Published in Glaucoma
Glaucoma & Corneal Hysteresis: Going Beyond Central Corneal Thickness
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Using corneal hysteresis, eyecare providers can quickly evaluate a glaucoma patient's response to treatment and the level of progression.
Glaucoma is defined by progressive visual field loss with characteristic changes to the optic nerve head. Age, cup-to-disc ratio, intraocular pressure (IOP), and central corneal thickness (CCT) are the currently-accepted elements for risk stratification in glaucoma progression. Although these factors have been studied extensively, glaucoma remains a difficult disease to manage.
Currently, IOP reduction remains the only modifiable factor eyecare providers use to treat and manage glaucoma. Alarmingly, 30 to 50% of glaucoma patients have “normal IOP,” which is defined as below 22mmHg.1 Furthermore, studies have shown that despite a 25% reduction in IOP, as many as 45% of glaucoma patients still had progressive visual field damage.2
This suggests we need to shift gears and focus on other risk factors, including tissue biomechanics, to supplement our glaucoma management.
The Ocular Hypertensive Treatment Study (OHTS) has proven corneal biomechanical properties are significant in the disease pathway of primary open-angle glaucoma (POAG). Central corneal thickness first made its claim to fame after the release of OHTS. This measurement quantifies a single cross-section of corneal thickness through ultrasound. In the OHTS, a measured CCT of 555 microns or less had a three-fold increased risk of developing POAG.3
However, the judgment of IOP under/overestimation is largely subjective with conventional ultrasound pachymetry in real-time clinical care. CCT is also inherently susceptible to inaccurate measurements from non-perpendicular or non-central probe placement. When utilizing CCT to assess risk, recognizing thick versus thin is what matters, and adjusting IOP due to corneal thickness is not necessary.
Corneal hysteresis (CH) is a biomechanical property with extensive published literature showing that it is an objective glaucoma risk factor. It is defined as the viscous dampening of the cornea or its ability to absorb and dissipate energy.
The Ocular Response Analyzer (ORA G3, Reichert Instruments) is a non-invasive instrument available that measures this biomechanical property in millimeters of mercury (mmHg). The device applies a rapid pulse of air to deform the cornea and then an optical sensor detects the differential inward and outward applanation points to determine the amount of energy absorbed by the cornea.4
This differs from Goldmann applanation tonometry (GAT), which measures IOP indirectly using the Imbert-Fick Law. This law describes the spring force necessary to applanate a 3.06mm diameter of the central cornea.5 CH offers a numerical estimation of the quality of corneal shock capability, which differs from a CCT quantity interpretation (thick versus thin CCT).
From a functional standpoint, there have been supportive data showing that CH can reflect the susceptibility of the optic nerve head to IOP and be a valuable measure for determining progression.6,7
The cornea, sclera, and lamina cribrosa are all composed of well-organized collagen fibrils responsible for the mechanical stiffness of the eye. These structures are made from extracellular matrices coded by the same genes that result in collagen formation.8
Therefore, an Ocular Response Analyzer measurement can directly record the “shock absorbing” capability of the cornea and extrapolate this data to reflect the lamina cribrosa. An average CH in non-diseased eyes is between 10.2 to 10.7 mmHg.9,10 If a lower shock-absorbing capability is noted, this increases the likelihood of retinal ganglion cell (RGC) axonal injury and death at the lamina cribrosa.8
The numerical value of CH is dynamic and fluctuates based on age-related soft-tissue reorganization and IOP diurnal fluctuation. These changes should be taken into account at each visit and contrasted with the CCT, which is often a stand-alone measurement that is not repeated more than once annually.
Glaucoma is a challenging disease to manage because, as eyecare providers, we are constantly weighing the risk and benefits of treatment options and trying to gauge how quickly a patient may progress. Corneal hysteresis has emerged as a vital asset for helping to guide our clinical decision-making.
CH represents the shock-absorbing ability of the eye, and we think of it as a surrogate measure for what’s occurring at the optic nerve. Based on prior research performed at our practice and similar findings in the literature, a low CH value decreases the threshold to either initiate treatment or treat it aggressively.
The most difficult glaucoma patients to treat are those who continue to progress despite responsive IOP reduction or those who have taken a sharp turn and are rapidly declining.
Every eyecare provider has stumbled upon these challenges, yet it is hard to assess the risk or rate of progression. While this is an ongoing issue, many studies continue to show that CH is a favorable tool for assessing glaucoma progression.
In a study investigating the relationship between initial corneal hysteresis and glaucoma severity in newly-diagnosed patients, it was found that in eyes with an initial corneal hysteresis of less than 10mmHg, there was a 2.9-times greater likelihood for moderate to severe glaucoma.11
This same subset of patients also had a higher baseline IOP measured with GAT. Comparatively, moderate to severe glaucoma patients with a CH greater than 10mmHg had a baseline IOP higher than even patients with mild glaucoma or POAG suspects.
In patients with untreated primary open-angle glaucoma, Prata et al found that baseline CH is associated with a linear cup-to-disc ratio.12 The higher the CH, the smaller the linear cup-to-disc ratio. While this study utilized optical coherence tomography (OCT) instrumentation for cup-to-disc measurements, in actual practice, CH can supplement relative risk factors in addition to routine biomicroscopy and cup-to-disc ratio.
Presently, CCT and CH are IOP-independent models that are associated with risk for glaucomatous progression. Congdon et al studied the association between glaucoma damage and both CCT and CH. The results of this study demonstrated that the factors predictive of visual field progression were age, treatment for glaucoma, and lower hysteresis.6 CCT was not found to be a predictive measure of visual field progression.6
However, in a study conducted by Medeiros et al, low CCT was proven to play a predictive role in glaucoma progression and was associated with a decline in visual field index (VFI) values, as supported by previous longitudinal studies.13
What can be concluded from this data? Medeiros et al support higher relevancy in CH compared to CCT. A comparison between CH and CCT revealed that CH explained 17.4% of the variation in glaucoma progression rate, whereas CCT explained only 5.2%.13
Glaucoma progression, while multifactorial, may have a higher association with the elastic properties of soft tissue as measured by CH rather than a single cross-sectional measurement that is provided by CCT alone.6 However, CCT should not be discredited as an independent variable.
Rather, it is important to recognize CH as a predictive parameter that should be included in the management of glaucoma, both for relative risk for a POAG diagnosis in addition to the risk for future progression. Clinically, CH allows for a fast interpretation that supplements routine testing of visual fields, IOP, and retinal nerve fiber layer (RNFL) OCT. Understanding the biomechanical characteristics of the cornea is imperative for assessing glaucoma patients.
It’s important to note that measuring CH is a single component of utilizing the biomechanical and physiological properties of the cornea to guide appropriate clinical decision-making in both glaucoma suspects and patients with POAG.
While there are many considerations to managing your glaucoma patients, it is important not to be bogged down by each individual piece of data.
The correlation between glaucoma and corneal hysteresis has provided a spotlight on the importance of looking at the biomechanical characteristics of the cornea. In addition, it can provide an important consideration in how responsive patients will be to treatment, progression rates, and the severity of the disease state.
- Murphy ML, Pokrovskaya O, Galligan M, et al. Corneal hysteresis in patients with glaucoma-like optic discs, ocular hypertension and glaucoma. BMC Ophthalmol. 2017;17(1):1. doi:10.1186/s12886-016-0396-9.
- Leske MC, Heijl A, Hyman L, et al. Early Manifest Glaucoma Trial: design and baseline data. Ophthalmology. 1999;106(11):2144-53. doi: 10.1016/s0161-6420(99)90497-9. PMID: 10571351.
- Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):714–720.
- Kaushik S, Pandav SS. Ocular Response Analyzer. J Curr Glaucoma Pract. 2012;6(1):17-19. doi: 10.5005/jp-journals-10008-1103. Epub 2012 Oct 16. PMID: 27990067; PMCID: PMC5159455.
- Kato Y, Nakakura S, Matsuo N, et al. Agreement among Goldmann applanation tonometer, iCare, and Icare PRO rebound tonometers; non-contact tonometer; and Tonopen XL in healthy elderly subjects. Int Ophthalmol. 2018;38(2):687-696. doi: 10.1007/s10792-017-0518-2. Epub 2017 Apr 9. PMID: 28393323.
- Congdon NG, Broman AT, Bandeen-Roche K, et al. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol. 2006;141(5):868–875. doi:10.1016/j.ajo.2005.12.007.
- De Moraes CG, Liebmann JM, Greenfield DS, et al; Low-pressure Glaucoma Treatment Study Group. Risk factors for visual field progression in the low-pressure glaucoma treatment study. Am J Ophthalmol. 2012;154(4):702-11. doi: 10.1016/j.ajo.2012.04.015. Epub 2012 Jul 25. PMID: 22835512.
- Grytz R, Girkin CA, Libertiaux V, et al. Perspectives on biomechanical growth and remodeling mechanisms in glaucoma. Mech Res Commun. 2012;42:92-106. doi: 10.1016/j.mechrescom.2012.01.007. PMID: 23109748; PMCID: PMC3482120.
- Carbonaro F, Andrew T, Mackey DA, et al. The heritability of corneal hysteresis and ocular pulse amplitude: a twin study. Ophthalmology. 2008;115:1545-1549.
- Shah S, Laiquzzaman M, Bhojwani R, et al. Assessment of the biomechanical properties of the cornea with the ocular response analyzer in normal and keratoconic eyes. Invest Ophthalmol Vis Sci. 2007;48(7):3026-31. doi: 10.1167/iovs.04-0694. PMID: 17591868.
- Schweitzer JA, Ervin M, Berdahl JP. Assessment of corneal hysteresis measured by the ocular response analyzer as a screening tool in patients with glaucoma. Clin Ophthalmol. 2018;12:1809–1813. doi:10.2147/OPTH.S168032.
- Prata TS, Lima VC, de Moraes CG, et al. Factors associated with topographic changes of the optic nerve head induced by acute intraocular pressure reduction in glaucoma patients. Eye (Lond). 2011;25(2):201–207. doi: 10.1038/eye.2010.179.
- Medeiros FA, Meira-Freitas D, Lisboa R, et al. Corneal hysteresis as a risk factor for glaucoma progression: a prospective longitudinal study. Ophthalmology. 2013;120(8):1533–1540. doi:10.1016/j.ophtha.2013.01.032.