• canine adipose-derived mesenchymal stem cell
• dog
• spontaneous chronic corneal epithelial defects
• subconjunctival injection
• tumor necrosis factor-alpha
• vascular endothelium growth factor-A

• None Chulalongkorn University

• anti-vegf
• cornea
• corneal neovascularization
• gene therapy

• Humans
• Corneal Neovascularization/diagnosis
• Corneal Neovascularization/therapy
• Corneal Neovascularization/etiology
• Angiogenesis Inhibitors/therapeutic use
• Disease Management

• Bevacizumab
• Bévacizumab
• Cornea
• Cornée
• Injection sous-conjonctivale
• Neovascularization
• Néovaisseaux
• Subconjunctival injections

• Anti-vascular endothelial growth factor agents
• Bevacizumab
• Corneal neovascularization
• Efficacy
• Safety

• FcRn mediated half-life extension
• bevacizumab
• mAb lysine variants
• pharmacokinetics
• proteomics

• Anterior segment
• Corneal vasculature
• Fine needle diathermy
• Optical coherence tomography angiography
• Ranibizumab

• Adult
• Aged
• Aged, 80 and over
• Diathermy
• Female
• Fluorescein Angiography
• Humans
• Male
• Middle Aged
• Pilot Projects
• Prospective Studies
• Ranibizumab/therapeutic use
• Tomography, Optical Coherence

• Herpes simplex keratitis
• Herpetic Eye Disease Study
• herpes simplex virus

• Anti-VEGF
• Corneal neovascularization
• Intrastromal bevacizumab

Several studies report the key role of the vascular endothelial growth factor (VEGF) signaling on angiogenesis and on tumor growth. This has led to the development of a number of VEGF-targeted agents to treat cancer patients by disrupting the tumor blood vessel supply. Of them, bevacizumab, an FDA-approved humanized monoclonal antibody against VEGF, is the most promising. Although the use of antibodies targeting the VEGF pathway has shown clinical benefits associated with a reduction in the tumor blood vessel density, the inhibition of VEGF-driven vascular effects is only part of the functional mechanism of these therapeutic agents in the tumor ecosystem. Compelling reports have demonstrated that VEGF confers, in addition to the activation of angiogenesis-related processes, immunosuppressive properties in tumors. It is also known that structural remodeling of the tumor blood vessel bed by anti-VEGF approaches affect the influx and activation of immune cells into tumors, which might influence the therapeutic results. Besides that, part of the therapeutic effects of antiangiogenic antibodies, including their role in the tumor vascular network, might be triggered by Fc receptors in an antigen-independent manner. In this mini-review, we explore the role of VEGF inhibitors in the tumor microenvironment with focus on the immune system, discussing around the functional contribution of both bevacizumab's Fab and Fc domains to the therapeutic results and the combination of bevacizumab therapy with other immune-stimulatory settings, including adjuvant-based vaccine approaches.

• Fc receptors
• angiogenesis
• bevacizumab
• immune-modulation
• immunity
• vascular endothelial growth factor

• Angiogenesis
• Cornea
• Eye
• Inflammation
• Limbal stem cell deficiency
• Neovascularization
• Vascularization

• corneal neovascularization
• pharmacotherapy
• ranibizumab
• vascular endothelial growth factor inhibitors

• cornea
• graft rejection
• high-risk
• immunosuppression
• neovascularization
• transplantation

Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type and FcγR humanized mice. This anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown, Fc cleavage, IgG-Fc inhibition, disruption of Fc-FcγR interaction, or elimination of FcRγ-initated signaling. Furthermore, bevacizumab’s Fc region potentiated its anti-angiogenic activity in humanized VEGFA mice. Finally, mice deficient in FcγRI exhibited increased developmental and pathological angiogenesis. These findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies.

• Angiogenesis
• Angiogenèse
• Anti-VEGF
• Corneal grafts
• Corneal neovascularization
• Greffes de cornée
• Herpetic keratitis
• Kératite herpétique
• Néovascularisation cornéenne

• anti VEGF therapy
• corneal neovascularization
• vascular endothelial growth factor

Bevacizumab is believed to be as effective and safe as ranibizumab for ophthalmic diseases; however, its magnitude of effectiveness and safety profile remain controversial. Thus, a meta-analysis and systematic review appears necessary.

PubMed and EMBASE were systematically searched with no restrictions. All relevant citations comparing ranibizumab and bevacizumab were considered for inclusion. Pooled effect estimates were obtained using a fixed- and random-effects meta-analysis.

Nine independent randomised-controlled clinical trials (RCTs) involving 2,289 participants were identified. Compared with bevacizumab, the overall combined weighted mean difference (WMD) of the mean change in visual acuity for ranibizumab was 0.52 letters (95% CI −0.11–1.14). The odds ratios (ORs) of gaining ≥15, gaining 5–14, losing 5–14 and losing ≤15 letters were 1.10 (95% CI 0.90–1.33), 0.93 (95% CI 0.77–1.11), 0.89 (95% CI 0.65–1.22) and 0.95 (95% CI 0.73–1.25), respectively. The risk of serious systemic events increased by 17% (95% CI 6%–27%, p = 0.0042) for bevacizumab treatment in comparison with ranibizumab. No statistically significant differences between the two treatments were found for the nonfatal arterial thrombotic events, ocular serious adverse, death from vascular and all causes events.

Bevacizumab is not inferior to ranibizumab as a treatment for achieving visual acuity. The use of bevacizumab was associated with an increased risk of developing serious systemic events. Weighing the costs and health outcomes is necessary when selecting between bevacizumab and ranibizumab for ophthalmic diseases. Due to the limitations of the available data, further research is needed.

• Antibodies, Monoclonal, Humanized/therapeutic use
• Bevacizumab
• Choroidal Neovascularization/drug therapy
• Eye Diseases/drug therapy
• Humans
• Randomized Controlled Trials as Topic
• Ranibizumab
• Retinal Neovascularization/drug therapy
• Visual Acuity