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E W GLAUCOMA 74 by Tony Realini, MD, MPH Caring for the late-stage glaucoma patient P a tients with advanced glaucoma present a set of clinical challenges that differ from patients with earlier forms of the dis- ease. These include issues related to quality of life associated with visual dysfunction, the detection of pro- gression, the high risk of visual dis- a bility or blindness associated with progression, and the psychosocial fears of blindness experienced by patients whose vision has slowly, relentlessly, and painlessly slipped away over time. Patients with ad- vanced glaucoma are generally less mobile than their unaffected same- age peers, have higher risks of f alling, and may be at risk for losing—or have already lost— their independence. Most commonly we encounter these patients in referral, or we make the diagnosis ourselves when they present as new patients to our prac- tices with vague, non-specific com- plaints of reduced vision or tunnel vision. Therapeutic considerations Setting a target intraocular pressure (IOP) is useful for most glaucoma pa- tients regardless of the stage of their disease. While there is no formula for determining target IOP, the com- mon factors considered include the stage of the disease, the patient's age and estimated life expectancy, the untreated IOP or IOP at which prior progression occurred, and any other risk factors such as ethnicity, family history of glaucoma and particularly glaucoma-related blindness, and the presence of secondary forms of glau- coma such as pseudoexfoliation. Target IOP is a clinical guessti- mate. We can only know if our target was low enough to prevent progression in retrospect, when, years later, the patient has not pro- gressed. In early glaucoma, we can be conservative in our guesstimate, knowing that if we don't aim low enough, we will have the opportu- nity to revise the target downward without significant clinical impact if progression does occur. In advanced glaucoma, where there is little or no functional cushion, target IOP should be liberally adjusted down- ward solely on the basis that even small amounts of progression can make the difference between being sighted and being blind. "There is less functional reserve in eyes with advanced glaucoma, so we must stay ahead of the curve and be proactive rather than reactive," said Kouros Nouri-Mahdavi, MD, University of California, Los Angeles. The factors that determine tar- get IOP are surrogates for the key issue: What is the risk of progression in a given patient? Recently, a tool for assessing the risk of glaucoma progression was developed and validated. Predictive risk factors included peak IOP, mean central corneal thickness (CCT), disc hemor- rhage, and beta-zone peripapillary atrophy. Target IOP should be revised downward in patients with advanced glaucoma who have a high risk of future progression. One factor that is not included in the calculator and may be impor- tant is a measure of ocular biome- chanics. In the Ocular Hypertension Treatment Study (OHTS), CCT was identified as a key risk factor for the progression to glaucoma. "The cornea is powerful in terms of risk," said Nathan Radcliffe, MD, Weill Cornell Med- ical College, New York. "In OHTS, CCT was a much more powerful predictor of progression than IOP." But CCT is also a surrogate measure—it tells us about the thick- ness of the cornea but not its biome- chanical properties. More recently, attention has focused on corneal hysteresis as an important measure of ocular biomechanical properties. "Corneal hysteresis represents the viscous damping of the cornea," said Dr. Radcliffe. In numerous studies, corneal hysteresis has been associated with both structural and functional progression, as well as the rate of visual field loss. "In a prospective study, baseline hysteresis predicted the risk of glaucoma pro- gression," he added. Interestingly, hysteresis also predicts the IOP-low- ering response to both medical and laser therapy. Low corneal hysteresis values may also be a justification for setting lower target IOP. "This parameter may represent a mechanical stress that the eye is experiencing," Dr. Radcliffe said. Monitoring considerations Strategies for detecting progression in people with advanced glaucoma necessarily differ from those in peo- ple with earlier stages of the disease. Clinical evaluation of the optic nerve head is of limited value, as it is unlikely a change could be detected in a glaucomatous eye with a cup- disc ratio of 0.9 or 0.95. Likewise, automated imaging of the optic nerve or retinal nerve fiber layer would not detect the small changes associated with progression in the late stages of the disease spectrum. Functional testing is more useful in late-stage glaucoma, but it too has limitations. "Because of the extensive field loss, there are fewer test locations with adequate sensitivity to detect changes over time," said Dr. Nouri- Mahdavi. To address this, we can switch from the standard size III stimulus to the bigger size V stimulus on stan- dard automated perimetry. "This in- creases the dynamic range of the test and decreases variability. The down- side is that the statistical tools used for detection of progression with size III stimulus are not available w ith non-standard testing parame- ters," he said. We can also switch from a 24-2 or 30-2 testing algorithm to the more central 10-2 strategy. "A 10-2 algorithm has been recently shown to detect progression more fre- quently than the 24-2 strategy in advanced glaucoma," Dr. Nouri- M ahdavi explained. When utilizing progression de- tection tools such as the Guided Pro- gression Analysis, keep in mind that the GPA stops providing any infor- mation once the visual field mean deviation (MD) reaches around –15 to –20 dB or worse. "In advanced glaucoma, trend analysis—such as the slope of the mean deviation or visual field index (VFI) over time—is more useful for progression detec- tion," he added. However, again, there is a caveat with using VFI in eyes in which the MD is approach- ing the –20 dB cutoff point. Visual field index has been shown to become quite variable around this cutoff point and beyond this point offers no practical advantage over MD. Clinical impact When caring for patients with ad- vanced glaucoma, be proactive in setting low target IOP. Treat aggres- sively, because the consequences of even small amounts of progression can be visually devastating. Finally, rely more heavily on functional test- ing than structural testing to detect progression, and consider getting vi- sual fields more often than usual— perhaps every four months. EW Editors note: Dr. Radcliffe has financial interests with Alcon (Fort Worth, Texas), Allergan (Irvine, Calif.), Iridex (Mountain View, Calif.), and Merck (Whitehouse Station, N.J.). Dr. Nouri-Mahdavi has financial interests with Allergan. Contact information Nouri-Mahdavi: nouri-mahdavi@jsei.ucla.edu Radcliffe: drradcliffe@gmail.com February 2011 February 2014 72-77 Glaucoma_EW February 2014-DL2_Layout 1 1/30/14 10:55 AM Page 74