Intravitreales Bevacizumab bei der neovaskulären altersabhängigen Makuladegeneration

The efficacy and safety of the therapeutic anti-VEGF concept has already been demonstrated for pegaptanib and ranibizumab. Bevacizumab acts as an antibody against all VEGF-A isoforms and has been developed for oncological indications with intravenous application. Initial reports on intravitreal administration in patients with neovascular age-related macular disease (AMD) have shown beneficial morphological and functional effects. In the meantime, bevacizumab has been used off-label in thousands of patients with AMD. However, data from prospective, controlled, randomized trials on both safety and efficacy are lacking. Herein recent experiences with bevacizumab are summarized and discussed. Furthermore, a web-based platform for online data registration and pooled analyses is presented.     

Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration

Angiogenesis has a causal role in many diseases, including neovascular age-related macular degeneration (AMD). Identification of key regulators of angiogenesis, including vascular endothelial growth factor (VEGF), fibroblast growth factor 2, pigment epithelium-derived growth factor, angiopoietins and extracellular matrix molecules, has facilitated the development of novel therapeutic agents that target the underlying pathological angiogenic process. Among these, VEGF serves as a "master switch" for many ocular neovascular conditions through its promotion of endothelial cell proliferation and survival, vascular permeability and ocular inflammation. Two anti-VEGF agents are now clinically available: bevacizumab, an antibody for metastatic colorectal cancer, and pegaptanib sodium, an aptamer for neovascular AMD. Unlike bevacizumab, which binds all VEGF isoforms, pegaptanib targets only VEGF165, the isoform responsible for pathological ocular neovascularization and thus an ideal target for treatment of AMD. Although other therapies targeting angiogenesis in AMD are in clinical development, to date, pegaptanib is the only therapy approved by the Food and Drug Administration of the United States for the treatment of all neovascular AMD and represents a valuable addition to the hitherto limited options available for patients.     

VEGF in age-related macular degeneration. Part II. VEGF inhibitors use in age-related macular degeneration treatment

Wet AMD remains a therapeutic challenge. VEGF inhibitors are new promising group of medical agents undergoing advanced clinical trials. Oncology is the main specialty using anti-VEGF therapy. Two agents were designed from the beginning as ophthalmologic medicines. These are pegaptanib and ranibizumab. In the paper there is mechanism, efficacy and safety data presented, especially coming from multi-center randomized clinical trials. Monoclonal VEGF-antibodies (ranibizumab and bevacizumab) seem to be most effective in wet AMD treatment. Because of important physiological VEGF role long-term observation is needed to confirm safety of VEGF inhibition.     

Anti-VEGF therapy: comparison of current and future agents

With the identification of vascular endothelial growth factor (VEGF) and the confirmation of its pathophysiologic link to retinal and choroidal angiogenesis, numerous agents have been designed to inhibit its activity. It is noteworthy that anatomic and visual benefits have been associated with the use of anti-VEGF agents such as pegaptanib (Macugen) and to a greater extent, ranibizumab (Lucentis) and bevacizumab (Avastin), particularly in the management of neovascular age-related macular degeneration (AMD). Clinical trials and case series have confirmed the utility of these agents. However, shortcomings of the current drugs such as short half-life, intraocular dosing, limited effectiveness in some patients, and potential systemic side effects continue to drive the development of new agents. In this article, we review current anti-VEGF therapies and discuss future developments.     

Management of pediatric choroidal neovascular membranes with intravitreal anti-VEGF agents: a retrospective consecutive case series

Objective: To report the results of pediatric choroidal neovascular membranes (CNVMs) secondary to a variety of etiologies treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents.Design: Retrospective case series.Participants: Four pediatric patients at the Hosptial for Sick Children with CNVMs secondary to a variety of etiologies.Methods: Each patient received multiple treatments with one of the following anti-VEGF agents: pegaptanib sodium, bevacizumab, or ranibizumab. Progress was monitored by clinical exam, optical coherence tomography (OCT), and fluorescein angiography.Results: The mean age of our patients was 11.5 years (range, 8–15 years). Patients were followed for a mean of 10 months (range, 4–14 months). One patient was treated with pegaptanib sodium, 2 with bevacizumab, and 1 with ranibizumab. Following treatment, 1 patient showed an improvement and 3 showed stabilization of vision with reduction of fluid on clinical exam and OCT, and cessation of leakage on the fluorescein angiogram. Patients required 2–5 injections of the anti-VEGF agent. No ocular or systemic adverse events were observed in any of our treated patients.Conclusions: Anti-VEGF agents were effective in the treatment of pediatric CNVMs in this case series. However, we do not know how these results would have differed from other treatment modalities, including observation. We did not observe any adverse side effects; however, larger studies are required to document the safety of these medications in the pediatric population where normal angiogenesis is occurring.     

Review of ranibizumab trials for neovascular age-related macular degeneration

Ranibizumab, a recombinant, humanized, monoclonal antibody antigen-binding fragment that neutralizes all VEGF-A isoforms, is the first US FDA-approved therapy for neovascular age-related macular degeneration (AMD) to result in improvement in visual acuity. The benefit of intravitreal ranibizumab applies to all angiographic subtypes of neovascular AMD and across all lesion sizes. The two original phase III studies (ANCHOR and MARINA) demonstrated sustained visual acuity (VA) gains over a two-year monthly dosing schedule. Following these trials, several studies looked at ways to decrease the treatment burden while maintaining similar visual gains. These trials included PIER, PrONTO, EXCITE, SUSTAIN, HORIZON, and CATT. Visual acuity data shows that monthly dosing of ranibizumab produces superior vision outcomes compared to a less-frequent, fixed-dosing schedule. Intravitreal ranibizumab is well tolerated and shown to have a very low rate of adverse ocular or systemic side-effects.     

Safety and complications of intravitreal injections performed in an Asian population in Singapore

There has been a rapid rise in the use of intravitreal injections, such as anti-vascular endothelial growth factor (anti-VEGF) agents, performed over the past few years for the treatment of ocular neovascular diseases. This study aims to review the systemic and ocular adverse events among patients treated at a tertiary eye center over a period of 8 years. A retrospective review of all intravitreal injections of anti-VEGF performed over an 8-year period at a tertiary eye care center in Singapore was done. We report the frequency of systemic and ocular adverse events and compared it among the various anti-VEGF agents. A total of 14 001 intravitreal injections were performed on 2225 patients from January 1, 2007 to December 31, 2014, and this included 9992 bevacizumab (71.4 %), 3306 ranibizumab (23.6 %) and 703 aflibercept (5.0 %) injections. Systemic complications related to treatment were 26 (1.17 %) deaths (from any cause), of which 11 (0.49 %) were from fatal thromboembolic events, 7 (0.31 %) non-fatal thromboembolic events and two (0.09 %) serious non-ocular hemorrhage. Ocular complications included one (0.007 %) endophthalmitis, three (0.021 %) traumatic cataracts, and one (0.007 %) retinal detachment. Rates of death and thromboembolic events were similar among ranibizumab (lucentis), bevacizumab (avastin) and aflibercept (Eylea). The systemic and ocular complications associated with intravitreal injections among Asian patients at a tertiary eye center are relatively low and reflect the safety of the treatments.     

Review of Ranibizumab Trials for Neovascular Age-Related Macular Degeneration

Ranibizumab, a recombinant, humanized, monoclonal antibody antigen-binding fragment that neutralizes all VEGF-A isoforms, is the first US FDA-approved therapy for neovascular age-related macular degeneration (AMD) to result in improvement in visual acuity. The benefit of intravitreal ranibizumab applies to all angiographic subtypes of neovascular AMD and across all lesion sizes. The two original phase III studies (ANCHOR and MARINA) demonstrated sustained visual acuity (VA) gains over a two-year monthly dosing schedule. Following these trials, several studies looked at ways to decrease the treatment burden while maintaining similar visual gains. These trials included PIER, PrONTO, EXCITE, SUSTAIN, HORIZON, and CATT. Visual acuity data shows that monthly dosing of ranibizumab produces superior vision outcomes compared to a less-frequent, fixed-dosing schedule. Intravitreal ranibizumab is well tolerated and shown to have a very low rate of adverse ocular or systemic side-effects.     

The impact of locally administrated VEGF inhibitors on vascular homeostasis--controversies concerning safety of intravitreal therapy in AMD patients

Intravitreal vascular endothelial growth factor (VEGF) inhibitors constitutes currently the first-line treatment in neovascular age-related macular degeneration (AMD). By intravitreal application of the drug, the dosage can be kept low while maximizing its effect on choroidal neovascularization and minimizing potential adverse systemic effects. However, the eye-blood barrier is often disrupted in ophthalmic neovascular disorders and the drugs can be detected in circulating blood despite being administered as an intraocular injection. As patients with AMD constitute a high-risk population for cardiovascular events, the safety of anti-VEGF therapies must be precisely and thoroughly assessed. In the present work, the recent reports documenting systemic safety of intravitreal VEGF inhibitors have been reviewed. Moreover, the novel methods to assess the potential systemic effect on vascular homeostasis as the consequence of such therapy have been also discussed.     

Ranibizumab治疗湿性年龄相关性黄斑变性的安全性分析

湿性年龄相关性黄斑变性（AMD）的主要病理改变为脉络膜新生血管（CNV）的形成，血管内皮生长因子（VEGF）水平的升高是其重要的发病机制之一。Ranibizumab是一种重组人源化抗VEGF单克隆抗体片段，能够抑制新生血管形成，玻璃体腔内注射ranibizumab治疗湿性AMD的疗效已得到多项临床研究的证实。此外，玻璃体腔内注射ranibizumab的耐受性良好，眼内与全身不良反应的风险未显著增加。其主要眼内不良事件为眼部炎症和一过性眼压升高，但发生率较低。主要的严重眼内不良事件的发生率〈4％。Ranibizumab应用后心脑血管意外的发生风险无显著增加，采取在每月随访监测的基础上降低注射频率的方法可能得到最佳的风险获益比。就近年来湿性AMD患者应用ranibizumab治疗的临床试验为基础，从循证医学角度讨论其玻璃体腔内注射的安全性。