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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
Contact Lens & Anterior Eye 29 (2006) 257–262 www.elsevier.com/locate/clae
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
b
Heart of England Foundation Trust, Solihull, UK 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: [email protected], [email protected] (S. Shah).
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 todate, 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
1367-0484/$ – see front matter # 2006 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clae.2006.09.006
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2. Materials and methods
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.
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 (DGH550, 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.
Fig. 2. Histogram of hysteresis and CRF.
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Fig. 3. Histogram of 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.
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Fig. 5. Scatter plot of relationship between hysteresis and CCT.
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 1:294 þ 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.
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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 phenomenon 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 mm3. 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
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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 deformation [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 environmental 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
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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.
Reference [1] Edmund C. Assessment of an elastic model in the pathogenesis of keratoconus. Acta Ophthalmol 1987;65:545–50. [2] Vito RP, Carnell PH. Finite element based mechanical models of the cornea for pressure loading and indenter loading. Refract Corneal Surg 1991;8:146–51. [3] Reichel E, Miller D, Blanco E, Mastanduno R. The elastic model of central and perilimbal bovine cornea. Ann Ophthalmol 1989;21: 205–8. [4] Orssengo GJ, Pye DC. Determination of the true intraocular pressure and modulus of elasticity of the human cornea in vivo. Bull Mathematical Biol 1999;61:551–72. [5] Friedenwald JS. Contribution to the theory and practice of tonometry. Am J Ophthalmol 1937;20:985–1024. [6] Mow CC. A theoretical model of the cornea for use in studies of tonometry. Bull Mathematical Biophys 1968;30:437–53. [7] Phillips CI, Quick MC. Impression tonometry and the effect of eye volume variation. Br J Ophthalmol 1960;44:149–93. [8] Doughty MJ, Zaman ML. Corneal thickness and its impact on intraocular pressure measures. A review and meta-analysis approach. Surv Ophthalmol 2000;44:367–408. [9] Ehlers N, Branson T, Sperling S. Applanation tonometry and corneal thickness. Acta Ophthalmol 1975;53:34–43. [10] Shah S, Chatterjee A, Mathai M, Kelly SP, Kwartz J, Henson D, et al. Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic. Ophthalmology 1999; 106:2154–60.
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[11] Argus WA. Ocular hypertension and central corneal thickness. Ophthalmology 1995;102:1810–2. [12] Herndon LW, Choudhri SA, Cox T, Damji KF, Shields MB, Allingham RR. Central corneal thickness in normal, glaucomatous and ocular hypertensive eyes. Arch Ophthalmol 1997;115:1137–41. [13] Shimmyo M, Ross AJ, Moy A, Mostafavi R. Intraocular pressure, Goldmann applanation tension, corneal thickness, and corneal curvature in Caucasians, Asians, Hispanics, and African Americans. Am J Ophthalmol 2003;136:603–13. [14] Brubaker RF. Tonometry and corneal thickness. Arch Ophthalmol 1999;117:104–5. [15] Liu J, Roberts CJ. Influence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis. J Cataract Refract Surg 2005;31:146–55. [16] Luce DA. Determining in-vivo biomechanical properties of the cornea with an ocular response analyser. J Refract Cataract Surg 2005;31: 156–62. [17] Tripathi RC, Tripathi BJ. Anatomy of the human eye and adenexa. In: Dawson H, editor. The eye. vegetative physiology and biochemistry. Florida, USA: Academic Press; 1984. p. 1–102.
[18] Muller LJ, Pels E, Vrensen GFJM. The specific architecture of the anterior stroma accounts for the maintenance of corneal curvature. Br J Ophthalmol 2001;85:437–43. [19] Edmund C. Corneal rigidity and ocular rigidity in normal and keratoconic eyes. Acta Ophthalmol 1988;66:134–40. [20] Purslow PP, Karwatowski WS. Ocular rigidity. Is engineering stiffness a more useful characterisation parameter than ocular rigidity? Ophthalmology 1996;103:1686–92. [21] Gloster J, Perkins ES. Distensibility of the human eye. Br J Ophthalmol 1959;43:97–101. [22] Brooks AMV, Robertson IF, Mahoney A. Ocular rigidity and intraocular pressure in keratoconus. Aust J Ophthalmol 1984;12:317–24. [23] Foster CS, Yamamoto GK. Ocular rigidity in keratoconus. Am J Ophthalmol 1978;86:802–6. [24] Mishima S. Corneal thickness. Surv Ophthalmol 1968;13:57–96. [25] Brandt JD, Beiser JA, Kass MA, Gordon MO. Central corneal thickness in the ocular hypertension treatment study (OHTS). Ophthalmology 2001;108:1779–88. [26] Shah S. Accurate intraocular pressure measurement-the myth of modern ophthalmology? Ophthalmology 2000;107:1805–7.
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
b
Heart of England Foundation Trust, Solihull, UK 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: [email protected], [email protected] (S. Shah).
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 todate, 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
1367-0484/$ – see front matter # 2006 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clae.2006.09.006
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2. Materials and methods
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.
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 (DGH550, 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.
Fig. 2. Histogram of hysteresis and CRF.
S. Shah et al. / Contact Lens & Anterior Eye 29 (2006) 257–262
Fig. 3. Histogram of 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.
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Fig. 5. Scatter plot of relationship between hysteresis and CCT.
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 1:294 þ 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.
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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 phenomenon 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 mm3. 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
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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 deformation [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 environmental 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
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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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