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Diurnal variations in corneal biomechanics in healthy young adults
BMC Ophthalmology volume 25, Article number: 90 (2025)
Abstract
Purpose
To assess the diurnal changes in corneal biomechanics in healthy young adults.
Methods
At Wenzhou Medical University Eye Hospital in China, a prospective case series. Each healthy subject had six Corvis ST examinations, from 10:00 on a first day to 6:00 on the following day, at 4-hour intervals. The data collected included the biomechanically corrected IOP (bIOP), the central corneal thickness (CCT) and six dynamic corneal response (DCR) parameters, namely deformation amplitude (DA), the ratio between DA values at the apex and 2 mm from the apex (DAR2), integrated inverse radius (IIR), the stiffness parameter at first applanation (SP-A1), Corvis biomechanical index (CBI) and the updated stress-strain index (SSIv2). A multilevel model was used to assess the changes in DCR parameters of patients over time during the examination period.
Results
Sixty-one subjects were included and intra-operator reproducibility was good for most DCR parameters at the 6 time points. DA, DAR2, IIR and CBI showed small fluctuations during the 24-hour cycle with mean values of 0.1, 0.16, 0.34, and 0.04 units, respectively, while SP-A1 showed higher variations averaging 20.57 units and SSIv2 had the least fluctuation within 0.10 units during 24-hour cycle. After correcting for the effects of CCT and bIOP, the diurnal fluctuations in IIR, CBI and SSIv2 were not statistically significant, unlike the fluctuations in DA, DAR2 and SP-A1, which remained significant.
Conclusions
Compared with the DA, DAR2, IIR and CBI, SP-A1 was more affected while SSIv2 was the less affected by the diurnal variations and associated corneal edema.
Introduction
Corneal biomechanics has recently become a topic of great interest in ophthalmology clinical research. Most of this work has been conducted in the past two decades, and significant improvements have been made as a result in the diagnosis and treatment optimization of ophthalmic diseases such as glaucoma [1] and keratoconus [2]. Corneal biomechanics commonly refers to both corneal stiffness and corneal viscoelasticity. Corneal overall stiffness describes the immediate response of the cornea to mechanical loading, and consists of a geometric part and a tissue material part. Studies have shown that corneal thickness dominates the geometric stiffness [3, 4], while the material stiffness is controlled by the tissue’s collagen fibril content and the cross-links, and changes with age [5, 6] and medical history [2, 7].
There are various methods used to evaluate the corneal stiffness in-vivo, including the Corvis ST. The instrument generates a rapid air pulse that acts on the cornea and measures its mechanical response [8], the analysis of which provides estimates of the intraocular pressure (IOP) and various repeatable dynamic corneal response (DCR) parameters [9]. Among the DCRs with evidenced strong correlation with corneal stiffness are the deformation amplitude (DA), the ratio between DA values at the apex and 2 mm from the apex (DAR2), the integrated inverse radius (IIR), the stiffness parameter at first applanation (SP-A1), the Corvis biomechanical index (CBI) and the updated stress-strain index (SSIv2). All these DCRs present measures of the cornea’s overall stiffness, except the SSIv2 which relates to the material stiffness [10]. The first group was reported to be correlated with CCT and IOP [11], while the SSIv2 seemed to be independent of both parameters as expected in a material stiffness measure [10].
Both CCT and IOP are known to fluctuate throughout the day [12], and therefore, it is clinically important to understand whether this fluctuation has much impact on the DCR measures. As the DCRs are often used in the detection and management of ocular diseases such as keratoconus [13] and glaucoma [14], their potential diurnal fluctuation may influence their efficacy. This point is the subject of the study presented in this paper, in which the diurnal changes in the Corvis ST DCRs are measured in healthy human subjects over a day. The study also considers whether these changes are correlated with the IOP and CCT fluctuations.
Methods
Participants
This prospective study involving 61 human participants, adhered to the tenets of the Declaration of Helsinki. This study has been approved by the Institutional Review Board (Ethics Committee of the School of Ophthalmology, Wenzhou Medical University, China). All participants are required to provide written informed consent prior to any research related activities, after explaining the nature of the study and its potential consequences. All subjects have accepted the 24-hour IOP measurement regime upon being briefed on the study’s benefits and before signing their consent form. The inclusion criteria were absence of ocular diseases (other than refractive errors), age between 18 and 45 years, and not wearing contact lenses for two weeks prior to the examination. The exclusion criteria were significant wake-sleep rhythm disturbances and hypnotic drug consumption, the presence of glaucoma suspect, pseudocystic exfoliation syndrome, intraocular surgery history, suspect or compatible keratoconus, and other eye diseases patients. All the patients were of East Asian race and of Han descent. The subjects underwent binocular examination, but to avoid simultaneous enrollment of both eyes, affecting the independence of the sample, only the right eye of each subject was included in data analysis.
Experimental design
Upon participants’ arrival at the hospital, the anterior and posterior segments of the eyes went through slit-lamp and fundoscopic examinations, and those who did not meet the inclusion criteria were excluded. The refractive error was then measured with an automatic optometer (AR-1 Nidek, Japan) and the axial length(AL) was measured with an IOL Master 500 (Carl Zeiss Meditec, Germany). Corneal biomechanical testing and IOP measurement with the Corvis ST (CVS, software version 1.03b1445, OCULUS Optikgeräte, Wetzlar, Germany) were performed 6 times from 10:00 to 6:00 the next morning at 4 h intervals (10:00, 14:00, 18:00, 22:00, 2:00, 6:00) [15]. Measurements were repeated 3 times at each time point to evaluate the repeatability of the CVS outputs. The average value of the 3 measurements at each time point was used in analysis. All measurements were taken by the same experienced operator.
The biomechanically corrected IOP (bIOP), the central corneal thickness (CCT) and the six CVS DCR parameters that have been consistently linked to corneal stiffness [16, 17] were recorded. These parameters included the DA, DAR2, IIR, SP-A1, CBI and SSIv2– the last parameter being a material stiffness measure that was recently proposed and found to have weak correlation with bIOP and CCT [10], and to be able to detect forme-fruste and subclinical keratoconus [18].
The researchers instructed the subjects to check in at the hospital for 24 h and to avoid strenuous exercise during that time. They performed normal indoor activities during wakefulness and went to bed at 23:00, then were awakened at 2:00 and 6:00 to avoid Valsava movements and were measured in sitting position. The parameter plot was generated from the average value at each time point, and the highest and lowest average values were determined. The parameter plot further allowed calculating the mean circadian value of the day, and the fluctuation– defined as the highest value minus the lowest value. The relative fluctuation was also calculated as the fluctuation divided by the mean circadian value. The fluctuation was calculated for bIOP, CCT, DA, DAR2, IIR, SP-A1, CBI and SSIv2.
Statistical analysis
Statistical analysis was performed using IBM SPSS version 20. The mean and standard deviation of bIOP, CCT, and the DCRs were calculated using the arithmetic mean and population standard deviation. Intraclass correlation coefficient (ICC), standard deviation (Sw) and coefficient of within-subject variation (CoV) were used to assess the repeatability of each parameter over three repeated CVS measurements– and this exercise was carried out at the six time points considered. The coefficient of variation (CoV) was calculated by dividing the mean of the 6 within-subject measurement means by Sw. An ICC above 0.70, and a CoV below 20% indicated good repeatability, while an ICC of > 0.60 and a CoV of < 20% indicated fair repeatability [19].
Multilevel modeling (MLM) was used to incorporate the subjects’ axis length as a fixed effect to analyze the changes of corneal biomechanical indexes at the detection time points, and to explore the relationship between corneal biomechanical indexes and bIOP and CCT. MLM is a powerful tool for modeling the expected relationship between dependent data (biomechanical indices) and independent data (bIOP, CCT, and time points) [20], it can establish the linear relationship of each DCR parameter with bIOP and CCT. In this analysis, p values < 0.05 were considered indicative of statistical significance.
Results
The mean age of all participants was 30.11 ± 8.26 years, gender ratio was 41/20 (female/male). The mean axial length, spherical equipment and astigmatism were 24.87 ± 1.23 mm, -3.75 ± 2.74 D, and 0.56 ± 0.66 D respectively. Table 1 shows the mean, standard deviation, ICC, Sw and CoV for bIOP, CCT and DCR parameters at the six consecutive time points. The results demonstrated a good repeatability of all metrics among all time points (ICC > 0.7, CoV < 20%) except for CBI in 10:00 (ICC = 0.697). Further, as the mean CBI was very low (0.15), its CoV was not calculated.
Figure 1 shows that bIOP was lowest at 2:00 (13.52 ± 1.93 mmHg), and highest at 10:00 (15.55 ± 2.20 mmHg) with progressive reduction over the nocturnal period. The bIOP fluctuation was 2.97 ± 1.10 mmHg (range: 1.50 to 6.29 mmHg), and the relative fluctuation was 20.30 ± 6.43% (range 10.43–35.41%). In contrast, CCT was largest at 2:00 (558.22 ± 32.95 μm) and lowest at 14:00 (544.22 ± 29.93 μm)– its fluctuation was 19.69 ± 7.20 μm (range 4.67 to 45.33 μm), and relative fluctuation was 3.57 ± 1.25% (range 0.92–7.66%). There was no significant difference in CCT over the four time periods during the day (between 10:00 and 22:00), but there were significant changes between 2:00 and 10:00 (p < 0.01), and between 6:00 and 10:00 (p < 0.01).
Figure 2 shows that without considering the effects of bIOP and CCT on DA, DAR2, IIR and SP-A1, the DCR values showed significant diurnal fluctuations (all p < 0.01). In contrast, there were no significant changes in CBI and SSIv2 during the 24-hour cycle except for CBI between 10:00 and 22:00 (p = 0.03). During 24-hour cycle, DA, DAR2, IIR, SP-A1, CBI and SSIv2 showed the fluctuations of 0.15 ± 0.06, 0.36 ± 0.16, 0.93 ± 0.35, 20.57 ± 6.66, 0.16 ± 0.17 and 0.10 ± 0.05 units. The relative fluctuation was 14.05% ± 5.64%, 8.54% ± 3.56%, 11.19% ± 4.31%, 22.01% ± 7.09% and 10.53% ± 4.62% for DA, DAR2, IIR, SP-A1 and SSIv2, respectively. The relative fluctuation of SP-A1 was the highest (p < 0.05), followed by DA and IIR, and the lowest was associated with DAR2 which was not statistically significant from SSIv2 (p = 0.064). Since the mean CBI was very low, the relative fluctuation was not calculated.
Figure 2 shows that DA and SP-A1 were affected by bIOP than by CCT, while DAR2, IIR and CBI were affected similarly by bIOP and CCT. SSIv2 was only influenced by CCT, but the effects were small and less than those observed for the other 5 DCRs. The fluctuations of SSIv2 were also minimal, 0.027 units (2.88%), after excluding the effects of bIOP and CCT.
In Table 2, MLM results are presented while using the 6 DCR metrics as outcome (dependent) variables, and CCT, bIOP and the 6 time points as the explanatory (independent) variables. After controlling CCT, the analysis indicated that all DCRs were correlated with bIOP (all p < 0.01) except for SSIv2 (p = 0.837) as expected [10], a 1-mmHg increase in bIOP was associated with − 0.036, -0.075, -0.238, 6.315, -0.023 and 0.001 units of change in DA, DAR2, IIR, SP-A1, CBI and SSIv2, respectively. After controlling bIOP, all DCR metrics showed correlation with CCT (all P < 0.01), a 10 μm increase in CCT was associated with − 0.010, -0.081, -0.204, 3.703, -0.041 and 0.013 units of change in DA, DAR2, IIR, SP-A1, CBI and SSIv2, respectively. Finally, after simultaneously correcting for the effects of CCT and bIOP, the fluctuations in IIR, CBI and SSIv2 were not significant (all p > 0.05), while the changes in DA, DAR2 and SP-A1 remained significant (all p < 0.05).
Discussion
Corneal biomechanics has become an important aspect of clinical ophthalmology with applications including prediction of structural and functional progression in glaucoma suspects [1], tracking progression of keratoconus [21], and evaluating the stiffening effect of corneal cross-linking [22]. A major breakthrough has led to the ability to measure corneal biomechanics in vivo using devices such as the Corvis ST. Recent research has confirmed the utility of the Corvis ST DCR parameters in quantifying corneal biomechanics, and in particular corneal stiffness [7]. This study seeks to add to this research by assessing the possible changes in the values of these parameters with the diurnal cycle. The results showed significant changes in all DCRs over the diurnal cycle except for SSIv2. However, after removing the effects of the diurnal fluctuations in bIOP and CCT, the changes in the DCRs reduced and became non-significant in also IIR and CBI.
The study also showed that CVS exhibits good repeatability in measuring the bIOP, CCT, and the 6 DCRs. This suggests that CVS measurements taken at any point during the day can result in reproducible bIOP, CCT, and DCRs data that can be used in clinical practice.
Previous studies using the Ocular Response Analyzer (ORA) failed to find significant daytime variations (8:00–17:00 and 9:00–19:00) in corneal biomechanics metrics [23,24,25]. And a further study arrived at a similar conclusion over a 24-hour period [26]. In contrast, other studies reported significant elevations in both the Corneal Hysteresis (CH) and the Corneal Resistance Factor (CRF)– both produced by ORA– on awakening [27, 28]. Similar to the CVS DCRs, the CH and CRF were correlated with corneal biomechanical behavior and varied with the diurnal cycle, and the associated changes in IOP and CCT. This is compatible with another earlier reports, in which the two ORA parameters were significantly influenced by IOP and CCT [29].
The stiffness parameter, SSIv2, considered in this study, was developed to represents the material stiffness of the corneal tissue [10], so was expected to show independence of IOP and CCT. In previous studies, this independence has been reported [10], but in others, some dependence on IOP was identified [7, 11]. The results of the present study should be seen in a different light. In this case, the cornea experienced changes in thickness over the diurnal cycle, which were due to changes in the tissue’s hydration. For this reason, the SSIv2 would be expected to change (indicating a material stiffness reduction) with CCT increases as was found in this study. In addition, even if the actual intraocular pressure does not change, bIOP (IOP calculated by nonlinear finite element simulation to significantly reduce the correlation with the major corneal stiffness parameter CCT, etc [30]). will still change with the daily variation of CCT, as the CCT considered in the bIOP algorithm will cause this variation.
On the other hand, the changes in the other DCRs, which denote the overall corneal stiffness, would be more complicated. As the overall stiffness is dependent on both the cornea’s geometry and material stiffness, the diurnal effects could cause corneal edema leading in turn to larger CCT and lower material stiffness (described below). The combined effect of these variations could in theory move the overall stiffness measures either way. In our study and after correcting for diurnal fluctuations of bIOP and CCT, the variations in 2 DCRs (IIR, CBI) were not significant over all time periods, between 10:00 and 6:00. However, for the other 3 DCR metrics (DA, DAR2, SP-A1), the variations were not significant over periods between time points 10:00, 14:00, 18:00 and 22:00. An interesting, related observation from the study is that the changes in these three DCRs mainly occurred during the periods when the daily changes in CCT were most pronounced, namely 2:00–10:00 and 6:00–10:00. The changes of the three DCRs were also not obvious during the period from 10:00 to 22:00 when CCT did not change significantly.
The CCT fluctuations reported herein are consistent with previous studies on the diurnal effects [31, 32]. CCT was greatest after waking from sleep with the eyes closed. According to previous studies, changes in CCT can be used as an indicator of corneal hydration [33], and in this regard, both the stroma and the epithelium swell proportionally (relative to their thicknesses) overnight due to edema caused by decreased evaporation of the tear film while sleeping [32]. Furthermore, reduction in oxygen levels beneath the closed eyelid overnight induces corneal anaerobic metabolism, and the resulting increased anaerobic respiration increases lactate ion production and leads to corneal stromal oedema [34]. Due to differences in collagen fibril interweaving in the anterior and posterior stroma [35, 36], the changes in stromal oedema at the macro scale caused by closed eyelids overnight take place mainly in the posterior stroma. In contrast, when the eyelids are open, the endothelial pump helps control corneal hydration and thickness [34], and this process means that after 2 h of opening eyelids, the edematous cornea drops to “normal” hydration levels [31].
After excluding the effects of 24-hour fluctuations in bIOP and CCT, the results of this study showed a statistically significant increases in DA at 2:00 and statistically significant decreases in SP-A1 compared to 10:00. The larger the CCT (caused by swelling), the larger the DA and DAR2, and the smaller SP-A1– all of which indicate stiffness decreases due to the edema caused by corneal hypoxia. However, there were no significant changes in IIR or CBI at 2:00 and 6:00 compared with 10:00, suggesting that these two metrics may be more stable and less susceptible to corneal edema than DA, DAR2 and SP-A1. Conversely, when fluctuations were not excluded, the differences between the SSIv2 at 10:00 and the SSIv2 at the rest of the time were not significant, indicating that SSIv2 had better stability than the other five DCRs.
The results regarding the relationship between bIOP and DCR parameters were similar to those of previous study [11]. Previous studies have shown that the five DCRs, DA, DAR2, IIR, SP-A1 and CBI have evident potential in the daily clinical diagnosis of keratoconus [7, 37]. In this study, a strong positive correlation was observed between changes in SP-A1 and changes in bIOP and CCT associated with the 24-hour diurnal fluctuations (all p < 0.001), indicating that increased bIOP and CCT cause higher corneal stiffness. This finding has important clinical applications for the detection of subclinical keratoconus.
The difference in stiffness parameter SP-A1 between subclinical keratoconus and healthy eyes ranged from 15 to 20 [38, 39], and this difference could be produced by an bIOP change of 2.4–3.2 mmHg or a CCT change of 40.5–54.0 μm as indiacated in this study. On the other hand, strong negative correlations were observed between the changes in DA, DAR2, IIR and that in CBI with the 24-hour fluctuations in bIOP and CCT (all p < 0.001), which also suggests that the increase in bIOP and CCT can lead to stiffness increases. As the corresponding change in this study, the difference in IIR between clinical subclinical keratoconus and healthy eye was approximately 1.3 [40] units and this difference could be caused by a 5.5 mmHg change in bIOP or a 63.8 μm change in CCT. Furthermore, the difference in CBI between subclinical conical cornea and healthy eye ranged from 0.13 to 0.20 [38, 39], and this difference can be caused by a 5.8–8.9 mmHg change in bIOP or a 31.4–48.2 μm change in CCT. Therefore, higher bIOP and/or CCT may reduce the effectiveness of the DCRs in detecting subclinical keratoconus. Like the other five DCR parameters, SSIv2 was also affected by bIOP and CCT, but to a much smaller extent. The SSIv2 fluctuation throughout the day was not influenced by corneal edema, supporting its potential for use in subclinical keratoconus detection as was reported in a previous study [18].
This study found that bIOP and/or CCT had an impact on IIR, CBI and SSIv2 parameters. However, these effects are measurable and controllable, making IIR, CBI, and SSIv2 valuable insights into the biomechanical properties of the cornea and promising as diagnostic parameters for subclinical keratoconus. However, these findings need to be supported by larger-scale, multicenter studies involving keratoconus patients.
It is well known that the biomechanical properties of cornea, such as elasticity, thickness and shape, affect the measurement of intraocular pressure (IOP) [41], and corneal biomechanical parameters (such as DA, SP-A1, CBI, and DA) are of great significance in the diagnosis and treatment of glaucoma [42,43,44], for example: SP-A1 can predict the progression of optic nerve structure and function in patients with suspected glaucoma [44]; DA is associated with susceptibility or risk of progression of glaucoma [42]; DA Ratio and IIR in patients with normal intraocular pressure glaucoma were significantly higher than those in healthy control group [42]. In this study, DA, DAR2, IIR, CBI and SP-A1 were all affected by 24-hour fluctuation of IOP and CCT. This makes it necessary to consider the effects of 24-hour fluctuations in IOP and CCT when evaluating the relationship between these corneal biomechanical parameters and glaucoma.
In this study, measurements were taken at intervals of 4 h over the course of a day and a night [15] for participants aged between 18 and 45 years since young people are more susceptible to diseases associated with changes in corneal biomechanics such as keratoconus [45]. The diurnal rate of corneal thickness change was 3.57%, which was similar to the average night-time corneal swelling reported in previous studies (including 3.06% [46] and 7.8% [47]). A limitation of the study is the reliance on only 6 measurements, the minimum required for a 24-hour IOP measurement [15]. Furthermore, a small sample size was used in this study due to the heavy demands on participants to spend a night in hospital with sleep interruptions. There was also no restriction on subjects yawning prior to measurement, which could have made the results impact-able.
In summary, this study analyzed the reproducibility of six CVS DCR parameters during the diurnal fluctuations of bIOP and CCT. All parameters were strongly correlated with bIOP and CCT, the effects of which on corneal biomechanical metrics should be considered. Some DCRs (IIR, CBI, SSIv2) appear to be less affected by corneal edema than others (DA, DAR2, SP-A1). The SP-A1 was the highest, while SSIv2 was the least affected DCRs by the diurnal variations and the associated IOP fluctuations. These outcomes have direct clinical benefits in guiding clinicians on the reliability of Corvis metrics when measured at different times of day and night.
What was known
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CCT and IOP are known to fluctuate throughout the day.
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DCR parameters provided by Corvis ST were correlated with IOP and CCT.
What this paper adds
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SP-A1 was the highest, while SSIv2 was the least affected by the diurnal variations in IOP and CCT.
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After correcting for the effects of CCT and bIOP, IIR, CBI and SSIv2 kept stable during 24-hour cycle.
Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
References
Qassim A, Mullany S, Abedi F, Marshall H, Hassall MM, Kolovos A, Knight LSW, Nguyen T, Awadalla MS, Chappell A, et al. Corneal stiffness parameters are predictive of structural and functional progression in Glaucoma suspect eyes. Ophthalmology. 2021;128(7):993–1004.
Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42(4):297–319.
Huseynova T, Waring GO, Roberts C, Krueger RR, Tomita M. Corneal biomechanics as a function of intraocular pressure and pachymetry by Dynamic Infrared Signal and Scheimpflug Imaging Analysis in normal eyes. Am J Ophthalmol. 2014;157(4):885–93.
Bao F, Deng M, Wang Q, Huang J, Yang J, Whitford C, Geraghty B, Yu A, Elsheikh A. Evaluation of the relationship of corneal biomechanical metrics with physical intraocular pressure and central corneal thickness in ex vivo rabbit eye globes. Exp Eye Res. 2015;137:11–7.
Daxer A, Misof K, Grabner B, Ettl A, Fratzl P. Collagen fibrils in the human corneal stroma: structure and aging. Investig Ophthalmol Vis Sci. 1998;39(3):644–8.
Liu G, Rong H, Pei R, Du B, Jin N, Wang D, Jin C, Wei R. Age distribution and associated factors of cornea biomechanical parameter stress-strain index in Chinese healthy population. BMC Ophthalmol. 2020;20(1):436.
Padmanabhan P, Lopes BT, Eliasy A, Abass A, Vinciguerra R, Vinciguerra P, Ambrósio R, Elsheikh A. Evaluation of corneal biomechanical behavior in vivo for healthy and keratoconic eyes using the stress–strain index. J Cataract Refract Surg. 2022;48(10):1162–7.
Hong J, Xu J, Wei A, Deng SX, Cui X, Yu X, Sun X. A New Tonometer—the Corvis ST Tonometer: clinical comparison with noncontact and Goldmann Applanation Tonometers. Invest Opthalmology Visual Sci. 2013;54(1):659.
Reznicek L, Muth D, Kampik A, Neubauer AS, Hirneiss C. Evaluation of a novel Scheimpflug-based non-contact tonometer in healthy subjects and patients with ocular hypertension and glaucoma. Br J Ophthalmol. 2013;97(11):1410–4.
Eliasy A. In Vivo Measurement of Corneal Stiffness and Intraocular Pressure to Enable Personalised Disease Management and Treatment. Ph.D. England: The University of Liverpool (United Kingdom); 2020.
Ye Y, Li Y, Zhu Z, Abu Said AZM, Nguelemo Mayopa K, Akiti S, Huang C, Lopes BT, Eliasy A, Miao Y, et al. Effect of mydriasis-caused intraocular pressure changes on corneal Biomechanical Metrics. Front Bioeng Biotechnol. 2021;9:751628.
Sakata R, Aihara M, Murata H, Saito H, Iwase A, Yasuda N, Araie M. Intraocular pressure Change over a habitual 24-Hour period after changing posture or drinking Water and related factors in normal tension Glaucoma. Invest Opthalmology Visual Sci. 2013;54(8):5313.
Henriquez M, Hadid M, Izquierdo L. A systematic review of subclinical Keratoconus and Forme Fruste Keratoconus. J Refractive Surg (Thorofare NJ: 1995). 2020;36(4):270–9.
Del Buey-Sayas M, Lanchares-Sancho E, Campins-Falcó P, Pinazo-Durán M, Peris-Martínez C. Corneal biomechanical parameters and central corneal thickness in Glaucoma patients, Glaucoma suspects, and a healthy Population. J Clin Med 2021, 10(12).
Mansouri K, Tanna AP, De Moraes CG, Camp AS, Weinreb RN. Review of the measurement and management of 24-hour intraocular pressure in patients with glaucoma. Surv Ophthalmol. 2020;65(2):171–86.
Vinciguerra R, Elsheikh A, Roberts CJ, Ambrósio R, Kang DSY, Lopes BT, Morenghi E, Azzolini C, Vinciguerra P. Influence of Pachymetry and intraocular pressure on dynamic corneal response parameters in healthy patients. J Refract Surg. 2016;32(8):550–61.
Roberts CJ, Mahmoud AM, Bons JP, Hossain A, Elsheikh A, Vinciguerra R, Vinciguerra P, Ambrósio R. Introduction of two novel stiffness parameters and interpretation of Air Puff–Induced Biomechanical deformation parameters with a dynamic Scheimpflug Analyzer. J Refract Surg. 2017;33(4):266–73.
Miao Y, Ma X, Qu Z, Eliasy A, Wu B, Xu H, Wang P, Zheng X, Wang J, Ye Y et al. Performance of updated stress-strain index in differentiating between normal, Forme-Fruste, subclinical and clinical keratoconic eyes. Am J Ophthalmol 2023.
Ali NQ, Patel DV, McGhee CNJ. Biomechanical responses of healthy and keratoconic corneas measured using a Noncontact Scheimpflug-based Tonometer. Invest Opthalmology Visual Sci. 2014;55(6):3651.
Kotecha A, Crabb DP, Spratt A, Garway-Heath DF. The relationship between diurnal variations in intraocular pressure measurements and central corneal thickness and corneal hysteresis. Invest Opthalmology Visual Sci. 2009;50(9):4229.
Zhao Y, Shen Y, Yan Z, Tian M, Zhao J, Zhou X. Relationship among corneal stiffness, thickness, and Biomechanical parameters measured by Corvis ST, Pentacam and ORA in Keratoconus. Front Physiol. 2019;10:740.
Zheng X, Weng Y, Wang Y, Xin Y, Wu J, Ziad Masoud Abu Said A, Nguelemo Mayopa K, Akiti S, Li X, Wang C, et al. Long-term effects of Riboflavin Ultraviolet-A–Induced CXL with different irradiances on the Biomechanics of in vivo rabbit corneas. J Refract Surg. 2022;38(6):389–97.
Oncel B, Dinc UA, Gorgun E, Ilgaz Yalvaç B. Diurnal Variation of Corneal Biomechanics and intraocular pressure in normal subjects. Eur J Ophthalmol. 2009;19(5):798–803.
González-Méijome JM, Queirós A, Jorge J, Díaz-Rey A, Parafita MA. Intraoffice Variability of Corneal Biomechanical Parameters and intraocular pressure (IOP). Optom Vis Sci. 2008;85(6):457–62.
Laiquzzaman M, Bhojwani R, Cunliffe I, Shah S. Diurnal variation of ocular hysteresis in normal subjects: relevance in clinical context. Clin Experimental Ophthalmol. 2006;34(2):114–8.
Kida T, Liu JHK, Weinreb RN. Effect of 24-Hour corneal biomechanical changes on intraocular pressure measurement. Invest Opthalmology Visual Sci. 2006;47(10):4422.
Shen M, Wang J, Qu J, Xu S, Wang X, Fang H, Lu F. Diurnal variation of ocular hysteresis, corneal thickness, and intraocular pressure. Optom Vis Sci. 2008;85(12):1185–92.
Lau W, Pye DC. Associations between diurnal changes in Goldmann Tonometry, corneal geometry, and Ocular Response Analyzer parameters. Cornea. 2012;31(6):639–44.
Narayanaswamy A, Chung RS, Wu R-Y, Park J, Wong W-L, Saw S-M, Wong TY, Aung T. Determinants of corneal Biomechanical properties in an adult Chinese Population. Ophthalmology. 2011;118(7):1253–9.
Akram J, Mir Mohi Sefat S, Daniel K, Ahmed E. Development and validation of a correction equation for Corvis tonometry. Comput Methods Biomech BioMed Eng 2015.
Shao P, Seiler TG, Eltony AM, Ramier A, Kwok SJJ, Scarcelli G, Ii RP, Yun S-H. Effects of corneal hydration on Brillouin Microscopy in vivo. Invest Opthalmology Visual Sci. 2018;59(7):3020.
Feng Y, Varikooty J, Simpson TL. Diurnal variation of corneal and corneal epithelial thickness measured using Optical Coherence Tomography. Cornea. 2001;20(5):480–3.
Hatami-Marbini H, Etebu E, Rahimi A. Swelling pressure and hydration behavior of Porcine corneal stroma. Curr Eye Res. 2013;38(11):1124–32.
Leung BK, Bonanno JA, Radke CJ. Oxygen-deficient metabolism and corneal edema. Prog Retin Eye Res. 2011;30(6):471–92.
Hatami-Marbini H, Jayaram SM. Effect of UVA/Riboflavin Collagen Crosslinking on Biomechanics of Artificially Swollen corneas. Invest Opthalmology Visual Sci. 2018;59(2):764.
Edelhauser HF. The balance between corneal transparency and Edema the Proctor lecture. Invest Opthalmology Visual Sci. 2006;47(5):1755.
Yang K, Xu L, Fan Q, Zhao* D, Ren* S. Repeatability and comparison of new Corvis ST parameters in normal and keratoconus eyes. Sci Rep. 2019;9(1):15379.
Koc M, Aydemir E, Tekin K, Inanc M, Kosekahya P, Kiziltoprak H. Biomechanical analysis of subclinical Keratoconus with Normal Topographic, Topometric, and Tomographic findings. J Refract Surg. 2019;35(4):247–52.
Ren S, Xu L, Fan Q, Gu Y, Yang K. Accuracy of new Corvis ST parameters for detecting subclinical and clinical keratoconus eyes in a Chinese population. Sci Rep. 2021;11(1):4962.
Chan TCY, Wang YM, Yu M, Jhanji V. Comparison of corneal tomography and a New Combined Tomographic Biomechanical Index in Subclinical Keratoconus. J Refract Surg. 2018;34(9):616–21.
Jun L, Cynthia JR. Influence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis. J Cataract Refract Surg 2005, 31(1).
Riccardo V, Salwah R, Neeru AV, Mark B, Gabriela C, Anshoo C, Robert C, Ahmed E, Colin EW. Corneal biomechanics and biomechanically corrected intraocular pressure in primary open-angle glaucoma, ocular hypertension and controls. Br J Ophthalmol 2019, 104(1).
Bianca NS, Nara GO, Fábio BD, Carolina NS, Alberto D-F, Felipe AM. Association between Rates of Visual Field Progression and intraocular pressure measurements obtained by different tonometers. Ophthalmology 2018, 126(1).
Ayub Q, Sean M, Farshad A, Henry M, Mark MH, Antonia K, Lachlan SWK, Thi N, Mona SA, Angela C et al. Corneal stiffness parameters are predictive of structural and functional progression in Glaucoma suspect eyes. Ophthalmology 2020, 128(7).
Godefrooij DA, de Wit GA, Uiterwaal CS, Imhof SM, Wisse RPL. Age-specific incidence and prevalence of Keratoconus: a Nationwide Registration Study. Am J Ophthalmol. 2017;175:169–72.
Mandell R, Fatt I. Thinning of the human cornea on awakening. Nature. 1965;208(5007):292–3.
Gerstman D. The biomicroscope and Vickers image splitting eyepiece applied to the diurnal variation in human central corneal thickness. J Microsc. 1972;96(3):385–8.
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Funding
This study was supported by the National Natural Science Foundation of China (82271049) and the Zhejiang Provincial Natural Science Foundation of China (LY20H120001).
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Design of the study (DZ, YFY, AE, FB, JL); Conduct of the study, data collection, analysis and interpretation (DZ, LW, ZQ, PW, YYY, LY, XY, XZ, HL, CW, JW, FB); Manuscript preparation and review (DZ, LW, ZQ, PW, YYY, LY, XY, XZ, HL, CW, JW, YFY, AE, FB, JL). All authors read and approved the final manuscript.
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The study followed the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of the Eye Hospital, Wenzhou Medical University. Signed informed consent was obtained from all participants after explaining the procedure.
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Prof Elsheikh is a consultant to Oculus Optikgeräte GmbH.
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Zhu, D., Wang, L., Qu, Z. et al. Diurnal variations in corneal biomechanics in healthy young adults. BMC Ophthalmol 25, 90 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12886-025-03913-3
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DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12886-025-03913-3