Seminars in Ophthalmology
ISSN: 0882-0538 (Print) 1744-5205 (Online) Journal homepage: http://www.tandfonline.com/loi/isio20
Relationship Between Corneal Hysteresis and Corneal Resistance Factor with Other Ocular Parameters Nicola Rosa MD, Michele Lanza, Maddalena De Bernardo, Giuseppe Signoriello & Paolo Chiodini To cite this article: Nicola Rosa MD, Michele Lanza, Maddalena De Bernardo, Giuseppe Signoriello & Paolo Chiodini (2014): Relationship Between Corneal Hysteresis and Corneal Resistance Factor with Other Ocular Parameters, Seminars in Ophthalmology, DOI: 10.3109/08820538.2013.874479 To link to this article: http://dx.doi.org/10.3109/08820538.2013.874479
Published online: 07 Feb 2014.
Submit your article to this journal
Article views: 72
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=isio20 Download by: [Washington University in St Louis]
Date: 11 November 2015, At: 02:17
Seminars in Ophthalmology, Early Online, 1–5, 2014 ! Informa Healthcare USA, Inc. ISSN: 0882-0538 print / 1744-5205 online DOI: 10.3109/08820538.2013.874479
ORIGINAL ARTICLE
Relationship Between Corneal Hysteresis and Corneal Resistance Factor with Other Ocular Parameters Nicola Rosa, MD1, Michele Lanza2,3, Maddalena De Bernardo1, Giuseppe Signoriello4, and Paolo Chiodini4
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015
1
Department of Medicine and Surgery, University of Salerno, Salerno, Italy, 2Multidisciplinary Department of Medical, Surgical and Dental Specialities, Seconda Universita` di Napoli, Naples, Italy, 3Centro Grandi Apparecchiature, Seconda Universita` di Napoli, Naples, Italy, and 4Biostatistics Unit, Department of Medicine and Public Health, Seconda Universita` di Napoli, Naples, Italy
ABSTRACT Purpose: To evaluate the relationship between corneal hysteresis (CH) and corneal resistance factor (CRF) with age, central corneal thickness (CCT), corneal curvature (KM), corneal volume (CV), and refractive error in naı¨ve eyes. Methods: 105 healthy subjects (58 male and 47 female) were included in this study. The ages ranged from 19 to 82 years (mean 43.1 ± 15.4 years) and refraction between 11 D and +6 D (mean 0.79 ± 2.95 D). CH and CRF obtained with the Ocular Response Analyzer (ORA) were correlated with age, refractive error, Goldmann Applanation Tonometry (GAT), and with CCT, KM, CV obtained with the Pentacam, and with CornealCompensated Intraocular Pressure (IOPcc) and Goldmann-correlated intraocular pressure measurement (IOPg) obtained with ORA. A multivariable mixed effect model was used to evaluate associations among these parameters. Results: CH ranged from 6.9 to 14.6 mmHg (mean 10.26 ± 1.49 mmHg); CRF ranged from 5.8 to 17 mmHg (mean 10.38 ± 1.64 mmHg). Multivariate analysis showed a statistically significant correlation between CH with CCT (p50.001), and KM (p50.001), and between CRF with CCT (p50.001) and GAT (p50.001). Conclusions: Our findings support the hypothesis that CH and CRF are related to the corneal shape and thickness, and show a decrease of CH with age. Keywords: Central corneal thickness, corneal curvature, corneal hysteresis, corneal resistance factor, corneal volume
INTRODUCTION
measurements of intraocular pressure with a Goldmann applanation tonometer (GAT).4 Until a few years ago, studies that focused on corneal characteristics were mainly limited to corneal thickness, curvature, and transparency. Recently, a new device has been introduced that is able to measure other corneal properties, such as corneal hysteresis (CH) and corneal resistance factor (CRF). CH is a direct measure of the corneal biomechanical properties and is a strain-rate-dependent corneal parameter that represents the cumulative effects of corneal thickness, hydration, rigidity, and other as-yet undetermined factors.5 CH seems to be an indication of viscous damping in the cornea, reflecting the
During the last few years, corneal characteristics have been widely studied with different devices, such as corneal topographs, tomographs, and confocal microscopes. These investigations have shown important results; e.g. in planning corneal refractive surgery, where the knowledge of corneal thickness and shape is mandatory. In eyes that have undergone PRK and LASIK, the study of the corneal surface is essential to understand the reasons for complaint after such surgery.1–3 Moreover, it is well known that corneal thickness and corneal curvature could influence the
Received 4 July 2013; accepted 8 December 2013; published online 5 February 2014 Correspondence: Nicola Rosa, MD, Department of Medicine and Surgery, University of Salerno, Salerno, Italy. E-mail: [email protected]
1
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015
2
N. Rosa et al.
capacity of corneal tissue to absorb and dissipate energy. CRF seems to indicate the overall resistance of the cornea, which, according to previous data, seems to be related to central corneal thickness and GATdetermined IOP, but not to corneal-compensated IOP (IOPcc).5 Most of the published studies on CH and CRF dealt with the measurements of intraocular pressure, but only some of them investigated the connection with other ocular parameters.5–24 For this reason, we decided to evaluate the relationship between these entities with age, refractive error as spherical equivalent (SE), IOPcc, IOPg, and Goldmann Applanation Tonometry (GAT) and other ocular parameters, such as central corneal thickness (CCT), corneal curvature, and corneal volume (CV). To the best of our knowledge, no other studies on healthy subjects analyze correlations among human corneal biomechanical properties and all the parameters evaluated in this manuscript.
MATERIALS AND METHODS In this study, we examined 204 eyes of 105 normal subjects (47 female and 58 male) with refraction ranging from 11 D to +6 D (mean 0.79 ± 2.95 D). The age of the patients ranged from 19 to 82 years (mean 43.1 ± 15.4 years). Subjects with ocular diseases, history of ocular surgery, or ocular trauma were excluded. Informed consent, according to the tenets of the Declaration of Helsinki, was obtained from each patient. All of the patients underwent a complete ophthalmic examination, including an evaluation with a Pentacam and Ocular Response Analyzer (ORA). Pentacam (Oculus, Wetzlar, Germany) uses a rotating Scheimpflug camera and a monochromatic slit-light source (blue LED at 475 nm) that rotate together around the optical axis of the eye to calculate a three-dimensional model of the anterior segment. This device was used to evaluate the CCT, CV (measured within 10 mm circle around the central cornea), and the Cornea Front Mean Keratometry (KM) values. For each exam, the 50 scan modality of measurement was used; the exam was considered to be reliable when the Quality Factor was ‘‘OK.’’ as suggested by the company. The ORA (Reichert Inc., Depew, NY, USA), similar to a non-contact tonometer, uses a metered, collimated air pulse to applanate the cornea and an infrared electro-optical system to record inward and outward applanation events. With this instrument, a precisely metered air pulse is delivered to the eye, causing the cornea to move inward, past a first applanation and into a slight concavity. As the pressure decreases, the cornea gradually recovers its normal configuration, passing through a second applanation state while returning from concavity to its normal convex curvature.
The difference between these inward and outward motion applanation pressures is called CH. This device is also able to provide another value: CRF, which is the result of clinical data analysis and is derived from specific combinations of the inward and outward applanation pressure signals.6 Best-signal examination, according to new ORA software, was utilized. GAT values ranged from 7 mmHg to 24 mmHg (15.01 ± 2.91 mmHg). Every patient was examined first with the Oculus Pentacam, then with ORA and, finally, GAT in order to not introduce bias in the evaluation of the cornea and the corneal biomechanical properties.
Statistical Analysis Continuous variables were reported as mean, standard deviation (SD), and range. Categorical variables were expressed as absolute number and percentage. Variability of CH and CRF between eyes was assessed by means of an Intra Class Correlation (ICC) coefficient with 95% confidence interval (CI).25 Typically, correlation coefficients are assessed using the Pearson or Spearman methods. Nevertheless, with repeated measurements, use of these traditional methods would erroneously ignore the number of subjects as the correct sample size, while instead using the total number of observations as the incorrect sample size, thereby increasing the degrees of freedom. As an alternative, all correlation coefficients were estimated using linear mixed-effects models that can account for the correlation between eyes, as described by Hamlett et al.26 Confidence intervals were calculated using the Fisher transformation. A linear mixed effects model was also used to perform multivariable models.27 Restricted maximum likelihood estimators were used to estimate model parameters. Statistical analysis was performed using SAS version 8.2 (SAS, Inc., Cary, NC, USA).
RESULTS Table 1 summarizes the range, mean, and SD of all the parameters evaluated in this study. Intra Class Correlation (ICC) coefficients are 0.618 for CH (95% CI 0.480 to 0.725) and 0.722 for CRF (95% CI 0.613 to 0.803), indicating that the values for the same subject (within cluster) were more similar than the values between subjects (between cluster). This correlation was accounted for in the analyses by means of a linear mixed effects model. A relevant positive linear correlation was found between CH and CRF (0.67 95% CI 0.55 to 0.76). Table 2 summarizes the univariate correlation between CH and CRF with Age, SE, CCT, KM, CV, IOPcc, IOPg, and GAT. CH and CRF were positively associated with CCT and CV, Seminars in Ophthalmology
Corneal Biomechanics in Naive Eyes 3 TABLE 1. Characteristics of subjects included in the study. Variables
Mean (SD)
CH, mm CRF, mm Age, year SE, D CCT, mm KM, D CV, mm3 IOPcc, mmHg IOPg, mmHg GAT, mmHG
10.26 10.38 43.1 0.79 555.8 43.34 60.56 16.36 15.71 15.01
TABLE 3. Results of multivariable linear mixed effects regression models with CH and CRF as dependent variables.
Range
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015
CH (1.49) (1.34) (15.4) (2.95) (32.7) (1.40) (3.61) (3.52) (3.59) (2.91)
6.9–14.6 5.8–17 18–82 11–+6 478–652 40.3–46.9 45.6–68.4 8.3–26.7 4.6–25.8 7–24
CH: corneal hysteresis; CRF: corneal resistance factor; SE: spherical equivalent; CCT: central corneal thickness; KM: Mean Keratometry; CV: corneal volume; IOP: intraocular pressure; GAT: Goldmann applanation tonometer
TABLE 2. Results of univariate association of CH and CRF with subject characteristics. Univariate correlation coefficient (95% CI) Variables Age, year SE, D CCT, mm KM, D CV, mm3 IOPcc, mmHg IOPg, mmHg GAT, mmHG
CH 0.23 0.02 0.26 0.16 0.32 0.47 0.07 0.01
( 0.4 to 0.04) ( 0.21 to 0.17) (0.07 to 0.43) ( 0.03 to 0.34) (0.14 to 0.48) ( 0.61 to 0.31) ( 0.26 to 0.12) ( 0.2 to 0.18)
CRF 0.08 0.02 0.31 0.13 0.34 0.18 0.44 0.42
( 0.27 to 0.11) ( 0.21 to 0.17) (0.13 to 0.47) ( 0.06 to 0.32) (0.16 to 0.50) ( 0.02 to 0.35) (0.27 to 0.58) (0.25 to 0.57)
CI: confidence interval; CH: corneal hysteresis; CRF: corneal resistance factor; SE: spherical equivalent; CCT: central corneal thickness; KM: Mean Keratometry; CV: corneal volume; IOP: intraocular pressure; GAT: Goldmann applanation tonometer.
while they were uncorrelated with age, SE, and KM. A negative correlation was found between CH and IOPcc, while CRF was positively associated with IOPg and GAT. Table 3 summarizes the results of multivariate analysis of CH and CRF with Age, SE, CCT, KM, and GAT. As expected, CV was strongly positively correlated with CCT and therefore excluded from the multivariate analyses. IOPcc and IOPg were excluded because they were strongly positively associated with GAT values. According to our results, CH is statistically positively associated with CCT and KM and negatively associated with age, whereas CRF is statistically positively associated with CCT, KM, and GAT. No correlation was found between CH and CRF with the refractive error.
DISCUSSION CH and CRF measure the complex visco-elastic structure of the human corneal tissue. !
2014 Informa Healthcare USA, Inc.
Variables Intercept Age, year SE, D CCT, mm KM, D GAT, mmHg
Parameter estimate 10.42 0.025 0.041 0.016 0.292 0.004
CRF p Value 0.008 0.001 0.266 50.001 50.001 0.900
Parameter estimate 14.57 0.020 0.032 0.022 0.248 0.196
p Value 50.001 0.013 0.399 50.001 0.002 50.001
CH: corneal hysteresis; CRF: corneal resistance factor; SE: spherical equivalent; CCT: central corneal thickness; KM: Mean Keratometry; GAT: Goldmann applanation tonometer
Lower CH and CRF values have been demonstrated in several conditions, such as keratoconic and post-LASIK eyes, which could reflect the disorganization of the stromal collagen lamellae.28 Lower CH has also been demonstrated in patients with primary open-angle and low-tension glaucoma,6,10,18 supporting the hypothesis that pathology in the lamina cribrosa may be detectable by changes in corneal biomechanics. For these reasons, CH measurements may prove to be useful in the diagnosis of conditions such as normal tension glaucoma and early keratoconus.10,18,19 In order to better explain CH and CRF, we tried to correlate them with CCT, CV, KM, refraction, and age. According to our results, CH decreases with age, whereas CRF is not affected by the aging process. In contrats, CRF seems to affect the IOP measurement, whereas CH does not. Regarding the correlation with CCT and Km, both CH and CRF increased as the corneas became thicker and steeper. Previously published studies investigated the relationship between CH and CRF with the other ocular parameters, but their results were not univocal, as summarized in Tables 4 and 5. Our findings of a positive correlation between CH and CCT agree with most of the authors that correlated these parameters, even if the CCT measurements were performed with different devices.6,13–15,20,21,29 Regarding the correlation between CH and age, our results contradict most of the authors who correlated these parameters,14,16,18,19,28,29 but agree with the results obtained by Fontes et al.,15 Narayanaswamy et al.,20 and Yu et al.21 The multivariate statistical analysis we performed could account for this difference. Our results regarding the relationship between CRF and the other parameters agree with those previously reported for the positive correlation with CCT.7,13–17,20,21,29 The data obtained for KM are not univocal, possibly because of the use of
4
N. Rosa et al.
TABLE 4. Most important findings published in previous papers comparing CH with other eye parameters.
DECLARATION OF INTEREST
Parameters
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015
Corneal Age Refraction Power IOP CCT CV Luce et al.6 Medeiros et al.7 Laiquzzaman et al.12 Shah et al.13 Touboul14 Fontes15 Franco et al.16 Hurmeric et al.17 Detry-Morel et al.18 Johnson et al.19 Narayanaswamy et al.20 Yu et al.22 Radhakrishnan et al.23 Ortiz et al.28 Kamiya et al.29
NE NE NE NE NSS SS NSS NE NSS NSS SS SS NE NSS NSS
NE NE NE NE NE NSS NE NE NE NE NSS SS NE NE NSS
NE NE NE NE NE NSS NSS NE NE NE NSS NE NE NE NSS
NSS NE NSS NE NSS NE NSS NSS NSS NE NSS NE NSS NE SS
SS NE NE SS SS SS SS SS NSS NSS SS SS NE NE SS
NE NE NE NE NE NE NE NE NE NE NE NE NE NE NE
CH: corneal hysteresis; IOP: intraocular pressure measured with Goldmann applanation tonometry; CCT: central corneal thickness; CV: corneal volume; NE: not evaluated; NSS: not statistically significant; SS: statistically significant
TABLE 5. Most important findings published in previous papers comparing CRF with other eye parameters. Parameters Corneal Age Refraction Power IOP CCT CV Luce et al.6 Medeiros et al.7 Laiquzzaman et al.12 Shah et al.13 Touboul14 Fontes15 Franco et al.16 Hurmeric et al.17 Detry-Morel et al.18 Johnson et al.19 Narayanaswamy et al.20 Yu et al.22 Radhakrishnan et al.23 Ortiz et al.28 Kamiya et al.29
NE NSS NE NE NSS SS NSS NE NSS NSS SS NSS NE NSS NSS
NE NSS NE NE NE NSS NSS NE NE NE NSS NSS NE NE NE
NE SS NE NE NE NSS NSS NE NE NE SS NE NE NE NSS
NE SS NE NE SS NE NSS NE NSS NE SS NE SS NE SS
NE SS NE SS SS SS SS SS NSS NSS SS SS NE NE SS
NE NE NE NE NE NE NE NE NE NE NE NE NE NE NE
CRF: corneal resistance factor; IOP: intraocular pressure measured with Goldmann applanation tonometry; CCT: central corneal thickness; CV: corneal volume; NE: not evaluated; NSS: not statistically significant; SS: statistically significant
different devices in the evaluation of the corneal power. In conclusion, our study confirms that CH and CRF are related to corneal thickness and shape in a normal population; the decrease of CH with age has to be taken into account where studies on keratoconus progression with and without treatment are performed.
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Hersh PS. A standardized classification of corneal topography after laser refractive surgery. J Refract Surg 1997;13: 571–575. 2. Rosa N, Cennamo G, Sebastiani A. Classification of corneal topographic patterns after PRK. J Refract Surg 2000;16: 481–483. 3. Rosa N, Lanza M, De Rosa G, Romano A. Anterior corneal surface after Nidek EC-5000 multipass and multizone photorefractive keratectomy for myopia. J Refract Surg 2002;18:460–462. 4. Whitacre MM, Stein R. Sources of error with use of Goldmann-type tonometers. Surv Ophthalmol 1993;38:1–30. 5. Martinez-de-la-Casa JM, Garcia-Feijoo J, Fernandez-Vidal A, et al. Ocular response analyzer versus Goldmann applanation tonometry for intraocular pressure measurements. Invest Ophthalmol Vis Sci 2006;47:4410–4414. 6. Luce D, Taylor D. Reichert ocular response analyzer measures corneal biomechanical properties and IOP provides new indicators for corneal specialties and glaucoma management. Depew, NY: Reichert Ophthalmic Instruments, March 2006. 7. Medeiros FA, Weinreb RN. Evaluation of the influence of corneal biomechanical properties on intraocular pressure measurements using the ocular response analyzer. J Glaucoma 2006;15:364–370. 8. Herndon LW. Measuring intraocular pressure: Adjustments for corneal thickness and new technologies. Current Opin Ophthalmol 2006;17:115–119. 9. Kirwan C, O’Keefe M, Lanigan B. Corneal hysteresis and intraocular pressure measurement in children using the Reichert ocular response analyzer. Am J Ophthalmol 2006; 142:990–992. 10. Congdon NG, Broman AT, Bandeen-Roche K, et al. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol 2006;141:868–875. 11. Kotecha A, Elsheikh A, Roberts CR, et al. Corneal thickness- and age-related biomechanical properties of the cornea measured with the ocular response analyzer. Invest Ophthalmol Vis Sci 2006;47:5337–5347. 12. Laiquzzaman M, Bhojwani R, Cunliffe I, Shah S. Diurnal variation of ocular hysteresis in normal subjects: Relevance in clinical context. Clin Experiment Ophthalmol 2006;34: 114–118. 13. 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;29:257–262. 14. Touboul D, Roberts C, Ke´rautret J, et al. Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. J Cataract Refract Surg 2008; 34:616–622. 15. Fontes BM, Ambro´sio Jr R, Alonso RS, et al. Corneal biomechanical metrics in eyes with refraction of 19.00 to +9.00 D in healthy Brazilian patients. J Refract Surg 2008;24: 941–945. 16. Franco S, Lira M. Biomechanical properties of the cornea measured by the Ocular Response Analyzer and their Seminars in Ophthalmology
Corneal Biomechanics in Naive Eyes 5
17.
18.
19.
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015
20.
21.
22.
!
association with intraocular pressure and the central corneal curvature. Clin Exp Optom 2009;92:469–475. Hurmeric V, Sahin A, Ozge G, Bayer A. The relationship between corneal biomechanical properties and confocal microscopy findings in normal and keratoconic eyes. Cornea 2010;29:641–649. Detry-Morel M, Jamart J, Pourjavan S. Evaluation of corneal biomechanical properties with the Reichert Ocular Response Analyzer. Eur J Ophthalmol 2011;21: 138–148. Johnson RD, Nguyen MT, Lee N, Hamilton DR. Corneal biomechanical properties in normal, forme fruste keratoconus, and manifest keratoconus after statistical correction for potentially confounding factors. Cornea 2011;30: 516–523. Narayanaswamy A, Chung RS, Wu RY, et al. Determinants of corneal biomechanical properties in an adult Chinese population. Ophthalmology 2011;118:1253–1259. Plakitsi A, O’Donnell C, Miranda MA, et al. Corneal biomechanical properties measured with the Ocular Response Analyser in a myopic population. Ophthalmic Physiol Opt 2011;31:404–412. Yu AY, Duan SF, Zhao YE, et al. Correlation between corneal biomechanical properties, applanation tonometry
2014 Informa Healthcare USA, Inc.
23.
24.
25. 26.
27.
28.
29.
and direct intracameral tonometry. Br J Ophthalmol 2012;96: 640–644. Radhakrishnan H, Miranda MA, O’Donnell C. Corneal biomechanical properties and their correlates with refractive error. Clin Exp Optom 2012;95:12–18. Terai N, Raiskup F, Haustein M, et al. Identification of biomechanical properties of the cornea: The ocular response analyzer. Curr Eye Res 2012;37:553–562. Shrout PE, Fleiss JL. Intraclass correlations: Uses in assessing rater reliability. Psychol Bull 1979;86:420–428. Hamlett A, Ryan L, Serrano-Trespalacios P, Wolfinger R. Mixed models for assessing correlation in the presence of replication. J Air Waste Manag Assoc 2003;53: 442–450. Cnaan A, Laird NM, Slasor P. Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. Stat Med 1997;16:2349–2380. Ortiz D, Pin˜ero D, Shabayek MH, et al. Corneal biomechanical properties in normal, post-laser in situ keratomileusis, and keratoconic eyes. J Cataract Refract Surg 2007;33: 1371–1375. Kamiya K, Hagishima M, Fujimura F, Shimizu K. Factors affecting corneal hysteresis in normal eyes. Graefes Arch Clin Exp Ophthalmol 2008;246:1491–1494.
ISSN: 0882-0538 (Print) 1744-5205 (Online) Journal homepage: http://www.tandfonline.com/loi/isio20
Relationship Between Corneal Hysteresis and Corneal Resistance Factor with Other Ocular Parameters Nicola Rosa MD, Michele Lanza, Maddalena De Bernardo, Giuseppe Signoriello & Paolo Chiodini To cite this article: Nicola Rosa MD, Michele Lanza, Maddalena De Bernardo, Giuseppe Signoriello & Paolo Chiodini (2014): Relationship Between Corneal Hysteresis and Corneal Resistance Factor with Other Ocular Parameters, Seminars in Ophthalmology, DOI: 10.3109/08820538.2013.874479 To link to this article: http://dx.doi.org/10.3109/08820538.2013.874479
Published online: 07 Feb 2014.
Submit your article to this journal
Article views: 72
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=isio20 Download by: [Washington University in St Louis]
Date: 11 November 2015, At: 02:17
Seminars in Ophthalmology, Early Online, 1–5, 2014 ! Informa Healthcare USA, Inc. ISSN: 0882-0538 print / 1744-5205 online DOI: 10.3109/08820538.2013.874479
ORIGINAL ARTICLE
Relationship Between Corneal Hysteresis and Corneal Resistance Factor with Other Ocular Parameters Nicola Rosa, MD1, Michele Lanza2,3, Maddalena De Bernardo1, Giuseppe Signoriello4, and Paolo Chiodini4
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015
1
Department of Medicine and Surgery, University of Salerno, Salerno, Italy, 2Multidisciplinary Department of Medical, Surgical and Dental Specialities, Seconda Universita` di Napoli, Naples, Italy, 3Centro Grandi Apparecchiature, Seconda Universita` di Napoli, Naples, Italy, and 4Biostatistics Unit, Department of Medicine and Public Health, Seconda Universita` di Napoli, Naples, Italy
ABSTRACT Purpose: To evaluate the relationship between corneal hysteresis (CH) and corneal resistance factor (CRF) with age, central corneal thickness (CCT), corneal curvature (KM), corneal volume (CV), and refractive error in naı¨ve eyes. Methods: 105 healthy subjects (58 male and 47 female) were included in this study. The ages ranged from 19 to 82 years (mean 43.1 ± 15.4 years) and refraction between 11 D and +6 D (mean 0.79 ± 2.95 D). CH and CRF obtained with the Ocular Response Analyzer (ORA) were correlated with age, refractive error, Goldmann Applanation Tonometry (GAT), and with CCT, KM, CV obtained with the Pentacam, and with CornealCompensated Intraocular Pressure (IOPcc) and Goldmann-correlated intraocular pressure measurement (IOPg) obtained with ORA. A multivariable mixed effect model was used to evaluate associations among these parameters. Results: CH ranged from 6.9 to 14.6 mmHg (mean 10.26 ± 1.49 mmHg); CRF ranged from 5.8 to 17 mmHg (mean 10.38 ± 1.64 mmHg). Multivariate analysis showed a statistically significant correlation between CH with CCT (p50.001), and KM (p50.001), and between CRF with CCT (p50.001) and GAT (p50.001). Conclusions: Our findings support the hypothesis that CH and CRF are related to the corneal shape and thickness, and show a decrease of CH with age. Keywords: Central corneal thickness, corneal curvature, corneal hysteresis, corneal resistance factor, corneal volume
INTRODUCTION
measurements of intraocular pressure with a Goldmann applanation tonometer (GAT).4 Until a few years ago, studies that focused on corneal characteristics were mainly limited to corneal thickness, curvature, and transparency. Recently, a new device has been introduced that is able to measure other corneal properties, such as corneal hysteresis (CH) and corneal resistance factor (CRF). CH is a direct measure of the corneal biomechanical properties and is a strain-rate-dependent corneal parameter that represents the cumulative effects of corneal thickness, hydration, rigidity, and other as-yet undetermined factors.5 CH seems to be an indication of viscous damping in the cornea, reflecting the
During the last few years, corneal characteristics have been widely studied with different devices, such as corneal topographs, tomographs, and confocal microscopes. These investigations have shown important results; e.g. in planning corneal refractive surgery, where the knowledge of corneal thickness and shape is mandatory. In eyes that have undergone PRK and LASIK, the study of the corneal surface is essential to understand the reasons for complaint after such surgery.1–3 Moreover, it is well known that corneal thickness and corneal curvature could influence the
Received 4 July 2013; accepted 8 December 2013; published online 5 February 2014 Correspondence: Nicola Rosa, MD, Department of Medicine and Surgery, University of Salerno, Salerno, Italy. E-mail: [email protected]
1
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015
2
N. Rosa et al.
capacity of corneal tissue to absorb and dissipate energy. CRF seems to indicate the overall resistance of the cornea, which, according to previous data, seems to be related to central corneal thickness and GATdetermined IOP, but not to corneal-compensated IOP (IOPcc).5 Most of the published studies on CH and CRF dealt with the measurements of intraocular pressure, but only some of them investigated the connection with other ocular parameters.5–24 For this reason, we decided to evaluate the relationship between these entities with age, refractive error as spherical equivalent (SE), IOPcc, IOPg, and Goldmann Applanation Tonometry (GAT) and other ocular parameters, such as central corneal thickness (CCT), corneal curvature, and corneal volume (CV). To the best of our knowledge, no other studies on healthy subjects analyze correlations among human corneal biomechanical properties and all the parameters evaluated in this manuscript.
MATERIALS AND METHODS In this study, we examined 204 eyes of 105 normal subjects (47 female and 58 male) with refraction ranging from 11 D to +6 D (mean 0.79 ± 2.95 D). The age of the patients ranged from 19 to 82 years (mean 43.1 ± 15.4 years). Subjects with ocular diseases, history of ocular surgery, or ocular trauma were excluded. Informed consent, according to the tenets of the Declaration of Helsinki, was obtained from each patient. All of the patients underwent a complete ophthalmic examination, including an evaluation with a Pentacam and Ocular Response Analyzer (ORA). Pentacam (Oculus, Wetzlar, Germany) uses a rotating Scheimpflug camera and a monochromatic slit-light source (blue LED at 475 nm) that rotate together around the optical axis of the eye to calculate a three-dimensional model of the anterior segment. This device was used to evaluate the CCT, CV (measured within 10 mm circle around the central cornea), and the Cornea Front Mean Keratometry (KM) values. For each exam, the 50 scan modality of measurement was used; the exam was considered to be reliable when the Quality Factor was ‘‘OK.’’ as suggested by the company. The ORA (Reichert Inc., Depew, NY, USA), similar to a non-contact tonometer, uses a metered, collimated air pulse to applanate the cornea and an infrared electro-optical system to record inward and outward applanation events. With this instrument, a precisely metered air pulse is delivered to the eye, causing the cornea to move inward, past a first applanation and into a slight concavity. As the pressure decreases, the cornea gradually recovers its normal configuration, passing through a second applanation state while returning from concavity to its normal convex curvature.
The difference between these inward and outward motion applanation pressures is called CH. This device is also able to provide another value: CRF, which is the result of clinical data analysis and is derived from specific combinations of the inward and outward applanation pressure signals.6 Best-signal examination, according to new ORA software, was utilized. GAT values ranged from 7 mmHg to 24 mmHg (15.01 ± 2.91 mmHg). Every patient was examined first with the Oculus Pentacam, then with ORA and, finally, GAT in order to not introduce bias in the evaluation of the cornea and the corneal biomechanical properties.
Statistical Analysis Continuous variables were reported as mean, standard deviation (SD), and range. Categorical variables were expressed as absolute number and percentage. Variability of CH and CRF between eyes was assessed by means of an Intra Class Correlation (ICC) coefficient with 95% confidence interval (CI).25 Typically, correlation coefficients are assessed using the Pearson or Spearman methods. Nevertheless, with repeated measurements, use of these traditional methods would erroneously ignore the number of subjects as the correct sample size, while instead using the total number of observations as the incorrect sample size, thereby increasing the degrees of freedom. As an alternative, all correlation coefficients were estimated using linear mixed-effects models that can account for the correlation between eyes, as described by Hamlett et al.26 Confidence intervals were calculated using the Fisher transformation. A linear mixed effects model was also used to perform multivariable models.27 Restricted maximum likelihood estimators were used to estimate model parameters. Statistical analysis was performed using SAS version 8.2 (SAS, Inc., Cary, NC, USA).
RESULTS Table 1 summarizes the range, mean, and SD of all the parameters evaluated in this study. Intra Class Correlation (ICC) coefficients are 0.618 for CH (95% CI 0.480 to 0.725) and 0.722 for CRF (95% CI 0.613 to 0.803), indicating that the values for the same subject (within cluster) were more similar than the values between subjects (between cluster). This correlation was accounted for in the analyses by means of a linear mixed effects model. A relevant positive linear correlation was found between CH and CRF (0.67 95% CI 0.55 to 0.76). Table 2 summarizes the univariate correlation between CH and CRF with Age, SE, CCT, KM, CV, IOPcc, IOPg, and GAT. CH and CRF were positively associated with CCT and CV, Seminars in Ophthalmology
Corneal Biomechanics in Naive Eyes 3 TABLE 1. Characteristics of subjects included in the study. Variables
Mean (SD)
CH, mm CRF, mm Age, year SE, D CCT, mm KM, D CV, mm3 IOPcc, mmHg IOPg, mmHg GAT, mmHG
10.26 10.38 43.1 0.79 555.8 43.34 60.56 16.36 15.71 15.01
TABLE 3. Results of multivariable linear mixed effects regression models with CH and CRF as dependent variables.
Range
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015
CH (1.49) (1.34) (15.4) (2.95) (32.7) (1.40) (3.61) (3.52) (3.59) (2.91)
6.9–14.6 5.8–17 18–82 11–+6 478–652 40.3–46.9 45.6–68.4 8.3–26.7 4.6–25.8 7–24
CH: corneal hysteresis; CRF: corneal resistance factor; SE: spherical equivalent; CCT: central corneal thickness; KM: Mean Keratometry; CV: corneal volume; IOP: intraocular pressure; GAT: Goldmann applanation tonometer
TABLE 2. Results of univariate association of CH and CRF with subject characteristics. Univariate correlation coefficient (95% CI) Variables Age, year SE, D CCT, mm KM, D CV, mm3 IOPcc, mmHg IOPg, mmHg GAT, mmHG
CH 0.23 0.02 0.26 0.16 0.32 0.47 0.07 0.01
( 0.4 to 0.04) ( 0.21 to 0.17) (0.07 to 0.43) ( 0.03 to 0.34) (0.14 to 0.48) ( 0.61 to 0.31) ( 0.26 to 0.12) ( 0.2 to 0.18)
CRF 0.08 0.02 0.31 0.13 0.34 0.18 0.44 0.42
( 0.27 to 0.11) ( 0.21 to 0.17) (0.13 to 0.47) ( 0.06 to 0.32) (0.16 to 0.50) ( 0.02 to 0.35) (0.27 to 0.58) (0.25 to 0.57)
CI: confidence interval; CH: corneal hysteresis; CRF: corneal resistance factor; SE: spherical equivalent; CCT: central corneal thickness; KM: Mean Keratometry; CV: corneal volume; IOP: intraocular pressure; GAT: Goldmann applanation tonometer.
while they were uncorrelated with age, SE, and KM. A negative correlation was found between CH and IOPcc, while CRF was positively associated with IOPg and GAT. Table 3 summarizes the results of multivariate analysis of CH and CRF with Age, SE, CCT, KM, and GAT. As expected, CV was strongly positively correlated with CCT and therefore excluded from the multivariate analyses. IOPcc and IOPg were excluded because they were strongly positively associated with GAT values. According to our results, CH is statistically positively associated with CCT and KM and negatively associated with age, whereas CRF is statistically positively associated with CCT, KM, and GAT. No correlation was found between CH and CRF with the refractive error.
DISCUSSION CH and CRF measure the complex visco-elastic structure of the human corneal tissue. !
2014 Informa Healthcare USA, Inc.
Variables Intercept Age, year SE, D CCT, mm KM, D GAT, mmHg
Parameter estimate 10.42 0.025 0.041 0.016 0.292 0.004
CRF p Value 0.008 0.001 0.266 50.001 50.001 0.900
Parameter estimate 14.57 0.020 0.032 0.022 0.248 0.196
p Value 50.001 0.013 0.399 50.001 0.002 50.001
CH: corneal hysteresis; CRF: corneal resistance factor; SE: spherical equivalent; CCT: central corneal thickness; KM: Mean Keratometry; GAT: Goldmann applanation tonometer
Lower CH and CRF values have been demonstrated in several conditions, such as keratoconic and post-LASIK eyes, which could reflect the disorganization of the stromal collagen lamellae.28 Lower CH has also been demonstrated in patients with primary open-angle and low-tension glaucoma,6,10,18 supporting the hypothesis that pathology in the lamina cribrosa may be detectable by changes in corneal biomechanics. For these reasons, CH measurements may prove to be useful in the diagnosis of conditions such as normal tension glaucoma and early keratoconus.10,18,19 In order to better explain CH and CRF, we tried to correlate them with CCT, CV, KM, refraction, and age. According to our results, CH decreases with age, whereas CRF is not affected by the aging process. In contrats, CRF seems to affect the IOP measurement, whereas CH does not. Regarding the correlation with CCT and Km, both CH and CRF increased as the corneas became thicker and steeper. Previously published studies investigated the relationship between CH and CRF with the other ocular parameters, but their results were not univocal, as summarized in Tables 4 and 5. Our findings of a positive correlation between CH and CCT agree with most of the authors that correlated these parameters, even if the CCT measurements were performed with different devices.6,13–15,20,21,29 Regarding the correlation between CH and age, our results contradict most of the authors who correlated these parameters,14,16,18,19,28,29 but agree with the results obtained by Fontes et al.,15 Narayanaswamy et al.,20 and Yu et al.21 The multivariate statistical analysis we performed could account for this difference. Our results regarding the relationship between CRF and the other parameters agree with those previously reported for the positive correlation with CCT.7,13–17,20,21,29 The data obtained for KM are not univocal, possibly because of the use of
4
N. Rosa et al.
TABLE 4. Most important findings published in previous papers comparing CH with other eye parameters.
DECLARATION OF INTEREST
Parameters
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015
Corneal Age Refraction Power IOP CCT CV Luce et al.6 Medeiros et al.7 Laiquzzaman et al.12 Shah et al.13 Touboul14 Fontes15 Franco et al.16 Hurmeric et al.17 Detry-Morel et al.18 Johnson et al.19 Narayanaswamy et al.20 Yu et al.22 Radhakrishnan et al.23 Ortiz et al.28 Kamiya et al.29
NE NE NE NE NSS SS NSS NE NSS NSS SS SS NE NSS NSS
NE NE NE NE NE NSS NE NE NE NE NSS SS NE NE NSS
NE NE NE NE NE NSS NSS NE NE NE NSS NE NE NE NSS
NSS NE NSS NE NSS NE NSS NSS NSS NE NSS NE NSS NE SS
SS NE NE SS SS SS SS SS NSS NSS SS SS NE NE SS
NE NE NE NE NE NE NE NE NE NE NE NE NE NE NE
CH: corneal hysteresis; IOP: intraocular pressure measured with Goldmann applanation tonometry; CCT: central corneal thickness; CV: corneal volume; NE: not evaluated; NSS: not statistically significant; SS: statistically significant
TABLE 5. Most important findings published in previous papers comparing CRF with other eye parameters. Parameters Corneal Age Refraction Power IOP CCT CV Luce et al.6 Medeiros et al.7 Laiquzzaman et al.12 Shah et al.13 Touboul14 Fontes15 Franco et al.16 Hurmeric et al.17 Detry-Morel et al.18 Johnson et al.19 Narayanaswamy et al.20 Yu et al.22 Radhakrishnan et al.23 Ortiz et al.28 Kamiya et al.29
NE NSS NE NE NSS SS NSS NE NSS NSS SS NSS NE NSS NSS
NE NSS NE NE NE NSS NSS NE NE NE NSS NSS NE NE NE
NE SS NE NE NE NSS NSS NE NE NE SS NE NE NE NSS
NE SS NE NE SS NE NSS NE NSS NE SS NE SS NE SS
NE SS NE SS SS SS SS SS NSS NSS SS SS NE NE SS
NE NE NE NE NE NE NE NE NE NE NE NE NE NE NE
CRF: corneal resistance factor; IOP: intraocular pressure measured with Goldmann applanation tonometry; CCT: central corneal thickness; CV: corneal volume; NE: not evaluated; NSS: not statistically significant; SS: statistically significant
different devices in the evaluation of the corneal power. In conclusion, our study confirms that CH and CRF are related to corneal thickness and shape in a normal population; the decrease of CH with age has to be taken into account where studies on keratoconus progression with and without treatment are performed.
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Hersh PS. A standardized classification of corneal topography after laser refractive surgery. J Refract Surg 1997;13: 571–575. 2. Rosa N, Cennamo G, Sebastiani A. Classification of corneal topographic patterns after PRK. J Refract Surg 2000;16: 481–483. 3. Rosa N, Lanza M, De Rosa G, Romano A. Anterior corneal surface after Nidek EC-5000 multipass and multizone photorefractive keratectomy for myopia. J Refract Surg 2002;18:460–462. 4. Whitacre MM, Stein R. Sources of error with use of Goldmann-type tonometers. Surv Ophthalmol 1993;38:1–30. 5. Martinez-de-la-Casa JM, Garcia-Feijoo J, Fernandez-Vidal A, et al. Ocular response analyzer versus Goldmann applanation tonometry for intraocular pressure measurements. Invest Ophthalmol Vis Sci 2006;47:4410–4414. 6. Luce D, Taylor D. Reichert ocular response analyzer measures corneal biomechanical properties and IOP provides new indicators for corneal specialties and glaucoma management. Depew, NY: Reichert Ophthalmic Instruments, March 2006. 7. Medeiros FA, Weinreb RN. Evaluation of the influence of corneal biomechanical properties on intraocular pressure measurements using the ocular response analyzer. J Glaucoma 2006;15:364–370. 8. Herndon LW. Measuring intraocular pressure: Adjustments for corneal thickness and new technologies. Current Opin Ophthalmol 2006;17:115–119. 9. Kirwan C, O’Keefe M, Lanigan B. Corneal hysteresis and intraocular pressure measurement in children using the Reichert ocular response analyzer. Am J Ophthalmol 2006; 142:990–992. 10. Congdon NG, Broman AT, Bandeen-Roche K, et al. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol 2006;141:868–875. 11. Kotecha A, Elsheikh A, Roberts CR, et al. Corneal thickness- and age-related biomechanical properties of the cornea measured with the ocular response analyzer. Invest Ophthalmol Vis Sci 2006;47:5337–5347. 12. Laiquzzaman M, Bhojwani R, Cunliffe I, Shah S. Diurnal variation of ocular hysteresis in normal subjects: Relevance in clinical context. Clin Experiment Ophthalmol 2006;34: 114–118. 13. 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;29:257–262. 14. Touboul D, Roberts C, Ke´rautret J, et al. Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. J Cataract Refract Surg 2008; 34:616–622. 15. Fontes BM, Ambro´sio Jr R, Alonso RS, et al. Corneal biomechanical metrics in eyes with refraction of 19.00 to +9.00 D in healthy Brazilian patients. J Refract Surg 2008;24: 941–945. 16. Franco S, Lira M. Biomechanical properties of the cornea measured by the Ocular Response Analyzer and their Seminars in Ophthalmology
Corneal Biomechanics in Naive Eyes 5
17.
18.
19.
Downloaded by [Washington University in St Louis] at 02:17 11 November 2015
20.
21.
22.
!
association with intraocular pressure and the central corneal curvature. Clin Exp Optom 2009;92:469–475. Hurmeric V, Sahin A, Ozge G, Bayer A. The relationship between corneal biomechanical properties and confocal microscopy findings in normal and keratoconic eyes. Cornea 2010;29:641–649. Detry-Morel M, Jamart J, Pourjavan S. Evaluation of corneal biomechanical properties with the Reichert Ocular Response Analyzer. Eur J Ophthalmol 2011;21: 138–148. Johnson RD, Nguyen MT, Lee N, Hamilton DR. Corneal biomechanical properties in normal, forme fruste keratoconus, and manifest keratoconus after statistical correction for potentially confounding factors. Cornea 2011;30: 516–523. Narayanaswamy A, Chung RS, Wu RY, et al. Determinants of corneal biomechanical properties in an adult Chinese population. Ophthalmology 2011;118:1253–1259. Plakitsi A, O’Donnell C, Miranda MA, et al. Corneal biomechanical properties measured with the Ocular Response Analyser in a myopic population. Ophthalmic Physiol Opt 2011;31:404–412. Yu AY, Duan SF, Zhao YE, et al. Correlation between corneal biomechanical properties, applanation tonometry
2014 Informa Healthcare USA, Inc.
23.
24.
25. 26.
27.
28.
29.
and direct intracameral tonometry. Br J Ophthalmol 2012;96: 640–644. Radhakrishnan H, Miranda MA, O’Donnell C. Corneal biomechanical properties and their correlates with refractive error. Clin Exp Optom 2012;95:12–18. Terai N, Raiskup F, Haustein M, et al. Identification of biomechanical properties of the cornea: The ocular response analyzer. Curr Eye Res 2012;37:553–562. Shrout PE, Fleiss JL. Intraclass correlations: Uses in assessing rater reliability. Psychol Bull 1979;86:420–428. Hamlett A, Ryan L, Serrano-Trespalacios P, Wolfinger R. Mixed models for assessing correlation in the presence of replication. J Air Waste Manag Assoc 2003;53: 442–450. Cnaan A, Laird NM, Slasor P. Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. Stat Med 1997;16:2349–2380. Ortiz D, Pin˜ero D, Shabayek MH, et al. Corneal biomechanical properties in normal, post-laser in situ keratomileusis, and keratoconic eyes. J Cataract Refract Surg 2007;33: 1371–1375. Kamiya K, Hagishima M, Fujimura F, Shimizu K. Factors affecting corneal hysteresis in normal eyes. Graefes Arch Clin Exp Ophthalmol 2008;246:1491–1494.
