Seminars in Ophthalmology

ISSN: 0882-0538 (Print) 1744-5205 (Online) Journal homepage: http://www.tandfonline.com/loi/isio20

Relationship Between Corneal Hysteresis and

Corneal Resistance Factor with Other Ocular
Parameters

Nicola Rosa MD, Michele Lanza, Maddalena De Bernardo, Giuseppe

Signoriello & Paolo Chiodini

To cite this article: Nicola Rosa MD, Michele Lanza, Maddalena De Bernardo, Giuseppe
Signoriello & Paolo Chiodini (2014): Relationship Between Corneal Hysteresis and Corneal
Resistance Factor with Other Ocular Parameters, Seminars in Ophthalmology, DOI:
10.3109/08820538.2013.874479

To link to this article: http://dx.doi.org/10.3109/08820538.2013.874479

Published online: 07 Feb 2014.

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 Seminars in Ophthalmology, Early Online, 1–5, 2014
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ISSN: 0882-0538 print / 1744-5205 online
DOI: 10.3109/08820538.2013.874479

ORIGINAL ARTICLE

Relationship Between Corneal Hysteresis and Corneal

Resistance Factor with Other Ocular Parameters
Nicola Rosa, MD1, Michele Lanza2,3, Maddalena De Bernardo1, Giuseppe Signoriello4,
and Paolo Chiodini4

1
Department of Medicine and Surgery, University of Salerno, Salerno, Italy, 2Multidisciplinary Department of
Medical, Surgical and Dental Specialities, Seconda Università di Napoli, Naples, Italy, 3Centro Grandi
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015

Apparecchiature, Seconda Università di Napoli, Naples, Italy, and 4Biostatistics Unit, Department of Medicine
and Public Health, Seconda Università di Napoli, Naples, Italy

ABSTRACT
Purpose: To evaluate the relationship between corneal hysteresis (CH) and corneal resistance factor (CRF) with
age, central corneal thickness (CCT), corneal curvature (KM), corneal volume (CV), and refractive error in naı̈ve
eyes. Methods: 105 healthy subjects (58 male and 47 female) were included in this study. The ages ranged from
19 to 82 years (mean 43.1 ± 15.4 years) and refraction between 11 D and +6 D (mean 0.79 ± 2.95 D). CH and
CRF obtained with the Ocular Response Analyzer (ORA) were correlated with age, refractive error, Goldmann
Applanation Tonometry (GAT), and with CCT, KM, CV obtained with the Pentacam, and with Corneal-
Compensated Intraocular Pressure (IOPcc) and Goldmann-correlated intraocular pressure measurement (IOPg)
obtained with ORA. A multivariable mixed effect model was used to evaluate associations among these
parameters. Results: CH ranged from 6.9 to 14.6 mmHg (mean 10.26 ± 1.49 mmHg); CRF ranged from 5.8 to
17 mmHg (mean 10.38 ± 1.64 mmHg). Multivariate analysis showed a statistically significant correlation
between CH with CCT (p50.001), and KM (p50.001), and between CRF with CCT (p50.001) and GAT
(p50.001). Conclusions: Our findings support the hypothesis that CH and CRF are related to the corneal shape
and thickness, and show a decrease of CH with age.
Keywords: Central corneal thickness, corneal curvature, corneal hysteresis, corneal resistance factor, corneal
volume

INTRODUCTION measurements of intraocular pressure with a

During the last few years, corneal characteristics
have been widely studied with different devices,
such as corneal topographs, tomographs, and confocal
microscopes. These investigations have shown
important results; e.g. in planning corneal refractive
surgery, where the knowledge of corneal thickness
and shape is mandatory. In eyes that have undergone
PRK and LASIK, the study of the corneal surface
is essential to understand the reasons for complaint
after such surgery.1–3
Moreover, it is well known that corneal thickness
and corneal curvature could influence the
Goldmann applanation tonometer (GAT).4
Until a few years ago, studies that focused on
corneal characteristics were mainly limited to corneal
thickness, curvature, and transparency. Recently, a
new device has been introduced that is able to
measure other corneal properties, such as corneal
hysteresis (CH) and corneal resistance factor (CRF).
CH is a direct measure of the corneal biomechanical
properties and is a strain-rate-dependent corneal
parameter that represents the cumulative effects of
corneal thickness, hydration, rigidity, and other as-yet
undetermined factors.5 CH seems to be an indication
of viscous damping in the cornea, reflecting the

Received 4 July 2013; accepted 8 December 2013; published online 5 February 2014
Correspondence: Nicola Rosa, MD, Department of Medicine and Surgery, University of Salerno, Salerno, Italy. E-mail: nrosa@unisa.it

1
 2 N. Rosa et al.
capacity of corneal tissue to absorb and dissipate
energy. CRF seems to indicate the overall resistance of
the cornea, which, according to previous data, seems
to be related to central corneal thickness and GAT-
determined IOP, but not to corneal-compensated IOP
(IOPcc).5 Most of the published studies on CH and
CRF dealt with the measurements of intraocular
pressure, but only some of them investigated the
connection with other ocular parameters.5–24 For this
reason, we decided to evaluate the relationship
between these entities with age, refractive error as
spherical equivalent (SE), IOPcc, IOPg, and
Goldmann Applanation Tonometry (GAT) and other
ocular parameters, such as central corneal thickness
(CCT), corneal curvature, and corneal volume (CV).
To the best of our knowledge, no other studies on
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healthy subjects analyze correlations among human
corneal biomechanical properties and all the param-
eters evaluated in this manuscript.
MATERIALS AND METHODS
In this study, we examined 204 eyes of 105 normal
subjects (47 female and 58 male) with refraction
ranging from 11 D to +6 D (mean 0.79 ± 2.95 D).
The age of the patients ranged from 19 to 82 years
(mean 43.1 ± 15.4 years). Subjects with ocular diseases,
history of ocular surgery, or ocular trauma were
excluded. Informed consent, according to the tenets of
the Declaration of Helsinki, was obtained from each
patient. All of the patients underwent a complete
ophthalmic examination, including an evaluation
with a Pentacam and Ocular Response Analyzer
(ORA). Pentacam (Oculus, Wetzlar, Germany) uses a
rotating Scheimpflug camera and a monochromatic
slit-light source (blue LED at 475 nm) that rotate
together around the optical axis of the eye to calculate
a three-dimensional model of the anterior segment.
This device was used to evaluate the CCT, CV
(measured within 10 mm circle around the central
cornea), and the Cornea Front Mean Keratometry
(KM) values. For each exam, the 50 scan modality of
measurement was used; the exam was considered to
be reliable when the Quality Factor was ‘‘OK.’’ as
suggested by the company. The ORA (Reichert Inc.,
Depew, NY, USA), similar to a non-contact tonometer,
uses a metered, collimated air pulse to applanate the
cornea and an infrared electro-optical system to
record inward and outward applanation events.
With this instrument, a precisely metered air pulse
is delivered to the eye, causing the cornea to move
inward, past a first applanation and into a slight
concavity.
As the pressure decreases, the cornea gradually
recovers its normal configuration, passing through a
second applanation state while returning from con-
cavity to its normal convex curvature.
The difference between these inward and outward
motion applanation pressures is called CH.
This device is also able to provide another value:
CRF, which is the result of clinical data analysis and is
derived from specific combinations of the inward and
outward applanation pressure signals.6
Best-signal examination, according to new ORA
software, was utilized. GAT values ranged from
7 mmHg to 24 mmHg (15.01 ± 2.91 mmHg).
Every patient was examined first with the Oculus
Pentacam, then with ORA and, finally, GAT in order
to not introduce bias in the evaluation of the cornea
and the corneal biomechanical properties.
Statistical Analysis
Continuous variables were reported as mean, stand-
ard deviation (SD), and range. Categorical variables
were expressed as absolute number and percentage.
Variability of CH and CRF between eyes was assessed
by means of an Intra Class Correlation (ICC) coeffi-
cient with 95% confidence interval (CI).25 Typically,
correlation coefficients are assessed using the Pearson
or Spearman methods. Nevertheless, with repeated
measurements, use of these traditional methods
would erroneously ignore the number of subjects as
the correct sample size, while instead using the total
number of observations as the incorrect sample size,
thereby increasing the degrees of freedom. As an
alternative, all correlation coefficients were estimated
using linear mixed-effects models that can account for
the correlation between eyes, as described by Hamlett
et al.26 Confidence intervals were calculated using the
Fisher transformation.
A linear mixed effects model was also used to
perform multivariable models.27 Restricted maximum
likelihood estimators were used to estimate model
parameters. Statistical analysis was performed using
SAS version 8.2 (SAS, Inc., Cary, NC, USA).
RESULTS
Table 1 summarizes the range, mean, and SD of all the
parameters evaluated in this study. Intra Class
Correlation (ICC) coefficients are 0.618 for CH (95%
CI 0.480 to 0.725) and 0.722 for CRF (95% CI 0.613 to
0.803), indicating that the values for the same subject
(within cluster) were more similar than the values
between subjects (between cluster). This correlation
was accounted for in the analyses by means of a linear
mixed effects model. A relevant positive linear
correlation was found between CH and CRF (0.67
95% CI 0.55 to 0.76). Table 2 summarizes the
univariate correlation between CH and CRF with
Age, SE, CCT, KM, CV, IOPcc, IOPg, and GAT. CH
and CRF were positively associated with CCT and CV,
Seminars in Ophthalmology
 Corneal Biomechanics in Naive Eyes 3

TABLE 1. Characteristics of subjects included in the study. TABLE 3. Results of multivariable linear mixed effects
regression models with CH and CRF as dependent variables.
Variables Mean (SD) Range
CH CRF
CH, mm 10.26 (1.49) 6.9–14.6
CRF, mm 10.38 (1.34) 5.8–17 Parameter Parameter
Age, year 43.1 (15.4) 18–82 Variables estimate p Value estimate p Value
SE, D 0.79 (2.95) 11–+6
CCT, mm 555.8 (32.7) 478–652 Intercept 10.42 0.008 14.57 50.001
KM, D 43.34 (1.40) 40.3–46.9 Age, year 0.025 0.001 0.020 0.013
CV, mm3 60.56 (3.61) 45.6–68.4 SE, D 0.041 0.266 0.032 0.399
IOPcc, mmHg 16.36 (3.52) 8.3–26.7 CCT, mm 0.016 50.001 0.022 50.001
IOPg, mmHg 15.71 (3.59) 4.6–25.8 KM, D 0.292 50.001 0.248 0.002
GAT, mmHG 15.01 (2.91) 7–24 GAT, mmHg 0.004 0.900 0.196 50.001

CH: corneal hysteresis; CRF: corneal resistance factor; SE:
spherical equivalent; CCT: central corneal thickness; KM: Mean
Keratometry; CV: corneal volume; IOP: intraocular pressure;
GAT: Goldmann applanation tonometer
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CH: corneal hysteresis; CRF: corneal resistance factor; SE:
spherical equivalent; CCT: central corneal thickness; KM: Mean
Keratometry; GAT: Goldmann applanation tonometer

Lower CH and CRF values have been demon-

TABLE 2. Results of univariate association of CH and CRF with strated in several conditions, such as keratoconic
subject characteristics. and post-LASIK eyes, which could reflect the
Univariate correlation coefficient (95% CI) disorganization of the stromal collagen lamellae.28
Lower CH has also been demonstrated in patients
Variables CH CRF
with primary open-angle and low-tension glau-
Age, year 0.23 ( 0.4 to 0.04) 0.08 ( 0.27 to 0.11) coma,6,10,18 supporting the hypothesis that path-
SE, D 0.02 ( 0.21 to 0.17) 0.02 ( 0.21 to 0.17) ology in the lamina cribrosa may be detectable by
CCT, mm 0.26 (0.07 to 0.43) 0.31 (0.13 to 0.47) changes in corneal biomechanics. For these reasons,
KM, D 0.16 ( 0.03 to 0.34) 0.13 ( 0.06 to 0.32) CH measurements may prove to be useful in the
CV, mm3 0.32 (0.14 to 0.48) 0.34 (0.16 to 0.50)
IOPcc, mmHg 0.47 ( 0.61 to 0.31) 0.18 ( 0.02 to 0.35) diagnosis of conditions such as normal tension
IOPg, mmHg 0.07 ( 0.26 to 0.12) 0.44 (0.27 to 0.58) glaucoma and early keratoconus.10,18,19
GAT, mmHG 0.01 ( 0.2 to 0.18) 0.42 (0.25 to 0.57) In order to better explain CH and CRF, we tried to
correlate them with CCT, CV, KM, refraction, and age.
CI: confidence interval; CH: corneal hysteresis; CRF: corneal
resistance factor; SE: spherical equivalent; CCT: central cor-
According to our results, CH decreases with age,
neal thickness; KM: Mean Keratometry; CV: corneal volume; whereas CRF is not affected by the aging process. In
IOP: intraocular pressure; GAT: Goldmann applanation contrats, CRF seems to affect the IOP measurement,
tonometer. whereas CH does not. Regarding the correlation with
CCT and Km, both CH and CRF increased as the
while they were uncorrelated with age, SE, and KM. corneas became thicker and steeper. Previously pub-
A negative correlation was found between CH and lished studies investigated the relationship between
IOPcc, while CRF was positively associated with IOPg CH and CRF with the other ocular parameters, but
and GAT. their results were not univocal, as summarized in
Table 3 summarizes the results of multivariate Tables 4 and 5. Our findings of a positive correlation
analysis of CH and CRF with Age, SE, CCT, KM, and between CH and CCT agree with most of the authors
GAT. As expected, CV was strongly positively that correlated these parameters, even if the CCT
correlated with CCT and therefore excluded from measurements were performed with different
the multivariate analyses. IOPcc and IOPg were devices.6,13–15,20,21,29 Regarding the correlation
excluded because they were strongly positively between CH and age, our results contradict most of
associated with GAT values. According to our results, the authors who correlated these param-
CH is statistically positively associated with CCT and eters,14,16,18,19,28,29 but agree with the results obtained
KM and negatively associated with age, whereas CRF by Fontes et al.,15 Narayanaswamy et al.,20 and
is statistically positively associated with CCT, KM, Yu et al.21
and GAT. No correlation was found between CH and The multivariate statistical analysis we per-
CRF with the refractive error. formed could account for this difference. Our
results regarding the relationship between CRF
and the other parameters agree with those previ-
DISCUSSION ously reported for the positive correlation with
CCT.7,13–17,20,21,29 The data obtained for KM are
CH and CRF measure the complex visco-elastic not univocal, possibly because of the use of
structure of the human corneal tissue.
! 2014 Informa Healthcare USA, Inc.
 4 N. Rosa et al.

TABLE 4. Most important findings published in previous DECLARATION OF INTEREST

papers comparing CH with other eye parameters.

Parameters The authors report no conflicts of interest. The authors

alone are responsible for the content and writing of
Corneal
the paper.
Age Refraction Power IOP CCT CV

Luce et al.6 NE NE NE NSS SS NE

Medeiros et al.7 NE NE NE NE NE NE
Laiquzzaman et al.12 NE NE NE NSS NE NE REFERENCES
Shah et al.13 NE NE NE NE SS NE
Touboul14 NSS NE NE NSS SS NE 1. Hersh PS. A standardized classification of corneal topog-
Fontes15 SS NSS NSS NE SS NE raphy after laser refractive surgery. J Refract Surg 1997;13:
Franco et al.16 NSS NE NSS NSS SS NE 571–575.
Hurmeric et al.17 NE NE NE NSS SS NE 2. Rosa N, Cennamo G, Sebastiani A. Classification of corneal
Detry-Morel et al.18 NSS NE NE NSS NSS NE topographic patterns after PRK. J Refract Surg 2000;16:
Johnson et al.19 NSS NE NE NE NSS NE 481–483.
Narayanaswamy et al.20 SS NSS NSS NSS SS NE 3. Rosa N, Lanza M, De Rosa G, Romano A. Anterior corneal
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015

Yu et al.22 SS SS NE NE SS NE surface after Nidek EC-5000 multipass and multizone

Radhakrishnan et al.23 NE NE NE NSS NE NE photorefractive keratectomy for myopia. J Refract Surg
Ortiz et al.28 NSS NE NE NE NE NE 2002;18:460–462.
Kamiya et al.29 NSS NSS NSS SS SS NE 4. Whitacre MM, Stein R. Sources of error with use of
Goldmann-type tonometers. Surv Ophthalmol 1993;38:1–30.
CH: corneal hysteresis; IOP: intraocular pressure measured 5. Martinez-de-la-Casa JM, Garcia-Feijoo J, Fernandez-Vidal
with Goldmann applanation tonometry; CCT: central corneal A, et al. Ocular response analyzer versus Goldmann
thickness; CV: corneal volume; NE: not evaluated; NSS: not applanation tonometry for intraocular pressure measure-
statistically significant; SS: statistically significant ments. Invest Ophthalmol Vis Sci 2006;47:4410–4414.
6. Luce D, Taylor D. Reichert ocular response analyzer
measures corneal biomechanical properties and IOP
provides new indicators for corneal specialties and glau-
TABLE 5. Most important findings published in previous coma management. Depew, NY: Reichert Ophthalmic
papers comparing CRF with other eye parameters. Instruments, March 2006.
7. Medeiros FA, Weinreb RN. Evaluation of the influence of
Parameters
corneal biomechanical properties on intraocular pressure
Corneal measurements using the ocular response analyzer.
Age Refraction Power IOP CCT CV J Glaucoma 2006;15:364–370.
8. Herndon LW. Measuring intraocular pressure:
Luce et al.6 NE NE NE NE NE NE Adjustments for corneal thickness and new technologies.
Medeiros et al.7 NSS NSS SS SS SS NE Current Opin Ophthalmol 2006;17:115–119.
Laiquzzaman et al.12 NE NE NE NE NE NE 9. Kirwan C, O’Keefe M, Lanigan B. Corneal hysteresis and
Shah et al.13 NE NE NE NE SS NE intraocular pressure measurement in children using the
Touboul14 NSS NE NE SS SS NE Reichert ocular response analyzer. Am J Ophthalmol 2006;
Fontes15 SS NSS NSS NE SS NE 142:990–992.
Franco et al.16 NSS NSS NSS NSS SS NE 10. Congdon NG, Broman AT, Bandeen-Roche K, et al. Central
Hurmeric et al.17 NE NE NE NE SS NE corneal thickness and corneal hysteresis associated with
Detry-Morel et al.18 NSS NE NE NSS NSS NE glaucoma damage. Am J Ophthalmol 2006;141:868–875.
Johnson et al.19 NSS NE NE NE NSS NE 11. Kotecha A, Elsheikh A, Roberts CR, et al. Corneal thick-
Narayanaswamy et al.20 SS NSS SS SS SS NE ness- and age-related biomechanical properties of the
Yu et al.22 NSS NSS NE NE SS NE cornea measured with the ocular response analyzer.
Radhakrishnan et al.23 NE NE NE SS NE NE Invest Ophthalmol Vis Sci 2006;47:5337–5347.
Ortiz et al.28 NSS NE NE NE NE NE 12. Laiquzzaman M, Bhojwani R, Cunliffe I, Shah S. Diurnal
Kamiya et al.29 NSS NE NSS SS SS NE variation of ocular hysteresis in normal subjects: Relevance
in clinical context. Clin Experiment Ophthalmol 2006;34:
CRF: corneal resistance factor; IOP: intraocular pressure 114–118.
measured with Goldmann applanation tonometry; CCT: 13. Shah S, Laiquzzaman M, Cunliffe I, Mantry S. The use of
central corneal thickness; CV: corneal volume; NE: not the Reichert ocular response analyser to establish the
evaluated; NSS: not statistically significant; SS: statistically relationship between ocular hysteresis, corneal resistance
significant factor and central corneal thickness in normal eyes. Cont
Lens Anterior Eye 2006;29:257–262.
14. Touboul D, Roberts C, Kérautret J, et al. Correlations
different devices in the evaluation of the corneal between corneal hysteresis, intraocular pressure, and
power. corneal central pachymetry. J Cataract Refract Surg 2008;
In conclusion, our study confirms that CH and CRF 34:616–622.
are related to corneal thickness and shape in a normal 15. Fontes BM, Ambrósio Jr R, Alonso RS, et al. Corneal
biomechanical metrics in eyes with refraction of 19.00 to
population; the decrease of CH with age has to be
+9.00 D in healthy Brazilian patients. J Refract Surg 2008;24:
taken into account where studies on keratoconus 941–945.
progression with and without treatment are 16. Franco S, Lira M. Biomechanical properties of the cornea
performed. measured by the Ocular Response Analyzer and their

Seminars in Ophthalmology

association with intraocular pressure and the central
corneal curvature. Clin Exp Optom 2009;92:469–475.
17. Hurmeric V, Sahin A, Ozge G, Bayer A. The relationship
between corneal biomechanical properties and confocal
microscopy findings in normal and keratoconic eyes.
Cornea 2010;29:641–649.
18. Detry-Morel M, Jamart J, Pourjavan S. Evaluation of
corneal biomechanical properties with the Reichert
Ocular Response Analyzer. Eur J Ophthalmol 2011;21:
138–148.
19. Johnson RD, Nguyen MT, Lee N, Hamilton DR. Corneal
biomechanical properties in normal, forme fruste kerato-
conus, and manifest keratoconus after statistical correction
for potentially confounding factors. Cornea 2011;30:
516–523.
20. Narayanaswamy A, Chung RS, Wu RY, et al. Determinants
of corneal biomechanical properties in an adult Chinese
population. Ophthalmology 2011;118:1253–1259.
21. Plakitsi A, O’Donnell C, Miranda MA, et al. Corneal
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015
biomechanical properties measured with the Ocular
Response Analyser in a myopic population. Ophthalmic
Physiol Opt 2011;31:404–412.
22. Yu AY, Duan SF, Zhao YE, et al. Correlation between
corneal biomechanical properties, applanation tonometry
! 2014 Informa Healthcare USA, Inc.
Corneal Biomechanics in Naive Eyes 5
and direct intracameral tonometry. Br J Ophthalmol 2012;96:
640–644.
23. Radhakrishnan H, Miranda MA, O’Donnell C. Corneal
biomechanical properties and their correlates with refract-
ive error. Clin Exp Optom 2012;95:12–18.
24. Terai N, Raiskup F, Haustein M, et al. Identification
of biomechanical properties of the cornea: The ocular
response analyzer. Curr Eye Res 2012;37:553–562.
25. Shrout PE, Fleiss JL. Intraclass correlations: Uses in
assessing rater reliability. Psychol Bull 1979;86:420–428.
26. Hamlett A, Ryan L, Serrano-Trespalacios P, Wolfinger R.
Mixed models for assessing correlation in the
presence of replication. J Air Waste Manag Assoc 2003;53:
442–450.
27. Cnaan A, Laird NM, Slasor P. Using the general linear
mixed model to analyse unbalanced repeated measures
and longitudinal data. Stat Med 1997;16:2349–2380.
28. Ortiz D, Piñero D, Shabayek MH, et al. Corneal biomech-
anical properties in normal, post-laser in situ keratomileu-
sis, and keratoconic eyes. J Cataract Refract Surg 2007;33:
1371–1375.
29. Kamiya K, Hagishima M, Fujimura F, Shimizu K. Factors
affecting corneal hysteresis in normal eyes. Graefes Arch
Clin Exp Ophthalmol 2008;246:1491–1494.