Corneal hysteresis is gaining respect

The measurement may be a step forward in predicting glaucoma progression.

By Kenneth Chang, MS and Vikas Chopra, MD

Corneal hysteresis (CH) has emerged as a likely indicator of glaucoma progression, primarily because of a piece of technology called the ORA, or ocular response analyzer. Compared with central corneal thickness (CCT) — the existing gold standard — numerous studies have shown CH to be more reliably correlated with glaucoma progression. Here's what ophthalmologists need to know.

Some history, part I

First, a little background on the role of central corneal thickness in glaucoma detection.

Over the years, studies have identified numerous risk factors predicting the onset and progression of primary open-angle glaucoma (POAG) with increased IOP as the principal risk factor. Using data from the 2002 Ocular Hypertension Treatment study, Gordon et al found that CCT measured via corneal pachymetry was inversely correlated with the development of POAG: multivariate hazards models found that each 40-μm decrease in CCT corresponded to a 71% greater risk.¹

This well-designed, longitudinal study showed that CCT is an independent and major predictor for progression to initial glaucoma damage among individuals with ocular hypertension, and physicians have since used CCT measurements in daily clinical practice for the evaluation of ocular hypertension and glaucoma.

However, using CCT in clinical practice comes with some important limitations. Our group from the Doheny Eye Institute reported that in the Hispanic population, CCT is an independent risk factor for the prevalence of glaucoma, but that correction algorithms to adjust the IOP based on CCT do not alter the relationship between IOP and glaucoma prevalence.2 Furthermore, CCT demonstrates very little variation between the eyes, while IOP can differ widely between them.

Another thing to keep in mind: kerato-refractive procedures, including LASIK for myopia, cause thinning of the cornea, which can lead to underestimation of IOP, as shown by applanation tonometry.

Some more history, part II

Our group also previously performed an analysis of the population data collected from the Los Angeles Latino Eye study.³ We reported that among 2,157 patients, IOP acquired by Goldmann applanation tonometry (GAT), which is considered our “gold standard,” measured significantly lower than IOP acquired via dynamic contour tonometry (DCT), which is reportedly more independent of corneal pachymetry measurements. The differences in IOP measurements between the two devices were widest in patients who had thinner corneas.

While IOP calculated by DCT is less swayed by CCT, the influence from corneal thickness on both is not negligible and needs to be carefully evaluated, especially in the setting of thin or thick corneas.

In addition to CCT, recent research suggests that biomechanical features of the eye warrant attention as a possible prognostic factor for glaucoma progression. An analysis of data from a cohort of 255 glaucoma patients participating in the 2007 Early Manifest Glaucoma trial revealed that CCT significantly correlated with glaucoma progression in patients with IOP ≥21 mmHg.⁴ This study by Leske et al found the relationship was not robust in patients with a baseline IOP lower than 21 mmHg. The authors suggested that the physical characteristics of the corneal tissues could play a larger role in glaucoma progression than previously understood.

Corneal hysteresis

Corneal hysteresis, measured in mmHg, is a biomechanical property of the cornea characterizing its ability to dampen and accommodate changes in IOP. It can be noninvasively measured via air jet applanation using the ORA (Reichert Technologies), which, conveniently, also simultaneously provides an IOP measurement. Specifically, CH represents the difference between the pressure at which the cornea flattens and the pressure at which it recoils back to its original form. This process typically takes 20 milliseconds to complete.

Several studies have compared CH to classic parameters for glaucoma progression. A 2005 report by Reichert evaluated CH in populations with keratoconus, Fuchs’ dystrophy, LASIK and healthy eyes.⁵ These researchers found that CH and CCT were poorly correlated. Of note, the patients with Fuchs’ dystrophy had the lowest CH values despite pathologically thickened corneas. Furthermore, they found a weak correlation between CH and IOP.

Touboul et al explained this relationship in 2008, with a prospective study of 498 eyes of 258 patients that did not show a strong correlation between CH and IOP or CCT.⁶ Their results suggest that GAT may underestimate IOP in eyes with lower CH, since applanation can be achieved at lower pressures.

Corneal-compensated IOP (IOPcc) is a modified parameter that adjusts for CH, which can also be collected by the ORA. It is not correlated with CCT, and LASIK does not seem to influence it.

In a retrospective study by Ehrlich et al, elevated IOPcc was found in patients originally determined to have normal IOP by GAT.⁷ The authors therefore felt that the use of IOPcc may help when monitoring glaucoma management, especially for normal-tension glaucoma patients. However, they acknowledged a high potential for false positives, and discouraged using IOPcc in glaucoma screening.

Corneal hysteresis and perimetry

Lower CH has also been associated with visual field (VF) loss. A 2006 retrospective study performed by Congdon et al found that CH and CCT correlated with different surrogates for glaucoma damage.⁸ Among the 230 patients, CCT predicted cup-to-disc ratio, while CH did not. On the contrary, axial length and lower CH, but not CCT, were significantly associated with previously documented VF progression.

The authors postulated that perhaps more elastic or distensible ocular tissues (represented by a more deformable cornea) could be more susceptible to glaucoma damage and glaucoma progression. While it is still unclear what corneal hysteresis actually measures, they advocated further investigation into expanding our understanding of the behavior of the cornea beyond just corneal thickness with regards to glaucoma.

In 2013, Medeiros and colleagues followed a prospective cohort of 68 glaucoma patients, measuring CH, IOP and CCT.⁹ They compared these values with the patients’ VF changes, which were assessed using the visual field index (VFI). Their data corroborated Congdon’s report, finding that lower CH was more closely associated with VFI deterioration compared to CCT.

They further postulated that CH potentiates the effect of increasing IOP on declining VFI, and that eyes with lower baseline CH values tended to progress faster than those eyes with higher baseline CH values.

Corneal hysteresis and optic nerves

A 2008 structural study by Wells et al may help explain this relationship by correlating physical properties of the cornea with optic nerve surface deformation in glaucoma.¹⁰

The researchers mapped the optic nerve before and after briefly increasing the IOP in 62 normal and 38 glaucoma patients. They found higher CH significantly correlated with increasing depth of the optic cup in glaucoma patients during this procedure, whereas other parameters, including CCT, did not demonstrate this.

While seemingly counterintuitive, differences in the distensibility of the cornea may apply to physical properties in other ocular tissues, including the optic nerves. The authors suggested that more compliant optic nerves could better tolerate excessive IOP.

This idea could hold implications in glaucoma, in which these structures would be better suited to endure the mechanical strain. Again, the authors advocated further studies to expand our understanding of ocular biomechanics beyond CCT measurements.

Corneal hysteresis and treatment paradigms

Other studies have investigated influence of CH on treatment results. In 2012, Agarwal and colleagues published a retrospective study of 57 POAG patients who underwent prostaglandin analogue therapy.¹¹ Interestingly, patients with lower CH experienced a significantly greater reduction in IOP when compared with patients with higher CH, which remained true after adjusting for IOP at baseline.

As described by Touboul and colleagues, it is possible that the underestimation of IOP in corneas with low hysteresis may be partially responsible for this. Despite no clear explanation for these results, they suggest that CH could predict which patients may be good candidates for treatment with prostaglandin analogues.

Additionally, CH has been shown to be a modifiable parameter that, like IOP, may potentially be targeted in the clinic. Sun et al followed 40 angle-closure glaucoma patients treated with a combination of IOP-lowering therapy consisting of medicine, trabeculectomy and peripheral iridectomy.¹²

They assessed IOP, CH and CCT at baseline, as well as at two and four weeks following treatment. The decrease in IOP following treatment was accompanied by a significant increase in CH (but still lower than normal values), whereas CCT did not change over the course of the study.

The authors suggested that ocular biomechanics may not be static, but that some alterations affecting corneal biomechanical properties occur during glaucoma development.

Conclusion

CH, gaining physicians' respect for its ability to be a more consistent predictor of glaucoma progression than CCT, has another advantage to recommend it: It can be rapidly and painlessly acquired using noncontact tonometry. Furthermore, it does not alter the measurement of IOP.

Preliminary findings have hinted at its potential to determine patient response to therapy, or serve as a modifiable risk factor for which a reference range can be established.

Clinicians should consider collecting this metric as part of the standard glaucoma exam. Future research may further elucidate the utility of CH in long-term monitoring and aid in treatment selection for glaucoma patients. OM

REFERENCES

About the Authors
	Kenneth Chang, MS, is a second-year medical student at the Herbert Wertheim College of Medicine of Florida International University. He has performed multiple research projects at the Doheny Eye Institute.
	Vikas Chopra, MD, is a fellowship-trained glaucoma and cataract specialist, and serves as the medical director of the UCLA Doheny Eye Center in Pasadena. He is a full-time faculty member and an associate professor of clinical ophthalmology at the David Geffen School of Medicine at UCLA, and the associate medical director of the Doheny Image Reading Center at the Doheny Eye Institute. He can be reached at vchopra@doheny.org.