https://orcid.org/0009-0008-0799-7057
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Abstract
We aimed to quantify the distribution of corneal biomechanics in healthy, myopic Chinese candidates for refractive surgery using an ocular response analyzer, and explore factors that influence corneal biomechanics. In this retrospective cross-sectional study, 1,090 eyes from 1090 myopic patients scheduled for refractive surgery at the Refractive Center of Dalian Third People’s Hospital between January 2021 and May 2022 were examined. Participants were categorized into three groups based on spherical equivalent power: low myopia (SE> −3.00D), moderate myopia (>−6.00D < SE ≤ −3.00D), and high myopia (SE ≤ −6.00D); then further categorized by central corneal thickness into four groups: < 500μm, 500 to <550μm, 550 to <600μm, and ≥600μm. The Ocular Response Analyzer was used to measure corneal hysteresis (CH) and corneal resistance factor (CRF). Differences in CH and CRF were compared across groups. Generalized estimating equations were applied to determine correlations between CH and CRF and variables such as sex, age, corneal keratometry, central corneal thickness, white-to-white corneal diameter, and spherical equivalent power. The average corneal hysteresis (CH) was 11.18 ± 1.35 mmHg, while the average corneal resistance factor (CRF) was 11.22 ± 1.64 mmHg. The average CRF values were significantly higher in men than in women (P < 0.05). In the high myopia group, CH values were significantly lower than those in the moderate and low myopia groups (P < 0.01). CH and CRF increased with corneal thickness across all groups, with statistically significant differences (P < 0.01). Generalized estimating equations showed a positive correlation between corneal thickness and curvature with both CH and CRF (all P < 0.01). Age was negative correlation between CH and CRF (all P < 0.05). Spherical equivalent power was positively correlated with CH (P < 0.01). Corneal thickness, curvature, and refractive power significantly affected corneal measurement values in individuals with myopia. The CH and CRF values increased with increasing corneal thickness and curvature, and CH was negatively correlated with the severity of myopia.
Citation: Ning J, Sun S, Yu T, Liu X, Jin L, Zhang L (2025) The impact of age, gender, and ocular parameters on corneal biomechanics in Chinese refractive candidates. PLoS One 20(6): e0325419. https://doi.org/10.1371/journal.pone.0325419
Editor: Anitha Venugopal, Aravind Eye Hospital, INDIA
Received: November 7, 2024; Accepted: May 13, 2025; Published: June 4, 2025
Copyright: © 2025 Ning et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: This research was supported by the following grants awarded to JL (Lin Jin): - Youth Science and Technology Star Project of Dalian (https://www.dl.gov.cn/) under Grant number 2021RQO33. NJL (Jiliang Ning): - The Third People’s Hospital of Dalian Research Start-up Fund (https://www.dl3y.com/) under Grant number 2024ky004. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
The cornea is a crucial component of the eye’s refractive system, contributing approximately 70% of its refractive power. Its viscoelastic biomechanical properties enable it to maintain optimal refractive and mechanical characteristics in response to various internal and external pressures, demonstrating a balance between softness and toughness [1]. Measuring corneal biomechanics is vital for diagnosing and prognosing various diseases, including screening for corneal ectasia and predicting various outcomes following corneal refractive surgery [2,3]. The ocular response analyzer (ORA; Reichert Ophthalmic Instruments, Buffalo, New York, USA) is widely used to measure corneal biomechanics in vivo [4]. It uses infrared signals and variable pulse airflow to assess corneal pressure changes during bidirectional applanation, providing two key parameters: corneal hysteresis (CH) and corneal resistance factor (CRF). CH represents the pressure difference between the two corneal applanations, indicating energy dissipation of the cornea during the stress process [5]. In contrast, the CRF is more closely related to the pressure experienced during the first applanation event and resistance to the initial elastic deformation [5]. Studies have explored corneal biomechanics across various ethnic groups [3,6–9]. However, there is currently a lack of large-sample studies investigating reference values for corneal viscoelastic properties in healthy Chinese candidates for myopic refractive surgery. The aim of this study was to establish reference values for corneal biomechanical measurements in this population. Additionally, we seek to investigate the effects of sex, age, corneal keratometry (K), central corneal thickness (CCT), white-to-white (WTW) corneal diameter, and spherical equivalents (SE) on corneal biomechanics.
Materials and methods
Research subjects
In this retrospective cross-sectional analysis, we included 1090 eyes of 1,090 patients with myopia (random selection of one eye of each patient) scheduled to undergo refractive surgery at the Refractive Center of the Dalian Third People’s Hospital between January 2021 and May 2022. Data were accessed for research purposes starting on February 3, 2023. The cohort consisted of 578 males and 512 females, aged 16–40 years, with an average age of 23.49 ± 6.42 years. Inclusion criteria required participants to have an annual progression of myopia not exceeding 0.50 D, no contact lens use or cessation of soft contact lenses for at least two weeks, and discontinuation of rigid lenses for more than three weeks or orthokeratology lenses for three months. Patients with keratoconus, suspected keratoconus, corneal dystrophy, glaucoma, diabetes, scarring, systemic diseases, previous eye surgeries, or eye trauma were excluded. The research protocol received approval from the Ethics Committee of the Dalian Third People’s Hospital (Approval Number: 2022-039-001). This study adhered to the principles outlined in the Declaration of Helsinki. In accordance with the requirements set forth by the ethics committee, the waiver of patient informed consent was granted. The authors did not have access to any information that could identify individual participants during or after the data collection process.
Method of examination
ORA was used to assess central CH and CRF in the examined eyes. During measurements, patients were instructed to relax and focus on a green light to maintain target fixation. Once the pressure sensor was properly aligned with the cornea, a gentle pulse of air was emitted, interacting with the cornea. After 3 milliseconds, the airflow stopped, and the device recorded a waveform and corresponding values. Each eye was measured three times, and the result with a signal score above 6 was included in the analysis. The Pentacam (Oculus Inc., Wetzlar, Germany) was used to measure the anterior segment parameters, including corneal keratometry (K), central corneal thickness (CCT), and corneal white-to-white (WTW) diameter. Spherical equivalent (SE) was determined from cycloplegic computer refraction results. All tests were performed using the same equipment by an experienced technician.
Statistical analysis
Statistical analyses were performed using SPSS version 26.0 (SPSS, Chicago, Illinois, USA). The normality of the measurement indicators in this study was assessed using the Kolmogorov-Smirnov test, which confirmed a normal distribution. Data are expressed as mean ± standard deviation (SD) with 95% confidence intervals (CI). An independent samples t-test was employed to compare biomechanical parameters between sexes. One-way analysis of variance (ANOVA) was used to evaluate the overall differences in corneal biomechanical parameters across various spherical equivalent (SE) and central corneal thickness (CCT) groups, with post-hoc comparisons performed using the Bonferroni test. Generalized estimating equations were utilized to examine the correlations between CH, CRF, sex, age, CCT, corneal keratometry (K), white-to-white (WTW) corneal diameter, and SE. Statistical significance was set at p < 0.05.
Results
This study involved 1,090 participants (578 males and 512 females) with an average age of 23.49 ± 6.42 years. The average SE, CCT, K, and corneal WTW diameter of the participants were −4.53 ± 2.12 D, 552.34 ± 30.16 μm, 43.31 ± 1.38 D, and 11.80 ± 0.41 mm, respectively. The mean CH and CRF were 11.18 ± 1.35 mmHg and 11.22 ± 1.64 mmHg, respectively. The results are summarized in Table 1.
Table 2 presents the comparison of corneal biomechanics between sexes. The mean CH value for males was 11.23 ± 1.37 mmHg, and 11.13 ± 1.32 mmHg for females, with no statistically significant difference (P = 0.246). However, the mean CRF value for males (11.32 ± 1.67 mmHg) was significantly higher than that for females (11.11 ± 1.60 mmHg), with a statistically significant difference (P < 0.05).
Table 3 shows the differences in corneal biomechanics across varying diopters. As the diopters increased, CH value decreased. The Dunn-Bonferroni post hoc test showed no statistical difference between the low and moderate myopia groups (P = 0.358), but all other comparisons were significant (P < 0.01). In contrast, no significant difference was identified in CRF across the diopter groups (P = 0.846).
Table 4 compares corneal biomechanics across varying corneal thicknesses. The examined eyes were grouped into four categories: < 500 μm, 500 to <550 μm, 550 to <600 μm, and ≥600 μm. The average CH values for these four groups were 9.90 ± 1.08, 10.69 ± 1.16, 11.53 ± 1.23, and 12.45 ± 1.48 mmHg, respectively, while the average CRF values were 9.38 ± 1.15, 10.54 ± 1.40, 11.67 ± 1.39, and 13.17 ± 1.74 mmHg, respectively. Both CH and CRF values increased sequentially with corneal thickness, and the overall difference being statistically significant (P < 0.01). The Dunn-Bonferroni post hoc test confirmed that the differences between the subgroups were statistically significant (P < 0.01).
Generalized estimating equations were used to assess correlations between CH, CRF, sex, age, CCT, K, WTW corneal diameter, and SE (Table 5). Age, CCT, K, and SE values were correlated with CH. Specifically, SE, CCT, K, and CH exhibited positive correlations (all P < 0.01), whereas age and CH showed a negative correlation (P < 0.05). CCT, K, and CRF were positively correlated (all P-values < 0.01). In contrast, age, WTW, and CRF demonstrated a negative correlation (P < 0.05).
Discussion
In recent years, advancements in corneal refractive surgery technology have improved outcomes for myopia correction. However, post-refractive ectasia can still occur in eyes without identifiable preoperative risk factors, with an incidence ranging from 0.011% to 0.09% [10]. Biomechanical decompensation plays a key role in corneal dilatation after refractive surgery [11], making it crucial to understand the biomechanical properties of myopic eyes to assess the predictability and safety of these surgeries. Our study found that the average CH and CRF values were 11.19 ± 1.37 mmHg and 11.22 ± 1.67 mmHg, respectively. Previous studies have reported CH and CRF distributions in healthy individuals. In a study of 2,039 healthy Caucasians, the average CH and CRF were 11.49 ± 1.89 mmHg and 11.40 ± 2.30 mmHg, respectively [3]. Among healthy Japanese participants, the average CH was 10.2 ± 1.3 mmHg [12], while healthy Thais had an average CH of 10.18 ± 1.48 mmHg. In healthy Saudi adults, CH averaged 11.16 ± 2.11 mmHg, and CRF averaged 11.07 ± 2.31 mmHg [6,8]. Differences between our study and these studies may be attributed to racial and geographic variations. Establishing population-specific norms for corneal biomechanics is important. This study, the largest of its kind, offers valuable insights for the preoperative evaluation of corneal refractive surgery candidates using the ORA.
Gender is generally not considered to significantly influence corneal biomechanics. In this study, we compared CH and CRF values in myopia patients by gender and found no significant difference in CH values between male and female patients. However, CRF was higher in males. After adjusting for confounding factors such as age, corneal thickness, corneal curvature, and diopter using generalized estimating equations, no statistically significant differences in CH and CRF were found between sexes. This aligns with previous studies by Oncel and El Massry et al., which reported no significant influence of gender on corneal biomechanical properties in myopic eyes [13,14]. Bahadir et al. measured the CH and CRF levels at various time points during the menstrual cycle (before, during, and after ovulation) in young women [15]. They found no significant changes in corneal biomechanics at different points in the measurement cycle, suggesting that estrogen and progesterone levels do not affect corneal biomechanics in non-pregnant women.
When myopic patients were categorized according to spherical equivalents (SE), CRF values did not differ significantly across myopia levels, but CH decreased as myopia increased. Our analysis indicated a relationship between CH and SE; however, we did not find any notable correlation between CRF and SE. This is consistent with earlier studies, which also noted a decrease in CH with increasing myopia [16–19]. In a similar vein, research conducted by Song and colleagues, along with Bueno-Gimeno and their team, identified an inverse relationship between axial length and CH [20,21]. Increasing myopia is associated with thinner scleral collagen fibers, decreased collagen content, and relatively low proteoglycan synthesis [22–24], contributing to scleral thinning and diminished mechanical properties. Given that the corneal stroma is a continuation of the sclera, changes in the sclera’s structure may reduce corneal viscoelasticity. This raised concerns about postoperative biomechanical stability in highly myopic patients undergoing corneal refractive surgery.
Corneal thickness is another significant factor affecting corneal viscoelasticity. In this study, CH and CRF values increased with greater corneal thickness. After controlling for sex, age, and other ocular parameters, we found a positive correlation between CH, CRF, and corneal thickness. These findings align with those of previous research [25–27]. Fontes et al. reported that even when corneal thickness was equalized, patients with keratoconus had lower CH and CRF values than those with healthy thin corneas [28]. Galletti also noted that adjusting for corneal thickness improved the detection of keratoconus using the corrected CRF index [29]. Establishing standardized ranges for CH and CRF across varying corneal thickness is important for assessing the normality of corneal biomechanics.
Age-related changes in corneal structure, including the growth of stromal fibrils and increased cross-linking [30], can also affect corneal biomechanics. In vitro experiments have shown that corneal stiffness, as measured by Young’s modulus, increases with age, while the hysteresis area decreases [31]. In vivo studies have confirmed a significant association among age, CH, and CRF. Ahmed et al. in a study of 997 eyes from 508 individuals aged 10–84 years, reported a considerable inverse correlation between age and both CH and CRF [14]. Similarly, Kamiya et al. found an inverse correlation between age and CH in a study of 204 healthy individuals aged 19–89 years [32]. Consistent with the aforementioned studies, our analysis model demonstrates that age has a statistically significant correlation with both CH and CRF. Our study also shows a positive correlation between corneal curvature and both CH and CRF, indicating that a steeper cornea has a stronger resistance to pressure, which aligns with the findings of Hwang et al [33]. Francis et al. and Matsumoto also suggested that corneal curvature influences corneal stiffness, with a steeper cornea corresponding to increased hardness [34,35]. This may be due to the fact that a steeper cornea requires greater deformation to achieve flattening, necessitating increased pressure, which in turn affects ORA measurement.
This study had several limitations. First, the participants were predominantly young, which may limit the generalizability of the findings. Future studies ought to encompass a wider age spectrum to delve deeper into how aging influences corneal biomechanics. Second, cross-sectional designs may hinder the ability to establish causal relationships; therefore, longitudinal studies with larger cohorts may be necessary to validate these findings in the future. Third, while participants under 18 years of age may lack refractive stability. China’s clinical guidelines (as outlined in ophthalmic expert consensus documents) permit corneal refractive surgery (e.g., LASIK, SMILE) for minors with myopia who demonstrate compelling career-specific requirements (such as eligibility criteria for military or police academy enrollment). This exception is strictly conditional upon comprehensive preoperative evaluation and documented informed consent obtained from both the minor and their legal guardian(s).
In summary, this study outlines the biomechanical characteristics of Chinese refractive surgery candidates and provides reference values for CH and CRF across different refractive powers and corneal thicknesses. Additionally, we examined the correlations between CH, CRF, and factors such as sex, age, corneal thickness, diopters, corneal keratometry, and corneal diameters. Our results show that corneal thickness and curvature are positively correlated with CH and CRF, while age and higher myopia are negatively correlated with CH.
References
- 1. Piñero DP, Alcón N. In vivo characterization of corneal biomechanics. J Cataract Refract Surg. 2014;40(6):870–87. pmid:24857436
- 2. Chong J, Dupps WJ Jr. Corneal biomechanics: Measurement and structural correlations. Exp Eye Res. 2021;205:108508. pmid:33609511
- 3. Celebi ARC, Kilavuzoglu AE, Altiparmak UE, Cosar Yurteri CB. Age-related change in corneal biomechanical parameters in a healthy Caucasian population. Ophthalmic Epidemiol. 2018;25(1):55–62. pmid:28891725
- 4. Kotecha A, Russell RA, Sinapis A, Pourjavan S, Sinapis D, Garway-Heath DF. Biomechanical parameters of the cornea measured with the Ocular Response Analyzer in normal eyes. BMC Ophthalmol. 2014;14:11. pmid:24479520
- 5. Dupps WJ Jr. Hysteresis: new mechanospeak for the ophthalmologist. J Cataract Refract Surg. 2007;33(9):1499–501. pmid:17720051
- 6. Rojananuangnit K. Corneal Hysteresis in Thais and Variation of Corneal Hysteresis in Glaucoma. Clin Optom (Auckl). 2021;13:287–99. pmid:34629920
- 7. Chua J, Nongpiur ME, Zhao W, Tham YC, Gupta P, Sabanayagam C, et al. Comparison of Corneal Biomechanical Properties between Indian and Chinese Adults. Ophthalmology. 2017;124(9):1271–9. pmid:28461014
- 8. Al-Arfaj K, Yassin SA, Al-Dairi W, Al-Shamlan F, Al-Jindan M. Corneal biomechanics in normal Saudi individuals. Saudi J Ophthalmol. 2016;30(3):180–4. pmid:28210179
- 9. Del Buey MA, Lavilla L, Ascaso FJ, Lanchares E, Huerva V, Cristóbal JA. Assessment of corneal biomechanical properties and intraocular pressure in myopic spanish healthy population. J Ophthalmol. 2014;2014:905129. pmid:24719755
- 10. Moshirfar M, Tukan AN, Bundogji N, Liu HY, McCabe SE, Ronquillo YC, et al. Ectasia After Corneal Refractive Surgery: A Systematic Review. Ophthalmol Ther. 2021;10(4):753–76. pmid:34417707
- 11. Zhao L, Yin Y, Hu T, Du K, Lu Y, Fu Q, et al. Comprehensive management of post-LASIK ectasia: From prevention to treatment. Acta Ophthalmol. 2023;101(5):485–503. pmid:36774646
- 12. Kamiya K, Hagishima M, Fujimura F, Shimizu K. Factors affecting corneal hysteresis in normal eyes. Graefes Arch Clin Exp Ophthalmol. 2008;246(10):1491–4. pmid:18546008
- 13. Oncel B, Dinc UA, Gorgun E, Yalvaç BI. Diurnal variation of corneal biomechanics and intraocular pressure in normal subjects. Eur J Ophthalmol. 2009;19(5):798–803. pmid:19787600
- 14. El Massry AAK, Said AA, Osman IM, Bessa AS, Elmasry MA, Elsayed EN, et al. Corneal biomechanics in different age groups. Int Ophthalmol. 2020;40(4):967–74. pmid:31916064
- 15. Bahadir Kilavuzoglu AE, Cosar CB, Bildirici I, Cetin O, Ozbasli E. Estrogen- and Progesterone-Induced Variation in Corneal Parameters According to Hormonal Status. Eye Contact Lens. 2018;44 Suppl 1:S179–84. pmid:28244931
- 16. Sedaghat M-R, Momeni-Moghaddam H, Azimi A, Fakhimi Z, Ziaei M, Danesh Z, et al. Corneal Biomechanical Properties in Varying Severities of Myopia. Front Bioeng Biotechnol. 2021;8:595330. pmid:33553113
- 17. Qiu K, Lu X, Zhang R, Wang G, Zhang M. Corneal Biomechanics Determination in Healthy Myopic Subjects. J Ophthalmol. 2016;2016:2793516. pmid:27525109
- 18. İnceoğlu N, Emre S, Ulusoy MO. Investigation of corneal biomechanics at moderate to high refractive errors. Int Ophthalmol. 2018;38(3):1061–7. pmid:28540493
- 19. Wu W, Dou R, Wang Y. Comparison of Corneal Biomechanics Between Low and High Myopic Eyes-A Meta-analysis. Am J Ophthalmol. 2019;207:419–25. pmid:31374186
- 20. Song Y, Congdon N, Li L, Zhou Z, Choi K, Lam DSC, 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(5):819–26. pmid:18328999
- 21. Bueno-Gimeno I, España-Gregori E, Gene-Sampedro A, Lanzagorta-Aresti A, Piñero-Llorens DP. Relationship among corneal biomechanics, refractive error, and axial length. Optom Vis Sci. 2014;91(5):507–13. pmid:24705484
- 22. Dhakal R, Vupparaboina KK, Verkicharla PK. Anterior Sclera Undergoes Thinning with Increasing Degree of Myopia. Invest Ophthalmol Vis Sci. 2020;61(4):6. pmid:32271887
- 23. He M, Wang W, Ding H, Zhong X. Corneal Biomechanical Properties in High Myopia Measured by Dynamic Scheimpflug Imaging Technology. Optom Vis Sci. 2017;94(12):1074–80. pmid:29135719
- 24. McBrien NA, Gentle A. Role of the sclera in the development and pathological complications of myopia. Prog Retin Eye Res. 2003;22(3):307–38. pmid:12852489
- 25. Du Y, Zhang Y, Zhang Y, Li T, Wang J, Du Z. Analysis of potential impact factors of corneal biomechanics in myopia. BMC Ophthalmol. 2023;23(1):143. pmid:37024820
- 26. Rosa N, Lanza M, De Bernardo M, Signoriello G, Chiodini P. Relationship Between Corneal Hysteresis and Corneal Resistance Factor with Other Ocular Parameters. Semin Ophthalmol. 2015;30(5–6):335–9. pmid:24506466
- 27. Strobbe E, Cellini M, Barbaresi U, Campos EC. Influence of age and gender on corneal biomechanical properties in a healthy Italian population. Cornea. 2014;33(9):968–72. pmid:25014149
- 28. Fontes BM, Ambrósio R Jr, Velarde GC, Nosé W. Corneal biomechanical evaluation in healthy thin corneas compared with matched keratoconus cases. Arq Bras Oftalmol. 2011;74(1):13–6. pmid:21670900
- 29. Galletti JG, Pförtner T, Bonthoux FF. Improved keratoconus detection by ocular response analyzer testing after consideration of corneal thickness as a confounding factor. J Refract Surg. 2012;28(3):202–8. pmid:22230059
- 30. 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(3):644–8. pmid:9501878
- 31. Elsheikh A, Wang D, Rama P, Campanelli M, Garway-Heath D. Experimental assessment of human corneal hysteresis. Curr Eye Res. 2008;33(3):205–13. pmid:18350431
- 32. Kamiya K, Shimizu K, Ohmoto F. Effect of aging on corneal biomechanical parameters using the ocular response analyzer. J Refract Surg. 2009;25(10):888–93. pmid:19835329
- 33. Hwang HS, Park SK, Kim MS. The biomechanical properties of the cornea and anterior segment parameters. BMC Ophthalmol. 2013;13:49. pmid:24083664
- 34. Francis BA, Hsieh A, Lai M-Y, Chopra V, Pena F, Azen S, et al. Effects of corneal thickness, corneal curvature, and intraocular pressure level on Goldmann applanation tonometry and dynamic contour tonometry. Ophthalmology. 2007;114(1):20–6. pmid:17070592
- 35. Matsumoto T, Makino H, Uozato H, Saishin M, Miyamoto S. The Influence of Corneal Thickness and Curvature on the Difference Between Intraocular Pressure Measurements Obtained with a Non-contact Tonometer and Those with a Goldmann Applanation Tonometer. Jpn J Ophthalmol. 2000;44(6):691. pmid:11094194