Eyeworld

EW GLAUCOMA 38 July 2015 by Tony Realini, MD, MPH, EyeWorld Contributing Writer Intracranial pressure The potential role of intracranial pressure (ICP) in the glaucoma process is easy to conceptualize. "The intraocular space and the intracranial space are 2 fluid-filled compartments separated by the lam- ina cribrosa," said Rand Allingham, MD, Duke University, Durham, N.C. If we believe that pressure on one side of the lamina cribrosa—IOP— matters, then why wouldn't pressure on the other side of the lamina cribrosa matter? One theory for the relevance of both IOP and ICP is that of laminar deformation caused by the translam- inar pressure difference of IOP and ICP, which can squeeze the axons of retinal ganglion cells as they travel through the nerve. Disruption of axonal transport can lead to retinal ganglion cell death—a hallmark of glaucoma. Intriguingly, ICP has been shown to be lower in people with both normal-tension and high-ten- sion glaucoma compared to normal subjects, Dr. Allingham said. "Cerebrospinal fluid pressure starts dropping after age 40–50, the same time in life when the prevalence of glaucoma begins to increase," he added. Clinical implications IOP still matters and likely always will for patients with glaucoma. In some patients, IOP may matter less than in others. The absolute level of IOP may matter less than its value relative to other biologic parameters, such as blood pressure or intracrani- al pressure. As we develop home and continuous tonometry tools, we will likely learn more about the complex relationship between IOP, glaucoma, and the whole body. EW Editors' note: Dr. Liebmann has financial interests with Reichert (Depew, N.Y.). Drs. Allingham, Harris, Kaufman, Quigley, Weinreb, and Wilson have no financial interests related to this article. Contact information Allingham: allin002@mc.duke.edu Harris: alharris@indiana.edu Kaufman: kaufmanp@mhub.ophth.wisc.edu Liebmann: jml18@earthlink.net Quigley: hquigley@jhmi.edu Weinreb: rweinreb@ucsd.edu Wilson: president@wayne.edu What aspect of IOP matters? Another limitation of our under- standing of IOP arises from its vari- ability. What aspect of IOP behavior is most responsible for glaucoma progression? Mean IOP? Peak IOP? In truth, we don't know, largely because we have such a low sam- pling rate for IOP assessment. We are limited to measuring IOP only a few times a year, and only during office hours on weekdays, in the sitting position. Home tonometry is com- ing into practice and will very likely provide insight into the patterns of IOP that are most likely to lead to progression. But perhaps not. IOP is un- doubtedly important. How, though, do we explain the patients with high IOP who never progress, or the patients with low IOP who go blind from glaucoma? Perhaps IOP's rele- vance is relative to other intertwined factors, such as blood pressure or intracranial pressure. Ocular perfusion pressure Ocular perfusion pressure (OPP) is the difference between system- ic blood pressure and IOP. OPP is reduced in situations where IOP is high and/or blood pressure is low. Both of these often happen simul- taneously at night. When OPP is low, the eye is relatively less well perfused, and the optic nerve (and other ocular structures) are at risk of ischemic injury. "A plethora of studies support that low OPP is a risk factor for the development of glaucoma," said Alon Harris, PhD, MS, Indiana Uni- versity School of Medicine, Bloom- ington. Among patients with low OPP, those who are being treated with systemic anti-hypertensive therapy are more at risk than those who are not on such therapy. "Perhaps these patients have larger nocturnal blood pressure dips associated with their therapy, or maybe their autoregulatory mecha- nism are impaired," Dr. Harris said. Interest in OPP's role in the glaucoma disease process is growing. "OPP could be incorporated into glaucoma management as a risk factor or as a therapeutic target. But first we need to better understand the complex relationship between blood pressure, IOP, and glaucoma," Dr. Harris said. Robert N. Weinreb, MD, University of California, San Diego, agreed. "IOP is clearly an important modifiable risk factor for glaucoma. The risk of glaucoma increases with the level of IOP." Jeffrey Liebmann, MD, New York University, put it succinctly: "IOP plays a role in every eye with glaucoma." IOP is not the whole story No one disputes the therapeutic benefit of IOP reduction. Major clinical trials have demonstrated the benefit of IOP reduction on the de- velopment of glaucoma in eyes with high IOP and on the progression of glaucoma in eyes with both normal and high IOP. But, as Harry Quigley, MD, Johns Hopkins University, Balti- more, pointed out, "IOP lowering is protective but limited. We don't know the ideal target IOP for pa- tients. Some get worse despite IOP reduction." Dr. Liebmann added, "Knowl- edge of IOP is not required to diagnose glaucoma or to detect its progression." Some of the weakness of asso- ciation between IOP and glaucoma may arise from the limitations we face when measuring IOP. "There is no gold standard for IOP measure- ment," Dr. Liebmann explained. I OP is, and will always be, a rele- vant component of any discus- sion about glaucoma. In recent years, however, its role in the disease process has undergone significant evolution. The history of IOP and glaucoma "Historically, IOP and glaucoma have been tightly bound and inexorably linked," said M. Roy Wilson, MD, Wayne State Univer- sity, Detroit. "The diagnosis and management of glaucoma have been based on our perspective of IOP for many years." Not so long ago, elevated IOP was considered to be the very defi- nition of glaucoma. Then it became a feature of the disease, which was recognized as a form of optic neu- ropathy. "Now it is considered a risk factor rather than a feature of the disease," Dr. Wilson said. IOP still matters This demotion in status does not diminish IOP's role in the develop- ment and progression of glaucoma. "IOP is a causal risk factor for glau- coma at all levels of IOP," said Paul Kaufman, MD, University of Wis- consin, Madison. "There is a dose- response relationship between IOP and the development of glaucoma. But age, central corneal thickness (CCT), and race are other significant risk factors for glaucoma." Evolving views on IOP and glaucoma Color Doppler imaging measures blood flow velocity in retrobulbar blood vessels including the central retinal artery (pictured). Outcome parameters include peak systolic and end diastolic blood flow velocities and calculated vascular resistance index. Source: Alon Harris, PhD, MS

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