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.

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.

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.

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.

多次玻璃体内注射抗VEGF药物对眼底血管性疾病患者角膜组织形态的影响

目的 探讨多次玻璃体内注射雷珠单抗和阿柏西普对湿性老年性黄斑变性(nAMD)、糖尿病黄斑水肿(DME)、视网膜静脉阻塞(RVO)患者角膜组织形态的影响。方法 前瞻性临床研究。选取2021年6月至2022年6月在我院眼内科注射中心治疗的患者共64例(64眼)作为研究对象;其中nAMD患者19例,DME患者20例,RVO患者25例。阿柏西普(40 g·L^(-1))治疗29例,雷珠单抗(10 g·L^(-1))治疗35例。所有入组病例均选取单眼注射,采取3+PRN的随访治疗方法。使用共聚焦显微镜行角膜神经检查,使用角膜内皮显微镜进行角膜厚度及角膜内皮细胞检查。比较nAMD、DME、RVO患者多次玻璃体内注射抗VEGF药物后角膜厚度、内皮细胞密度、变异系数、平均面积、六角形细胞比例、神经纤维长度、神经纤维密度,比较每次注射不同药物后1个月与基线时上述指标变化。结果 术前,DME组患者内皮细胞密度低于nAMD组和RVO组,DME组患者内皮细胞平均面积高于nAMD组和RVO组,差异均有统计学意义(均为P<0.05),三种不同疾病患者其余指标差异均无统计学意义(均为P>0.05)。注射抗VEGF药物3次后,DME组患者内皮细胞密度低于nAMD组和RVO组,内皮细胞平均面积高于nAMD组和RVO组,差异均有统计学意义(均为P<0.05);DME组患者神经纤维长度短于nAMD组和RVO组,差异均有统计学意义(均为P<0.05)。自从第2次注射阿柏西普后,nAMD组患者内皮细胞密度均较术前减少,差异均有统计学意义(均为P<0.05);每次注射后六角形细胞比例均较术前减少,差异均有统计学意义(均为P<0.05);其余指标注射后与术前相比,差异均无统计学意义(均为P>0.05)。自从第2次注射雷珠单抗后,RVO组患者内皮细胞密度均较术前减少,差异均有统计学意义(均为P<0.05)。结论 多次玻璃体内注射抗VEGF药物会一定程度降低角膜内皮六角形细胞比例及内皮细胞密度,注射药物后DME组的神经纤维长度显著低于nAMD组和RVO组。

基于马尔科夫模型的雷珠单抗或阿柏西普治疗糖尿病性黄斑水肿的成本-效用对比

目的对比阿柏西普与雷珠单抗治疗糖尿病性黄斑水肿的成本和效用,以期借助药物经济学的视角,为治疗方案的选择提供参考。方法提取临床用药模式建立马尔科夫模型,模拟在10年内两种治疗方案的生存状态,分别计算成本和健康效用,获得增量成本效用比(ICUR)。与1倍的2022年我国人均国内生产总值(GDP)为意愿支付阈值(WTP)比较,选取成本-效用具有优势的方案。结果在模拟期限内,阿柏西普方案对比雷珠单抗方案,ICUR为61024.22元/质量调整生命年(QALY),低于WTP,具有明显的经济性。单因素敏感性分析显示,使用阿柏西普使视力改善的转移概率、雷珠单抗每年注射次数是ICUR的重要影响因素。概率敏感性分析显示,在WTP为1倍GDP时,阿柏西普具有显著的成本-效用优势,经济概率为63.7%,结果较为稳健。结论对于治疗糖尿病性黄斑水肿,相比于雷珠单抗,阿柏西普更具有成本-效用优势。

和营利水方治疗视网膜静脉阻塞继发黄斑水肿的疗效观察

目的观察和营利水方治疗视网膜静脉阻塞继发黄斑水肿(RVO-ME)的临床疗效。方法纳入2021年1月—2023年6月上海中医药大学附属龙华医院诊治的RVO-ME患者110例(110只眼)。随机分为治疗组和对照组,最终纳入治疗组54例(54只眼)、对照组49例(49只眼)。对照组予阿柏西普眼内注射液玻璃体腔内注射治疗。治疗组在对照组的基础上联合和营利水方口服。分别于治疗前、治疗后1、3、6、12个月检测2组受试者的最佳矫正视力(BCVA),采用光学相干断层扫描血管成像(OCTA)检测黄斑中心凹厚度(CMT)、视网膜浅层毛细血管丛血流密度(SCP)、视网膜深层毛细血管丛血流密度(DCP)、中心凹无血管区(FAZ)面积、非圆度指数(AI)和FAZ范围300μm宽度内的血流密度(FD-300),记录数据并做统计分析。结果(1)BCVA:治疗组治疗后各时间点的BCVA均较治疗前提高,差异均有统计学意义(t_(1个月)=34.093、t_(3个月)=57.481、t_(6个月)=59.741、t_(12个月)=46.442,均P=0.000)。对照组治疗后各时间点BCVA均较治疗前提高,差异均有统计学意义(t_(1个月)=29.606、t_(3个月)=49.027、t_(6个月)=48.711、t_(12个月)=30.826,均P=0.000)。治疗后2组间比较,治疗组治疗后各时间点的BCVA均优于对照组,差异均有统计学意义(t_(1个月)=3.646、t_(3个月)=5.068、t_(6个月)=6.758、t_(12个月)=11.549,均P=0.000)。(2)CMT:治疗组治疗后各时间点的CMT均较治疗前降低,差异均有统计学意义(t_(1个月)=34.702、t_(3个月)=52.204、t_(6个月)=51.470、t_(12个月)=41.842,均P=0.000)。对照组治疗后各时间点的CMT均较治疗前降低,差异均有统计学意义(t_(1个月)=34.950、t_(3个月)=42.529、t_(6个月)=46.152、t_(12个月)=43.355,均P=0.000)。治疗后2组间比较,治疗组治疗后各时间点的CMT均低于对照组,差异均有统计学意义(t_(1个月)=2.438,P=0.017;t_(3个月)=6.649、t_(6个月)=3.776、t_(12个月)=6.138,均P=0.000)。(3)SCP:治疗组治疗后1个月与治疗前比较,差异无统计学意义(P>0.05),治疗后3、6、12个月的SCP均提高,差异均有统计学意义(t_(3个月)=17.613、t_(6个月)=13.095、t_(12个月)=4.640,均P=0.000)。对照组治疗后1个月的SCP较治疗前下降,差异有统计学意义(t=12.963,P=0.000),其余各时间点的SCP均无明显变化,差异均无统计学意义(P>0.05)。治疗后2组间比较,治疗组治疗后各时间点的SCP均高于对照组,差异均有统计学意义(t_(1个月)=16.639、t_(3个月)=16.125、t_(6个月)=11.443,均P=0.000;t_(12个月)=2.975,P=0.004)。(4)DCP:治疗组治疗后1个月与治疗前比较,差异无统计学意义(P>0.05),治疗后3、6、12个月的DCP均升高,差异均有统计学意义(t_(3个月)=9.261、t_(6个月)=6.833、t_(12个月)=4.749,均P=0.000)。对照组治疗后1、3、6个月的DCP均较治疗前下降,差异均有统计学意义(t_(1个月)=26.876、t_(3个月)=10.916,均P=0.000;t_(6个月)=3.486,P=0.001),治疗后12个月的DCP无明显变化,差异无统计学意义(P>0.05)。治疗后2组间比较,治疗组治疗后各时间点的DCP均高于对照组,差异均有统计学意义(t_(1个月)=23.077、t_(3个月)=17.558、t_(6个月)=10.694、t_(12个月)=7.299,均P=0.000)。(5)FAZ面积:治疗组治疗后1个月与治疗前比较,差异无统计学意义(P>0.05),其余各时间点的FAZ均下降,差异均有统计学意义(t_(3个月)=20.915、t_(6个月)=16.959、t_(12个月)=9.167,均P=0.000)。对照组治疗后1个月的FAZ较治疗前升高,差异有统计学意义(t=22.974,P=0.000),其余各时间点的FAZ均无明显变化,差异均无统计学意义(P>0.05)。治疗后2组间比较,治疗组治疗后各时间点的FAZ面积均小于对照组,差异均有统计学意义(t_(1个月)=21.963、t_(3个月)=16.895、t_(6个月)=12.043、t_(12个月)=6.758,均P=0.000)。(6)AI:治疗组治疗后3、6个月的AI均较治疗前下降,差异均有统计学意义(t_(3个月)=5.654、t_(6个月)=3.934,均P=0.000),其余时间点的AI均无明显变化,差异均无统计学意义(P>0.05)。对照组治疗后1个月的AI较治疗前升高,差异有统计学意义(t=7.797,P=0.000),其余时间点的AI均无明显变化,差异均无统计学意义(P>0.05)。治疗后2组间比较,治疗组治疗后1、3、12个月的AI均低于对照组,差异均有统计学意义(t_(1个月)=8.029,P=0.000;t_(3个月)=3.379,P=0.001;t_(12个月)=2.305,P=0.023)。而2组治疗后6个月的AI比较,差异无统计学意义(P>0.05)。(7)FD-300:治疗组治疗后3、6个月的FD-300较治疗前升高,差异有统计学意义(t_(3个月)=6.022、t_(6个月)=5.020,均P=0.000),其余各时间点均无明显变化,差异无统计学意义(P>0.05)。对照组治疗后1、3个月的FD-300较治疗前降低,差异有统计学意义(t_(1个月)=12.729、t_(3个月)=4.391,均P=0.000),其余各时间点的FD-300均无明显变化,差异均无统计学意义(P>0.05)。治疗后2组间比较,治疗组治疗后1、3、6个月的FD-300均高于对照组,差异均有统计学意义(t_(1个月)=7.324、t_(3个月)=8.912、t_(6个月)=5.158,均P=0.000)。而2组治疗后12个月的FD-300比较,差异无统计学意义(P>0.05)。(8)注射次数:治疗组平均注射(4.83±0.38)次,低于对照组的(5.17±0.46)次,差异有统计学意义(t=4.104,P=0.000)。结论和营利水方可改善RVO-ME患者视网膜血流,减少注射次数,值得临床推广。

阿柏西普联合雷珠单抗治疗效果欠佳的糖尿病黄斑水肿的疗效分析

目的探讨阿柏西普联合雷珠单抗治疗效果欠佳的糖尿病黄斑水肿患者的效果。方法回顾性选取2021年9月—2022年9月广州医科大学第六附属医院收治的90例糖尿病黄斑水肿患者的临床资料,依据用药方案不同分为两组。对照组(n=45,均为单侧眼病变)用雷珠单抗持续治疗,观察组(n=45,均为单侧眼病变)用雷珠单抗联合阿柏西普治疗。比较两组治疗后的视力、眼压、视网膜厚度、不良反应发生情况。结果观察组在治疗前的视力、黄斑中心厚度、眼压与单一组比较,差异无统计学意义(P均>0.05)。治疗后,观察组的视力较对照组明显提高,观察组的黄斑中心凹厚度和眼压对比对照组明显降低,差异有统计学意义(P均<0.05)。两组不良反应发生情况对比,差异无统计学意义(P>0.05)。结论对于雷珠单抗治疗效果欠佳的糖尿病黄斑水肿患者,雷珠单抗联合阿柏西普治疗对患者的视力提高作用明显,对视网膜结构的改善成效突出,治疗安全有效。

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。

阿柏西普对比康柏西普治疗湿性年龄相关性黄斑变性药物经济学评价

目的 对比阿柏西普与康柏西普治疗湿性年龄相关性黄斑变性的成本和效用,以期借助药物经济学的视角,为治疗方案的选择提供参考。方法 采用Markov模型,模拟在5年内两种治疗方案的生存状态,分别计算成本和健康产出,进行成本-效用分析获得增量成本效用比(ICUR)。采用单因素敏感性分析判断参数对ICUR的影响;采用概率敏感性分析判断各模型参数的不确定性对研究结果产生的影响。以1倍的2022年我国人均国内生产总值(GDP)为意愿支付阈值(WTP),判断其经济性。结果 在模拟期限内,与阿柏西普方案相比,康柏西普方案ICUR为-1 528 840元/质量调整生命年(QALY),低于WTP,具有明显的经济性。单因素敏感性分析显示,两种治疗方案轻度与中度视力状态之间的转移概率及每年注射阿柏西普次数是ICUR的重要影响因素。概率敏感性分析显示,在WTP为1倍GDP时,康柏西普具有显著的成本-效用优势(概率为65.9%),结果较为稳健。结论 对于治疗湿性年龄相关性黄斑变性,康柏西普相比与阿柏西普,具有成本-效用优势。

多次玻璃体腔注射抗血管内皮生长药物对黄斑水肿患者角膜生物力学的作用

目的观察多次玻璃体腔注射抗血管内皮生长因子(VEGF)药物对角膜生物力学的作用。方法前瞻性病例对照研究。选取玻璃体腔注射抗VEGF治疗的患者共64例(64只眼),其中,湿性老年性黄斑变性(nAMD)19例(19只眼),糖尿病黄斑水肿(DME)20例(20只眼),视网膜静脉阻塞(RVO)黄斑水肿25例(25只眼)。阿柏西普(2 mg/0.05 ml)治疗29例(29只眼),雷株单抗(0.5 mg/0.05 ml)治疗35例(35只眼)。经过3次连续注射治疗的患者共64例(64只眼),经过4次连续注射治疗的患者共10例(10只眼)。使用眼反应分析仪(ORA)对角膜生物力学指标进行测量。比较每次注药后1个月与注射前的角膜阻力因子(CRF)、角膜滞后量(CH)、角膜补偿眼压值(IOPcc)、可重复的模拟Goldmann眼压值(IOPg)的变化。比较使用阿柏西普和雷株单抗两种不同药物多次玻璃体腔注射后以上所有指标的变化,同时比较nAMD、DME、RVO三种不同疾病多次玻璃体腔注射抗VEGF药物后以上所有指标的变化。结果(1)雷株单抗/阿柏西普多次注射后角膜生物力学各指标在术后各时间点较术前相比,差异无统计学意义;(2)注射次数与角膜生物力学各项指标的改变无明显相关性;(3)术前基线时,角膜生物力学等各指标在3种不同疾病患者基线时差异无统计学意义;(4)注射3次后,DME组的CH值较RVO组和AMD组升高,且差异有统计学意义。结论多次玻璃体腔注射抗VEGF药物使DME组的CH值则显著高于RVO组和AMD组。糖尿病黄斑水肿患者多次玻璃体腔注射抗VEGF药物对角膜生物力学会产生一定影响。

阿柏西普联合羟苯磺酸钙在糖尿病视网膜病变黄斑水肿中的疗效观察

目的探讨阿柏西普联合羟苯磺酸钙在糖尿病视网膜病变黄斑水肿中的治疗效果。方法回顾性选取2020年10月—2023年10月天水市中医医院收治的100例糖尿病视网膜病变黄斑水肿患者的临床资料,以不同的治疗方案分为两组,各50例,对照组患者给予阿柏西普玻璃体腔内注射,研究组患者则在对照组基础上联合口服羟苯磺酸钙胶囊。比较两组的治疗效果。结果研究组患者治疗总有效率高于对照组,差异有统计学意义(P<0.05);治疗后,两组的眼压均明显降低,且研究组低于对照组,差异有统计学意义(P<0.05);治疗后,两组的最佳矫正视力均明显升高,且研究组高于对照组,差异有统计学意义(P<0.05);治疗后,两组的黄斑中心凹厚度均明显减小,且研究组小于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论在阿柏西普玻璃体腔内注射治疗糖尿病视网膜病变黄斑水肿过程中联用羟苯磺酸钙,疗效安全显著,对促进患者病情恢复、提高生活质量具有积极意义。

阿柏西普联合口服止血祛瘀明目片治疗PDR的临床观察

目的 观察阿柏西普联合止血祛瘀明目片治疗增殖性糖尿病视网膜病变(PDR)的临床疗效。方法 收集2020年1月—2021年1月于山东省眼科医院确诊的PDR阴虚肝旺证患者50例(100只眼),随机分为对照组和治疗组,对照组脱落12只眼,治疗组脱落5只眼,最终纳入对照组20例(38只眼),治疗组23例(45只眼)。对照组予阿柏西普玻璃体腔内注射治疗,治疗组予在对照组治疗基础上口服止血祛瘀明目片治疗。分别于治疗前和治疗后第1、3、6个月测量患者最佳矫正视力(BCVA),光学相干断层扫描血管成像(OCTA)检测参数:黄斑中心凹视网膜厚度(CMT)、黄斑旁中心凹视网膜厚度(CPFT)、黄斑中心无血管区(FAZ)的面积、周长(perim)及类圆指数(AI)并记录中医证候积分。结果 2组治疗前BCVA、CMT、CPFT及黄斑区毛细血管参数、中医症候积分比较,差异均无统计学意义(P>0.05)。(1)BCVA:治疗后第3个月对照组BCVA和治疗组治疗后第3个月、第6个月BCVA均较治疗前改善(对照组:t=2.197,P=0.031。治疗组:t_(3个月)=2.148,P=0.034;t_(6个月)=4.045,P=0.000)。2组间比较,治疗后第6个月治疗组BCVA改善优于对照组,差异有统计学意义(t=-2.239,P=0.027)。其余各治疗时间点较治疗前,及2组间比较差异均无统计学意义(P>0.05)。(2)OCTA检测参数:(1)CMT。治疗后对照组1、3个月和治疗组1、3、6个月CMT较治疗前变薄,差异均有统计学意义(对照组:t_(1个月)=2.330,P=0.023;t_(3个月)=5.940,P=0.000。治疗组:t_(1个月)=2.955,P=0.004;t_(3个月)=7.279,P=0.000;t_(6个月)=4.952,P=0.000),其余治疗后2组各时间点CMT较治疗前,及2组间治疗后各时间点比较,差异均无统计学意义(P>0.05)。(2)CPFT。对照组治疗后3个月和治疗组治疗后3、6个月CPFT较治疗前变薄,差异均有统计学意义(对照组:t_(3个月)=3.117,P=0.003。治疗组:t_(3个月)=3.354,P=0.001;t_(6个月)=2.343,P=0.022)。余2组各时间点CPFT较治疗前,及2组组间比较差异无统计学意义(P>0.05)。(3)深层毛细血管丛中央凹血流密度。2组间比较,治疗后6个月治疗组DCP中央凹VD改善优于对照组,差异有统计学意义(t=-2.028,P=0.045),余2组间比较及治疗后2组各时间点较治疗前,差异均无统计学意义(P>0.05)。(4)其他指标。治疗后2组各时间点FAZ的面积、perim、AI,余血流密度均值较治疗前及2组间治疗后比较,差异均无统计学意义(P>0.05)。(3)中医证候积分:治疗后6个月,治疗组中医证候积分较治疗前降低,差异有统计学意义(t=4.828,P=0.000)。2组间比较,治疗组中医证候积分较对照组低,差异有统计学意义(t=-6.273,P=0.000),其余对照组治疗后各时间点与治疗前相比及2组间比较,差异无统计学意义(P>0.05)。结论 止血祛瘀明目片未引起明显缺血及不良反应,其化瘀止血作用可促进玻璃体出血的吸收,阿柏西普联合止血祛瘀明目片能明显提高PDR阴虚肝旺证患者的视力,对血流无明显影响,能够一定程度上改善视功能和微血管循环,为中西医结合治疗该病提供了一定依据。

羟苯磺酸钙联合阿柏西普玻璃体腔内注射治疗糖尿病视网膜病变的效果

目的:观察糖尿病视网膜病变患者采取羟苯磺酸钙联合阿柏西普玻璃体腔内注射治疗的效果。方法:选取2019年6月—2022年3月于苏州市相城人民医院就诊的92例糖尿病视网膜病变患者作为研究对象,采用随机数表法将患者分为常规组(46例,阿柏西普玻璃体腔内注射治疗)与研究组(46例,羟苯磺酸钙联合阿柏西普玻璃体腔内注射治疗)。比较两组治疗前及治疗后1个月、2个月、3个月后最佳矫正视力(BCVA)、5 mm直径范围内黄斑视网膜体积(TMV)、黄斑中心凹厚度(CMT),比较两组临床疗效、不良反应。结果:两组治疗后1个月、2个月、3个月BCVA、TMV优于治疗前,治疗后2个月、3个月BCVA、TMV优于治疗后1个月,且研究组治疗后1个月、2个月、3个月BCVA高于常规组,TMV低于常规组,差异有统计学意义(P<0.05)。两组治疗后1个月、2个月、3个月CMT低于治疗前,治疗后2个月、3个月CMT低于治疗后1个月,治疗后3个月CMT低于治疗后2个月,且研究组治疗后1个月、2个月、3个月CMT低于常规组,差异有统计学意义(P<0.05)。研究组总有效率高于常规组,差异有统计学意义(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:糖尿病视网膜病变患者采取羟苯磺酸钙联合阿柏西普玻璃体腔内注射治疗效果显著,可改善视力及黄斑水肿,且安全可靠。

石斛酚抑制碱烧伤大鼠角膜新生血管的实验研究

目的 探讨石斛酚抑制碱烧伤大鼠角膜新生血管(corneal neovascularization, CNV)的作用。方法 构建SD大鼠角膜碱烧伤模型,随机分成正常对照组、模型对照组、低浓度石斛酚组、高浓度石斛酚组、阿柏西普组,每组各10只。低浓度石斛酚组、高浓度石斛酚组、阿柏西普组分别于伤后第1天结膜下注射2.5 mg/0.05 mL、5 mg/0.05 mL石斛酚,2 mg/0.05 mL阿柏西普。伤后第3、7、14天,观察并计算角膜新生血管占全角膜面积的百分比、角膜混浊评分并测量角膜厚度。碱烧伤第14天,处死全部大鼠,通过苏木素-伊红(HE)染色和免疫组化观察角膜组织中VEGF和CD34蛋白表达水平,以及通过ELISA检测各组VEGF、IL-1β、TNF-α的蛋白含量。结果 碱烧伤后第7、14天,低浓度石斛酚组、高浓度石斛酚组、阿柏西普组角膜新生血管面积占全角膜面积百分比均显著低于模型对照组(所有P<0.05)。碱烧伤后第14天,高浓度石斛酚组角膜混浊评分显著小于模型对照组(P<0.05),模型对照组、低浓度石斛酚组角膜厚度均显著高于正常对照组(所有P<0.001)。但是,高浓度石斛酚组、阿柏西普组角膜厚度与正常对照组相比较,均无显著性差异(所有P>0.05)。此外,低浓度石斛酚组、高浓度石斛酚组、阿柏西普组角膜组织中VEGF、IL-1β、TNF-α蛋白表达均显著低于模型对照组(所有P<0.01)。结论 结膜下注射石斛酚对碱烧伤大鼠角膜新生血管有抑制作用,并能促进角膜水肿的吸收。

阿柏西普在增殖型糖尿病视网膜病变患者中的应用效果

目的 分析阿柏西普在增殖型糖尿病视网膜病变(PDR)患者中的应用效果。方法 选取2019年7月至2021年7月我院收治的80例PDR患者为研究对象,将其随机分为对照组(n=40,玻璃体切除术治疗)和研究组(n=40,阿柏西普+玻璃体切除术治疗)。比较两组的治疗效果。结果 研究组的治疗总有效率为95.00%,高于对照组的77.50%(P<0.05)。治疗后,研究组的收缩期血流峰值流速(PSV)、舒张末期血流速度(EDV)高于对照组,阻力指数(RI)及血管内皮生长因子(VEGF)、促红细胞生成素(EPO)、血管生成素-2(Ang-2)、缺氧诱导因子-1α(HIF-1α)、miR-210水平低于对照组(P<0.05)。术后1周、1个月、3个月,研究组的最佳矫正视力高于对照组(P<0.05)。结论 阿柏西普+玻璃体切除术治疗PDR患者可取得理想疗效,能改善血流动力学、血清指标及提高术后视力,值得临床推广及应用。