Treat-and-extend versus alternate dosing strategies with anti-vascular endothelial growth factor agents to treat center involving diabetic macular edema: A systematic review and meta-analysis of 2,346 eyes

Surv Ophthalmol. 2022 Sep-Oct;67(5):1346-1363. doi: 10.1016/j.survophthal.2022.04.003. Epub 2022 Apr 25.


Anti-vascular endothelial growth factor (Anti-VEGF) agents are the standard of care for diabetic macular edema (CI-DME) with vision loss. They are commonly administered using several treatment protocols, including fixed, pro re nata (PRN) and treat-and-extend (T&E) regimens. Because of the lack of evidence defining an ideal treatment paradigm, we systematically compared T&E with fixed or PRN regimens. Visual acuity improvement was similar when comparing T&E to fixed or PRN dosing at 12 and 24 months. Regarding anatomic outcomes, no significant difference was found between T&E and fixed regimens for central retinal thickness or central subfoveal thickness at 12 and 24 months. Similarly, no significant difference was found for central retinal thickness at 12 months for T&E versus PRN regimen. Regarding total number of injections, no significant difference existed between T&E versus fixed regimens at 12 months. PRN regimens delivered fewer injections compared to T&E regimens at 12 months. The results of this analysis support that visual acuity and anatomic outcomes at 12 and 24 months are similar between T&E with either fixed or PRN regimens. More head-to-head trials comparing T&E versus fixed and PRN dosing are needed to provide visual and functional outcome data beyond year 2. PROSPERO Registration: CRD42021249362.

Keywords: Aflibercept; Diabetes; Diabetic macular edema; Diabetic retinopathy; Faricimab; Intravitreal anti-VEGF; Ranibizumab; Retina; VEGF; Vascular endothelial growth factor.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Diabetes Mellitus*
  • Diabetic Retinopathy* / complications
  • Diabetic Retinopathy* / drug therapy
  • Endothelial Growth Factors / therapeutic use
  • Humans
  • Intravitreal Injections
  • Macular Edema* / drug therapy
  • Macular Edema* / etiology
  • Ranibizumab / therapeutic use
  • Treatment Outcome


  • Angiogenesis Inhibitors
  • Endothelial Growth Factors
  • Ranibizumab