Intracranial pressure and glaucoma: Is there a new therapeutic perspective on the horizon?

Abstract

Primary open-angle glaucoma is one of the leading causes of irreversible blindness worldwide. Raised intraocular pressure is the most important modifiable risk factor and lowering it remains the mainstay therapeutic approach for slowing optic nerve damage and visual field progression in glaucoma patients. An intriguing finding of clinical retrospective and prospective studies is that intracranial pressure is lower in patients with glaucoma. Furthermore, in a recent study on monkeys subjected to an implantation of a lumboperitoneal cerebrospinal fluid shunt to lower intracranial pressure, chronic reduction in intracranial pressure was associated with the development of glaucoma-like pathology in half of the monkeys. In addition, a very recent study demonstrated that patients whose intracranial pressure has been lowered following ventriculoperitoneal shunt placement, as treatment for normal pressure hydrocephalus, have a significantly increased risk of developing normal-tension glaucoma. These findings suggest that a reduced intracranial pressure may play an important role in the pathogenesis of glaucoma. This may be due to an abnormally high pressure difference across the lamina cribrosa resulting in biomechanical changes of the optic nerve head and/or to a deficient clearance of toxic substances, particularly in the subarachnoid space of the optic nerve and/or in the ‘ocular glymphatic system’. The search for drugs or medical devices useful to ameliorate glaucoma by lowering the trans-lamina cribrosa pressure difference and/or by facilitating cerebrospinal fluid circulation may therefore be an important area for future research. In this article, we propose that infusion of artificial cerebrospinal fluid through an implantable pump into the intrathecal space surrounding the spinal cord could be a new promising strategy for the treatment of glaucoma. Although the implantation of such a cerebrospinal fluid pump is a relatively invasive intervention, it seems worthwhile to make every effort to identify new therapies for patients who suffer from this devastating disease, especially given the significant number of patients for whom non-invasive treatment options are ineffective.