Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy

Expert Opin Biol Ther. 2016;16(3):365-74. doi: 10.1517/14712598.2016.1131265. Epub 2016 Jan 12.


Introduction: The pathophysiology of diabetic macular edema (DME) is complex, involving vascular endothelial growth factor (VEGF) and other inflammatory mediators. DME is currently treated first-line with intravitreal anti-VEGF treatments, though some cases are refractory to multiple anti-VEGF treatments.

Areas covered: This article examines the evolution of treatment practices for DME, with discussion of the recent studies that guide treatment for refractory cases of DME. A literature search was performed using the following terms: anti-VEGF, DME, aflibercept, bevacizumab, ranibizumab, refractory macular edema, and VEGF.

Expert opinion: Focal extrafoveal DME may be treated first-line with laser. In patients with center-involving DME and only mild vision loss, consider starting treatment with bevacizumab, especially when cost is an issue, whereas aflibercept may be considered more strongly in patients with moderate visual loss or worse. There are no standard protocols that define 'treatment failure,' but several studies have reported that switching from bevacizumab to either ranibizumab or aflibercept will result in further reduction of CSFT and improvement in BCVA. Further study with prospective randomized trials is warranted to validate these findings. Switching to intravitreal corticosteroids may be of particular benefit to pseudophakic patients. Anti-VEGF combination with sustained-release corticosteroids also appears promising for refractory DME.

Keywords: Aflibercept; Avastin; DME; Eylea; Iluvien; Lucentis; Ozurdex; VEGF; bevacizumab; dexamethasone; diabetic macular edema; fluocinolone acetonide; ranibizumab.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Angiogenesis Inhibitors / therapeutic use*
  • Bevacizumab / therapeutic use
  • Dexamethasone / therapeutic use
  • Diabetic Retinopathy / drug therapy*
  • Drug Therapy, Combination
  • Fluocinolone Acetonide / therapeutic use
  • Glucocorticoids / therapeutic use*
  • Humans
  • Macular Edema / drug therapy*
  • Ranibizumab / therapeutic use
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use
  • Recombinant Fusion Proteins / therapeutic use
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors


  • Adrenal Cortex Hormones
  • Angiogenesis Inhibitors
  • Glucocorticoids
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • Fluocinolone Acetonide
  • aflibercept
  • Bevacizumab
  • Dexamethasone
  • Receptors, Vascular Endothelial Growth Factor
  • Ranibizumab