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

Abstract

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.

Real-World Results of Intravitreal Ranibizumab, Bevacizumab, or Triamcinolone for Diabetic Macular Edema

“…As for CMT, the eyes with a higher initial CMT were found to be more likely to benefit from anatomical improvement (p = 0.001). This is consistent with previous knowledge of worse baseline VA and higher initial CMT being associated with better visual gains; however, CMT has previously not been shown to be predictive of final anatomical outcomes [12].…”

Galectin‐1 promotes choroidal neovascularization and subretinal fibrosis mediatedviaepithelialmesenchymal transition

“…In concert with VEGFA, galectin-1 colocalization with VEGFR2-expressing endothelial cells in neovascular AMD, also seen in proliferative diabetic retinopathy (17), would be a common feature for enhancing inflammation-related angiogenesis in the eye, which is driven by the VEGFR2-mediated ERK1/2 phosphorylation and subsequent CCL-2/ MCP1 and ICAM1 expression. Major cellular participants in the pathogenesis of AMD and diabetic retinopathy are originally different (i.e., RPE and Müller glia) but functionally equivalent in that both cell types express galectin-1 (17,18) on top of VEGFA to modify the VEGFR2-mediated disease activity, which may in part explain the robust existence of anti-VEGF-refractory patients in the treatment of these vision-threatening disorders (46)(47)(48).…”

Pulmonary vascular dysfunction in metabolic syndrome

“…; Behl & Kotwani, ; Ashraf et al . ; Okonkwo & DiPietro, ). Diabetic nephropathy is also characterized by increased angiogenesis (McGinn et al .…”