The translaminar pressure gradient (TLPG) is largely influenced by the difference between intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFP), but modulated by the buffering effect of orbital tissue and pia mater, which limits the reduction in retrolaminar tissue pressure as intracranial CSFP falls below 0 mm Hg. Across the lamina cribrosa, the central retinal vein experiences the greatest pressure gradient (TLPG) of any vein in the body. When CSFP rises, the minimum IOP required to induce venous pulsation pressure (VPP) rises with CSFP (r=0.95, slope=0.90). Lowering IOP in glaucoma patients leads to a reduction in VPP (P=0.0003). The normal human central retinal vein endothelial cells in the lamina region resemble typical arterial endothelia and are quite unlike other venous cells. It is likely that the TLPG is increasing retinal vein shear and in glaucoma this effect is likely to be increased with possible wall effects.