Eyeworld

EW GLAUCOMA 53 S everal key studies in the past decade have con- firmed that IOP is a risk factor for the develop- ment and progression of glaucoma. Other established risk fac- tors include age, African ancestry, central corneal thickness, and cup- ping of the optic nerve. More re- cently, IOP fluctuation has emerged as a possible risk factor for glaucoma progression. IOP fluctuations can be thought of as low-frequency changes, such as the circadian rhythm in which IOP is highest at night in the supine po- sition, and high-frequency changes, as can occur with eye movements or blinking, according to J. Crawford Downs, Ph.D., associate scientist and research director, Ocular Biomechan- ics Laboratory, Devers Eye Institute, Portland, Ore. In this framework, IOP variations between office visits can be thought of as very low-fre- quency changes. "A recent analysis of data from the Advanced Glaucoma Interven- tion Study suggests that IOP fluctuation between office visits is associated with worsening visual fields," he said. Less is known about high-frequency IOP fluctuations. "Data from our primate lab demon- strates that saccadic eye movements can raise IOP by 5-9 mm Hg for 100- 200 milliseconds, and blinking can raise IOP by up to 15 mm Hg. It re- mains unclear, however, if these IOP fluctuations contribute to the onset or progression of glaucoma," he said. How might IOP fluctuation lead to progressive optic nerve damage? One theory is that IOP fluctuation causes intermittent deformation of the optic nerve head with resulting axonal damage. Recently, there has been growing interest in the biome- chanical behavior of the optic nerve head in response to changes in IOP. Is the healthy eye designed to dampen IOP fluctuations? Structures such as the corneo-scleral shell, the trabecular meshwork, the choroid, and the optic nerve head all have biomechanical properties that could play a role in dampening IOP fluctu- ation. This observation might explain why glaucoma is generally a condi- tion associated with aging. The sclera and lamina cribrosa stiffen with age, and a stiffer eye may be less able to expand in response to rapid changes in IOP. Thus, the optic nerves of older individuals may be more at risk for damage resulting from IOP fluctuation. Further, exposure to chronically elevated IOP can also induce con- nective tissue remodeling in both the sclera and the lamina, which may serve to further stiffen these tis- sues. This may explain why patients with advanced glaucoma tend to get worse over time. These observations raise an im- portant clinical question: When treating our glaucoma patients, should we aim to reduce IOP fluctu- ation? Arthur J. Sit, M.D., ophthal- mology department, Mayo Clinic, Rochester, Minn., says no. "There are several reasons why this is both inappropriate and impractical," he said. "First, we have no standard def- inition of IOP fluctuation. Are we in- terested in 24-hour IOP variation or the between-visits variation we ob- serve that occurs over months? How should we characterize this fluctua- tion? Should we use the range, which is susceptible to outlying val- ues of peak or trough IOP? Or should we focus on the standard de- viation of multiple IOP measure- ments? This is more difficult to measure in clinical practice." He also pointed out that there is little or no data supporting reduc- tion of IOP fluctuation. "The studies we have to date suggest that there may be a relationship between IOP fluctuation and progression, but none have specifically evaluated the therapeutic benefit of reducing IOP fluctuation," he said. "Also, IOP fluctuation is not an independent parameter—it is correlated to mean IOP, which may be the more impor- tant IOP parameter upon which to base treatment strategy." His approach is pragmatic. "Our goal in treating glaucoma remains the reduction of IOP. Reduction of IOP fluctuations is a secondary ben- efit of this therapy but shouldn't be our primary goal." Joseph Caprioli, M.D., glau- coma chief, Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Ange- les, has a different view of the data. "There may be a subset of patients in whom IOP fluctuation is an im- portant contributor to disease pro- gression," he said. He acknowledged that the sig- nificance of IOP fluctuation has been inconsistent between studies, but he made an important observa- tion: "The studies that found no ef- fect of IOP fluctuation enrolled patients with early disease and high IOP. Conversely, the studies that found a relationship between IOP fluctuation and glaucoma progres- sion enrolled patients with advanced disease and generally lower IOP. Per- haps IOP fluctuations are more im- portant in eyes with advanced disease and lower IOP." Applying these observations, he said, "In patients who have moder- ate to advanced disease and who are progressing at what seem to be rea- sonably low IOPs, perhaps we should think about IOP modulation rather than IOP reduction, with the aim of reducing IOP fluctuation in these patients." EW Editors' note: Dr. Downs and Caprioli have no financial interests related to their comments. Dr. Sit did not disclose any relevant financial interests. Contact information Caprioli: caprioli@ucla.edu Downs: cdowns@deverseye.org Sit: sit.arthur@mayo.edu February 2011 June 2011 by Tony Realini, M.D. Does pressure fluctuation matter in glaucoma? ous shunt. We look forward to addi- tional follow-up to fully assess the relative merits of the Ahmed Glau- coma Valve and Baerveldt Glaucoma Implant in the surgical management of refractory glaucomas. EW References 1. Ramulu PY, Corcoran KJ, Corcoran SL, Robin AL. Utilization of various glaucoma sur- geries and procedures in Medicare beneficiar- ies from 1995 to 2004. Ophthalmology 2007;114:2265-2270. 2. Chen PP, Yamamoto T, Sawada A, et al. Use of antifibrosis agents and glaucoma drainage devices in the American and Japanese Glau- coma Societies. J Glaucoma 1997;6:192-196. 3. Desai MA, Gedde SJ, Feuer WJ, Whi W, Chen PP, Parrish RK. Practice preferences for glau- coma surgery: A survey of the American Glau- coma Society in 2008. Ophthalmic Surg Lasers Imaging. In press. 4. Ayyala RS, Zurakowski D, Monshizadeh R, et al. Comparison of double-plate Molteno and Ahmed glaucoma valve in patients with ad- vanced uncontrolled glaucoma. Ophthalmic Surg Lasers 2002;33:94-101. 5. Smith MF, Doyle JW, Sherwood MB. Com- parison of the Baerveldt glaucoma implant with the double-plate Molteno drainage im- plant. Arch Ophthalmol 1995;113:444-447. 6. Tsai JC, Johnson CC, Kammer JA, Dietrich MS. The Ahmed shunt versus the Baerveldt shunt for refractory glaucoma. II: Longer-term outcomes from a single surgeon. Ophthalmol- ogy 2006;113:913-917. 7. Wang JC, See JL, Chew PT. Experience with the use of Baerveldt and Ahmed glaucoma drainage implants in an Asian population. Ophthalmology 2004;111:1383-1388. 8. Barton K, Gedde SJ, Budenz DL, et al. The Ahmed Baerveldt Comparison Study: Method- ology, baseline patient characteristics, and in- ABOUT THE AUTHOR Dr. Gedde is professor of ophthalmology and residency program director, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine. He can be contacted at 305-326-6435 or sgedde@med.miami.edu. Results continued from page 52 traoperative complications. Ophthalmology 2011;118:435-442. 9. Budenz DL, Barton K, Feuer WJ, et al. Treat- ment outcomes in the Ahmed Baerveldt Comparison Study after one year of follow-up. Ophthalmology 2011;118:443-452. 10. Heuer DK, Lloyd MA, Abrams DA, et al. Which is better? One or two? A randomized clinical trial of single-plate versus double- plate Molteno implantation for glaucomas in aphakia and pseudophakia. Ophthalmology 1992;99:1512-1519.

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