www.elsevier.com/locate/clae

Contact Lens & Anterior Eye 29 (2006) 257–262

The use of the Reichert ocular response analyser to establish the

relationship between ocular hysteresis, corneal resistance

factor and central corneal thickness in normal eyes

Sunil Shah a,b,c,*, Mohammed Laiquzzaman a, Ian Cunliffe a,b,c, Sanjay Mantry a,c

a Heart of England Foundation Trust, Solihull, UKb Ophthalmic Research Group Neurosciences Research Institute, Aston University, Birmingham, UK

c Birmingham and Midland Eye Centre, Birmingham, UK

Abstract

Purpose: The aim of this study was to measure ocular hysteresis and corneal resistance factor (CRF), novel methods of analysing ocular

rigidity/elasticity and to determine the relationship between central corneal thickness (CCT), hysteresis and CRF in normal subjects.

Design: Prospective, cross-sectional, clinical trial.

Participants: The study included 207 normal eyes.

Methods: Hysteresis and CRF were measured by the ocular response analyser. The CCTwas measured using a hand held ultrasonic pachymeter.

Main outcome measures: Ocular hysteresis and CRF in normal patients and their relationship with CCT.

Results: The mean hysteresis was 10.7 � 2.0 mmHg standard deviation (S.D.) (range 6.1–17.6 mmHg); the mean CRF was 10.3 � 2.0 (range

5.7–17.1 mmHg). The mean CCT was 545.0 � 36.4 mm (471–650 mm). The relationship between hysteresis and CCT; CRF and CCT; CRF

and hysteresis were significant ( p < 0.0001).

Conclusion: This study demonstrated that corneal hysteresis increased with increasing CCT, however, the correlation was moderate. It would

appear that CCT, hysteresis and CRF may measure different biomechanical aspects of ocular rigidity and are likely to be useful additional

measurement to CCT in the assessment of ocular rigidity when measuring intraocular pressure (IOP). This may be of particular importance

when trying to correct IOP measurements for increased or decreased ocular rigidity.

# 2006 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Keywords: Hysteresis; Central corneal thickness; Elasticity; Rigidity

1. Introduction

The cornea is a mechanically tough membrane that forms

a barrier between the eye and the external environment.

Several studies have been performed in the past to determine

the rigidity (elasticity) of the cornea [1–4]. Primarily these

were performed to study tonometry [5–7].

Various studies have argued that intraocular pressure

(IOP) measured by the applanation tonometer does not

* Corresponding author at: Heart of England Foundation Trust, Lode

Lane, Solihull, West Midlands B91 2JL, UK. Tel.: +44 121 424 4074;

fax: +44 121 424 5462.

E-mail addresses: sunilshah@doctors.net.uk,

sunilshah@doctors.org.uk (S. Shah).

1367-0484/$ – see front matter # 2006 British Contact Lens Association. Publi

doi:10.1016/j.clae.2006.09.006

always give a true reading [8–12]. More recent studies have

demonstrated the importance of central corneal thickness

(CCT) measurements when trying to assess true IOP rather

than measured IOP [13]. However, these studies were

essentially using CCT as a measure of ocular rigidity and to-

date, CCT has been the most convenient measure of this

parameter [14]. Recently, Liu and Roberts [15] reported that

in their model, tonometry readings did not always reflect

true IOP values—they deviated when CCT, curvature or

biomechanical properties varied from normal values.

Previous studies that have tried to determine ocular

rigidity, have either been performed in vitro and/or involved

complicated mathematical calculations and thus are not

practical for clinicians. To-date, there has not been any easy

method reported to determine the biomechanical properties

shed by Elsevier Ltd. All rights reserved.

S. Shah et al. / Contact Lens & Anterior Eye 29 (2006) 257–262258

Fig. 1. Measurement of ocular hysteresis. 1, convex cornea; 2, flat cornea;

3, concave cornea; 4, flat cornea; 5, convex cornea. Reproduced with

permission from Reichert1.

of the cornea in vivo. Reichert ophthalmic instruments

(Buffalo, NY) have developed a new device: the ocular

response analyser (ORA) which is an adaptation of their

non-contact tonometer that allows measurement of IOP as

well as new measurements called hysteresis and corneal

resistance factor (CRF).

Hysteresis and CRF are determined by releasing an air

puff from the ORA that causes inward and then outward

corneal motion which in turn provides two applanation

measurements during a single measurement process (Fig. 1).

It has been suggested by Reichert that hysteresis may be a

measurement which is the result of the damping of the

cornea because of its visco-elastic properties and is derived

from the difference of the two applanation measurements

during the applanation process. Thus the hysteresis is a

measure of visco-elasticity due to the combined effect of the

corneal thickness and rigidity etc [16]. The ORA also

provides a basis for an additional parameter: CRF. Reichert

believes that CRF is dominated by the elastic properties of

the cornea and appears to be an indicator of the overall

‘‘resistance’’ of the cornea.

This study was performed to measure ocular hysteresis

and CRF and to determine the relationship between CCT,

hysteresis and CRF in normal subjects.

Fig. 2. Histogram of hy

2. Materials and methods

A total of 207 normal eyes of volunteers (42 males and 63

females) were studied. The patients were recruited from the

staff and the relatives of the patients attending the

ophthalmology clinic in a teaching hospital in Birmingham,

UK. The mean age of the subjects was 62.1 � 18.1 years

standard deviation (S.D.) (range 18.0–87.0 years). All

patients had normal eyes on history and examination. None

of the patients were suffering from glaucoma or had suffered

any previous eye surgery/injury or eye infection. They were

not using any topical ocular medication. There was no

history of systemic disease affecting eye.

The study and data accumulation was performed with

approval from the Local Ethical Committee and informed

consent was obtained from each subject participating in

this study.

Hysteresis and CRF were measured while the subject

was sitting comfortably in a chair using the ORA. The

patient was asked to fixate at the target (a red blinking

light) in the ORA, and the ORA was activated by pressing a

button attached to the computer. A non-contact probe

scanned the central area of the eye and released an air puff.

A signal was then sent to the ORA. The ORA then

displayed the IOP, hysteresis and CRF on the monitor of

the computer attached to the ORA (software version 3).

Hysteresis and CRF of both eyes was measured, only one

measurement was taken for each eye. The CCT was

measured using a hand held ultrasonic pachymeter (DGH-

550, DGH Technology Inc., Exton, PA). The patient was

seated in a chair and drop of topical anaesthetic

Proxymethacaine (Bausch & Lomb, Rochester, NY) was

instilled in both eyes prior to performing pachymetry. The

patient was asked to fixate at a target in order to minimise

any eye movement and to avoid damage to the corneal

epithelium. The pachymeter probe was gently placed onto

the mid-pupillary axis in a perpendicular orientation. Upon

contact with the corneal surface, the CCT value was

displayed on the monitor attached to the probe. Three

readings were taken and the mean value was used as

the CCT.

steresis and CRF.

S. Shah et al. / Contact Lens & Anterior Eye 29 (2006) 257–262 259

Fig. 3. Histogram of CCT. Fig. 5. Scatter plot of relationship between hysteresis and CCT.

3. Statistical analysis of data

Several computer packages were used to analyse and

present the data obtained. These included Excel (Microsoft

Corporation, Redmond, WA) and Medcalc (Med Calc

Software, Mariakerke, Belgium).

For general statistical reporting, the mean values

from each data set were calculated along with the S.D.

The distribution of values within each data set were

evaluated graphically. The level of statistical significance

was chosen at p < 0.05. All graphs were constructed using

Medcalc.

4. Results

The mean CCT for all eyes was 545.0 � 36.4 mm S.D.

(range 471–650 mm), hysteresis was 10.7 � 2.0 mmHg S.D.

(range 6.1–17.6 mmHg) and CRF was 10.3 � 2.0 mmHg

S.D. (range 5.7–17.1 mmHg).

Fig. 4. Scatter plot of relationship between CRF and hysteresis.

Figs. 2 and 3 show the frequency of distribution of CCT

and hysteresis and CRF. Fig. 4 is the scatter plot

demonstrating the relationship between CRF and hysteresis.

The correlation coefficient was strong (r = 0.8) and the

relationship was significant ( p < 0.0001). The regression

equation for Fig. 4 is:

CRF ¼ 1:294þ 0:846 hysteresis:

Figs. 5 and 6 are scatter plots demonstrating the

relationship between hysteresis and CCT; CCT and CRF,

respectively.

Regression equations for Figs. 5 and 6 are:

Hysteresis ¼ 0:023� 1:776 CCT

CRF ¼ 0:025� 3:499CCT:

The correlation coefficients were moderate (r = 0.426

and 0.467, respectively) but the relationship was significant

( p < 0.0001) between the three parameters.

Fig. 6. Scatter plot of relationship between CRF and CCT.

S. Shah et al. / Contact Lens & Anterior Eye 29 (2006) 257–262260

Fig. 7. Bland and Altman graph.

Fig. 7 is a Bland and Altman plot which demonstrates that

hysteresis and CRF are not measures of the same parameter.

The data was analysed separately for two eyes (right and

left eyes) and difference was not found to be statistically

significant (paired t-test).

5. Discussion

The corneal stroma constitutes 90% of the corneal

thickness and is a highly specialised tissue which is

responsible for its mechanical and refractive properties [17].

The specific architecture of the most anterior part of the

corneal stroma (100–120 mm) has been suggested to be

responsible for the stability of the corneal shape [18]. The

exact mechanism which maintains the corneal contour itself

is not known, but may be due to the passive distension of

corneal tissues by the IOP. It is the distensibility of the eye

that is maintained due to the corneal mass, the elastic

properties of corneal tissue and the mechanical force acting

on this tissue [1]. However, rigidity or elasticity per se of

corneas are known to vary greatly between individuals [14],

and these parameters have only recently been widely

accepted as important when measuring IOP.

Several studies in the past have been conducted to

investigate the elasticity of the human cornea. Elasticity of a

given tissue can be described as a relationship between stress

and strain [19]. Stress can be described as the force per unit

cross-section applied on a given tissue material. Strain

measures the stretch of a material and can be calculated as a

change in length of the tissue divided by its original length.

Previous studies have investigated the rigidity (elasticity)

of the cornea by pressure and indenter loading [2] but the

results were not found to be consistent. Edmund [1]

investigated rigidity (elasticity) of the cornea by measuring

the radius of the central corneal curvature, the coefficient of

radius variation, the CCT and the coefficient of thickness

variation. Others tried to describe ocular rigidity (elasticity)

using engineering terms for simplicity [20]. Friedenwald [5],

in 1937, devised a formula for ocular rigidity where KP (an

assumed constant scleral rigidity) = dP/dV (V is intraocular

volume and P is the IOP). Further studies found that K was

not constant; K was found to decrease with IOP in human

eyes [21]. It was therefore clear that this was a very

complicated subject.

Purslow and Karwatowski [20] went on to report on an

analysis of ocular rigidity (elasticity) in basic engineering

terms. They analysed various theories and formulae to

determine the ocular rigidity (elasticity). These formulae

were based on the assumption that the eye is perfectly

elastic, a spherical tissue and had a uniform wall thickness

and that the wall material was isotropic and homogenous.

The authors commented that the assumption of homogenous

mechanical properties between sclera and cornea was

‘inherently less defensible’ and that this was a major

problem with such a simplistic model. They suggested that

the engineering analysis only helps to separate the

mechanical properties of the ocular shell from the

morphological factors. They concluded that the phenom-

enon of ocular rigidity (elasticity) was complex, and even

with very simplifying assumptions, the analysis did not lead

to a simple result.

Brooks et al. [22] investigated ocular rigidity in the eyes

of 85 keratoconic patients and 20 normal subjects. They

calculated the ocular rigidity coefficient from a combination

of applanation tonometry and impression tonometry

(Schiotz) using the Friedenwald nomogram and the line

of best fit. Foster and Yamamoto [23] measured ocular

rigidity of the 80 normal human eyes using the Friedenwald

nomogram and reported the rigidity as 2.40 � 0.37 mm�3.

They were of opinion that the Friedenwald method of

calculating ocular rigidity is not accurate and does not

reflect the true visco-elastic properties of the keratoconic

eyes. Orssengo and Pye [4], more recently, determined the

modulus of corneal rigidity (elasticity) in vivo from the

corneal dimensions and applanation tonometry. Although

all these studies are very interesting and have tried to

establish ocular rigidity by different methods but they all

involve complicated mathematical calculations [1,19,22,23]

and are impractical for clinicians. They also report varying

results.

The ORA is a new device developed by Reichert which is

a non-contact tonometer that measures IOP as well as new

metrics; hysteresis and CRF. The ORA is an attempt to make

the measurement of rigidity and elasticity easily accessible

to clinicians for all patients.

Measuring corneal biomechanical properties by the

applanation of a force to the cornea requires a procedure

capable of separating the contributions of the corneal

resistance and the IOP because the corneal resistance and

true IOP are basically independent. The ORA releases a

precisely metered air pulse which causes the cornea to move

inwards. Thus the cornea passes through applanation

(inward applanation), and then to the past applanation phase

S. Shah et al. / Contact Lens & Anterior Eye 29 (2006) 257–262 261

where its shape becomes slightly concave. Milliseconds

after applanation, the air puff shuts off, resulting in a

pressure decrease in a symmetrical fashion. During this

phase, the cornea tries to regain its normal shape and the

cornea again passes through an applanation phase (outward

applanation). Theoretically, these two pressures should be

the same but this is not the case. This is described as the

dynamic corneal response which is said to be the resistance

to applanation manifested by the corneal tissue due to its

visco-elastic properties. The difference between the outward

and inward pressures is termed hysteresis and is measured in

mmHg. Hysteresis is said to be a measurement of viscous

properties whereas the CRF is dominated by elastic

properties of cornea and is an overall indicator of the

corneal resistance.

The cornea reacts to stress as a visco-elastic material, i.e.

for a given stress, the resultant corneal strain is time

dependent. The visco-elastic response consists of an

immediate deformation followed by a rather slow deforma-

tion [19]. The immediate elastic response of the ocular

tunics seems to reflect the immediate elastic properties of the

collagen fibres; the steady state elastic response reflects the

properties of the corneal matrix [19]. The two applanation

pressure readings – ‘inward’ and ‘outward applanation’ – are

perhaps the result of immediate elastic response and delayed

or steady state elastic response, respectively, of the corneal

tissue.

Luce [16] reported the first ever measure of corneal

hysteresis on the ORA. He reported corneal hysteresis in

normal, keratoconus, Fuchs’ dystrophy, and post-LASIK

patients from pooled data from a large number of users and

machines. He reported that hysteresis varied over a dynamic

range of 1.8–14.6 mmHg.

The results of this study on normal eyes performed on a

single instrument also demonstrated a wide range of

individual variation in hysteresis (6.1–17.6 mmHg). The

histogram (Fig. 2) shows the distribution of hysteresis and

CRF. The data was further analysed to assess the correlation

between CRF and hysteresis and the graph (Fig. 4) showed

the relationship was significant p < 0.0001 and correlation

coefficient strong (r = 0.8). However, the Bland and Altman

plot (Fig. 7) confirms that hysteresis and CRF are not the

same measured parameters.

A review by Mishima [24] proposed that CCT in man

averages 518 mm but Doughty and Zaman [8] found that in

recent years, higher value of CCT have been reported and

this, they suggest, may be due to the change in environ-

mental factors or other factors such as diet and living style. A

very wide range (450–600 mm) of values for CCT has been

reported for ‘normal’ corneas [8].

The results in this study also showed wide individual

variations of CCT (471–650 mm). The histogram (Fig. 3)

shows the distribution of CCT, the frequency of the CCT was

highest in the range between 521.0 and 540.0 mm. The

scatter plot (Fig. 5) shows the relationship between CCT and

hysteresis. The regression line shows hysteresis increasing

with increasing CCT (the slope was moderate and the

correlation coefficient r = 0.426 is moderate). This study

found a stronger relationship between these two parameters

than reported by Luce [16].

The scatter plot (Fig. 6) shows the relationship between

CCT and CRF. The graph showed CRF increased with

increasing CCT, the correlation was moderate (r = 0.467)

but the relationship was significant ( p < 0.0001). A

regression analysis reveals that the regression equations

for the relationship between CCT and hysteresis; CCT and

CRF were not the same.

In summary, the results of this study showed that

hysteresis and CRF measured by the ORA have a positive

but moderate correlation to CCT; the higher the CCT the

higher the hysteresis (visco-elasticity) and CRF (elasticity).

The results of this study suggest that hysteresis and CRF and

CCT are related but are not measurements of the same

physical/biomechanical parameter.

The ORA may be a measure of the corneal rigidity in

vivo. The measurement of hysteresis and CRF is easy and

can be performed by any trained technician. It may be

helpful in the future for long term monitoring of glaucoma

and other disease processes of the cornea, for eyes where

IOP measurement is important. It may provide additional

factors over and above CCT for cases in which corneal

biomechanics are important and help with the assessment of

the accuracy of IOP (in the manner that CCT has been found

to be in the ocular hypertension study) [25,26]. Further

studies need to be done to establish the relevance and

usefulness of these measures.

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