Pathogenesis theory and intracranial pressure

[caption id="attachment_6191" align="alignnone" width="750"] John P Berdahl MD[/caption] A new understanding of the role of intracranial pressure (ICP) in glaucoma may help to overcome some of the longstanding mysteries surrounding the disease and encourage development of new strategies for prevention and treatment. “We’ve never seen the dark side of the moon. Glaucoma is much the same, as ophthalmologists we have only looked at one side of glaucoma, the eye, but not the intracranial side, even though the optic nerve spends more time in the brain, than in the eye,” John P Berdahl MD, of Sioux Falls, South Dakota, told the 2016 ASCRS•ASOA Symposium & Congress in New Orleans, USA. While the received teaching is that glaucoma is a one-pressure disease, it now seems more likely that an imbalance between the intraocular pressure (IOP) and the ICP plays a role in the disease. Dr Berdahl proposes that the cupping of the optic disk seen in glaucoma is caused by posterior directed forces when the IOP is higher than the ICP. The optic nerve bows backward and cupping occurs. The other principal manifestation of glaucoma, visual field loss, is caused by ganglion cell death, as the axonal transport needs are not met by the optic nerve because it cannot get through the high pressure environment in the eye, he suggests. “We know that ICP affects the optic nerve. We see it in idiopathic intracranial hypertension, where high cerebrospinal fluid (CSF) pressure causes the optic nerve to bow forward. In glaucoma, you have the reverse, where high IOP and low ICP cause the optic nerve to bow backwards,” he explained. CRITICAL DELIVERY He hypothesises that when IOP is elevated, axonal transport via the optic nerve is reduced, inhibiting the critical delivery of metabolic needs and waste removal within the eye. If the IOP is extremely high or the ICP is very low, axonal transport is stopped at the level of the lamina cribrosa, so the needs of the optic nerve are not met, the nerve slowly withers, and disease follows. Dr Berdahl and colleagues at the Mayo Clinic tested this hypothesis in a retrospective study of people who had undergone lumbar puncture, comparing the charts of those who had glaucoma with those who did not. It turned out the glaucoma patients did indeed have low ICPs compared with the control group. Patients with normal-tension glaucoma had even lower ICP. Those with ocular hypertension had higher ICP, balancing out their high IOP. These findings were subsequently confirmed by prospective studies conducted in China. A closer look at the glaucoma patients in the Mayo Clinic database also showed that ICP started to decline at age 65, the same age that glaucoma incidence begins to increase in the general population. “Why does IOP, or transcorneal pressure difference as I prefer to call it, matter? Because it is a surrogate for the translaminar pressure difference, across the laminar cribrosa, the difference between the IOP and the ICP. I believe that glaucoma is the IOP minus the ICP divided by the thickness of the laminar cribrosa and its biomechanical properties, multiply by time, you get the disease,” he told the session. LOCAL VACUUM He suggested that it might be possible to treat glaucoma by a applying a local vacuum against the ambient atmospheric pressure pushing on the eye. He conducted studies in cadaver eyes where he was able to ‘dial in’ eye pressure with the use of specially designed vacuum goggles. Dr Berdahl’s ideas may find an application in space travel. Visual impairment due to intracranial pressure (VIIP) has been observed in astronauts who spent extended amounts of time in the International Space Station. They developed symptoms including global flattening, hyperopic shift, choroidal folds and optic disk oedema. With a new programme under way looking to send humans to Mars as early as 2030, NASA is supporting Dr Berdahl’s research. He has started a company which is developing goggles that would potentially address this problem. John P Berdahl: john.berdahl@vancethompsonvision.com

Tags: glaucoma, intracranial pressure