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SMAD specific E3 ubiquitin protein ligase 1 accelerates diabetic macular edema progression by WNT inhibitory factor 1

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World Journal of Diabetes 2025年第3期16卷 216-231页

作者： Li-Fang Liang Jia-Qi Zhao Yi-Fei Wu Hui-Jie Chen Tian Huang Xiao-He Lu Department of Ophthalmology Zhujiang HospitalSouthern Medical UniversityGuangzhou 515282Guangdong ProvinceChina

BACKGROUND diabetic macular edema(DME)is the most common cause of vision loss in people with *** junction disruption of the retinal pigment epithelium(RPE)cells has been reported to induce DME ***-specific E3 ubiquitin protein ligase(SMURF)1 was associated with the tight junctions of ***,the mechanism of SMURF1 in the DME process remains *** To investigate the role of SMURF1 in RPE cell tight junction during *** ARPE-19 cells treated with high glucose(HG)and desferrioxamine mesylate(DFX)for establishment of the DME cell *** mice models were constructed by streptozotocin *** trans-epithelial electrical resistance and permeability of RPE cells were *** expressions of tight junction-related and autophagy-related proteins were *** interaction between insulin like growth factor 2 mRNA binding protein 2(IGF2BP2)and SMURF1 mRNA was verified by RNA immunoprecipitation(RIP).SMURF1 N6-methyladenosine(m6A)level was detected by methylated *** SMURF1 and vascular endothelial growth factor(VEGF)were upregulated in ***1 knockdown reduced HG/DFX-induced autophagy,which protected RPE cell tight junctions and ameliorated retinal damage in DME ***1 activated the Wnt/β-catenin-VEGF signaling pathway by promoting WNT inhibitory factor(WIF)1 ubiquitination and ***2BP2 upregulated SMURF1 expression in an m6A modification-dependent *** M6A-modified SMURF1 promoted WIF1 ubiquitination and degradation,which activated autophagy to inhibit RPE cell tight junctions,ultimately promoting DME progression.

关键词： diabetic macular edema Retinal pigment epithelium cells Autophagy SMAD specific E3 ubiquitin protein ligase 1 WNT inhibitory factor 1 N6-methyladenosine modification Vascular endothelial growth factor signaling pathway

Intravitreal corticosteroids for diabetic macular edema:a network meta‑analysis of randomized controlled trials

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Eye and Vision 2021年第1期8卷 353-365页

作者： Lu Gao Xu Zhao Lei Jiao Luosheng Tang Department of Ophthalmology The Second Xiangya HospitalCentral South University139 Middle Renmin RoadChangsha 410011HunanChina Department of Ophthalmology The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Anesthesiology The Second Xiangya HospitalCentral South UniversityChangsha 410011HunanChina School of Medicine Taizhou UniversityTaizhouZhejiangChina

Background:To evaluate the efficacy and safety of different intravitreal corticosteroids for treating diabetic macular edema(DME).Methods:Four databases were systematically searched for randomized controlled trials comparing different intravitreal corticosteroids for treating *** primary outcome was the change in best-corrected visual acuity(BCVA)within 6 months after the first injection(short-term BCVA).Secondary outcomes were the change in BCVA over 1 year(long-term BCVA)and changes in central macular thickness(CMT)and intraocular pressure(IOP)within 6 months after the first *** meta-analysis was performed to aggregate the results from the individual ***:Nineteen trials involving 2839 eyes were *** triamcinolone acetonide(TA)injections(≥8 mg and 4-8 mg),fluocinolone acetonide(FA)implants(0.5μg/day)and dexamethasone(DEX)implants(700μg)improved short-term BCVA(mean changes in logMAR[95%confidence interval]−0.27[−0.40,−0.15];−0.12[−0.18,−0.06];−0.10[−0.21,−0.01];and−0.06[−0.11,−0.01]).Intravitreal TA injections(4 mg,multiple times),FA implants(0.5μg/day and 0.2μg/day),and DEX implants(350μg)improved long-term BCVA(mean changes in logMAR[95%confidence interval]−0.11[−0.21,−0.02];−0.09[−0.15,−0.03];−0.09[−0.14,−0.02];and−0.04[−0.07,−0.01]).All intravitreal corticosteroids reduced CMT,and different dosages of TA did not show significant differences in increasing ***:Intravitreal corticosteroids effectively improved BCVA in DME patients,with higher dosages showing greater *** was not inferior to FA or DEX and may be considered a low-cost alternative choice for DME *** long-term efficacy and safety of different corticosteroids deserve further investigation.

关键词： diabetic macular edema Corticosteroids Triamcinolone acetonide Fluocinolone acetonide Dexamethasone Best-corrected visual acuity Central macular thickness Intraocular pressure Network meta-analysis Randomized controlled trial

Optical coherence tomography angiography metrics in different stages of diabetic macular edema

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Eye and Vision 2024年第3期10卷 13-20页

作者： Ruyi Han Ruowen Gong Wei Liu Gezhi Xu Eye Institute and Department of Ophthalmology Eye and ENT Hospital of Fudan University83 Fenyang RoadShanghai200031People’s Republic of China Key Laboratory of Visual Impairment and Restoration Fudan UniversityShanghaiPeople’s Republic of China Key Laboratory of Myopia(Fudan University) Chinese Academy of Medical SciencesNational Health CommissionShanghaiPeople’s Republic of China

Background To investigate the optical coherence tomography angiography(OCTA)characteristics of diabetic macular edema(DME)at different *** This study was a cross-sectional *** diagnosed with DME were *** was classified into early,advanced,and severe *** vessel density(VD)in the superficial vascular plexus(SVP),deep vascular plexus(DVP)and foveal avascular zone(FAZ)parameters,including FAZ area,FAZ perimeter,acircularity index and foveal VD in a 300-μm-wide region around the FAZ(FD-300),were calculated by the AngioVue software.A multivariate generalized estimating equation was used to evaluate the associations between visual acuity and OCTA *** Ninety-two eyes from 74 patients with DME were included in this *** to early(P=0.006)and advanced DME(P=0.003),the acircularity index was higher in severe *** whole and parafoveal VD in the DVP decreased in eyes with severe DME compared to early DME(P=0.018,P=0.005,respectively)and advanced DME(P=0.035,P=0.012,respectively).In the multivariate generalized estimating equation,DME severity,FAZ area and foveal thickness were positively associated with worse visual acuity(P=0.001,P=0.007 and P=0.001,respectively).Conclusion Compared to early and advanced DME,severe DME showed increased irregularity in the FAZ and more extensive vessel damage in the *** severity level of DME,larger FAZ area,and increased foveal thickness could be risk factors for poor visual *** registration The protocol was published in the Chinese Clinical Trial Registry(ChiCTR2000033082).

关键词： Optical coherence tomography angiography diabetic macular edema Vessel density Acircularity index

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 *** major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser ***,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many *** might result from the incomplete recovery of retinal ganglion cell ***,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 *** 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 *** patients will be followed up for 12 *** primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after *** 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 *** measure is the incidence of adverse events at 1,3,6,9,and 12 months after *** 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 *** trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal

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

Prognostic factors of short-term outcomes of intravitreal ranibizumab in diabetic macular edema

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International Journal of Ophthalmology(English edition) 2017年第5期10卷 765-771页

作者： I-An Lai Wei-Cherng Hsu Chung-May Yang Yi-Ting Hsieh Department of Ophthalmology Taipei Tzu Chi HospitalBuddhist Tzu Chi Medical Foundation New Taipei 231Taiwan China School of Medicine Tzu Chi University Hualien 970 Taiwan Department of Ophthalmology National Taiwan University Hospital Taipei 10002 Taiwan China

AIM：To evaluate the prognostic factors for short-term visual and anatomical improvement of intravitreal ranibizumab（IVR） for diabetic macular edema（DME）.METHODS：Fifty-one eyes from 35 patients that received three consecutive monthly IVR for DME with moderate visual loss were retrospectively recruited; all cases had their baseline best-corrected visual acuity（BCVA） between 20/400 and 20/40. BCVA and central subfield thickness（CST） at baseline and month 3 were collected. Linear mixed models were used to evaluate the prognostic factors for visual and anatomical improvement at month ***：Younger age, poorer baseline BCVA and proliferative diabetic retinopathy（PDR） were correlated with better visual improvement at month 3（P=0.002, 0.0001 and 0.007, respectively）. Thicker CST and the presence of subretinal fluid at baseline were correlated with a greater reduction in CST（P〈0.0001 and P=0.018, respectively）. The presence of epiretinal membrane or previous posterior subtenon injection of triamcinolone acetonide（PSTA） were associated with a smaller reduction in CST（P=0.029 and 0.018, respectively）, but had no significant effects in visual improvement at month 3（P〉0.05 for both）.CONCLUSION：For eyes with DME and moderate visual loss, those with younger age, poorer baseline BCVA or PDR tend to have better visual improvement after three consecutive monthly IVR. Epiretinal membrane or previous PSTA result in less resolution of CST, but do not significantly affect visual improvement.

关键词： diabetic macular edema anti-vascular endothelial growth factor ranibizumab diabetic retinopathy epiretinal membrane

Subthreshold micropulse laser versus intravitreal anti-VEGF for diabetic macular edema patients with relatively better visual acuity

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International Journal of Ophthalmology(English edition) 2020年第10期13卷 1606-1611页

作者： Sezen Akkaya Banu Acιkalιn Yusuf Emre Dogan Fatih Coban Departmant of Ophthalmology Saglιk Bilimleri UniversityFSM Training and Research Hospitallstanbul 34752Turkey

AIM:To compare the effects of yellow(577 nm)subthreshold micropulse laser(SML)and intravitreal(IV)anti-vascular endothelial growth factor(VEGF)treatment in patients with diabetic macular edema(DME)with relatively better visual acuity[best corrected visual acuity(BCVA)≤0.15 log MAR].METHODS:The medical records of 76 eyes of 47 patients underwent IV(0.5 mg)anti-VEGF injection or SML for the DME with relatively better BCVA were *** IV group received three consecutive monthly IV anti-VEGF injections,then were retreated as *** laser treatment group was treated at baseline and 3 mo,and then retreated at 6 and 9 mo if *** participants were followed up for one *** mean BCVA and mean central macular thickness(CMT)values changes over the follow-up were ***:Twenty-four and 23 patients were assigned to the SML and IV subgroups,*** mean number of treatments was 3.64±0.76 in SML group and 5.85±1.38 in IV group(P<0.05).The subgroups were similar with regard to the mean BCVA score at baseline and at the 1st and 3rd months,but the score of SML group was better than that of IV group at the 6th,9th,and 12th months(P<0.05).The decrease in the mean CMT values from baseline values was higher in SML group at the 6th,9th,and 12th months(P<0.05).CONCLUSION:Yellow SML treatment is superior to IV anti-VEGF injection in DME patients with relatively better BCVA for increasing visual acuity and decreasing CMT at 6,9,and 12 *** can be a good alternative first-line therapy for DME with BCVA≤0.15 log MAR.

关键词： diabetic macular edema subthreshold micropulse laser anti-VEGF injection

Dexamethasone implant in naive versus refractory patients with diabetic macular edema:a Meta-analysis

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1898-1904页

作者： Qian Xu Chao Yang Jie Luan Department of Ophthalmology Zhongda HospitalSoutheast UniversityNanjing 210009Jiangsu ProvinceChina School of Medicine Southeast UniversityNanjing 210009Jiangsu ProvinceChina

AIM:To evaluate the efficacy and safety of the intravitreal dexamethasone implant in naive and refractory patients with diabetic macular edema(DME).METHODS:PubMed,Embase,Web of Science,and Medline databases were *** main outcomes were best-corrected visual acuity(BCVA)and central retinal thickness(CRT).The secondary outcomes included mean number of injections,intraoperative or postoperative complications including intraocular pressure(IOP)elevation and ***:Ten comparative studies involving a total of 1000 DME eyes including 402 naive eyes and 598 refractory eyes were *** postoperative BCVA in the naive group was significantly better than in the refractory group[mean difference(MD)-0.11,95% confidence interval(CI)-0.17 to-0.05,P=0.0003;MD 8.69,95%CI 5.08 to 12.30,P<0.00001].Additionally,the naive group got greater improvement of BCVA change as well as more gains of BCVA letters than the refractory group[MD 7.71,95%CI 2.02 to 13.40,P=0.008;odds ratio(OR)2.99,95%CI 2.05 to 4.37,P<0.00001].The subgroup analysis revealed that the naive group had significantly higher BCVA gains of≥5,≥10,and≥15 letters compared to the refractory group(P=0.002,0.0001,0.003,respectively).No significant difference was detected between the two groups in either postoperative CRT(MD-22.36,95%CI-46.39 to 1.66,P=0.07)or the overall mean number of injections(MD-0.08,95%CI-0.38 to 0.22,P=0.61).Intraoperative and postoperative complications including the elevation of IOP(OR 0.47,95%CI 0.20 to 1.13,P=0.09)and cataract(OR 1.78,95%CI 0.97 to 3.24,P=0.06)showed no significant differences between the two groups during the follow-up ***:Intravitreal dexamethasone implants for DME can improve anatomical and functional outcomes in both naive and refractory eyes and have a well-acceptable safety ***,naive eyes maintain better visual outcomes than refractory *** provides further evidence of better visual response when used for naive eyes as firstline

关键词： diabetic macular edema dexamethasone implant refractory eyes systemic review

Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 297-303页

作者： De-Shuang Li Hong-Xia Liao Jing-Lin Zhang Bo Qin Shenzhen Aier Eye Hospital Aier Eye HospitalJinan UniversityShenzhen 518031Guangdong ProvinceChina Guangzhou Aier Eye Hospital Jinan UniversityGuangzhou 510040Guangdong ProvinceChina

AIM:To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide(TA)in treating diabetic macular edema(DME)and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after ***:Totally 67 DME patients(67 eyes)and 30 cataract patients(32 eyes)were enrolled as the DME group and the control group,*** DME group was divided into the aflibercept group(34 cases)and the aflibercept combined with TA group(combined group,33 cases).The aqueous humor of both groups was collected during the study *** aqueous levels of vascular endothelial growth factor(VEGF),monocyte chemoattractant protein-1(MCP-1),interleukin-6(IL-6),interleukin-8(IL-8),and interleukin-1β(IL-1β)were detected using a microsphere suspension array technology(Luminex 200TM).Aqueous cytokines,best-corrected visual acuity(BCVA),central macular thickness(CMT),and complications before and after treatment were compared between the aflibercept group and combined ***:The concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group(all P0.05).CONCLUSION:The cytokines VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor of DME patients are significantly *** and aflibercept combined with TA have good efficacy in DME patients,can effectively reduce CMT,improve the patient’s vision,and have high *** combined with TA can quickly downregulate the aqueous humor cytokines and help to relieve macular edema ***,the long-term eff

关键词： diabetic macular edema aqueous humor cytokines aflibercept triamcinolone acetonide

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema:optical coherence tomography and optical coherence tomography angiography

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 670-675页

作者： De-Shuang Li Hong-Xia Liao Chuan-He Zhang Jian-Guo Huang Wei Chen Jing-Lin Zhang Bo Qin Shenzhen Aier Eye Hospital Aier Eye HospitalJinan UniversityShenzhen 518031Guangdong ProvinceChina Department of Ophthalmology the University of Hong Kong-Shenzhen HospitalShenzhen 518000Guangdong ProvinceChina Guangzhou Aier Eye Hospital Jinan UniversityGuangzhou 510040Guangdong ProvinceChina

AIM:To analyze the relationship between optical coherence tomography(OCT)and OCT angiography(OCTA)imaging in patients with diabetic macular edema(DME)who are treated with a combination of aflibercept and triamcinolone acetonide(TA).METHODS:A total of 76 eyes newly diagnosed DME were included in this *** were randomly assigned to receive either aflibercept or a combination of aflibercept and *** once a month for a total of three *** macular thickness(CMT),number of hyperreflective foci(HRF),height of subretinal fluid(SRF),and area of foveal avascular zone(FAZ)were evaluated using OCT and OCTA at baseline and after each monthly ***:Both groups showed improvement in best corrected visual acuity(BCVA)and reduction in macular edema after treatment,and the difference in BCVA between the two groups was statistically significant after each treatment(P<0.05).The difference in CMT between the two groups was statistically significant after the first two injections(P<0.01),but not after the third injection(P=0.875).The number of HRF(1mo:7.41±8.25 vs 10.86±7.22,P=0.027;2mo:5.33±6.13 vs 9.12±8.61,P=0.034;3mo:3.58±3.00 vs 6.37±5.97,P=0.007)and height of SRF(1mo:82.39±39.12 vs 105.77±42.26μm,P=0.011;2mo:36.84±10.02 vs 83.59±37.78μm,P<0.01;3mo:11.57±3.29 vs 45.43±12.60μm,P<0.01)in combined group were statistically significant less than aflibercept group after each injection,while the area of FAZ showed no significant change before and after treatment in both ***:The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and ***,both aflibercept and combination therapy show no significant change in the area of FAZ.

关键词： diabetic macular edema optical coherence tomography optical coherence tomography angiography hyperreflective foci subretinal fluid foveal avascular zone aflibercept