To determine the interdependence of intracranial pressure(ICP) and intraocular pressure(IOP) and how it affects optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left eye, and anterior chamber in the left eye. This allowed ICP, lumbar cistern pressure(LCP), optic nerve subarachnoid space pressure(ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from lowering ICP(via shunting cerebrospinal fluid(CSF) from the ventricle) were recorded. At baseline, all examined pressures were different(ICP>LCP>ONSP), but correlated(P<0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient(TLPG) remained stable(ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as ICP declined(ICP-IOP independent zone). The optic nerve pressure gradient(ONPG) and trans-optic nerve pressure gradient(TOPG) increased linearly as ICP decreased through both the ICP-IOP dependent and independent zones. We conclude that ICP and IOP are coupled in a specific pressure range, but when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. This change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma. To determine the interdependence of intracranial pressure (IOP) and how it touched optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left This allowed ICP, lumbar cistern pressure (LCP), optic nerve subarachnoid space pressure (ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from reduced ICP At baseline, all attended rates were different (ICP> LCP> ONSP), but correlated (P <0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient (TLPG) remained stable (ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as I CP optic nerve pressure gradient (ONPG) and trans-optic nerve pressure gradient (TOPG) increased linearly as ICP decreased through both ICP-IOP dependent zone. ICP and IOP when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma.