 weeks post-STZ injection. Control, age- and sex-matched db/db diabetic mice fed a standard chow diet were also included in this study. Ocular surface inflammation was assessed using ELISA to quantify inflammatory cytokine proteins and wheat germ agglutinin (WGA) staining was utilized to highlight corneal surface irregularities. Clinical signs were evaluated by corneal fluorescein staining, tear production measurements, and tear sodium (Na+) concentration assessments. These evaluations were conducted 4, 6, 8 and 16-weeks post-diabetes onset in WT and OPN-/- mice and were compared to those obtained in non-diabetic controls. Statistical analysis was performed using a two-way ANOVA, with significance set at P < 0.05. Both WT and OPN-/- mice developed T2D within 4 and 8 weeks, respectively, following HFD + STZ treatment. Corneal OPN levels in WT diabetic mice increased ~2-fold at 2 weeks and ~4-fold at 16 weeks compared to non-diabetic controls, with similar elevations observed in their tear fluid. Diabetic db/db mice also exhibited elevated OPN levels in the blood and ocular surface, which persisted as diabetes progressed. Enhanced fluorescein staining, indicating corneal irregularities, appeared in WT mice at 8 weeks and in OPN-/- mice at 10 weeks post-T2D induction. Additionally, WGA staining showed a significant reduction in fluorescence intensity in WT mice treated with HFD and STZ, confirming corneal surface irregularities that were delayed in OPN-/- mice. Elevated tear sodium concentration was observed in both WT and OPN-/- diabetic mice without affecting tear production rates. Notably, OPN levels increased early, at week 2, following HFD and STZ treatment, preceding changes in interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9). Upregulation of IL-6 became apparent at 6 weeks in WT mice and was delayed until 10 weeks in OPN-/- mice post-T2D induction. Elevated OPN levels were detected early post-T2D induction in diabetic WT and db/db mice corneas without initial subclinical changes. This early increase in OPN precedes other proinflammatory cytokines associated with eventual ocular surface inflammation as diabetes progresses. Persistence of OPN also correlated with clinical signs such as increased corneal surface irregularities and elevated tear Na+ concentration. Future research will explore OPN's role as a biomarker in ocular surface disease (OSD), including dry eye disease (DED), and investigate its impact on inflammatory processes and other mechanistic pathways in diabetic ocular complications.

Intraretinal Microvascular Abnormalities in Eyes with Advanced Stages of Nonproliferative Diabetic Retinopathy: Comparison Between UWF-FFA, CFP, and OCTA-The RICHARD Study.

This study aimed to evaluate intraretinal microvascular abnormalities (IRMA) in eyes with advanced nonproliferative diabetic retinopathy (NPDR) using multimodal approach in co-located areas focusing on central retina (up to 50°) and to look at possible correlations between IRMA and other structural changes, like ischemia and presence of microaneurysms. The RICHARD study (NCT05112445) included 60 eyes from 60 patients with type2 diabetes with moderate-severe NPDR, diabetic retinopathy severity levels 43, 47, and 53 (DRSS). IRMA were defined as capillary tortuosity covering a minimum circular area of 300µm (calculated to correspond to the Early Treatment Diabetic Retinopathy Study standard photo 8A) and were identified using multimodal imaging with distinct fields of view (FoV): color fundus photography (CFP) using a Topcon TRC-50DX camera (Topcon Medical Systems, Japan), Optos California ultra wide field fundus fluorescein angiography (UWF-FFA) (Optos plc, UK), and swept-source optical coherence tomography angiography (SS-OCTA) (PLEX® Elite 9000, ZEISS, USA). Different areas of the retina were examined: central macula (up to 20°) and posterior pole (between 20° and 50°). Multimodal imaging was used to identify IRMA in co-located areas (FoV < 50°) including UWF-FFA, CFP, and SS-OCTA. In eyes with DRSS levels 47 and 53, IRMA were identified in both areas of the retina, while in eyes with DRSS level 43, IRMA were detected only outside of the central macula (FoV > 20°). Our results show that when evaluating the presence of IRMA (FoV < 50°), UWF-FFA detected 203 IRMA, SS-OCTA detected 133 IRMA, and CFP detected 104 IRMA. Our results also show that the presence of IRMA was positively associated with presence of microaneurysms. Identification of IRMA in eyes with advanced NPDR is better achieved by UWF-FFA than CFP and SS-OCTA. A statistically significant correlation was found between the presence of IRMA and the increase in number of microaneurysms. ClinicalTrials.gov, identifier NCT05112445.

Genetically mimicked effects of thyroid dysfunction on diabetic retinopathy risk: a 2-sample univariable and multivariable Mendelian randomization study.

Thyroid dysfunction exhibits a heightened prevalence among people with diabetes compared to those without diabetes. Furthermore, TD emerges as a notable correlated risk factor for the onset of diabetic retinopathy. Using data from the FinnGen database (R9), we investigated the causal relationship between thyroid dysfunction (TD) and four stages of diabetic retinopathy (DR). A two-sample univariable Mendelian randomization (UVMR) approach was employed to estimate the total causal effect of TD on four stages of DR, while multivariable Mendelian randomization (MVMR) was used to assess the direct causal effect. The meta-analysis was conducted to summarize the collective effect of TD on four stages of DR. The inverse variance weighted (IVW) method was the primary approach for Mendelian randomization analysis, with heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analyses performed to validate the robustness of the findings. In UVMR analysis, thyrotoxicosis (TOS) was significantly associated with an increased risk of diabetic retinopathy across four stages (OR, 1.10-1.19; P<0.025). However, MVMR analysis, after adjusting for Graves' disease (GD) and/or rheumatoid arthritis (RA), revealed no significant association between TOS and the four stages of diabetic retinopathy. The Meta-analysis demonstrated the collective effect of TOS on diabetic retinopathy across all stages [OR=1.11; 95% CI (1.08-1.15); P<0.01]. In UVMR analysis, the estimates for hypothyroidism (HPT) and GD were similar to those for TOS. In the MVMR analysis, after adjusting for RA, the significant effect of HPT on DR and non-proliferative diabetic retinopathy (NPDR) remained. Additionally, MVMR analysis suggested that the estimates for GD on DR were not affected by TOS, except for GD-proliferative diabetic retinopathy (PDR). However, no significant correlation persisted after adjusting for RA, including for GD-PDR. Our study demonstrated a significant association between thyroid dysfunction TD and DR, with the relationship being particularly pronounced in HPT-DR.

Tactics and results of glaucoma surgical treatment at various stages of retinopathy of prematurity

Tactics and results of glaucoma surgical treatment at various stages of retinopathy of prematurity

Cystatin C: its correlation with some markers of immune system, inflammation, and its role in progression of diabetic retinopathy in type 2 diabetes

Aim: To study the correlations between Cystatin C (Cys-C) level and values of the markers of immune system and inflammation, and clinical manifestations of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM).Material and Methods. 3 groups of patients with type 2 diabetes and different stages of diabetic retinopathy were formed (21 people in each). Group I – with nonproliferative diabetic retinopathy (NPDR), Group II – with pre-proliferative diabetic retinopathy (PPDR), Group III – with proliferative diabetic retinopathy (PDR). The comparison group included patients with type 2 diabetes without vascular complications. Clinical study included: visometry, tonometry, assessing critical flicker fusion frequency, biomicroscopy of the anterior segment of the eye, ophthalmoscopy, biomicroscopy and ultrasound of the retina, crystalline lens, vitreous body, photographic recording of the fundus, optical coherence tomography. The content of Cystatin C (Cys-C), soluble forms of molecules B7.2 (CD86), 4-1BB, CTLA-4, Tim-3, LAG-3, PD-1, PD-L1, Galectin-9, proteins sICAM-1, SAA, NGAL and enzymes (MPO, MMP-2, MMP-9) was examined in the blood serum with the use of multiplex analysis.Results. As DR progresses, the level of Cys-C increases and becomes higher than in individuals with diabetes: with NPDR higher by 94.1% (p &lt; 0.001), with PPDR – higher by 293.6% (p &lt; 0.001). In individuals with PDR, the concentration of Cys-C is maximum. With DR, the amount of PD-1, PD-1L, NGAL, ICAM-1, MMP-9, and MPO increases in the blood serum; as the severity of DR worsens, the levels of ICAM-1, MPO, and MMP-9 increase. Direct correlations were found between the Cys-C values, on the one hand, and the values of some studied indicators, on the other.Conclusions. In type 2 diabetes and DR, the amount of Cys-C in the blood serum increases relative to individuals with diabetes without microangiopathy; in groups with worsening severity of ophthalmopathy, an increase in Cys-C concentration was recorded with a statistically significant difference between the groups. In groups with DR, the level of ICAM-1, MMP-9, and MPO increases with increasing severity. Moderate direct correlations were found between the amount of Cys-C on the one hand and PD-1, PD-L1, as well as the noticeable ones with the values of ICAM-1, NGAL, MMP-9, MPO on the other. A direct noticeable correlation was revealed between the level of Cys-C and the values of the fundus scale.

Diabetic Retinopathy Diagnosis based on Convolutional Neural Network in the Russian Population: A Multicenter Prospective Study.

Diabetic retinopathy is the most common complication of diabetes mellitus and is one of the leading causes of vision impairment globally, which is also relevant for the Russian Federation. To evaluate the diagnostic efficiency of a convolutional neural network trained for the detection of diabetic retinopathy and estimation of its severity in fundus images of the Russian population. In this cross-sectional multicenter study, the training data set was obtained from an open source and relabeled by a group of independent retina specialists; the sample size was 60,000 eyes. The test sample was recruited prospectively, 1186 fundus photographs of 593 patients were collected. The reference standard was the result of independent grading of the diabetic retinopathy stage by ophthalmologists. Sensitivity and specificity were 95.0% (95% CI; 90.8-96.4) and 96.8% (95% CI; 95.5- 99.0), respectively; positive predictive value - 98.8% (95% CI; 97.6-99.2); negative predictive value - 87.1% (95% CI, 83.4-96.5); accuracy - 95.9% (95% CI; 93.3-97.1); Kappa score - 0.887 (95% CI; 0.839-0.946); F1score - 0.909 (95% CI; 0.870-0.957); area under the ROC-curve - 95.9% (95% CI; 93.3-97.1). There was no statistically significant difference in diagnostic accuracy between the group with isolated diabetic retinopathy and those with hypertensive retinopathy as a concomitant diagnosis. The method for diagnosing DR presented in this article has shown its high accuracy, which is consistent with the existing world analogues, however, this method should prove its clinical efficiency in large multicenter multinational controlled randomized studies, in which the reference diagnostic method would be unified and less subjective than an ophthalmologist.

A COMPARATIVE STUDY OF PRE-CORNEAL TEAR FILM BETWEEN DIABETICS AND NON-DIABETICSUSING OCULAR SURFACE DISEASE INDEX

Purpose: To determine distinctive characteristics of pre-corneal tear film in eyes of diabetics and compare them with non-diabetics. Design: Hospitalbasedobservationalcross-sectional study. Methods: The study was done in thedepartmentofophthalmology from July2022-December2023. Patients presenting to outpatient department of ophthalmology who were of age&gt;45 years, have a history of diabetes for more than three years and those without diabetes as control groups were chosen.300patients weretaken forthestudyand dividedinto two groups(150 diabetics and 150 non-diabetics). Sample size was decided based on a convenient sampling method.Ocular surface disease index(OSDI) questionnaire was used to assess symptoms and signs.Corneal sensitivity test, Tear film breakup time(TBUT) and Schirmer tests were done. The corneal and conjunctival stains were used. Chi-square test was used to examine outcomes. Other tests were applied accordingly. Results: Diabetic patients had poorer OSDI scores compared to Non-diabetic patients(p 0.001*). Patients with diabetes had reduced corneal sensitivity(p&lt;0.05*). Schirmer II and TBUT values were significantly prolonged in Diabetics compared to Non-diabetcs(p&lt;0.05*). Duration of diabetes significantly increased the severity of dry eye. Dry eye was more prevalent in diabetic retinopathy patients(p=0.02*). Strong association was found between HbA1C and severity of diabetic retinopathy with P&lt;0.05*. Conclusion:The duration of diabetes and stage of retinopathy are closely linked to the occurrence and severity of tear film dysfunction. Early detection and treatment are vital for preventing dry eye syndrome and its potential progression to vision-threatening complications, through simple non-invasive methods.

Interconnections between diabetic corneal neuropathy and diabetic retinopathy: diagnostic and therapeutic implications.

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus. Diabetic corneal neuropathy refers to the progressive damage of corneal nerves. Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature. However, growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit, which includes both the retinal vascular structures and neural tissues. Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening. However, diabetic corneal neuropathy is commonly overlooked and underdiagnosed, leading to severe ocular surface impairment. Several studies have found that these two conditions tend to occur together, and they share similarities in their pathogenesis pathways, being triggered by a status of chronic hyperglycemia. This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy, whether diabetic corneal neuropathy precedes diabetic retinopathy, as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy. We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

Resveratrol Protects Müller Cells Against Ferroptosis in the Early Stage of Diabetic Retinopathy by Regulating the Nrf2/GPx4/PTGS2 Pathway.

The aim of this study was to investigate the anti-ferroptotic effect of resveratrol (RSV) on retinal Müller cells (RMCs) in the early stages of diabetic retinopathy (DR) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPx4)/prostaglandin-endoperoxide synthase 2 (PTGS2). The retina was obtained from normal and diabetic Sprague-Dawley rats or wild-type and Nrf2 knockout (KO) diabetic mice, with or without RSV (10mg/kg/d) treatment for 12weeks. RMCs transfected with or without SiNrf2 were cultured with high glucose and RSV (20mM). The retinal neurofunctional changes were measured by electroretinogram (ERG). The retinal inner nuclear layer cell mitochondrial morphological changes were detected by transmission electron microscopy. The cell viabilities were measured by cell counting kit-8 (CCK-8) assay. The levels of Fe2+, malonic dialdehyde (MDA), and glutathione (GSH) were measured by colorimetric method. The expression of Nrf2, GPx4, and PTGS2 was detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunocytochemistry. In vivo, RSV inhibited retinal neurofunctional changes and mitochondrial morphological changes; decreased Fe2+, MDA, and PTGS2; and increased GSH, Nrf2, and GPx4 in retina of DM rats. In vitro, RSV decreased MDA and PTGS2 and increased cell viability, GSH, Nrf2, and GPx4. In vivo and vitro, the role of Nrf2-regulated signaling pathway in anti-ferroptosis by RSV was further confirmed using Nrf2 KO mice and pre-transfected SiNrf2 in RMCs. These findings indicated that RSV is a potential therapeutic option for DR and that Nrf2/GPx4/PTGS2 plays a role in the anti-ferroptosis mechanism of RSV on RMCs.

Evaluating the performance of a non-uniform squash function in Capsule networks for early diabetic retinopathy detection using fundus image analysis

Diabetic retinopathy, known as one of the most crucial neurovascular barriers to diabetes, has affected the retina, leading to a potential risk of blindness. The harm is not isolated to personal health, with negative effects felt at the economic and social level in entire communities. The consequences of vision loss secondary to diabetic retinopathy on quality of life, independent living, and employment can be significant. It is necessary to adopt a comprehensive approach for effective management of underlying diabetes, which includes early detection, timely intervention, supportive care, and management of comorbid conditions. Critical to this is a precise classification of its stages for disease analysis. A manual diagnosis, on the other hand, requires qualified individuals to recognize the subtle nuances of the condition, making it a lengthy process. This study aims to develop a computer-assisted system for analyzing retinal fundus images to identify and classify different stages of diabetic retinopathy. A dataset of eye fundus images was used by the proposed network to classify the presence and severity of blindness and its stages. The proposed model uses a non-uniform squash function in capsule neural networks. The motive behind employing a non-uniform squash function was to encourage the model to allocate greater attention and stability to intricate images throughout the training phase. The proposed model's efficiency is assessed meticulously with pre-trained CNN methods like InceptionV3, VGG16, VGG19, and Xception. The proposed capsule network model has been revamped to address the shortcomings of prior research with care. The method stands out with an impressive 99.84 % training accuracy and 98.68 % validation accuracy. Diabetic retinopathy, though rare in occurrence, poses significant challenges due to the high cost of diagnosis, rendering it inaccessible to rural and remote communities with limited access to tests and check-ups.