ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.