The gut-eye axis:from brain neurodegenerative diseases to age-related macular degeneration

Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.

Indirubin alleviates retinal neurodegeneration through the regulation of PI3K/AKT signaling

Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries,including glaucoma,diabetic retinopathy,traumatic optic neuropathy and optic neuritis,etc.The current clinical treatment is not very effective.We investigated indirubin,one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill,in the present study for its role in retinal neurodegeneration.Indirubin exhibited no detectable tissue toxicity in vivo or cytotoxicity in vitro.Moreover,indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in vivo.Furthermore,indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in vitro.In addition,indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative stress.Mechanically,indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 signaling.In conclusion,indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush injury.The present study provides a potential therapeutic medicine for retinal neurodegenerative diseases.

Safety profile of 0.0015%tafluprost eye drops in China:a post-marketing observational study

AIM:To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension(OH)in clinical practice in China.METHODS:This post-marketing observational study included patients who received tafluprost to lower intraocular pressure(IOP)within 30d between September 2017 and March 2020 in 20 hospitals in China.Adverse drug reactions(ADRs)during tafluprost treatment and within 30d after the treatment were collected.RESULTS:A total of 2544 patients were included in this study,of them 58.5%(1488/2544)had primary open angle glaucoma(POAG),21.9%(556/2544)had OH and 19.7%(500/2544)used tafluprost for other reasons.Of 359 ADRs occurred in 10.1%(258/2544)patients,and no serious adverse event occurred.The most common ADR was conjunctival hyperemia(128 ADRs in 124 patients,4.9%).Totally 1670 participants(65.6%)combined tafluprost with carbonic anhydrase inhibitors(CAIs;37.1%,620/1670),sympathomimetics(33.5%,559/1670),β-blockers(33.2%,555/1670),other prostaglandin analogs(PGAs;15.6%,260/1670)and other eye drops(15.1%,253/1670).The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs(23 ADRs in 23 patients,8.8%,23/260)and the lowest was in combination with CAIs(16 ADRs in 16 patients,2.6%,16/620).Tafluprost was applied in primary angle-closure glaucoma(41.6%,208/500),after glaucoma surgery(17.8%,89/500)and after non-glaucoma surgery(15.8%,79/500).CONCLUSION:Tafluprost is safe for POAG and OH,and tolerable when combined with other eye drops and under various clinical circumstances.

Development and Validation of an Automatic Ultrawide-Field Fundus Imaging Enhancement System for Facilitating Clinical Diagnosis:A Cross-Sectional Multicenter Study

In ophthalmology,the quality of fundus images is critical for accurate diagnosis,both in clinical practice and in artificial intelligence(AI)-assisted diagnostics.Despite the broad view provided by ultrawide-field(UWF)imaging,pseudocolor images may conceal critical lesions necessary for precise diagnosis.To address this,we introduce UWF-Net,a sophisticated image enhancement algorithm that takes disease characteristics into consideration.Using the Fudan University ultra-wide-field image(FDUWI)dataset,which includes 11294 Optos pseudocolor and 2415 Zeiss true-color UWF images,each of which is rigorously annotated,UWF-Net combines global style modeling with feature-level lesion enhancement.Pathological consistency loss is also applied to maintain fundus feature integrity,significantly improving image quality.Quantitative and qualitative evaluations demonstrated that UWF-Net outperforms existing methods such as contrast limited adaptive histogram equalization(CLAHE)and structure and illumination constrained generative adversarial network(StillGAN),delivering superior retinal image quality,higher quality scores,and preserved feature details after enhancement.In disease classification tasks,images enhanced by UWF-Net showed notable improvements when processed with existing classification systems over those enhanced by StillGAN,demonstrating a 4.62%increase in sensitivity(SEN)and a 3.97%increase in accuracy(ACC).In a multicenter clinical setting,UWF-Net-enhanced images were preferred by ophthalmologic technicians and doctors,and yielded a significant reduction in diagnostic time((13.17±8.40)s for UWF-Net enhanced images vs(19.54±12.40)s for original images)and an increase in diagnostic accuracy(87.71%for UWF-Net enhanced images vs 80.40%for original images).Our research verifies that UWF-Net markedly improves the quality of UWF imaging,facilitating better clinical outcomes and more reliable AI-assisted disease classification.The clinical integration of UWF-Net holds great promise for enhancing diagnostic processes and patient care in ophthalmology.

Optical coherence tomography angiography for macular microvessels in ischemic branch retinal vein occlusion treated with conbercept:predictive factors for the prognosis

AIM:To evaluate the predicative factors of visual prognosis using optical coherence tomography angiography(OCTA)in ischemic branch retinal vein occlusion(BRVO)patients with macular edema(ME)after anti-vascular endothelial growth factor(VEGF)treatment.METHODS:In this retrospective analysis,data from 60 patients(60 eyes)with a definite diagnosis of ischemic BRVO with ME by fundus fluorescein angiography(FFA)were studied.The eyes with ME according to spectral domain optical coherence tomography(SD-OCT)underwent intravitreal conbercept(IVC)and 3+pro re nata(PRN)regimen.The injection times were recorded.Two weeks after injection,fundus laser photocoagulation was performed in the non-perfusion area of the retina.The patients were followed up once a month for 6mo.The bestcorrected visual acuity(BCVA),foveal avascular zone(FAZ),and A-circularity index(AI),at 6mo and the baseline were compared.RESULTS:All patients showed significant improvement in BCVA from 0.82±0.32 to 0.39±0.11 logMAR(P<0.001).The mean central macular thickness(CMT)significantly decreased from 476.22±163.54 to 298.66±109.23μm.Both the FAZ area and AI at 6mo were significantly higher than those at the baseline:the FAZ area increased(0.38±0.02 vs 0.39±0.02 mm^(2),P<0.05);the AI increased(1.27±0.02 vs 1.31±0.01,P=0.000).The baseline BCVA showed a significantly positive correlation with the baseline FAZ area,FAZ perimeter(PERIM)and AI,final visual gain(FVG)and injection times,respectively(P<0.001).FVG showed a significantly negative correlation with the FAZ area,PERIM,AI and injection times,but a significantly positive correlation with vessel densities(VDs)300μm area around FAZ(FD-300;P<0.001).Injection times was positively correlated with the baseline FAZ area,and AI,but inversely correlated with the baseline FD-300(P<0.001).However macular ischemia was noted in 5 cases during follow-up.CONCLUSION:Using OCTA to observe macular ischemia and quantify parameters can better predict the final visual prognosis of patients before treatment.The changes in FAZ parameters may influence the visual prognosis and injection times.

EphA3 deficiency in the hypothalamus promotes high-fat diet-induced obesity in mice

Erythropoietin-producing hepatocellular carcinoma A3(EphA3)is a member of the largest subfamily of tyrosine kinase receptors-Eph receptors.Previous studies have shown that EphA3 is associated with tissue development.Recently,we have found that the expression of EphA3 is elevated in the hypothalamus of mice with diet-induced obesity(DIO).However,the role of EphA3 in hypothalamic-controlled energy metabolism remains unclear.In the current study,we demonstrated that the deletion of EphA3 in the hypothalamus by CRISPR/Cas9-mediated gene editing promotes obesity in male mice with high-fat diet feeding rather than those with normal chow diet feeding.Moreover,the deletion of hypothalamic EphA3 promotes high-fat DIO by increasing food intake and reducing energy expenditure.Knockdown of EphA3 leads to smaller intracellular vesicles in GT1-7 cells.The current study reveals that hypothalamic EphA3 plays important roles in promoting DIO.

Artificial intelligence in individualized retinal disease management

Owing to the rapid development of modern computer technologies,artificial intelligence(AI)has emerged as an essential instrument for intelligent analysis across a range of fields.AI has been proven to be highly effective in ophthalmology,where it is frequently used for identifying,diagnosing,and typing retinal diseases.An increasing number of researchers have begun to comprehensively map patients’retinal diseases using AI,which has made individualized clinical prediction and treatment possible.These include prognostic improvement,risk prediction,progression assessment,and interventional therapies for retinal diseases.Researchers have used a range of input data methods to increase the accuracy and dependability of the results,including the use of tabular,textual,or image-based input data.They also combined the analyses of multiple types of input data.To give ophthalmologists access to precise,individualized,and high-quality treatment strategies that will further optimize treatment outcomes,this review summarizes the latest findings in AI research related to the prediction and guidance of clinical diagnosis and treatment of retinal diseases.

A Two-Phase Paradigm for Joint Entity-Relation Extraction

An exhaustive study has been conducted to investigate span-based models for the joint entity and relation extraction task.However,these models sample a large number of negative entities and negative relations during the model training,which are essential but result in grossly imbalanced data distributions and in turn cause suboptimal model performance.In order to address the above issues,we propose a two-phase paradigm for the span-based joint entity and relation extraction,which involves classifying the entities and relations in the first phase,and predicting the types of these entities and relations in the second phase.The two-phase paradigm enables our model to significantly reduce the data distribution gap,including the gap between negative entities and other entities,aswell as the gap between negative relations and other relations.In addition,we make the first attempt at combining entity type and entity distance as global features,which has proven effective,especially for the relation extraction.Experimental results on several datasets demonstrate that the span-based joint extraction model augmented with the two-phase paradigm and the global features consistently outperforms previous state-ofthe-art span-based models for the joint extraction task,establishing a new standard benchmark.Qualitative and quantitative analyses further validate the effectiveness the proposed paradigm and the global features.

The national multi-center artificial intelligent myopia prevention and control project

In recent years,the incidence of myopia has increased at an alarming rate among children and adolescents in China.The exploration of an effective prevention and control method for myopia is in urgent need.With the development of information technology in the past decade,artificial intelligence with the Internet of Things technology(AIoT)is characterized by strong computing power,advanced algorithm,continuous monitoring,and accurate prediction of long-term progression.Therefore,big data and artificial intelligence technology have the potential to be applied to data mining of myopia etiology and prediction of myopia occurrence and development.More recently,there has been a growing recognition that myopia study involving AIoT needs to undergo a rigorous evaluation to demonstrate robust results.

Stress-deconcentrated ultrasensitive strain sensor with hydrogen-bonding-tuned fracture resilience for robust biomechanical monitoring

Recently,rapid advances in flexible strain sensors have broadened their application scenario in monitoring of various mechanophysiological signals.Among various strain sensors,the crack-based strain sensors have drawn increasing attention in monitoring subtle mechanical deformation due to their high sensitivity.However,early generation and rapid propagation of cracks in the conductive sensing layer result in a narrow working range,limiting their application in monitoring large biomechanical signals.Herein,we developed a stress-deconcentrated ultrasensitive strain(SDUS)sensor with ultrahigh sensitivity(gauge factor up to2.3×10^(6))and a wide working range(0%-50%)via incorporating notch-insensitive elastic substrate and microcrack-tunable conductive layer.Furthermore,the highly elastic amine-based polymer-modified polydimethylsiloxane substrate without obvious hysteresis endows our SDUS sensor with a rapid response time(2.33 ms)to external stimuli.The accurate detection of the radial pulse,joint motion,and vocal cord vibration proves the capability of SDUS sensor for healthcare monitoring and human-machine communications.

Annotation and quality control specifications for fundus color photograph

1.Scope This article sets terms and definitions,basic requirements,annotat-ing requirements,and quality control for fundus color photograph an-notating.This article applies to the fundus color photograph of annotating and quality control of four ocular diseases signs for the purpose of referral or screening,including glaucoma,macular disorders,high myopic macular degeneration and diabetic retinopathy.Note:When referring to this article,please pay attention to the scope of annotating the signs of macular disorders in this document.