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Objective To assess the efficacy and safety ofintravitreal aflibercept injection (IAI) compared with photodynamic therapy (PDT) in the treatment of Chinese patients with predominantly classic subfoveal choroidal neovascularization (CNV) lesions secondary to neovascular age-related macular degeneration (nAMD).Methods A randomized,double-blind,multi-center phase-3 clinical trial lasting for 52weeks (from December 2011 to August 2014).Subjects were randomized in a 3:1 ratio to either IAI group or PDT-to-IAI group.Subjects in the IAI group received 2 mg IAI at baseline and at week 4,8,16,24,32,40,48,with sham injection at week 28,36.Subjects in the PDT-to-IAI group were forced to receive PDT once at baseline and more time at week 12,24 if PDT retreatment conditions were met.Sham injections were given in PDT-to-IAI group at baseline and at week 4,8,16 and 24,followed by 2 mg IAI at week 28,32,36,40,48.The primary outcome of efficacy were the change in mean Best Corrected Visual Acuity (BCVA) from baseline to week 28,and that of week 52.Safety evaluation included the percentage of subjects who suffered treatment emergent adverse events (TEAEs).Results Among the 304 subjects enrolled,there were 228 and 76 cases in IAI group and PDT-to-IAI group respectively.At week 28,the changes of mean BCVA in IAI group,PDT-to-IAI group compared to baseline were +14.0,+3.9 letters,respectively.At week 52,the changes of mean BCVA in two groups were + 15.2,+8.9 letters respectively with the difference of +6.2 letters (95％CI 2.6-9.9,P=0.000 9).At week 52,the mean foveal retinal thickness in the two groups decreased by-189.6,-170.0 μm,respectively.Subjects with the most BCVA increase in IAI group were those aged ＜65,and those with active CNV lesion area ＜50％ of total lesion area.The most common TEAEs in IAI group and PDT-to-IAI group are macular fibrosis [11.8％ (27/228),6.6％ (5/76)] and BCVA decline [6.6％ (15/228),21.1％ (16/76)].There were 3 cases of arterial thromboembolic events defined in the antiplatelet experimental collaboration group,but all were considered unrelated to interventions.Conclusions The efficacy of aflibercept is superior to that of PDT in nAMD patients in China.The therapeutic effect of aflibercept persisted to week 52 in all subjects.The rate of adverse events was consistent with the safety data of aflibercept known before.
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Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs,including monoclonal antibodies (such as bevacizumab and ranibizumab) and fusion protein agents (such as aflibercept and conbercept) have been proven to be effective in the treatment of wet age-related macular degeneration (wAMD).However,there are still some patients with poor efficacy,such as no response to initial treatment or poor response,and even relapse during the course of treatment.In view of the different targets and molecular characteristics of anti-VEGF drugs,the switch of anti-VEGF drugs and the adjustment of delivery pattern,dosages and intervals have been the strategies to cope with the poor efficacy in clinic.However,there are some differences in the results of current studies.Overall,the recovery of retinal anatomical outcome achieves more benefits,and it is relatively difficult to improve visual acuity.To determine which regimen would get the biggest benefits,a large number of randomized controlled clinical trials and long study period will be needed.
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Anti-vascular endothelial growth factor (VEGF) drugs,including monoclonal antibodies (such as bevacizumab and ranibizumab) and fusion protein agents (such as aflibercept and conbercept) have been clinically proven to be effective to treat exudative age-related macular degeneration AMD).However,there are still some patients do not or poorly respond to the initial anti-VEGF agents,usually after several injections,ophthalmologists may switch to another anti-VEGF agent.In general,switching of anti-VEGF agent is considered for recurrent AMD,AMD resistance to anti-VEGF treatments.Current switching protocols include the replacement of monoclonal antibodies with fusion protein agents,the replacement of fusion protein agents with monoclonal antibodies,the substitution of one monoclonal antibody with another one,and the replacement of monoclonal antibodies with fusion protein agents and switching back with monoclonal antibodies.However,current researches on the switching of anti-VEGF drugs for exudative AMD are mostly retrospective and single-arm studies,and there are some differences in the results of different studies.Therefore,for patients with exudative AMD who do not respond to or respond poorly to anti-VEGF drugs,the efficacy of switching of anti-VEGF drugs is uncertain right now.Switching ofanti-VEGF agents may improve the retinal anatomical outcome of the affected eye but may not necessarily improve visual acuity.Thus it is an option in the clinical practice to treat AMD.To determine the benefits of above mentioned switching regimens,randomized controlled clinical trials with large sample number and long study period will be needed.
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According to the best corrected visual acuity and the morphological changes of the macular fovea,responses to the neovascular age-related macular degeneration (nAMD) who receive anti-vascular endothelial growth factor (VEGF) therapy show large variability,including poor and non-responders.Various factors will be reviewed to account for poor and non-response to anti-VEGF therapy,such as the related susceptibility genes,factors related with the development of choroidal neovascularization and morphologic parameters,pharmacokinetics and tachyphylaxis.The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy to improve the therapeutic outcome of nAMD.
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Objective To observe the baseline characteristics and visual outcomes after two years follow-up of exudative age-related macular degeneration (AMD) patients treated with ranibizumb. Methods Forty-four eyes of 44 patients with exudative AMD were enrolled into this retrospective study, 19 were men and 25 were women. The mean age was 78 years (range 64–92 years). All patients were underwent best corrected visual acuity (BCVA, Early Treatment of Diabetic Retinopathy Study), fundus color photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT). The mean BCVA was (50.36±14.43) letters, the mean central foveal thickness (CFT) was (291.95± 82.19)μm, and the fluorescence leakage area of choroidal neovascularization (CNV) was (7.61±5.84) mm2. All patients received three initial intravitreous injection of ranibizumb (IVR) and were retreated with monthly IVR when needed. The mean follow up time was 25.6 months (range 24–29 months). On 1, 2, 3, 6, 12, 18 and 24 months after treatment, BCVA and OCT were repeated. On 3, 6, 12, 18 and 24 months after treatment, FFA and ICGA were repeated. The change of BCVA, CFT and fluorescence leakage area of CNV were observed. The association of baseline characteristics and two year visual outcomes were analyzed. Results On 1, 2, 3, 6, 12, 18 and 24 months after treatment, the BCVA were improved significantly (t=?1.89,?3.51,?4.61,?4.04,?5.77,?4.69;P0.05). Conclusion Two year visual outcomes of exudative AMD patients treated with ranibizumb is negative correlated with baseline BCVA and fluorescence leakage area of CNV, but not correlated with baseline CFT.
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Background Intravitreal injection of ranibizumab (IVR) is one of the most effective therapies for neovascular age-related macular degeneration (nAMD).Understanding the influence of IVR on retinal pigment epithelium (RPE) and choroidal thickness is helpful for us to choose the operative times and timing based on pharmacologic effects and tissue response.However,limited studies are available about quantitative analysis of RPE atrophic area and subfoveal choroidal thickness after IVR for nAMD.Objective This study was to report the changes of RPE atrophic area and subfoveal choroidal thickness after IVR for nAMD.Methods A prospective series cases-observational study was designed.Forty-one eyes of 41 consecutive patients with nAMD were enrolled in Renmin Hospital of Wuhan University from January 2015 to June 2015,and written informed consent was obtained from each patient prior to entering the cohort.The affected eyes received intravitreal injection of 0.05 ml ranibizumab (10 mg/ml) and then followed up monthly for 12 months.The RPE atrophy area around macula and subfoveal choroidal thickness were measured by a newly developed RPE analysis software spectral-domain optical coherence tomography (OCT) and enhanced depth imaging of SD-OCT (EDI-OCT),respectively,and the RPE atrophy area and choroidal thickness changes were compared before IVR and 3,6 and 12 months after IVR.The correlation between RPE atrophy area and choroidal thickness before and after IVR was analyzed.Results All the patients finished the treating procedure and follow up.The visual acuity (logMAR) after IVR was considerably improved in comparison with before IVR (F=7.631,P＜0.001).The mean subfoveal choroidal thickness value was (264.55 ± 100.95) μm before IVR,and that of 3,6,12 months after IVR was (247.42±105.46),(246.81± 99.85) and (253.97±101.15)μm,respectively,showing a significant difference among different time points (F =2.030,P ＜ 0.05),and the mean subfoveal choroidal thickness values 3,6,12 months after IVR were evidently thinned in comparison with before IVR (all at P＜0.05).No significant difference was found in RPE atrophic area among different time points (F=0.116,P =0.951).Weak linear correlations were seen between RPE atrophy area and choroidal thickness (r =-0.185),the RPE atrophy area change values and choroidal thickness change values between IVR ＞ 6 times and ≤ 6 times (r =0.297,-0.327),but these results were not statistically significant (P =0.248,0.282,0.103).At the end of the follow up,weak linear correlations were seen in RPE atrophy area change values and choroidal thickness change values with IVR times (r,=-0.266,0.342),but these results were not statistically significant (P =0.148,0.060).Conclusions IVR for nAMD can lead to subfoveal choroid atrophy instead of RPE atrophy.IVR does not accelerate the atrophy progression of both RPE and choroid.
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Neovascular age-related macular degeneration is also known as wet age-related macular degeneration (wAMD) , which is now one of potentially blinding diseases in elder population worldwide.The application of anti-vascular endothelial growth factor (VEGF) drugs is becoming the first-line therapy for wAMD at present.However, during the long-term follow up, we find that the vision of some patients dose not improve even falls after treatment, or the vision is unable to keep for a long term after its improvement.Hence,to find the key factors that affect the therapeutical effect is the focus issue nowadays.There are many factors that affect wAMD curative effect,including the limitation of drug itself, the personal conditions of the patients, the features of the choriodal neovascularization (CNV) , the formulation and implementation of the treatment regimen, etc.Imaging features of CNV and treatment timing can serve as the available indexs to analyze the prognosis.In addition,reasonable and optimized managing regimens for wAMD probably is an approach to improve the treating effect.Understanding of the factors that affect curative effect of wAMD is benefit for us to setup the individualized therapy and achieve the best vision.Ophthalmologists should fully recognize the importance of wAMD individualized treatment and management.
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The therapeutic effect of anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) was determined by a number of factors.Comprehensive thorough analysis of clinical features,imaging results and treatment response can predict the potential efficacy and possible vision recovery for the patient,and also can optimize the treatment regime to make a personalized therapy plan.Precise medicine with data from genomics,proteomics and metabolomics study will provide more objective and accurate biology basis for individual precise treatment.The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy,to achieve individualized precise diagnosis and treatment,to improve the therapeutic outcome of nAMD.
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Choroidal neovascularization (CNV) is the key characteristic of neovascular age-related macular degeneration (nAMD),and the effective therapy is intravitreal injection of anti vascular endothelial growth factor (VEGF) agents based on clinical and basic research.In the meantime the challenge is how to further improve the inhibiting effect for CNV and visual function of anti-VEGF treatment on nAMD.The new strategy and drug delivery devices for anti-VEGF treatment will optimize the clinical scheme.From bench to bedside,the research on targeted treatment of angiogenesis brings the bloom of nAMD medical therapy.
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Purpose: To evaluate retinal morphology and function of patients with advanced neovascular age-related macular degeneration (AMD) before, during, and after treatment with ranibizumab. Methods: Twenty-one eyes diagnosed with advanced AMD were studied with optical coherence tomography (OCT) and multifocal electroretinography (mfERG). Three intravitreal injections of ranibizumab were administered at 1-month intervals. Evaluations were performed before the first injection (D0) and at 30 (D30), 60 (D60), and 90 days (D90) after the first injection and compared to an age-matched control group (n=21 eyes). Results: The thickness of macular retinal layers increased before treatment due to the presence of intraretinal fluid. A thick retinal pigment epithelium-choriocapillaris complex (RPE-CC) suggested the presence of choroidal neovascular membrane. Intraretinal edema decreased after treatment (P<0.01), but persisting RPE-CC thickness resulted in a subretinal scar. Three different annular retinal areas were studied with mfERG (from center to periphery: rings R1, R2, and R3). The amplitude of the first negative component (N1) decreased in R1, R2, and R3 at D30, D60, and D90 when compared with that in controls (P<0.05); the N1 implicit time was delayed in R3 at D30 (P<0.05). The amplitude of the first positive component (P1) was reduced in R1 and R2 at D30, D60, and D90 when compared with that in controls (P<0.01); the P1 implicit time was delayed in R1 at D0 and D60 (P<0.05), in R2 at D0, D30, and D90 (P<0.01), and in R3 at D30 and D60 (P<0.05). Conclusion: Ranibizumab reduces intraretinal edema, even in advanced cases. Central macular activity appeared to increase after the initiation of treatment, improving over time. .
Objetivo: Avaliar a morfologia e função da retina em pacientes com doença macular relacionada à idade (DMRI), neovascular avançada, antes, durante e após o tratamento com ranibizumabe. Métodos: Vinte e um olhos com diagnóstico de DMRI avançada foram avaliados pela tomografia de coerência óptica (OCT) e eletrorretinografia multifocal (mfERG). Três injeções intravítreas de ranibizumabe foram administradas em intervalos de 1 mês. As avaliações foram realizadas antes da primeira injeção (D0) e aos 30 (D30), 60 (D60), e 90 dias (D90) após a primeira injeção e comparados com um grupo controle (n=21 olhos). Resultados: A espessura macular estava aumentada antes do tratamento devido à presença de fluido intrarretiniano, e o aumento da espessura do complexo EPR-CC foi compatível com a presença de membrana neovascular coroidal. O edema intrarretiniano diminuiu após o tratamento (P<0,01). Três diferentes áreas retinianas anulares (do centro para a periferia: anéis R1, R2 e R3) foram consideradas no mfERG. A amplitude do componente N1 diminuiu nos anéis R1, R2 e R3 em D30, D60 e D90 comparados com o grupo controle (P<0,05); e o tempo implícito de N1 aumentou no anel R3 em D30 (P<0,05). A amplitude do componente P1 diminuiu em R1 e R2 nos dias D30, D60 e D90 comparados com os controles (P<0,01); o tempo implícito de N1 aumentou no anel R1 em D0 e D60 (P<0,05), no anel R2 em D0, D30 e D90 (P<0,01) e no anel R3 em D30 e D60 (P<0,05). Conclusão: O ranibizumabe reduziu o edema intrarretiniano, mesmo em casos avançados. A atividade central macular parece aumentar após o início do tratamento e melhorar ao longo do tempo. .
Subject(s)
Clinical Coding/standards , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections/diagnosisABSTRACT
Exudative age-related macular degeneration (AMD) is the leading cause of central vision loss in elderly population,and its primary pathological mechanism is the formation of choroidal neovascularization (CNV).Recently,it is found that the balance of angiogenesis and antiangiogenic factors plays an important role in the formation of CNV,and the main factors are vascular endothelial growth factor (VEGF) and pigment epitheliumderived factor (PEDF).The targeting therapy for these cytokines provides a new approach to the treatment of exudative AMD.Anti-VEGF therapy is of great effect on controlling CNV and improving visual acuity in exudative AMD patients.The purpose of this review was to summarize current advance in the study of cytokines associated with the pathogenesis of exudative AMD and its targeting therapy.
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Comparison of age-related macular degeneration treatments trials(CATT)reported the results of the first year:At 1 year,bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule.Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly.Bevacizumab is a monoclonal antibody(MAb)and full-length anti-VEGF antibody that successfully prevents binding of all the biologically active isoforms of VEGF to the receptor.Ranibizumab is a isolated antigen-binding fragment (Fab)from bevacizumab using recombinant genetic techniques.Ranibizumab has been clinically evaluated in 4 Phase Ⅰ/Ⅱ studies.The cost of Avastin is ＄50 per dose compared with ＄ 2000 per dose for Ranibizumab.If Avastin could improve vision and macular anatomy,then it would not only be clinically superior to Ranibizumab.The CATT data support the continued global use of intravitreal bevacizumab as an effective.low-cost alternative to ranibizumab,particularly for patients paying all costs out of pocket.
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The introduction of anti-vascular endothelial growth factor (VEGF) therapy represents a landmark in the management of wet age-related macular degeneration (AMD).However,as a new therapy,several problems such as durability of the therapeutic effects,medication side effects,and medication selection have emerged.We should make appoint of improving the therapeutic effect and safety by realizing the limitation of the therapy,monitoring the clinical potential adverse reactions of anti-VEGF agents,and recommending individualized treatment.
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Objective To evaluate the efficacy and safety of photodynamic therapy(PDT)combined with intravitreaIinjection of bevacizumab for choroidal neovascularization(CNV)caused by agerelated macular degeneration(AMD). Methods A total of 21 eyes of 21 patients with AMD,which was diagnosed by examination of visual acuity,intraocular pressure,ocular fundus,fundus color photography,fundus fluoreseein angiography(FFA),indocyanine green angiography(ICGA)and optic coherence tomography(OCT),were underwent PDT combined with intravitreal injection of Bevacizumab.The patients,15 males(15 eyes)and 6 females(6 eyes),aged from 56 to 78 years,with the average of 68.6years.The best corrected visual acuity:counting fingers/10cm-0.9,logMAR was 1.04±0.41.CNV located in below or side central fovea of macula.There was obvious leakage of fluorescein which examined by FFA and ICGA.The average of retinal thickness of macular foveal was(258.91±78.66)μm.The treatment method of PDT has to according to the way of PDT for TAP and Verteporfin PDT for VIP.Intravitreal infeetion with 1.5mg bevacizumab was performed after three days under surface anesthesia.Follow-up time was 1,3,6,12 months after the treatment. Resuits At last visit,the best corrected visual acuity:counting fingers/10 cm-1.5,logMAR was 1.04±0.41,and the differences are statistically significant compared with before.The BCVA improved four or more lines in 6 eyes(28.57%),improved two to four lines in 9 eyes(42.86%),stabilized(±1 line or no change)in 6 eyes(28.57%)and decreased in none.The average intraocular pressure was(15.20±2.41)mmHg after surgery,and the differences was not statistically significant compared with before(P＞0.05).FFA and lCGA showed CNV complete closure in 13 eyes(61.90%).partial closure in 8 eyes(38.10%).The average of retinal thickness of macular foveal was(127.38±20.14)μm(P＜0.01). Conclusion Combining treatment with PDT and intravitreal injection of Bevacizumab is safe and effective for CNV which caused by AMD.It has significant improvement in BCVA.1eakage of CNV and retinal edema.