Global trends in diabetic eye disease research from 2012 to 2021

Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

DCFNet:An Effective Dual-Branch Cross-Attention Fusion Network for Medical Image Segmentation

Automatic segmentation of medical images provides a reliable scientific basis for disease diagnosis and analysis.Notably,most existing methods that combine the strengths of convolutional neural networks(CNNs)and Transformers have made significant progress.However,there are some limitations in the current integration of CNN and Transformer technology in two key aspects.Firstly,most methods either overlook or fail to fully incorporate the complementary nature between local and global features.Secondly,the significance of integrating the multiscale encoder features from the dual-branch network to enhance the decoding features is often disregarded in methods that combine CNN and Transformer.To address this issue,we present a groundbreaking dual-branch cross-attention fusion network(DCFNet),which efficiently combines the power of Swin Transformer and CNN to generate complementary global and local features.We then designed the Feature Cross-Fusion(FCF)module to efficiently fuse local and global features.In the FCF,the utilization of the Channel-wise Cross-fusion Transformer(CCT)serves the purpose of aggregatingmulti-scale features,and the Feature FusionModule(FFM)is employed to effectively aggregate dual-branch prominent feature regions from the spatial perspective.Furthermore,within the decoding phase of the dual-branch network,our proposed Channel Attention Block(CAB)aims to emphasize the significance of the channel features between the up-sampled features and the features generated by the FCFmodule to enhance the details of the decoding.Experimental results demonstrate that DCFNet exhibits enhanced accuracy in segmentation performance.Compared to other state-of-the-art(SOTA)methods,our segmentation framework exhibits a superior level of competitiveness.DCFNet’s accurate segmentation of medical images can greatly assist medical professionals in making crucial diagnoses of lesion areas in advance.

Therapeutic effect of Keap1-Nrf2-ARE pathway-related drugs on age-related eye diseases through anti-oxidative stress

Age-related eye diseases,including cataract,glaucoma,diabetic retinopathy(DR),and age-related macular degeneration(AMD),are the leading causes of vision loss in the world.Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye.The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body.This pathway is also active in the development of age-related eye diseases.A variety of drugs have been shown to treat agerelated eye diseases through the Keap1-Nrf2-ARE(Kelch-like ECH-Associating protein 1-nuclear factor erythroid 2 related factor 2-antioxidant response element)pathway.This review describes the role of oxidative stress in the development of age-related eye diseases,the function and regulation of the Keap1-Nrf2-ARE pathway,and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.

Changes of optic nerve head microcirculation in high myopia

AIM:To analyze the correlation of age,spherical equivalent(SE),and axial length(AL)with the microcirculation of optic nerve head(ONH)in high myopia(HM).METHODS:In this cross-sectional clinical study,164 right eyes were included.Optical coherence tomography angiography(OCTA)was used to detect ONH vessel density.Eyes were classified based on age,SE,and AL.Groups of Age1,Age2,and Age3 were denoted for age classification(Age1<20y,20y≤Age2<30y,Age3≥30y);Groups SE1,SE2,and SE3 for the SE classification(-9≤SE1<-6 D,-12≤SE2<-9 D,SE3<-12 D);Groups AL1,AL2,AL3,and AL4 for the AL classification(AL1<26 mm,26≤AL2<27 mm,27≤AL3<28 mm,AL4≥28 mm).RESULTS:No significant difference was observed in vessel density among the Age1,Age2,and Age3 groups(all P>0.05)and the SE1,SE2,and SE3 groups(all P>0.05).No significant difference was observed in the intrapapillary vascular density(IVD)among AL1,AL2,AL3,and AL4 groups(P>0.05).However,a significant decrease was found in the peripapillary vascular density(PVD)in the AL1,AL2,AL3,and AL4 groups(F=3.605,P=0.015),especially in the inferotemporal(IT;F=6.25,P<0.001),temporoinferior(TI;F=2.865,P=0.038),and temporosuperior(TS;F=6.812,P<0.001)sectors.The IVD was correlated with age(r=-0.190,P<0.05)but not with SE or AL(P>0.05).The PVD was correlated with AL(r=-0.236,P<0.01)but not with age or SE(P>0.05).CONCLUSION:With the increase of AL,the IVD remains stable while the PVD decreases,especially in the three directions of temporal(IT,TI,and TS).The main cause of microcirculation reduction may be related to AL elongation rather than an increase in age or SE.

Protective effects of piperine on the retina of mice with streptozotocin-induced diabetes by suppressing HIF-1/VEGFA pathway and promoting PEDF expression

AIM:To evaluate the protective mechanisms of piperine in the retina of mice with streptozotocin-induced diabetes.METHODS:In experiments in vitro,stimulation by chemical hypoxia was established in ARPE-19 cells.Then,the expression of hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor A(VEGFA),and pigment epithelium-derived factor(PEDF)was assessed at the m RNA and protein levels.In experiments in vivo,diabetes mellitus was established by intraperitoneally injecting 150 mg/kg streptozotocin once.After 3 wk of the onset of diabetes,15 mg/kg piperine was intraperitoneally injected once daily for 1 or 3 wk.Then,the retinal morphology and m RNA and protein expression were assessed.RESULTS:In hypoxia,1-100μmol/L piperine significantly decreased the expression of VEGFA m RNA and increased the expression of PEDF m RNA without affecting HIF-1αm RNA.Meanwhile,100μmol/L piperine substantially decreased the protein level of VEGFA and increased the protein level of PEDF.The HIF-1αprotein level was also hampered by piperine.In the diabetic retina of mice,the morphological damage was alleviated by piperine.Likewise,the retinal vascular leakage was substantially decreased by piperine.Further,the protein levels of HIF-1αand VEGFA were significantly reduced by piperine.Moreover,the level of the antiangiogenic factor of PEDF dramatically increased by piperine.CONCLUSION:Piperine may exert protective effects on the retina of mice with diabetes via regulating the pro-antiangiogenic homeostasis composed of HIF-1/VEGFA and PEDF.

Sodium iodate-induced retina degeneration observed in non-separate sclerochoroid/retina pigment epithelium/retina whole mounts

Background:Sodium iodate(SI)is a chemical widely applied to induce retina degeneration in animal models.SI treatment caused formation of rosettes/folds in the outer nuclear layer(ONL)of the rat retina,but it was previously unclear whether SI also forms rosettes in mice.In addition,SI induced retina degeneration was never addressed in non-separate sclerochoroid/retina pigment epithelium/retina whole mount.Here we displayed features of retina degeneration including rosette formation in mice and developed a morphological analytic assessment using sclerochoroid/retina pigment epithelium/retina whole mounts.Methods:SI was intraperitoneally injected in Sprague-Dawley(SD)rats and C57BL/6J mice using a single dose(50 mg/kg)or with a dose range(10 to 50 mg/kg)in BALB/C mice.Rat retinas were investigated up to 2-week post-injection by histology and whole mounts,and mouse retinas were investigated up to 3-week post-injection by histology,fluorescent staining of sections and/or sclerochoroid/retina pigment epithelium/retina whole mounts for the morphological evaluations of the SI-induced retina damage.Results:SI-induced retina damage caused photoreceptor(PR)degeneration and rosettes/folds formation,as well as retina pigment epithelium degeneration and inward migration.It displayed mixed nuclei from choroid to PRs,due to layer disorganization,as shown by single horizontal images in the sclerochoroid/retina pigment epithelium/retina whole mounts.Measurement of the PR rosette area induced by SI provided a quantitative,morphological evaluation of retina degeneration.Conclusions:The method of non-separate sclerochoroid/retina pigment epithelium/retina whole staining and mount allows us to observe the integral horizontal view of damage from sclera to PR layers,which cannot be addressed by using sectioned and separate whole mount methods.This method is applicable for morphological evaluation of retina damage,especially in the subretinal layer.

Clinical observations of acute onset of myopic optic neuropathy in a real-world setting

AIM: To describe the clinical features of acute myopic onset of optic neuropathy and observe the effects of retrobulbar and systemic glucocorticoid therapy in a realworld setting.METHODS: A retrospective observational case series included 18 patients with a clinical diagnosis of acute onset of myopic optic neuropathy in a real-world setting. While the patients were using retrobulbar and systemic glucocorticoid therapy, various imaging examination data were analysed, and the clinical features of myopic optic neuropathy were summarized for 6 mo to 2 y. RESULTS: The included group of patients with acute onset of myopic optic neuropathy consisted mostly of females(n=11). The visual field(VF) showed abnormalities in bilateral eyes, including the spread of physiological blind spots, central and paracentral dark spots, and centripetal peripheral VF reduction;but central vision with no subjective changes. The visual evoked potential(VEP) was abnormal in all eyes with vision loss. The best corrected visual acuity(BCVA) was improved from 1.04±0.63 to 0.47±0.57(log MAR) af ter glucocor ticoid treatment(P<0.05). In patients with a short course(within 1 wk), recovery was fast and achieved the same BCVA as recorded before the onset within 6 d. However, in patients with the long course(1 to 2 wk), recovery was slow and did not achieve the BCVA recorded before the onset within 10 d. The changes of intraocular pressure(IOP) were not obvious before and after treatment(18.68±5.30 vs 19.55±5.34 mm Hg, P>0.05). There was no recurrence during long-term followup observation.CONCLUSION: The acute onset of myopic optic neuropathy is characterized by BCVA and VF abnormalities in bilateral eyes. Retrobulbar and systemic glucocorticoid therapy is effective.

Enhancing cellular behavior in repaired tissue via silk fibroin-integrated triboelectric nanogenerators

Triboelectric nanogenerators(TENGs)have emerged as a promising approach for generating electricity and providing electrical stimuli in medical electronic devices.Despite their potential benefits,the clinical implementation of TENGs faces challenges such as skin compliance and a lack of comprehensive assessment regarding their biosafety and efficacy.Therefore,further research is imperative to overcome these limitations and unlock the full potential of TENGs in various biomedical applications.In this study,we present a flexible silk fibroin-based triboelectric nanogenerator(SFB-TENG)that features an on-skin substrate and is characterized by excellent skin compliance and air/water permeability.The range of electrical output generated by the SFB-TENG was shown to facilitate the migration and proliferation of Hy926,NIH-3T3 and RSC96 cells.However,apoptosis of fibroblast NIH-3T3 cells was observed when the output voltage increased to more than 20 V at a frequency of 2 Hz.In addition,the moderate electrical stimulation provided by the SFB-TENG promoted the cell proliferation cycle in Hy926 cells.This research highlights the efficacy of a TENG system featuring a flexible and skin-friendly design,as well as its safe operating conditions for use in biomedical applications.These findings position TENGs as highly promising candidates for practical applications in the field of tissue regeneration.