ObjectiveTo observe the clinical efficiency of intravitreal Conbercept on exudative age-related macular degeneration (eAMD). MethodsThis is an open and prospective study without control trial. Twenty eyes from 20 patients (19 males and 1 female) with eAMD diagnosed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were enrolled in this study. Before the injection, best-corrected visual acuity (BCVA) of early treatment of diabetic retinopathy study (ETDRS), non-contact tonometer, ophthalmoscope, fundus photography, fundus fluorescein angiograph (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) were examined. The initial average letters of ETDRS acuity were 41.20±22.61, range from 8 to 80. The initial average central retina thickness (CRT) was (345.25±131.96) μm, range from 152 to 770 μm.All affected eyes were treated with intravitreal conbercept 0.05 ml (10 mg/ml). The patients were followed up for 6 to 9 months, with the mean time of (7.35±0.99) months.The BCVA, CRT after treatment were compared with baseline using paired t-test. ResultsDuring the 1, 3, 6, 12 months after treatment and the latest follow up, the mean BCVA were all improved with statistically significant difference (t=5.85, 7.09, 7.44, 7.25; P < 0.05). At 1 month ater treatment, the mean BCVA was obviously improved in 6 eyes (30%), improved in 8 eyes (40%), stable in 6 eyes (30%). At latest follow up, the mean BCVA was obviously improved in 6 eyes (30%), improved in 9 eyes (45%), stable in 5 eyes (25%). During the 1, 3, 6, 12 months after treatment and the latest follow up, the mean CRT were all decreased with statistically significant difference (t=3.34, 3.78, 3.47, 3.44; P < 0.05). At latest follow up, the leakage in macula lutea disappeared in 6 eyes (30%), decreased in 11 eyes (55%) and increased in 3 eyes (15%). No adverse events such as secondary retinal detachment or endoophthalmitis were found during the follow-up duration. ConclusionIntravitreal conbercept is a safe and effective approach for eAMD, may improve visual acuity, exudation and macular edema.
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.
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.
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 of anti-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.
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.
ObjectiveTo assess the efficacy and safety of intravitreal 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).MethodsA randomized, double-blind, multi-center phase-3 clinical trial lasting for 52 weeks (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).ResultsAmong 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.ConclusionsThe 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.
Wet age-related macular degeneration (wAMD) is caused by choroidal neovascularization (CNV), which occurs when the choroidal new capillaries reach the RPE layer and photoreceptor cell layer through the ruptured Bruch membrane, leading to neovascularization bleeding, leakage, and scarring. In view of the important role of VEGF in the development of CNV, targeted therapy with various intraocular anti-VEGF drugs is the first-line treatment for wAMD. However, the efficacy of anti-VEGF drugs in the treatment of wAMD is affected by a variety of factors, and some patients still have problems such as unresponsiveness, drug resistence, tachyphylaxis, long-term repeated injections, and severe adverse effects. It is the direction of future researches to deeply explore the physiological and pathological process of wAMD, find the cause of CNV formation, and seek better therapies.
ObjectiveTo observe the efficacy of intravitreal injection of aflibercept (IVA) in the treatment of exudative age-related macular degeneration (wAMD) combined with RPE detachment (PED).MethodsA retrospective case study. From June 2018 to June 2019, 32 eyes (overall group) of 27 wAMD patients with PED were included in the study. All eyes were treated with IVA. The initial loading dose was 2.0 mg, which was injected once a month for 2 consecutive months and and then use a PRN regimen after evaluation. According to the maximum height of PED (PEDH) 2 months after treatment, the overall group was divided into the response group and the partial response group, with 20 (62.50%) and 12 (37.50%) eyes respectively. The response group: PEDH decreased by ≥25% compared with before treatment. The partial response: PEDH decreased by ＜25%. The macular fovea was scanned with the 3D-OCT 2000 instrument from Topcon (Japan). PEDH, PED area (PEDA), PED volume (PEDV), and macular foveal retinal thickness (CMT) were measured. There was no significant difference in BCVA, CMT, PEDH, PEDA, and PEDV of the eyes in the response group and the partial response group (t=－0.791, －0.488, －0.900, －1.130, －0.400; P=0.435, 0.630, 0.380, 0.270, 0.690). The changes of BCVA, PEDH, PEDA, PEDV, CMT in each group were observed before treatment and 1, 2, 4, and 6 months after treatment. The comparison of BCVA and PED-related indicators and CMT before and after treatment were performed by repeated measures analysis of variance.ResultsCompared with before treatment, the BCVA, CMT, PEDH, PEDA and PEDV of the eyes in the overall group, the response group, and the partial response group were obviously improved after treatment. Among them, there were statistically significant differences in all indicators of the overall group and the response group (FBCVA=5.871, 3.798; P=0.001, 0.019. FCMT=24.526, 14.109; P=0.000, 0.001. FPEDH=12.569, 12.091; P=0.000, 0.000. FPEDA=7.534, 6.286; P=0.000, 0.000. FPEDV=5.139, 4.104; P=0.004, 0.014); there was no statistically significant difference in PED-related indicators in the partial response group (FPEDH=3.210, P=0.054; FPEDA=1.913, P=0.183; FPEDV=3.500, P=0.051), the difference between BCVA and CMT was statistically significant (FBCVA=3.033, P=0.027; FCMT=11.140, P=0.001). Two months after treatment, the eye number of PEDH reduction rate ＜25%, 25%-＜50%, 50%-＜75%, and ≥75% were 12 (37.50%), 8 (25.00%), 9 (28.13%), and 3 (9.38%) in the overall group, respectively. And PED in one eye (3.13%) was completely eliminated. Six months after treatment, the proportion was 13 (40.23%), 5 (15.63%), 7 (21.88%) and 7 (21.88%), respectively, among which 4 eyes (12.50%) with PED were completely resolved.ConclusionsAflibercept treatment of wAMD combined with PED can restore its anatomical indicators and improve visual function of patients in a short time; the efficacy of PED in the PRN stage is related to the efficacy of the loading dose stage.