SEARCH

SEARCH BY CITATION

Keywords:

  • corneal biomechanics;
  • corneal hysteresis;
  • corneal resistance factor;
  • intraocular pressure;
  • myopia;
  • Ocular Response Analyser

Abstract

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENTS
  7. GRANTS AND FINANCIAL SUPPORT
  8. REFERENCES

Purpose:  The aim was to study the link between refractive error and corneal biomechanical properties.

Methods:  Corneal hysteresis and corneal resistance factor were measured using the Ocular Response Analyser in 117 participants. The spherical equivalent refractive error of the participants ranged between -9.00 and +3.00 D.

Results:  Corneal hysteresis and corneal resistance factor showed a considerable degree of variability between individuals. Corneal hysteresis was not found to correlate significantly with refractive error (p = 0.82). Corneal resistance factor showed a weak but significant correlation with spherical equivalent refractive error (r2= 0.04; p = 0.03), with myopic participants exhibiting a higher corneal resistance factor compared with non-myopes.

Conclusions:  Refractive error accounted for four per cent of the variance in corneal resistance factor measurements, indicating that patients with mild to moderate myopia have higher corneal resistance compared with non-myopes.

Development of refractive errors is associated with structural changes in the eye, especially of the axial length and/or corneal curvature. Some of the changes might be associated with emmetropisation, while others might cause refractive errors. Eyes with high myopia are known to have larger axial lengths and vitreous depths.1,2 Myopic eyes also have thinner retinas with degenerative changes and altered scleral thickness and viscoelasticity.1,3,4 Whether changes to the cornea occur with myopia is still under debate.5–7 Myopes are claimed to have flatter corneal curvature, decreased central corneal thickness (CCT) and decreased corneal endothelial cell density compared with non-myopes.8 Therefore, it is possible that the biomechanical properties of the cornea might alter with refractive error. If any such changes were a precursor to refractive development, their measurement might be a useful way of identifying individuals at risk of myopisation.

Corneal biomechanics have been traditionally studied by in vitro techniques that assess factors such as viscoelasticity, hydration et cetera.9–11 Recently, it has become possible to measure the biomechanical properties of the cornea in a clinical setting with the Ocular Response Analyser (ORA; Reichert Corp, Buffalo, NY, USA). The ORA produces repeatable measurements of corneal biomechanical properties and IOP measurements.12,13

The ORA obtains two applanation pressures, as the cornea has an inward (P1) and outward (P2) movement during the applanation and recovery phase.14 The difference between the two applanation pressure values is known as corneal hysteresis (CH; P1-P2). According to the manufacturer, CH is a result of a viscous damping in the corneal tissue, that is, it is the ‘energy absorption capability’ of the cornea. Luce14 showed that CH is altered in clinical conditions such as keratoconus, Fuchs’ dystrophy and glaucoma. Using P1 and P2, the corneal resistance factor (CRF) is derived to describe the corneal resistance properties (CRF = P1-kP2, where k = 0.7 was found by maximising the correlation between CRF and CCT). According to the Reichert Corporation, the CRF is an indicator of the overall ‘resistance’ of the cornea and of the total corneal response—a cumulative effect of both the viscous and elastic resistance encountered by the air jet. The manufacturer states that the CRF is significantly correlated with CCT and Goldmann tonometry (IOPg) but not with corneal compensated intraocular pressure (IOPcc).

The corneal biomechanical properties in myopes have been studied recently in Singaporean and Chinese populations.15–17 Lim and colleagues15 found that in Singaporean children, CH and CRF were not associated with refractive error or axial length. They also found that flatter corneas were associated with lower CH and CRF. In a study of Chinese children, Song and colleagues17 found that CH showed no correlation with spherical equivalent refractive error but it did correlate with axial length. They found that CH correlated with spherical equivalent refractive error in Chinese children but CRF did not, although both CH and CRF correlated with axial length. Corneal biomechanical properties are known to change with age,18 hence, these findings might not be applicable to adult populations. Shen and colleagues16 measured CH and CRF in highly myopic adults (myopia greater than 9.00 D). They found that CH but not CRF was significantly lower in patients with high myopia when compared with the normal population. The differences in CH were small (means and standard deviations 9.9 ± 1.7 mmHg for the high myopes versus 11.1 ± 1.5 mmHg for the controls). In all of these studies, there were large inter-subject differences (up to several mmHg) in the values of the parameters at any level of refractive error. Plakitsi and colleagues19 studied the association between myopia and corneal biomechanical properties in a predominantly Caucasian population and showed only a weak correlation of CH and IOPcc with the refractive error of normal adult subjects and no correlation in the case of CRF.

In summary, these previous studies have produced conflicting results. The main aim of the present study was to measure the corneal biomechanical properties (CH and CRF) in an adult population to investigate the association between spherical equivalent refractive error and corneal biomechanical properties. In addition, given that measuring corneal biomechanical properties with the ORA is a relatively new technique, by taking these measurements on a relatively large cohort, we provide some normative data for biomechanical properties measured by this approach.

METHODS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENTS
  7. GRANTS AND FINANCIAL SUPPORT
  8. REFERENCES

One hundred and seventeen participants took part in the study, which included 41 males and 76 females. The median age of the subjects was 21 years and the interquartile range was eight years (range: 18 to 65 years). Spherical equivalent refractive error ranged from -9.00 to +3.00 D (mean: -1.78 ± 2.26 D) and the mean cylindrical error was -0.70 ± 0.82 D. All participants had a visual acuity of 6/6 or better, no history of ocular surgery, glaucoma, diabetes or other systemic disease and were not taking any medications. The study followed the tenets of the Declaration of Helsinki. All subjects gave informed consent after being told the purpose of the experiment. The project protocol was approved by the Senate Committee on the Ethics of Research on Human Beings of the University of Manchester.

The Ocular Response Analyser was used to measure monocular CH and CRF with the subjects seated and the head stabilised with a brow bar. The subject was asked to remain stationary and to fixate on the target (red blinking light inside the non-contact probe). The ORA is activated by the examiner and a non-contact probe starts scanning the central area of the eye releasing an air puff when aligned. An initial measurement was performed as a demonstration for the subjects. This initial reading was discarded from the statistical analysis. The process was repeated until three ORA measurements with good quality readings were obtained. After each measurement the ORA graphically displays the corneal response. According to the manufacturer, good quality readings are those where both force in and out applanation signal peaks on the ORA waveform are fairly symmetrical in height.

The refractive error of the participants was measured objectively with an open-view Canon R-1 Auto Refractor (Canon, Tokyo, Japan). No cycloplegics were used. The subjects viewed a six metre target monocularly through the open-field auto-refractor. The Canon R-1 auto-refractor provides refraction results that are highly valid/accurate compared with subjective refraction in the absence of cycloplegia.20,21

For ease of mathematical and graphical representation, the sphero-cylindrical refractive errors obtained from the autorefractor were converted into Fourier power vectors22 using the equations:

  • image
  • image
  • image

where S is the sphere, C the cylinder, α the cylinder axis, M the spherical equivalent refractive error and J180 and J45 are the powers of two Jackson cross-cylinder components.

Data analysis

The relationships between the corneal biomechanical properties, refractive error and age were analysed by means of a linear regression (least squares). A linear regression (least squares) was also performed to study the relationships between spherical equivalent refractive error and both IOPg and IOPcc and the relationships among these parameters and the corneal biomechanical properties. A multiple regression analysis with age, CH, CRF and IOPg as covariates was performed to predict the changes in spherical equivalent. A linear relationship was found to best describe the data obtained. Pearson's correlation was used to test the relationship between CH and CRF. Statistical significance was taken as p < 0.05 with analysis of variance (ANOVA) and unpaired student t-test (GraphPad Prism 5.01, GraphPad Software Inc, San Diego, CA, USA and SPSS 16.0, SPSS Inc. Chicago, IL, USA).

RESULTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENTS
  7. GRANTS AND FINANCIAL SUPPORT
  8. REFERENCES

The distribution of the study parameters is presented in Figure 1.

image

Figure 1. Box-and-whisker plot for corneal hysteresis (CH), corneal resistance factor (CRF), intraocular pressure (IOP) Goldmann (IOPg) and IOP corneal compensated (IOPcc). Average and standard deviation values are presented in mmHg.

Download figure to PowerPoint

The association between CH and spherical equivalent refractive error is shown in Figure 2. The data show a considerable degree of variability between individuals and no significant correlation is seen between CH and spherical equivalent refractive error (p = 0.82). Three readings of CH were taken for each individual and these three readings showed some variability. Figure 3 shows the variance in the CH measurements as a function of spherical equivalent refractive error. As can be noted from Figure 3, the variability is high in some individuals in comparison to others; however, the magnitude of variance is not linked to the spherical refractive error (p = 0.09).

image

Figure 2. Corneal hysteresis as a function of spherical equivalent refractive error (r2 < 0.01; p = 0.82)

Download figure to PowerPoint

image

Figure 3. Variance in corneal hysteresis as a function of spherical equivalent refractive error (r2= 0.02; p = 0.09)

Download figure to PowerPoint

Figure 4 shows the CRF as a function of refractive error. A weak but significant correlation is found between CRF and spherical equivalent refractive error (r2= 0.04, p = 0.03, y = -0.14x + 10.42), with the myopic individuals having a slightly higher CRF in comparison to non-myopes. As with the CH values, inter-subject variability was found to be high and the variance of CRF measurements was not linked to the spherical equivalent refractive error (Figure 5; p = 0.20). A significant correlation between CH and CRF was also observed (r = 0.83, p < 0.01). No significant correlation was found between J180 and J45 and CH and CRF measurements (p > 0.05).

image

Figure 4. Corneal resistance factor as a function of spherical equivalent refractive error (r2= 0.04; p = 0.03)

Download figure to PowerPoint

image

Figure 5. Variance in corneal resistance factor measurements as a function of spherical equivalent refractive error (r2= 0.01; p = 0.20)

Download figure to PowerPoint

Figure 6 shows the relationship between spherical equivalent refractive error and IOPg and IOPcc. A significant correlation was found between spherical equivalent refractive error and Goldmann and corneal compensated IOP (r2= 0.10, p < 0.01, y = -0.43x + 14.46; and r2= 0.07, p < 0.01, y = -0.36x + 14.69, for IOPg and IOPcc, respectively), with higher myopes having higher IOP compared with lower myopes and emmetropes.

image

Figure 6. Relationship between spherical equivalent refractive error and IOPg A. r2= 0.10; p < 0.01 and IOPcc B. r2= 0.07; p < 0.01

Download figure to PowerPoint

IOPg was not significantly correlated with CH (p = 0.52); however, a significant correlation was found between IOPg and CRF with the IOPg increasing with increases in CRF (r2= 0.37, p < 0.01, y = 0.33x + 5.71). IOPcc was negatively correlated with CH (r2= 0.24, p < 0.01, y = -0.25x + 14.60) but was not correlated with CRF (p = 0.38).

Figure 7 shows a histogram with the mean values of CH and CRF as a function of age. There was no significant effect of age on either CH or CRF (r2= 0.01, p = 0.30 and r2= 0.01, p = 0.42, respectively), perhaps due to the limited number of subjects over 40 years of age participating in the study. The variability in CH and CRF values was not linked to the age of the participants.

image

Figure 7. Histogram showing the mean values of corneal hysteresis (light grey) and corneal resistance factor (dark grey) as a function of age. The error bars represent the standard error of the mean for each number of subjects (n).

Download figure to PowerPoint

Differences in corneal biomechanical properties according to participants’ gender were also investigated. Only CH was significantly different between males and females (t = 2.19, p = 0.04), generally being higher in females (mean ± standard error of the mean: 11.02 ± 0.18 mmHg) than in males (10.39 ± 0.21 mmHg).

The results from multiple regression analysis (Table 1) confirmed the previous results showing that only CRF is able to predict changes in spherical equivalent refractive error.

Table 1. Regression analysis looking at the impact of age, corneal hysteresis, corneal resistance factor and IOPg on spherical equivalent
 bSE bβR2
  • p < 0.05.

  • CH: corneal hysteresis, CRF: corneal resistance factor, IOPg: Goldmann tonometry

Step 1    
Constant-2.440.59 0.01
Age0.030.020.11
Step 2   ΔR2
Constant-2.271.66 0.00
Age0.030.020.11
CH-0.020.14-0.01
Step 3    
Constant-1.451.60 0.10*
Age0.030.020.11
CH0.690.240.46*
CRF-0.790.22-0.57*
Step 4    
Constant27.8328.29 0.01
Age0.030.020.13
CH-7.347.75-4.94
CRF8.639.086.24
IOPg-2.832.73-3.83

DISCUSSION

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENTS
  7. GRANTS AND FINANCIAL SUPPORT
  8. REFERENCES

The present study shows a weak correlation between CRF and refractive error and no significant correlation between CH and refractive error in an adult Western population. These findings are broadly in line with previous findings from Lim and colleagues,15 although the values for CH and CRF found in the present study are lower in comparison (CH in the present study of 10.80 ± 1.52 mmHg versus 11.78 ± 1.55 mmHg15 and CRF in the present study of 10.67 ± 1.64 mmHg versus 11.81 ± 1.71 mmHg15). The previous studies examined corneal biomechanical properties in a far Eastern population,15,16 where the prevalence of myopia is considerably higher than that in the Western population.

The differences between the values of CH and CRF found in the present study and the previous work could be due to changes with age18 as the participants in the present study were adults while Lim and colleagues15 included only children. The CH and CRF values in the present study were in accordance with the data of Shen and colleagues.16 The maximum magnitude of myopia in the present study was -9.00 D, whereas all patients in the myopic group investigated by Shen and colleagues16 had myopia greater than -9.00 D. They16 found a significant relationship between CH and myopia with high myopes having lower CH; however, the CRF showed no significant difference between high myopes and normals. We found a weak but significant correlation (r2= 0.04) between CRF and refractive error with the CRF being higher in myopes. This is contrary to what would be expected, as myopes tend to have axial elongation and therefore would be expected to have lower CRF. Nevertheless, IOPg was correlated with spherical equivalent refractive error (r2= 0.10). Since the results showed a moderate correlation between IOPg and CRF (r2= 0.37), the correlation between spherical equivalent and CRF can be explained in part or in total by differences in intraocular pressure in different refractive errors. Contrary to the study of Song and colleagues,17 no significant correlation was found between IOPg and CH. As both CRF and CH are calculated from P1 and P2, by definition there should not be a correlation between these two parameters, although because k is a constant mathematically a correlation is possible (in fact a correlation between CH and CRF was observed in our data). IOPg is likely to interfere with the resistance of the cornea to applanate and therefore its correlation with CRF, but it is not likely to be related to the viscous properties of the cornea and its capacity to absorb energy as described by CH.

Both CRF and CH increase as CCT increases.16,23 We did not measure CCT in the present study but most studies show that there is no significant difference in CCT between myopes and emmetropes.5,6,16 The only exception being Chang and colleagues,8 who found a lower CCT in myopes in comparison to emmetropes. The present study indicates that approximately four per cent of the variability in CRF is linked to refractive error with the participants with higher levels of myopia having higher CRF. If, as suggested by Chang and colleagues,8 an inverse correlation between CCT and refractive error does exist, it is possible that this correlation could weaken the statistical power of the association found between CRF and refractive error in the present study. CRF is a measure of corneal resistance, which is independent of IOPcc, but is strongly correlated with CCT, corneal hydration and perhaps to some other aspects of corneal biomechanics.16,24

Considerable variation was found among measurements for a few individuals included in the study, while most presented small variations in the data. This variation was not linked to the refractive error or the age of the participants. A within-subject standard deviation of 1.5 to 2.0 mmHg for CH and CRF has been reported in the literature.12,13 The within-subject standard deviation in the present study ranged between 0.06 and 1.7 mmHg with a mean of 0.80 mmHg for CH and between 0.06 and 1.65 mmHg with a mean of 0.68 mmHg for CRF. These findings are comparable to the previous literature and unlikely to be influenced by any other clinical parameters.

Corneal rigidity increases with increasing age, whereas corneal viscoelastic properties reduce with age.25,26 CH and CRF are both measurements of corneal viscosity/viscoelasticity and are determined using the values of the corneal applanation and recovery phases. After applanation, a more rigid cornea is expected to take longer to return to its normal shape as its viscoelastic properties are reduced. Previous studies have shown that CH and the CRF decrease with increasing age.13,18 The present study found no significant link between age and CH and CRF values. This is perhaps due to the preponderance of younger subjects (typically under 40 years) in the present study.

In conclusion, the present study showed only a very weak correlation between CRF and spherical equivalent refractive error (up to -9.00 D) and no correlation was found between CH and refractive error. The systematic changes in CRF with spherical equivalent refractive error were small and might be explained by differences in IOPg with refractive error.

ACKNOWLEDGEMENTS

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENTS
  7. GRANTS AND FINANCIAL SUPPORT
  8. REFERENCES

We thank Grafton Optical, Birmingham, UK for lending us the Ocular Response Analyser for the duration of the study. None of the authors has a financial interest in the instrument mentioned in the manuscript.

GRANTS AND FINANCIAL SUPPORT

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENTS
  7. GRANTS AND FINANCIAL SUPPORT
  8. REFERENCES

Marco A Miranda was supported by a research grant from Ciba Vision.

REFERENCES

  1. Top of page
  2. Abstract
  3. METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGEMENTS
  7. GRANTS AND FINANCIAL SUPPORT
  8. REFERENCES
  • 1
    Reiner A, Shih YF, Fitzgerald ME. The relationship of choroidal blood flow and accommodation to the control of ocular growth. Vision Res 1995; 35: 12271245.
  • 2
    Wildsoet CF. Stuctural Correlates of Myopia. Oxford: Butterworth-Heinemann, 1998.
  • 3
    McBrien NA, Jobling AI, Gentle A. Biomechanics of the sclera in myopia: extracellular and cellular factors. Optom Vis Sci 2009; 86: E23-E30.
  • 4
    Phillips JR, McBrien NA. Form deprivation myopia: elastic properties of sclera. Ophthalmic Physiol Opt 1995; 15: 357362.
  • 5
    Cho P, Lam C. Factors affecting the central corneal thickness of Hong Kong-Chinese. Curr Eye Res 1999; 18: 368374.
  • 6
    Fam HB, How AC, Baskaran M, Lim KL, Chan YH, Aung T. Central corneal thickness and its relationship to myopia in Chinese adults. Br J Ophthalmol 2006; 90: 14511453.
  • 7
    Zadnik K, Mutti DO, Friedman NE, Adams AJ. Initial cross-sectional results from the Orinda Longitudinal Study of Myopia. Optom Vis Sci 1993; 70: 750758.
  • 8
    Chang SW, Tsai IL, Hu FR, Lin LL, Shih YF. The cornea in young myopic adults. Br J Ophthalmol 2001; 85: 916920.
  • 9
    Andreassen TT, Simonsen AH, Oxlund H. Biomechanical properties of keratoconus and normal corneas. Exp Eye Res 1980; 31: 435441.
  • 10
    Elsheikh A, Wang D, Pye D. Determination of the modulus of elasticity of the human cornea. J Refract Surg 2007; 23: 808818.
  • 11
    Zeng Y, Yang J, Huang K, Lee Z, Lee X. A comparison of biomechanical properties between human and porcine cornea. J Biomech 2001; 34: 533537.
  • 12
    Gonzalez-Meijome JM, Queiros A, Jorge J, Diaz-Rey A, Parafita MA. Intraoffice variability of corneal biomechanical parameters and intraocular pressure (IOP). Optom Vis Sci 2008; 85: 457462.
  • 13
    Moreno-Montanes J, Maldonado MJ, Garcia N, Mendiluce L, Garcia-Gomez PJ, Segui-Gomez M. Reproducibility and clinical relevance of the ocular response analyzer in non-operated eyes: corneal biomechanical and tonometric implications. Invest Ophthalmol Vis Sci 2008; 49: 968974.
  • 14
    Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg 2005; 31: 156162.
  • 15
    Lim L, Gazzard G, Chan YH, Fong A, Kotecha A, Sim EL, Tan D et al. Cornea biomechanical characteristics and their correlates with refractive error in Singaporean children. Invest Ophthalmol Vis Sci 2008; 49: 38523857.
  • 16
    Shen M, Fan F, Xue A, Wang J, Zhou X, Lu F. Biomechanical properties of the cornea in high myopia. Vision Res 2008; 48: 21672171.
  • 17
    Song Y, Congdon N, Li L, Zhou Z, Choi K, Lam DS, Pang CP et al. Corneal hysteresis and axial length among Chinese secondary school children: the Xichang Pediatric Refractive Error Study (X-PRES) report no. 4. Am J Ophthalmol 2008; 145: 819826.
  • 18
    Kotecha A, Elsheikh A, Roberts CR, Zhu H, Garway-Heath DF. Corneal thickness- and age-related biomechanical properties of the cornea measured with the ocular response analyzer. Invest Ophthalmol Vis Sci 2006;47: 53375347.
  • 19
    Plakitsi A, O'Donnell C, Miranda MA, Charman WN, Radhakrishnan H. Corneal biomechanical properties measured with the Ocular Response Analyser in a myopic population. Ophthalmic Physiol Opt 2011; 31: 404412.
  • 20
    McBrien NA, Millodot M. Clinical evaluation of the Canon Autoref R-1. Am J Optom Physiol Opt 1985; 62: 786792.
  • 21
    Rosenfield M, Chiu NN. Repeatability of subjective and objective refraction. Optom Vis Sci 1995; 72: 577579.
  • 22
    Thibos LN, Wheeler W, Horner D. Power vectors: an application of Fourier analysis to the description and statistical analysis of refractive error. Optom Vis Sci 1997; 74: 367375.
  • 23
    Shah S, Laiquzzaman M, Cunliffe I, Mantry S. 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. Cont Lens Anterior Eye 2006; 29: 257262.
  • 24
    Lu F, Xu S, Qu J, Shen M, Wang X, Fang H, Wang J. Central corneal thickness and corneal hysteresis during corneal swelling induced by contact lens wear with eye closure. Am J Ophthalmol 2007; 143: 616622.
  • 25
    Daxer A, Misof K, Grabner B, Ettl A, Fratzl P. Collagen fibrils in the human corneal stroma: structure and aging. Invest Ophthalmol Vis Sci 1998; 39: 644648.
  • 26
    Malik NS, Moss SJ, Ahmed N, Furth AJ, Wall RS, Meek KM. Ageing of the human corneal stroma: structural and biochemical changes. Biochim Biophys Acta 1992; 1138: 222228.