Association between arterial blood pressure, cerebrospinal fluid pressure and intraocular pressure in the pathophysiology of optic nerve head diseases

The term ‘intraocular pressure’ has traditionally been referred to the ‘pressure in the eye’, although in a strictly physically meaning, the ophthalmologic term ‘intraocular pressure’ only describes the transcorneal pressure difference between the intraocular space and the extraocular surrounding air. An eye with an ‘intraocular pressure’ of 20 mmHg thus has a physically correctly defined pressure of 780 mmHg as sum of the atmospheric pressure (760 mmHg) plus 20 mmHg. For more than 150 years, the intraocular pressure (IOP) defined as transcorneal pressure difference has been considered to be the main risk factor in the pathogenesis of glaucoma. It is, however, the transoptic nerve head pressure difference that directly affects the optic nerve head (Fig. 1). It is defined pressure in the intraocular compartment minus pressure in the retrobulbar cerebrospinal fluid space (orbital cerebrospinal fluid pressure [CSF-P]). Taking into the orbital CSF-P as counter-pressure against the IOP, hypotheses may be formed on the pathogenesis of optic nerve head diseases such as glaucoma, retinal vein occlusions and arterial hypertensive retinopathy. The first hypothesis is that a low orbital CSF-P is associated with the pathogenesis of glaucomatous optic neuropathy. If IOP is normal and orbital CSF-P is abnormally low, the trans-lamina cribrosa pressure difference is increased. It leads to a similar situation as if the IOP is elevated and orbital CSF-P is normal. The situation described first would be normal-(intraocular-)pressure glaucoma. The situation described last is high(intraocular-)pressure glaucoma. Accordingly, experimental studies and clinical studies suggested that the CSF-P is abnormally low in patients with normal(intraocular-)pressure glaucoma. The CSF-P is physiologically correlated with IOP and arterial blood pressure, which is correlated with IOP, so that the pressures in all three fluid-filled compartments (arterial blood system, brain and intraocular space) are correlated with each other. Previous studies showed an association between normal-(intraocular-)pressure glaucoma, low systemic arterial blood pressure and low body mass index. The hypothesis is that in normal(intraocular-)pressure glaucoma, a low arterial blood pressure is associated with a more marked reduction in CSF-P than reduction in IOP. It results in an increased translamina cribrosa pressure difference, similar as if the IOP is elevated as in high-(intraocular-)pressure glaucoma. It may explain why the optic nerve head appearance is similar in normal-(intraocular-)pressure glaucoma and in high-(intraocular-)pressure glaucoma, despite marked differences in IOP. Studies have shown an age-related increase in the prevalence of normal-(intraocular-)pressure glaucoma, and a higher prevalence of normal-(intraocular-)pressure glaucoma in Japanese. A recent study by Ren et al. suggested that the CSF-P was correlated with higher body mass index and younger age (own data). It may explain the increased prevalence of normal-pressure glaucoma in elderly Japanese with the lower body mass index. Arterial hypertension is associated with ocular hypertension, however, not with an increased prevalence of glaucoma. The anti-glaucomatous effect of arterial hypertension may be explained by its association with an elevated CSF-P. As a corollary, the increased prevalence of nocturnal arterial blood pressure dipping in patients with normal-(intraocular-)pressure glaucoma may be explained by an associated nocturnal dipping in CSF-P. The second hypothesis is that an elevated CSF-P may be associated with retinal vein occlusions in arterial hypertensive patients, as the central retinal vein passes through the retrobulbar CSF-P space (Fig. 1). An elevated orbital CSF-P should therefore be a risk factor for the