Potential anti-vascular endothelial growth factor therapies for central retinal vein occlusion

Abstract

Central retinal vein occlusion (CRVO) remains an important cause of visual loss. Impaired venous drainage leads to retinal hypoxia with upregulation and release of vascular endothelial growth factor (VEGF). VEGF increases vascular permeability and leads to the breakdown of the blood-retinal barrier, with the development of macular oedema. Treatment strategies for macular oedema in CRVO currently under evaluation focus on VEGF blockage. Bevacizumab is a humanized monoclonal antibody that blocks VEGF. It has been evaluated in a clinical trial that compared intravitreal injections of bevacizumab 1.25 mg with sham injections every 6 weeks. At the end of a 24-week follow-up period, 60.0% of patients in the bevacizumab group had gained ≥ 15 letters compared with 20.0% in the control group (p=0.003). Aflibercept (previously VEGF Trap-Eye) is a 115 kD decoy receptor fusion protein. Aflibercept is capable of binding both VEGF and placental growth factor (PlGF). By blocking both VEGF and PlGF, aflibercept could be more effective than other anti-VEGF drugs. Two clinical trials have evaluated the efficacy of aflibercept for the treatment of macular oedema in CRVO: COPERNICUS and GALILEO. Both included a similar 6-month phase, during which patients were randomized to receive either an intravitreal injection of aflibercept 2 mg or a sham injection every month. In a second 6-month phase of the GALILEO study, patients in the treatment group were treated on an as needed (PRN) basis with aflibercept, while patients in the placebo group continued with sham injections. In the second 6-month phase in the COPERNICUS study, all patients were treated with aflibercept on a PRN basis. Treatment with aflibercept led to an improvement in visual acuity of ≥ 15 letters in 55.3% (COPERNICUS) and 60.2% of patients (GALILEO). Patients initially in the placebo group and then treated PRN gained only a mean of 3.8 letters, with 30.1% achieving a visual gain of ≥ 15 letters (COPERNICUS). The percentage of patients that improved by ≥ 15 letters was 32.4% for the group receiving sham injections throughout the GALILEO study. In summary, VEGF blockage has been proven to improve visual outcomes in patients with macular oedema due to CRVO. However, an important disadvantage of anti-VEGF drugs is the need for frequent reinjections and even more frequent control visits. Further advances are needed in order to improve quality of life and reduce the burden to healthcare systems.