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Intense pulsed light‑based treatment for the improvement of symptoms in glaucoma patients treated with hypotensive eye drops

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Eye and Vision 2024年第2期10卷 12-21页

作者： Jose Maria Martinez‑de‑la‑Casa Carlos Oribio‑Quinto Almudena Milans‑del‑Bosch Pilar Perez‑Garcia Laura Morales‑Fernandez Javier Garcia‑Bella Jose Manuel Benitez‑del‑Castillo Julian Garcia‑Feijoo David P.Pinero ophthalmology unit Department of Ophthalmology and ORLFaculty of MedicineHospital Clinico San-CarlosUniversidad Complutense de MadridInstituto de Investigacion Sanitaria del Hospital Clinico San-Carlos(IdISSC)28040 MadridSpain Department of Immunology Ophthalmology and ORLSchool of MedicineInstituto de Investigaciones Oftalmologicas Ramon CastroviejoUniversidad Complutense de MadridMadridSpain Department of Optics Pharmacology and AnatomyUniversity of AlicanteAlicanteSpain

Background:Ocular surface disease in glaucoma patients is a significant ocular co-morbidity that can affect 40%to 59%of these patients worldwide.The current study was aimed at evaluating the potential clinical benefit of an intense pulsed light(IPL)-based treatment in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments.To our knowledge,this is the first series analyzing the therapeutic effect of this treatment option in this type of patients.Methods:This non-comparative prospective case series study enrolled a total of 30 glaucoma patients ranging in age from 57 to 94 years old and treated with hypotensive eyedrops for years with dry eye symptomatology.All patients received four sessions of IPL treatment using the Optima IPL system(Lumenis,Yokneam,Israel)adjusted to the official optimized Lumenis setting.Changes in symptomatology,corneal staining,conjunctival hyperemia,non-invasive break-up time(NIBUT),tear osmolarity,tear meniscus height(TMH),meiboscore and meibomian gland expressibility was analyzed after treatment.Results:Statistically significant reductions were observed after IPL treatment in the symptomatology scores measured with different questionnaires[ocular surface disease index(OSDI),standard patient evaluation of eye dryness(SPEED)and symptom assessment questionnaire in dry eye(SANDE)]as well as with the visual analogue scale(P<0.001).Mean change in OSDI was−15.0±11.3.A significant reduction was found after treatment in the corneal staining score(P<0.001).A significant reduction was found in tear film meniscus height(P=0.012),as well as in tear film osmolarity(P=0.001).A significant reduction was also found in meibomian gland expressibility(P=0.003),changing the percentage of grade 3 eyes from 44.4%before IPL to 17.2%after treatment.Conclusions:IPL therapy combined with meibomian gland expression(MGX)seems to be an effective option to improve symptomatology in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatment

关键词： Glaucoma Intense pulsed light Dry eye Meibomian glands

Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure

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Neural Regeneration Research 2024年第11期19卷 2522-2531页

作者： Shaojun Wang Siti Tong Xin Jin Na Li Pingxiu Dang Yang Sui Ying Liu Dajiang Wang Division of ophthalmology The Third Medical Center of PLA General HospitalBeijingChina Department of ophthalmology Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure.Our results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and fibroblasts.The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure.We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression.We found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of inflammation.This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure.These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

关键词： apoptosis axon degeneration high intraocular pressure microglia ocular hypertension photoreceptor cells retina retinal degeneration retinal ganglion cells single-cell RNA sequencing

Philippine retinoblastoma initiative multi-eye center study 2010-2020

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International Journal of ophthalmology(English edition) 2024年第1期17卷 144-156页

作者： Roland Joseph D.Tan Gary John V.Mercado Patricia E.Cabrera Paulita Pamela P.Astudillo Rolando Enrique D.Domingo Josept Mari S.Poblete Charmaine Grace M.Cabebe Adriel Vincent R.Te Melissa Anne S.Gonzales Jocelyn G.Sy Beltran Alexis A.Aclan Jayson T.So Fatima G.Regala Kimberley Amanda K.Comia Josemaria M.Castro Mara Augustine S.Galang Aldous Dominic C.Cabanlas Benedicto Juan E.Aguilar Gabrielle S.Evangelista Jo Michael Maniwan Andrei P.Martin Calvin Y.Martinez John Alfred H.Lim Rena Ivy Bascuna Rachel M.Ng Kevin B.Agsaoay Kris Zanna A.Acluba-Arao Ellaine Rose V.Apostol Beatriz M.Prieto Department of ophthalmology and Visual Sciences Philippine General HospitalManila 1000Philippines Department of ophthalmology Baguio General Hospital and Medical CenterBaguio City 2600Philippines Department of ophthalmology Manila Doctors HospitalManila 1000Philippines Department of ophthalmology Rizal Medical CenterPasig City 1600Philippines Department of ophthalmology Jose B.Lingad Memorial Regional HospitalPampanga 2000Philippines Department of ophthalmology Southern Philippines Medical CenterDavao City 8000Philippines Department of ophthalmology East Avenue Medical CenterQuezon City 1100Philippines Department of ophthalmology Northern Mindanao Medical CenterCagayan de Oro City 9000Philippines Department of ophthalmology Cebu Velez General HospitalCebu City 6000Philippines Legazpi Eye Center Legazpi City 4500Philippines Department of ophthalmology Cagayan Valley Medical CenterTuguegarao City 3500Philippines

AIM:To provide a comprehensive and more representative national data on the disease,especially on treatment options and outcomes,and to determine access of retinoblastoma patients from Luzon,Visayas and Mindanao to eye care,and determine if access is associated with delay in consultation,staging and outcomes.METHODS:Cohort study of retinoblastoma patients seen in eleven institutions located in the three major areas of the Philippines namely Luzon,Vizayas and Mindanao from 2010-2020.RESULTS:Totally 636 patients,involving 821 eyes,were included.Majority(57%)were from Luzon and were seen in institutions in Luzon(72%).Annually,58±10 new cases were seen with 71%having unilateral disease.Median delay of consultation remained long at 9(3,17)mo,longest in patients with unilateral disease(P<0.02)and those from the Visayas(P<0.003).Based on the International Retinoblastoma Staging System,only 35%of patients had Stage 1 while 47%already had extraocular disease.Enucleation was the most common treatment received by 484 patients while intravenous chemotherapy was received by 469.There were 250(39%)patients alive,195(31%)dead,85(13%)abandoned,17(3%)refused and 89(14%)with no data.CONCLUSION:This study presents the largest cohort of retinoblastoma patients in the Philippines in terms of patients’and participating institutions’number and geographical location and type of institution(private and public).It also presents more comprehensive data on the treatments used and outcomes(survival,globe salvage,and vision retention rates).Delay in consultation was still long among patients leading to advanced disease stage and lower survival rate.Despite increasing capacity to diagnose and manage retinoblastoma in the country,the delay of consultation remains long primarily due to accessibility issues to eye care institutions especially in the Visayas and financial concerns.The delay was still significant that overall survival rate remain low.

关键词： retinoblastoma Philippines clinical profile

Reliability of a computerized system for strabismus screening

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International Journal of ophthalmology(English edition) 2024年第1期17卷 126-130页

作者： Supaporn Tengtrisorn Alan Frederick Geater Department of ophthalmology Faculty of MedicinePrince of Songkla UniversityHat-YaiSongkla 90110Thailand Epidemiology unit Faculty of MedicinePrince of Songkla UniversityHat-YaiSongkla 90110Thailand

AIM:To evaluate the reliability of Photo-Hirschberg screening for global strabismus performed by non-specialized personnel.METHODS:Participants at three sites were enrolled.One person at each site was trained in visual acuity measurement and use of the computerized system.Visual acuity was measured,and strabismus testing was performed using two flash photographs.All data from the three primary observers were sent to an experienced assistant researcher,who was blinded to the primary results,for re-evaluation.The primary and re-evaluation results of the Photo-Hirschberg screenings using weighted kappa for agreement were compared.RESULTS:The study included 181 participants(88 males and 93 females)and the results for primary and re-evaluation screenings were corresponded.Ten participants with contrasting results presented with unclear corneal light reflex.Sensitivity and specificity were 100%[95%confidence interval(CI):29.0%-100%]and 99.4%(95%CI:96.6%-100%),respectively,based on the Agresti test of the primary evaluation,considering the re-evaluated classification as true.CONCLUSION:The computerized system can be used for primary strabismus screening by non-specialized personnel,with 98.8%agreement with specialists.However,it cannot be used as a substitute for professional examination.

关键词： strabismus screening computerized system Photo-Hirschberg screening

Bone morphogenetic protein-6 suppresses TGF-β_(2)-induced epithelial-mesenchymal transition in retinal pigment epithelium

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International Journal of ophthalmology(English edition) 2024年第4期17卷 646-652页

作者： Xuan Liu Ming Liu Meng Ji Bo Ma Yu-Cen Hou Xin-Yue Yao Qiao-Chu Cheng Li Chen Department of ophthalmology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of ophthalmology Xi’an No.1 HospitalXi’an 710000Shaanxi ProvinceChina Shaanxi Institute of ophthalmology Xi’an 710000Shaanxi ProvinceChina Department of ophthalmology Ankang Hospital of Traditional Chinese MedicineAnkang 725000Shaanxi ProvinceChina

AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)group.The cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell chamber.The EMT-related indexes and BMP-6 protein levels were detected by Western blotting.Furthermore,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression group.The EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were detected.RESULTS:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly enhanced.TGF-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in RPE.Similarly,the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced.BMP-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.

关键词： bone morphogenetic protein-6 epithelialmesenchymal transition transforming growth factor-β_(2) retinal pigment epithelial cells cell migration

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

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International Journal of ophthalmology(English edition) 2024年第4期17卷 676-685页

作者： Ting-Ting Feng Xiang Gao An-Ran Liang Bo-Wen Zhao Guang-Hui He Song Chen Clinical College of ophthalmology Tianjin Medical UniversityTianjin 300070China Tianjin Key Laboratory of ophthalmology and Visual Science Tianjin Eye InstituteTianjin Eye HospitalTianjin 300020China Key Laboratory of ophthalmology Anyang Eye HospitalAnyang 455000Henan ProvinceChina Department of ophthalmology Jining No.1 People’s HospitalJining 272011Shandong ProvinceChina

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.

关键词： vitreous proliferative diabetic retinopathy proteome 4D label-free

Building the toolbox for in vivo glia-to-neuron reprogramming

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Neural Regeneration Research 2024年第6期19卷 1171-1172页

作者： Ye Xie Bo Chen Departments of ophthalmology and Neuroscience Icahn School of Medicine at Mount Sinai

Unlike regenerative-competent species that possess a remarkable intrinsic capacity to replenish lost neurons and restore neurocircuits spontaneously, the central nervous system in adult mammals lacks the ability to compensate for the neuronal loss caused by neurodegenerative diseases or traumatic injuries resulting in permanent loss of functionality. Inspired by earlier discoveries that radial glia or astrocytes isolated from the postnatal cortex can generate neurons,

关键词： CONVERSION DISEASE

OCTA characteristics in non-arteritic central retinal artery occlusion and correlation with visual acuity

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International Journal of ophthalmology(English edition) 2024年第2期17卷 289-296页

作者： Hong-Xia Gong Bin Wu Shi-Yong Xie Wei Zhang Song Chen Tianjin Key Lab of ophthalmology and Visual Science Department of Ophthalmology for Integrated Traditional Chinese and Western MedicineTianjin Eye HospitalTianjin 300020China Clinical College of ophthalmology Tianjin Medical UniversityTianjin 300010China Eye Hospital Affiliated to Nankai University Tianjin 300020China

AIM:To observe the retinal and choroidal circulations in patients with non-arteritic permanent central retinal artery occlusion(NA-CRAO)via optical coherence tomography angiography(OCTA)and analyze their correlation with visual acuity.METHODS:Sixty-two eyes with clinically confirmed acute NA-CRAO were included in the study and divided into:A type(mild n=29),B type(moderate n=27)and C type(severe n=6)based on the degree of visual loss,retinal edema,and arterial blood flow delay in fundus fluorescence angiography(FFA).Contralateral healthy eyes were used as the control group.Best-corrected visual acuity(BCVA),slit lamp microscopy,indirect ophthalmoscopy,fundus color photography,OCTA,and FFA were performed.Spearman’s correlation analysis was used to determine the correlations between retinal and choroidal vessels and visual acuity.RESULTS:There were no statistically significant differences in age,gender,and intraocular pressure among the three types and the control group(P>0.05).Vessel density in deep capillary plexus(VD-DCP)significantly decreased(P<0.05)in all three types of NA-CRAO patients compared to the control group.Vessel density in superficial vascular plexus(VD-SVP)significantly decreased(P<0.05)in type A patients and choriocapillaris flow area significantly decreased(P<0.05)in type B and type C patients compared to the control group;while outer retinal flow areas significantly increased in the type A(P<0.05)and decreased in type C patients(P<0.05).The retinal thickness significantly increased in type C group(P<0.05).The VD-SVP at fovea in the type A was significantly lower than both of type B and C.The VD-SVP at nasal parafovea in type A and B was significantly lower than type C(P<0.05).The logMAR BCVA of type A was significantly better than that of type B and C groups(P<0.05).Spearman’s correlation analysis showed that the logMAR BCVA was positively correlated with VD-SVP at fovea(r=0.679,P=0.031)and nasal parafovea(r=0.826,P=0.013).CONCLUSION:OCTA is valuable for assessing retinal ischemia,and evaluatin

关键词： non-arteritic central retinal artery occlusion fundus fluorescence angiography optical coherence tomography angiography retinal vessel density visual acuity

Clinical features and possible pathogenesis of multiple evanescent white dot syndrome with different retinal diseases and events:a narrative review

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International Journal of ophthalmology(English edition) 2024年第3期17卷 583-595页

作者： Chun-Li Chen Yi-Zhe Cheng Zhi-Han Zhang Ge Wang Xiao-Yan Peng Department of ophthalmology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Beijing ophthalmology and Visual Science Key Laboratory Beijing 100730China State Key Laboratory of ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510600Guangdong ProvinceChina

●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS.However,as the number of reported cases increases,secondary MEWDS occurs in other related retinal diseases and injuries,exhibiting some special characteristics.The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy(MFC/PIC),acute zonal occult outer retinopathy,best vitelliform macular dystrophy,pseudoxanthoma elasticum,and ocular toxoplasmosis.The related retinal injury is laser photocoagulation,surgery,and trauma.Although primary MEWDS often have a self-limiting course,secondary MEWDS may require treatment in some cases,according to the severity of concomitant diseases and complications.Notably,MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation,needs positive treatment with corticosteroids.The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch’s membrane.The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances.Its prognosis and treatment depend on the severity of complications.Current studies propose that the etiology is associated with immune factors,including viral infection,inflammation in choroid and Bruch’s membrane,and antigen exposure caused by retinal and/or choroidal insults.More pathogenic studies should be conducted in the future.Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.

关键词： multiple evanescent white dot syndrome punctate inner choroidopathy multifocal choroiditis secondary multiple evanescent white dot syndrome