Stroke incidence increases with diabetic retinopathy severity and macular edema in type 1 diabetes.

BACKGROUND: As the retina is suggested to mirror the brain, we hypothesized that diabetic retinopathy and macular edema are indicative of stroke risk in type 1 diabetes and sought to assess this association in individuals with type 1 diabetes. METHODS: We included 1,268 adult FinnDiane Study participants with type 1 diabetes (age 38.7 ± 11.8 years, 51.7% men vs. 48.3% women, and 31.5% had diabetic kidney disease), data on baseline diabetic retinopathy severity, and first stroke during our observational follow-up. Retinopathy was graded by the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and macular edema as clinically significant (CSME) or not. Strokes identified from registries were confirmed from medical files. Adjusted hazard ratios (HR) for stroke by retinopathy severity and CSME were calculated by Cox models adjusted for clinical confounders, including diabetic kidney disease. RESULTS: During median 18.0 (14.1-19.3) follow-up years, 130 strokes (96 ischemic, 34 hemorrhagic) occurred. With no-very mild (ETDRS 10-20) retinopathy as reference, the adjusted HR for stroke was 1.79 (95%CI 1.02-3.15) in non-proliferative (ETDRS 35-53), and 1.69 (1.02-2.82) in proliferative (ETDRS 61-85) retinopathy. Corresponding adjusted HR for ischemic stroke was 1.68 (0.91-3.10) in non-proliferative and 1.35 (0.77-2.36) in proliferative retinopathy. The adjusted HR for hemorrhagic stroke was 2.84 (0.66-12.28) in non-proliferative and 4.31 (1.16-16.10) in proliferative retinopathy. CSME did not increase HR for any stroke type after adjustment for clinical confounders (data not shown). CONCLUSIONS: Stroke incidence increases with the severity of diabetic retinopathy independently of comorbid conditions, including diabetic kidney disease.

[Evaluation of the management and follow-up of diabetic patients in the prevention of diabetic retinopathy]. / Evaluación del manejo y seguimiento de los pacientes diabéticos en la prevención de la retinopatía diabética.

OBJECTIVE: Diabetes mellitus is a chronic disease with high morbidity and mortality, affecting 537 million adults worldwide. Spain is the second European country in prevalence, with 14.8% in the population aged twenty/seventy-nine years; with 11.6 cases per 1,000 people/year. Diabetic retinopathy (DR) is the fifth cause of vision loss worldwide and the seventh cause of blindness/visual impairment among members of the National Organization of the Blind in Spain (ONCE). Early detection of DR prevents blindness in diabetics and is conditioned by glycosylated hemoglobin. The aim of this paper was to analyze the management of diabetic patients in Aljarafe region (Seville) and identify opportunities for improvement in the coordination of their follow-up between the Primary Care physician and the ophthalmologist. METHODS: A retrospective observational study (2016-2019) was carried out, with patients registered in the diabetic census of the twenty-eight municipalities of Aljarafe. The primary care and hospital health history, and telemedicine program were consulted. About statistical analysis, for qualitative variables, totals and percentages were calculated; for quantitative variables, mean and standard deviation (if normally distributed) and median and quartiles (if non-normally distributed). RESULTS: There were 17,175 diabetics registered in Aljarafe (5.7% of the population); 14,440 patients (84.1%) had some determination of hemoglobin during the period, 9,228 (63.9%) had all of them in the appropriate range. Fundoscopic control was performed on 12,040 diabetics (70.1%), and of those who did not, 346 (10.6%) had all of them out of range. There were 1,878 (10.9%) patients without fundoscopic or metabolic control, 1,019 (54.3%) were women, 1,219 (64.9%) were under sixty-five years of age, 1,019 (54.3%) had severe comorbidity. CONCLUSIONS: Most patients have adequate screening, and more than half have determinations within range. However, a significant percentage with no glycated hemoglobin within range lack fundoscopic control, and another smaller group lack fundoscopic or metabolic control, with inter-municipal variability. We propose to improve communication channels between levels.

OBJECTIVE: La diabetes mellitus es una enfermedad crónica con alta morbimortalidad que afecta a 537 millones de adultos en el mundo. España es el segundo país europeo en prevalencia, con un 14,8% en población de veinte-setenta y nueve años, con 11,6 casos por cada 1.000 personas/año. La retinopatía diabética (RD) es la quinta causa de pérdida de visión a nivel mundial y la séptima causa de ceguera/discapacidad visual entre afiliados a la Organización Nacional de Ciegos de España (ONCE). La detección precoz de RD previene la ceguera en diabéticos y está condicionada por la hemoglobina glicosilada. El objetivo de este trabajo fue analizar el manejo de los pacientes diabéticos en la comarca del Aljarafe (Sevilla) e identificar oportunidades de mejora en la coordinación de su seguimiento entre el médico de Atención Primaria y el médico oftalmólogo. METHODS: Se realizó un estudio observacional retrospectivo (2016-2019) con los pacientes registrados en el censo de diabéticos de los veintiocho municipios del Aljarafe. Se consultó la historia de salud de Atención Primaria y Hospital, así como el programa de Telemedicina. En cuanto al análisis estadístico, para variables cualitativas se calcularon totales y porcentajes; para variables cuantitativas, media y distribución estándar (si distribución normal), y la mediana y cuartiles (distribución no normal). RESULTS: Se registraron 17.175 diabéticos en el Aljarafe (5,7% de población); 14.440 pacientes (84,1%) tenían alguna determinación de hemoglobina durante el periodo, 9.228 (63,9%) las tenían todas en rango adecuado. Tenían control fundoscópico 12.040 diabéticos (70,1%), y de los que no, 346 (10,6%) tenían todas fuera de rango. Hubo 1.878 (10,9%) pacientes sin control fundoscópico ni metabólico, 1.019 (54,3%) eran mujeres, 1.219 (64,9%) menores de sesenta y cinco años, 1.019 (54,3%) con comorbilidad grave. CONCLUSIONS: La mayoría de los pacientes presentan un cribado adecuado y, más de la mitad, determinaciones en rango. Sin embargo, un porcentaje relevante con ninguna hemoglobina glicosilada en rango carecen de control fundoscópico, y otro grupo menor está sin control fundoscópico ni metabólico, con variabilidad intermunicipios. Planteamos mejorar los circuitos de comunicación entre niveles.

Artificial intelligence-based prediction of diabetic retinopathy evolution (EviRed): protocol for a prospective cohort.

INTRODUCTION: An important obstacle in the fight against diabetic retinopathy (DR) is the use of a classification system based on old imaging techniques and insufficient data to accurately predict its evolution. New imaging techniques generate new valuable data, but we lack an adapted classification based on these data. The main objective of the Evaluation Intelligente de la Rétinopathie Diabétique, Intelligent evaluation of DR (EviRed) project is to develop and validate a system assisting the ophthalmologist in decision-making during DR follow-up by improving the prediction of its evolution. METHODS AND ANALYSIS: A cohort of up to 5000 patients with diabetes will be recruited from 18 diabetology departments and 14 ophthalmology departments, in public or private hospitals in France and followed for an average of 2 years. Each year, systemic health data as well as ophthalmological data will be collected. Both eyes will be imaged by using different imaging modalities including widefield photography, optical coherence tomography (OCT) and OCT-angiography. The EviRed cohort will be divided into two groups: one group will be randomly selected in each stratum during the inclusion period to be representative of the general diabetic population. Their data will be used for validating the algorithms (validation cohort). The data for the remaining patients (training cohort) will be used to train the algorithms. ETHICS AND DISSEMINATION: The study protocol was approved by the French South-West and Overseas Ethics Committee 4 on 28 August 2020 (CPP2020-07-060b/2020-A01725-34/20.06.16.41433). Prior to the start of the study, each patient will provide a written informed consent documenting his or her agreement to participate in the clinical trial. Results of this research will be disseminated in peer-reviewed publications and conference presentations. The database will also be available for further study or development that could benefit patients. TRIAL REGISTRATION NUMBER: NCT04624737.

Association of the systemic immuno-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio with diabetic microvascular complications.

Background: The systemic immuno-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are widely used and have been shown to be predictive indicators of various diseases. Diabetic nephropathy (DN), retinopathy (DR), and peripheral neuropathy (DPN) are the most prominent and common microvascular complications, which have seriously negative impacts on patients, families, and society. Exploring the associations with these three indicators and diabetic microvascular complications are the main purpose. Methods: There were 1058 individuals with type 2 diabetes mellitus (T2DM) in this retrospective cross-sectional study. SII, NLR, and PLR were calculated. The diseases were diagnosed by endocrinologists. Logistic regression and subgroup analysis were applied to evaluate the association between SII, NLP, and PLR and diabetic microvascular complications. Results: SII, NLR, and PLR were significantly associated with the risk of DN [odds ratios (ORs): 1.52, 1.71, and 1.60, respectively] and DR [ORs: 1.57, 1.79, and 1.55, respectively] by multivariate logistic regression. When NLR ≥2.66, the OR was significantly higher for the risk of DPN (OR: 1.985, 95% confidence interval: 1.29-3.05). Subgroup analysis showed no significant positive associations across different demographics and comorbidities, including sex, age, hypertension, HbA1c (glycated hemoglobin), and dyslipidemia. Conclusion: This study found a positive relationship between NLR and DN, DR, and DPN. In contrast, SII and PLR were found to be only associated with DN and DR. Therefore, for the diagnosis of diabetic microvascular complications, SII, NLR and PLR are highly valuable.

Short Term Effect of Pre-Operative Anti-VEGF on Angiogenic and Fibrotic Profile of Fibrovascular Membranes of Proliferative Diabetic Retinopathy.

Purpose: Adjuvant, pre-operative intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have been used to reduce peri-operative bleeding in eyes undergoing pars-plana vitrectomy for complications of proliferative diabetic retinopathy (PDR). To address the concern over their potential off-target effects of progressive fibrous contraction, we sought to dissect the transcriptional changes in the surgically extracted fibrovascular membranes (FVMs). Methods: We analyzed surgically extracted FVMs from 10 eyes: 4 eyes pretreated with intravitreal bevacizumab (IVB) and 6 untreated eyes. FVMs were digested into single cells, mRNA was extracted from endothelial cell-enriched (microbead selection with CD31) and non-endothelial cell compartments, followed by RT-qPCR quantification. We then compared the relative expression of genes involved in angiogenesis, endothelial cell integrity, and myofibroblastic processes between treated and untreated FVMs. Results: Endothelial cells from IVB pretreated FVMs showed significant reduction of VEGFA, VEGF receptors (FLT1 and KDR), and angiopoietin 2 expression as well as increased vascular endothelial cadherin and endothelin, suggesting reduced angiogenesis and enhanced vascular integrity. The non-endothelial cell fraction showed decreased expression of VEGFA and fibronectin, without significant difference in the expression of other profibrotic factors. Conclusions: Our findings confirm that adjuvant pre-operative IVB decreased fibronectin and increase endothelin-1 expression without affecting other profibrotic gene expression, uncovering an important interaction between IVB and endothelin-1 that deserves further study.

Attention-based deep learning framework for automatic fundus image processing to aid in diabetic retinopathy grading.

BACKGROUND AND OBJECTIVE: Early detection and grading of Diabetic Retinopathy (DR) is essential to determine an adequate treatment and prevent severe vision loss. However, the manual analysis of fundus images is time consuming and DR screening programs are challenged by the availability of human graders. Current automatic approaches for DR grading attempt the joint detection of all signs at the same time. However, the classification can be optimized if red lesions and bright lesions are independently processed since the task gets divided and simplified. Furthermore, clinicians would greatly benefit from explainable artificial intelligence (XAI) to support the automatic model predictions, especially when the type of lesion is specified. As a novelty, we propose an end-to-end deep learning framework for automatic DR grading (5 severity degrees) based on separating the attention of the dark structures from the bright structures of the retina. As the main contribution, this approach allowed us to generate independent interpretable attention maps for red lesions, such as microaneurysms and hemorrhages, and bright lesions, such as hard exudates, while using image-level labels only. METHODS: Our approach is based on a novel attention mechanism which focuses separately on the dark and the bright structures of the retina by performing a previous image decomposition. This mechanism can be seen as a XAI approach which generates independent attention maps for red lesions and bright lesions. The framework includes an image quality assessment stage and deep learning-related techniques, such as data augmentation, transfer learning and fine-tuning. We used the architecture Xception as a feature extractor and the focal loss function to deal with data imbalance. RESULTS: The Kaggle DR detection dataset was used for method development and validation. The proposed approach achieved 83.7 % accuracy and a Quadratic Weighted Kappa of 0.78 to classify DR among 5 severity degrees, which outperforms several state-of-the-art approaches. Nevertheless, the main result of this work is the generated attention maps, which reveal the pathological regions on the image distinguishing the red lesions and the bright lesions. These maps provide explainability to the model predictions. CONCLUSIONS: Our results suggest that our framework is effective to automatically grade DR. The separate attention approach has proven useful for optimizing the classification. On top of that, the obtained attention maps facilitate visual interpretation for clinicians. Therefore, the proposed method could be a diagnostic aid for the early detection and grading of DR.

Management after cataract surgery for patients with diabetic retinopathy: a systematic review and meta-analysis.

PURPOSE: To evaluate the safety and effectiveness of various treatment modalities in patients with diabetic retinopathy (DR) who underwent cataract surgery. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted using the PubMed, Embase, Cochrane Library, and CNKI databases up to December 22, 2021. The safety and efficacy of treatment modalities were assessed using the risk ratio (RR) to compare the progression of DR and the mean difference to evaluate the best corrected visual acuity (BCVA) and macular thickness (MT). RESULTS: The meta-analysis of the RCTs revealed that anti-VEGF (anti-vascular endothelial growth factor) drugs significantly reduced the progression of DR [RR: 0.37 (95%CI 0.19, 0.70), P = 0.002] and improved BCVA [mean difference = - 0.06 (- 0.12, - 0.01), P = 0.03] in patients with pre-existing DR who underwent cataract surgery. Steroid drugs also showed a significant reduction in macular thickness [mean difference = - 55.63 (- 90.73, - 20.53), I2 = 56%, P = 0.002] in DR patients two weeks after cataract surgery compared to the control group. The safety profiles of different management options did not differ significantly. CONCLUSION: The present meta-analysis suggests that anti-VEGF drugs can effectively slow down the progression of diabetic retinopathy, improve BCVA, and reduce MT in DR patients who underwent cataract surgery. Steroid drugs also show promise in reducing MT. However, further studies with larger sample sizes are required to compare the efficacy and safety of different management options in a multi-center clinical setting.

Assessment of the severity of diabetic polyneuropathy aids in predicting the risk of developing diabetic complications in patients with untreated diabetes.

This study aimed to determine the efficacy of assessing the severity of diabetic polyneuropathy (DPN) in patients with untreated diabetes. Seventy-two patients with untreated type 2 diabetes who were hospitalized for glycemic control were enrolled and divided into the following two groups: patients who had no prior diagnosis and patients who were unattended or had discontinued treatment. Electrophysiological criteria consistent with Baba's classification were used to diagnose and assess the severity of DPN. The patients were divided into three subgroups: no DPN (stage 0), mild DPN (stage 1), and moderate or more-severe DPN (stages 2-4). Intergroup comparisons were performed for the clinical characteristics and the results of the nerve conduction studies. Twenty-two (30%), 25 (35%), and 25 (35%) patients were categorized into the no DPN, mild DPN, and moderate or more-severe DPN subgroups, respectively. The number of patients who were unattended or had discontinued treatment in the moderate or more-severe DPN subgroup was significantly higher than that in the no DPN subgroup. The patients in the moderate or more-severe DPN subgroup had an increased risk of developing diabetic retinopathy and nephropathy, with odds ratios of 19.5 and 11.0 for advanced stages of retinopathy and nephropathy, respectively. Thus, the assessment of the severity of DPN could aid in the prediction of the risk of developing diabetic complications in patients with untreated diabetes.

Diabetes in spotlight: current knowledge and perspectives of photobiomodulation utilization.

Introduction: Diabetes is a global health concern characterized by chronic hyperglycemia resulting from insulinopenia and/or insulin resistance. The rising prevalence of diabetes and its associated complications (ulcers, periodontitis, healing of bone defect, neuropathy, retinopathy, cardiopathy and nephropathy) necessitate innovative therapeutic approaches. Photobiomodulation (PBM), involves exposing tissues and cells to low-energy light radiation, leading to biological effects, largely via mitochondrial activation. Methods: This review evaluates preclinical and clinical studies exploring the potential of PBM in diabetes and its complications, as well all clinical trials, both planned and completed, available on ClinicalTrials database. Results: This review highlights the variability in PBM parameters across studies, hindering consensus on optimal protocols. Standardization of treatment parameters and rigorous clinical trials are needed to unlock PBM's full therapeutic potential. 87 clinical trials were identified that investigated PBM in diabetes mellitus (with 5,837 patients planned to be treated with PBM). Clinical trials assessing PBM effects on diabetic neuropathy revealed pain reduction and potential quality of life improvement. Studies focusing on wound healing indicated encouraging results, with PBM enhancing angiogenesis, fibroblast proliferation, and collagen density. PBM's impact on diabetic retinopathy remains inconclusive however, requiring further investigation. In glycemic control, PBM exhibits positive effects on metabolic parameters, including glucose tolerance and insulin resistance. Conclusion: Clinical studies have reported PBM-induced reductions in fasting and postprandial glycemia without an increased hypoglycemic risk. This impact of PBM may be related to its effects on the beta cells and islets in the pancreas. Notwithstanding challenges, PBM emerges as a promising adjunctive therapy for managing diabetic neuropathy, wound healing, and glycemic control. Further investigation into its impact on diabetic retinopathy and muscle recovery is warranted.

Transcriptional patterns of human retinal pigment epithelial cells under protracted high glucose.

BACKGROUND: The retinal pigment epithelium (RPE) is essential for retinal homeostasis. Comprehensively exploring the transcriptional patterns of diabetic human RPE promotes the understanding of diabetic retinopathy (DR). METHODS AND RESULTS: A total of 4125 differentially expressed genes (DEGs) were screened out from the human primary RPE cells subjected to prolonged high glucose (HG). The subsequent bioinformatics analysis is divided into 3 steps. In Step 1, 21 genes were revealed by intersecting the enriched genes from the KEGG, WIKI, and Reactome databases. In Step 2, WGCNA was applied and intersected with the DEGs. Further intersection based on the enrichments with the GO biological processes, GO cellular components, and GO molecular functions databases screened out 12 candidate genes. In Step 3, 13 genes were found to be simultaneously up-regulated in the DEGs and a GEO dataset involving human diabetic retinal tissues. VEGFA and ERN1 were the 2 starred genes finally screened out by overlapping the 3 Steps. CONCLUSION: In this study, multiple genes were identified as crucial in the pathological process of RPE under protracted HG, providing potential candidates for future researches on DR. The current study highlights the importance of RPE in DR pathogenesis.

A case report: co-occurrence of probable Vogt-Koyanagi-Harada disease and diabetic retinopathy.

BACKGROUND: Bilateral retinal detachment and choroidal detachment in a patient are rare occurrences. The presence of bilateral diabetic retinopathy (DR) in such a case is even rarer and complicates the condition. CASE PRESENTATION: In this study, we document a case of unconventional VKH. Manifestations in this patient included intense peripheral retinal detachment and choroidal detachment, along with vitreous opacities akin to cotton wool spots, concurrent with DR. The diagnosis was considered as probable VKH with DR. Treatment according to VKH protocols, including high-dose corticosteroids, yielded positive results. CONCLUSIONS: VKH can co-occurrence with DR. VKH manifestations vary, and early, aggressive, and long-term treatment is essential. The complexity of treatment increases with concurrent DR, necessitating the use of immunosuppressants.

Prevalence and incidence of diabetic retinopathy in patients with diabetes of Latin America and the Caribbean: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to assess the prevalence and incidence of diabetic retinopathy in patients with diabetes of Latin America and the Caribbean. METHODS: We searched Web of Science (WoS)/Core Collection, WoS/MEDLINE, WoS/Scielo, Scopus, PubMed/Medline and Embase databases until January 16, 2023. We meta-analyzed prevalences according to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). RESULTS: Forty-three prevalence studies (47 585 participants) and one incidence study (436 participants) were included. The overall prevalence of retinopathy in patients with T1DM was 40.6% (95% CI: 34.7 to 46.6; I2: 92.1%) and in T2DM was 37.3% (95% CI: 31.0 to 43.8; I2: 97.7), but the evidence is very uncertain (very low certainty of evidence). In meta-regression, we found that age (T1DM) and time in diabetes (T2DM) were factors associated with the prevalence. On the other hand, one study found a cumulative incidence of diabetic retinopathy of 39.6% at 9 years of follow-up. CONCLUSIONS: Two out of five patients with T1DM or T2DM may present diabetic retinopathy in Latin America and the Caribbean, but the evidence is very uncertain. This is a major public health problem, and policies and strategies for early detection and opportunely treatment should be proposed.

RAAS in diabetic retinopathy: mechanisms and therapies.

Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.

Aflibercept Off-Target Effects in Diabetic Macular Edema: An In Silico Modeling Approach.

Intravitreal aflibercept injection (IAI) is a treatment for diabetic macular edema (DME), but its mechanism of action (MoA) has not been completely elucidated. Here, we aimed to explore IAI's MoA and its multi-target nature in DME pathophysiology with an in silico (computer simulation) disease model. We used the Therapeutic Performance Mapping System (Anaxomics Biotech property) to generate mathematical models based on the available scientific knowledge at the time of the study, describing the relationship between the modulation of vascular endothelial growth factor receptors (VEGFRs) by IAI and DME pathophysiological processes. We also undertook an enrichment analysis to explore the processes modulated by IAI, visualized the effectors' predicted protein activity, and specifically evaluated the role of VEGFR1 pathway inhibition on DME treatment. The models simulated the potential pathophysiology of DME and the likely IAI's MoA by inhibiting VEGFR1 and VEGFR2 signaling. The action of IAI through both signaling pathways modulated the identified pathophysiological processes associated with DME, with the strongest effects in angiogenesis, blood-retinal barrier alteration and permeability, and inflammation. VEGFR1 inhibition was essential to modulate inflammatory protein effectors. Given the role of VEGFR1 signaling on the modulation of inflammatory-related pathways, IAI may offer therapeutic advantages for DME through sustained VEGFR1 pathway inhibition.

Association between the response of intravitreal antivascular endothelial growth factor injection and systemic factors of diabetic macular edema.

BACKGROUND: This study investigated the effects of systemic factors in response to intravitreal injections in patients with macular edema due to non-proliferative diabetic retinopathy (NPDR). METHODS: We retrospectively reviewed the medical records of patients treated with intravitreal injections for macular edema secondary to NPDR between January 2018 and January 2021. The patients were divided into three groups according to the injection response. When patients with diabetic macular edema showed 20µ or more reduction in central retinal thickness compared to baseline, they were classified as responsive group, and if not, they were classified as refractory group. The responsive group was further divided into the complete and incomplete response groups. Patients with complete disappearance of edema at seven months were classified as the complete response group, whereas those in which edema did not disappear were classified as the incomplete response group. The clinical characteristics of each group, including medical history, ophthalmic examination results, and laboratory examination results at the time of diagnosis, were analyzed. RESULTS: Of the 112 eyes (91 patients) that satisfied the inclusion criteria, 89 (77 patients) in the responsive group and 23 (14 patients) in the refractory group were included in the analysis. The responsive group was further divided into the complete (51 eyes) and incomplete (38 eyes) response groups. The refractory group had significantly higher glycated hemoglobin levels and significantly lower estimated glomerular filtration rates than the responsive group (p = 0.026 and p = 0.012, respectively). In the multivariate logistic regression analysis, both factors were found to be significant in predicting the degree of response (all p < 0.05). No factor showed a significant difference between the incomplete and complete response groups(all p > 0.05). CONCLUSIONS: In macular edema caused by NPDR, low glomerular filtration rates and high glycated hemoglobin levels may be used as predictors of poor response to intravitreal injection therapy. In addition to blood glucose control, education should be provided regarding the need for the continuous monitoring of renal function.

Sterile endophthalmitis after intravitreal injection of triamcinolone acetonide: case report and literature review.

Objectives: The first purpose is to present the diagnosis and therapeutic approach in a patient with sterile endophthalmitis associated with triamcinolone acetonide injection. The secondary objective is to assess the incidence of this complication and to summarize the risk factors described in the literature. Case presentation: A 76-year-old male patient presented for painless, unilateral, decreased visual acuity, four days after cataract surgery and simultaneously intravitreal triamcinolone acetonide injection for diabetic macular edema in the right eye. The diagnosis of sterile endophthalmitis was made. Eight days after the presentation, the symptoms subsided, the maximum corrected visual acuity reaching that before the procedures. Discussions: The incidence of sterile endophthalmitis varies in the literature between 0% and 23.8%. Visual prognosis is good, although the pathogenesis is not fully understood. Preservatives in injectable solutions have been suggested, however, there are studies in which inflammation was also present with preservative-free products. The particle size of triamcinolone was analyzed, demonstrating an association between smaller particles and an increased frequency of adverse reactions of this type. History of uveitis, posterior capsule rupture following cataract surgery, and Irvine-Gass syndrome are other associations described. Conclusion: The physiopathological mechanism of sterile endophthalmitis is not fully understood. However, the visual prognosis is good, the final vision being dependent on the underlying pathology.

Evaluation of clinical outcomes of raised intraocular pressure following intravitreal triamcinolone acetonide injection.

Aim: To assess the incidence, risk factors, and treatment outcomes in intravitreal triamcinolone acetonide injection (IVTA) induced intraocular pressure rise and to compare IOP rise in 1-mg and 2-mg IVTA. Materials and methods: Prospective observational study conducted in all eyes receiving IVTA. Any pre-existing glaucoma and patients who received IVTA or dexamethasone implant in the last 6 months were excluded. Results: 9 between 61-70 years of age developed an IOP spike. The mean and standard deviation of age in years was 61.95 ± 8.70. Maximum eyes had ME due to Diabetic Retinopathy (53.3%). All cases of uveitic ME were reported to have an IOP spike. 2 out of 3 high myopic eyes and 1 eye with thyroid abnormality had an IOP spike. High IOP was found in 13 eyes, with more than 25 mm Hg rise in 4 eyes and more than 5 mm Hg rise from baseline IOP in 9 eyes. The mean and standard deviation of time taken for IOP raise (in days) was 46.39 ± 37.68. A total of 38 eyes received 1 mg of IVTA and the rest 22 received 2 mg of IVTA. 23.7% of 1 mg eyes experienced an IOP rise while it was 18.2% in eyes with 2 mg IVTA. The injection was repeated in 12 eyes and 41.7% developed an IOP spike among them. The independent "t" test results showed that there was a significant difference in the mean of IOP (Pre-injection) concerning the IOP rise (P=0.007*). 1 eye had IVTA crystals in the anterior chamber with raised IOP of 30 mm Hg. 1 out of 13 eyes with raised IOP needed 2 AGMs, the other 12 eyes responded well to 1 AGM. Discussion: IVTA is widely used in refractory cases of ME and steroid-induced glaucoma is the most common side effect of IVTA. To the best of our knowledge, there is a lack of literature on prospective studies on IVTA-associated risk factors, patterns of IOP elevation, and treatment outcomes. The pre-injection mean ± SD baseline IOP for uneventful eyes was 12.87±2.65 and the pre-injection mean IOP for eyes with IOP event was 15.23±2.89 (P=0.007*). Conclusion: We proposed that TA is an independent risk factor for post-intravitreal injection IOP spike. IVTA causes a maximum IOP spike at 1 to 2 months and has a protracted course that responds to anti-glaucoma medications. High baseline IOP, a repeated dose of IVTA, the presence of TA crystals in the anterior chamber, and high myopia were associated with significant IOP elevation. Abbreviations: ACD = Anterior chamber depth, AS = Anterior segment, AGM = Anti-glaucoma medications, ARMD = Age-related macular degeneration, BCVA = Best-corrected visual acuity, BRVO = Branch retinal vein occlusion, CCT = Central corneal thickness, CRVO = Central retinal vein occlusion, CME = Cystoid macular edema, CNVM = Choroidal neovascularization membrane, CSME = Clinically significant macular edema, DR = Diabetic retinopathy, ERM = Epiretinal membrane, IOP = Intraocular pressure, IGS = Irvine-Grass syndrome, GAGs = Glycosaminoglycans, IVTA = Intravitreal triamcinolone acetonide injection, ME = Macular edema, NVG = Neovascular glaucoma, OHT = Ocular hypertension, PDS = Pigment dispersion syndrome, PACG = Primary closed angle glaucoma, POAG = Primary open-angle glaucoma, PXF = Pseudoexfoliation, VA = Visual acuity, VEGF = Vascular endothelial growth factors, VH = Vonherick's grading, SD = Standard deviation, TA = Triamcinolone acetonide, TIGR = Trabecular meshwork inducible glucocorticoid response.

Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes.

INTRODUCTION: Diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality. RESEARCH DESIGN AND METHODS: In adults with type 1 diabetes, 49 metabolites previously associated with either DR or DKD were assessed in relation to presence of DSPN. Metabolites overlapping in significance with presence of all three complications were assessed in relation to microvascular burden severity (additive number of complications-ie, presence of DKD±DR±DSPN) using linear regression models. Subsequently, the same metabolites were assessed with progression to endpoints: soft microvascular events (progression in albuminuria grade, ≥30% estimated glomerular filtration rate (eGFR) decline, or any progression in DR grade), hard microvascular events (progression to proliferative DR, chronic kidney failure, or ≥40% eGFR decline), and hard microvascular or macrovascular events (hard microvascular events, cardiovascular events (myocardial infarction, stroke, or arterial interventions), or cardiovascular mortality), using Cox models. All models were adjusted for sex, baseline age, diabetes duration, systolic blood pressure, HbA1c, body mass index, total cholesterol, smoking, and statin treatment. RESULTS: The full cohort investigated consisted of 487 participants. Mean (SD) follow-up was 4.8 (2.9, 5.7) years. Baseline biothesiometry was available in 202 participants, comprising the cross-sectional cohort. Eight metabolites were significantly associated with presence of DR, DKD, and DSPN, and six with additive microvascular burden severity. In the full cohort longitudinal analysis, higher levels of 3,4-dihydroxybutanoic acid (DHBA), 2,4-DHBA, ribonic acid, glycine, and ribitol were associated with development of events in both crude and adjusted models. Adding 3,4-DHBA, ribonic acid, and glycine to a traditional risk factor model improved the discrimination of hard microvascular events. CONCLUSIONS: While prospective studies directly assessing the predictive ability of these markers are needed, our results strengthen the role of clinical metabolomics in relation to risk assessment of diabetic complications in chronic type 1 diabetes.

OCTDL: Optical Coherence Tomography Dataset for Image-Based Deep Learning Methods.

Optical coherence tomography (OCT) is a non-invasive imaging technique with extensive clinical applications in ophthalmology. OCT enables the visualization of the retinal layers, playing a vital role in the early detection and monitoring of retinal diseases. OCT uses the principle of light wave interference to create detailed images of the retinal microstructures, making it a valuable tool for diagnosing ocular conditions. This work presents an open-access OCT dataset (OCTDL) comprising over 2000 OCT images labeled according to disease group and retinal pathology. The dataset consists of OCT records of patients with Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), Epiretinal Membrane (ERM), Retinal Artery Occlusion (RAO), Retinal Vein Occlusion (RVO), and Vitreomacular Interface Disease (VID). The images were acquired with an Optovue Avanti RTVue XR using raster scanning protocols with dynamic scan length and image resolution. Each retinal b-scan was acquired by centering on the fovea and interpreted and cataloged by an experienced retinal specialist. In this work, we applied Deep Learning classification techniques to this new open-access dataset.

Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy.

BACKGROUND: Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME. METHODS: A retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated. RESULTS: The logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson's R = 0.44, p < 0.001). CONCLUSION: The developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model's robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.