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 bett...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 reviewed.The IV group received three consecutive monthly IV anti-VEGF injections,then were retreated as needed.The laser treatment group was treated at baseline and 3 mo,and then retreated at 6 and 9 mo if needed.All participants were followed up for one year.The mean BCVA and mean central macular thickness(CMT)values changes over the follow-up were evaluated.RESULTS:Twenty-four and 23 patients were assigned to the SML and IV subgroups,respectively.The 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 mo.SML can be a good alternative first-line therapy for DME with BCVA≤0.15 log MAR.展开更多
AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF) in patients with macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: Twen...AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF) in patients with macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: Twenty-eight eyes from twenty-eight treatment-na?ve patients(14 males and 14 females) with RVO-ME were included in this retrospective study.The retinal vein occlusion(RVO) was comprised of both central retinal vein occlusion(CRVO,n=14) and branch retinal vein occlusion(BRVO,n=14).Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months,in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept.All eyes were imaged with optical coherence tomography angiography(OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection.The visual acuity(VA),central macular thickness(CMT),the number of hyperreflective foci(HRF) recognized as an inflammatory sign in OCT images,and non-perfusion area(NPA),were compared before and after anti-VEGF treatments.RESULTS: The mean interval between baseline and follow-up was 29.4±0.79(range,27-48)d.Compared with the baseline,the VA improved(log MAR 1.5±0.1 vs 0.8±0.1,P<0.05) and CMT decreased(460±34.0 μm vs 268.8±12.0 μm,P<0.05),significantly,after antiVEGF treatment.The number of HRF was decreased significantly(76.5±4.8 vs 47.8±4.3,P<0.05) after antiVEGF treatment.CONCLUSION: Anti-VEGF therapy is effective in treating RVO-ME.The mechanisms for the decreased HRF and the reduction of NPA by anti-VEGF therapy merits further exploration.展开更多
AIM: To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD). ·METHO...AIM: To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD). ·METHODS: This retrospective study includes 35 eyes of 35 patients treated with intravitreal bevacizumab (IVB, 1.25mg/0.05mL) and 30 eyes of 30 patients with intravitreal ranibizumab (IVR, 0.5mg/0.05mL) who had Fast RNFL analysis (Stratus TM ); IOP measurements were taken 30 minutes and 24 hours after each injection. RESULTS: The mean ages were 68.0±7.5 and 69.1±7.7 years in the IVR and IVB groups, respectively (P =0.55). They underwent (6.3±1.9) and (5.1±1.3) injections (P = 0.07) over (13.6±2.1) and (14.05±2.6) months (P =0.45) in the IVR and IVB groups, respectively. Changes in overall and temporal RNFL thickness in IVR-treated eyes (105.3± 6.9μm and 74.4±11.2μm) were not different from those in untreated eyes in the IVR group (104.6±8.4μm and 75.1±12.6μm) (P =0.57 and P =0.41, respectively). Similarly, overall and temporal RNFL thickness in IVB-treated eyes (105.8±8.1μm and 74.5±11.8μm) were not different from those in untreated eyes in the IVB group (104.6±8μm and 74.8±12.9μm) (P=0.42 and P=0.80, respectively). The frequencies of IOP rise (P=0.60) and changes in RNFL thickness from baseline (P =0.16) were comparable between groups. CONCLUSION: Repeated intravitreal injection of ranibizumab or bevacizumab does not seem have adverse effects on RNFL thickness or IOP in wet AMD patients.展开更多
AIM: To analyze concentrations of vascular endothelial growth factor(VEGF) and fibrosis-related factors in vitreous fluid of proliferative diabetic retinopathy(PDR) patients pretreated with intravitreal anti-VEGF inje...AIM: To analyze concentrations of vascular endothelial growth factor(VEGF) and fibrosis-related factors in vitreous fluid of proliferative diabetic retinopathy(PDR) patients pretreated with intravitreal anti-VEGF injections(IVI) at different time periods prior to pars plana vitrectomy(PPV), and their correlation with the degree of vitreoretinal fibrosis and explore the optimal timing of preoperative IVI.METHODS: The prospective case-control study from January 2019 to July 2020 included 31 eyes with PDRrelated complications(PDR group) and 21 eyes with nondiabetic ocular disease(control group) requiring PPV. PDR eyes were divided into four groups based on timing of PPV: 3 d after IVI(3-day group);5 d after IVI(5-day group);7 or more days after IVI(≥7-day group);and no IVI. Vitreous fluid samples(0.5-1.0 m L) were collected prior to switching on the infusion before routine 23-G PPV. Concentrations of VEGF, basic fibroblast growth factor(b FGF), periostin(PN), interleukin(IL)-6, IL-8, and tumor necrosis factor(TNF)-α were measured by immunoassay, and concentration differences for each cytokine were compared among the groups. The degree of vitreoretinal fibrosis was graded intraoperatively, and the correlation between the changes in cytokine levels and the severity of vitreoretinal fibrosis was analyzed by univariate ordinal logistic regression analysis.RESULTS: PDR eyes without IVI had significantly higher VEGF, b FGF, PN, and IL-6 concentrations than nondiabetic eyes(all P<0.05), and had a significantly higher concentration of VEGF(P<0.05) and a significantly lower concentration of IL-8(P<0.05) than PDR eyes with IVI. Statistically significant differences were also observed for concentrations of VEGF, b FGF, PN, IL-6, and IL-8 among 3-day, 5-day, and ≥7-day groups(all P<0.05);meanwhile there was no significant difference in TNF-α among groups(P=0.226). The 5-day group had the lowest concentration of VEGF and the ≥7-day group had the highest concentration of b FGF and PN. The degree of vitreoretinal fibrosis was significantly higher in the ≥7-day group compared to the 3-day(P=0.015) and 5-day group(P=0.039), and vitreoretinal fibrosis correlated significantly with concentrations of b FGF, PN, IL-6, and IL-8(all P<0.05). Univariate ordinal logistic regression analysis showed that b FGF was an independent risk factor for the severity of vitreoretinal fibrosis in PDR patients pre-treated with IVI.CONCLUSION: The vitreous concentrations of VEGF, b FGF, PN, IL-6, and IL-8 change after pretreatment with IVI before PPV in PDR patients. The degree of vitreoretinal fibrosis is higher in patients with a longer time between IVI treatment and PPV, which may be related to the angiofibrosis switch. The results suggest that PPV should be performed 5 d after IVI administration in PDR patients.展开更多
Age related macular degeneration (AMD) is a complex progres- sive neurodegenerative disease causing blindness in 30-35 million people worldwide. It affects the macula region of the retina leading to severe vision lo...Age related macular degeneration (AMD) is a complex progres- sive neurodegenerative disease causing blindness in 30-35 million people worldwide. It affects the macula region of the retina leading to severe vision loss and legal blindness in individuals 〉 50 years of age (Wong et al., 2014). The precise aetiology of AMD is unknown but smoking, age and genetic factors are major risk factors for AMD predisposition (Ding et al., 2009). The genetic basis of AMD is well described with a recent study from the International AMD gene consortium (IAMDGC) reporting 52 genetic variants across 34 loci associated with the risk of AMD pathogenesis and explaining more than 50% of the genetic heritabilitv of the disease (Fritsche et al., 2016).展开更多
Purpose: To evaluate the short-term efficacy of intravitreal anti-VEGF (Lucentis) and sub-tenon injection of triamcinolone acetonide for choroidal neovascularization (CNV) associated with multifocal choroiditis (MC). ...Purpose: To evaluate the short-term efficacy of intravitreal anti-VEGF (Lucentis) and sub-tenon injection of triamcinolone acetonide for choroidal neovascularization (CNV) associated with multifocal choroiditis (MC). Methods: Eight eyes of 8 patients treated with intravitreal anti-VEGF and posterior sub-tenon injection of Triamcinolone Acetonide (TA) for subfoveal or juxtafoveal CNV associated with MC were retrospectively reviewed. Best corrected visual acuity (BCVA), results of fundus fluorescein angiography (FFA)/indocyanine green angiography (ICGA), optical coherence tomography (OCT) at baseline and 3, 6 months after treatment were compared. Results: All of the 8 patients showed significant improvement in BCVA at 3 and 6 months after treatment (P < 0.05). FFA/ICGA showed decrease or cessation of inflammation in 8 patients (100%). 7 patients (87.5%) had no significant active leakage while 1 patient (12.5%) had persistent leakage from the neovascular lesion at 3-month follow up. 6 months after treatment, no recurrence of inflammation occurred and no active leakage in all 8 patients. OCT showed reduced CNV area and alleviated edema. There are no severe treatment-related side effects expect slight eye pain during infusion in one patient. Intraocular pressure was all normal in follow up. Conclusion: Although the follow-up time and the number of patients in this study were limited, the use of intravitreal anti-VEGF combined with sub-tenon injection of TA was associated with improvement of visual acuity in patients with CNV secondary to MC. Further studies including a greater number of patients with longer follow up time are needed.展开更多
Dear Sir,Ifound the article by Sobac1etal[1]very interesting.The authors concluded that repeated intravitreal injection(IVI)of ranibizumab or bevacizumab didn’t seem have adverse effects on retinal nerve fiber layer(...Dear Sir,Ifound the article by Sobac1etal[1]very interesting.The authors concluded that repeated intravitreal injection(IVI)of ranibizumab or bevacizumab didn’t seem have adverse effects on retinal nerve fiber layer(RNFL)thickness in wet age-related macular degeneration(AMD)patients.展开更多
Background To evaluate whether the specific choroidal neovascularization(CNV)characteristics measured using optical coherence tomography angiography(OCTA)can predict the 6-month prognosis of neovascular age-related ma...Background To evaluate whether the specific choroidal neovascularization(CNV)characteristics measured using optical coherence tomography angiography(OCTA)can predict the 6-month prognosis of neovascular age-related macular degeneration(nAMD)after anti-vascular endothelial growth factor(anti-VEGF)therapy.Methods Patients with type 1,type 2,or mixed-type neovascularization(NV)were prospectively included.Participants underwent an initial loading phase of three consecutive monthly intravitreal injections of Conbercept(0.5 mg)and were switched to a pro re nata(PRN)treatment strategy.OCTA images were evaluated for eyes that underwent follow-up assessments for more than 6 months.CNV lesions were manually segmented,and the CNV area,vessel area,greatest vascular caliber(GVC),and greatest linear dimension(GLD)were compared between responders and non-responders.Two masked graders independently measured the above-mentioned parameters using OCTA,and consistency was assessed using the intraclass correlation coefficient(ICC)values.Multiple logistic regression analysis was performed to evaluate the effect of a 3-month change in the CNV area,GLD,and GVC on the 6-month response to anti-VEGF agents.Results Among the 60 eyes of 60 patients with nAMD,39 were responders and 21 were non-responders.The proportion of CNV types was significantly different between responders and non-responders(P=0.009).Patients with type 2 or mixed NV seemed more likely to respond to the treatment(28.2%vs.0.0%,and 30.8%vs.23.8%,respectively).The change in GVC showed a significant difference between responders(−4.98±17.17μm)and non-responders(11.01±14.10μm)after three monthly intravitreal anti-VEGF injections.Multiple logistic regression analysis showed that only the change in GVC remained significant after controlling for baseline GVC,injection number,and CNV type(adjusted OR=1.083;P=0.008).Conclusions Type 2 and mixed-type NV were significantly associated with a better response to anti-VEGF therapy.Changes in GVC after 3 months of treatment were significantly associated with a response to anti-VEGF therapy at 6 months.展开更多
Purpose:To establish a comprehensive treatment strategy and evaluate the efficacy of combination of anti-vascular endothelial growth factor(VEGF)injection,pars plana vitrectomy(PPV),endoscopic pan-retinal photocoagula...Purpose:To establish a comprehensive treatment strategy and evaluate the efficacy of combination of anti-vascular endothelial growth factor(VEGF)injection,pars plana vitrectomy(PPV),endoscopic pan-retinal photocoagulation(PRP),and endoscopic cyclophotocoagulation(ECP)surgery for neovascular glaucoma(NVG)patients.Methods:This retrospective study included 30 patients(30 eyes)who were suffering from NVG and treated with PPV&PRP&ECP(ECP group,16 eyes),or Ahmed glaucoma valve implantation(Ahmed group,14 eyes).The intraocular pressure(IOP),number of postoperative anti-glaucoma medications,best-corrected visual acuity(BCVA),successful rate of surgery,and postoperative complications were recorded and statistically analyzed at the time points of preoperative,1-day,1-month,3-months,6-months,and 12-months after operation.Results:An obvious reduction in IOP and number of postoperative anti-glaucoma medications were observed in both the ECP group and Ahmed group after operation(P<0.05),and the ECP group showed a significantly lower IOP compared to the Ahmed group at the 6-months(P=0.014)and 12-months(P=0.047)postoperative time points,while there was no significant difference of medication number between the two groups except for 1-day after surgery.The BCVA showed no marked difference between the two groups preoperatively and postoperatively(P>0.05),while it was significantly improved in ECP group at 3-months(P=0.001),6-months(P=0.004),and 12-months(P=0.010)time points comparing with preoperative BCVA.The surgical success rates in ECP group were also slightly higher than Ahmed group.And the complications after operation showed no marked differences.Conclusions:The comprehensive treatment of PPV,endoscopic PRP,and ECP surgery for NVG patients after antiVEGF injection can control IOP effectively and be friendly to patients’BCVA without obvious serious complications throughout a 12-months follow-up period.展开更多
目的分析缺血性视网膜静脉阻塞继发黄斑水肿(RVO-ME)患者基线血清己糖激酶1抗体滴度与抗血管内皮生长因子(VEGF)治疗后视力改善的相关性。方法招募2017年6月至2020年2月在首都医科大学宣武医院确诊为缺血性RVO-ME并接受初始抗VEGF治疗...目的分析缺血性视网膜静脉阻塞继发黄斑水肿(RVO-ME)患者基线血清己糖激酶1抗体滴度与抗血管内皮生长因子(VEGF)治疗后视力改善的相关性。方法招募2017年6月至2020年2月在首都医科大学宣武医院确诊为缺血性RVO-ME并接受初始抗VEGF治疗的53例患者,其中缺血性视网膜中央静脉阻塞(CRVO)23例(CRVO组),缺血性视网膜分支静脉阻塞(BRVO)30例(BRVO组)。另选取该院同期30例行超声乳化的白内障患者作为对照组。研究对象行基线血清己糖激酶1抗体滴度检测、眼科常规检查和光学相干断层成像(OCT)检查。所有RVO-ME患者按照“3+按需治疗方案(pro re nata,PRN)”向玻璃体内注射抗VEGF药物治疗。随访12个月,采用多元线性回归分析缺血性RVO-ME患者抗VEGF治疗后视力改善的影响因素。结果CRVO组基线logMAR BCVA高于对照组和BRVO组,CRVO组和BRVO组基线CRT、基线血清己糖激酶1抗体滴度高于对照组,且CRVO组基线CRT、基线血清己糖激酶1抗体滴度高于BRVO组,差异有统计学意义(P<0.05)。RVO-ME患者基线血清己糖激酶1抗体滴度与随访6个月(r=0.377,P=0.005)、9个月(r=0.362,P=0.008)和12个月(r=0.465,P<0.001)时BCVA改善呈正相关,与随访12个月时中断EZ横向长度减少值(r=0.401,P=0.001)呈正相关。多元线性回归分析结果显示,基线logMAR BCVA、基线血清己糖激酶1抗体滴度是缺血性RVO-ME患者抗VEGF治疗随访12个月时BCVA改善的影响因素(P<0.05)。结论己糖激酶1抗体作为一种新的血清生物标志物,与缺血性RVO-ME患者抗VEGF治疗后的视力改善相关。展开更多
肝细胞癌(hepatocellular carcinoma,HCC)是全球高发的恶性肿瘤。程序性死亡蛋白-1(programmed death protein-1,PD-1)/程序性死亡蛋白配体-1(programmed death protein ligand-1,PD-L1)抑制剂可通过阻断T细胞负调节信号,抑制肿瘤细胞...肝细胞癌(hepatocellular carcinoma,HCC)是全球高发的恶性肿瘤。程序性死亡蛋白-1(programmed death protein-1,PD-1)/程序性死亡蛋白配体-1(programmed death protein ligand-1,PD-L1)抑制剂可通过阻断T细胞负调节信号,抑制肿瘤细胞免疫逃逸途径,重新激活抗肿瘤免疫应答过程,成为晚期HCC治疗的新手段。然而,长期临床结果显示,采用PD-1/PD-L1抑制剂单药治疗晚期HCC的病人仍存在较高的复发率和转移率。免疫联合疗法是目前针对晚期HCC患者的新的治疗策略,其中PD-1/PD-L1抑制剂联合抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物在晚期HCC治疗中显示出了良好的疗效和安全性。PD-1/PD-L1抑制剂联合抗VEGF药物可通过参与癌症免疫循环途径抑制肝癌细胞的生长。该文就PD-1/PD-L1抑制剂联合抗VEGF药物在晚期HCC治疗中的临床研究作一综述。展开更多
Angiogenesis is crucial for tumor development, growth and metastasis. Vascular endothelial growth factor (VEGF) has been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated ang...Angiogenesis is crucial for tumor development, growth and metastasis. Vascular endothelial growth factor (VEGF) has been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis, and blocking the activity of VEGF can starve tumors. Avastin, which is a humanized anti-VEGF antibody, has been successfully applied in clinics since 2004. However, the price of Avastin is extremely high for Chinese people. Here, we report a novel human anti-VEGF neutralizing antibody, MIL60, which shows an affinity comparable to that of Avastin (the KD value of MIL60 was 44.5 pM, while that of Avastin was 42.7 pM). MIL60 displays favorable actions in inhibiting VEGF-triggered endothelial cell proliferation (the IC5o value of M IL60 was 31-6.4 ng/ml and that of Avastin was 47--.8.1 ng/ml), migration (8 pg/ml or 0.8 pg/ml MIL60 versusthe control: P〈O.05) and tube formation (2 I^g/ml or 0.2 lzg/ml MIL60 versusthe control: P〈O.05) viathe VEGFR2 signaling pathway. Moreover, MIL60 was shown to inhibit tumor growth and angiogenesis in vivo in xenograft models of human colon carcinoma and ovarian cancer using immunotherapy and immunohistochemistry analysis (MIL60 versus N.S.: P=0.0007; Avastin versus N.S.: P=0.00046). These data suggest that MIL60 is a potential therapeutic, anti-angiogenic agent. Our work provides a novel anti-VEGF antibody, which can be considered an anti-tumor antibody candidate and a new option for patients with various cancers.展开更多
Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprag...Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin.Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset.rMC-1 cells(rat Müller cell line)were treated with glyoxal for 24 h with or without ranibizumab.The expression levels of inwardly rectifying K^(+)channel 4.1(Kir4.1),aquaporin 4(AQP4),Dystrophin 71(Dp71),VEGF-A,glutamine synthetase(GS)and sodium-potassium-ATPase(Na^(+)-K^(+)-ATPase)were examined using Western blot.VEGF-A in the supernatant of the cell culture was detected with ELISA.The intracellular potassium and sodium levels were detected with specific indicators.Results:Compared with normal control,protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas,which were prevented by ranibizumab.The above changes were recapitulated in vitro.Similarly,the intracellular potassium level in glyoxal-treated rMC-1 cells was increased,while the intracellular sodium level and Na^(+)-K^(+)-ATPase protein level remained unchanged,compared with control.However,ranibizumab treatment decreased intracellular sodium,but not potassium.Conclusion:Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A.It also caused a reduction in intracellular osmotic pressure.展开更多
Background:To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities(IRMAs)in response to anti-vascular endothelial growth factor(anti-VEGF)treatment,documented ...Background:To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities(IRMAs)in response to anti-vascular endothelial growth factor(anti-VEGF)treatment,documented by optical coherence tomography angiography(OCTA)in diabetic eyes.Methods:In this retrospective study,IRMAs were evaluated with multimodal imaging(fundus photography,fluorescein angiography,OCTA)in treatment-naïve diabetic eyes before and after anti-VEGF treatment for diabetic macular edema(DME)and/or proliferative diabetic retinopathy(PDR)and compared to diabetic control eyes with similar diabetic retinopathy(DR)severity that did not receive anti-VEGF therapy.The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline,then after anti-VEGF therapy in treated eyes or after observation in control eyes.Characterization of interval changes in an IRMA were based on the following parameters:branching,vessel caliber and area of adjacent capillary non-perfusion.Results:The treated group included 45 IRMA foci from 15 eyes of 11 patients,while the control group included 27 IRMA foci from 15 eyes of 14 patients.Following anti-VEGF treatment,enface OCTA demonstrated that 14 foci of IRMA(31%)demonstrated regression with normalization of appearance of the capillary bed,20 IRMAs(44%)remained unchanged,six IRMAs(13%)progressed with enlargement or development of new IRMAs and five IRMAs(11%)demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out.In the control group,17 IRMA(63%)remained stable,8 IRMAs(29.6%)progressed and 2 experienced total obliteration(7.4%).The difference in rank order between the two groups was statistically significant(p=0.022).Conclusions:In eyes with DR status post anti-VEGF therapy,foci of IRMAs have a variable course demonstrating one of four possible outcomes:regression,stabilit,progression or complete obliteration.In contrast,none of the untreated control diabetic eyes demonstrated regression of IRMAs,consistent with known progression of DR severity in high risk eyes.Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as well as the response to anti-VEGF treatment.展开更多
文摘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 reviewed.The IV group received three consecutive monthly IV anti-VEGF injections,then were retreated as needed.The laser treatment group was treated at baseline and 3 mo,and then retreated at 6 and 9 mo if needed.All participants were followed up for one year.The mean BCVA and mean central macular thickness(CMT)values changes over the follow-up were evaluated.RESULTS:Twenty-four and 23 patients were assigned to the SML and IV subgroups,respectively.The 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 mo.SML can be a good alternative first-line therapy for DME with BCVA≤0.15 log MAR.
基金Supported by the National Natural Science Foundation of China (No.81970811No.81970810+1 种基金No.82171062)Domestic Science and Technology Cooperation Project of Shanghai Municipal Science and Technology Commission (No.21015800700)。
文摘AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF) in patients with macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: Twenty-eight eyes from twenty-eight treatment-na?ve patients(14 males and 14 females) with RVO-ME were included in this retrospective study.The retinal vein occlusion(RVO) was comprised of both central retinal vein occlusion(CRVO,n=14) and branch retinal vein occlusion(BRVO,n=14).Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months,in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept.All eyes were imaged with optical coherence tomography angiography(OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection.The visual acuity(VA),central macular thickness(CMT),the number of hyperreflective foci(HRF) recognized as an inflammatory sign in OCT images,and non-perfusion area(NPA),were compared before and after anti-VEGF treatments.RESULTS: The mean interval between baseline and follow-up was 29.4±0.79(range,27-48)d.Compared with the baseline,the VA improved(log MAR 1.5±0.1 vs 0.8±0.1,P<0.05) and CMT decreased(460±34.0 μm vs 268.8±12.0 μm,P<0.05),significantly,after antiVEGF treatment.The number of HRF was decreased significantly(76.5±4.8 vs 47.8±4.3,P<0.05) after antiVEGF treatment.CONCLUSION: Anti-VEGF therapy is effective in treating RVO-ME.The mechanisms for the decreased HRF and the reduction of NPA by anti-VEGF therapy merits further exploration.
文摘AIM: To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD). ·METHODS: This retrospective study includes 35 eyes of 35 patients treated with intravitreal bevacizumab (IVB, 1.25mg/0.05mL) and 30 eyes of 30 patients with intravitreal ranibizumab (IVR, 0.5mg/0.05mL) who had Fast RNFL analysis (Stratus TM ); IOP measurements were taken 30 minutes and 24 hours after each injection. RESULTS: The mean ages were 68.0±7.5 and 69.1±7.7 years in the IVR and IVB groups, respectively (P =0.55). They underwent (6.3±1.9) and (5.1±1.3) injections (P = 0.07) over (13.6±2.1) and (14.05±2.6) months (P =0.45) in the IVR and IVB groups, respectively. Changes in overall and temporal RNFL thickness in IVR-treated eyes (105.3± 6.9μm and 74.4±11.2μm) were not different from those in untreated eyes in the IVR group (104.6±8.4μm and 75.1±12.6μm) (P =0.57 and P =0.41, respectively). Similarly, overall and temporal RNFL thickness in IVB-treated eyes (105.8±8.1μm and 74.5±11.8μm) were not different from those in untreated eyes in the IVB group (104.6±8μm and 74.8±12.9μm) (P=0.42 and P=0.80, respectively). The frequencies of IOP rise (P=0.60) and changes in RNFL thickness from baseline (P =0.16) were comparable between groups. CONCLUSION: Repeated intravitreal injection of ranibizumab or bevacizumab does not seem have adverse effects on RNFL thickness or IOP in wet AMD patients.
基金Supported by the Guiding Science and Technology Plan Project of Huainan City(No.2020044)Construction Project of Key Medical and Health of Anhui Province in 2021。
文摘AIM: To analyze concentrations of vascular endothelial growth factor(VEGF) and fibrosis-related factors in vitreous fluid of proliferative diabetic retinopathy(PDR) patients pretreated with intravitreal anti-VEGF injections(IVI) at different time periods prior to pars plana vitrectomy(PPV), and their correlation with the degree of vitreoretinal fibrosis and explore the optimal timing of preoperative IVI.METHODS: The prospective case-control study from January 2019 to July 2020 included 31 eyes with PDRrelated complications(PDR group) and 21 eyes with nondiabetic ocular disease(control group) requiring PPV. PDR eyes were divided into four groups based on timing of PPV: 3 d after IVI(3-day group);5 d after IVI(5-day group);7 or more days after IVI(≥7-day group);and no IVI. Vitreous fluid samples(0.5-1.0 m L) were collected prior to switching on the infusion before routine 23-G PPV. Concentrations of VEGF, basic fibroblast growth factor(b FGF), periostin(PN), interleukin(IL)-6, IL-8, and tumor necrosis factor(TNF)-α were measured by immunoassay, and concentration differences for each cytokine were compared among the groups. The degree of vitreoretinal fibrosis was graded intraoperatively, and the correlation between the changes in cytokine levels and the severity of vitreoretinal fibrosis was analyzed by univariate ordinal logistic regression analysis.RESULTS: PDR eyes without IVI had significantly higher VEGF, b FGF, PN, and IL-6 concentrations than nondiabetic eyes(all P<0.05), and had a significantly higher concentration of VEGF(P<0.05) and a significantly lower concentration of IL-8(P<0.05) than PDR eyes with IVI. Statistically significant differences were also observed for concentrations of VEGF, b FGF, PN, IL-6, and IL-8 among 3-day, 5-day, and ≥7-day groups(all P<0.05);meanwhile there was no significant difference in TNF-α among groups(P=0.226). The 5-day group had the lowest concentration of VEGF and the ≥7-day group had the highest concentration of b FGF and PN. The degree of vitreoretinal fibrosis was significantly higher in the ≥7-day group compared to the 3-day(P=0.015) and 5-day group(P=0.039), and vitreoretinal fibrosis correlated significantly with concentrations of b FGF, PN, IL-6, and IL-8(all P<0.05). Univariate ordinal logistic regression analysis showed that b FGF was an independent risk factor for the severity of vitreoretinal fibrosis in PDR patients pre-treated with IVI.CONCLUSION: The vitreous concentrations of VEGF, b FGF, PN, IL-6, and IL-8 change after pretreatment with IVI before PPV in PDR patients. The degree of vitreoretinal fibrosis is higher in patients with a longer time between IVI treatment and PPV, which may be related to the angiofibrosis switch. The results suggest that PPV should be performed 5 d after IVI administration in PDR patients.
基金funding from the National Health and Medical Research Council of Australia (NHMRC) project grant 1008979Senior Research Fellowship 1028444 (PNB)+1 种基金Melbourne International research ScholarshipMelbourne International fee remission scholarship from the University of Melbourne Australia
文摘Age related macular degeneration (AMD) is a complex progres- sive neurodegenerative disease causing blindness in 30-35 million people worldwide. It affects the macula region of the retina leading to severe vision loss and legal blindness in individuals 〉 50 years of age (Wong et al., 2014). The precise aetiology of AMD is unknown but smoking, age and genetic factors are major risk factors for AMD predisposition (Ding et al., 2009). The genetic basis of AMD is well described with a recent study from the International AMD gene consortium (IAMDGC) reporting 52 genetic variants across 34 loci associated with the risk of AMD pathogenesis and explaining more than 50% of the genetic heritabilitv of the disease (Fritsche et al., 2016).
文摘Purpose: To evaluate the short-term efficacy of intravitreal anti-VEGF (Lucentis) and sub-tenon injection of triamcinolone acetonide for choroidal neovascularization (CNV) associated with multifocal choroiditis (MC). Methods: Eight eyes of 8 patients treated with intravitreal anti-VEGF and posterior sub-tenon injection of Triamcinolone Acetonide (TA) for subfoveal or juxtafoveal CNV associated with MC were retrospectively reviewed. Best corrected visual acuity (BCVA), results of fundus fluorescein angiography (FFA)/indocyanine green angiography (ICGA), optical coherence tomography (OCT) at baseline and 3, 6 months after treatment were compared. Results: All of the 8 patients showed significant improvement in BCVA at 3 and 6 months after treatment (P < 0.05). FFA/ICGA showed decrease or cessation of inflammation in 8 patients (100%). 7 patients (87.5%) had no significant active leakage while 1 patient (12.5%) had persistent leakage from the neovascular lesion at 3-month follow up. 6 months after treatment, no recurrence of inflammation occurred and no active leakage in all 8 patients. OCT showed reduced CNV area and alleviated edema. There are no severe treatment-related side effects expect slight eye pain during infusion in one patient. Intraocular pressure was all normal in follow up. Conclusion: Although the follow-up time and the number of patients in this study were limited, the use of intravitreal anti-VEGF combined with sub-tenon injection of TA was associated with improvement of visual acuity in patients with CNV secondary to MC. Further studies including a greater number of patients with longer follow up time are needed.
文摘Dear Sir,Ifound the article by Sobac1etal[1]very interesting.The authors concluded that repeated intravitreal injection(IVI)of ranibizumab or bevacizumab didn’t seem have adverse effects on retinal nerve fiber layer(RNFL)thickness in wet age-related macular degeneration(AMD)patients.
基金supported by Frontier Project of Hospital Development Center(SHDC12016105)Clinical Research Innovation Team Project of Shanghai General Hospital(CTCCR-2016A02)+2 种基金Scientific Project of Shanghai Municipal Health Commission(201940151)Shanghai Collaborative Innovation Center for Translational Medicine(TM201917)Shanghai Hospital Development Center(SHDC2020CR2040B and SHDC2020CR5014).
文摘Background To evaluate whether the specific choroidal neovascularization(CNV)characteristics measured using optical coherence tomography angiography(OCTA)can predict the 6-month prognosis of neovascular age-related macular degeneration(nAMD)after anti-vascular endothelial growth factor(anti-VEGF)therapy.Methods Patients with type 1,type 2,or mixed-type neovascularization(NV)were prospectively included.Participants underwent an initial loading phase of three consecutive monthly intravitreal injections of Conbercept(0.5 mg)and were switched to a pro re nata(PRN)treatment strategy.OCTA images were evaluated for eyes that underwent follow-up assessments for more than 6 months.CNV lesions were manually segmented,and the CNV area,vessel area,greatest vascular caliber(GVC),and greatest linear dimension(GLD)were compared between responders and non-responders.Two masked graders independently measured the above-mentioned parameters using OCTA,and consistency was assessed using the intraclass correlation coefficient(ICC)values.Multiple logistic regression analysis was performed to evaluate the effect of a 3-month change in the CNV area,GLD,and GVC on the 6-month response to anti-VEGF agents.Results Among the 60 eyes of 60 patients with nAMD,39 were responders and 21 were non-responders.The proportion of CNV types was significantly different between responders and non-responders(P=0.009).Patients with type 2 or mixed NV seemed more likely to respond to the treatment(28.2%vs.0.0%,and 30.8%vs.23.8%,respectively).The change in GVC showed a significant difference between responders(−4.98±17.17μm)and non-responders(11.01±14.10μm)after three monthly intravitreal anti-VEGF injections.Multiple logistic regression analysis showed that only the change in GVC remained significant after controlling for baseline GVC,injection number,and CNV type(adjusted OR=1.083;P=0.008).Conclusions Type 2 and mixed-type NV were significantly associated with a better response to anti-VEGF therapy.Changes in GVC after 3 months of treatment were significantly associated with a response to anti-VEGF therapy at 6 months.
基金supported by the Clinical diagnosis and treatment technology and translational application in Beijing (Z211100002921049).
文摘Purpose:To establish a comprehensive treatment strategy and evaluate the efficacy of combination of anti-vascular endothelial growth factor(VEGF)injection,pars plana vitrectomy(PPV),endoscopic pan-retinal photocoagulation(PRP),and endoscopic cyclophotocoagulation(ECP)surgery for neovascular glaucoma(NVG)patients.Methods:This retrospective study included 30 patients(30 eyes)who were suffering from NVG and treated with PPV&PRP&ECP(ECP group,16 eyes),or Ahmed glaucoma valve implantation(Ahmed group,14 eyes).The intraocular pressure(IOP),number of postoperative anti-glaucoma medications,best-corrected visual acuity(BCVA),successful rate of surgery,and postoperative complications were recorded and statistically analyzed at the time points of preoperative,1-day,1-month,3-months,6-months,and 12-months after operation.Results:An obvious reduction in IOP and number of postoperative anti-glaucoma medications were observed in both the ECP group and Ahmed group after operation(P<0.05),and the ECP group showed a significantly lower IOP compared to the Ahmed group at the 6-months(P=0.014)and 12-months(P=0.047)postoperative time points,while there was no significant difference of medication number between the two groups except for 1-day after surgery.The BCVA showed no marked difference between the two groups preoperatively and postoperatively(P>0.05),while it was significantly improved in ECP group at 3-months(P=0.001),6-months(P=0.004),and 12-months(P=0.010)time points comparing with preoperative BCVA.The surgical success rates in ECP group were also slightly higher than Ahmed group.And the complications after operation showed no marked differences.Conclusions:The comprehensive treatment of PPV,endoscopic PRP,and ECP surgery for NVG patients after antiVEGF injection can control IOP effectively and be friendly to patients’BCVA without obvious serious complications throughout a 12-months follow-up period.
文摘目的分析缺血性视网膜静脉阻塞继发黄斑水肿(RVO-ME)患者基线血清己糖激酶1抗体滴度与抗血管内皮生长因子(VEGF)治疗后视力改善的相关性。方法招募2017年6月至2020年2月在首都医科大学宣武医院确诊为缺血性RVO-ME并接受初始抗VEGF治疗的53例患者,其中缺血性视网膜中央静脉阻塞(CRVO)23例(CRVO组),缺血性视网膜分支静脉阻塞(BRVO)30例(BRVO组)。另选取该院同期30例行超声乳化的白内障患者作为对照组。研究对象行基线血清己糖激酶1抗体滴度检测、眼科常规检查和光学相干断层成像(OCT)检查。所有RVO-ME患者按照“3+按需治疗方案(pro re nata,PRN)”向玻璃体内注射抗VEGF药物治疗。随访12个月,采用多元线性回归分析缺血性RVO-ME患者抗VEGF治疗后视力改善的影响因素。结果CRVO组基线logMAR BCVA高于对照组和BRVO组,CRVO组和BRVO组基线CRT、基线血清己糖激酶1抗体滴度高于对照组,且CRVO组基线CRT、基线血清己糖激酶1抗体滴度高于BRVO组,差异有统计学意义(P<0.05)。RVO-ME患者基线血清己糖激酶1抗体滴度与随访6个月(r=0.377,P=0.005)、9个月(r=0.362,P=0.008)和12个月(r=0.465,P<0.001)时BCVA改善呈正相关,与随访12个月时中断EZ横向长度减少值(r=0.401,P=0.001)呈正相关。多元线性回归分析结果显示,基线logMAR BCVA、基线血清己糖激酶1抗体滴度是缺血性RVO-ME患者抗VEGF治疗随访12个月时BCVA改善的影响因素(P<0.05)。结论己糖激酶1抗体作为一种新的血清生物标志物,与缺血性RVO-ME患者抗VEGF治疗后的视力改善相关。
文摘肝细胞癌(hepatocellular carcinoma,HCC)是全球高发的恶性肿瘤。程序性死亡蛋白-1(programmed death protein-1,PD-1)/程序性死亡蛋白配体-1(programmed death protein ligand-1,PD-L1)抑制剂可通过阻断T细胞负调节信号,抑制肿瘤细胞免疫逃逸途径,重新激活抗肿瘤免疫应答过程,成为晚期HCC治疗的新手段。然而,长期临床结果显示,采用PD-1/PD-L1抑制剂单药治疗晚期HCC的病人仍存在较高的复发率和转移率。免疫联合疗法是目前针对晚期HCC患者的新的治疗策略,其中PD-1/PD-L1抑制剂联合抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物在晚期HCC治疗中显示出了良好的疗效和安全性。PD-1/PD-L1抑制剂联合抗VEGF药物可通过参与癌症免疫循环途径抑制肝癌细胞的生长。该文就PD-1/PD-L1抑制剂联合抗VEGF药物在晚期HCC治疗中的临床研究作一综述。
文摘Angiogenesis is crucial for tumor development, growth and metastasis. Vascular endothelial growth factor (VEGF) has been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis, and blocking the activity of VEGF can starve tumors. Avastin, which is a humanized anti-VEGF antibody, has been successfully applied in clinics since 2004. However, the price of Avastin is extremely high for Chinese people. Here, we report a novel human anti-VEGF neutralizing antibody, MIL60, which shows an affinity comparable to that of Avastin (the KD value of MIL60 was 44.5 pM, while that of Avastin was 42.7 pM). MIL60 displays favorable actions in inhibiting VEGF-triggered endothelial cell proliferation (the IC5o value of M IL60 was 31-6.4 ng/ml and that of Avastin was 47--.8.1 ng/ml), migration (8 pg/ml or 0.8 pg/ml MIL60 versusthe control: P〈O.05) and tube formation (2 I^g/ml or 0.2 lzg/ml MIL60 versusthe control: P〈O.05) viathe VEGFR2 signaling pathway. Moreover, MIL60 was shown to inhibit tumor growth and angiogenesis in vivo in xenograft models of human colon carcinoma and ovarian cancer using immunotherapy and immunohistochemistry analysis (MIL60 versus N.S.: P=0.0007; Avastin versus N.S.: P=0.00046). These data suggest that MIL60 is a potential therapeutic, anti-angiogenic agent. Our work provides a novel anti-VEGF antibody, which can be considered an anti-tumor antibody candidate and a new option for patients with various cancers.
基金supported by grants from the National Natural Science Foundation of China(81570852,81970810,81970811)National Major Scientific and Technological Special Project for“Significant New Drugs Development”during the Thirtieth Five-year Plan Period(2019ZX09301113).
文摘Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin.Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset.rMC-1 cells(rat Müller cell line)were treated with glyoxal for 24 h with or without ranibizumab.The expression levels of inwardly rectifying K^(+)channel 4.1(Kir4.1),aquaporin 4(AQP4),Dystrophin 71(Dp71),VEGF-A,glutamine synthetase(GS)and sodium-potassium-ATPase(Na^(+)-K^(+)-ATPase)were examined using Western blot.VEGF-A in the supernatant of the cell culture was detected with ELISA.The intracellular potassium and sodium levels were detected with specific indicators.Results:Compared with normal control,protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas,which were prevented by ranibizumab.The above changes were recapitulated in vitro.Similarly,the intracellular potassium level in glyoxal-treated rMC-1 cells was increased,while the intracellular sodium level and Na^(+)-K^(+)-ATPase protein level remained unchanged,compared with control.However,ranibizumab treatment decreased intracellular sodium,but not potassium.Conclusion:Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A.It also caused a reduction in intracellular osmotic pressure.
文摘Background:To examine the baseline morphological characteristics and alterations in intraretinal microvascular abnormalities(IRMAs)in response to anti-vascular endothelial growth factor(anti-VEGF)treatment,documented by optical coherence tomography angiography(OCTA)in diabetic eyes.Methods:In this retrospective study,IRMAs were evaluated with multimodal imaging(fundus photography,fluorescein angiography,OCTA)in treatment-naïve diabetic eyes before and after anti-VEGF treatment for diabetic macular edema(DME)and/or proliferative diabetic retinopathy(PDR)and compared to diabetic control eyes with similar diabetic retinopathy(DR)severity that did not receive anti-VEGF therapy.The morphological characteristics of IRMAs on enface OCTA imaging were graded by masked readers at baseline,then after anti-VEGF therapy in treated eyes or after observation in control eyes.Characterization of interval changes in an IRMA were based on the following parameters:branching,vessel caliber and area of adjacent capillary non-perfusion.Results:The treated group included 45 IRMA foci from 15 eyes of 11 patients,while the control group included 27 IRMA foci from 15 eyes of 14 patients.Following anti-VEGF treatment,enface OCTA demonstrated that 14 foci of IRMA(31%)demonstrated regression with normalization of appearance of the capillary bed,20 IRMAs(44%)remained unchanged,six IRMAs(13%)progressed with enlargement or development of new IRMAs and five IRMAs(11%)demonstrated complete obliteration defined as IRMA disappearance with advancing capillary drop-out.In the control group,17 IRMA(63%)remained stable,8 IRMAs(29.6%)progressed and 2 experienced total obliteration(7.4%).The difference in rank order between the two groups was statistically significant(p=0.022).Conclusions:In eyes with DR status post anti-VEGF therapy,foci of IRMAs have a variable course demonstrating one of four possible outcomes:regression,stabilit,progression or complete obliteration.In contrast,none of the untreated control diabetic eyes demonstrated regression of IRMAs,consistent with known progression of DR severity in high risk eyes.Morphologic evaluation of IRMAs with OCTA may help to monitor changes in retinal blood flow as well as the response to anti-VEGF treatment.