Impact of intraocular pressure on venous outflow from the globe: a hypothesis regarding IOP-dependent vascular damage in normal-tension and hypertensive glaucoma.

Increasing focus on so-called normal-tension glaucoma has raised questions concerning the mechanism by which intraocular pressure (IOP) may play a role in the pathophysiology of glaucomatous optic neuropathy. However, examination of pressure-relationships suggests that an increase of a few mm Hg in IOP within the normal-tension range may double the magnitude of one important physiologic parameter, the magnitude of the intravascular waterfall effect at the exit of the central retinal vein (CRV) from the globe. This, in turn, increases the pulsatility or the velocity and turbulence of blood flow, depending on the extent of the restriction to venous outflow at the passage of the CRV through the lamina cribrosa. In the absence of such restriction, increased CRV pulsatility, especially in combination with brief IOP spikes, can be expected to cause foci of microvascular collapse in the optic nerve head. These foci can be converted to permanent vascular defects depending on additional risk factors, such as abnormal blood rheology ro platelet aggregation. Greater than normal laminal restrictions can, on the other hand, reduce perfusion pressure and can cause turbulence-induced endothelial damage and thickening of the CRV wall, ultimately further reducing perfusion pressure. These considerations suggest the hypothesis that the size and configuration of the venous outflow channel through the lamina cribrosa is a primary determinant of the extent of vascular and ultimately neuronal damage that occurs at a given IOP level in normal-tension and hypertensive primary open-angle glaucoma.