Switching between anti-VEGF agents in the management of refractory diabetic macular edema: A systematic review

Refractory diabetic macular edema (DME) to monthly intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy has a prevalence of approximately 40% in landmark clinical trials. Options for these patients include use of intravitreal steroids, focal laser, or switching to an alternative anti-VEGF agent. We summarize the key conclusions from studies analyzing the efficacy of switching anti-VEGF agents for refractory DME. Twenty-four studies were included in analysis. The most common definitions of refractory in the included studies were a central retinal thickness (CRT) greater than 300μm or a reduction in CRT less than 10% after at least 3-6 prior anti-VEGF injections. Switching to intravitreal aflibercept (IVA) from either intravitreal ranibizumab (IVR) or bevacizumab (IVB) is associated with moderate to significant improvement in central subfield thickness and may be an appropriate choice for patients with refractory DME. The improvement in retinal thickness and edema is typically seen after the first 3 injections of IVA post-switch. Switching to IVR has also demonstrated improvement in CRT at 3-6 months post switch in large sample population studies. Future studies are required to elucidate the ideal time point for a switch in anti-VEGF agent or which patients would benefit from this change.