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The role of vascular endothelial growth factor ( VEGF ), including in retinal vascular diseases, has been well studied, and pharmacological blockade of  VEGF  is the gold standard of treatment for neovascular age‐related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor ( PGF , previously known as Pl GF ), a homologue of  VEGF , is a multifunctional peptide associated with angiogenesis‐dependent pathologies in the eye and non‐ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for  PGF  in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen‐induced retinopathy, laser‐induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of  PGF  have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of  PGF  in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of  PGF ‐specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both  VEGF  and  PGF  may provide superior outcomes in certain patients compared with treatment that inhibits only  VEGF . This review summarizes current knowledge of  PGF , including its relationship to  VEGF  and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about  PGF  that can serve as a pathway for future basic, translational and clinical research.

Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases