NOV 2012

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58 EW GLAUCOMA February 2011 November 2012 Risk assessment in glaucoma evolving by Tony Realini, M.D. tudinal studies that ocular perfusion pressure (OPP) is an important risk factor for glaucoma. OPP is defined as arterial blood pressure minus IOP and can be thought of as the trans- vascular pressure gradient across which blood must cross to perfuse ocular tissues. When OPP falls below 50 mm Hg, the risk of glaucoma increases significantly. It is possible to modify OPP by P opulation projections indicate that within the next few decades, the proportion of elderly will skyrocket worldwide, resulting in more people with glaucoma than ever before. Determining whom to treat, and how aggressively to treat, requires a careful assessment of individual risk of incurring significant visual im- pairment. Risk assessment in glau- coma has improved substantially in the past decade, thanks in large part to the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention EyeWorld factoid It is estimated that over 2.2 million Americans have glaucoma, but only half of those know they have it Source: Glaucoma Research Foundation Study (EGPS). More recently, new risk factors have emerged, such as ocular perfusion pressure and cere- brospinal fluid pressure, among others. In light of the evolving risk profile for glaucoma, how are we to approach risk assessment in glau- coma? Traditional risk factors "High intraocular pressure (IOP) remains the most important and best established risk factor for glau- coma," said Stefano Miglior, M.D., University of Milan. "Others include asymmetric IOP, low central corneal thickness, increasing age and cup- disc ratio, cup-disc ratio asymmetry, and increasing pattern standard deviation on the visual field." Many of these factors are incor- porated into the OHTS-EGPS risk calculator, which can be found online at ohts.wustl.edu/risk/calcu- lator.html, and provides a 5-year risk of conversion from ocular hyperten- sion to glaucoma. Based on this 5- year risk, clinicians and patients can determine whether treatment makes sense in an evidence-based manner. Ocular perfusion pressure The evidence continues to mount from both cross-sectional and longi- modifying blood pressure. But since higher OPP is beneficial to glaucoma risk, this would mean raising blood pressure. Raising blood pressure is generally not practical and not currently advisable, he said. "There is no evidence that raising OPP by raising blood pressure would be beneficial in reducing the risk of glaucoma," said Fotis Topouzis, M.D., University of Thessaloniki, as the risk of death increased two-fold for every 20 mm Hg elevation in blood pressure. A more practical approach might be to ask whether patients are being over treated for systemic hypertension and poten- tially could undergo a reduction in medications. "There are a significant number of people who only have white-coat hypertension and may not require treatment," he said. "And those patients who are the nighttime dippers—whose blood pressure dips very low during the night—may be over treated and should have less aggressive antihypertensive therapy." There is another way to improve OPP, and it's a familiar one. "Lower- ing IOP raises OPP," Dr. Topouzis pointed out. He suggested that when evaluating patients at risk for glau- coma, OPP should be among the as- sessments. "If OPP is low, then target IOP should be adjusted downward to help raise OPP. If OPP is high, per- haps a higher IOP can be tolerated." Antihypertensive risks Further complicating the already complex relationship between blood pressure and glaucoma is the obser- vation from several key studies that blood pressure therapy may increase the risk of glaucoma. The EGPS re- ported that, independent of having elevated blood pressure, being on therapy with a diuretic antihyper- tensive agent significantly raised the risk of developing glaucoma, said Dr. Miglior. In addition, he said, the Rotterdam study identified calcium channel blocker therapy as a risk factor for glaucoma as well. The mechanisms by which these drugs increase glaucoma risk remain unclear, and the impact of these therapies on glaucoma risk assess- ment remains a challenge to quan- tify. Cerebrospinal fluid pressure Several recent studies have revealed that low cerebrospinal fluid (CSF) pressure may also be a risk factor for glaucoma. This is thought to be mediated by the translaminar pressure gradient, which is defined as IOP minus CSF pressure. The lower the CSF pressure, the higher the translaminar pressure difference. The mechanism by which a translaminar pressure gradient might cause optic nerve damage remains speculative. "CSF pressure is interesting but of limited utility in clinical practice," said Dr. Miglior. This is because most patients would not consent to the lumbar puncture needed to accurately measure CSF pressure. Also, modifying CSF pres- sure is impractical. Drugs that lower CSF pressure—such as systemic carbonic anhydrase inhibitors—can be avoided, but otherwise modifying the translaminar pressure gradient boils down to IOP reduction, he said. Clinical impact The emergence of novel risk factors for glaucoma may help us to better under- stand the pathophysiology of this complex disease, but most of these new risk factors do not lend them- selves directly to beneficial modifica- tion. It is impractical and potentially unwise to raise blood pressure or CSF pressure. Interestingly, the impact of both of these risk factors can be blunted by doing what we do best: lowering IOP. Until we better under- stand the elusive nature of glauco- matous optic neuropathy, IOP reduction remains the standard ther- apy for glaucoma. EW Editors' note: Dr. Miglior has no finan- cial interests related to this article. Contact information Miglior: stefano.miglior@unimib.it Topouzis: nliori@goldair.gr

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