Comparison between Bevacizumab, Ranibizumab and Aflibercept in management of macular edema secondary to diabetic maculopathy, retinal vein occlusion and choroidal neovascularization

Abstract

Macular edema continues to remain a leading cause of severe visual loss worldwide. In the past decade, a number of advances in pharmacotherapeutics have dramatically improved outcomes in these patients. VEGF inhibitors have become firmly established as the standard of care in the treatment of macular edema secondary to different diseases. Recent developments in our understanding of the pathogenesis of macular edema and healthy homeostasis have and will continue to result in the generation of more specific and potent therapeutic agents. Many studied proved the critical role of VEGF in pathogenesis of macular edema. Understanding this role helped in treatment of many diseases, Physician and patients are now pursuing gains in VA instead of maintenance or reduction in rate of visual loss. The introduction of anti-vascular endothelial growth factor (anti-VEGF) drugs to ophthalmology over the last decade has revolutionized the treatment of exudative AMD and holds great promise for DME and RVO.

Bevacizumabis a full-length monoclonal antibody, which binds to and inhibits all isoforms of VEGF A. On receiving 1.25 mg of bevacizumab, the vitreous half-life is 4.32 days. The antibody fragment ranibizumab, by blocking all VEGF isoforms, has proven to be highly effective not only in reducing macular edema and preventing further vision loss, but also in producing clinically meaningful improvements in vision., the vitreoushalf-life is 2.88 days. VEGF Trap appears to have a higher VEGF binding affinity than bevacizumab and, unlike ranibizumab, can bind other members of the VEGF family. VEGF Trap may, thus, offer a longer duration between doses when compared to ranibizumab and bevacizumab.The half-life in animals is about 5 days; however, the half-life in the human eye is estimated to be about 7.13 days. Reported ocular side effects from IVI of this drugs was endophthalmitis, sterile intraocular inflammation, acute and chronic increased IOP, ocular hemorrhage and rhegmatogenous retinal detachment. Systemic adverse events include non ocular hemorrhage, included acute blood pressure elevations, cerebrovascular accidents, myocardial infarctions and aneurysms. Regarding DME, the DRCR.net conducted a large, prospective RCT that compared the three anti-VEGF agents, ranibizumab, bevacizumab, and aflibercept for the treatment of DME (Protocol T). In protocol T, intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved DMEwith no significant difference between them, however at worse levels of initial visual acuity, aflibercept was more effective at improving vision. On the other hand, other studies comparing ranibizumab and bevacizumab showed that ranibizumab is associated with more improvement in BCVA and the mean number of injections is higher with bevacizumab. Patientswith DME unresponsive to ranibizumab and/or bevacizumab demonstrate visual and anatomical improvements after conversion to Aflibercept. Regarding RVO,all the three drugs showed same efficacy in improving visual acuity, however ranibizumab showed superiority to bevacizumab in decreasing macular edema on OCT in some studies. As in DME, conversion to aflibercept in patients with RVO unresponsive to ranibizumab and/or bevacizumab result in stabilization of the vision, improved macular anatomy, and extension of the injection interval. Also in senile AMD, no significant difference was found in the mean improvement in BCVA or central retinal thickness between the three drugs but less number of injections was needed with aflibercept. Unlike DME and ranibizumab, there were no apparent differences in visual acuity outcomes after switch to AFL in patients unresponsive to RBZ and/or bevacizumab. No significant difference in ocular or systemic side effects was reported between the three drugs.