The pathogenesis of normal (intraocular) pressure
glaucoma has remained unclear so far. As hospital-based studies showed an association of normal-pressure
glaucoma with low systemic blood pressure, particularly at night, and with vasospastic symptoms, it has been hypothesized that a
vascular factor may play a primary role in the pathogenesis of normal-pressure
glaucoma. That assumption may, however, be contradicted by the morphology of the optic nerve head. Eyes with normal-pressure
glaucoma and glaucomatous eyes with high-intraocular pressure can show a strikingly similar appearance of the optic nerve head, including a loss of neuroretinal rim, a deepening of the optic cup, and an enlargement of parapapillary
atrophy. These features, however, are not found in any (other) vascular
optic neuropathy, with the exception of an enlargement and deepening of the optic cup in arteritic anterior ischaemic
optic neuropathy. One may additionally take into account (i) that it is the trans-lamina cribrosa pressure difference (and not the trans-corneal pressure difference, i.e. the so-called intraocular pressure) which is of importance for the physiology and pathophysiology of the optic nerve head; (ii) that studies have shown that the anatomy of the optic nerve head including the intraocular pressure, the anatomy and biomechanics of the lamina cribrosa and peripapillary sclera, retrobulbar orbital cerebrospinal fluid pressure and the retrobulbar optic nerve tissue pressure may be of importance for the pathogenesis of the highly myopic type of chronic
open-angle glaucoma; (iii) that studies have suggested a physiological association between the pressure in all three fluid filled compartments, i.e. the systemic arterial blood pressure, the cerebrospinal fluid pressure and the intraocular pressure; (iv) that an experimental investigation suggested that a low cerebrospinal fluid pressure may play a role in the pathogenesis of normal (intraocular) pressure
glaucoma; and (v) that recent clinical studies reported that patients with normal (intraocular) pressure
glaucoma had significantly lower cerebrospinal fluid pressure and a higher trans-lamina cribrosa pressure difference when compared to normal subjects. One may, therefore, postulate that a low cerebrospinal fluid pressure may be associated with normal (intraocular) pressure
glaucoma. A low systemic blood pressure, particularly at night, could physiologically be associated with a low cerebrospinal fluid pressure, which leads to an abnormally high trans-lamina cribrosa pressure difference and as such to a similar situation as if the cerebrospinal fluid pressure is normal and the intraocular pressure is elevated. This model could explain why patients with normal (intraocular) pressure
glaucoma tend to have a low systemic blood pressure, and why eyes with normal (intraocular) pressure
glaucoma and eyes with high-pressure
glaucoma, in contrast to eyes with a direct vascular
optic neuropathy, show profound similarities in the appearance of the optic nerve head.