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.

Risk evaluation for diabetic retinopathy in Chinese renalbiopsied type 2 diabetes mellitus patients

AIM:To investigate diabetic retinopathy(DR)prevalence in Chinese renal-biopsied type 2 diabetes mellitus(T2DM)patients with kidney dysfunction,and to further evaluate its relationship with diabetic nephropathy(DN)incidence and the risk factors for DR development in this population.METHODS:A total of 84 renal-biopsied T2DM patients were included.Fundus and imaging examinations were employed for DR diagnosis.Demographic information and clinical measures along with renal histopathology were analyzed for comparisons between the DR and non-DR groups.Risk factors on DR development were analyzed with multiple logistic regression.RESULTS:DR prevalence was 50%in total.The incidences of DN,non-diabetic renal disease(NDRD)and mixed-type pathology were 47.6%,19.0%and 33.3%in the DR group respectively,while 11.9%,83.3%and 4.8%in the non-DR group.Systolic blood pressure,ratio of urinary albumin to creatine ratio,urinary albumin,24-hours urinary protein,the incidence and severity of DN histopathology were found statistically increased in the DR group.Multiple logistic regression analysis showed histopathological DN incidence significantly increased the risk of DR development[odds ratio(OR)=21.664,95%confidential interval(CI)5.588 to 83.991,P<0.001 for DN,and OR=45.475,95%CI 6.949 to 297.611,P<0.001 for mixed-type,respectively,in reference to (NDRD)],wherein DN severity positively correlated.CONCLUSION:Renal histopathological evidence indicates DN incidence and severity increases the risk of DR development in Chinese T2DM patients inexperienced of regular fundus examinations.

Retinal vascular morphological characteristics in diabetic retinopathy: an artificial intelligence study using a transfer learning system to analyze ultra-wide field images

AIM:To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy(DR)and in patients with or without diabetic macular edema(DME).METHODS:The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study.The severity of DR patients was graded as mild,moderate and severe non-proliferative diabetic retinopathy(NPDR)according to the international clinical diabetic retinopathy(ICDR)disease severity scale classification,and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods.The presence of DME was determined by optical coherence tomography(OCT),and differences in vascular morphological characteristics were compared between patients with and without DME.RESULTS:Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99%and a Dice metric of 0.76.Compared with the healthy group,the DR group had smaller vessel angles(33.68±3.01 vs 37.78±1.60),smaller fractal dimension(Df)values(1.33±0.05 vs 1.41±0.03),less vessel density(1.12±0.44 vs 2.09±0.36)and fewer vascular branches(206.1±88.8 vs 396.5±91.3),all P<0.001.As the severity of DR increased,Df values decreased,P=0.031.No significant difference between the DME and non-DME groups were observed in vascular morphological characteristics.CONCLUSION:In this study,an artificial intelligence retinal vessel segmentation system is used with 99%accuracy,thus providing with relatively satisfactory performance in the evaluation of quantitative vascular morphology.DR patients have a tendency of vascular occlusion and dropout.The presence of DME does not compromise the integral retinal vascular pattern.

Construction and validation of a neovascular glaucoma nomogram in patients with diabetic retinopathy after pars plana vitrectomy

BACKGROUND Neovascular glaucoma(NVG)is likely to occur after pars plana vitrectomy(PPV)for diabetic retinopathy(DR)in some patients,thus reducing the expected benefit.Understanding the risk factors for NVG occurrence and building effective risk prediction models are currently required for clinical research.AIM To develop a visual risk profile model to explore factors influencing DR after surgery.METHODS We retrospectively selected 151 patients with DR undergoing PPV.The patients were divided into the NVG(NVG occurrence)and No-NVG(No NVG occurrence)groups according to the occurrence of NVG within 6 months after surgery.Independent risk factors for postoperative NVG were screened by logistic regression.A nomogram prediction model was established using R software,and the model’s prediction accuracy was verified internally and externally,involving the receiver operator characteristic curve and correction curve.RESULTS After importing the data into a logistic regression model,we concluded that a posterior capsular defect,preoperative vascular endothelial growth factor≥302.90 pg/mL,glycosylated hemoglobin≥9.05%,aqueous fluid interleukin 6(IL-6)≥53.27 pg/mL,and aqueous fluid IL-10≥9.11 pg/mL were independent risk factors for postoperative NVG in patients with DR(P<0.05).A nomogram model was established based on the aforementioned independent risk factors,and a computer simulation repeated sampling method was used to internally and externally verify the nomogram model.The area under the curve(AUC),sensitivity,and specificity of the model were 0.962[95%confidence interval(95%CI):0.932-0.991],91.5%,and 82.3%,respectively.The AUC,sensitivity,and specificity of the external validation were 0.878(95%CI:0.746-0.982),66.7%,and 95.7%,respectively.CONCLUSION A nomogram constructed based on the risk factors for postoperative NVG in patients with DR has a high prediction accuracy.This study can help formulate relevant preventive and treatment measures.

Prophylactic Pattern Scanning Laser Retinal Photocoagulation for Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats: Preliminary Experimental Results

Research Background and Purpose: The number of diabetic patients is rapidly increasing, making it crucial to find methods to prevent diabetic retinopathy (DR), a leading cause of blindness. We investigated the effects of prophylactic pattern scanning laser retinal photocoagulation on DR development in Spontaneously Diabetic Torii (SDT) fatty rats as a new prevention approach. Methods: Photocoagulation was applied to the right eyes of 8-week-old Spontaneously Diabetic Torii (SDT) fatty rats, with the left eyes serving as untreated controls. Electroretinography at 9 and 39 weeks of age and pathological examinations, including immunohistochemistry for vascular endothelial growth factor and glial fibrillary acidic protein at 24 and 40 weeks of age, were performed on both eyes. Results: There were no significant differences in amplitude and prolongation of the OP waves between the right and left eyes in SDT fatty rats at 39 weeks of age. Similarly, no significant differences in pathology and immunohistochemistry were observed between the right and left eyes in SDT fatty rats at 24 and 40 weeks of age. Conclusion: Prophylactic pattern scanning retinal laser photocoagulation did not affect the development of diabetic retinopathy in SDT fatty rats.

Diabetic retinopathy:A review on its pathophysiology and novel treatment modalities

Diabetes mellitus(DM)is a chronic metabolic non-communicable disease with the ability to cause serious microvascular and macrovascular complications throughout the body,including in the eye.Diabetic retinopathy(DR),present in onethird of patients with diabetes,is a vision-threatening complication caused by uncontrolled diabetes,which greatly affects the retinal blood vessels and the lightsensitive inner retina,eventually leading to blindness.Several epidemiological studies elucidate that DR can vary by age of onset,duration,types of diabetes,and ethnicity.Recent studies show that the pathogenesis of diabetic retinopathy has spread its roots beyond merely being the result of hyperglycemia.The complexity of its etiopathology and diagnosis makes therapeutic intervention challenging.This review throws light on the pathological processes behind DR,the cascade of events that follow it,as well as the available and emerging treatment options.

Application of non-mydriatic fundus photography-assisted telemedicine in diabetic retinopathy screening

BACKGROUND Early screening and accurate staging of diabetic retinopathy(DR)can reduce blindness risk in type 2 diabetes patients.DR’s complex pathogenesis involves many factors,making ophthalmologist screening alone insufficient for prevention and treatment.Often,endocrinologists are the first to see diabetic patients and thus should screen for retinopathy for early intervention.AIM To explore the efficacy of non-mydriatic fundus photography(NMFP)-enhanced telemedicine in assessing DR and its various stages.METHODS This retrospective study incorporated findings from an analysis of 93 diabetic patients,examining both NMFP-assisted telemedicine and fundus fluorescein angiography(FFA).It focused on assessing the concordance in DR detection between these two methodologies.Additionally,receiver operating characteristic(ROC)curves were generated to determine the optimal sensitivity and specificity of NMFP-assisted telemedicine,using FFA outcomes as the standard benchmark.RESULTS In the context of DR diagnosis and staging,the kappa coefficients for NMFPassisted telemedicine and FFA were recorded at 0.775 and 0.689 respectively,indicating substantial intermethod agreement.Moreover,the NMFP-assisted telemedicine’s predictive accuracy for positive FFA outcomes,as denoted by the area under the ROC curve,was remarkably high at 0.955,within a confidence interval of 0.914 to 0.995 and a statistically significant P-value of less than 0.001.This predictive model exhibited a specificity of 100%,a sensitivity of 90.9%,and a Youden index of 0.909.CONCLUSION NMFP-assisted telemedicine represents a pragmatic,objective,and precise modality for fundus examination,particularly applicable in the context of endocrinology inpatient care and primary healthcare settings for diabetic patients.Its implementation in these scenarios is of paramount significance,enhancing the clinical accuracy in the diagnosis and therapeutic management of DR.This methodology not only streamlines patient evaluation but also contributes substantially to the optimization of clinical outcomes in DR management.

Non-linear relationship between age and subfoveal choroidal thickness in Chinese patients with proliferative diabetic retinopathy

BACKGROUND No study has investigated the change regularity between age and subfoveal choroidal thickness(SFCT)in proliferative diabetic retinopathy(PDR).AIM To investigate the relationship between the SFCT and age in Chinese patients with PDR.METHODS This was a cross-sectional retrospective study.The participants were hospitalized individuals with type 2 diabetes who underwent vitrectomy for PDR.Contralateral eyes that met the criteria were included in the study.All necessary laboratory tests were performed at the time of admission.Central macular thickness(CMT)and SFCT were two quantitative assessments made using enhanced depth imaging optical coherence tomography.CMT was measured automatically and SFCT was measured manually with digital calipers provided by the Heidelberg Eye Explorer software.RESULTS The final analysis included a total of 234 individuals with PDR.The average age was 55.60 years old±10.03 years old,and 57.69%of the population was male.Univariate analysis revealed a significant negative connection between age and SFCT in patients with PDR[β=-2.44,95%confidence interval(95%CI):-3.46 to-1.42;P<0.0001].In the fully adjusted model,the correlation between SFCT and age remained steady(β=-1.68,95%CI:-2.97 to-0.39;P=0.0117).Spline smoothing showed that the relationship between SFCT and age in patients with PDR was non-linear,with an inflection point at 54 years of age.CONCLUSION Our findings suggest that age is a key determinant of choroidal thickness.The non-linear link between SFCT and age in PDR patients should be taken into account.

DeepSVDNet:A Deep Learning-Based Approach for Detecting and Classifying Vision-Threatening Diabetic Retinopathy in Retinal Fundus Images

Artificial Intelligence(AI)is being increasingly used for diagnosing Vision-Threatening Diabetic Retinopathy(VTDR),which is a leading cause of visual impairment and blindness worldwide.However,previous automated VTDR detection methods have mainly relied on manual feature extraction and classification,leading to errors.This paper proposes a novel VTDR detection and classification model that combines different models through majority voting.Our proposed methodology involves preprocessing,data augmentation,feature extraction,and classification stages.We use a hybrid convolutional neural network-singular value decomposition(CNN-SVD)model for feature extraction and selection and an improved SVM-RBF with a Decision Tree(DT)and K-Nearest Neighbor(KNN)for classification.We tested our model on the IDRiD dataset and achieved an accuracy of 98.06%,a sensitivity of 83.67%,and a specificity of 100%for DR detection and evaluation tests,respectively.Our proposed approach outperforms baseline techniques and provides a more robust and accurate method for VTDR detection.

TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes

●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

Diabetic retinopathy identification based on multi-sourcefree domain adaptation

AIM:To address the challenges of data labeling difficulties,data privacy,and necessary large amount of labeled data for deep learning methods in diabetic retinopathy(DR)identification,the aim of this study is to develop a source-free domain adaptation(SFDA)method for efficient and effective DR identification from unlabeled data.METHODS:A multi-SFDA method was proposed for DR identification.This method integrates multiple source models,which are trained from the same source domain,to generate synthetic pseudo labels for the unlabeled target domain.Besides,a softmax-consistence minimization term is utilized to minimize the intra-class distances between the source and target domains and maximize the inter-class distances.Validation is performed using three color fundus photograph datasets(APTOS2019,DDR,and EyePACS).RESULTS:The proposed model was evaluated and provided promising results with respectively 0.8917 and 0.9795 F1-scores on referable and normal/abnormal DR identification tasks.It demonstrated effective DR identification through minimizing intra-class distances and maximizing inter-class distances between source and target domains.CONCLUSION:The multi-SFDA method provides an effective approach to overcome the challenges in DR identification.The method not only addresses difficulties in data labeling and privacy issues,but also reduces the need for large amounts of labeled data required by deep learning methods,making it a practical tool for early detection and preservation of vision in diabetic patients.

Key genes and regulatory networks for diabetic retinopathy based on hypoxia-related genes:a bioinformatics analysis

AIM:To prevent neovascularization in diabetic retinopathy(DR)patients and partially control disease progression.METHODS:Hypoxia-related differentially expressed genes(DEGs)were identified from the GSE60436 and GSE102485 datasets,followed by gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Potential candidate drugs were screened using the CMap database.Subsequently,a protein-protein interaction(PPI)network was constructed to identify hypoxia-related hub genes.A nomogram was generated using the rms R package,and the correlation of hub genes was analyzed using the Hmisc R package.The clinical significance of hub genes was validated by comparing their expression levels between disease and normal groups and constructing receiver operating characteristic curve(ROC)curves.Finally,a hypoxia-related miRNA-transcription factor(TF)-Hub gene network was constructed using the NetworkAnalyst online tool.RESULTS:Totally 48 hypoxia-related DEGs and screened 10 potential candidate drugs with interaction relationships to upregulated hypoxia-related genes were identified,such as ruxolitinib,meprylcaine,and deferiprone.In addition,8 hub genes were also identified:glycogen phosphorylase muscle associated(PYGM),glyceraldehyde-3-phosphate dehydrogenase spermatogenic(GAPDHS),enolase 3(ENO3),aldolase fructose-bisphosphate C(ALDOC),phosphoglucomutase 2(PGM2),enolase 2(ENO2),phosphoglycerate mutase 2(PGAM2),and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3).Based on hub gene predictions,the miRNA-TF-Hub gene network revealed complex interactions between 163 miRNAs,77 TFs,and hub genes.The results of ROC showed that the except for GAPDHS,the area under curve(AUC)values of the other 7 hub genes were greater than 0.758,indicating their favorable diagnostic performance.CONCLUSION:PYGM,GAPDHS,ENO3,ALDOC,PGM2,ENO2,PGAM2,and PFKFB3 are hub genes in DR,and hypoxia-related hub genes exhibited favorable diagnostic performance.

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept:a quantitative analysis based on 4D label-free technique

AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of PDR.METHODS:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free technology.Statistically differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were analyzed.RESULTS:A total of 12 samples were analyzed.The proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were down-regulated.We found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept treatment.GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR.In addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural regulation.In addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in PDR.CONCLUSION:Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR.Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.

Automatic diagnosis of diabetic retinopathy using vision transformer based on wide-field optical coherence tomography angiography

Diabetic retinopathy(DR)is one of the major causes of visual impairment in adults with diabetes.Optical coherence tomography angiography(OCTA)is nowadays widely used as the golden criterion for diagnosing DR.Recently,wide-field OCTA(WF-OCTA)provided more abundant information including that of the peripheral retinal degenerative changes and it can contribute in accurately diagnosing DR.The need for an automatic DR diagnostic system based on WF-OCTA pictures attracts more and more attention due to the large diabetic population and the prevalence of retinopathy cases.In this study,automatic diagnosis of DR using vision transformer was performed using WF-OCTA images(12 mm×12 mm single-scan)centered on the fovea as the dataset.WF-OCTA images were automatically classified into four classes:No DR,mild nonproliferative diabetic retinopathy(NPDR),moderate to severe NPDR,and proliferative diabetic retinopathy(PDR).The proposed method for detecting DR on the test set achieves accuracy of 99.55%,sensitivity of 99.49%,and specificity of 99.57%.The accuracy of the method for DR staging reaches up to 99.20%,which has been proven to be higher than that attained by classical convolutional neural network models.Results show that the automatic diagnosis of DR based on vision transformer and WF-OCTA pictures is more effective for detecting and staging DR.

Periodontal disease:A silent factor in the development and progression of diabetic retinopathy

The global increase in the prevalence of type 2 diabetes mellitus(T2DM)and its complications presents significant challenges to public health.Recently,periodontal disease(PD)was recognized as a factor that is likely to influence the progression of T2DM and its complications due to its potential to exacerbate systemic inflammation and oxidative stress.In this editorial,we comment on the article published by Thazhe Poyil et al in the very recent issue of the World Journal of Diabetes in 2024,which investigated the correlation between PD and diabetic retinopathy(DR)in T2DM patients,with emphasis on the association between periodontal swollen surface area,glycated hemoglobin(HbA1c),interleukin-6(IL-6),and lipoprotein(a).The findings by Thazhe Poyil et al are significant as they demonstrate a strong link between PD and DR in T2DM patients.This correlation highlights the importance of addressing periodontal health in diabetes management to potentially reduce the risk and severity of DR,a complication of diabetes.The integration of periodontal evaluation and treatment into diabetes care protocols may lead to improved glycemic control and better overall outcomes for T2DM patients.A few studies have established an interconnection between PD and diabetic complication,specifically DR,in T2DM patients,which we aim to highlight in this editorial.Emphasis was placed on the different mechanisms that suggest a bidirectional relationship between PD and T2DM,where the presence of periodontal inflammation negatively influenced glycemic control and contributed to the development and progression of DR through shared inflammatory and vascular mechanisms.This article highlights the importance of collaboration amongst diabetes specialists,ophthalmologists,periodontists,and public health professionals to advance the prevention,early detection,and treatment of PD and DR.This will improve the health and quality of life of T2DM patients.Moreover,the editorial highlights the need for further research on the specific molecular and immunological mechanisms that underlie the link between periodontitis and DR,with identification of common inflammatory biomarkers and signaling pathways.This is expected to facilitate effective direction of therapeutic objectives,thereby improving the management of diabetes and its complications through integrated care that incorporates oral health.

Systemic immune-inflammation index,neutrophilto-lymphocyte ratio,and platelet-to-lymphocyte ratio in patients with type 2 diabetes at different stages of diabetic retinopathy

AIM:To investigate systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),and plateletto-lymphocyte ratio(PLR)levels in patients with type 2 diabetes at different stages of diabetic retinopathy(DR).METHODS:This retrospective study included 141 patients with type 2 diabetes mellitus(DM):45 without diabetic retinopathy(NDR),47 with non-proliferative diabetic retinopathy(NPDR),and 49 with proliferative diabetic retinopathy(PDR).Complete blood counts were obtained,and NLR,PLR,and SII were calculated.The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic(ROC)curves.The relationships between DR stages and SII,PLR,and NLP were assessed using multivariate logistic regression.RESULTS:The average NLR,PLR,and SII were higher in the PDR group than in the NPDR group(P=0.011,0.043,0.009,respectively);higher in the NPDR group than in the NDR group(P<0.001 for all);and higher in the PDR group than in the NDR group(P<0.001 for all).In the ROC curve analysis,the NLR,PLR,and SII were significant predictors of DR(P<0.001 for all).The highest area under the curve(AUC)was for the PLR(0.929 for PLR,0.925 for SII,and 0.821 for NLR).Multivariate regression analysis indicated that NLR,PLR,and SII were statistically significantly positive and independent predictors for the DR stages in patients with DM[odds ratio(OR)=1.122,95%confidence interval(CI):0.200–2.043,P<0.05;OR=0.038,95%CI:0.018–0.058,P<0.05;OR=0.007,95%CI:0.001–0.01,P<0.05,respectively).CONCLUSION:The NLR,PLR,and SII may be used as predictors of DR.

Intravitreal conbercept injection with panretinal photocoagulation for high-risk proliferative diabetic retinopathy with vitreous hemorrhage

AIM:To assess the clinical efficacy and safety of combining panretinal photocoagulation(PRP)with intravitreal conbercept(IVC)injections for patients with high-risk proliferative diabetic retinopathy(HR-PDR)complicated by mild or moderate vitreous hemorrhage(VH),with or without diabetic macular edema(DME).METHODS:Patients diagnosed with VH with/without DME secondary to HR-PDR and received PRP combined with IVC injections were recruited in this retrospective study.Upon establishing the patient’s diagnosis,an initial IVC was performed,followed by prompt administration of PRP.In cases who significant bleeding persisted and impeded the laser operation,IVC was sustained before supplementing with PRP.Following the completion of PRP,patients were meticulously monitored for a minimum of six months.Laser therapy and IVC injections were judiciously adjusted based on fundus fluorescein angiography(FFA)results.Therapeutic effect and the incidence of adverse events were observed.RESULTS:Out of 42 patients(74 eyes),29 were male and 13 were female,with a mean age of 59.17±12.74y(33-84y).The diabetic history was between 1wk and 26y,and the interval between the onset of visual symptoms and diagnosis of HR-PDR was 1wk-1y.The affected eye received 2.59±1.87(1-10)IVC injections and underwent 5.5±1.02(4-8)sessions of PRP.Of these,68 eyes received PRP following 1 IVC injection,5 eyes after 2 IVC injections,and 1 eye after 3 IVC injections.Complete absorption of VH was observed in all 74 eyes 5-50wk after initial treatment,with resolution of DME in 51 eyes 3-48wk after initial treatment.A newly developed epiretinal membrane was noted in one eye.Visual acuity significantly improved in 25 eyes.No complications such as glaucoma,retinal detachment,or endophthalmitis were reported.CONCLUSION:The study suggests that the combination of PRP with IVC injections is an effective and safe modality for treating diabetic VH in patients with HR-PDR.

Scheme Based on Multi-Level Patch Attention and Lesion Localization for Diabetic Retinopathy Grading

Early screening of diabetes retinopathy(DR)plays an important role in preventing irreversible blindness.Existing research has failed to fully explore effective DR lesion information in fundus maps.Besides,traditional attention schemes have not considered the impact of lesion type differences on grading,resulting in unreasonable extraction of important lesion features.Therefore,this paper proposes a DR diagnosis scheme that integrates a multi-level patch attention generator(MPAG)and a lesion localization module(LLM).Firstly,MPAGis used to predict patches of different sizes and generate a weighted attention map based on the prediction score and the types of lesions contained in the patches,fully considering the impact of lesion type differences on grading,solving the problem that the attention maps of lesions cannot be further refined and then adapted to the final DR diagnosis task.Secondly,the LLM generates a global attention map based on localization.Finally,the weighted attention map and global attention map are weighted with the fundus map to fully explore effective DR lesion information and increase the attention of the classification network to lesion details.This paper demonstrates the effectiveness of the proposed method through extensive experiments on the public DDR dataset,obtaining an accuracy of 0.8064.

Mendelian randomization analysis of causal relationship between cheese intake and diabetic retinopathy

AIM:To assess whether there is a possible causal link between the intake of cheese and the risk of diabetic retinopathy(DR)utilizing a two-sample Mendelian randomization(MR)analysis.METHODS:The research data were obtained from summary statistics of genome-wide association studies(GWAS).Genetic loci closely related to cheese intake were extracted as instrumental variables(IVs),and DR was the outcome variable.The data were extracted from individuals of European ethnicity.The data of cheese intake consisted of 451486 samples with 9851867 single nucleotide polymorphisms(SNPs),while the DR data consisted of 206234 samples with 16380446 SNPs.Sixty-one genetic loci closely related to cheese intake were selected as IVs.MR analysis was performed by inverse-variance weighted(IVW)method and MR-Egger regression respectively.The causal relationship between cheese intake and DR was evaluated using odds ratios(ORs)and 95%confidence intervals(CIs).Egger-intercept test was used to test horizontal pleiotropy and sensitivity analysis was performed by leave-one-out test.RESULTS:The P value of the IVW method was less than 0.05,indicating a significant negative correlation between cheese intake and DR.MR-Egger regression showed that the intercept was 0.01 with a standard error of 0.022,and a P-value of 0.634,indicating no evidence of horizontal pleiotropy affecting the IVs related to the exposure factors.Besides,heterogeneity tests confirmed the absence of heterogeneity,and the“leave-one-out”sensitivity analysis demonstrated that the results were stable.CONCLUSION:Cheese intake is causally negatively correlated with the occurrence of DR,and cheese intake could reduce the risk of DR.

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.