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BJO Online First, published on January 2, 2015 as 10.1136/bjophthalmol-2014-305962

Clinical science

Signicance of corneal biomechanical properties in

patients with progressive normal-tension glaucoma
Jong Hyuk Park, Roo Min Jun, Kyu-Ryong Choi
Department of Ophthalmology,
Institute of Ophthalmology &
Optometry, Ewha Womans
University School of Medicine,
Seoul, Republic of Korea
Correspondence to
Dr Kyu-Ryong Choi,
Department of Ophthalmology,
Ewha Womans University
Mokdong Hospital, 911-1,
Mok-dong Yangcheon-ku,
Seoul 158-710, Republic of
Korea; ckrey02@ewha.ac.kr
Received 6 August 2014
Revised 3 December 2014
Accepted 5 December 2014

ABSTRACT
Aim To investigate the clinical signicance of corneal
biomechanical properties assessed using an ocular
response analyser in patients with progressing normaltension glaucoma (NTG).
Methods In this retrospective study, we included 82
eyes of 82 NTG patients who had been receiving topical
anti-glaucoma medications. Patients were allocated to
two groups based on the mean value of corneal
hysteresis (CH) and the status of progression. The
assessment of progression was based on the trend
analysis using mean deviation slope. Uni- and
multivariable logistic analyses were constructed to
identify factors associated with increased odds of
progression, including CH, central corneal thickness
(CCT), and retinal nerve bre layer (RNFL) thickness.
Results Forty-six eyes (56.1%) reached the progression
criteria. Eyes with progression had lower CCT (530.2
38.6 vs 549.438.3 m, p=0.03), thinner average
RNFL thickness (70.616.1 vs 82.817.4 m, p<0.01),
lower CH (9.41.3 vs 10.81.4 mm Hg, p<0.01), and
lower corneal resistance factor (9.31.3 vs 10.4
1.8 mm Hg, p<0.01) than eyes without progression.
CH and CCT were signicantly correlated (r=0.44,
p<0.01). Upon multivariable analysis, CH ( (B)=0.32
per mm Hg lower, p<0.01) and average RNFL thickness
(=0.96 per m lower, p=0.04) remained statistically
signicant.
Conclusions Corneal biomechanical properties are
correlated and associated with the progression of visual
eld damage in NTG patients. These ndings suggest
that CH can be used as one of the prognostic factors for
progression, independent of corneal thickness or
intraocular pressure.

INTRODUCTION

To cite: Park JH, Jun RM,

Choi K-R. Br J Ophthalmol
Published Online First:
[please include Day Month
Year] doi:10.1136/
bjophthalmol-2014-305962

The compression and deformation of the lamina

cribrosa and the consecutive retinal ganglion cell
(RGC) damage have been implicated in the pathogenesis of glaucomatous optic neuropathy.1 These
structural deteriorations in the optic nerve head
(ONH) connective tissue are observed mainly in
primary open-angle glaucoma (POAG) eyes.
However, the similar structural changes occur in
normal-tension glaucoma (NTG) eyes, even at
normal intraocular pressure (IOP). Recent reports
have shown that NTG patients have a thinner
lamina cribrosa than POAG patients and the
thinner lamina may lead to deformation of the
lamina and blockage of axonal transport, even with
lower translaminar tissue pressure gradients.2 3
NTG showed a 2.7% prevalence of glaucoma in
the Namil study in Korea, which accounted for
77% of POAG.4 Although the pathogenesis of
NTG is unclear, many previous studies have

identied old age, myopic refractive error, thin

cornea, disc haemorrhages, high baseline IOP, and
baseline visual eld (VF) loss as risk factors for VF
progression in NTG.5 6 Evaluating baseline risk
factor values associated with progression will be
benecial for monitoring NTG patients at high risk
for rapid deterioration. In particular, corneal parameters such as central corneal thickness (CCT) are
signicant because over one million people
undergo laser in situ keratomileusis (LASIK) procedures annually.7 The corneal thinning from this
refractive surgery affects glaucoma risk assessment.8
Therefore, CCT and IOP measurements with
Goldmann applanation tonometry are confronted
with limitations in monitoring patients at risk for
both myopia and glaucoma.
In addition to CCT, other corneal biomechanical
properties that could inuence Goldmann applanation tonometry, such as corneal hysteresis (CH),
have been proposed as potential risk factors for
glaucoma. The Ocular Response Analyser (ORA;
Reichert Ophthalmic Instruments Inc, Depew, New
York, USA), a non-contact tonometer, measures
both CH and corneal resistance factor (CRF).
Recent studies found reduced CH in glaucomatous
eyes9 10 and demonstrated an association between
low CH and glaucomatous progression.11 12
Mechanical damage in glaucoma has been hypothesised to involve the biomechanical properties of the
ONH, which are mainly related to the stiffness of
the lamina cribrosa, scleral canal wall, and peripapillary sclera.13 Corneal parameters (CCT and CH)
may be associated with the ONH response to
pressure-induced damage.14 15
We investigated the association between either
corneal biomechanical properties or ONH parameters
and VF progression in patients with medically-treated
NTG to determine which variables are better correlated or associated with glaucomatous progression.

METHODS
This retrospective study was approved by the
Institutional Review Board of Ewha Womans
University Mokdong Hospital, Seoul, Korea, and
was conducted in accordance with the tenets of the
Declaration of Helsinki. A total of 82 subjects with
NTG were included in this study between January
and December 2013. Patients were recruited from
outpatients at the glaucoma clinic of Ewha Womans
University Mokdong Hospital. Subjects were
included if they had an established diagnosis of
NTG made by a glaucoma specialist (K-RC) based
on glaucomatous optic disc damage and abnormal
VF test results. Signs of glaucomatous optic disc
damage were considered diffuse or localised neuroretinal rim loss, excavation, and retinal nerve

Park JH, et al. Br J Ophthalmol 2015;0:16. doi:10.1136/bjophthalmol-2014-305962

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Clinical science
bre layer (RNFL) defects. An abnormal VF was dened as a
pattern standard deviation outside of the 95% normal condence limits or a Glaucoma Hemield Test result outside
normal limits. At least two consecutive abnormal VF examinations were required, with the most recent test performed within
12 months of enrolment. NTG was diagnosed in the presence
of repeatable IOP 21 mm Hg, glaucomatous optic disc
changes, and VF loss.
Each patient underwent a comprehensive ophthalmologic
examination, including a review of medical history, slit-lamp
biomicroscopy, Goldmann applanation tonometry, gonioscopy,
dilated fundoscopic examination using a 90-diopter lens, measurements of corneal biomechanical properties using an ORA,
stereoscopic optic disc photography, spectral-domain optical
coherence tomography (SD-OCT), and a VF test. Here the measurements of corneal biomechanical properties and SD-OCT
were performed either after the nal VF test or on the same day
of the nal VF test. After ophthalmic evaluation, the right eye
was randomly selected for inclusion in cases in which both eyes
of the patient were eligible for the study. To be included in this
study, patients were required to have a best-corrected visual
acuity of 20/40 or better, refractive error of spherical refraction
within 6.0 dioptres and cylinder correction within 3.0 dioptres, and the presence of a normal anterior chamber and an
open-angle on slit-lamp and gonioscopic examinations. In addition, we required patients to have clear media, no history of
retinal disease (eg, diabetic retinopathy, macular degeneration,
retinal detachment) or laser therapy, or optic nerve abnormalities including non-glaucomatous optic neuropathy. We excluded
patients with a history of treatment with medications that might
affect retinal thickness (eg, intravitreal anti-vascular endothelial
growth factor (anti-VEGF) therapy).

CH measurement
CH measurements were acquired after VF tests for progression
evaluation were performed. The ORA determines corneal biomechanical properties using an applied forcedisplacement relationship and provides IOP and various corneal parameters.
Details of the technology have been described previously.12
Major parameters measured by ORA were CH, CRF,
Goldmann-correlated IOP (IOPg), and the corneal compensated
IOP (IOPcc).

RNFL thickness and choroidal thickness measurement

SD-OCT images were obtained using a Heidelberg Spectralis
(Heidelberg Instruments, Inc, Heidelberg, Germany). First, the
SD-OCT was used to obtain peripapillary RNFL thickness measurements. We evaluated the peripapillary RNFL thickness in
the temporal quadrant (31645), superior quadrant (46135),
nasal quadrant (136225), and inferior quadrant (226315).
Next, the SD-OCT images were obtained by enhanced-depth
imaging, a method that improves resolution of choroidal detail
when the focus is manually placed more posteriorly than in
standard retinal SD-OCT images. The images were viewed and
measured using the attached measuring software in the
Heidelberg
Spectralis
OCT
(V.1.5.12.0;
Heidelberg
Engineering). The choroid was measured from the inner surface
of the sclera to the outer portion of the hyperreective line that
corresponded to the retinal pigment epithelium.

VF analysis and progression determination

All patients had a reliable VF analysis (Humphrey Field Analyser
(Carl Zeiss Inc, Dublin, California, USA)) using Swedish
Interactive Threshold Algorithm standard 30-2 perimetry.
2

Patients with any other ophthalmic or neurologic condition that

could result in a VF defect were excluded. Only reliable VF test
results (false-positive errors <15%; false-negative errors <15%;
xation loss <20%) were included in the analysis. For each
patient, the VF test was performed at 6- to 12-month intervals.
We determined VF progression by global trend analysis using
mean deviation (MD) slope. The MD slope, MD change per
year (dB/year), was obtained from linear regression analysis of
the HFA II Glaucoma Progression Analysis (GPA) software. We
classied the progression of VF damage by setting the cut-off
value 0 of the MD slope, and dened the progressors as a
negative slope. For the calculation of the MD slope using the
HFA, those patients with more than ve VF tests were included
for progression analysis. Data with poor reliability and subjects
with fewer than ve VF tests were not utilised in the MD slope
calculation.

Statistical analysis
We divided the enrolled subjects into two groups, according to
the CH as assessed by ORA. We compared the clinical and
ocular data of patients eyes with low versus high CH and those
with progressive versus non-progressive VF damage. Differences
for continuous variables including age, refraction error, and IOP
were compared using an independent Students t test.
Differences for categorical data including gender and disease
status were compared using the 2 test. Simple and multiple
regression analyses were constructed to determine variables
associated with increased odds of progression; multivariable
models were constructed from univariable predictors with
p<0.05. In this model, CH, CCT, and RNFL thickness were all
entered as independent variables. All data were analysed with
statistical analysis software (SPSS, V.21.0; SPSS Inc, Chicago,
Illinois, USA). All statistical tests were two-sided with a 0.05
level of signicance.

RESULTS
Eighty-two eyes in 82 NTG patients treated with topical antiglaucoma medications were enrolled in this study. The mean
observation period was 76.948.7 months, and the mean
global rate of change in the MD value was 0.060.95 dB/year
(range 2.35 to 3.55 dB/year). Forty-six eyes (56.1% of those
enrolled) reached our predened progression criteria. Their
mean rate of localised VF change was 0.10.9 dB/year.
Table 1 lists the clinical and ocular characteristics of all subjects. Because the mean CH as determined by ORA was
10.08 mm Hg overall, we set this as the cut-off value for CH.
Figure 1 shows the distribution curve for the CH of 82 eyes.
Based on the mean CH (10.08 mm Hg), we divided 82 patients
into low CH (39 patients) and high CH (43 patients) groups.
Table 2 shows clinical and demographic information for eyes
with low versus high CH. Eyes with low CH had thinner
central corneas compared to eyes with high CH (525.842.2 vs
549.733.3 m, p<0.01). They also had lower CRF (8.81.1
vs 10.51.5 mm Hg, p<0.01), lower IOPcc (14.02.8 vs 16.6
3.5 mm Hg, p<0.01), and thinner RNFLs in the inferior
quadrant (78.226.7 vs 98.432.5 m, p<0.01). Of the 39
eyes with low CH, 26 (66.7%) showed progression of VF
damage while 13 (33.3%) showed no progression. Of the 43
eyes with high CH, 15 (34.9%) showed progression of VF
damage, whereas 28 (65.1%) showed no progression.
Table 3 shows clinical background data for eyes with and
without progressive VF damage. There were statistically signicant differences in the CCT ( p=0.03), CRF ( p<0.01), IOPcc
(p=0.03), and CH (p<0.01). The mean values of CH were
Park JH, et al. Br J Ophthalmol 2015;0:16. doi:10.1136/bjophthalmol-2014-305962

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Clinical science
Table 1 Characteristics of normal-tension glaucoma patients
(n=82)

Table 2

Age (years)
Gender, female (%)
Diabetes (%)
Hypertension (%)
Spherical equivalent (diopter)
Baseline IOP (mm Hg)
Mean follow-up IOP (mm Hg)
CCT (m)
CRF (mm Hg)
CH (mm Hg)
IOPg (mm Hg)
IOPcc (mm Hg)
Axial length (mm)
Baseline MD (dB)
Baseline PSD (dB)
MD slope (dB/year)
Number of VF tests
Number of glaucoma medications
Follow-up periods (months)

Variables

56.513.5
35 (42.7%)
12 (14.6%)
23 (28.0%)
2.43.5
17.23.6
12.32.8
538.539.4
9.81.6
10.11.5
14.33.4
15.33.5
24.71.9
4.23.1
5.23.4
0.10.9
9.95.1
1.70.8
76.948.7

(2679)

(8.5 to 2.5)
(921)
(719)
(429640)
(6.715.6)
(6.414.9)
(7.224.9)
(8.323.0)
(21.7529.32)
(14.14 to 1.09)
(1.6815.29)
(2.35 to 3.55)
(318)
(14)
(9240)

Values are presented as meanSD (range).

CCT, central corneal thickness; CH, corneal hysteresis; CRF, corneal resistance factor;
GAT, Goldmann applanation tonometry; IOP, intraocular pressure; IOPcc,
corneal-compensated IOP; IOPg, Goldmann-correlated IOP; MD, mean deviation;
ORA, Ocular Response Analyser; PSD, pattern SD; RNFL, retinal nerve fibre layer;
VF, visual field.

10.8 mm Hg in eyes without progressive VF damage and

9.4 mm Hg in eyes with progressive VF damage. Eyes with progressive VF damage showed thinner RNFLs in the inferior
quadrant ( p<0.01), temporal quadrant ( p=0.01), nasal quadrant ( p=0.02), and the average of all quadrants ( p<0.01). CH
had a moderate and signicant correlation with CCT (Pearsons
r=0.44, p<0.01) and IOPcc (Pearsons r=0.52, p<0.01).
There was also a weak and signicant association between CH
and RNFL thickness in the average, temporal, and inferior
quadrants (table 4).

Clinical data for eyes with high vs low CH

Age (years)
Gender, female (%)
Spherical equivalent (diopter)
Baseline IOP (mm Hg)
Mean follow-up IOP (mm Hg)
CCT (m)
CRF (mmHg)
CH (mm Hg)
Axial length (mm)
Vertical cup/disc ratio
Subfoveal choroidal thickness
RNFL thickness (average)
RNFL thickness (superior)
RNFL thickness (temporal)
RNFL thickness (nasal)
RNFL thickness (inferior)
Baseline MD (dB)
Baseline PSD (dB)
Number of VF tests
Number of glaucoma
medications
Follow-up periods (months)
MD slope (dB/year)
Progression of visual field
damage (positive/negative)

Eyes with low

CH (n=39)

Eyes with high

CH (n=43)

p Values

57.8714.2
14 (35.9%)
1.93.4
17.44.2
12.23.2
525.842.2
8.81.1
8.91.0
24.41.8
0.70.1
244.884.3
72.118.8
88.430.4
58.218.2
64.230.9
78.226.7
3.72.5
4.92.9
10.15.3
1.80.8

55.412.8
21 (48.8%)
2.73.5
17.03.1
12.42.4
549.733.3
10.51.5
11.11.1
24.81.8
0.60.1
245.799.0
79.415.9
89.023.5
66.220.7
64.219.6
98.432.5
4.73.6
5.53.8
9.74.9
1.50.6

0.41
0.23
0.30
0.61
0.75
<0.01
<0.01
<0.01
0.33
0.09
0.96
0.06
0.92
0.06
0.98
<0.01
0.16
0.39
0.18
0.03

80.854.8
0.31.1
26/13

73.342.8
0.20.7
15/28

0.49
0.02
<0.01

Values are presented as meanSD.

CCT, central corneal thickness; CH, corneal hysteresis; CRF, corneal resistance factor;
GAT, Goldmann applanation tonometry; IOP, intraocular pressure; MD, mean
deviation; ORA, Ocular Response Analyser; PSD, pattern SD; RNFL, retinal nerve fibre
layer; VF, visual field.

In univariable regression analysis, CH (B=0.39, p<0.01),

CRF (B=0.59, p<0.01), CCT (B=0.97, p<0.01), baseline MD
(B=1.31, p=0.04), and RNFL thickness of the average
(B=0.96, p<0.01), temporal (B=0.97, p=0.01), and inferior
(B=0.97, p<0.01) quadrants were signicantly correlated with
VF progression. In multivariable logistic regression analysis, CH
(B=0.32, p<0.01) and average RNFL thickness (B=0.96,
p=0.04) remained statistically signicant (table 5).

DISCUSSION

Figure 1 Distribution of corneal hysteresis (CH) for all subjects. Note:

the mean CH value was 10.08 mm Hg and the SD was 1.51 mm Hg
(range 6.414.9 mm Hg).
Park JH, et al. Br J Ophthalmol 2015;0:16. doi:10.1136/bjophthalmol-2014-305962

The progression rates in patients receiving ocular hypotensive

medication were reported to be between 0.1 and 0.35 dB/
year for NTG.16 The estimated MD slope of 0.1 dB/year in
the current study, with a mean IOP of 12.3 mm Hg, is consistent
with previous reports. Some patients, however, showed a rapid
functional progression even though their IOP was maintained
within normal range. Therefore, it is clinically important to
predict the risk of progression and identify the prognostic
factors associated with progression. However, the present
modalities to evaluate the probability of glaucomatous progression had some limitations in screening NTG patients receiving
refractive surgery or ocular hypotensive therapy. In the current
study, we evaluated the effect of corneal biomechanical properties measured by ORA in eyes with progressive NTG and investigated the association of CH with NTG progression.
Low CCT has been identied as a signicant risk factor for
the development of glaucoma. In the Ocular Hypertension
Treatment Study (OHTS)17 and the Early Manifest Glaucoma
3

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Clinical science
Table 3 Clinical data for eyes with and without progressive VF
damage

Variables
Age (years)
Gender, female (%)
Spherical equivalent
(diopter)
Baseline IOP
(mm Hg)
Mean follow-up IOP
(mm Hg)
CCT (m)
CRF (mm Hg)
CH (mm Hg)
IOPg (mm Hg)
IOPcc (mm Hg)
Axial length (mm)
Vertical cup/disc ratio
Subfoveal choroidal
thickness
RNFL thickness
(average)
RNFL thickness
(superior)
RNFL thickness
(temporal)
RNFL thickness
(nasal)
RNFL thickness
(inferior)
Baseline MD (dB)
Baseline PSD (dB)
MD slope (dB/year)
Number of VF tests
Number of glaucoma
medications
Follow-up periods
(months)

Eyes without
progressive VF
damage (n=36)

Eyes with
progressive VF
damage (n=46)

53.911.1
18 (50.0%)
2.43.4

58.614.9
17 (37.0%)
2.33.6

0.12
0.27
0.90

17.03.8

17.33.5

0.72

12.72.5

12.13.1

0.31

549.438.3
10.41.8
10.81.4
14.33.5
14.42.9
24.51.7
0.60.1
267.9102.1

530.238.6
9.31.3
9.41.3
14.33.4
15.93.7
24.82.0
0.70.1
228.479.8

0.03
<0.01
<0.01
0.99
0.03
0.49
0.38
0.07

82.817.4

70.616.1

<0.01

91.826.1

86.327.5

0.36

68.922.3

57.316.2

0.01

71.632.3

58.416.3

0.02

100.434.4

79.725.7

<0.01

4.83.3
5.73.5
0.60.8
9.15.2
1.50.6

3.62.9
4.93.3
0.60.5
10.54.9
1.80.8

0.07
0.29
<0.01
0.24
0.06

73.254.3

79.844.4

0.54

p Values

Values are presented as meanSD.

CCT, central corneal thickness; CH, corneal hysteresis; CRF, corneal resistance factor;
dB, decibel; GAT, Goldmann applanation tonometry; IOP, intraocular pressure; IOPcc,
corneal-compensated IOP; IOPg, Goldmann-correlated IOP; MD, mean deviation; ORA,
Ocular Response Analyser; PSD, pattern SD; RNFL, retinal nerve fibre layer; VF, visual
field.

Trial,18 every 40 m decrease in the CCT increased the risk of

developing a VF defect by 71% and 25%, respectively.
However, CCT was reported not to contribute to VF defect progression in patients with NTG who took topical anti-glaucoma
medications.6 We found that eyes with progressive VF damage
showed thinner central corneas than those without progressive
VF damage, but low CCT was not associated with VF progression in multivariable logistic regression analysis. This implies
that corneal factors other than corneal thickness are probably
associated with glaucoma progression.
The corneal tissue has both viscous and elastic properties in
order to absorb and dissipate applied energy.19 CH reects the
viscous damping in the cornea as a measure of the ability to
resist and repulse after absorbing an external force applied. CRF
is calculated from CH through a linear combination of both
inward and outward applanation pressures. Several studies have
demonstrated that eyes with glaucoma showed lower CH than
normal eyes or those with ocular hypertension.20 Furthermore,
4

Table 4

Factors associated with CH and CCT

CH

CCT

Variable

p Values

p Values

Age
Spherical equivalent (diopter)
Axial length (mm)
Baseline VF MD (dB)
Baseline VF PSD (dB)
IOP g (mm Hg)
IOP cc (mm Hg)
CH (mm Hg)
CCT (m)
Vertical cup/disc ratio
RNFL thickness (average)
RNFL thickness (superior)
RNFL thickness (temporal)
RNFL thickness (nasal)
RNFL thickness (inferior)
Subfoveal choroidal thickness

0.14
0.22
0.18
0.19
0.13
0.06
0.52

0.44
0.13
0.25
0.04
0.32
0.04
0.29
0.14

0.23
0.05
0.12
0.08
0.25
0.62
<0.01

<0.01
0.25
0.02
0.76
<0.01
0.74
0.01
0.23

0.39
0.36
0.37
0.06
0.09
0.43
0.16
0.44

0.05
0.01
0.14
0.14
0.15
0.12
0.19

<0.01
<0.01
<0.01
0.58
0.41
<0.01
0.15
<0.01

0.64
0.93
0.23
0.21
0.17
0.29
0.10

Values in bold indicate associations that were statistically significant (p<0.05).

CCT, central corneal thickness; CH, corneal hysteresis; IOP cc, corneal-compensated
IOP; IOP g, Goldmann-correlated IOP; MD, mean deviation; PSD, pattern SD; RNFL,
retinal nerve fibre layer; VF, visual field.

lower CH might be associated with, and is a potential risk

factor for, rapid glaucoma progression. De Moraes et al11
demonstrated that lower CH was associated with VF progression and could be a marker of increased optic disc susceptibility
to glaucomatous damage, or may be the result of glaucomatous
damage itself. In the prospective longitudinal study, Medeiros
et al12 demonstrated that each 1 mm Hg decrease in CH was
associated with an increase of 0.25%/year in VF index decline.
However, the subjects of both studies were primarily POAG
patients, and it is not reasonable to apply those results to NTG
eyes. Recent studies found structural differences between POAG
and NTG that might be responsible for the different inuence
of IOP on the ONH tissues, and presented the possibility that
different pathophysiologic mechanisms might be involved in
NTG and POAG.3 21 In NTG, normal IOP induces change in
the ONH connective tissue causing RGC damage, similar to
POAG. Park et al3 found that the laminar thickness was thinner
in NTG patients than POAG patients and demonstrated that the
thinner lamina cribrosa of NTG may have contributed to the
structural susceptibility to deformation and mechanical damage,
even at normal IOP and with lower translaminar tissue pressure
gradients. The ndings of the current study that CH and CRF
were signicantly lower in eyes with progressive VF damage,
and low CH (B=0.32, p<0.01) was signicantly associated with
VF progression, presumably resulted from the structural vulnerability of thinner lamina cribrosa in NTG eyes.
Congdon et al10 argued that the association of low CH with
VF progression became non-signicant after adjusting for the
axial length, which supports a probable relationship between
CH and the elasticity of other ocular tissues. CH is a physical
property related to the ability of connective tissues to dampen
pressure changes, and is connected with extracellular matrix
components of the cornea that may be related to those of posterior ocular tissues such as sclera. Previous studies have demonstrated that CH might correlate with the viscoelastic properties
of the posterior segment of the eye, especially of the lamina cribrosa and peripapillary sclera, which are the main load-bearing
Park JH, et al. Br J Ophthalmol 2015;0:16. doi:10.1136/bjophthalmol-2014-305962

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Clinical science
Table 5

Logistic regression with visual field progression as a binary outcome

Variable

Univariable model*
(95% CI)

Age (per decade older)

Gender (female)
Presence of diabetes
Presence of hypertension
Spherical equivalent (diopter)
Baseline VF MD (dB)
Baseline VF PSD (dB)
Baseline IOP (mm Hg)
CH (mm Hg)
CRF (mm Hg)
IOPg (mm Hg)
IOPcc (mm Hg)
CCT (m)
Axial length (mm)
Vertical cup/disc ratio
Subfoveal choroidal thickness
RNFL thickness (average)
RNFL thickness (superior)
RNFL thickness (temporal)
RNFL thickness (nasal)
RNFL thickness (inferior)
Number of VF tests
Number of glaucoma medications

1.03
1.74
1.51
0.83
1.03
1.31
1.13
1.15
0.39
0.59
1.01
1.14
0.97
1.29
8.04
0.99
0.96
0.99
0.97
0.97
0.97
1.04
1.74

(0.99
(0.71
(0.36
(0.26
(0.91
(1.01
(0.90
(0.98
(0.24
(0.42
(0.88
(0.99
(0.95
(0.97
(0.26
(0.98
(0.93
(0.97
(0.94
(0.95
(0.96
(0.94
(0.92

to
to
to
to
to
to
to
to
to
to
to
to
to
to
to
to
to
to
to
to
to
to
to

Multivariable model
p Values

1.06)
4.27)
6.35)
2.58)
1.18)
1.69)
1.41)
1.34)
0.67)
0.85)
1.14)
1.31)
0.99)
1.72)
240.1)
1.00)
0.98)
1.01)
0.99)
1.00)
0.99)
1.14)
3.30)

0.12
0.23
0.57
0.82
0.64
0.04
0.29
0.09
<0.01
<0.01
0.99
0.07
<0.01
0.08
0.23
0.04
<0.01
0.36
0.01
0.06
<0.01
0.41
0.09

(95% CI)

p Values

1.18 (0.96 to 1.44)

0.12

0.32 (0.17 to 0.62)

1.04 (0.52 to 2.04)

<0.01
0.84

0.99 (0.97 to 1.01)

0.35

0.99 (0.98 to 1.00)

0.96 (0.92 to 0.99)

0.08
0.04

0.97 (0.94 to 1.01)

0.09

0.98 (0.96 to 1.01)

0.13

*Univariable model includes each variable independently.

Stepwise multivariable model includes CH and CCT along with other clinical variables.
CCT, central corneal thickness; CH, corneal hysteresis; CRF, corneal resistance factor; GAT, Goldmann applanation tonometry; IOP, intraocular pressure; IOPcc, corneal-compensated IOP;
IOPg, Goldmann-correlated IOP; MD, mean deviation; PSD, pattern SD; RNFL, retinal nerve fibre layer; VF, visual field.

structures of the ONH. Wells et al14 showed that CH was associated with increased deformation of the optic nerve surface
during transient IOP elevations, and demonstrated that CH may
be a surrogate measure of lamina cribrosa backward bowing/
optic disc compliance. In other words, CH may be a parameter
to determine the structural susceptibility of the posterior ocular
tissues surrounding the ONH, independent of more recognised
risk factors for glaucoma progression such as IOP or CCT.
Although we cannot clarify whether lower CH was a consequence of, or a predisposition toward, the thinner lamina cribrosa or lower scleral thickness, we can assume that low CH
reects the increased stiffness and the structural weakness
against stress or strain of posterior ocular tissues. Furthermore,
we can suggest that the greater the degree of structural vulnerability, the more probable that the VF defect will progress.
In the present study, we conrmed a dependence of CH on
IOPcc and found that eyes with VF progression have a lower
CH and a higher IOPcc than eyes without VF progression. This
inverse relationship between CH and IOP is in agreement with
previous studies.12 22 However, IOPcc was not signicantly associated with VF progression in logistic regression models. In our
cross-sectional study, all the subjects were normotensive and
there was no difference in the baseline and the mean follow-up
IOP between progressing and non-progressing eyes. In addition,
the number of glaucoma medications was similar in both
groups. Since these conditions suggested that we could exclude
the impact of an initial IOP or IOP uctuation during follow-up
on VF progression, we believe that the current study could
focus on the relationship between CH and VF progression.
However, further longitudinal studies tracing the change of true
IOP and CH are needed to conrm our hypothesis.
Park JH, et al. Br J Ophthalmol 2015;0:16. doi:10.1136/bjophthalmol-2014-305962

Few studies have investigated the relationship between CH

and both structural and functional changes in glaucomatous
eyes. Lower CH was reported to be signicantly associated with
larger and deeper cups.23 Mansouri et al24 investigated the relationship between CH and both functional and structural glaucoma severity as determined by VF MD or RNFL thickness
measurements. They found weak correlations between CH and
measures of structural and functional damage. The current
study examined the association between both CH and ONH
parameters measured by SD-OCT and the progression of VF
damage. We found that eyes with low CH and progressive VF
loss tended to have lower RNFL thickness, and the average
RNFL thickness showed an independently signicant association
with the progression of VF damage in our multivariable analyses. Our results imply that both CH and RNFL thickness are
associated with the progression of VF damage. This supports
the hypothesis that decreased damping capacity of the cornea
(represented by low CH) as well as increased structural susceptibility of the ONH complex are related to the progression of
glaucoma.
There are several limitations to this study. First, the studys
retrospective nature does not allow identication of a cause
effect relationship between CH and VF progression. Ideally,
prospective studies that assess the CH at baseline should address
whether low CH is indeed a risk factor for progression, as was
shown with CCT in the OHTS. Second, although denition of
progression is not standardised, we focused only on a global
index, the MD slope, in this study. We have to consider including the analysis of VF damages from the probability maps,
point-wise linear regression, or pattern deviation based VF
index. We would like to examine these issues in further studies
5

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Clinical science
in the near future. Finally, patients in this study were treated
with IOP-lowering therapy, and their IOP was within normal
limits at the time of measurement with ORA and during
follow-up. CH may have been increased by IOP-lowering
therapy; the change in CH with IOP lowering is generally mild
and was approximately 0.5 mm Hg. As a result, this study
cannot exclude the pharmacologic effect of anti-glaucoma medications on CH.

CONCLUSIONS
The present study revealed that CH is signicantly and independently associated with VF progression in patients with NTG.
As patients with low CH may experience faster VF deterioration, CH measurements in NTG patients may be valuable in
practice. Prospective longitudinal studies are needed to investigate the relationship between corneal biomechanics and long
term risk of glaucoma progression.
Acknowledgements The authors would like to thank Kyung Ae Kong
(Department of Preventive Medicine, Ewha Womans University, Seoul, Korea) for her
statistical advice.
Contributors Conception and design of study: JHP, K-RC. Conduct of study: JHP.
Collection and management of data: JHP. Analysis and interpretation of data: JHP,
RMJ, K-RC. Preparation of manuscript: JHP, RMJ, K-RC. Review and approval of
manuscript: JHP, RMJ, K-RC.
Competing interests None.

9
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12

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14

15
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Patient consent Obtained.

Ethics approval Ethics approval was provided by the Institutional Review Board at
Ewha Womans University Mokdong Hospital, Seoul, Korea. All parts of the study
were performed according to the tenets of the Declaration of Helsinki.
Provenance and peer review Not commissioned; externally peer reviewed.

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Park JH, et al. Br J Ophthalmol 2015;0:16. doi:10.1136/bjophthalmol-2014-305962

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Significance of corneal biomechanical

properties in patients with progressive
normal-tension glaucoma
Jong Hyuk Park, Roo Min Jun and Kyu-Ryong Choi
Br J Ophthalmol published online January 2, 2015

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