Objective To observe the efficacy and safety of intravitreal injection of Ranibizumab(Lucentis) on exudative age－related macular degeneration (AMD). Methods To analyze retrospectively the clinical data of 56 patients with exudative AMD, which was diagnosed by examination of ETDRS charts, color fundus photograph, fluorescein angiography(FFA) or indocyanine green angiography(ICGA) and optical coherence tomography(OCT), were underwent intravitreal injection Lucentis 0.5 mg. Before the treatment, the ETDRS charts letter of 56 eyes was 25.1; choroidal neovascularization(CNA) was leaky which examined by FFA and ICGA; the average thickness of retina was 303.45 mu;m. Ranibizumab injection therapeutic times were 2.8, the average therapeutic times were 3.1. Follow－up time was 6－12 months (mean 8.7 months). Visual acuity (ETDRS charts letter), retinal thickness, leakage of CNV and operative complications before and after the treatment were analyzed. Results At the end of the follow－up period, the mean letter of ETDRS charts was 38.5, increased 13.4 letters (P＜0.01), the ETDRS charts improved 15 or more letters in 22 eyes (39.3%), decreased more than 15 letters in 2 eyes (3.6%); the foveal thickness on OCT images were 303.45 mu;m before treatment and 191.35 mu;m a fter treatment, decreased significantly (P＜0.00); FFA and/ or ICGA showed CNV complete closure in 12 eyes (21.4%), partial closure in 33 eyes (58.9%), no change in 9 eyes (16.1%) and new CNV in 1 eye (1.8%); Slight complications after operation disappeared during one week. Conclusion Intravitreal injection of Ranibizumab for exudative AMD was well tolerated, with an improvement in VA, FFA or ICGA , and OCT. (Chin J Ocul Fundus Dis,2008,24:160-163)
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.
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 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.
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.
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.
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.