Characteristics of Corneal Morphology and Biomechanics in Children with Allergic Conjunctivitis and Association with Eye-Rubbing

Characteristics of Corneal Morphology and Biomechanics in Children with Allergic Conjunctivitis and Association with Eye-Rubbing | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Characteristics of Corneal Morphology and Biomechanics in Children with Allergic Conjunctivitis and Association with Eye-Rubbing Yanning Yang, xiaoguang niu, aijiao qin, wenbo Zhang, shujuan wu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6772194/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective : To characterize corneal topographic and biomechanical alterations in children with allergic conjunctivitis and evaluate their association with eye-rubbing frequency. Methods : This cross-sectional study enrolled children aged 8-14 years with diagnosed perennial/seasonal allergic conjunctivitis treated at our institution (January 2023-March 2025). All participants underwent routine ophthalmologic examinations, corneal topography, and visualized corneal biomechanics assessments. The results were compared with age- and sex-matched healthy controls. Eye-rubbing frequency was documented, and correlation analyses were conducted between eye-rubbing frequency and altered corneal topographic and biomechanical parameters. Results : No significant differences were found between the allergic conjunctivitis group and the control group regarding age, sex, or spherical equivalent. Among corneal topographic parameters, front elevation at the thinnest point（Fe）and front difference deviation (Df) were significantly higher in the allergic group compared to controls; no significant differences were found for other indices. In terms of corneal biomechanical parameters, the first applanation length and stiffness parameter at first applanation were significantly lower in the allergic group, while other indices showed no significant difference. Fe and Df were positively correlated with eye-rubbing frequency and fully mediated the effect of eye rubbing on the Tomographic and Biomechanical Index (TBI). However, first applanation length and stiffness parameter were not correlated with eye-rubbing frequency and did not mediate its effect on TBI. Conclusions : Children with allergic conjunctivitis exhibit increased anterior corneal surface height and front difference deviation compared to healthy controls. These abnormalities are associated with the frequency of eye rubbing, which influences the TBI via changes in Fe and Df. Health sciences/Diseases/Eye diseases/Corneal diseases Health sciences/Health care/Diagnosis/Physical examination Allergic conjunctivitis Eye rubbing Corneal topography Biomechanics Figures Figure 1 Figure 2 Figure 3 Introduction Allergic conjunctivitis (AC) is a common ocular surface disease, particularly prevalent among children and adolescents, primarily presenting as eye redness, itching, tearing, and a foreign body sensation. Due to poor self-control in children, these symptoms often lead to inadvertent eye rubbing, which can cause mechanical damage to the cornea[ 1 ]. Consequently, allergic conjunctivitis not only affects the patient’s learning and daily life but also, due to ocular surface inflammation and mechanical trauma caused by eye rubbing, is associated with various other ocular surface diseases. For instance, spring catarrhal conjunctivitis may result in “shield ulcers” of the cornea [ 2 ]. Frequent eye rubbing can compromise the corneal epithelial barrier, increasing the risk of infection, and may lead to structural abnormalities and mechanical changes in the cornea. Studies have shown that prolonged eye rubbing in AC patients can cause transient intraocular pressure (IOP) elevation and disrupt the collagen structure of the cornea, leading to a reduction in corneal hysteresis (CH) and corneal resistance factor (CRF) [ 3 ]. Both CH and CRF are key biomechanical parameters that reflect corneal stiffness. This biomechanical weakening may result in corneal thinning or even corneal ectasia in genetically predisposed individuals. Corneal biomechanics play a crucial role in maintaining the integrity of corneal structure. A reduction in CH and CRF in AC patients implies a decreased ability of the cornea to resist deformation. Therefore, allergic conjunctivitis may be associated with certain corneal ectatic diseases[ 4 ]. Keratoconus(KC), the most common corneal ectasia, is characterized by progressive thinning and protrusion of the cornea, leading to irregular astigmatism and severe visual dysfunction. Research indicates that allergic conjunctivitis and eye rubbing may accelerate the progression of keratoconus, and even lead to rupture of the posterior elastic layer of the cornea, causing acute corneal edema [ 5 ]. Although the close relationship between AC, eye rubbing, and KC is widely recognized [ 6 , 7 ], there is limited research on the changes in corneal morphology and biomechanics in pediatric patients with allergic conjunctivitis. This study aims to examine corneal morphology and biomechanics in children and adolescents with allergic conjunctivitis, and perform correlation analysis between various parameters and eye-rubbing frequency. The goal is to identify early corneal morphological and biomechanical changes due to eye rubbing in allergic conjunctivitis, evaluate sensitive indicators for the progression of AC to KC. Materials and Methods 1、Study Design and Participants: This is a cross-sectional observational study. A total of 8-14-year-old patients diagnosed with allergic conjunctivitis who visited our hospital between January 2023 to March 2025 were included. Additionally, 20 healthy age- and gender-matched controls were selected from the same period. This study was approved by the Ethics Committee of Wuhan Aier Eye Hospital Hanyang (HYEYE2022091301JM), and was conducted in accordance with the Declaration of Helsinki. The study has been registered with the Chinese Clinical Trial Registration Center (ChiCTR2200064660). All patients and their legal guardians were informed of the purpose of the study, and written informed consent was obtained prior to participation. Inclusion Criteria: Patients with seasonal or perennial allergic conjunctivitis and a history of allergy lasting more than 2 years. Exclusion Criteria: Myopia greater than − 6.0 diopters, astigmatism greater than − 2.0 diopters, to avoid the potential impact of high myopia or astigmatism on corneal morphology or biomechanics; active ocular inflammation other than allergic reactions; high intraocular pressure or glaucoma; systemic diseases such as diabetes or vitamin A deficiency; history of ocular surgery or trauma; prior use of orthokeratology lenses or other types of corneal contact lenses; and patients unable to cooperate with the examination. 2、Allergic conjunctivitis Diagnostic Criteria: according to the criteria in the DECA document [ 8 ], the clinical diagnostic criteria for allergic conjunctivitis in this study are the presence of the following two essential conditions: (1) Symptoms: eye itching, possibly accompanied by a foreign body sensation, increased secretion in the conjunctival sac. (2) Signs: conjunctival hyperemia, swelling, papillae, which were proven by slit-lamp examination. Patients presenting with Horner–Trantas dots and corneal epithelial disorder were excluded from participation in this study. To increase the accuracy of the diagnosis, total IgE antibody levels in the tears of patients were measured using a total IgE antibody testing kit (GIC-S100, Helmen Precision Instruments Co, Ltd, Suzhou, China). The normal range for total IgE antibodies in human eye surface wash fluid is 0-2.5 IU/ml. A result greater than 2.5 IU/ml is considered positive, indicating a diagnosis of AC[ 9 ]. 3、Eye Rubbing Frequency Assessment: The data collection for eye rubbing frequency involved two main aspects. First, a questionnaire survey was conducted, in which the patients or their guardians were asked about the patient’s history of eye rubbing. The frequency of eye rubbing was scored from 0 to 5, where 0 indicated no eye rubbing at all and 5 indicated continuous eye rubbing. A score of 3 or above was considered clinically significant [10]. Additionally, during the physician’s consultation, the physician closely observed whether the patient rubbed their eyes for a continuous period of five minutes. If the patient did not rub their eyes during the observation period, it was considered negative. The results of the face-to-face observation were compared with the questionnaire responses, and only those patients with consistent results were included in the study, while those with inconsistent results were excluded. All questionnaire collection and face-to-face observations were conducted by the same experienced physician. 4、Corneal Morphology Examination: All patients underwent routine preoperative examinations, including measurements of uncorrected and best-corrected visual acuity, slit-lamp examination, non-contact tonometry, dry eye-related tests, and fundus examination. Corneal morphology was evaluated using the Pentacam three-dimensional anterior segment analysis system (Oculus, Germany). Morphometric parameters included: central corneal thickness (CCT), flat and steep keratometry (Kf and Ks), mean central keratometry (Km), maximum keratometry (Kmax), anterior elevation at the thinnest point(Front elevation), posterior elevation at the thinnest point༈Back elevation༉, index of surface variance (ISV), index of vertical asymmetry (IVA), keratoconus index (KI), central keratoconus index (CKI), index of height asymmetry (IHA), and index of height decentration (IHD). Enhanced ectasia detection parameters comprised: front difference deviation (Df), back difference deviation (Db), progression average deviation (Dp), thinnest point thickness deviation (Dt), Ambrosio relational thickness deviation (Da), and Belin/Ambrosio Enhanced Ectasia Total Deviation Index (BAD-D). 5、Corneal biomechanical evaluation was performed using the Scheimpflug-based Corvis ST 72100 non-contact tonometer (Oculus,Germany). The following biomechanical parameters were documented: intraocular pressure (IOP), biomechanical-corrected IOP (bIOP), central corneal thickness (CCT), first applanation time (A1T), first applanation velocity (A1V), first applanation length (A1L), second applanation time (A2T), second applanation velocity (A2V), second applanation length (A2L), deformation amplitude (DA), time to highest concavity (HCT), peak distance (PD), radius at highest concavity (HC radius), maximum deformation amplitude ratio at 2 mm (max DA ratio [2 mm]), Ambrosio relational thickness horizontal (ARTh), stiffness parameter at first applanation (SP-A1), Corvis biomechanical index (CBI), and tomography-biomechanics combined index (TBI). 6、Statistical Analysis: Data from only one eye of each patient were selected for statistical analysis. For patients with allergic conjunctivitis, the eye with the more severe allergic reaction was selected. For patients with bilateral allergic reactions of equal severity and for the normal control group, the right eye was chosen as the research subject. Statistical analysis was performed using IBM Statistical Package for the Social Sciences (SPSS) Statistics v.26 (IBM Corp., NY, US). The Kolmogorov-Smirnov test was used to assess the normality of the data. For normally distributed data, the mean ± standard deviation ( \(\:\stackrel{-}{x}\) ± s) was used. Independent sample t-tests and Mann-Whitney U tests were applied to evaluate differences between two groups for normally or non-normally distributed variables, respectively. The chi-square test was used to compare categorical variables. Pearson correlation analysis and regression analysis were employed to examine the relationship between eye rubbing frequency and corneal morphology and biomechanical parameters. Mediation Effect Analysis Using SPSS Macro PROCESS 4.1 Based on Bootstrap for Multiple Classification Independent Variables. A P-value of < 0.05 was considered statistically significant. Results 1.Patient characteristics: In this study, a total of 86 patients were included, with 66 patients in the allergic conjunctivitis (AC) group, comprising 23 cases of seasonal allergic conjunctivitis and 43 cases of perennial allergic conjunctivitis. The normal control group included 20 cases. The basic demographic information of the two groups is shown in Table 1 . There were no statistically significant differences between the two groups in terms of age, gender, intraocular pressure, and spherical equivalent. 2.Corneal Morphological Parameters: Among corneal morphological parameters, all except for Df, Db, Dp, Dt, and Da followed a normal distribution. Statistical analysis revealed that in patients with allergic conjunctivitis, the average anterior surface height at the thinnest point of the cornea (Front elevation, Fe) was 4.83 ± 2.66, which was significantly higher than the normal control group (3.10 ± 1.33). Furthermore, front difference deviation (Df) was 1.87 (0.94, 2.37) in the AC group, compared to 0.85 (0.53, 1.46) in the control group. The AC group was significantly higher than the normal control group, and the difference was statistically significant. For other parameters such as BAD-D, ISV, and IHD, which indicate corneal regularity, although the AC group had higher values than the normal group, no statistically significant differences were observed between the two groups. There were no significant differences in other indicators between the two groups. A comparison of corneal morphological parameters between the two groups is shown in Table 2 . 3.Corneal Biomechanical Parameters: Among all corneal biomechanical parameters, except for CBI and TBI, the other parameters followed a normal distribution. In the comparison of corneal biomechanical parameters between the two groups, differences were found in A1L and SP-A1, with these two parameters being lower in patients with allergic conjunctivitis compared to the normal control group. No statistically significant differences were observed for other parameters, including CBI and TBI, between the two groups. A comparison of corneal biomechanical parameters between the two groups is shown in Table 3 . 4.Relationship Between Eye-Rubbing Frequency and Differential Corneal Morphological and Biomechanical Parameters: In this study, all patients with allergic conjunctivitis exhibited eye-rubbing behavior. A principal component analysis (PCA) was performed on four parameters, setting eigenvalues greater than 1. The results showed that the anterior surface height at the thinnest point of the cornea (Fe) and SP-A1 had higher loadings and clearer assignments. After performing a rotated component matrix analysis, Df and Fe together constituted Principal Component 1, reflecting changes in anterior corneal morphology, while A1L and SP-A1 formed Principal Component 2, reflecting corneal biomechanical characteristics. We conducted a correlation analysis between Fe, Df, A1L, SP-A1, and different eye-rubbing frequencies, finding that both the anterior surface height at the thinnest point (Fe) and Df were positively correlated with eye-rubbing frequency. No correlation was found between the other two biomechanical parameters and eye-rubbing frequency. Table 1 Demographics of AC group and control group AC(n = 66) nAC(n = 20) T/χ 2 P Age 10.6 ± 1.79 11.3 ± 2.72 -0.393 0.167 Sex, male, n(%) 54(81.8%) 13(65%) 2.522 0.112 IOP(mmHg) 14.5 ± 3.64 14.2 ± 2.98 0.327 0.745 spherical equivalent(SE) -1.625 ± 0.570 -1.400 ± 0.459 -1.227 0.228 Table 2 Comparison of corneal topographic parameters between AC patients and the normal control group. * For non-normally distributed data, continuous variables are presented as median and interquartile range (IQR), and between-group comparisons were performed using the Mann-Whitney U test. AC(n = 66) nAC(n = 20) T/Z P CCT 558.58 ± 34.60 565.70 ± 17.51 -1.23 0.223 Kf 42.04 ± 1.26 42.48 ± 1.54 -1.30 0.199 Ks 43.31 ± 1.52 43.97 ± 1.72 -1.65 0.103 Km 42.66 ± 1.37 43.22 ± 1.58 -1.53 0.129 Kmax 43.89 ± 1.56 44.60 ± 1.73 -1.73 0.087 front elevation 4.83 ± 2.66 3.10 ± 1.33 3.92 0.000 back elevation 7.24 ± 3.53 7.35 ± 3.95 -0.12 0.908 Df* 1.87(0.94, 2.37) 0.85(0.53, 1.46) -3.21 0.001 Db* -0.08(-0.80, 1.03) 0.31(-0.14, 0.89) -0.89 0.374 Dp* 0.78(0.51, 1.41) 0.58(0.01, 1.17) -1.76 0.079 Dt* -0.17(-0.72, 0.64) -0.50(-0.92, 0.02) -1.42 0.155 Da* 0.50(0.11, 0.93) 0.38(-0.14, 0.58) -1.67 0.096 BAD-D 1.05 ± 0.61 0.89 ± 0.67 0.97 0.336 ISV 24.91 ± 17.37 21.85 ± 7.14 0.77 0.446 IVA 0.17 ± 0.15 0.24 ± 0.35 -0.80 0.434 KI 1.03 ± 0.03 1.04 ± 0.03 -0.97 0.335 CKI 1.01 ± 0.01 1.01 ± 0.00 1.39 0.170 IHA 5.58 ± 4.96 7.01 ± 6.29 -1.05 0.296 IHD 0.04 ± 0.16 0.01 ± 0.01 0.87 0.389 Table 3 Comparison of corneal biomechanical parameters between AC patients and the normal control group. AC(n = 66) nAC(n = 20) T/Z P IOP 14.53 ± 3.64 14.61 ± 2.96 -0.07 0.944 b-IOP 14.42 ± 3.03 14.34 ± 2.52 0.09 0.933 B-CCT 563.40 ± 26.77 549.17 ± 10.62 3.08 0.004 A1 time 7.45 ± 0.60 7.67 ± 0.72 -1.26 0.218 A1 velocity 0.12 ± 0.02 0.12 ± 0.01 0.61 0.541 A1 length 2.21 ± 0.29 2.42 ± 0.22 -3.49 0.001 A2 time 22.37 ± 0.58 22.20 ± 0.99 0.74 0.464 A2 velocity -0.26 ± 0.04 -0.23 ± 0.04 -2.18 0.062 A2 length 1.90 ± 0.35 1.99 ± 0.58 -0.61 0.545 DA 1.00 ± 0.13 0.97 ± 0.11 1.02 0.313 HCT 17.43 ± 0.54 17.63 ± 0.49 -1.31 0.194 PD 4.86 ± 0.32 4.75 ± 0.30 1.32 0.192 HC radius 6.81 ± 0.73 7.08 ± 1.06 -0.96 0.347 max DAratio (2 mm) 4.30 ± 0.50 4.17 ± 0.52 0.93 0.356 ARTh 515.35 ± 73.66 516.80 ± 90.26 -0.07 0.942 SP-A1 113.64 ± 20.98 124.54 ± 8.56 -3.39 0.001 CBI 0.00(0.00, 0.05) 0.00(0.00, 0.03) -0.40 0.689 TBI 0.27(0.11, 0.43) 0.34(0.09, 0.51) -0.26 0.798 * For non-normally distributed data, continuous variables are presented as median and interquartile range (IQR), and between-group comparisons were performed using the Mann-Whitney U test. To further explore the impact of eye-rubbing frequency on the four differential indicators, we classified eye-rubbing frequency as negative for frequencies 1 and 2, and positive for frequencies 3, 4, and 5, based on previous literature [10]. Subsequently, a receiver operating characteristic (ROC) curve was plotted. The ROC curve (Fig. 1) showed that the area under the curve (AUC) for Fe was 0.844, for Df was 0.676, for A1L was 0.534, and for SP-A1 was 0.532. This again demonstrated that Fe had the closest association with eye-rubbing behavior, while A1L and SP-A1 showed weaker associations. In addition, TBI, as the most important corneal biomechanical parameter for diagnosing keratoconus [ 11 ], showed no statistically significant difference between the AC group and the normal control group. However, we conducted a correlation analysis between TBI and the frequency of eye rubbing and found a positive correlation (r = 0.351, P = 0.004). As the frequency of eye rubbing increased, TBI also increased. To further explore the relationship between these parameters and the frequency of eye rubbing, we performed a regression analysis on the frequency of eye rubbing, Fe, Df, and TBI in AC patients, excluding confounding factors such as age, gender, and corneal thickness. After controlling for variables, the effect of eye rubbing frequency on Df was 1.021 with a significance of 0.001, on Fe was 1.144 with a significance of 0.000, and on TBI was − 0.076 with a significance of 0.001, all showing significant effects(Figure 2 ). 5. Mediation effect analysis: To clarify whether differential corneal morphology and biomechanical parameters play a mediating role in the “eye rubbing frequency → corneal morphology and biomechanics → TBI” pathway, we further conducted a mediation effect analysis on eye rubbing frequency, differential parameters, and TBI. Model construction: The independent variable X is the frequency of eye rubbing, the mediator variables M include Fe, Df, A1L, and SP-A1, and the dependent variable Y is TBI, with age, gender, and other confounding factors controlled. Mediation effect test for Fe and Df: In the direct effect, the influence between X and Y was 0.1064, with a goodness of fit R² of 0.1234, which indicates a good fit, with a corresponding p-value of 0.3095 > 0.05. Therefore, the direct effect was not significant. Through the mediation effect analysis, after adding two mediator variables Fe and Df between the independent variable X and the dependent variable Y, the total mediation effect value = 0.0298 + 0.0154 + 0.0030 = 0.0483, and both BootLLCI and BootULCI were on the side of 0, indicating that the total mediation effect was significant. Based on the analysis above, the total effect value of the model was 0.0077 + 0.0574 = 0.0651, with a goodness of fit of 0.2906, which suggests a good fit. The corresponding P-value was 0.0038, indicating that the model was statistically significant. Overall, the direct effect was not significant, the mediation effect was significant, and the total model was significant, suggesting that the mediator variables played a significant mediating role, representing a full mediation effect. Mediation effect test for A1L and SP-A1: In the direct effect, the influence between X and Y was 0.058, with a goodness of fit R² of 0.2290, indicating a good fit, with a corresponding p-value of 0.0091 < 0.05, so the direct effect was significant. Through the mediation effect analysis, after adding two mediator variables A1L and SP-A1 between the independent variable X and the dependent variable Y, the total mediation effect value = 0.0041 + 0.00244 + 0.0016 = 0.0081, but BootLLCI and BootULCI were on both sides of 0, indicating that the mediation effect was not significant. Based on the analysis above, the total effect value of the model was 0.058 + 0.0081 = 0.0661, with a goodness of fit of 0.2901, indicating a good fit. The corresponding P-value was 0.0034 < 0.05, suggesting that the model was statistically significant. Overall, the direct effect was significant, the mediation effect was not significant, and the total model was significant, indicating that the mediator variables did not play a significant mediating role, representing an ineffective mediation effect. Through the above mediation effect analysis, we found that the frequency of eye rubbing can influence TBI by affecting the two parameters, Fe and Df, and that Fe and Df exhibited a full mediation effect. In contrast, the corneal biomechanical parameters A1L and SP-A1 did not have a mediation effect on the influence of eye rubbing frequency on TBI. Discussion This study found that in pediatric patients with allergic conjunctivitis, deviations in corneal topographic parameters—specifically anterior elevation at the thinnest corneal point and front difference deviation—were significantly higher than those in healthy controls. Among corneal biomechanical parameters, the first applanation length (A1L) and stiffness parameter at first applanation (SP-A1) were lower compared to the normal group. However, only Fe and Df exhibited a positive correlation with eye-rubbing frequency, while no correlation was observed between A1L or SP-A1 and eye-rubbing frequency. Furthermore, Fe and Df demonstrated complete mediation effects in the pathway linking eye-rubbing frequency to the tomographic-biomechanical index (TBI). Therefore, a potential pathological pathway linking eye-rubbing frequency, anterior corneal surface morphology, and corneal biomechanical abnormalities may exist in patients with AC. KC is a severe blinding corneal disorder with unclear etiology, generally attributed to genetic and environmental interactions. Allergic conjunctivitis has been implicated in KC; Studies suggest that the incidence of KC is higher in allergic conjunctivitis populations, and patients with both conditions show reduced sensitivity to corneal collagen cross-linking therapy, resulting in poorer outcomes [ 12 , 13 ]. However, the mechanism by which AC contributes to the onset or progression of KC remains unknown. Studies suggest that KC originates from biomechanical alterations, with subsequent corneal morphological changes being a consequence of these biomechanical disruptions. Consequently, corneal biomechanical measurements may aid in the early diagnosis of KC [ 14 ]. Huo et al. demonstrated that subclinical keratoconus and forme fruste keratoconus exhibit significant abnormalities in the first applanation time and integrated radius, with subclinical cases showing weaker biomechanical parameters than forme fruste types. These findings indicate that corneal biomechanical parameters may serve as indicators for assessing the severity of early-stage KC [ 15 ]. AC can also induce alterations in corneal morphology and biomechanics. Wang et al. conducted corneal topography and Corvis ST examinations in AC patients, revealing significantly higher values of index of surface variance (ISV), index of vertical asymmetry (IVA), KC index (KI), index of height decentration (IHD), and Belin/Ambrosio Enhanced Ectasia Display total deviation index (BAD-D) compared to non-AC groups. However, among biomechanical parameters, only the tomographic-biomechanical index (TBI) showed a marked increase [ 16 ]. A limitation of this study was its inclusion of patients with a mean age of 18 years, whereas KC typically manifests during adolescence. This age discrepancy may introduce bias when investigating the AC-KC relationship. To address this, the current study focuses on pediatric patients aged 8–14 years, a population with plastic corneal morphology and heightened susceptibility to external influences, thereby providing a more suitable cohort for elucidating the AC-KC interplay. This study revealed that patients with AC exhibit higher anterior corneal elevation compared to healthy controls. This parameter is critical for assessing corneal morphology, with maintenance influenced by the combined roles of the epithelium, Bowman’s layer, and anterior stroma. The biomechanical contribution of the corneal epithelium remains debated [17]. Elsheikh [ 18 ] proposed that the epithelium, being significantly softer than the stroma, contributes minimally to corneal biomechanics, whereas Ziaei [ 19 ] demonstrated that the epithelium regulates stromal hydration and may indirectly modulate corneal stiffness. Studies suggest that thinning of the epithelium and Bowman’s layer in KC compromises corneal mechanical stability [ 20 ]. In AC, both eye-rubbing and ocular surface inflammation directly affect the corneal epithelium. Wang et al. [ 16 ] reported reduced epithelial thickness but increased variability in AC patients, further supporting epithelial involvement. Our findings of elevated anterior corneal elevation in AC patients—positively correlated with eye-rubbing frequency and demonstrating the highest predictive value (via ROC analysis) at the thinnest corneal point—suggest that AC and eye-rubbing preferentially alter anterior elevation (Fe), with earlier and more pronounced effects compared to other parameters. Some studies argue that anterior elevation may be influenced by multiple factors (e.g., corneal diameter) [ 21 ], limiting its reliability for detecting irregularity. Enhanced ectasia indices, such as front elevation difference deviation (Df), back elevation difference deviation (Db), progression average thickness deviation (Dp), thinnest corneal thickness deviation (Dt), Ambrosio relational thickness deviation (Da), and the Belin/Ambrosio Enhanced Ectasia Display total deviation index (BAD-D), reflect localized thickness progression rates and may better capture true corneal morphological changes. Notably, Df is less affected by corneal diameter or other confounders [ 22 ]. In this study, AC patients showed abnormal Df values compared to controls, with Df also correlating with eye-rubbing frequency. Principal component analysis indicated that Df and Fe jointly characterize anterior corneal morphological alterations. Thus, integrating anterior elevation and its variation (Df) may better identify early corneal changes in AC. In this study, no significant differences were observed between the two groups regarding other corneal topography parameters. This finding contrasts with previous research. We hypothesize that the possible reason for this discrepancy is that the patients selected for this study were relatively younger and had a simple case of AC, with less severe ocular surface inflammation. Corneal biomechanics has become an essential tool in the early diagnosis of KC. Combined with artificial intelligence and other tools, it can significantly improve the diagnostic capability for early-stage KC [ 23 ]. This study found that only A1L and SP-A1 showed significant differences between the AC patients and the normal control group. Both A1L and SP-A1 reflect corneal stiffness. A1L refers to the horizontal length of the area that is first flattened when the cornea is subjected to airflow, and this parameter reflects the deformation characteristics of the cornea under dynamic stress. It is one of the important indicators for evaluating corneal biomechanical properties. Normal corneas, with strong biomechanical stability, require a longer horizontal distance to achieve deformation balance when first flattened. In contrast, the overall stiffness of KC corneas is reduced, and they deform more easily under airflow, thus requiring less force to flatten and resulting in a shorter horizontal length of the flattened area, leading to a reduction in A1L. Zhang et al. [ 24 ] found that in patients with suspected KC, both A1-Length and A2-Length were significantly smaller. Similarly, A1L was also significantly lower in VKC patients [ 25 ], consistent with the results of this study. SP-A1, as a stiffness parameter, quantifies the cornea’s resistance to deformation. It represents the ratio of force to displacement during the first corneal flattening and is an important indicator of the Corvis ST test. A larger SP-A1 value indicates less deformation, reflecting higher corneal stiffness, while in KC patients, corneal stiffness is reduced, resulting in greater deformation under force and a smaller SP-A1 value [ 26 ]. Some studies [ 27 ] suggest that the SP-A1 in subclinical keratoconus (SKC) eyes is about 86% of that in healthy corneas, while in diagnosed KC eyes, SP-A1 is approximately 53% of the healthy cornea’s value. This indicates that SP-A1 is significantly lower in KC compared to healthy corneas and SKC. As the severity of KC increases from mild to moderate and severe stages, SP-A1 decreases (all P 0.7). As the condition worsens, SP-A1 continues to decrease, making SP-A1 a potential biomechanical indicator for assessing the severity of KC Eye rubbing is considered a risk factor for the development of KC in patients with allergic conjunctivitis (AC) [ 28 ]. Yang et al. reported that 69.09% of KC patients had a history of eye rubbing, and multivariate regression analysis revealed a strong association between eye rubbing and KC [ 29 ]. Eye rubbing not only exerts mechanical stimulation on the corneal epithelium and stroma, disrupting the epithelial barrier, but also damages the collagen structure of the cornea, thereby inducing structural abnormalities. In addition, eye rubbing can elevate the expression of proteases and inflammatory factors in the tear film [ 30 ]. In AC, ocular surface inflammation leads to increased inflammatory mediators, and mechanical damage from eye rubbing further affects both the epithelium and stromal fibers of the cornea. These changes ultimately compromise corneal biomechanical stability. Therefore, both mechanical and inflammatory stimuli may synergistically contribute to alterations in corneal morphology and biomechanics, potentially triggering the onset of KC. Li et al. found that after just one minute of eye rubbing, SP-A1 decreased, while deformation amplitude and peak distance increased, and A1-time became shorter [ 31 ]. In the present study, two anterior corneal surface parameters, Fe and Df, were found to be significantly associated with the frequency of eye rubbing, whereas the other two corneal biomechanical parameters were not correlated with eye rubbing behavior. This suggests that in AC patients, eye rubbing primarily affects the anterior corneal surface morphology, without exerting a direct influence on corneal biomechanics. To further clarify these effects, we conducted a regression analysis after controlling for potential confounding factors such as age, sex, and central corneal thickness. The results demonstrated that eye rubbing frequency still had a significant impact on Fe and Df. The formation of anterior surface morphology as captured in corneal topography is influenced by the tear film, corneal epithelium, and the anterior stroma. Both the tear film and corneal epithelium in AC patients are abnormal, which forms the basis for the impact of eye rubbing on anterior surface parameters. As for the two corneal biomechanical parameters, since no correlation with eye rubbing was found, we hypothesize that biomechanical changes may not be solely influenced by mechanical stimulation but could involve more complex inflammatory pathways. It is generally considered that among all corneal biomechanical parameters, the tomographic biomechanical index (TBI) holds the highest diagnostic value for KC [ 32 , 33 , 34 ]. TBI is a composite value derived from a combination of corneal morphological data measured by the Pentacam and corneal biomechanical parameters obtained using Corvis ST. TBI has become one of the most important biomechanical parameters for diagnosing KC.Wang observed that among patients with AC, only TBI exhibited significant differences in corneal biomechanical parameters, with AC patients showing markedly higher TBI values compared to normal controls [ 18 ]. In the present study, although no significant difference in TBI was observed between pediatric AC patients and controls, differences were found in parameters such as A1L and SP-A1. These findings suggest a potential risk of biomechanical imbalance in AC patients. The absence of a statistically significant difference in TBI between the two groups in our study may be attributable to the younger age of the participants. Additionally, a positive correlation between TBI and eye-rubbing frequency was identified. To further explore the relationship among eye-rubbing frequency, corneal morphological and biomechanical parameters, and TBI, a mediation analysis was conducted. The results indicated that eye-rubbing frequency influences TBI through Fe and Df which were found to exert a full mediating effect. In contrast, A1L and SP-A1 did not exhibit a mediating effect. These findings further support the notion that, in AC patients, the impact of eye rubbing on the cornea initially manifests on the anterior corneal surface. As the disease progresses, it may lead to a cascade of biomechanical alterations, ultimately compromising corneal mechanical stability and resulting in corneal ectasia. This study has several limitations. First, the sample size was relatively small. Second, the cross-sectional design restricts causal inference. Third, the enrolled children were predominantly younger than the typical age of KC onset, necessitating long-term longitudinal follow-up to determine whether the observed corneal morphological and biomechanical abnormalities in AC patients can serve as predictive indicators for KC development. Only through extended observation can the causal relationship between AC and KC be conclusively established. Declarations Abstract Objective To characterize corneal topographic and biomechanical alterations in children with allergic conjunctivitis and evaluate their association with eye-rubbing frequency. Methods This cross-sectional study enrolled children aged 8–14 years with diagnosed perennial/seasonal allergic conjunctivitis treated at our institution (January 2023-March 2025). All participants underwent routine ophthalmologic examinations, corneal topography, and visualized corneal biomechanics assessments. The results were compared with age- and sex-matched healthy controls. Eye-rubbing frequency was documented, and correlation analyses were conducted between eye-rubbing frequency and altered corneal topographic and biomechanical parameters. Results No significant differences were found between the allergic conjunctivitis group and the control group regarding age, sex, or spherical equivalent. Among corneal topographic parameters, front elevation at the thinnest point(Fe)and front difference deviation (Df) were significantly higher in the allergic group compared to controls; no significant differences were found for other indices. In terms of corneal biomechanical parameters, the first applanation length and stiffness parameter at first applanation were significantly lower in the allergic group, while other indices showed no significant difference. Fe and Df were positively correlated with eye-rubbing frequency and fully mediated the effect of eye rubbing on the Tomographic and Biomechanical Index (TBI). However, first applanation length and stiffness parameter were not correlated with eye-rubbing frequency and did not mediate its effect on TBI. Conclusions Children with allergic conjunctivitis exhibit increased anterior corneal surface height and front difference deviation compared to healthy controls. These abnormalities are associated with the frequency of eye rubbing, which influences the TBI via changes in Fe and Df. Funding: This study was supported by the Research Fund of Aier Ophthalmology Hospital Group (No. AGK2304D20) References Ben-Eli H, Erdinest N, Solomon A. Pathogenesis and complications of chronic eye rubbing in ocular allergy. Curr Opin Allergy Clin Immunol,2019,19(5):526-534. doi: 10.1097/ACI.0000000000000571. Hehar NK, Chigbu DI. Vernal Keratoconjunctivitis: Immunopathological Insights and Therapeutic Applications of Immunomodulators. Life (Basel),2024,14(3):361. doi: 10.3390/life14030361. Emre S, Başer E, Oztürk B, et al. Corneal biochemical features of patients with vernal keratoconjunctivitis. Graefes Arch Clin Exp Ophthalmol,2013,251(2):555-8. Sharma N, Rao K, Maharana PK, Vajpayee RB. Ocular allergy and keratoconus. Indian J Ophthalmol, 2013,61(8):407-9. doi: 10.4103/0301-4738.116063. Aichi T, Kitazawa K, Kozaki R, et al. Identification of risk factors for persistent corneal edema associated with acute corneal hydrops in keratoconus. Jpn J Ophthalmol,2025,18. doi: 10.1007/s10384-025-01193-4. Xu H, Wen Y, Zheng H, et al. Allergic disease and keratoconus: A two-sample univariable and multivariable Mendelian randomization study. World Allergy Organ J,2024,17(12):100993. doi: 10.1016/j.waojou.2024.100993. Lo ACQ, Lo CCW. The association between keratoconus and the risk factors of eye rubbing, atopy and other allergic diseases (conjunctivitis, rhinitis, asthma and eczema): a meta-analysis. Int Ophthalmol,2023,43(5):1451-1452. doi: 10.1007/s10792-022-02542-9. Sánchez-Hernández MC, Montero J, Rondon C, Benitez del Castillo JM, Velázquez E, Herreras JM, Fernández-Parra B, Merayo-Lloves J, Del Cuvillo A, Vega F, Valero A, Panizo C, Montoro J, Matheu V, Lluch-Bernal M, González ML, González R, Dordal MT, Dávila I, Colás C, Campo P, Antón E, Navarro A; SEAIC 2010 Rhinoconjunctivitis Committee; Spanish Group Ocular Surface-GESOC. Consensus document on allergic conjunctivitis (DECA). J Investig Allergol Clin Immunol,2015,25(2):94-106. Liu X, Wang G, He J, et al. Novel Application of Immunochromatographic Assay for Measurement of Total Tear Immunoglobulin E. Cornea,2024,43(1):13-17. Millodot M, Shneor E, Albou S, et al. Prevalence and associated factors of keratoconus in Jerusalem: a cross-sectional study. Ophthalmic Epidemiol,2011,18(2):91-7. Wu Y, Guo LL, Tian L, et al. Comparative analysis of the morphological and biomechanical properties of normal cornea and keratoconus at different stages. Int Ophthalmol，2021，41(11):3699-3711. doi: 10.1007/s10792-021-01929-4. Naderan M, Rajabi MT, Zarrinbakhsh P, et al. Effect of allergic diseases on keratoconus severity. Ocul Immunol Inflamm,2017,25(3):418–23. Sağlık A, Özcan G, Uçakhan Ö. Risk factors for progression following corneal collagen crosslinking in keratoconus. Int Ophthalmol,2021,41(10):3443-3449. doi: 10.1007/s10792-021-01908-9. Herber R, Ramm L, Spoerl E, et al. Assessment of corneal biomechanical parameters in healthy and keratoconic eyes using dynamic bidirectional applanation device and dynamic Scheimpflug analyzer. J Cataract Refract Surg,2019,45(6):778-788. doi: 10.1016/j.jcrs.2018.12.015. Huo Y, Chen X, Cao H, et al. Biomechanical properties analysis of forme fruste keratoconus and subclinical keratoconus. Graefes Arch Clin Exp Ophthalmol,2023,261(5):1311-1320. doi: 10.1007/s00417-022-05916-y. Wang Q, Deng Y, Li S, et al. Corneal biomechanical changes in allergic conjunctivitis. Eye Vis (Lond),2021,8(1):17. doi: 10.1186/s40662-021-00241-7. Vellara HR, Patel DV. Biomechanical properties of the keratoconic cornea: a review. Clinical & experimental optometry: journal of the Australian Optometrical Association,2015,98(1):31-38. doi:10.1111/cxo.12211. Elsheikh A, Alhasso D, Rama P. Assessment of the epithelium's contribution to corneal biomechanics. Exp Eye Res,2008,86(2):445-51. doi: 10.1016/j.exer.2007.12.002. Ziaei M, Gokul A, Vellara H, et al. Measurement of In Vivo Biomechanical Changes Attributable to Epithelial Removal in Keratoconus Using a Noncontact Tonometer. Cornea,2020,39(8):946-951. doi: 10.1097/ICO.0000000000002344. Reinstein DZ, Archer TJ, Gobbe M. Corneal epithelial thickness profile in the diagnosis of keratoconus. J Refract Surg,2009,25(7):604-10. doi: 10.3928/1081597X-20090610-06. Lin Q, Shen Z. Effect of white-to-white corneal diameter on biomechanical indices assessed by Pentacam Scheimpflug corneal tomography and corneal visualization Scheimpflug technology. Int Ophthalmol,2022,42(5):1537-1543. doi: 10.1007/s10792-021-02144-x. Ding L, Wang J, Niu L, et al. Pentacam Scheimpflug Tomography Findings in Chinese Patients With Different Corneal Diameters. J Refract Surg,2020,36(10):688-695. doi: 10.3928/1081597X-20200730-02. Wang X, Maeno S, Wang Y, et al. Early diagnosis of keratoconus using corneal biomechanics and OCT derived technologies. Eye Vis (Lond),2025,12(1):18. doi: 10.1186/s40662-025-00435-3. Zhang YH, Wang Y, Li LY, et al. Study on corneal biomechanical properties of suspicious keratoconus patients in corneal topography. Zhonghua Yan Ke Za Zhi,2019,55(6):442-447. Chinese. doi: 10.3760/cma.j.issn.0412-4081.2019.06.007. Zhang X, Huang F, Qiu J, et al. Corneal biomechanical properties in vernal keratoconjunctivitis and its subtypes: a preliminary study. Int Ophthalmol,2023 ,43(6):2083-2090. doi: 10.1007/s10792-022-02608-8. Peyman A, Sepahvand F, Pourazizi M, et al. Corneal biomechanics in normal and subclinical keratoconus eyes. BMC Ophthalmol,2023,23(1):459. doi: 10.1186/s12886-023-03215-6. Liu GY, Jing LL, Li J, et al. Evaluation of two biomechanical stiffness indexes in the diagnosis of keratoconus and their changes after corneal collagen cross-linking surgery. Zhonghua Yan Ke Za Zhi,2022,58(8):584-591. Chinese. doi: 10.3760/cma.j.cn112142-20211027-00507. Sahebjada S, Al-Mahrouqi HH, Moshegov S, et al. Eye rubbing in the aetiology of keratoconus: a systematic review and meta-analysis. Graefes Arch Clin Exp Ophthalmol,2021,259(8):2057-2067. doi: 10.1007/s00417-021-05081-8. Yang K, Li D, Xu L, et al. Independent and interactive effects of eye rubbing and atopy on keratoconus. Front Immunol,2022,29;13:999435. doi:10.3389/fimmu.2022.999435. Zareian R, Susilo ME, Paten JA, et al. Human Corneal Fibroblast Pattern Evolution and Matrix Synthesis on Mechanically Biased Substrates. Tissue Eng Part A,2016 ,22(19-20):1204-1217. doi: 10.1089/ten.TEA.2016.0164. Li X, Wei A, Yang Y, et al. Effect of eye rubbing on corneal biomechanical properties in myopia and emmetropia. Front Bioeng Biotechnol,2023,11:1168503. doi: 10.3389/fbioe.2023.1168503. Sedaghat MR, Momeni-Moghaddam H, Ambrósio R Jr, et al. Diagnostic ability of corneal shape and biomechanical parameters for detecting frank keratoconus. Cornea,2018, 37(8):1025-1034. doi: 10.1097/ICO.0000000000001639. Ganesh M, Arora R, Titiyal JS. Combined corneal biomechanical and tomographical indices in subclinical and forme fruste keratoconus. Indian J Ophthalmol,2024，72(9):1337-1345. doi: 10.4103/IJO.IJO_766_24. Chan TCY, Wang YM, Yu M, et al. Comparison of Corneal Tomography and a New Combined Tomographic Biomechanical Index in Subclinical Keratoconus. J Refract Surg,2018,34(9):616-621. doi: 10.3928/1081597X-20180705-02. Additional Declarations There is no conflict of interest Supplementary Files Table3.docx Table 3 Table2.docx Table 2 Table1.docx Table 1 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6772194","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":509773299,"identity":"389e5661-311b-4271-a1c5-b1e0e2dbde89","order_by":0,"name":"Yanning 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03:10:17","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6772194/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6772194/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91074246,"identity":"bc02a0dd-063b-4d20-a526-bf8beceba17c","added_by":"auto","created_at":"2025-09-11 11:02:34","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":76212,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves showing the effects of eye-rubbing behavior on differential corneal morphology and corneal biomechanical parameters.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6772194/v1/30fddf0ba1889d3d925b7c3b.jpg"},{"id":91072391,"identity":"bb1725d9-3fbc-415c-b36b-bf2bc235a4ba","added_by":"auto","created_at":"2025-09-11 10:54:34","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":59076,"visible":true,"origin":"","legend":"\u003cp\u003eRegression analysis of eye-rubbing frequency with Df, Fe, and TBI after adjusting for confounding factors (age, gender, and corneal thickness).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6772194/v1/13165c8356efe315dd47585a.jpg"},{"id":91072392,"identity":"b28d5ad0-f84d-4418-a491-08c02a4d9c53","added_by":"auto","created_at":"2025-09-11 10:54:34","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":29567,"visible":true,"origin":"","legend":"\u003cp\u003eUnnumbered image in the Result section.\u003c/p\u003e","description":"","filename":"unno1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6772194/v1/246b257db57414e114a2a8ac.jpg"},{"id":91087711,"identity":"2a5b4d4d-38d3-4e2f-8b50-259dccbe7c36","added_by":"auto","created_at":"2025-09-11 12:38:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":741541,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6772194/v1/e6d66fc6-b11f-49a5-8460-b8e412f2157d.pdf"},{"id":91070855,"identity":"bebb10a6-ff86-4d91-b5a5-88a29009c5b7","added_by":"auto","created_at":"2025-09-11 10:46:34","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16665,"visible":true,"origin":"","legend":"Table 3","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-6772194/v1/be6275366ac1c7e3a860439c.docx"},{"id":91070856,"identity":"34c84e28-ecbf-449f-8f9d-8cc6ee175be3","added_by":"auto","created_at":"2025-09-11 10:46:34","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":16841,"visible":true,"origin":"","legend":"Table 2","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6772194/v1/36da746ac3799ba643530078.docx"},{"id":91070863,"identity":"337587af-a853-4202-8871-877382601948","added_by":"auto","created_at":"2025-09-11 10:46:34","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":15517,"visible":true,"origin":"","legend":"Table 1","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6772194/v1/1e88975112cfecdac233defb.docx"}],"financialInterests":"There is no conflict of interest","formattedTitle":"Characteristics of Corneal Morphology and Biomechanics in Children with Allergic Conjunctivitis and Association with Eye-Rubbing","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAllergic conjunctivitis (AC) is a common ocular surface disease, particularly prevalent among children and adolescents, primarily presenting as eye redness, itching, tearing, and a foreign body sensation. Due to poor self-control in children, these symptoms often lead to inadvertent eye rubbing, which can cause mechanical damage to the cornea[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Consequently, allergic conjunctivitis not only affects the patient\u0026rsquo;s learning and daily life but also, due to ocular surface inflammation and mechanical trauma caused by eye rubbing, is associated with various other ocular surface diseases. For instance, spring catarrhal conjunctivitis may result in \u0026ldquo;shield ulcers\u0026rdquo; of the cornea [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Frequent eye rubbing can compromise the corneal epithelial barrier, increasing the risk of infection, and may lead to structural abnormalities and mechanical changes in the cornea. Studies have shown that prolonged eye rubbing in AC patients can cause transient intraocular pressure (IOP) elevation and disrupt the collagen structure of the cornea, leading to a reduction in corneal hysteresis (CH) and corneal resistance factor (CRF) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Both CH and CRF are key biomechanical parameters that reflect corneal stiffness. This biomechanical weakening may result in corneal thinning or even corneal ectasia in genetically predisposed individuals.\u003c/p\u003e\u003cp\u003eCorneal biomechanics play a crucial role in maintaining the integrity of corneal structure. A reduction in CH and CRF in AC patients implies a decreased ability of the cornea to resist deformation. Therefore, allergic conjunctivitis may be associated with certain corneal ectatic diseases[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Keratoconus(KC), the most common corneal ectasia, is characterized by progressive thinning and protrusion of the cornea, leading to irregular astigmatism and severe visual dysfunction. Research indicates that allergic conjunctivitis and eye rubbing may accelerate the progression of keratoconus, and even lead to rupture of the posterior elastic layer of the cornea, causing acute corneal edema [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough the close relationship between AC, eye rubbing, and KC is widely recognized [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], there is limited research on the changes in corneal morphology and biomechanics in pediatric patients with allergic conjunctivitis. This study aims to examine corneal morphology and biomechanics in children and adolescents with allergic conjunctivitis, and perform correlation analysis between various parameters and eye-rubbing frequency. The goal is to identify early corneal morphological and biomechanical changes due to eye rubbing in allergic conjunctivitis, evaluate sensitive indicators for the progression of AC to KC.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e1、Study Design and Participants: This is a cross-sectional observational study. A total of 8-14-year-old patients diagnosed with allergic conjunctivitis who visited our hospital between January 2023 to March 2025 were included. Additionally, 20 healthy age- and gender-matched controls were selected from the same period. This study was approved by the Ethics Committee of Wuhan Aier Eye Hospital Hanyang (HYEYE2022091301JM), and was conducted in accordance with the Declaration of Helsinki. The study has been registered with the Chinese Clinical Trial Registration Center (ChiCTR2200064660). All patients and their legal guardians were informed of the purpose of the study, and written informed consent was obtained prior to participation.\u003c/p\u003e\u003cp\u003eInclusion Criteria: Patients with seasonal or perennial allergic conjunctivitis and a history of allergy lasting more than 2 years.\u003c/p\u003e\u003cp\u003eExclusion Criteria: Myopia greater than \u0026minus;\u0026thinsp;6.0 diopters, astigmatism greater than \u0026minus;\u0026thinsp;2.0 diopters, to avoid the potential impact of high myopia or astigmatism on corneal morphology or biomechanics; active ocular inflammation other than allergic reactions; high intraocular pressure or glaucoma; systemic diseases such as diabetes or vitamin A deficiency; history of ocular surgery or trauma; prior use of orthokeratology lenses or other types of corneal contact lenses; and patients unable to cooperate with the examination.\u003c/p\u003e\u003cp\u003e2、Allergic conjunctivitis Diagnostic Criteria: according to the criteria in the DECA document [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], the clinical diagnostic criteria for allergic conjunctivitis in this study are the presence of the following two essential conditions: (1) Symptoms: eye itching, possibly accompanied by a foreign body sensation, increased secretion in the conjunctival sac. (2) Signs: conjunctival hyperemia, swelling, papillae, which were proven by slit-lamp examination. Patients presenting with Horner\u0026ndash;Trantas dots and corneal epithelial disorder were excluded from participation in this study. To increase the accuracy of the diagnosis, total IgE antibody levels in the tears of patients were measured using a total IgE antibody testing kit (GIC-S100, Helmen Precision Instruments Co, Ltd, Suzhou, China). The normal range for total IgE antibodies in human eye surface wash fluid is 0-2.5 IU/ml. A result greater than 2.5 IU/ml is considered positive, indicating a diagnosis of AC[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e3、Eye Rubbing Frequency Assessment: The data collection for eye rubbing frequency involved two main aspects. First, a questionnaire survey was conducted, in which the patients or their guardians were asked about the patient\u0026rsquo;s history of eye rubbing. The frequency of eye rubbing was scored from 0 to 5, where 0 indicated no eye rubbing at all and 5 indicated continuous eye rubbing. A score of 3 or above was considered clinically significant [10]. Additionally, during the physician\u0026rsquo;s consultation, the physician closely observed whether the patient rubbed their eyes for a continuous period of five minutes. If the patient did not rub their eyes during the observation period, it was considered negative. The results of the face-to-face observation were compared with the questionnaire responses, and only those patients with consistent results were included in the study, while those with inconsistent results were excluded. All questionnaire collection and face-to-face observations were conducted by the same experienced physician.\u003c/p\u003e\u003cp\u003e4、Corneal Morphology Examination: All patients underwent routine preoperative examinations, including measurements of uncorrected and best-corrected visual acuity, slit-lamp examination, non-contact tonometry, dry eye-related tests, and fundus examination. Corneal morphology was evaluated using the Pentacam three-dimensional anterior segment analysis system (Oculus, Germany). Morphometric parameters included: central corneal thickness (CCT), flat and steep keratometry (Kf and Ks), mean central keratometry (Km), maximum keratometry (Kmax), anterior elevation at the thinnest point(Front elevation), posterior elevation at the thinnest point༈Back elevation༉, index of surface variance (ISV), index of vertical asymmetry (IVA), keratoconus index (KI), central keratoconus index (CKI), index of height asymmetry (IHA), and index of height decentration (IHD). Enhanced ectasia detection parameters comprised: front difference deviation (Df), back difference deviation (Db), progression average deviation (Dp), thinnest point thickness deviation (Dt), Ambrosio relational thickness deviation (Da), and Belin/Ambrosio Enhanced Ectasia Total Deviation Index (BAD-D).\u003c/p\u003e\u003cp\u003e5、Corneal biomechanical evaluation was performed using the Scheimpflug-based Corvis ST 72100 non-contact tonometer (Oculus,Germany). The following biomechanical parameters were documented: intraocular pressure (IOP), biomechanical-corrected IOP (bIOP), central corneal thickness (CCT), first applanation time (A1T), first applanation velocity (A1V), first applanation length (A1L), second applanation time (A2T), second applanation velocity (A2V), second applanation length (A2L), deformation amplitude (DA), time to highest concavity (HCT), peak distance (PD), radius at highest concavity (HC radius), maximum deformation amplitude ratio at 2 mm (max DA ratio [2 mm]), Ambrosio relational thickness horizontal (ARTh), stiffness parameter at first applanation (SP-A1), Corvis biomechanical index (CBI), and tomography-biomechanics combined index (TBI).\u003c/p\u003e\u003cp\u003e6、Statistical Analysis: Data from only one eye of each patient were selected for statistical analysis. For patients with allergic conjunctivitis, the eye with the more severe allergic reaction was selected. For patients with bilateral allergic reactions of equal severity and for the normal control group, the right eye was chosen as the research subject. Statistical analysis was performed using IBM Statistical Package for the Social Sciences (SPSS) Statistics v.26 (IBM Corp., NY, US). The Kolmogorov-Smirnov test was used to assess the normality of the data. For normally distributed data, the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{x}\\)\u003c/span\u003e\u003c/span\u003e\u0026plusmn; s) was used. Independent sample t-tests and Mann-Whitney U tests were applied to evaluate differences between two groups for normally or non-normally distributed variables, respectively. The chi-square test was used to compare categorical variables. Pearson correlation analysis and regression analysis were employed to examine the relationship between eye rubbing frequency and corneal morphology and biomechanical parameters. Mediation Effect Analysis Using SPSS Macro PROCESS 4.1 Based on Bootstrap for Multiple Classification Independent Variables. A P-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cp\u003e1.Patient characteristics: In this study, a total of 86 patients were included, with 66 patients in the allergic conjunctivitis (AC) group, comprising 23 cases of seasonal allergic conjunctivitis and 43 cases of perennial allergic conjunctivitis. The normal control group included 20 cases. The basic demographic information of the two groups is shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There were no statistically significant differences between the two groups in terms of age, gender, intraocular pressure, and spherical equivalent.\u003c/p\u003e\u003cp\u003e2.Corneal Morphological Parameters: Among corneal morphological parameters, all except for Df, Db, Dp, Dt, and Da followed a normal distribution. Statistical analysis revealed that in patients with allergic conjunctivitis, the average anterior surface height at the thinnest point of the cornea (Front elevation, Fe) was 4.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.66, which was significantly higher than the normal control group (3.10\u0026thinsp;\u0026plusmn;\u0026thinsp;1.33). Furthermore, front difference deviation (Df) was 1.87 (0.94, 2.37) in the AC group, compared to 0.85 (0.53, 1.46) in the control group. The AC group was significantly higher than the normal control group, and the difference was statistically significant. For other parameters such as BAD-D, ISV, and IHD, which indicate corneal regularity, although the AC group had higher values than the normal group, no statistically significant differences were observed between the two groups. There were no significant differences in other indicators between the two groups. A comparison of corneal morphological parameters between the two groups is shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e3.Corneal Biomechanical Parameters: Among all corneal biomechanical parameters, except for CBI and TBI, the other parameters followed a normal distribution. In the comparison of corneal biomechanical parameters between the two groups, differences were found in A1L and SP-A1, with these two parameters being lower in patients with allergic conjunctivitis compared to the normal control group. No statistically significant differences were observed for other parameters, including CBI and TBI, between the two groups. A comparison of corneal biomechanical parameters between the two groups is shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e4.Relationship Between Eye-Rubbing Frequency and Differential Corneal Morphological and Biomechanical Parameters: In this study, all patients with allergic conjunctivitis exhibited eye-rubbing behavior. A principal component analysis (PCA) was performed on four parameters, setting eigenvalues greater than 1. The results showed that the anterior surface height at the thinnest point of the cornea (Fe) and SP-A1 had higher loadings and clearer assignments. After performing a rotated component matrix analysis, Df and Fe together constituted Principal Component 1, reflecting changes in anterior corneal morphology, while A1L and SP-A1 formed Principal Component 2, reflecting corneal biomechanical characteristics. We conducted a correlation analysis between Fe, Df, A1L, SP-A1, and different eye-rubbing frequencies, finding that both the anterior surface height at the thinnest point (Fe) and Df were positively correlated with eye-rubbing frequency. No correlation was found between the other two biomechanical parameters and eye-rubbing frequency.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographics of AC group and control group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAC(n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003enAC(n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eT/χ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.393\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.167\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, male, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54(81.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13(65%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.522\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.112\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIOP(mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.327\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.745\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003espherical equivalent(SE)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-1.625\u0026thinsp;\u0026plusmn;\u0026thinsp;0.570\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-1.400\u0026thinsp;\u0026plusmn;\u0026thinsp;0.459\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.227\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.228\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of corneal topographic parameters between AC patients and the normal control group. * For non-normally distributed data, continuous variables are presented as median and interquartile range (IQR), and between-group comparisons were performed using the Mann-Whitney U test.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAC(n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003enAC(n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eT/Z\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e558.58\u0026thinsp;\u0026plusmn;\u0026thinsp;34.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e565.70\u0026thinsp;\u0026plusmn;\u0026thinsp;17.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.223\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKf\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42.48\u0026thinsp;\u0026plusmn;\u0026thinsp;1.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.199\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43.31\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43.97\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.103\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42.66\u0026thinsp;\u0026plusmn;\u0026thinsp;1.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43.22\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.129\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKmax\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.087\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003efront elevation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.10\u0026thinsp;\u0026plusmn;\u0026thinsp;1.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eback elevation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.24\u0026thinsp;\u0026plusmn;\u0026thinsp;3.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.35\u0026thinsp;\u0026plusmn;\u0026thinsp;3.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.908\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDf*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.87(0.94, 2.37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.85(0.53, 1.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-3.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDb*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.08(-0.80, 1.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.31(-0.14, 0.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.374\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDp*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.78(0.51, 1.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.58(0.01, 1.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.079\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDt*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.17(-0.72, 0.64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.50(-0.92, 0.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.155\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDa*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.50(0.11, 0.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.38(-0.14, 0.58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.096\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBAD-D\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.336\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eISV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.91\u0026thinsp;\u0026plusmn;\u0026thinsp;17.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.85\u0026thinsp;\u0026plusmn;\u0026thinsp;7.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.446\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIVA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.434\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.335\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCKI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.170\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIHA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.58\u0026thinsp;\u0026plusmn;\u0026thinsp;4.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.01\u0026thinsp;\u0026plusmn;\u0026thinsp;6.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.296\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIHD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.389\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of corneal biomechanical parameters between AC patients and the normal control group.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAC(n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003enAC(n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eT/Z\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIOP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.53\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.61\u0026thinsp;\u0026plusmn;\u0026thinsp;2.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.944\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eb-IOP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.42\u0026thinsp;\u0026plusmn;\u0026thinsp;3.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.34\u0026thinsp;\u0026plusmn;\u0026thinsp;2.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.933\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eB-CCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e563.40\u0026thinsp;\u0026plusmn;\u0026thinsp;26.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e549.17\u0026thinsp;\u0026plusmn;\u0026thinsp;10.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA1 time\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.218\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA1 velocity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.541\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA1 length\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-3.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA2 time\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.464\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA2 velocity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-2.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.062\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA2 length\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.545\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.313\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.194\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.192\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHC radius\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.347\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emax DAratio (2 mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.356\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eARTh\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e515.35\u0026thinsp;\u0026plusmn;\u0026thinsp;73.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e516.80\u0026thinsp;\u0026plusmn;\u0026thinsp;90.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.942\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSP-A1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e113.64\u0026thinsp;\u0026plusmn;\u0026thinsp;20.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e124.54\u0026thinsp;\u0026plusmn;\u0026thinsp;8.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-3.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCBI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.00(0.00, 0.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.00(0.00, 0.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.689\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTBI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.27(0.11, 0.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.34(0.09, 0.51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.798\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e* For non-normally distributed data, continuous variables are presented as median and interquartile range (IQR), and between-group comparisons were performed using the Mann-Whitney U test.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTo further explore the impact of eye-rubbing frequency on the four differential indicators, we classified eye-rubbing frequency as negative for frequencies 1 and 2, and positive for frequencies 3, 4, and 5, based on previous literature [10]. Subsequently, a receiver operating characteristic (ROC) curve was plotted. The ROC curve (Fig.\u0026nbsp;1) showed that the area under the curve (AUC) for Fe was 0.844, for Df was 0.676, for A1L was 0.534, and for SP-A1 was 0.532. This again demonstrated that Fe had the closest association with eye-rubbing behavior, while A1L and SP-A1 showed weaker associations.\u003c/p\u003e\u003cp\u003eIn addition, TBI, as the most important corneal biomechanical parameter for diagnosing keratoconus [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e11\u003c/span\u003e], showed no statistically significant difference between the AC group and the normal control group. However, we conducted a correlation analysis between TBI and the frequency of eye rubbing and found a positive correlation (r\u0026thinsp;=\u0026thinsp;0.351, P\u0026thinsp;=\u0026thinsp;0.004). As the frequency of eye rubbing increased, TBI also increased. To further explore the relationship between these parameters and the frequency of eye rubbing, we performed a regression analysis on the frequency of eye rubbing, Fe, Df, and TBI in AC patients, excluding confounding factors such as age, gender, and corneal thickness. After controlling for variables, the effect of eye rubbing frequency on Df was 1.021 with a significance of 0.001, on Fe was 1.144 with a significance of 0.000, and on TBI was \u0026minus;\u0026thinsp;0.076 with a significance of 0.001, all showing significant effects(Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e5. Mediation effect analysis: To clarify whether differential corneal morphology and biomechanical parameters play a mediating role in the \u0026ldquo;eye rubbing frequency \u0026rarr; corneal morphology and biomechanics \u0026rarr; TBI\u0026rdquo; pathway, we further conducted a mediation effect analysis on eye rubbing frequency, differential parameters, and TBI. Model construction: The independent variable X is the frequency of eye rubbing, the mediator variables M include Fe, Df, A1L, and SP-A1, and the dependent variable Y is TBI, with age, gender, and other confounding factors controlled.\u003c/p\u003e\u003cp\u003eMediation effect test for Fe and Df: In the direct effect, the influence between X and Y was 0.1064, with a goodness of fit R\u0026sup2; of 0.1234, which indicates a good fit, with a corresponding p-value of 0.3095\u0026thinsp;\u0026gt;\u0026thinsp;0.05. Therefore, the direct effect was not significant.\u003c/p\u003e\u003cp\u003eThrough the mediation effect analysis, after adding two mediator variables Fe and Df between the independent variable X and the dependent variable Y, the total mediation effect value\u0026thinsp;=\u0026thinsp;0.0298\u0026thinsp;+\u0026thinsp;0.0154\u0026thinsp;+\u0026thinsp;0.0030\u0026thinsp;=\u0026thinsp;0.0483, and both BootLLCI and BootULCI were on the side of 0, indicating that the total mediation effect was significant.\u003c/p\u003e\u003cp\u003eBased on the analysis above, the total effect value of the model was 0.0077\u0026thinsp;+\u0026thinsp;0.0574\u0026thinsp;=\u0026thinsp;0.0651, with a goodness of fit of 0.2906, which suggests a good fit. The corresponding P-value was 0.0038, indicating that the model was statistically significant. Overall, the direct effect was not significant, the mediation effect was significant, and the total model was significant, suggesting that the mediator variables played a significant mediating role, representing a full mediation effect.\u003c/p\u003e\u003cp\u003eMediation effect test for A1L and SP-A1: In the direct effect, the influence between X and Y was 0.058, with a goodness of fit R\u0026sup2; of 0.2290, indicating a good fit, with a corresponding p-value of 0.0091\u0026thinsp;\u0026lt;\u0026thinsp;0.05, so the direct effect was significant.\u003c/p\u003e\u003cp\u003eThrough the mediation effect analysis, after adding two mediator variables A1L and SP-A1 between the independent variable X and the dependent variable Y, the total mediation effect value\u0026thinsp;=\u0026thinsp;0.0041\u0026thinsp;+\u0026thinsp;0.00244\u0026thinsp;+\u0026thinsp;0.0016\u0026thinsp;=\u0026thinsp;0.0081, but BootLLCI and BootULCI were on both sides of 0, indicating that the mediation effect was not significant.\u003c/p\u003e\u003cp\u003eBased on the analysis above, the total effect value of the model was 0.058\u0026thinsp;+\u0026thinsp;0.0081\u0026thinsp;=\u0026thinsp;0.0661, with a goodness of fit of 0.2901, indicating a good fit. The corresponding P-value was 0.0034\u0026thinsp;\u0026lt;\u0026thinsp;0.05, suggesting that the model was statistically significant. Overall, the direct effect was significant, the mediation effect was not significant, and the total model was significant, indicating that the mediator variables did not play a significant mediating role, representing an ineffective mediation effect.\u003c/p\u003e\u003cp\u003eThrough the above mediation effect analysis, we found that the frequency of eye rubbing can influence TBI by affecting the two parameters, Fe and Df, and that Fe and Df exhibited a full mediation effect. In contrast, the corneal biomechanical parameters A1L and SP-A1 did not have a mediation effect on the influence of eye rubbing frequency on TBI.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study found that in pediatric patients with allergic conjunctivitis, deviations in corneal topographic parameters\u0026mdash;specifically anterior elevation at the thinnest corneal point and front difference deviation\u0026mdash;were significantly higher than those in healthy controls. Among corneal biomechanical parameters, the first applanation length (A1L) and stiffness parameter at first applanation (SP-A1) were lower compared to the normal group. However, only Fe and Df exhibited a positive correlation with eye-rubbing frequency, while no correlation was observed between A1L or SP-A1 and eye-rubbing frequency. Furthermore, Fe and Df demonstrated complete mediation effects in the pathway linking eye-rubbing frequency to the tomographic-biomechanical index (TBI). Therefore, a potential pathological pathway linking eye-rubbing frequency, anterior corneal surface morphology, and corneal biomechanical abnormalities may exist in patients with AC.\u003c/p\u003e\u003cp\u003eKC is a severe blinding corneal disorder with unclear etiology, generally attributed to genetic and environmental interactions. Allergic conjunctivitis has been implicated in KC; Studies suggest that the incidence of KC is higher in allergic conjunctivitis populations, and patients with both conditions show reduced sensitivity to corneal collagen cross-linking therapy, resulting in poorer outcomes [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, the mechanism by which AC contributes to the onset or progression of KC remains unknown.\u003c/p\u003e\u003cp\u003eStudies suggest that KC originates from biomechanical alterations, with subsequent corneal morphological changes being a consequence of these biomechanical disruptions. Consequently, corneal biomechanical measurements may aid in the early diagnosis of KC [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Huo et al. demonstrated that subclinical keratoconus and forme fruste keratoconus exhibit significant abnormalities in the first applanation time and integrated radius, with subclinical cases showing weaker biomechanical parameters than forme fruste types. These findings indicate that corneal biomechanical parameters may serve as indicators for assessing the severity of early-stage KC [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAC can also induce alterations in corneal morphology and biomechanics. Wang et al. conducted corneal topography and Corvis ST examinations in AC patients, revealing significantly higher values of index of surface variance (ISV), index of vertical asymmetry (IVA), KC index (KI), index of height decentration (IHD), and Belin/Ambrosio Enhanced Ectasia Display total deviation index (BAD-D) compared to non-AC groups. However, among biomechanical parameters, only the tomographic-biomechanical index (TBI) showed a marked increase [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A limitation of this study was its inclusion of patients with a mean age of 18 years, whereas KC typically manifests during adolescence. This age discrepancy may introduce bias when investigating the AC-KC relationship. To address this, the current study focuses on pediatric patients aged 8\u0026ndash;14 years, a population with plastic corneal morphology and heightened susceptibility to external influences, thereby providing a more suitable cohort for elucidating the AC-KC interplay.\u003c/p\u003e\u003cp\u003eThis study revealed that patients with AC exhibit higher anterior corneal elevation compared to healthy controls. This parameter is critical for assessing corneal morphology, with maintenance influenced by the combined roles of the epithelium, Bowman\u0026rsquo;s layer, and anterior stroma. The biomechanical contribution of the corneal epithelium remains debated [17]. Elsheikh [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e] proposed that the epithelium, being significantly softer than the stroma, contributes minimally to corneal biomechanics, whereas Ziaei [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e] demonstrated that the epithelium regulates stromal hydration and may indirectly modulate corneal stiffness. Studies suggest that thinning of the epithelium and Bowman\u0026rsquo;s layer in KC compromises corneal mechanical stability [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In AC, both eye-rubbing and ocular surface inflammation directly affect the corneal epithelium. Wang et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] reported reduced epithelial thickness but increased variability in AC patients, further supporting epithelial involvement. Our findings of elevated anterior corneal elevation in AC patients\u0026mdash;positively correlated with eye-rubbing frequency and demonstrating the highest predictive value (via ROC analysis) at the thinnest corneal point\u0026mdash;suggest that AC and eye-rubbing preferentially alter anterior elevation (Fe), with earlier and more pronounced effects compared to other parameters.\u003c/p\u003e\u003cp\u003eSome studies argue that anterior elevation may be influenced by multiple factors (e.g., corneal diameter) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e21\u003c/span\u003e], limiting its reliability for detecting irregularity. Enhanced ectasia indices, such as front elevation difference deviation (Df), back elevation difference deviation (Db), progression average thickness deviation (Dp), thinnest corneal thickness deviation (Dt), Ambrosio relational thickness deviation (Da), and the Belin/Ambrosio Enhanced Ectasia Display total deviation index (BAD-D), reflect localized thickness progression rates and may better capture true corneal morphological changes. Notably, Df is less affected by corneal diameter or other confounders [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this study, AC patients showed abnormal Df values compared to controls, with Df also correlating with eye-rubbing frequency. Principal component analysis indicated that Df and Fe jointly characterize anterior corneal morphological alterations. Thus, integrating anterior elevation and its variation (Df) may better identify early corneal changes in AC.\u003c/p\u003e\u003cp\u003eIn this study, no significant differences were observed between the two groups regarding other corneal topography parameters. This finding contrasts with previous research. We hypothesize that the possible reason for this discrepancy is that the patients selected for this study were relatively younger and had a simple case of AC, with less severe ocular surface inflammation.\u003c/p\u003e\u003cp\u003eCorneal biomechanics has become an essential tool in the early diagnosis of KC. Combined with artificial intelligence and other tools, it can significantly improve the diagnostic capability for early-stage KC [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. This study found that only A1L and SP-A1 showed significant differences between the AC patients and the normal control group. Both A1L and SP-A1 reflect corneal stiffness. A1L refers to the horizontal length of the area that is first flattened when the cornea is subjected to airflow, and this parameter reflects the deformation characteristics of the cornea under dynamic stress. It is one of the important indicators for evaluating corneal biomechanical properties. Normal corneas, with strong biomechanical stability, require a longer horizontal distance to achieve deformation balance when first flattened. In contrast, the overall stiffness of KC corneas is reduced, and they deform more easily under airflow, thus requiring less force to flatten and resulting in a shorter horizontal length of the flattened area, leading to a reduction in A1L. Zhang et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e24\u003c/span\u003e] found that in patients with suspected KC, both A1-Length and A2-Length were significantly smaller. Similarly, A1L was also significantly lower in VKC patients [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e25\u003c/span\u003e], consistent with the results of this study.\u003c/p\u003e\u003cp\u003eSP-A1, as a stiffness parameter, quantifies the cornea\u0026rsquo;s resistance to deformation. It represents the ratio of force to displacement during the first corneal flattening and is an important indicator of the Corvis ST test. A larger SP-A1 value indicates less deformation, reflecting higher corneal stiffness, while in KC patients, corneal stiffness is reduced, resulting in greater deformation under force and a smaller SP-A1 value [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Some studies [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e27\u003c/span\u003e] suggest that the SP-A1 in subclinical keratoconus (SKC) eyes is about 86% of that in healthy corneas, while in diagnosed KC eyes, SP-A1 is approximately 53% of the healthy cornea\u0026rsquo;s value. This indicates that SP-A1 is significantly lower in KC compared to healthy corneas and SKC. As the severity of KC increases from mild to moderate and severe stages, SP-A1 decreases (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Furthermore, ROC curve analysis shows that SP-A1 not only has relatively good diagnostic power for SKC (AUC\u0026thinsp;=\u0026thinsp;0.802) but also for various stages of KC (AUC\u0026thinsp;\u0026gt;\u0026thinsp;0.7). As the condition worsens, SP-A1 continues to decrease, making SP-A1 a potential biomechanical indicator for assessing the severity of KC\u003c/p\u003e\u003cp\u003eEye rubbing is considered a risk factor for the development of KC in patients with allergic conjunctivitis (AC) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Yang et al. reported that 69.09% of KC patients had a history of eye rubbing, and multivariate regression analysis revealed a strong association between eye rubbing and KC [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Eye rubbing not only exerts mechanical stimulation on the corneal epithelium and stroma, disrupting the epithelial barrier, but also damages the collagen structure of the cornea, thereby inducing structural abnormalities. In addition, eye rubbing can elevate the expression of proteases and inflammatory factors in the tear film [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In AC, ocular surface inflammation leads to increased inflammatory mediators, and mechanical damage from eye rubbing further affects both the epithelium and stromal fibers of the cornea. These changes ultimately compromise corneal biomechanical stability. Therefore, both mechanical and inflammatory stimuli may synergistically contribute to alterations in corneal morphology and biomechanics, potentially triggering the onset of KC. Li et al. found that after just one minute of eye rubbing, SP-A1 decreased, while deformation amplitude and peak distance increased, and A1-time became shorter [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In the present study, two anterior corneal surface parameters, Fe and Df, were found to be significantly associated with the frequency of eye rubbing, whereas the other two corneal biomechanical parameters were not correlated with eye rubbing behavior. This suggests that in AC patients, eye rubbing primarily affects the anterior corneal surface morphology, without exerting a direct influence on corneal biomechanics.\u003c/p\u003e\u003cp\u003eTo further clarify these effects, we conducted a regression analysis after controlling for potential confounding factors such as age, sex, and central corneal thickness. The results demonstrated that eye rubbing frequency still had a significant impact on Fe and Df. The formation of anterior surface morphology as captured in corneal topography is influenced by the tear film, corneal epithelium, and the anterior stroma. Both the tear film and corneal epithelium in AC patients are abnormal, which forms the basis for the impact of eye rubbing on anterior surface parameters. As for the two corneal biomechanical parameters, since no correlation with eye rubbing was found, we hypothesize that biomechanical changes may not be solely influenced by mechanical stimulation but could involve more complex inflammatory pathways.\u003c/p\u003e\u003cp\u003eIt is generally considered that among all corneal biomechanical parameters, the tomographic biomechanical index (TBI) holds the highest diagnostic value for KC [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. TBI is a composite value derived from a combination of corneal morphological data measured by the Pentacam and corneal biomechanical parameters obtained using Corvis ST. TBI has become one of the most important biomechanical parameters for diagnosing KC.Wang observed that among patients with AC, only TBI exhibited significant differences in corneal biomechanical parameters, with AC patients showing markedly higher TBI values compared to normal controls [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the present study, although no significant difference in TBI was observed between pediatric AC patients and controls, differences were found in parameters such as A1L and SP-A1. These findings suggest a potential risk of biomechanical imbalance in AC patients. The absence of a statistically significant difference in TBI between the two groups in our study may be attributable to the younger age of the participants.\u003c/p\u003e\u003cp\u003eAdditionally, a positive correlation between TBI and eye-rubbing frequency was identified. To further explore the relationship among eye-rubbing frequency, corneal morphological and biomechanical parameters, and TBI, a mediation analysis was conducted. The results indicated that eye-rubbing frequency influences TBI through Fe and Df which were found to exert a full mediating effect. In contrast, A1L and SP-A1 did not exhibit a mediating effect.\u003c/p\u003e\u003cp\u003eThese findings further support the notion that, in AC patients, the impact of eye rubbing on the cornea initially manifests on the anterior corneal surface. As the disease progresses, it may lead to a cascade of biomechanical alterations, ultimately compromising corneal mechanical stability and resulting in corneal ectasia.\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, the sample size was relatively small. Second, the cross-sectional design restricts causal inference. Third, the enrolled children were predominantly younger than the typical age of KC onset, necessitating long-term longitudinal follow-up to determine whether the observed corneal morphological and biomechanical abnormalities in AC patients can serve as predictive indicators for KC development. Only through extended observation can the causal relationship between AC and KC be conclusively established.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eAbstract Objective\u003c/h2\u003e\u003cp\u003eTo characterize corneal topographic and biomechanical alterations in children with allergic conjunctivitis and evaluate their association with eye-rubbing frequency.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003cp\u003eThis cross-sectional study enrolled children aged 8\u0026ndash;14 years with diagnosed perennial/seasonal allergic conjunctivitis treated at our institution (January 2023-March 2025). All participants underwent routine ophthalmologic examinations, corneal topography, and visualized corneal biomechanics assessments. The results were compared with age- and sex-matched healthy controls. Eye-rubbing frequency was documented, and correlation analyses were conducted between eye-rubbing frequency and altered corneal topographic and biomechanical parameters.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003cp\u003eNo significant differences were found between the allergic conjunctivitis group and the control group regarding age, sex, or spherical equivalent. Among corneal topographic parameters, front elevation at the thinnest point(Fe)and front difference deviation (Df) were significantly higher in the allergic group compared to controls; no significant differences were found for other indices. In terms of corneal biomechanical parameters, the first applanation length and stiffness parameter at first applanation were significantly lower in the allergic group, while other indices showed no significant difference. Fe and Df were positively correlated with eye-rubbing frequency and fully mediated the effect of eye rubbing on the Tomographic and Biomechanical Index (TBI). However, first applanation length and stiffness parameter were not correlated with eye-rubbing frequency and did not mediate its effect on TBI.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003cp\u003eChildren with allergic conjunctivitis exhibit increased anterior corneal surface height and front difference deviation compared to healthy controls. These abnormalities are associated with the frequency of eye rubbing, which influences the TBI via changes in Fe and Df.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThis study was supported by the Research Fund of Aier Ophthalmology Hospital Group (No. AGK2304D20)\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBen-Eli H, Erdinest N, Solomon A. Pathogenesis and complications of chronic eye rubbing in ocular allergy. Curr Opin Allergy Clin Immunol,2019,19(5):526-534. doi: 10.1097/ACI.0000000000000571. \u003c/li\u003e\n\u003cli\u003eHehar NK, Chigbu DI. Vernal Keratoconjunctivitis: Immunopathological Insights and Therapeutic Applications of Immunomodulators. Life (Basel),2024,14(3):361. doi: 10.3390/life14030361.\u003c/li\u003e\n\u003cli\u003eEmre S, Başer E, Ozt\u0026uuml;rk B, et al. Corneal biochemical features of patients with vernal keratoconjunctivitis. 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Pentacam Scheimpflug Tomography Findings in Chinese Patients With Different Corneal Diameters. J Refract Surg,2020,36(10):688-695. doi: 10.3928/1081597X-20200730-02. \u003c/li\u003e\n\u003cli\u003eWang X, Maeno S, Wang Y, et al. Early diagnosis of keratoconus using corneal biomechanics and OCT derived technologies. Eye Vis (Lond),2025,12(1):18. doi: 10.1186/s40662-025-00435-3.\u003c/li\u003e\n\u003cli\u003eZhang YH, Wang Y, Li LY, et al. Study on corneal biomechanical properties of suspicious keratoconus patients in corneal topography. Zhonghua Yan Ke Za Zhi,2019,55(6):442-447. Chinese. doi: 10.3760/cma.j.issn.0412-4081.2019.06.007. \u003c/li\u003e\n\u003cli\u003eZhang X, Huang F, Qiu J, et al. Corneal biomechanical properties in vernal keratoconjunctivitis and its subtypes: a preliminary study. Int Ophthalmol,2023 ,43(6):2083-2090. doi: 10.1007/s10792-022-02608-8.\u003c/li\u003e\n\u003cli\u003ePeyman A, Sepahvand F, Pourazizi M, et al. Corneal biomechanics in normal and subclinical keratoconus eyes. BMC Ophthalmol,2023,23(1):459. doi: 10.1186/s12886-023-03215-6. \u003c/li\u003e\n\u003cli\u003eLiu GY, Jing LL, Li J, et al. Evaluation of two biomechanical stiffness indexes in the diagnosis of keratoconus and their changes after corneal collagen cross-linking surgery. Zhonghua Yan Ke Za Zhi,2022,58(8):584-591. Chinese. doi: 10.3760/cma.j.cn112142-20211027-00507. \u003c/li\u003e\n\u003cli\u003eSahebjada S, Al-Mahrouqi HH, Moshegov S, et al. Eye rubbing in the aetiology of keratoconus: a systematic review and meta-analysis. Graefes Arch Clin Exp Ophthalmol,2021,259(8):2057-2067. doi: 10.1007/s00417-021-05081-8.\u003c/li\u003e\n\u003cli\u003eYang K, Li D, Xu L, et al. Independent and interactive effects of eye rubbing and atopy on keratoconus. Front Immunol,2022,29;13:999435. doi:10.3389/fimmu.2022.999435.\u003c/li\u003e\n\u003cli\u003eZareian R, Susilo ME, Paten JA, et al. Human Corneal Fibroblast Pattern Evolution and Matrix Synthesis on Mechanically Biased Substrates. Tissue Eng Part A,2016 ,22(19-20):1204-1217. doi: 10.1089/ten.TEA.2016.0164.\u003c/li\u003e\n\u003cli\u003eLi X, Wei A, Yang Y, et al. Effect of eye rubbing on corneal biomechanical properties in myopia and emmetropia. Front Bioeng Biotechnol,2023,11:1168503. doi: 10.3389/fbioe.2023.1168503.\u003c/li\u003e\n\u003cli\u003eSedaghat MR, Momeni-Moghaddam H, Ambr\u0026oacute;sio R Jr, et al. Diagnostic ability of corneal shape and biomechanical parameters for detecting frank keratoconus. Cornea,2018, 37(8):1025-1034. doi: 10.1097/ICO.0000000000001639. \u003c/li\u003e\n\u003cli\u003eGanesh M, Arora R, Titiyal JS. Combined corneal biomechanical and tomographical indices in subclinical and forme fruste keratoconus. Indian J Ophthalmol,2024，72(9):1337-1345. doi: 10.4103/IJO.IJO_766_24. \u003c/li\u003e\n\u003cli\u003eChan TCY, Wang YM, Yu M, et al. Comparison of Corneal Tomography and a New Combined Tomographic Biomechanical Index in Subclinical Keratoconus. J Refract Surg,2018,34(9):616-621. doi: 10.3928/1081597X-20180705-02. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Allergic conjunctivitis, Eye rubbing, Corneal topography, Biomechanics","lastPublishedDoi":"10.21203/rs.3.rs-6772194/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6772194/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: To characterize corneal topographic and biomechanical alterations in children with allergic conjunctivitis and evaluate their association with eye-rubbing frequency.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This cross-sectional study enrolled children aged 8-14 years with diagnosed perennial/seasonal allergic conjunctivitis treated at our institution (January 2023-March 2025). All participants underwent routine ophthalmologic examinations, corneal topography, and visualized corneal biomechanics assessments. The results were compared with age- and sex-matched healthy controls. Eye-rubbing frequency was documented, and correlation analyses were conducted between eye-rubbing frequency and altered corneal topographic and biomechanical parameters.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: No significant differences were found between the allergic conjunctivitis group and the control group regarding age, sex, or spherical equivalent. Among corneal topographic parameters, front elevation at the thinnest point（Fe）and front difference deviation (Df) were significantly higher in the allergic group compared to controls; no significant differences were found for other indices. In terms of corneal biomechanical parameters, the first applanation length and stiffness parameter at first applanation were significantly lower in the allergic group, while other indices showed no significant difference. Fe and Df were positively correlated with eye-rubbing frequency and fully mediated the effect of eye rubbing on the Tomographic and Biomechanical Index (TBI). However, first applanation length and stiffness parameter were not correlated with eye-rubbing frequency and did not mediate its effect on TBI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Children with allergic conjunctivitis exhibit increased anterior corneal surface height and front difference deviation compared to healthy controls. These abnormalities are associated with the frequency of eye rubbing, which influences the TBI via changes in Fe and Df.\u003c/p\u003e","manuscriptTitle":"Characteristics of Corneal Morphology and Biomechanics in Children with Allergic Conjunctivitis and Association with Eye-Rubbing","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-11 10:46:29","doi":"10.21203/rs.3.rs-6772194/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4687ca00-3fa4-4b41-a1db-63b1cf25e9ea","owner":[],"postedDate":"September 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":54145718,"name":"Health sciences/Diseases/Eye diseases/Corneal diseases"},{"id":54145719,"name":"Health sciences/Health care/Diagnosis/Physical examination"}],"tags":[],"updatedAt":"2025-09-11T12:30:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-11 10:46:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6772194","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6772194","identity":"rs-6772194","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}