427

GUEST EDITORIAL

Corneal hysteresis and beyond:

Does it involve the sclera?
Cynthia J. Roberts, PhD
Columbus, Ohio

This guest editorial is one of a series looking back at applanation pressure in the outward direction due to energy
landmark articles published in the JCRS. This special dissipation in the viscoelastic material. For example, a stiffer
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series commemorates the 25th anniversary of the
joint Journal of Cataract & Refractive Surgery. This
issue: Determining in vivo biomechanical properties
of the cornea with an ocular response analyzer.
J Cataract Refract Surg 2005;31:156–162.
The publication of Dave Luce’s visionary article on corneal
hysteresis (CH), a new biomechanical parameter produced
by the ocular response analyzer (ORA), not only sparked a
completely new line of inquiry but also made corneal
biomechanics relevant for the clinician.1 The ORA was the
first clinical tool that allowed studies of biomechanics in
multiple subspecialties across the globe, from keratoconus
and refractive surgery to glaucoma. Prior to 2005, ocular
biomechanics were analyzed with ex vivo models and
computer simulations. After 2005, clinicians developed new
collaborations with basic scientists and engineers as they
sought to understand how biomechanics affected disease
development and progression in a pressurized, fluid-filled
shell and how biomechanical response to surgical inter-
ventions affected outcomes. Since 2005, nearly 800 clinical
articles that directly investigated CH in cross-sectional and
longitudinal studies have been published. Many bio-
mechanical technical articles have also been published
including advanced algorithms based on deep learning and
artificial intelligence, all of which advance our un-
derstanding in this important field.
Ocular biomechanical assessment quantifies the response
to an applied load. That load can be destructive, as in
ex vivo studies, or nondestructive to be of clinical value. For
the ORA, an air puff is used to deform the cornea, making it
function also as a noncontact tonometer. It is important to
understand what CH represents and what it does not. It
does not correspond to stiffness or elastic modulus, as is
often misinterpreted in the literature. It does not represent
elastic resistance to deformation.2 Low CH can be asso-
ciated with a more compliant cornea, as in keratoconus, or
with a stiffer cornea, as with aging or higher intraocular
pressure (IOP).1,3 The inverse relationship with IOP is well
documented, such that CH is reduced as IOP increases.3
CH is a viscoelastic parameter that represents the different
pathways between loading and unloading, such that the
applanation pressure inward is greater than the unloading
eye with higher IOP is less capable of dissipating energy,
resulting in lower CH. Both viscous and elastic responses
contribute to CH, and different proportions can result in
similar CH.4 This is likely the reason that CH is not different
1 year after crosslinking (CXL) the keratoconic cornea,
despite evidence of stiffening in the infrared and pressure
signals.5 Both the first and second applanation pressures
increase after CXL, without a change in the difference be-
tween them, which is the formula for CH (Figure 1). The
elastic changes that represent stiffening are masked by the
viscous changes that are also induced with CXL.
Analysis of the pressure and infrared signals or waveform
of the ORA provides additional important information
regarding biomechanics of response, as illustrated with the
CXL example. Custom signal analysis was first reported in
Figure 1. Ocular response analyzer examination from a keratoconic
subject, prior to CXL in red, and 1 year after CXL in blue.5 Note that
both the loading Peak 1 and unloading Peak 2 are substantially
greater post-CXL, indicating substantial stiffening; in addition, the
blue post-CXL pressure curve is greater than the red pre-CXL
pressure curve, also consistent with stiffening. However, inward
applanation pressure, P1, and outward applanation pressure, P2,
both increased such that the difference between them is not
substantially altered. Since CH is P1–P2, there is no change in CH
despite obvious indications of stiffening. CH is affected by both
elastic and viscous modifications to the tissue, and in the case of
CXL, the elastic modifications are masked by the viscous modifi-
cations. CH = corneal hysteresis; CXL = corneal crosslinking;
FWHM2 = Full Width Half Maximum of Peak 2; Time1 = 1st ap-
planation time; Time2 = 2nd applanation time

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428 GUEST EDITORIAL

Figure 2. Orbscan corneal tomography 2 years after bilateral LASIK in the left column, adapted from Kérautret et al.6 The unstable eye is in the top row with
the corresponding ORA examination on the right. The contralateral stable eye is in the bottom row with the corresponding ORA examination on the right. Note
the corneal hysteresis is quite similar between both eyes. However, the amplitudes of Peak 1 and Peak 2 are substantially lower in the top row unstable eye,
consistent with evolving iatrogenic ectasia indicated by the corresponding tomography showing increased central elevation on both the anterior (upper left)
and posterior (upper right) surfaces, increased curvature (lower left) and corresponding decreased pachymetry (lower right). ORA = ocular response analyzer

comparing contralateral eyes after a refractive procedure, the signal morphology was dramatically distinct, with the
one of which was stable and one of which was unstable with unstable eye having lower peaks with an appearance similar
evolving iatrogenic ectasia.6 Both eyes had similar CH, but to keratoconus, as seen in Figure 2.

Figure 3. Box plot analysis of the

11 significantly different wave-
form-derived values from the oc-
ular response analyzer, between
eyes with a scleral buckle to treat
retinal detachment and the un-
treated fellow eyes, using the
dataset from Taroni et al.8 All
values contained a component of
the unloading phase of the air
puff–induced deformation, in-
cluding the 3 standard parame-
ters (IOPcc, CRF, and CH) in the
top row, which were calculated
from the inward and outward
applanation pressures and the
remaining 8 waveform parameters
were associated with Peak 2. No

waveform parameters associated with Peak 1 during the loading phase were significantly different between the fellow eyes. It is proposed that
this is driven by the significantly stiffer sclera in the treated eyes, which drove a faster recovery from concave to convex. CH = corneal
hysteresis; CRF = corneal resistance factor; IOPcc = corneal-compensated intraocular pressure

Volume 47 Issue 4 April 2021

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 GUEST EDITORIAL
Investigators have reported that low CH is predictive of
glaucomatous damage cross-sectionally and glaucomatous
progression in longitudinal studies.7 However, an impor-
tant question that arises with these associations is how a
biomechanical parameter of the cornea is connected to
damage at the optic nerve? It has been suggested that the
biomechanical response of the cornea may be a surrogate
for the biomechanics at the back of the eye. However, there
is recent evidence that the sclera contributes to the mea-
sured corneal response. In a comparison of contralateral
eyes of 18 subjects, where one eye received a scleral buckle
to treat retinal detachment, it was reported that the treated
eyes with much stiffer sclera, resulted in a significantly
lower CH than the fellow eyes with no treatment.8 There
was no statistically significant difference in IOP measured
with Goldmann applanation tonometry between eyes. In
analysis of the ORA waveform using custom software, it
was found that 2 signal features were different, including a
shorter Time2 indicating an abbreviated recovery, and
smaller Full Width Half Max2 of the second peak indicating
greater velocity in the recovery or unloading phase. Figure 3
shows the result of further analysis using the 38 waveform-
derived parameters developed by the manufacturer.9 Of the
11 significantly different values between treated and un-
treated eyes, 3 were standard reported parameters that
included both loading and unloading applanation pres-
sures, and 8 were waveform parameters that were all as-
sociated with the second peak in the unloading phase.
Specifically, a stiffer sclera resulted in increased aspect2,
which is the second peak aspect ratio (height/width) and the
length of this peak’s perimeter (path2). The greater aspect
ratio included a lower peak width (w2) and higher slopes of
peak rise and fall (uslope2 and dslop2), all indicating rapid
corneal movement, and lower area under the second peak
(p2area). In other words, the stiffer sclera drove a faster
recovery of the concavity to the natural convex shape.
The scleral influence on corneal response to an air puff is
consistent with ex vivo and modeling studies, which
demonstrate that a stiffer sclera will resist fluid displace-
ment as the cornea becomes concave, thus limiting corneal
deformation.10–12 This can be misinterpreted as a stiffer
corneal response. Conversely, a more compliant sclera may
allow greater deformation, which might be misinterpreted
as a more compliant cornea. The scleral contribution will be
greater as deformation increases, which explains why those
components of the signal associated with unloading are the
ones involved with interpreting scleral response. It is
proposed that the sclera is the connection between CH and
glaucomatous damage at the optic nerve.
These studies lead us to a new interpretation of CH that
actually represents ocular hysteresis. The cornea is the point at
which the load is applied and the response measured; however,
the entire eye is involved in dissipating the energy and con-
tributing to the reported parameters. This response is not
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429
confined to the cornea, and it is anticipated the specific in-
volvement of the sclera will generate many additional clinical
biomechanical studies with a focus on dissecting the compo-
nents of the waveform that indicate specific ocular structures.
Unfortunately, Dave Luce passed away in 2017. It is un-
likely that he could have realized the broad scope of his in-
vention when the concept of corneal hysteresis was published
in the first JCRS special issue on corneal biomechanics in
2005.13 In the current year of 2021, there is no end in sight as
to how CH and other new biomechanical parameters may
impact patient care and ultimately preserve vision.
Acknowledgments
Atieh Yousefi Koupaei, PhD, performed the statistical analysis
of the ocular response waveform parameters in Figure 3.
REFERENCES
1. Luce D. Determining in vivo biomechanical properties of the cornea with an
ocular response analyzer. J Cataract Refract Surg 2005;31:156–162
2. Roberts CJ. Concepts and misconceptions in corneal biomechanics.
J Cataract Refract Surg 2014;40:862–869
3. Kotecha A, Elsheikh A, Roberts C, Zhu HG, Garway-Heath DF. Corneal
thickness- and age-related biomechanical properties of the cornea mea-
sured with the ocular response analyzer. Invest Ophthalmol Vis Sci 2006;47:
5337–5347
4. Glass DH, Roberts CJ, Litsky AS, Weber PA. A viscoelastic biomechanical
model of the cornea describing the effect of viscosity and elasticity on
hysteresis. Invest Ophthalmol Vis Sci 2008;49:3919–3926
5. Vinciguerra P, Albé E, Mahmoud AM, Trazza S, Hafezi F, Roberts CJ.
Intra- and postoperative variation in ocular response analyzer parameters
in keratoconic eyes after corneal cross-linking. J Refract Surg 2010;28:
1–8
6. Kérautret J, Colin J, Touboul D, Roberts C. Biomechanical characteristics of
the ectatic cornea. J Cataract Refract Surg 2008;34:510–513
7. Zimprich L, Diedrich J, Bleeker A, Schweitzer JA. Corneal hysteresis as a
biomarker of glaucoma: current insights. Clin Ophthalmol 2020;14:
2255–2264
8. Taroni L, Bernabei F, Pellegrini M, Roda M, Toschi PG, Mahmoud AM,
Schiavi C, Giannaccare G, Roberts CJ. Corneal biomechanical response
alteration after scleral buckling surgery for rhegmatogenous retinal detach-
ment. Am J Ophthalmol 2020;217:49–54
9. Luce D, Taylor D. Ocular response analyzer. In: Roberts CJ, Liu J, eds.
Corneal Biomechanics: From Theory to Practice. Amsterdam, the Nether-
lands: Kugler Publications; 2016:67–86
10. Metzler K, Mahmoud AM, Liu J, Roberts CJ. Deformation response of
paired donor corneas to an air puff: intact whole globe vs mounted
corneoscleral rim. J Cataract Refract Surg 2014;40:888–896
11. Nguyen BA, Reilly MA, Roberts CJ. Biomechanical contribution of the sclera
to dynamic corneal response in air-puff induced deformation in human
donor eyes. Exp Eye Res 2020;191:107904
12. Nguyen BA, Roberts CJ, Reilly MA. Biomechanical impact of the sclera on
corneal deformation response to an air-puff: a finite-element study. Front
Bioeng Biotechnol 2019;6:210
13. Roberts CJ, Ed. Special issue: corneal biomechanics. J Cataract Refract
Surg 2005;31
Disclosures: C.J. Roberts is a consultant for Oculus Optikgeräte
GmbH and Ziemer Ophthalmic Systems AG.
First author:
Cynthia J. Roberts, PhD
Departments of Ophthalmology & Visual Sciences; and Bio-
medical Engineering, The Ohio State University, Columbus, Ohio
Volume 47 Issue 4 April 2021