Annals of Biomedical Engineering, Vol. 34, No. 10, October 2006 ( 2006) pp. 16281640 DOI: 10.

1007/s10439-006-9191-8

Evaluation of Goldmann Applanation Tonometry Using a Nonlinear Finite Element Ocular Model
AHMED ELSHEIKH ,1 DEFU WANG,1 AACHAL KOTECHA,2,3 MICHAEL BROWN,1 and DAVID GARWAY-HEATH2,3
1 Division of Civil Engineering, Faculty of Engineering, University of Dundee, Dundee, DD1 4HN, UK; 2Glaucoma Research Unit, Moorelds Eye Hospital, London, EC1V 2PD, UK; and 3Department of Optometry and Visual Science, City University, London, UK

(Received 22 February 2006; accepted 29 August 2006; published online: 28 September 2006)

AbstractGoldmann applanation tonometry (GAT) is the internationally accepted standard for intra-ocular pressure (IOP) measurement, which is important for the diagnosis of glaucoma. The technique does not consider the effect of the natural variation in the corneal thickness, curvature and material properties. As these parameters affect the structural resistance of the cornea, their variation is expected to lead to inaccuracies in IOP determination. Numerical Analysis based on the nite element method has been used to simulate the loading conditions experienced in GAT and hence assess the effect of variation in corneal parameters on GAT IOP measurements. The analysis is highly nonlinear and considers the hyper-elastic J-shaped stressstrain properties of corneal tissue observed in laboratory tests. The results reveal a clear association between both the corneal thickness and material properties, and the measured IOP. Corneal curvature has a considerably lower effect. Similar trends have been found from analysis of clinical data involving 532 patients referred to the Glaucoma Unit at Moorelds Hospital, and from earlier mathematical analyses. Nonlinear modelling is shown to trace the behaviour of the cornea under both IOP and tonometric pressure, and to be able to provide additional, and potentially useful, information on the distribution of stress, strain, contact pressure and gap closure. KeywordsTonometry, Numerical modelling. Intra-ocular pressure, Cornea,

INTRODUCTION Intra-ocular pressure (IOP) measurement in tonometry is important for the diagnosis and management of a number of conditions, most notably glaucoma, the second most common cause of irreversible blindness in the world. Goldmann applanation tonometry (GAT) developed in the mid-1950s, is still the internationally accepted standard for IOP determination. It makes a pseudo-static measurement of the force required to atten a xed area of the central cornea and uses this force to estimate the value of IOP. The natural variation in the central corneal thickness (CCT), corneal curvature and material properties, which have a direct bearing on the corneal structural resistance, can aect the accuracy of IOP measurement, and since IOP is a major risk factor for glaucoma and forms part of the classication of ocular hypertension and normal tension glaucoma,13 errors in IOP measurement can lead to the misdiagnosis of these conditions. The possible impact of corneal thickness on IOP measurement using GAT was identied and discussed briey by Goldmann and Schmidt.16 Later studies by Ehlers and co-workers9 drew attention to the effect of CCT on IOP measurement, and the interest in this effect grew further with the advent of refractive surgery procedures involving an iatrogenic thinning of the cornea, see Refs. [5 ,7,18,29,32]. The overall conclusion that can be drawn from these studies is that IOP measurements using tonometry are affected by differences in CCT. While the vast majority of the studies were based on statistical analyses of clinical data, mathematical analysis was successfully used in a number of studies including those by Orssengo and Pye29 and by Liu and Roberts25 and produced results with a similar trend. All found that high CCT led to IOP overestimations while low CCT led to IOP underestimations. However, there is no agreement yet
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ABBREVIATIONS CCT GAT IOP IOPG IOPT PCT central corneal thickness Goldmann applanation tonometry intra-ocular pressure intra-ocular pressure as measured by GAT true intra-ocular pressure peripheral corneal thickness

Address correspondence to Ahmed Elsheikh CEng MICE PhD, Division of Civil Engineering, Faculty of Engineering, University of Dundee, Dundee, DD1 4HN, UK. Electronic mail: a.i.h.elsheikh@ dundee.ac.uk

0090-6964/06/1000-1628/0

2006 Biomedical Engineering Society

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on the pressure correction factors that should be used to consider CCT variations. Other sources of tonometry errors include the corneal curvature as has been reported by Gunvant et al.,18 Liu and Roberts25 and Kanngiesser et al.23 Furthermore, wound healing following surgical procedures is also believed to lead to changes in the biomechanical properties of corneal tissue. These changes, although not yet quantied, are expected to inuence the structural resistance of the cornea and might therefore affect the accuracy of IOP measurements in tonometry.25 The aim of this study is to use numerical modelling based on nonlinear nite element analysis to create a representative model of the GAT procedure. Numerical modelling is adopted as it has the potential to represent real life conditions without having to adopt the simplications necessary with mathematical closed form solutions. The development of the numerical model has undergone a number of stages to optimise its construction and improve its accuracy. The complexity of the ocular structure, both at the microscopic and macroscopic levels, makes it essential to distinguish between the parameters that have a considerable eect on behaviour (and which should therefore be incorporated in model construction), and the parameters which can be ignored for their negligible eect. The construction of the model was followed by a validation process against experimental tests before it was used in a parametric study in which GAT procedure was simulated with dierent values of corneal thickness, curvature and material properties. The results are compared against the outcome of statistical analysis of new clinical data and the results of earlier mathematical analysis.

on the models behaviour. The parameters that were found to have a small or a negligible effect (with an effect on results below 1%) were not considered in the nal construction of the model. The parameters considered in the study10 were the thickness variation between the limbus and the corneal centre, representation of the boundary conditions along the edge of the cornea, the material properties and the corneal topography. The density of the nite element mesh and the cornea discretisation method were also considered. According to the ndings of this study, an optimum model construction involves the following details:

 The discretisation method shown in Fig. 1 is used to

ensure all element internal angles are kept within practical limits (20 and 80). The model follows the structural form of diamatic skeletal domes built in structural engineering applications.27  Solid six-noded elements are used with six degrees of freedom per node (u, v, w, hx, hy, hz). These elements have been found to closely simulate the behaviour of experimental test specimens while enabling a good representation of corneal variable thickness.  The model has a number of element layers to enable tracing the stress and strain distributions across the corneal thickness. The number of layers is at least two under uniform pressures (e.g. IOP) and six under concentrated effects such as point loads and tonometry pressures. This feature is also important for future development of the numerical model as it

MODEL CONSTRUCTION Nonlinear nite element modelling was used in this research to enable a detailed representation of biomechanical behaviour and to provide a systematic approach to determine the impact of variation in corneal parameters on tonometry. The complexity of the structure and form of the cornea at both the microscopic and macroscopic levels presented a particular challenge during the development of the numerical models. On one hand, there was a desire to simulate the real structure of the cornea in order to improve accuracy, but on the other there was a practical requirement to simplify the models and keep them at a reasonable level of complexity to reduce computational cost. In order to strike the best balance between computational cost and accuracy, a study10 was conducted to identify the effect of individual parameters

FIGURE 1. Discretisation method adopted in construction of corneal modelmodel shown has 6 segments, 7 rings and 294 elements per layer.

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allows the use of different material properties for the epithelium, endothelium and stroma when they become available. The minimum number of elements in each layer is 294, arranged in six segments and seven rings. Although the model predictions with this number of elements are close to experimental observations, more elements, and hence a ner mesh, would be needed if smooth contour distributions are to be obtained. The thickness variation between a minimum at the centre to a maximum along the limbus is modelled to approximate natural topography. The corneal model is provided with edge roller supports oriented at 23 to the limbal plane. This choice of boundary conditions and orientation angle creates working conditions similar to those created by the actual connection to the sclera, see Fig. 2. In arriving at this angle, a whole eye model was compared to a cornea-only model provided with edge roller supports. The angle or orientation of the roller supports was varied until the behaviour predictions of the two models under both distributed pressure and concentrated load were in close agreement (less than 2% on average). Details of this study can be found in Refs. [1,10]. The corneo-scleral intersection is oval (elliptical) with the temporalnasal diameter (DTN) 10% larger

than the inferiorsuperior diameter (DIS). At the same time, constant curvature is assumed along the corneas two main meridian lines. This choice of topography, which represents an approximation of the actual aspheric form of the cornea, was necessary because of (1) the lack of available corneal topography maps and (2) the need to adopt an easy to dene and modify topography in the numerical models.  The nonlinear material properties of corneal tissue observed in laboratory tests1 are incorporated in the model. The stressstrain relationship observed demonstrates clear hyper-elastic behaviour with an initial low stiffness phase followed by another with much higher stiffness. The effect of using a simplied linear-elastic material model in Goldmann tonometry modelling is illustrated in this paper. The nonlinear material stressstrain property is incorporated using a hyper-elastic material model based on Ogdens strain energy function28: U
N X 2ui i1

a2 i

kai kai kai 3 1 2 3

N X 1 Jel 12i Di i1

1 where U is the strain energy per unit volume, ki are the principal stretches, N is a material parameter dening

(a)

Angle

(b) 0.025
Intra-ocular pressure (N/mm2)
0.02 0.015 0.01 0.005 0 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7

Cornea model - 15 roller supports Cornea model - 20 roller supports Cornea model - 23 roller supports Cornea model - 30 roller supports Cornea model - 40 roller supports Whole eye model

Central corneal rise (mm)

FIGURE 2. Corneal model with roller edge supports to simulate actual connection with the sclera. (a) Angle h found from comparisons with a full ocular model to be 23 (Ref. [10]), (b) comparison of behaviour predictions between a whole eye model and a cornea only model under IOP and with different angles h.

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the order of the equation, ui, ai, and Di are temperature-dependent material parameters and Jel is the elastic volume ratio. The Abaqus software package20 is used in this work. The analyses consider both geometric nonlinearities due to change of joint coordinates and material nonlinearities. In tracing the nonlinear behaviour the Riks arc method31 is adopted. In this method, load increments vary according to the current stage of overall behaviour and are controlled automatically such that a solution is obtained even after the point of mechanical failure.

CORNEAL MATERIAL PROPERTIES The material properties of corneal tissue clearly have an eect on the structural resistance of the cornea, and hence the accuracy of IOP measurement. Despite this logical association, the material properties have rarely been considered an important parameter in earlier attempts to improve the accuracy of tonometry. A recent exception is the work published by Liu and Roberts25 which found the material properties to have a profound effect on GAT IOP. There is a wide variation between the material properties reported in earlier publications.33 The variation seems to be related to three main factors, the pressure or stress at which Youngs modulus (E) is determined, the test method and the test strain rate. Hoeltzel et al.,21 for instance, reports two values of E, 0.34 N/mm2 under IOP = 10 mmHg (0.0013 N/ mm2) and 4.1 N/mm2 under IOP = 400 mmHg (0.053 N/mm2). Kampeier et al.22 also reports a lower E = 0.4 N/mm2 at strain = 0.02 and a higher E = 3.00 N/mm2 at strain = 0.08. Other researchers present a hyper-elastic material model with E increasing gradually with strain, yet still the values of initial E vary considerably. For example, Bryant and McDonnell3 have an initial value of 0.08 N/mm2, Zeng et al.36 have E = 0.27 N/mm2 and Nash et al.26 have E = 20.1 N/mm2 (all at strain = 0.01). Another likely reason for the variation is the test method. The strip testing adopted by Nash et al.26 has a number of inherent geometric inefciencies related to the initial curved form of the corneal specimen, which does not lend itself to strip testing.11 On the other hand, ination testing used for example by Bryant and McDonnell,3 which maintains the cornea in its natural working condition, is considered more accurate and its load application speed more representative of the normal state. For this reason, the test method is expected to have a signicant effect on the values of E obtained experimentally. Another factor that adds to the variation in material models is the highly visco-elastic behaviour of corneal tissue. This behaviour makes the material properties dependent on the strain rate used in testing. For this reason, it is signicant that the studies discussed above adopted dierent strain rates and in some cases, the strain rates were not reported. In this work, a stressstrain relationship of the form shown in Fig. 3 with an initial E = 0.30 N/mm2 is used. This relationship has been obtained from a limited experimental study conducted earlier by the authors11 and is quite similar to the results reported by Hoeltzel et al.,21 Kampeier et al.22 and Zeng et al.36 However, as will be seen below, the parametric studies on effect of CCT and R have been repeated considering

CORNEAL THICKNESS Several recent studies measured corneal thickness in recognition of its likely eect on tonometry measurements. Most studies concentrated on the central corneal thickness and used analysis of clinical observations to give its average value and range of variation. The average values of CCT vary slightly between studies, for instance: 0.548 mm is reported by Cho and Cheung4 and 0.545 mm for the right eye and 0.547 mm for the left eye by Lam and Chan.24 The natural variation of CCT in the population was also estimated in earlier studies including Feltgen et al.12 who reported values between 0.448 and 0.713 mm. In the present numerical study, a wider range of variation in CCT is considered; between 0.320 and 0.720 mm to go beyond the natural range. The relationship between the CCT and the peripheral corneal thickness (PCT) is not yet established. While it is known that PCT is always larger than CCT, it is not clear whether PCT changes with CCT, and if so by what degree. In this study, it is assumed that PCT is always 0.150 mm larger than CCT. This is compatible with the corneal dimensions of the Gullstrands No. 1 schematic eye,1 in which CCT = 0.520 mm and PCT = 0.670 mm.

CORNEAL CURVATURE Corneal curvature variation has been considered as another possible cause of error in tonometry measurements.6 The radius of anterior curvature, R, the term used to describe corneal curvature, is found by Doughty and Zaman6 to change between 7.53 and 8.09 mm for children, 7.58 and 8.14 mm for adults, and 7.36 and 7.86 mm for elderly adults. Similar values, between 7.60 and 8.14 mm, are reported by Dubbelman et al.8 A wider range of variation in R between 7.20 and 8.40 mm is considered in this study to determine the effect of corneal curvature on IOP measurements.

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0.14 0.12

ELSHEIKH et al.

Stress (N/mm2)

0.1 0.08 0.06 0.04 0.02 0 0 0.02

Model with initial E = 0.30 N/mm2 Model with initial E = 0.08 N/mm2

0.04

0.06

0.08

0.1

0.12

0.14

Strain (mm/mm)
FIGURE 3. Material studies. models considered in parametric

another material model with initial E = 0.08 N/mm2 to demonstrate the effect of variation in material properties on GAT IOP. This additional model, which was obtained from work by Bryant and McDonnell,3 is also shown in Fig. 3. Note should be made that the material properties obtained from ination tests and reported in the literature were recorded after loading the cornea to the ination point. Before this point, the corneal behaviour was unstable and the readings remained inconsistent until the cornea had taken its natural inated form. For this reason and since the numerical models described in this paper are based on these material properties, these models can only describe the behaviour beyond the ination point.

RESULTS Analysis of a Case with Calibration Dimensions GAT is based on the modied ImbertFick law, which states that the tonometric pressure, and the eect of surface tension along the edge of the tonometer caused by the tear lm, equal the IOP and the eect of the bending resistance of the cornea, see Fig. 4. Using experimental observations made by Goldmann and Schmidt,17 Ehlers et al.9 and Whitacre et al.,34 it is found that for certain corneal dimensions, the effect of surface tension cancels out the effect of bending resistance. As a result, the external tonometry pressure at applanation, (also called the intra-ocular pressure measured using Goldmann tonometry, or IOPG) equals the true intra-ocular pressure, denoted IOPT. In this special case, the correction factor, K = IOPG/IOPT equals 1. The corneal dimensions at which this special case arises are called the calibration dimensions, namely CCT = 0.520 mm and R = 7.80 mm. Numerical modelling of GAT starts with this special case and the value of the numerical

correction factor is compared with the expected value of 1 found experimentally. In this work, a corneal model with 17,424 six-noded solid elements arranged in 6 layers and 22 rings is used. This large number of elements has been necessary to model the concentrated eect of tonometry and to create a ne mesh at the contact area with the tonometer. The tonometer model, which has a 3.06 mm diameter, uses similar solid elements. The anterior surface of the cornea and the posterior surface of the tonometer are described in the analysis as contact surfaces to prevent over-closure of the gap between them. The edge supports of the cornea are roller supports set at 23 to the limbal plane in order to represent the eect of connection with the sclera.10 The material properties used in the analysis have an initial Youngs modulus, E = 0.30 N/mm2. When analysed using the Ogden strain formula given in Eq. (1) and assuming a forth order (N = 4) for improved accuracy, the following values of u and a parameters are obtained: u1 = )110.3, u2 = 55.64, u3 = 108.2, u4 = )53.54, a1 = 14.97, a2 = 16.06, a3 = 12.93, a4 = 11.99. These values provide a close t with the stressstrain relationship with initial E = 0.30 N/mm2 shown in Fig. 3. Note that since the extrabrillar matrix of the cornea is principally water, the corneal tissue is characterized as a nearly incompressible material.3,19,22,30,33 In Abaqus,22 materials dened as incompressible are given an elastic volume ratio, Jel, of 1. Further, when the material response is incompressible, the solution to the analysis problem cannot be obtained in terms of the displacement history only since a hydrostatic pressure can be added without changing the displacements. This difculty is removed in Abaqus by treating the pressure as an independently interpolated basic solution variable, coupled to the displacement solution through the constitutive theory and the compatibility condition, with this coupling implemented by a Lagrange multiplier. This process is implemented through the use of hybrid elements that use a mixture of displacement and stress variables with
Tonometric pressure Bending resistance Surface tension

FIGURE 4. Corneal deformation under IOP and tonometric pressure.

In t ra -

oc

re ssu pre r ul a

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an augmented variational principle to approximate the equilibrium equations and compatibility conditions. Further details of this process can be found in the program documentation.20 The analysis starts by subjecting the corneal model to an IOP with a predetermined value of 0.002 N/mm2 (15 mmHgapproximately at middle of normal IOP range), acting as uniform pressure on the internal faces of the internal layer of solid elements. After ination under full IOP, the model is subjected to contact pressure from the tonometer, which is pushed gradually and concentrically against the cornea until complete applanation is achieved. The stress distributions recorded during this process are shown in Fig. 5. It can be seen that increases in stress are limited to the tonometer contact area with limited effect elsewhere. The closure of gap between the tonometer and the corneal anterior surface is continuously monitored during the analysis to determine the point at which applanation has occurred. Figure 6 shows the progress of gap closure over ve stages of the analysis, the last of which represents the point of full applanation. The contact stress distribution between the tonometer and the corneal anterior surface is also monitored during the progress of applanation. It is interesting to observe how the maximum values of contact stress change location with the progress of applanation, see Fig. 7. At the start, the stress is highest at the centre of

the tonometer as this is where the contact is initiated. Then as applanation progresses, the area of highest contact stress shifts away from the centre and nally locates at approximately half the tonometer radius at full applanation. At applanation, the force required to push the tonometer model to this point is divided by the contact area to obtain the external pressure. This pressure is produced in actual tonometry by two eects, one is the tonometry pressure (referred to as Goldmann IOP or IOPG) and the other is the eect of tear lm surface tension. The value of surface tension is taken as 0.0455 N/m from work carried out at the University of New South Wales and not yet published. This value is slightly less than that for water, 0.0728 N/m. The surface tension acts along the edge of the contact area. Therefore, its eect on the IOPG calculations is determined by multiplying the surface tension by the tonometer perimeter (2 1.53p) and dividing it by the contact area (1.532p). The resulting pressure is subtracted from the previously calculated external pressure to calculate IOPG. In the analysis, the true intra-ocular pressure (IOPT) applied is 0.002 N/mm2 (15 mmHg) and the external pressure is determined as 0.002074 N/mm2. The small effect of tear lm surface tension is 0.0455 10)3 (2 1.53p)/(1.532p) = 0.000059 N/mm2. Therefore IOPG = 0.002074 0.000059 = 0.002015 N/mm2 = 15.11 mmHg. This

FIGURE 5. Stress distribution during the analysis: (a) following application of IOP = 0.002 N/mm2 (15 mmHg), (b) following full applanationview without tonometer, (c) following full applanationview with tonometer. Contours are drawn on model with original undeformed geometry. Stress range: red = 0.09 N/mm2, blue = 0.00 N/mm2.

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FIGURE 6. Closure of gap between the tonometer and the corneal anterior surface over ve stages of analysisthe last stage marks the full applanation pointFigure shows the tonometer and part of the corneal anterior surface with contours drawn on model with original undeformed geometry. Gap width range: red = 0.150 mm, blue = 0.00 mm.

FIGURE 7. Distribution of contact pressure on the tonometer surface with the progress of applanationgure shows the tonometer and part of the corneal anterior surface with contours drawn on model with original undeformed geometry. Contact stress range: red = 0.0045 N/mm2, blue = 0.00 N/mm2.

gives a correction factor = 15.11/15 = 1.007. This value is close to 1.0, which is expected with the calibration dimensions. Eect of Material Modelling Approaches The analysis of the above case with the calibration dimensions has been repeated with the adoption of a constant E equal to the initial E of the model (E = 0.30 N/mm2). In this case, applanation is achieved under an external pressure of 0.001714 N/mm2. After removing the effect of surface tension, IOPG is found as 0.001655 N/mm2 or 12.42 mmHgwith an error of 2.58 mmHg or 17.2%. Further study of the behaviour of the numerical model with both the linear and nonlinear material denitions reveals signicant differences in behaviour. For instance Fig. 8 shows the anterior displacement of points along a corneal meridian line starting from the centre. The model with

hyper-elastic material denition demonstrates a nonlinear displacement rate during both ination and applanation, giving a strong indication that the stress regime within the model rose beyond the initial low stiffness phase of the material. This behaviour is not detected with linear material denition where the displacement rate is almost linear and as a result, applanation is achieved at a different pressure level. It has therefore been concluded that the nonlinear material model should be used in all further GAT modelling since the stresses generated during the procedure could exceed those associated with the rst low-stiness phase of material behaviour. Parametric Study 1Eect of Variation in CCT Figure 9 shows numerical estimation of the effect of CCT variation on IOP measurements using GAT (IOPG). The gure shows the results obtained with

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After application of IOP
After application of IOP

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(a)

Beforea pplication of IOP

Before application of IOP

(b)

Point of applanation

8.3

8.8

Anterior displacement of corneal surface (mm)

8.2 8.1 8.0 7.9 7.8 7.7 7.6 Centre point Intermediate point Intermediate point Intermediate point Intermediate point

Anterior displacement of corneal surface (mm)

8.6

8.4

8.2

Centre point Intermediate point Intermediate point Intermediate point Intermediate point Point under edge of tonometer Point outside tonometer area

8.0

Point under edge of tonometer Point outside tonometer area

7.8

7.6

IOP = 0 to 15 mmHg

Tonometric pressure (exceeding point of applanation)

IOP = 0 to 15 mmHg

Tonometric pressure (exceeding point of applanation)

FIGURE 8. Anterior displacement of the corneal surface under the tonometer during both ination and applanation. (a) Model with nonlinear material properties, (b) model with linear material properties.

two material models, with initial Youngs modulus, E = 0.30 and 0.08 N/mm2, respectively. Within the CCT range considered (between 0.320 and 0.720 mm), IOPG changes by 7.03 and 2.35 mmHg (or 1.75 and 0.60 mmHg per 0.100 mm variation in CCT) for the two material models, respectively. In all cases, R is kept constant at 7.8 mm. The effect of CCT on IOPG for the rst material model (0.0175 mmHg per 1 lm) is comparable to values obtained earlier in population based studies. Earlier values include 0.015 and 0.018 by

Foster et al.,15 0.018 and 0.024 by Foster et al.14 and 0.019 mmHg by Wolfs et al.35 The results indicate that IOP is overestimated with CCT values larger than 0.520 mm and underestimated with CCT values below it. There is also evidence that the change in material stiness has a clear eect on the response to CCT variation. With a stier material, the corneal resistance increases and makes the CCT thickness eect on IOPG more pronounced.

Parametric Study 2Eect of Variation in R

22 21 20
Material model with initial E = 0.30 N/mm2 Material model with initial E = 0.08 N/mm2

IOPG (mmHg)

19 18 17 16 15 14 13 12 0.3 0.4 0.5 0.6 0.7 0.8

CCT (mm)
FIGURE 9. Numerical estimation of the inuence of CCT on IOP measurement using GAT for two material models IOPT = 15 mmHg in all cases.

The numerical estimation of the eect of corneal curvature, as described by the anterior radius, R, on IOPG is depicted in Fig. 10. In this numerical study, R is varied between 7.2 and 8.4 mm, while CCT is kept unchanged at 0.520 mm. The study has been conducted twice for material models with initial Youngs modulus of 0.30 and 0.08 N/mm2. As R increases, the corneal curvature decreases leading to a reduction in the structural resistance and hence an underestimation of IOP. With R increasing from 7.2 to 8.4 mm, IOPG reduces by 1.63 and 1.58 mmHg (or 1.35 and 1.32 mmHg per 1.0 mm variation in R) for the two material models, respectively. The changes in IOPG are more pronounced with R below the calibration value of 7.8 mm.

Point of applanation

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2

ELSHEIKH et al.

Material model with initial E = 0.08 N/mm2

16 15 14 13 12 7 7.2 7.4 7.6 7.8 8 8.2 8.4 8.6

Anterior radius, R (mm)

FIGURE 10. Numerical estimation of the inuence of R on IOP measurement using GAT for two material models. IOPT = 15 mmHg in all cases.

Parametric Study 3Eect of Variation in Material Constitutive Relationship The third parametric study considers ve material models including the models with initial Youngs modulus, E = 0.30 and 0.08 N/mm2. The other three models have an initial E = 0.15, 0.60 and 1.20 N/ mm2. The results of considering different material models on IOPG are illustrated in Fig. 11. The change in IOPG caused by the maximum change in material properties (from E = 0.08 to 1.20 N/mm2) is 17.0 mmHg, most of which is observed when the material model is stiffer than 0.30 N/mm2. Clinical Data: Methods The results from the modelling study were compared to those obtained from a clinical dataset from the Glaucoma Research Unit, Moorelds Eye Hospital, London. GAT IOP, ultrasound measured CCT and central corneal curvature measurements were acquired from 532 eyes of 532 new referrals to the Unit over a 14-month period. None of the patients were taking topical IOP-lowering medication. Measurement of CCT and corneal curvature were obtained by one of four technicians, and GAT IOP measurements were made by a single experienced clinician. CCT measurements were performed using a contact ultrasound pachymeter (20 MHz solid tip probe; Optikron 2000, Roma, Italy). R measurements were made with a noncontact keratometer (IOLMaster; Carl Zeiss Meditec, AG, Germany). The device measures the curvature of a 2.3 mm diameter circular area of the central cornea. Only one eye per patient was used in the analysis. In an attempt to isolate the relative eects of R and CCT on GAT IOP measurements, two analyses were performed. The rst investigated the eect of varying

CCT on GAT IOP measurements for three R ranges (110 eyes with R = 6.87.5 mm, 317 eyes with R = 7.517.9 mm, 105 eyes with R = 7.918.6 mm) whilst the second assessed the effect of R on GAT IOP measurements for three CCT ranges (126 eyes with CCT = 410530 lm, 290 eyes with CCT = 531 590 lm, 116 eyes with CCT = 591660 lm). The results are presented graphically in Figs. 12 and 13. Linear predictive models were chosen to assess the relationships between corneal parameters and GAT IOP measurement. The purpose of this exercise was to assess how clinical ndings related to our numerical studies, and it was felt that a linear analysis would give a good indication of agreement, if any. GAT IOP measurements increased with increasing CCT in all R groups, of the order between 1.6 and 3.3 mmHg per 0.1 mm increase in CCT. The trend was most signicant in the 7.58.6, or at and middle ranges of corneal curvature, where CCT accounted for approximately 7.5% of the measurement variation. This suggests that although the effect of CCT has a statistically signicant effect on GAT IOP measurements, its effect is small compared with other sources of measurement variation. Other sources of variation include the technique of IOP measurement in the clinical setting (which is subject to both inter- and intra-observer variation), variation in IOPT, variation in the effect of CCT at different IOPT, and, potentially, variation in corneal material properties, all of which will add to the spread of data. This measurement imprecision is a source of noise which may mask the effect of corneal parameters on IOP measurement. Therefore, it is possible that the effect of CCT may be a greater predictor of GAT IOP measurement than the ndings suggest. The composite graph showing the linear trends for all three R ranges suggests that the GAT IOP measurement is somewhat underestimated

IOPG (mmHg)

35 30

IOPG (mmHg)

25 20 15 10 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4

Initial E (N/mm2)
FIGURE 11. Numerical estimation of the inuence of material properties on IOP measurement using GAT. IOPT = 15 mmHg in all cases.

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35 30

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(a)

IOPG = 0.0162xCCT + 8.8808 R2 = 0.0246

35 30

(b)

IOPG = 0.0334xCCT - 1.0115 R2 = 0.0746

IOPG (mmHg)

20 15 10 5 0 400 500 600 700

IOPG (mmHg)

25

25 20 15 10 5 0
400 500 600 700

CCT (m)

CCT (m)

35 30

(c)

IOPG = 0.0305xCCT + 0.3053 R2 = 0.0761

25 20

(d)

IOPG (mmHg)

IOPG (mmHg)

25 20 15 10 5 0 400
500 600 700

15

R=6.8 to 7.50
10 5 0 400

R=7.51 TO 7.9 R=7.91 to 8.6

500

600

700

CCT (m)

CCT (m)

FIGURE 12. Analysis of clinical observation to determine the effect of CCT variations on intra-ocular pressure readings using GAT. (a) Observations for patients with anterior radius between 6.8 and 7.5 mm, (b) observations for patients with anterior radius between 7.51 and 7.9 mm, (c) observations for patients with anterior radius between 7.91 and 8.6 mm, (d) linear trend lines for the above three cases.

in at corneas (R range 7.58.6 mm) compared with more curved corneas (R range 6.87.5 mm). Changes in R produce similar effects, but, as in the numerical model, are not as signicant as changes in CCT, and only account for up to 2% of the measurement error. As R becomes progressively greater, the result is an underestimation of IOP of the order of 2 mmHg per 1 mm change in R, although the effect is considerably smaller in the middle range of CCT between 531 and 590 lm. Overall, the clinical data suggests that in eyes with steep (R between 6.8 and 7.5 mm) and thick (591 660 lm) corneas, the GAT IOP measurement is overestimated.

DISCUSSION There is strong evidence that nonlinear material properties should be adopted in reproducing the behaviour of the human cornea under Goldmann tonometry. The displacement change during both ination and

applanation is nonlinear, giving an indication that the stress regime within the model rose beyond the initial low stiness phase of the material. Simplifying the analysis by considering only the initial Youngs modulus leads to considerable results variation and signicant underestimation of intra-ocular pressure. The numerical model has been successful in obtaining a correction factor close to 1 for an eye with the calibration dimensions (CCT = 0.520 mm, R = 7.8 mm) and with a nonlinear material model with an initial E of 0.30 N/mm2. This case was studied in detail to show that the GAT procedure did not lead to notable changes in the stress distribution in the cornea outside the applanated area. The analysis also showed that the contact pressure between the tonometer and the anterior cornea was not uniform, but reached its maximum value along a ring with about half the tonometer radius. The model with the nonlinear material properties predicts a clear eect of CCT and R variation on IOP as measured using Goldmann tonometry. The effect is more pronounced with CCT values above 0.520 mm and R

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35 30

ELSHEIKH et al.

(a)

IOPG = -2.335xR + 34.102 R2 = 0.0192

35 30

(b)

IOPG = -0.2557xR + 19.718 R2 = 0.0002

IOPG (mmHg)

20 15 10 5 0 6.6 7.1 7.6 8.1 8.6

IOPG (mmHg)

25

25 20 15 10 5 0
6.6 7.1 7.6 8.1 8.6

R (mm)
35 30

R (mm)

(c)

IOPG = -2.0711xR + 35.302 R2 = 0.0161

25 20

(d)

IOPG (mmHg)

IOPG (mmHg)

25 20 15 10 5 0 6.6

15 10 5 0

CCT = 410 - 530 CCT = 531 - 590 CCT = 591 - 659

7.1

7.6

8.1

8.6

6.6

7.1

7.6

8.1

8.6

R (mm)

R (mm)

FIGURE 13. Analysis of clinical observation to determine the effect of anterior radius variations on intra-ocular pressure readings using GAT. (a) Observations for patients with CCT between 410 and 530 lm, (b) observations for patients with CCT between 531 and 590 lm, (c) observations for patients with CCT between 591 and 660 lm, (d) linear trend lines for the above three cases.

below 7.8 mmcollectively termed the calibration dimensions. With IOPT of 15 mmHg, a nonlinear material model with initial Youngs modulus, E = 0.30 N/mm2, increasing CCT from 0.520 mm to 0.620 and 0.720 mm (i.e. increases by 19% and 38%) results in IOP overestimations by 12.0% (16.96 ) 15.11 = 1.85 mmHg) and 30.8% (19.84 ) 15.11 = 4.73 mmHg), respectively. Reducing CCT by the same percentages leads to smaller IOP underestimations of 9.0% (15.11 ) 13.73 = 1.38 mmHg) and 15.0% (15.11 ) 12.71 = 2.30 mmHg). The study with a less stiff material model (initial E = 0.08 N/mm2) shows consistently smaller effect of CCT variation on IOP measurement. The eect of changes in R is less notable. Reducing R from 7.8 mm to 7.5 and 7.2 mm results in IOP overestimations of 3.1% (15.59 ) 15.11 = 0.48 mmHg) and 6.4% (16.07 ) 15.11 = 0.96 mmHg), respectively. On the other hand, increasing R to 8.1 and 8.4 mm leads to slightly smaller effects of 3.1% (15.11 ) 14.63 = 0.48 mmHg) and 4.1% (15.11 ) 14.49 = 0.62 mmHg). The effects on IOP measurement are again slightly reduced when using the less stiff material model. These results are compatible with the previously reported eect of CCT and R on the structural resistance

of the cornea against applanation. Also as CCT is the factor with the higher effect on the structural resistance, it is expected that its variation will lead to larger discrepancies in IOP measurement. The material model is also found to have a profound eect on IOP measurements when studied separately. The range of variation in initial Youngs modulus is varied within a wide range (0.081.2 N/ mm2). The effect of increasing the material stiffness by a factor of 4 (from 0.30 to 1.2 N/mm2) is found to lead to a large overestimation of IOP by 100.9% (30.35 ) 15.11 = 15.24 mmHg) while reducing the stiffness by the same factor (from 0.30 to 0.08 N/mm2) only results in 11.9% underestimation of IOP (15.11 ) 13.31 = 1.80 mmHg). It should be noted here that clinical research is needed to determine the actual range of variation in material stiffness to be expected between different people, during the life span of the same person and even during the different hours of day. The results of the numerical study have been compared with the statistical results of the clinical data and also the earlier mathematical predictions made by Liu and Roberts25 and by Orssengo and Pye.29 The data

Assessment of Goldmann Tonometry Using Numerical Modelling

1639

available for comparison were provided by Liu and Roberts who used CCT = 0.526 mm, R = 7.8 mm and E = 0.19 N/mm2. Orssengo and Pye used CCT = 0.520 mm, R = 7.8 mm and E was taken as a function in IOP in the form E = 0.0229 IOPT. The comparisons are shown in Figs. 1416. The overall trends in all cases are similar and there is a notable measure of agreement between the results, particularly between our data and those obtained by Liu and Roberts. The clinical data also shows a similar trend to the numerical results in spite of three possible sources of error. Firstly, referrals to the Glaucoma Unit are usually on the basis of high IOP, unlike the numerical

40 35

IOPG (mmHg)

30 25 20 15 10 0.1 0.3 0.5 0.7 0.9 1.1 1.3

Present work Orssengo and Pye Liu and Roberts

Initial E (N/mm2)
FIGURE 16. Effect of material stiffness on IOP measurement as predicted by the present numerical study, and the mathematical modelling carried out by Liu and Roberts and Orssengo and Pye. In their analysis, Liu and Roberts used CCT = 0.526 mm and R = 7.8 mm. Orssengo and Pye used CCT = 0.520 mm and R = 7.8 mm. These values were also adopted in present numerical analysis.

25 23 21

IOPG (mmHg)

19 17 15 13 11 9 7 5 0.4 0.45 0.5 0.55 0.6 0.65 0.7

Present work Orssengo and Pye Liu and Roberts Clinical data

CCT (mm)
FIGURE 14. Effect of CCT variation on IOP measurement as predicted by the present numerical study, the mathematical modelling carried out by Liu and Roberts and by Orssengo and Pye, and the statistical analysis of clinical data for eyes with R between 7.51 and 7.9 mm. In their analysis, Liu and Roberts used R = 7.8 mm and E = 0.19 N/mm2. Orssengo and Pye used R = 7.8 mm and E = 0.0229 IOPT.

models which have a moderate IOP of 15 mmHg. Secondly, the clinical dataset is likely to have a higher than usual percentage of individuals with stiffer and/or thicker corneas, as these properties result in overestimated IOP measurements. Thirdly, the assumption of an almost spherical topography in the numerical models represents an approximation of the actual corneal topography. However, the match between the numerical and clinical data remains encouraging and should be indicative of the validity of the simulations used.

REFERENCES
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20 19 18

IOPG (mmHg)

17 16 15 14 13 12 11 10 7 7.5 8 8.5 9

Present work Orssengo and Pye Liu and Roberts Clinical data

R (mm)
FIGURE 15. Effect of R variation on IOP measurement as predicted by the present numerical study, the mathematical modelling carried out by Liu and Roberts and Orssengo and Pye, and the statistical analysis of clinical data for eyes with CCT between 460 and 530 lm. In their analysis, Liu and Roberts used CCT = 0.526 mm and E = 0.19 N/mm2. Orssengo and Pye used CCT = 0.520 mm and E = 0.0229 IOPT.

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