Predicting outcomes to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular oedema: a review of the literature

Diabetic macular oedema affects visual acuity to a varying degree. The current treatment of choice is intravitreal anti-vascular endothelial growth factor (VEGF) that has proven both its anatomical and visual efficacy in several large randomised clinical trials (RCTs). Although most patients respond well to anti-VEGF agents, some, however, show a moderate or even poor response. There is no clear consensus as to how to manage these patients, or define them. In addition, identifying early in the course of treatment which patients will respond and which patients will not is paramount to any personalised treatment regimen. Most large RCTs such as RESTORE and Protocol I have attempted post hoc analyses to identify demographic, clinical, optical coherence tomography (OCT) and fluorescein angiography findings that might predict patient response. Although some factors were found to be predictive, the lack of uniformity between the different RCTs means that no consensus exists as to which of these factors can be reliably used. This review looks at the large diabetic macular oedema RCTs such as RESTORE, Protocol I, READ-2 and BOLT in an attempt to identify common prognostic indicators between the various studies. We also attempted to look at several other OCT parameters such as the inner segment-outer segment (IS-OS) layer, the external limiting membrane layer, and choroidal thickness to help determine whether they can truly predict visual outcomes in patients being treated with anti-VEGF therapy. Finally, we provide a simplified summary about which factors might be relevant in clinical practice to help guide physicians in treatment decisions.