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

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 injection.METHODS:Totally 67 DME patients(67 eyes)and 30 cataract patients(32 eyes)were enrolled as the DME group and the control group,respectively.The 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 period.The 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 group.RESULTS: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 P<0.01).After 1mo of surgery,the concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group(all P<0.01).The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment(P<0.01).However,the difference was not statistically significant after 3mo of treatment(P>0.05).CONCLUSION:The cytokines VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor of DME patients are significantly increased.Aflibercept and aflibercept combined with TA have good efficacy in DME patients,can effectively reduce CMT,improve the patient’s vision,and have high safety.Aflibercept combined with TA can quickly downregulate the aqueous humor cytokines and help to relieve macular edema rapidly.However,the long-term efficacy is comparable to that of aflibercept alone.

Background diseases and the number of previous intravitreal aflibercept injections on immediate intraocular pressure increase and vitreous reflux rate in phakic eyes

●AIM:To evaluate the effect of background diseases and number of previous intravitreal aflibercept injections(IVAIs)on immediate intraocular pressure(IOP)increase and vitreous reflux(VR)rate and to evaluate the correlation of both age and axial length with immediate IOP increase and VR rate.●METHODS:This study included 105 patients with cystoid macular edema secondary to retinal vein occlusion,35 patients with diabetic macular edema,69 patients with neovascular age-related macular degeneration(nAMD),and 12 patients with myopic choroidal neovascularization,which underwent first-time IVAI.The correlation of immediate IOP increase and VR rates with the four background diseases was investigated.Moreover,the correlation of age with immediate IOP increase and VR rate as well as correlation of axial length with immediate IOP increase and VR rate were evaluated.Further,54 patients with nAMD were treated with IVAI>10 times(multiple IVAIs).Moreover,the correlation of immediate IOP increase and VR rates with first-time and multiple IVAIs in nAMD was determined.●RESULTS:The immediate IOP increase(P=0.16)and VR rates(P=0.50)were almost similar among the four background diseases.The immediate postinjection IOP and age,VR rate and age,immediate postinjection IOP and axial length,or VR rate and axial length were not correlated in the four background diseases.The immediate IOP increase(P=0.66)and VR rates(P=0.28)did not significantly differ between first-time and multiple IVAIs in nAMD.●CONCLUSION:Background diseases and number of previous IVAIs have no effect on immediate IOP increase and VR rate.Further,age and axial length have no correlation on immediate IOP increase and VR rate.

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

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 study.They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA.Injections once a month for a total of three injections.Central 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 treatment.RESULTS: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 groups.CONCLUSION:The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF.However,both aflibercept and combination therapy show no significant change in the area of FAZ.

Comparison of efficacy of conbercept,aflibercept,and ranibizumab ophthalmic injection in the treatment of macular edema caused by retinal vein occlusion:a Meta-analysis

AIM:To evaluate and compare the anatomical and functional outcomes and negative effects of the three anti-vascular endothelial growth factor(VEGF)drugs in the treatment of macular edema(ME)due to retinal vein occlusion(RVO)based on the evidence pooled from current clinical trials and observational studies.METHODS:A systematic literature search was conducted on nine online databases from inception until April 30,2022.The main endpoints were best corrected visual acuity(BCVA),central macular thickness(CMT),and adverse events(AEs).Cumulative Meta-analysis was conducted to synthesize the outcomes of the drugs.The retrieved data were analyzed using Stata software(version 12.0).RESULTS:A total of 20 studies comprising 1674 eyes met the inclusion criteria to the Meta-analysis.It was observed that conbercept and aflibercept had better visual acuity effects compared with ranibizumab at 1mo[weight mean difference(WMD)=-0.03,P=0.001;WMD=-0.05,P=0.019],but the effects were not different from that of ranibizumab at 6mo.Moreover,there was not statistically significant dif ference in the propor tion of patients gaining≥15 letters at 12-24mo between aflibercept and ranibizumab[odds ratio(OR)=1.16,P=0.427].Conbercept had higher mean CMT change effects at 1mo(WMD=-14.43,P=0.014)and 6mo(WMD=-35.63,P≤0.001)compared with ranibizumab.Meanwhile,the mean CMT change effects at 1mo(WMD=-10.14,P=0.170),6mo(WMD=-26.98,P=0.140)and 12-24mo(WMD=-12.34,P=0.071)were comparable among the groups.Similarly,AEs were not significantly different among the treatments(OR=0.75,P=0.305;OR=1.04,P=0.89).The stability of effect size of mean BCVA and CMT improved with the increase in sample size.Aflibercept and conbercept required fewer injections compared with ranibizumab.CONCLUSION:This is the first study to evaluate the efficacy and AEs of intravitreal administration of conbercept,ranibizumab,and aflibercept in the treatment of RVOME.Intravitreal aflibercept or conbercept results in better mean change in vision and CMT reduction compared with ranibizumab.Conbercept can be considered to be a promising and innovative drug with good anti-VEGF effects.

Morphological and functional changes in the macular area in diabetic macular edema after a single intravitreal injection of aflibercept

AIM:To evaluate the changes in macular morphology and function after a single intravitreal injection of aflibercept in diabetic macular edema(DME)using optical coherence tomography angiography(OCTA)and MP-3 microperimetry.METHODS:Twenty-eight patients(42 eyes)diagnosed with DME were treated with intravitreal injection of aflibercept.The changes in best corrected visual acuity(BCVA),central retinal thickness(CRT),foveal avascular zone(FAZ)area,vessel density of superficial retinal capillary plexus(SVD),vessel density of deep retinal capillary plexus(DVD),mean light sensitivity(MLS),2°fixation rate(P1),4°fixation rate(P2),and other indicators 1mo after treatment were compared;of these,BCVA was conver ted into logarithm of the minimum angle of resolution(logMAR),and the correlation among the factors was analyzed.RESULTS:After treatment,logMAR BCVA was 0.47±0.24,which was significantly better than that before treatment(0.63±0.28,P<0.001).The CRT was 359.21±107.87μm after treatment,which was significantly lower than before treatment(474.10±138.20μm,P<0.001).The FAZ area,SVD,and DVD were not significantly changed after treatment compared with the baseline.MLS was 22.16±4.20 dB after treatment,which was significantly higher than before treatment(19.63±4.23 dB,P<0.001).P2 significantly increased after treatment than before treatment(P=0.007).P1 had no significant change after treatment than before treatment(P=0.086).CONCLUSION:A single intravitreal injection of aflibercept effectively reduces macular edema and improves retinal sensitivity,fixation stability,and visual acuity,possibly without causing significant changes in the retinal vascular condition in a short time.

One-year outcomes of resveratrol supplement with aflibercept versus aflibercept monotherapy in wet agerelated macular degeneration

AIM:To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration(AMD).METHODS:Fifty naïve and previously untreated patients suffering from wet AMD,were randomly assigned in two subgroups of 25 patients each.All the participants were treated with 3 monthly intravitreal injections of 2.0 mg aflibercept(IAIs)followed by injections“according to need”,while in one group the patients also received daily two tablets of resveratrol oral supplement.Prior to treatment initiation,a complete ophthalmological examination,including best corrected visual acuity(BCVA)and contrast sensitivity evaluation,optical coherence tomography(OCT)scans,fundus autofluorescence(FAF),fluorescein angiography,indocyanine green angiography,and OCT angiography(OCTA),was performed to every participant,while all of them completed the Hospital Anxiety and Depression Scale(HADS)questionnaire,in order to assess their quality of life(QoL)status.The patients were assessed monthly for 1y with FAF,and OCT or OCTA;the main endpoints were the number IAIs,the changes in BCVA,in contrast sensitivity,and in patients’QoL status.RESULTS:No significant differences were present between the groups regarding the baseline demographic and clinical data.Over the 12-month period,a similar number of IAIs was applied in both groups(4.52±1.00 vs 4.28±0.90,P=0.38),while the rest of the clinical data also did not differ significantly after the completion of the study period.However,for HADS Depression(11.88±2.51 vs 8.28±1.54,P<0.001)and HADS Anxiety(11.92±2.52 vs 7.76±1.51,P<0.001)questionnaires values,the score was significantly better in patients who received resveratrol supplements.Moreover,a statistically significant difference was detected in the mean change from baseline values of contrast sensitivity(0.17±0.19 vs 0.35±0.24,P=0.005),HADS Depression(0.08±1.38 vs-3.88±1.48,P<0.001),and HADS Anxiety(0.36±1.98 vs-5.12±2.70,P<0.001)scores,in favour of the patients treated with resveratrol supplements.CONCLUSION:The resveratrol oral supplement is a complementary treatment in cases of wet AMD,highlighting its effectiveness in improving patients’QoL status.

Complications of Ziv-Aflibercept in Choroidal and Retinal Vascular Diseases

Introduction: The modern ophthalmology trends are changing rapidly every day with the introduction of much newer studies and research. Numerous anti-vascular endothelial growth factors (VEGF) are utilized as the mainstay in the treatment of intraocular vascular pathologies. The rationale of this study is to add to the literature regarding the safety and efficacy profile of the ziv-aflibercept as there is insubstantial data in patients with intraocular vascular pathologies being treated with this injection with prime focus on the complications of the injection. Materials and Methods: A prospective observational study was conducted at Opthalmology Department, Lahore General Hospital, Lahore between 14 August 2018 and 23 December 2019. Patients with choroidal and retinal vascular diseases like diabetic macular edema (DME), age-related macular degeneration (AMD) and retinal vein occlusion (RVO) who had no active infection of eye and had no history of myocardial infarction or cerebrovascular accident were added in this study. Results: Best-corrected visual acuity was significantly improved at 4, 8, and 12 weeks as compared to the baseline (p Conclusion: The use of ziv-aflibercept injection via intravitreal route under aseptic conditions for choroidal and retinal vascular diseases is effective as well as safe with mild and treatable ocular side effects.

Aflibercept治疗湿性AMD和黄斑水肿的相关研究现状

Aflibercept是一种可溶性诱导受体,可结合血管内皮生长因子-A和胎盘生长因子,从而阻止同源血管内皮生长因子受体的结合和激活,抑制视网膜血管增生,导致新生血管退化。作为眼科一种新的抗血管生成物,其药代动力学、安全性和耐受性等获得了临床研究依据,目前主要用于湿性年龄相关性黄斑变性和黄斑水肿的治疗,现将Aflibercept在湿性年龄相关性黄斑变性和黄斑水肿治疗中的相关研究作一综述。

Vascular endothelial growth factor trap-eye(Aflibercept) for the management of diabetic macular edema

Diabetic retinopathy(DR)is the most common cause of visual loss among working age individuals.Diabetic macular edema(DME)is an important complication of DR that affects around one third of the patients with DR.Several treatments have been approved for DME ranging from blood pressure and glycemic control to photocoagulation and more recently the use of vascular endothelial growth factor(VEGF)antagonists.The index review discusses aflibercept(EYLEA-Regeneron Pharmaceuticals,Inc.,Tarrytown,New York,NY,and Bayer Healthcare Pharmaceuticals,Berlin,Germany)in the context of other VEGF antagonists currently available for the treatment of DME.A systematic search of literature was conducted on PubMed,Scopus,and Google Scholar with no limitation on language or year of publication.Pre-clinical studies of aflibercept have shown a higher affinity of this molecule for vascular endothelial growth factor A(VEGF-A)along with a longer duration of action as compared to other VEGF antagonists.Recent clinical trials have shown visual outcome results for aflibercept to be similarly favorable as compared to other available agents with the added benefit of fewer required injections and less frequent monitoring.Aflibercept presents a potential exciting new addition to the armamentarium of current VEGF antagonists available for the treatment of DME and other retinal vascular diseases.However,further studies are indicated to confirm the role,safety,and efficacy of aflibercept for DME.

FOLFIRI3-aflibercept in previously treated patients with metastatic colorectal cancer

AIM To evaluate the efficacy and safety of the modified FOLFIRI3-aflibercept as second-line therapy in patients with metastatic colorectal cancer.METHODS This is a retrospective multicenter cohort, evaluating the efficacy and safety of the association of aflibercept with FOLFIRI3(day 1: aflibercept 4 mg/kg, folinic acid 400 mg/m^2, irinotecan 90 mg/m^2, 5-fluorouracil infusion 2400 mg/m^2 per 46 h; day 3: irinotecan 90 mg/m^2) in patients with previously treated metastatic colorectal cancer. The primary endpoint was overall response rate(ORR). Secondary endpoints were disease control rate(DCR), progression-free survival(PFS), overall survival(OS), and safety.RESULTS Among 74 patients treated in four French centers, nine were excluded due to prior use of aflibercept(n = 3), more than one prior treatment line in irinotecanna?ve patients(n = 3), and inadequate liver function(n = 3). In the "irinotecan-na?ve" patients(n = 30), ORR was 43.3% and DCR was 76.7%. Median PFS and OS were 11.3 mo(95%CI: 6.1-29.0) and 17.0 mo(95%CI: 13.0-17.3), respectively. The most common(> 5%) grade 3-4 adverse events were diarrhea(37.9%), neutropenia(14.3%), stomatitis and anemia(10.4%), and hypertension(6.7%). In the "pre-exposed irinotecan" patients(n = 35), 20(57.1%) received ≥ 2 prior lines of treatment. ORR was 34.3% and DCR was 60.0%. Median PFS and OS were 5.7 mo(95%CI: 3.9-10.4) and 14.3 mo(95%CI: 12.8-19.5), respectively.CONCLUSION Minimally modified FOLFIRI has improvement dramatically the FOLFIRI3-aflibercept efficacy, whatever prior use of irinotecan. A prospective randomized trial is warranted to compare FOLFIRI-aflibercept to FOLFIRI3-aflibercept.

Chorioretinal response to intravitreal aflibercept injection in acute central serous chorioretinopathy

AIM: To evaluate chorioretinal responses to intravitreal aflibercept injection(IAI) in patients with acute central serous chorioretinopathy(CSC). METHODS: Seventy-one eyes from 71 patients with symptomatic CSC for less than six months were included. Thirty-five eyes received a single IAI and 36 eyes were observed without treatment. Best-corrected visual acuity(BCVA), central subfield foveal thickness(CSFT), and subfoveal choroidal thickness(SFCT) were assessed at baseline and at 1, 2, and 3 mo. RESULTS: The mean SFCT in the IAI group decreased at 1 mo, rebounded at 2 mo and remained stable at 3 mo compared to the baseline, while significant change was not noted in the observation group. The mean CSFT decreased significantly during the 3-month study period in both groups, and was significantly lower in the IAI group at 1 mo(P<0.001). A rebound of CSFT between 1 and 2 mo was noted in 14 eyes(40.0%) in the IAI group and in 1 eye(2.8%) in the observation group(P<0.001). The significant visual improvement was achieved from 1 mo in the IAI group, and from 2 mo in the observation group. The rate of complete absorption of subretinal fluid at 3 mo did not differ between the two groups.(45.7% vs 41.7%, P=0.813). CONCLUSION: A single IAI for acute CSC induce a transient decrease in SFCT and CSFT, which implies that IAI may have a pharmacological effect on the underlying hyperpermeable choroid in acute CSC.

Impact of switching from ranibizumab to aflibercept on the number of intravitreous injection and follow up visit in wet AMD:results of real life ELU study

●AIM:To study if one of the two molecules could lead to a lower number of follow up visits and intra-vitreous injection(IVI)with the same efficacy.●METHODS:ELU(or"elected"in French)study is a retrospective study conducted in real life in patients presenting suboptimal response after ranibizumab IVI(phase 1)and secondary switched to aflibercept(phase 2).The number of follow up visits and IVI were compared in both phases.Visual acuity(VA)evolution and"switching"reasons were secondary analyzed.●RESULTS:We retrospectively included data of 33 patients(38 eyes)with age-related macular degeneration(AMD;mean age:77±7.7 y).The number of monthly follow up visits[median(Q1;Q3)]:was significantly lower with aflibercept(phase 2),respectively 1.0(0.81;1.49)visits in phase 1,versus 0.79(0.67;0.86)visits in phase 2.The median number of monthly IVI also significantly decreased in phase 2,respectively 0.67(0.55;0.90)IVI in phase 1,versus 0.55(0.45;0.67)IVI in phase 2.The mean VA evolution(VA final-VA initial)was similar in both phases,(P>0.05).Whatever the reason for"switching"(loss of efficacy,tachyphylaxis,tolerance problems),there was no incidence on VA evolution over the time.●CONCLUSION:Our results show that switching from ranibizumab to aflibercept in"suboptimal"patients significantly reduce the number of follow up visits and IVI,with a comparable efficacy.This decrease in visit number could improve patients’quality of life and reduce surgical risk by reducing the number of injections.

Comparison of intravitreal aflibercept and dexamethasone implant in the treatment of macular edema associated with diabetic retinopathy or retinal vein occlusion:a Meta-analysis and systematic review

·AIM:To compare the efficacy and safety of intravitreal aflibercept with dexamethasone implant in the treatment of macular edema(ME)associated with diabetic retinopathy(DR)or retinal vein occlusion(RVO).·METHODS:A comprehensive search of studies comparing dexamethasone and aflibercept in patients with ME was conducted at PubMed,Embase,and Cochrane Central Register of Controlled Trials from the beginning of library to April 16,2021.Extracting the data including bestcorrected visual acuity(BCVA),central retinal thickness(CRT),number of injections and serious adverse events(SAEs)from the final qualified articles.RevMan 5.3 software was used for Meta-analysis of the included studies.·RESULTS:Totally 7 studies with 369 eyes were included.The causes of ME in the final screening study included RVO and DR.Compared with the aflibercept treatment group,the BCVA of the dexamethasone implant treatment group showed no significant difference in the follow-up for 3 mo[mean difference(MD):-0.05,95%confidence interval(CI):-0.11,0.02;P=0.17]and 12 mo(MD:-0.01,95%CI:-0.38,0.37;P=0.98),but it was slightly worse than the aflibercept group at 6 mo(MD:0.12.95%CI:0.03,0.21;P=0.008).In terms of CRT reduction,there was no significant difference between the two groups at 3 mo(MD:-28.14,95%CI:-79.95,23.67;P=0.29),6 mo(MD:27.67,95%CI:-84.89,140.24;P=0.63),and 12 mo(MD:-59.00,95%CI:-127.37,9.37;P=0.09).However,dexamethasone implant had fewer injections,but more adverse events such as elevated intraocular pressure(IOP)and cataract.·CONCLUSION:Intravitreal injection of aflibercept and dexamethasone implant can both effectively increase BCVA and reduce CRT.Compared with aflibercept,dexamethasone implant is not inferior in improving vision and reducing CRT in the initial treatment period(3 mo)and long-term treatment period(12 mo).Besides,it has fewer injections and more likely to cause elevated IOP and cataract.

Incidence and management of ZIv-aflibercept related toxicities in colorectal cancer

Ziv-afilbercept(Zaltrap, Ziv) is a humanized fusion protein constructed by joining the vascular endothelial growth factor(VEGF) binding portions of human VEGF receptors 1 and 2 to the Fc portion of human immunoglobulin IgG 1. Recently, a randomized, open-label, phase Ⅲ study compared 5-fluorouracil, leucovorin, irinotecan(FOLFIRI)/Ziv with FOLFIRI/placebo in patients who had been previously treated with oxaliplatin based chemotherapy for metastatic colon cancer(mC RC). Patients who had received prior bevacizumab therapy were also eligible. This study showed that the addition of Ziv improved overall survival with median survival time of 13.5 mo vs 12.06 mo in ziv vs placebo arm. Ziv also improved progression free survival from 4.67 mo to 6.9 mo with a response rate of 19.8% in the Ziv/FOLFIRI group vs 11.1% in FOLFIRI alone group. This led to the approval of Ziv in combination with FOLFIRI in metastatic colon cancer patients treated with prior oxaliplatin regimens. The mostcommon side effects were diarrhea, stomatitis, fatigue, hypertension, weight loss, loss of appetite, abdominal pain, and headache. As the use of Ziv has become more widespread in oncology practices, familiarity with the toxicity profile of the drug and the use of practice guidelines for their treatment has become increasing important. This review will address the toxicities noted in trials using Ziv for the treatment of mC RC, and will provide recommendations for toxicity management.

Retrospective evaluation of FOLFIRI3 alone or in combination with bevacizumab or aflibercept in metastatic colorectal cancer

BACKGROUND The treatment of metastatic colorectal cancer(mCRC) relies of chemotherapy. The efficacy of the standard FOLFIRI-therapy could be improved by a modification of the regimen by splitting the dose of irinotecan on day 1 and day 3 in the FOLFIRI3 regimen.AIM To determine safety and efficacy of FOLFIRI3 regimen.METHODS This is a monocentric retrospective study evaluating the efficacy and safety of the FOLFIRI3 regimen given alone or in combination with bevacizumab or aflibercept in patients with previously treated mCRC.RESULTS One hundred and fifty-three consecutive patients were included(18 treated with FOLFIRI3, 99 with FOLFIRI3 plus bevacizumab and 36 with FOLFIRI3 plus aflibercept). The overall response rate(ORR) and disease control rate were 51%and 62%, respectively. Similar ORRs were observed in all 3 cohorts. Median progression-free survival(PFS) and overall survival(OS) were 3.9 mo(95%CI:3.2-4.9) and 9.4 mo(95%CI: 6.6-12), respectively. Median PFS and OS values were improved in the FOLFIRI3 plus aflibercept group. The most common grade 3-4 adverse events were diarrhoea(21.6%) and neutropenia(11.8%), and these toxicities were more frequent in the FOLFIRI3 plus aflibercept group. According to the multivariate Cox proportional model, previous surgery of metastasis andaflibercept were associated with outcomes.CONCLUSION The modification of the FOLFIRI regimen impacted treatment response of mCRC patients. The addition of an antiangiogenic agent, in particular aflibercept,enhanced the clinical benefit and improved survival.

Aflibercept for diabetic macular oedema： a Meta-analysis of randomized controlled trials

AIM： To evaluate the relative efficacy and safety of aflibercept for treatment of diabetic macular oedema （DMO）. METHODS： A comprehensive search in MEDLINE, CENTRAL and EMBASE was undertaken for randomized controlled trials （RCTs） comparing intravitreal anti-vascular endothelial growth factor （anti-VEGF） versus another treatment. Primary outcome measures were proportion of patients with at least 15 letters of gain or loss on a logMAR visual acuity chart, and change in best corrected visual acuity （BCVA） and central macular thickness （CMT） from baseline. Safety outcomes were rates of death, thromboembolic events and any systemic or ocular serious adverse events. The final search was performed on November 2017. RESULTS： Four RCTs were included. Only one trial compared efficacy and safety of aflibercept with bevacizumab and ranibizumab over 1 or 2y. Three trials were included for Meta-analysis comprising 661 patients （331 in the aflibercept, and 330 in the photocoagulation group）. Aflibercept was more efficacious compared to photocoagulation in the proportion of patients with at least 15 letters of improvement and worsening, and in improvement of BCVA and reduction in CMT at 1 or 2y. The safety estimates at 1 or 2y did not differ statistically. CONCLUSION： Aflibercept offers superior benefits over photocoagulation in improving and preserving vision, with no differences in safety. Further comparative effectiveness trials between aflibercept and other anti-VEGF agents will aid ophthalmologists in treatment decisions.

Fixed bimonthly aflibercept in nave and switched neovascular age-related macular degeneration patients:one year outcomes

AIM: To determine real life clinical outcomes in poorly responsive and treatment-nave neovascular age-related macular degeneration(nv AMD) patients using bimonthly fixed dosing aflibercept regimen.METHODS: This was a retrospective study of 165 eyes with nv AMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata(PRN) ranibizumab/bevacizumab due to poor response(107 eyes), or treatment- nave( 58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity(BCVA) and central retinal thickness(CRT)from baseline were assessed using the Wilcoxon signedrank test. The proportion of patients maintaining BCVA(<15 letters loss) at 12 mo was also evaluated.RESULTS: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and nave aflibercept groups respectively(P <0.01). BCVA was maintained in 95.3% of switched and 96.6% of nave patients. CRT at month 12 showed a decrease of -6.16 μm in the switched group and -35.36 μm in the nave group(P <0.01).Patients previously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6 mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections(nave group), 7.5 injections(switched group) and 4 clinic visits per year.CONCLUSION: Fixed bimonthly aflibercept is effective in both treatment-nave and poorly responsive nv AMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.

Intravitreal aflibercept in neovascular age-related macular degeneration previously treated with ranibizumab

AIM：To report the change in visual acuity and central macular thickness（CMT）following treatment with intravitreal aflibercept injections in patients with neovascular agerelated macular degeneration（n AMD）with suboptimum response to ranibizumab.METHODS：This was a retrospective study. The inclusion criteria were patients with n AMD who responded poorly to ranibizumab. Patients then received either 3 consecutive aflibercept injections followed by pro re nata（PRN）treatment or PRN alone. Primary endpoints were mean change in bestcorrected visual acuity（BCVA）and CMT at 12 mo. Secondary endpoints were number of injections and adverse events.RESULTS：Forty-nine eyes from 49 patients met the inclusion criteria and completed 12-month follow up on aflibercept. Thirty-eight eyes received 3 consecutive aflibercept injections followed by PRN treatment and 11 eyes received PRN injections alone. At 12 mo,mean BCVA improved by one letters（log MAR 0.56±0.31 to 0.54±0.34）and mean CMT decreased from 303.9±82.1 to 259.2±108.3 μm.Four percent of eyes gained 15 letters or more,6% lost more than 15 letters and the remaining 90% had stable BCVA. The mean number of aflibercept injections was 6.There was one case of infectious endophthalmitis.CONCLUSION：Intravitreal aflibercept in patients with n AMD with a previous suboptimal response to ranibizumab resulted in an anatomical improvement in macular appearance at 12 mo without a corresponding improvement in visual acuity.

Choroidal structural changes determined by the binarization method after intravitreal aflibercept treatment in neovascular age-related macular degeneration

AIM:To assess the choroidal structural alterations after intravitreal injection of aflibercept in neovascular agerelated macular degeneration(n AMD).METHODS:Fifty eyes with treatment-naive n AMD were evaluated at baseline,3^(rd),and 12^(th) month.Fifty eyes of 50 healthy subjects were also included as controls.Choroidal thickness(CT)was measured in the subfoveal region.Total circumscribed choroidal area(CA),luminal area(LA),stromal area(SA),and choroidal vascularity index(CVI)was calculated using Image J.RESULTS:At baseline,subfoveal CT was increased in n AMD patients compared to controls(P=0.321).Eyes with n AMD had a significantly increased total circumscribed CA and SA(P=0.041,0.005,respectively).The CVI was decreased(P=0.038).In the 3^(rd) month,the subfoveal CT,LA,and CVI revealed a decrease(P=0.005,P=0.039,0.043,respectively).In the 12th month,subfoveal CT,LA,and CVI were decreased in comparison to baseline measures(P<0.001,0.006,0.010,respectively).CONCLUSION:Significant structural alterations are found after intravitreal aflibercept treatment during the 12-month follow-up,in particular at the third month,in eyes with n AMD.

抗血管生成剂Aflibercept

异常的血管生成被认为是某些疾病,如癌症和湿性老年性黄斑变性（AMD）的病理基础,而抑制血管生成的最有效方法之一就是靶向阻断血管内皮生长因子（VEGF）信号通路,包括直接靶向VEGF、