This invention relates to compositions and methods for the treatment or prophylaxis of glaucoma and ocular hypertension, and for lowering of intraocular pressure. The invention provide VEGFR-1 agonists and combinations of vascular endothelial growth factor B (VEGF-B) with placenta growth factor (PLGF), ‘ Secreted protein acidic cysteine-rich’ (SPARC) antagonists, insulin, insulin like growth factor, their isoforms, their analoges, their gene-engineered modifications. Furthermore, the formentioned compositions and combinations are provided for coadministration with antiglaucoma agents, currently in clinical use, for the treatment or prophylaxis of glaucoma and ocular hypertension, for lowering of intraocular pressure, for increasing success rate of surgical procedures for the treatment or prophylaxis of glaucoma, and for preserving retinal ganglion cells.