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Two become one:combination of two risk factors in a new glaucoma animal model

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Neural Regeneration Research 2024年第5期19卷 982-983页

作者： Nils Kluge Sabrina Reinehr Experimental eye Research institute University Eye HospitalRuhr-University BochumBochumGermany

Glaucoma is a group of eye diseases characterized by progressive loss of retinal ganglion cells(RGCs)and optic nerve degeneration.During this process,the visual field is reduced,and blindness may ultimately occur.Worldwide,glaucoma is the second leading cause of blindness,with about 80 million people affected.Glaucoma is a multifactorial disease and due to its complexity,the exact pathomechanisms are not fully understood yet.However,different risk factors,such as elevated intraocular pressure(IOP),age,or myopia,have been identified to date(EGS,2021).

关键词： elevated exact glaucoma

RDH12-associated retinal degeneration caused by a homozygous pathogenic variant of 146C>T and literature review

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 311-316页

作者： Jin Li Yi-Qun Hu Hong-Bo Cheng Ting Wang Long-Hao Kuang Tao Huang Xiao-He Yan Shenzhen eye Hospital Jinan UniversityShenzhen Eye InstituteShenzhen 518040Guangdong ProvinceChina

AIM:To describe the clinical,electrophysiological,and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant.METHODS:The patient underwent a complete ophthalmologic examination including best-corrected visual acuity,anterior segment and dilated fundus,visual field,spectral-domain optical coherence tomography(OCT)and electroretinogram(ERG).The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result.Then we reviewed the characteristics of the patients reported with the same variant.RESULTS:A 30-year male presented with severe early retinal degeneration who complained night blindness,decreased visual acuity,vitreous floaters and amaurosis fugax.The best corrected vision was 0.04 OD and 0.12 OS,respectively.The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye.Autofluorescence shows bilateral symmetrical hypo-autofluorescence.ERG revealed that the amplitudes of a-and b-wave were severely decreased.Multifocal ERG showed decreased amplitudes in the local macular area.A homozygous missense variant c.146C>T(chr14:68191267)was found.The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied.CONCLUSION:An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported.The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.

关键词： RDH12 gene inherited retinal degeneration homozygous pathogenic variant clinical feature multi-mode imaging

Evaluation of dry eye disease symptomatology and mental health status among patients with different COVID-19 statuses

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 822-830页

作者： Fang Ruan Wen-Jun Kong Qian Fan Hong-Wei Dong Wei Zhang Wen-Bin Wei Ying Jie Department of Ophthalmology Beijing You’an HospitalCapital Medical UniversityBeijing Infectious Eye Disease Diagnosis and Treatment CenterBeijing 100069China Beijing Tongren eye Center Beijing Tongren HospitalCapital Medical UniversityBeijing Institute of OphthalmologyBeijing Ophthalmology and Visual Sciences Key LabBeijing 100730China Tianjin eye Hospital Tianjin Key Lab of Ophthalmology and Visual ScienceTianjin Eye InstituteNankai University Affiliated Eye HospitalNankai University Eye InstituteNankai UniversityClinical College of OphthalmologyTianjin Medical UniversityTianjin 300020China

AIM:To evaluate dry eye disease(DED)symptomatology and mental health status in different COVID-19 patients.METHODS:A cross-sectional observational design was used.Totally 123 eligible adults(46.34%of men,age range,18-59y)with COVID-19 included in the study from August to November,2022.Ocular Surface Disease Index(OSDI),Five-item Dry eye Questionnaire(DEQ-5),Hospital Anxiety and Depression Scale(HADS),and Pittsburgh Sleep Quality Index(PSQI)were used in this study.RESULTS:OSDI scores were 6.82(1.25,15.91)in asymptomatic carriers,7.35(2.50,18.38)in mild cases,and 16.67(4.43,28.04)in recurrent cases,with 30.00%,35.56%,and 57.89%,respectively evaluated as having DED symptoms(χ2=7.049,P=0.029).DEQ-5 score varied from 2.00(0,6.00)in asymptomatic carriers,3.00(0,8.00)in mild cases,and 8.00(5.00,10.00)in recurrent cases,with 27.50%,33.33%,and 55.26%,respectively assessed as having DED symptoms(χ2=8.532,P=0.014).The prevalence of clinical anxiety(50.00%)and depression(47.37%)symptoms were also significantly higher in patients with recurrent infection(χ2=24.541,P<0.001;χ2=30.871,P<0.001).Recurrent infection was a risk factor for high OSDI scores[odds ratio,2.562;95%confidence interval(CI),1.631-7.979;P=0.033]and DEQ-5 scores(odds ratio,3.353;95%CI,1.038-8.834;P=0.043),whereas having a fixed occupation was a protective factor for OSDI scores(odds ratio,0.088;95%CI,0.022-0.360;P=0.001)and DEQ-5 scores(odds ratio,0.126;95%CI,0.039-0.405;P=0.001).CONCLUSION:Patients with recurrent COVID-19 have more severe symptoms of DED,anxiety,and depression.

关键词： COVID-19 dry eye disease recurrent infection mental health

Clinical associations of corneal neuromas with ocular surface diseases

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Neural Regeneration Research 2024年第1期19卷 140-147页

作者： Charmaine Jan Li Toh Chang Liu Isabelle Xin Yu Lee Molly Tzu Yu Lin Louis Tong Yu-Chi Liu Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore Singapore eye Research institute Singapore Department of Cornea and External eye Disease Singapore National Eye CentreSingapore Ophthalmology and Visual Sciences Academic Clinical Program Duke-NUS Medical SchoolSingapore

Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

关键词： cornea corneal diseases corneal nerve corneal neuropathy in vivo confocal microscopy microneuroma neuroma ocular surface diseases

Bibliometric analysis of hotspots and trends of global myopia research

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 940-950页

作者： Xing-Yang Wu Hui-Hui Fang Yan-Wu Xu Yan-Ling Zhang Shao-Chong Zhang Wei-Hua Yang Shenzhen eye institute Shenzhen Eye HospitalJinan UniversityShenzhen 518040Guangdong ProvinceChina School of Future Technology South China University of TechnologyGuangzhou 510641Guangdong ProvinceChina

AIM:To gain insights into the global research hotspots and trends of myopia.METHODS:Articles were downloaded from January 1,2013 to December 31,2022 from the Science Core Database website and were mainly statistically analyzed by bibliometrics software.RESULTS:A total of 444 institutions in 87 countries published 4124 articles.Between 2013 and 2022,China had the highest number of publications(n=1865)and the highest H-index(61).Sun Yat-sen University had the highest number of publications(n=229)and the highest H-index(33).Ophthalmology is the main category in related journals.Citations from 2020 to 2022 highlight keywords of options and reference,child health(pediatrics),myopic traction mechanism,public health,and machine learning,which represent research frontiers.CONCLUSION:Myopia has become a hot research field.China and Chinese institutions have the strongest academic influence in the field from 2013 to 2022.The main driver of myopic research is still medical or ophthalmologists.This study highlights the importance of public health in addressing the global rise in myopia,especially its impact on children’s health.At present,a unified theoretical system is still needed.Accurate surgical and therapeutic solutions must be proposed for people with different characteristics to manage and intervene refractive errors.In addition,the benefits of artificial intelligence(AI)models are also reflected in disease monitoring and prediction.

关键词： bibliometric analysis myopia global trends

Intelligent diagnosis of retinal vein occlusion based on color fundus photographs

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 1-6页

作者： Yu-Ke Ji Rong-Rong Hua Sha Liu Cui-Juan Xie Shao-Chong Zhang Wei-Hua Yang eye Hospital Nanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina College of Electronic Information Engineering Nanjing University of Aeronautics and AstronauticsNanjing 210000Jiangsu ProvinceChina Shenzhen eye institute Shenzhen Eye HospitalJinan UniversityShenzhen 518000Guangdong ProvinceChina

AIM:To develop an artificial intelligence(AI)diagnosis model based on deep learning(DL)algorithm to diagnose different types of retinal vein occlusion(RVO)by recognizing color fundus photographs(CFPs).METHODS:Totally 914 CFPs of healthy people and patients with RVO were collected as experimental data sets,and used to train,verify and test the diagnostic model of RVO.All the images were divided into four categories[normal,central retinal vein occlusion(CRVO),branch retinal vein occlusion(BRVO),and macular retinal vein occlusion(MRVO)]by three fundus disease experts.Swin Transformer was used to build the RVO diagnosis model,and different types of RVO diagnosis experiments were conducted.The model’s performance was compared to that of the experts.RESULTS:The accuracy of the model in the diagnosis of normal,CRVO,BRVO,and MRVO reached 1.000,0.978,0.957,and 0.978;the specificity reached 1.000,0.986,0.982,and 0.976;the sensitivity reached 1.000,0.955,0.917,and 1.000;the F1-Sore reached 1.000,0.9550.943,and 0.887 respectively.In addition,the area under curve of normal,CRVO,BRVO,and MRVO diagnosed by the diagnostic model were 1.000,0.900,0.959 and 0.970,respectively.The diagnostic results were highly consistent with those of fundus disease experts,and the diagnostic performance was superior.CONCLUSION:The diagnostic model developed in this study can well diagnose different types of RVO,effectively relieve the work pressure of clinicians,and provide help for the follow-up clinical diagnosis and treatment of RVO patients.

关键词： deep learning artificial intelligence Swin Transformer diagnostic model retinal vein occlusion color fundus photographs

Neuroprotective effects of acteoside in a glaucoma mouse model by targeting Serta domain-containing protein 4

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 625-637页

作者： Hui-Jie Hao Ya-Hong Li Bo Yu Xun Liu Yan Zhang Xiao-Li Xing Tianjin Key Laboratory of Retinal Functions and Diseases Tianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China

AIM:To explore the therapeutic effect and main molecular mechanisms of acteoside in a glaucoma model in DBA/2J mice.METHODS:Proteomics was used to compare the differentially expressed proteins of C57 and DBA/2J mice.After acteoside administration in DBA/2J mice,anterior segment observation,intraocular pressure(IOP)monitoring,electrophysiology examination,and hematoxylin and eosin staining were used to analyze any potential effects.Immunohistochemistry(IHC)assays were used to verify the proteomics results.Furthermore,retinal ganglion cell 5(RGC5)cell proliferation was assessed with cell counting kit-8(CCK-8)assays.Serta domain-containing protein 4(Sertad4)mRNA and protein expression levels were measured by qRT-PCR and Western blot analysis,respectively.RESULTS:Proteomics analysis suggested that Sertad4 was the most significantly differentially expressed protein.Compared with the saline group,the acteoside treatment group showed decreased IOP,improved N1-P1 wave amplitudes,thicker retina,and larger numbers of cells in the ganglion cell layer(GCL).The IHC results showed that Sertad4 expression levels in DBA/2J mice treated with acteoside were significantly lower than in the saline group.Acteoside treatment could improve RGC5 cell survival and reduce the Sertad4 mRNA and protein expression levels after glutamate injury.CONCLUSION:Sertad4 is differentially expressed in DBA/2J mice.Acteoside can protect RGCs from damage,possibly through the downregulation of Sertad4,and has a potential use in glaucoma treatment.

关键词： glaucoma acteoside Serta domaincontaining protein 4 proteomics mice

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

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World Journal of Diabetes 2024年第4期15卷 654-663页

作者： Yi Shi Yan-Xin Zhang Ming-Fei Jiao Xin-Jun Ren Bo-Jie Hu Ai-Hua Liu Xiao-Rong Li Surgical Retina Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China Glaucoma Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China Ocular Trauma Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China

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.

关键词： Diabetic retinopathy Retinopathy Neovascular Glaucoma Risk factors Nomogram

Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential

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World Journal of Stem Cells 2024年第5期16卷 512-524页

作者： Hang Zhang Ling-Zi Wu Zhen-Yu Liu Zi-Bing Jin Beijing institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing 100730China

BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.AIM To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles(EVs)influence anomalous cell junction and differentiation potential.METHODS We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation.Chromo-somal karyotype analysis,flow cytometry,and immunofluorescent staining were utilized for hiPSC identification.Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential.Additionally,EVs were isolated from the supernatant,and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.RESULTS The generated hiPSCs,both with and without a MERTK mutation,exhibited normal karyotype and expressed pluripotency markers;however,hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential,as confirmed by transcriptomic and proteomic profiling.Furthermore,hiPSC-derived EVs were involved in various biological processes,including cell junction and differentiation.CONCLUSION HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential.Furthermore,hiPSC-derived EVs played a regulatory role in various biological processes,including cell junction and differentiation.

关键词： Cell junction Cellular differentiation Extracellular vesicle Human induced pluripotent stem cells Transcriptomics Proteomics