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Philippine retinoblastoma initiative multi-eye center study 2010-2020

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

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Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

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Neural Regeneration Research 2024年第4期19卷 923-928页

作者： Xiangjun Li Chunyan Li Hai Huang Dan Bai Jingyi Wang Anqi Chen Yu Gong Ying Leng department of ophthalmology Affiliated Hospital of Beihua University department of Endocrinology Affiliated Hospital of Beihua University

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.

关键词： choroidal thickness diabetic macular edema laser photocoagulation retinal ganglion cell-inner plexiform layer thickness retinal ganglion cells retinal nerve fiber layer thickness thickness of the macular area vascular endothelial growth factor visual acuity

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Cannabinoids and endocannabinoids as therapeutics for nervous system disorders:preclinical models and clinical studies

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Neural Regeneration Research 2024年第4期19卷 788-799页

作者： R.Scott Duncan Sean M.Riordan Matthew C.Gernon Peter Koulen department of ophthalmology School of MedicineUniversity of Missouri department of Biomedical Sciences School of MedicineUniversity of Missouri

Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human body.They have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human diseases.Some of these include central nervous system(CNS)diseases and dysfunctions such as forms of epilepsy,multiple sclerosis,Parkinson’s disease,pain and neuropsychiatric disorders.In addition,the endogenously produced cannabinoid lipids,endocannabinoids,are critical for normal CNS function,and if controlled or modified,may represent an additional therapeutic avenue for CNS diseases.This review discusses in vitro cellular,ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS pathologies.In addition,the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS diseases.Cannabinoids and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.

关键词： anandamide cannabidiol cannabinoid endocannabinoid epilepsy multiple sclerosis neurodegeneration neuroprotection tetrahydrocannabinol

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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

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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

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Reduced macular thickness and vascular density in abnormal glucose metabolism patients: A meta-analysis of optical coherence tomography (OCT) and OCT angiography studies

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中华医学杂志(英文版) 2024年第9期137卷 1054-1068页

作者： Fu Xiangyu Ren Xiang Chen Wenyue Chen Danian department of ophthalmology West China Hospital Sichuan University Chengdu Sichuan China Research Laboratory of ophthalmology and Vision Sciences State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu Sichuan China department of ophthalmology The People’s Hospital of Guizhou Province Guiyang Guizhou China

Background: Alterations in macular thickness and vascular density before clinically visible diabetic retinopathy (DR) remain inconclusive. This study aimed to determine whether retinal manifestations in abnormal glucose metabolism (AGM) patients differ from those in the healthy individuals.Methods: PubMed, Embase, and Web of Science were searched between 2000 and 2021. The eligibility criteria were AGM patients without DR. Primary and secondary outcomes measured by optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed and expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). A random-effects model was used in the data synthesis. The potential publication bias for the variables was evaluated using Egger’s test.Results: A total of 86 observational studies involving 13,773 participants and 15,416 eyes were included. OCT revealed that compared to healthy controls, the total macular thickness of AGM patients was thinner, including the thickness of fovea (–0.24, 95% CI [–0.39, –0.08];P = 0.002,I2 = 87.7%), all regions of parafovea (–0.32, 95% CI [–0.54, –0.11];P = 0.003;I2 = 71.7%) and the four quadrants of perifovea; the thickness of peripapillary retinal nerve fiber layer (pRNFL), macular retinal nerve fiber layer (mRNFL), and ganglion cell layer (GCL) also decreased. OCTA indicated that the superficial and deep vascular density decreased, the foveal avascular zone (FAZ) area enlarged, and the acircularity index (AI) reduced in AGM individuals.Conclusions: Retinal thinning and microvascular lesions have occurred before the advent of clinically detectable DR; OCT and OCTA may have the potential to detect these preclinical changes.Registration: PROSPERO; http://www.***.york.***.uk/prospero/; No. CRD42021269885.

关键词： Abnormal glucose metabolism Optical coherence tomography Optical coherence tomography angiography Diabetic retinopathy Prediabetes Meta-analysis

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Neuroimaging in atypical normal tension glaucoma:debating routine implementation in the absence of classic neurological findings

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International Journal of ophthalmology(English edition) 2024年第3期17卷 509-517页

作者： Umay Güvenç Gülizar Demirok Güner Üney Selma Uzman ophthalmology department Ankara Training and Research HospitalAnkara 06230Turkey

●AIM:To assess the necessity of neuroimaging in patients with neurological or atypical findings of normal tension glaucoma(NTG)who do not exhibit typical glaucoma manifestations.●METHODS:A retrospective analysis was conducted on 90 atypical NTG patients who underwent cranial magnetic resonance imaging(MRI)due to atypical symptoms.The demographic characteristics,clinical parameters,and radiological findings were recorded.●RESULTS:Among the patients,66.7%had abnormal radiology results,with the most common findings being gliosis(34.4%),sequelae of cerebrovascular events and vascular malformations(14.4%),and benign intracranial mass lesions(11%).Non-glaucomatous visual field defects were more frequently observed in patients with abnormal neuroimaging results.However,there were no significant differences in intraocular pressure,optic disc parameters,retinal nerve fiber layer thickness,and visual field indices between patients with normal and abnormal radiological results.The mean age of the patients was 58.74y.Interestingly,there was a significant age difference,with the abnormal radiology group having a higher median age(P=0.021).●CONCLUSION:The study highlights the importance of cranial imaging in older NTG patients to detect underlying pathologies and prevent misdiagnosis.It suggests that neuroimaging may be warranted in NTG patients with atypical visual field defects incompatible with glaucoma.However,routine neuroimaging in all NTG patients without classic neurological signs may not be necessary.

关键词： normal tension glaucoma neuroimaging atypical visual field defects

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Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing

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Current Medical Science 2024年第2期44卷 419-425页

作者： Jia-xun LI Ling-rui MENG Bao-ke HOU Xiao-lu HAO Da-jiang WANG Ling-hui QU Zhao-hui LI Lei ZHANG Xin JIN department of Senior ophthalmology the Third Medical Center of PLA General HospitalBeijing 100853China department of ophthalmology the 74th Army Group HospitalGuangzhou 510318China

Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on electrooculogram.The potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and photoreceptor.In this study,the complete clinical characteristics of two Chinese ARB families were summarized.Methods:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family members.Results:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB families.The novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1.Another novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.Conclusion:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes.The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

关键词： autosomal recessive bestrophinopathy BEST1 gene third-generation sequencing mutation

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MP-3 microperimeter in early primary open angle glaucoma with a new pattern

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International Journal of ophthalmology(English edition) 2024年第5期17卷 861-868页

作者： Shuang Liang Li-Tao Wang Xiao-Li Liu Jia-Liang Duan Dan-Yan Liu department of ophthalmology of the Second Hospital of Hebei Medical University Shijiazhuang 050000Hebei ProvinceChina department of ophthalmology Shijiazhuang People’s HospitalShijiazhuang 050000Hebei ProvinceChina

AIM:To investigate macular microperimetry in patients with early primary open angle glaucoma(POAG)using a new custom-made pattern,and analyze the characteristics of macular sensitivity.METHODS:This case-control study included 38 patients with POAG,who were divided into pre-perimetric glaucoma(18 eyes of 18 patients),early-stage(20 eyes of 20 patients),and control(20 eyes of 20 patients)groups.All subjects underwent standard 24-2 humphrey visual field test.An MP-3 microperimeter with a new custom-made pattern(28 testing points distributed in four quadrants,covering the central 10°of the retina)was used to evaluate macular sensitivity.Ganglion cell complex(GCC)thicknesses were examined using an RS-3000 Advance OCT system.The features of structure and function were analysed per quadrant.RESULTS:The pre-perimetric glaucoma group had significantly lower inferior hemifield macular sensitivity compared to controls(P<0.05).The early-stage POAG group had significantly lower average,inferior hemifield,inferonasal,and inferotemporal mean sensitivities compared to the pre-perimetric glaucoma group(P<0.05),and lower macular sensitivity in all sectors compared to controls(P<0.05).Regarding GCC thickness,all sectors in the early-stage POAG group became thinner compared to those in controls(P<0.05);whereas all sectors in the early-stage POAG group,except the superonasal quadrant,became thinner compared to those in the pre-perimetric glaucoma group(P<0.05).Macular sensitivity and GCC thickness were significantly associated in each sector.The inferotemporal quadrant had the highest correlation coefficients(0.840).The structure-function relationship for the inferonasal and inferotemporal sectors was stronger compared to the corresponding superior sectors.CONCLUSION:Microperimetry reveals variations in macular sensitivity in patients with early glaucoma earlier than conventional perimetry,particularly in pre-perimetric glaucoma cases in which it might be undetectable by conventional methods.The new custom-made pattern may improve th

关键词： early primary open angle glaucoma macular sensitivity microperimetry optical coherence tomography ganglion cell complex

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Sutured scleral fixation of existing subluxated/dislocated acrylic one-piece intraocular lenses

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International Journal of ophthalmology(English edition) 2024年第4期17卷 665-669页

作者： Wei-Yu Huang Yung-Jen Chen department of ophthalmology Chi Mei Medical CenterTainan City 710TaiwanChina department of ophthalmology Chang Gung Memorial HospitalKaohsiung City 833TaiwanChina

AIM:To evaluate the visual and refractive outcomes in cases after sutured scleral fixation of existing subluxated or dislocated acrylic one-piece intraocular lenses(IOLs).METHODS:This study retrospectively enrolled a consecutive series of patients who underwent a surgery of sutured existing subluxated or dislocated IOLs from October 2018 to June 2020.All patients underwent comprehensive preoperative and postoperative ophthalmologic examination,and data were collected including age,sex,surgical indications,best-corrected visual acuity,refractive error,intraocular pressure.Presence of intraoperative and postoperative surgical complications was documented.RESULTS:A total of 20 consecutive cases were enrolled for analysis with mean final follow-up period 9.8±5.3mo.Visual acuity improved from a mean of 0.35(0.46±0.32 logMAR)preoperatively to 0.61(0.21±0.18 logMAR)at the 3-month follow-up(P=0.002).The mean amount of preoperative keratometric astigmatism and total postoperative refractive astigmatism was-1.24±0.80 diopters(D)and-1.42±0.97 D,respectively.There was no statistically significant difference between preoperative and postoperative astigmatism(P=0.156).The mean IOL-induced astigmatism was-0.23±0.53 D.The mean spherical equivalent at the 3-month follow-up was-0.1±0.94 D.No major complications were noted during the follow-up period.CONCLUSION:Surgical techniques using sutured scleral fixation of existing subluxated or dislocated acrylic one-piece IOLs result in favorable visual and refractive outcomes without major complications.

关键词： intraocular lens dislocation intraocular lens subluxation lens dislocation lens subluxation scleral fixation

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