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.
Integrins is a family of multi-functional cell-adhesion molecules, heterodimeric receptors that connect extracellular matrix to actin cytoskeleton in the cell cortex, thus regulating various physiological and pathological processes. Risuteganib (Luminate®) is a novel broad-spectrum integrin inhibitor. Based on multiple biological functions of anti-angiogenesis, vitreolysis, and neuroprotection, risuteganib is hopeful in treating several fundus diseases such as diabetic macular edema, vitreomacular traction, and non-exudative age-related macular degeneration. By far, risuteganib has successfully met the endpoints for three phase 2 studies and is preparing to enter the phase 3 of diabetic macular edema clinical trials. Overall the risuteganib is safe with no serious ocular or systemic adverse events. Given the unique mechanism of action and longer duration of efficacy, intravitreal injection of risuteganib has the potential to serve as a primary therapy, or adjunctive therapy to anti-VEGF agents.
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.
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)
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.
Objective To observe the clinical efficacy of intravitreal Ranibizumab on exudative agerelated macular degeneration (AMD).Methods The clinical data of 46 patients（52 eyes）with exudative AMD were analyzed retrospectively. All patients were diagnosed by examination of early treatment of diabetic retinopathy study (ETDRS) charts, color fundus photograph，fluorescein angiography（FFA）or indocyanine green angiography（ICGA）and optical coherence tomography（OCT）.They received intravitreal injection of 0.05 ml (10 mg/ml) Ranibizumab, once per month for 3 months. Further injection may be required if the monthly followup indicated. A total of 52 eyes received 214 times of injections, each eye received 2-6 injections (mean 4.12). The Followup duration was 12 months. Vision acuity, fovea thickness and CNV leakage before and after treatment were analyzed.Results At the 12th month after treatment, the mean letter of ETDRS charts was 37.80 (11.40 letters more that pretreatment index,Plt;0.01). FFA and (or) ICGA showed complete closures choroidal neovascularization (CNV) in 11 eyes（21.20%），partial closures in 34 eyes (65.40%)，no change in four eyes (7.70%)，lesion growth in two eyes（3.80%）and new lesion in one eye (1.90%).OCT indicated the average of fovea thickness was 187.50 mu;m (122.80 mu;m less than the pretreatment index, Plt;0.01).Conclusion Intravitreal injection of Ranibizumab for exudative AMD according to this therapeutic schedule was well tolerated，with an improvement in visual acuity，FFA or ICGA and OCT.
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.