Eyeworld

EW GLAUCOMA 140 April 2016 by Tony Realini, MD, MPH have shown that CH is significantly different when measuring the same cornea in its native setting than when remeasuring on an artificial anterior chamber, even when corne- al thickness and IOP are controlled. The message? "Corneal hysteresis is capturing information about struc- tures behind the cornea." And the biomechanical prop- erties of these structures are highly relevant to glaucoma. "In an eye with a stiff sclera, an increase in IOP will posteriorly displace the lamina more so than in an eye with a compliant sclera," said Massimo Fazio, PhD, Birmingham, Alabama. "In humans, we observed a correlation between magnitude of laminar deformation in response to acute IOP elevation and CH and CRF. In an animal model of glauco- ma, a research group showed that mice with stiffer sclera were more likely to develop glaucomatous axonal loss than mice with more elastic sclera." Clinical implications Corneal hysteresis may be an important link between eye wall structure and glaucoma risk. At pres- ent, however, CH's status as a risk factor is much like that of CCT in the pre-OHTS years: All signs point to its relevance, but without a study to quantify the risk, we don't have adequate information to incorporate CH measurements into the global risk assessment of our glaucoma patients. In the meantime, it is rea- sonable to consider CH qualitative- ly: A normal value probably doesn't change risk much, a low value may increase risk, and a high value may decrease risk. EW Editors' note: Drs. Dupps and Fazio have no financial interests related to their comments. Dr. Medeiros has financial interests with Reichert. Contact information Dupps: bjdupps@sbcglobal.net Fazio: massimof@uab.edu Medeiros: fmedeiros@glaucoma.ucsd.edu than CCT does in terms of glaucoma risk. In fact, it does. "Thickness and biomechanics are distinct properties of the cor- nea," said William Dupps, MD, PhD, Cleveland. "They are often covariate—thicker corneas tend to be stiffer and vice versa—but can also vary independently." As an example, the impact of CH on glaucoma risk is independent of that of CCT. "Clinical studies have shown that low CH is more predictive of glaucoma progression than low CCT," he said. One possible explanation for this is that, like CCT, lower CH values can lead to underestimation of IOP measured by Goldmann tonometry. Therefore, eyes with low CH may be undertreated—because their IOP looks lower than it really is—and this undertreatment may be why eyes with lower CH tend to progress more. There is a second possible explanation: CH is telling us how well equipped the eye is to handle fluctuations in IOP. Whole eye biomechanics IOP fluctuations are important in glaucoma, and they occur frequent- ly. There are short-term IOP fluctu- ations that occur throughout the day and long-term IOP fluctuations that occur over days, weeks, or even months. There are also ultra-short-term IOP variations. With every heart- beat, every blink, and every saccade, significant IOP spikes occur. So why doesn't everyone get glaucoma? Because healthy eyes can damp- en these spikes. In healthy eyes, the eye wall stretches, and the entire ocular volume increases slightly with the IOP spikes associated with pulse, blink, and saccades. Eyes with glaucoma, conversely, have lower CH—lower damping ability—and in these eyes, the eye wall may not effectively dampen the effects of increased pressure. Measurements of CH depend on more than just the cornea, Dr. Dupps said. Donor eye experiments each is likely to produce different IOP measurement artifacts by virtue of different stress-strain relation- ships. A parameter that actually re- flects the cornea's response to stress might have greater value than CCT in understanding the biomechanical complexity of corneal structure. Corneal hysteresis Over the past decade or so, corneal hysteresis has gained attention as a clinically relevant biomechanical property that has utility in assessing glaucoma risk. "Corneal hysteresis is measured using a modified air-puff tonometer, the Ocular Response Analyzer [Reichert, Depew, New York]," explained Felipe A. Medeiros, MD, PhD, La Jolla, California. A metered jet of air is applied to the cornea with the goal of flattening—or applanating—the central cornea. The jet begins softly, increases as needed to achieve applanation, and then decreases to zero. The cornea's response is to move from its normal configuration to a flattened state, then slightly beyond flat, before returning to its normal configura- tion—passing through the applana- tion configuration a second time as it returns to normal. "The pressure at which each of these 2 applanations occurs is slightly different," Dr. Medeiros said. "This difference—termed corne- al hysteresis—is a biomechanical measure of the cornea's viscoelastic damping property." Corneal hysteresis (CH) is important in glaucoma. In normal eyes, the average CH value is 10 mm Hg. Values of 8 mm Hg or lower can be considered clinically significant- ly low and may be associated with increased glaucoma risk. "Low CH is associated with pro- gressive visual field worsening even after adjustment for age, corneal thickness, and Goldmann IOP," he said. "Also, eyes with low CH have faster visual field progression rates." It is reasonable to wonder whether CH tells us anything more Corneal and scleral properties may play a role in glaucoma pathophysiology W hy do some glauco- ma patients with low IOP get worse, while others with high IOP remain stable for years? Sensitivity to IOP forces—and susceptibility to glaucoma progres- sion—are among the many myster- ies of glaucoma risk assessment. At the 2016 annual meeting of the American Glaucoma Society in Fort Lauderdale, Florida, a pan- el of glaucoma experts discussed the potential role of corneoscleral biomechanical properties in the pathophysiology of glaucoma. Central corneal thickness We have known for decades that variations in central corneal thick- ness (CCT) affect the accuracy of applanation tonometry. Goldmann tonometry tends to underestimate IOP in eyes with thin corneas and overestimate IOP in eyes with thick corneas. This qualitative associa- tion proved difficult to apply to risk assessment until 2002, when the Ocular Hypertension Treatment Study (OHTS) defined the quantita- tive relationship between CCT and the risk of converting from ocular hypertension to manifest open-an- gle glaucoma. CCT is not a true biomechanical property in that it doesn't directly describe the relationship between applied mechanical stresses and resulting tissue deformations. CCT is a surrogate. In general, thinner corneas are less structurally rigid and thicker corneas more rigid. But consider 3 corneas, all with CCT of 550. The first is a healthy cornea. The second has stromal and epithe- lial edema. The third has previously undergone LASIK. Despite having identical CCT, each of these corneas likely exhibits very different biome- chanical properties: When appla- nated with a Goldmann tonometer, Ocular biomechanics and glaucoma risk Presentation spotlight

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