Regional Mechanical Asymmetry: A Key Feature of the Optic Nerve Head in High Myopia Associated with Structural Remodeling

Regional Mechanical Asymmetry: A Key Feature of the Optic Nerve Head in High Myopia Associated with Structural Remodeling | 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 Research Article Regional Mechanical Asymmetry: A Key Feature of the Optic Nerve Head in High Myopia Associated with Structural Remodeling Kaiming Ruan, Zhengxi Zhang, Zihao Zou, Dan Cheng, Yuchen Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8797848/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Purpose To investigate regional mechanical asymmetry of the optic nerve head (ONH) in high myopia. Methods Swept-source OCT imaging was performed before and during controlled acute intraocular pressure (IOP) elevation. Three-dimensional strain was calculated using digital volume correlation, from which global strain (von Mises) and regional mechanical asymmetry (temporal–nasal strain gradient) were derived. Based on the measured strain response to IOP elevation, an effective, IOP-normalized Young’s modulus was estimated to characterize relative regional ONH tissue stiffness. Structural parameters included Bruch’s membrane opening area (BMOA), lamina cribrosa depth (LCD), gamma zone area, and BMO-minimum rim width. Results This study included 25 highly myopic eyes and 20 normal control eyes. The high myopia group exhibited larger BMOA and gamma zone area, as well as greater global strain (5.84 ± 1.47% vs. 4.84 ± 0.96%; p = 0.01) and T–N strain gradient (0.54 ± 0.38 vs. 0.19 ± 0.32; p < 0.01). Temporal ONH stiffness was significantly reduced relative to the nasal region. Multivariate analyses showed that the T-N strain gradient was independently associated with larger BMOA and gamma zone area, while global strain was associated with BMOA. A higher T-N strain gradient was also associated with greater LCD in univariate analysis. Conclusions Regional mechanical asymmetry is a key biomechanical feature of the highly myopic ONH and is independently linked to multiple aspects of structural remodeling. These findings highlight the role of regional mechanical asymmetry and suggest a potential biomechanical biomarker for early risk assessment in high myopia. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Pathologic myopia is a leading cause of irreversible vision impairment worldwide, primarily driven by profound structural alterations in the posterior segment of the eye. 1 Among these changes, remodeling of the optic nerve head (ONH) is of particular concern due to its strong association with an increased risk of myopic optic neuropathy and glaucoma. 2–7 Although morphological changes such as enlargement of the Bruch’s membrane opening (BMO), development of parapapillary gamma zone atrophy, and posterior bowing of the lamina cribrosa have been widely reported in myopic eyes 8 , the fundamental biomechanical mechanisms driving this remodeling remain incompletely characterized. While intraocular pressure (IOP) is the principal mechanical stressor, the ONH itself serves as the primary load-bearing structure within its anatomical region. 9–11 In high myopia, structural weakening of ONH tissues may compromises this integrity, creating a permissive environment for stress concentration and tissue deformation. Recent advances in optical coherence tomography (OCT) biomechanics, particularly digital volume correlation (DVC), now enable in vivo quantification of three-dimensional tissue strain in response to controlled IOP elevation. 12–14 Our prior work has revealed a consistent nasotemporal asymmetry of structural remodeling in highly myopic eyes. 15–18 Recent longitudinal studies have demonstrated that in highly myopic glaucoma, temporal visual field deterioration and papillomacular bundle damage occur earlier and progress more rapidly than in non-myopic glaucoma, highlighting a distinct pattern of regional vulnerability. 19 However, the local biomechanical mechanisms underlying this preferential temporal susceptibility of the optic nerve head remain poorly understood, as most existing studies have focused primarily on structural–functional associations rather than region-specific mechanical behavior. We therefore hypothesized that regional mechanical asymmetry, particularly along the temporal–nasal (T–N) axis, is linked to the characteristic structural remodeling observed in myopic eyes. To test this hypothesis, the present study introduces the concept of a T–N strain gradient to characterize spatial mechanical asymmetry within the ONH. We conducted a biomechanical investigation integrating ONH strain responses to acute IOP elevation with multi-parametric structural analysis. The specific objectives were: (1) to quantify and compare both global and regional strain patterns between highly myopic and control eyes under standardized IOP elevation; and (2) to determine whether these mechanical parameters—especially the T–N strain gradient—are independently associated with key structural remodeling metrics, including BMO area, gamma zone area, lamina cribrosa depth, and BMO-minimum rim width. Methods Study Participants This prospective, cross-sectional study was approved by the Ethics Committee of Wenzhou Medical University and adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants (H2025-025-K-24). A total of 45 subjects were recruited, and the right eye of each participant was selected for analysis. The cohort consisted of 25 eyes with high myopia (HM) and 20 normal control (NC) eyes. All subjects underwent a comprehensive ophthalmic examination. The HM group was defined by an axial length (AL) ≥ 26.0 mm. The NC group comprised eyes with AL between 22.0 and 26.0 mm. Exclusion criteria were as follows: visual field defects; glaucomatous optic neuropathy; pathologic myopia as defined by the META-PM classification 20 ; prior intraocular surgery or ocular trauma; contact lens wear within one month; and any systemic disease that may affect the eye, such as diabetic retinopathy. SS-OCT Image Acquisition and Loading Paradigms All eyes were imaged using a commercial swept-source OCT system (VG200S; SVision Imaging, Henan, China). A three-dimensional raster scanning protocol was employed to acquire volumes centered on the optic nerve head (ONH), covering a 3 × 3 mm area. Each volume consisted of 512 horizontal B-scans, and each B-scan contained 512 A-scans. To optimize image quality, each B-scan was averaged 8 times to reduce speckle noise. All imaging was performed under cycloplegia. Each eye underwent swept-source OCT scanning of the ONH under two standardized mechanical loading conditions: a baseline state and an acute IOP-induced state (Figure 1A). At baseline, two reference volumes were acquired in the primary gaze position. For the IOP-induced condition, a calibrated pressure gauge (SH-II-10, Nanjing NSCING Co., Ltd) applied a gentle, perpendicular force of 0.65 N to the temporal lower eyelid, producing an acute IOP elevation monitored with an iCare tonometer (iCare Pro, Finland) before and during the loading. A second OCT volume was then obtained under sustained pressure. The acquisition workflow and mechanical loading paradigm are illustrated schematically in Figure Digital Volume Correlation and Strain Calculation The three-dimensional displacement field within the ONH between the baseline and loaded states was computed using the digital volume correlation (DVC) module in Amira 2024 (Thermo Fisher Scientific). Prior to DVC computation, the ONH region was segmented and extracted from the full volumetric dataset to isolate the region of interest (Figure 1B). A rigid registration algorithm was then applied to the extracted volumes to correct for any potential global motion between the acquisition of the reference and deformed states. DVC analysis was performed with the following optimized parameters: a subvolume size of 100 μm isotropic cube was selected to provide an optimal balance between spatial resolution and computational stability. (Figure 1C) The iterative calculation was set to run for a maximum of 200 cycles or until a convergence criterion of u = 0.001 was met, whichever occurred first. The raw strain values obtained from DVC were normalized to account for interindividual variations in the actual achieved IOP elevation. The final corrected strain was calculated as: corrected strain = raw strain × (18 / ΔIOP), where 18 mmHg represents the target IOP elevation used for standardization across all subjects. The resulting displacement vector field was subsequently used to compute the Lagrangian finite strain tensor. From this tensor, the scalar von Mises strain (a measure of total deformation magnitude) and the principal strains (E1: maximum tensile strain, E2: intermediate strain, E3: maximum compressive strain) were derived for quantitative comparative analysis. Regional mechanical asymmetry was quantified by the temporal-nasal (T-N) strain gradient, defined as the absolute difference in sectoral von Mises strain between the temporal and nasal quadrants. (Figure 2, mechanical assessment) Quantification of ONH Structural Parameters Four key parameters of ONH structural remodeling were analyzed from the baseline OCT volumes obtained before mechanical loading, using previously established methods from our laboratory. 15,17 All measurements were performed using 18 radial B-scans covering a 6×6 mm area centered on the ONH. (Figure 2, ONH structural remodeling).Briefly, Bruch’s membrane opening area (BMOA) was derived from manually identified BMO points and calculated as the area enclosed by their projection onto a best-fit plane; the parapapillary gamma zone area was defined as the region between the BMO boundary and the optic disc margin on the scanning laser ophthalmoscopy image; lamina cribrosa depth (LCD) was obtained as the mean perpendicular distance from the BMO plane to the anterior lamina cribrosa across predefined sampling locations; and BMO–minimum rim width (BMO–MRW) was defined as the smallest distance from the BMO point to the internal limiting membrane across all radial scans. Conceptual Interpretation of Acute IOP-Induced Deformation To provide theoretical support for the experimentally observed strain–IOP relationships, the optic nerve head (ONH) tissue was modeled as a linear viscoelastic material. The ONH and lamina cribrosa are primarily composed of collagen-rich connective tissues, which are known to exhibit time-dependent deformation under sustained mechanical loading. However, in the present study, intraocular pressure (IOP) elevation was applied over a short duration and maintained at a constant level prior to image acquisition, thereby approximating a quasi-static loading condition. Specifically, the elevated IOP was sustained for approximately 10 seconds before swept-source OCT imaging. This interval was sufficient to allow transient viscoelastic responses to largely dissipate, enabling strain measurements to reflect a mechanically stabilized state. Under these experimental conditions, the constitutive behavior of ONH tissues was described using a Kelvin–Voigt viscoelastic model: This simplification permits direct interpretation of the experimentally observed linear relationship between applied loading and measured strain as an effective elastic response. In vivo quantification of absolute ONH tissue stress is not feasible due to geometric complexity and material heterogeneity. Accordingly, IOP was treated as a normalized surrogate for the applied mechanical load, consistent with prior in vivo biomechanical studies of the ONH. The target IOP elevation was set to approximately 18 mmHg, a magnitude commonly used to induce measurable ONH deformation while remaining within a physiologically safe range and a near-linear mechanical response regime. Based on this framework, an effective Young’s modulus was defined as the proportional coefficient relating IOP elevation to the regional strain response: The effective Young’s modulus reported in this study therefore represents an apparent, IOP-normalized biomechanical parameter, reflecting relative regional stiffness rather than an intrinsic material constant. This formulation enables direct comparison of biomechanical behavior between normal control and high myopia eyes, as well as between nasal and temporal regions of the ONH. Statistical Analysis Statistical analyses were performed using SPSS Statistics (Version 26; IBM Corp., USA). Independent samples t-tests and chi-square tests were used to compare continuous and categorical demographic variables between groups, respectively. Linear regression analyses (both univariate and multivariate) were employed to identify factors associated with the structural remodeling parameters. The multivariate models were adjusted for potential confounders. A p-value of less than 0.05 was considered statistically significant. Results Subject Characteristics A total of 45 subjects were included in the final analysis. Baseline characteristics and structural parameters of the high myopia (HM) and normal control (NC) groups are summarized in Table 1 . The two groups showed no significant differences in age, sex distribution, baseline intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, or radial peripapillary capillary (RPC) density (all p > 0.05). The HM group had a significantly longer axial length than the NC group (27.44 ± 1.82 mm vs. 24.87 ± 1.01 mm; p < 0.001). The HM group exhibited a significantly larger Bruch's membrane opening area (BMOA) (3.44 ± 1.10 mm² vs. 2.67 ± 0.54 mm²; p = 0.01) and a larger gamma zone area (1.38 ± 0.80 mm² vs. 0.72 ± 0.39 mm²; p < 0.01) compared to the NC group. No significant inter-group differences were found in lamina cribrosa depth (LCD) or BMO-minimum rim width (BMO-MRW) (p = 0.22 and p = 0.57, respectively). Table 1 Comparison of Parameters Between High Myopia and Normal Contral NC n = 20 HM n = 25 P value CLINICAL PARAMETER Age, years 25.80 ± 3.09 25.20 ± 5.41 0.66 Sex, male/female 12/8 16/9 0.79 Axial length, mm 24.87 ± 1.01 27.44 ± 1.82 < 0.001 Baseline IOP, mmHg 17.41 ± 2.90 16.66 ± 2.44 0.36 RNFL, µm 123.20 ± 13.97 121.50 ± 16.35 0.71 RPC, % 25.55 ± 4.04 25.50 ± 5.73 0.98 ONH STRUCTURAL REMODELING BMOA, mm² 2.67 ± 0.54 3.44 ± 1.10 0.01 LCD, mm 431.30 ± 70.69 455.82 ± 61.88 0.22 GAMA Area, mm² 0.72 ± 0.39 1.38 ± 0.80 < 0.01 BMO-MRW, um 229.86 ± 32.56 235.23 ± 30.96 0.57 IOP, intraocular pressure; RNFL, retinal nerve fiber layer; RPC, radial peripapillary capillary; BMOA, Bruch membrane opening area; LCD, lamina cribrosa depth; BMO-MRW, Bruch membrane opening-minimum rim width. ONH Biomechanical Measurements Strain Measurements The biomechanical responses of the ONH under acute IOP elevation are presented in Table 2 and Fig. 4. The HM group demonstrated a significantly higher global mechanical response, represented by von Mises strain, than the NC group (5.84 ± 1.47% vs. 4.84 ± 0.96%; p = 0.01). This increased strain in HM eyes was primarily manifested as significantly greater compression (E3: -5.13 ± 1.42% vs. -4.12 ± 0.85%; p < 0.01). Furthermore, the HM group exhibited significant regional mechanical asymmetry, evidenced by a higher temporal-nasal (T-N) strain gradient (0.54 ± 0.38 vs. 0.19 ± 0.32; p < 0.01). Table 2 Comparison of ONH Biomechanical Measurements between Normal Control and High Myopia Groups NC HM P value Acute IOP-Induced Strain, % von Mise 4.84 ± 0.96 5.84 ± 1.47 0.01 E1 3.99 ± 0.93 4.65 ± 1.32 0.07 E2 -0.13 ± 0.25 -0.28 ± 0.32 0.09 E3 -4.12 ± 0.85 -5.13 ± 1.42 < 0.01 ONH Biomechanical Imbalance T-N Strain Gradient 0.19 ± 0.32 0.54 ± 0.38 < 0.01 IOP, intraocular pressure; T-N, temporal-nasal. The accuracy of the DVC method was characterized by a baseline noise level of 2.04 ± 0.74% strain, calculated from two repeated OCT acquisitions under baseline conditions (NC: 1.87 ± 0.56%; HM: 2.18 ± 0.86%; p = 0.19). The reliability of the acute IOP-induced strain measurement protocol, evaluated in a subset of 10 healthy eyes, demonstrated good intraoperator repeatability (ICC = 0.83) and intersession reproducibility (ICC = 0.76), while interoperator reproducibility was moderate (ICC = 0.67). Bland-Altman analysis (Fig. 3) corroborated these findings, showing no systematic bias with the majority of data points within the limits of agreement. Estimation of Regional Effective Young’s Modulus Linear regression analysis revealed a strong linear relationship between intraocular pressure and the regional strain gradient across all groups and regions. Based on the constitutive framework described above, the slope of this relationship was directly interpreted as the effective Young’s modulus. The estimated effective Young’s moduli were as follows: NC–Nasal: 0.0542 MPa, NC–Temporal: 0.0492 MPa, HM–Nasal: 0.0479 MPa, HM–Temporal: 0.0403 MPa. These findings indicate that both myopia-related changes and regional differences in material behavior contribute to the observed strain distribution within the ONH. Factors Associated with Structural Remodeling Parameters The factors associated with key structural remodeling parameters are detailed in Tables 3 – 6 . For BMOA (Table 3 ): In the multivariate analysis of all subjects, both a higher global strain (von Mises) (β = 0.27, p < 0.01) and a larger T-N Strain Gradient (β = 0.85, p = 0.01) were identified as independent factors associated with a larger BMOA, after adjusting for axial length. For gamma zone area (Table 4 ), in the multivariate model, larger T–N strain gradient was independently associated with larger gamma zone area (β = 0.63, p = 0.02). For LCD (Table 5 ), univariate analysis revealed that a larger T-N Strain Gradient was significantly associated with a deeper LCD (β = 59.85, p = 0.02). No other biomechanical factors showed a significant association. For BMO-MRW (Table 6 ), no significant associations were found between the biomechanical parameters (global strain or T-N Gradient) and BMO-MRW. Table 3 Factors Associated with Bruch Membrane Opening Area Indicators Univariate Analysis Multivariate Analysis β B P value β B P value Age, years 0.01 0 0.96 - - - Axial length, mm 0.32 0.16 0.03 0.13 0.07 0.28 Baseline IOP, mmHg 0.11 0.04 0.49 - - - Acute IOP-Induced Strain, % 0.58 0.41 < 0.001 0.38 0.27 < 0.01 T-N Strain Gradient, % 0.55 1.36 < 0.001 0.34 0.85 0.01 IOP, intraocular pressure; T-N, temporal-nasal. Table 4 Factors Associated with lamina cribrosa depth Indicators Univariate Analysis β B P value Age, years 0.04 0.62 0.78 Axial length, mm 0.02 0.78 0.88 Baseline IOP, mmHg -0.17 -4.34 0.26 Acute IOP-Induced Strain, % 0.03 1.59 0.83 T-N Strain Gradient, % 0.35 59.85 0.02 IOP, intraocular pressure; T-N, temporal-nasal. Table 5 Factors Associated with Gamma Area Indicators Univariate Analysis Multivariate Analysis β B P value β B P value Age, years 0.04 0.01 0.82 - - - Axial length, mm 0.38 0.14 < 0.01 0.23 0.08 0.08 Baseline IOP, mmHg 0.06 0.02 0.68 - - - Acute IOP-Induced Strain, % 0.5 0.27 < 0.001 0.27 0.15 0.06 T-N Strain Gradient, % 0.52 0.96 < 0.001 0.34 0.63 0.02 IOP, intraocular pressure; T-N, temporal-nasal. Table 6 Factors Associated with BMO-MRW Indicators Univariate Analysis β B P value Age, years -0.32 -2.25 0.03 Axial length, mm 0.01 0.19 0.94 Baseline IOP, mmHg -0.07 -0.89 0.63 Acute IOP-Induced Strain, % -0.08 -1.78 0.62 T-N Strain Gradient, % -0.18 -14.78 0.23 BMO-MRW, Bruch membrane opening-minimum rim width; IOP, intraocular pressure; T-N, temporal-nasal. The significant relationships identified through linear regression analyses are visually demonstrated in Fig. 5, which presents scatterplots illustrating the associations between the key biomechanical factors and ONH structural remodeling parameters. Discussion This study provides, to our knowledge, the first in vivo evidence linking regional mechanical asymmetry within the ONH to multifaceted structural remodeling in high myopia. First, we validated acute IOP-induced ONH strain measurements, demonstrating good repeatability and reproducibility of von Mises strain. Second, highly myopic eyes exhibited not only elevated global strain but, more importantly, a significantly larger T-N strain gradient than controls. Third, regional mechanical asymmetry was independently associated with structural remodeling in myopic discs. Collectively, these findings indicate that the mechanical vulnerability of the myopic ONH is not merely a matter of generalized weakening but is characterized by distinct spatial heterogeneity, which appears to be a key driver of asymmetric structural remodeling. Swept-source OCT (SS-OCT) offers distinct advantages, including higher acquisition rates and enhanced penetration depth, enabling more reliable visualization of deep ONH structures, particularly the lamina cribrosa, under dynamic loading conditions. 15,17,21,22 The accuracy of our DVC methodology was first verified by calculating baseline noise from repeated OCT acquisitions under identical conditions, yielding a strain value of 2.04 ± 0.74% (NC: 1.87 ± 0.56%; HM: 2.18 ± 0.86%; p = 0.19), which is consistent with previous reports 13,23 Building upon this validation, we further evaluated measurement reliability across multiple dimensions. The demonstrated reliability of acute IOP-induced strain measurements (intraoperator:ICC=0.83; intersession:ICC=0.76; interoperator ICC=0.67) represents the first validation accounting for both temporal variations and observer-dependent factors in a clinical setting. Our implementation of sectoral DVC analysis represents a technical advancement, enabling, to our knowledge, the first in vivo quantification of regional ONH strain heterogeneity. The linear strain correction based on individual IOP elevation (ΔIOP) was justified by previous studies confirming minimal nonlinear effects beyond 18 mmHg, ensuring accurate inter-subject comparisons. 13 The morphological remodeling of the ONH in myopia has been well characterized both histologically and clinically. 8,24 In moderately myopic eyes, the Bruch’s membrane opening (BMO) typically shifts toward the temporal or inferotemporal direction, producing a nasal overhang of Bruch’s membrane and its temporal absence, which defines the parapapillary gamma zone. 25 This shift contributes to optic disc ovalization, elongation of the fovea–disc distance, and stretching of papillomacular vessels and nerve fiber bundles. 8,15,26 In highly myopic eyes, further expansion and thinning of the lamina cribrosa and the peripapillary scleral flange occur, accompanied by the development of circular gamma and delta zones. 27,28 These features reflect progressive remodeling of both superficial and deep ONH structures under mechanical loading in myopic eyes. In our cohort, highly myopic eyes demonstrated significant enlargement in BMOA and gamma zone area, while showing no significant differences in LCD or BMO-MRW compared with controls. Our study extends these structural observations by revealing a fundamental biomechanical disparity: highly myopic eyes exhibited not only greater overall deformation (von Mises strain: 5.84 ± 1.47% vs. 4.84 ± 0.96%; p = 0.01) but also more pronounced regional mechanical asymmetry (T–N strain gradient: 0.54 ± 0.38 vs. 0.19 ± 0.32; p < 0.01). The concurrent increase in global strain and T–N asymmetry suggests that highly myopic eyes experience both amplified and spatially uneven mechanical loading across the ONH, with the temporal region being particularly susceptible to deformation. To further elucidate the biomechanical basis of this regional asymmetry, we introduced a constitutive modeling framework and derived an effective Young’s modulus from the linear relationship between IOP elevation and regional strain gradient. Under a quasi-static loading condition (10 s sustained IOP elevation), the ONH response was approximated using a Kelvin–Voigt viscoelastic model, allowing the slope of the IOP–strain relationship to be interpreted as an apparent, IOP-normalized Young’s modulus. Using this approach, highly myopic eyes exhibited lower effective Young’s moduli than normal controls in both nasal and temporal regions, indicating increased mechanical compliance. Moreover, the temporal ONH consistently demonstrated a lower effective modulus than the nasal ONH, with this nasal–temporal difference being more pronounced in HM.(Figure 4) These findings provide direct biomechanical evidence that regional differences in tissue compliance contribute to asymmetric ONH deformation. The strong independent associations between the T–N strain gradient and multiple structural parameters (BMOA: β=0.85, p=0.01; gamma zone: β=0.63, p=0.02) support regional mechanical asymmetry as a fundamental driver of myopic ONH remodeling. The observed spatial variation in effective Young’s modulus provides a plausible mechanical explanation for this relationship, whereby regions with lower stiffness undergo greater deformation under equivalent IOP loading. These relationships persisted after adjustment for axial length, indicating that mechanical factors provide additional information beyond geometric elongation. Interestingly, although lamina cribrosa depth (LCD) did not differ significantly between the HM and NC groups, its significant correlation with the T–N strain gradient (β=59.85, p=0.02) suggests that posterior bowing of the lamina cribrosa is more closely governed by localized mechanical asymmetry than by axial elongation per se. This observation implies that subtle mechanical asymmetry may precede overt morphological changes detectable by conventional structural measures. Together, these findings suggest that an asymmetric mechanical environment—arising from regional heterogeneity in effective tissue stiffness—may initiate a cascade of remodeling events, from superficial BMO displacement and gamma zone formation to deeper lamina cribrosa bowing. This sequential remodeling may underlie the increased susceptibility of highly myopic eyes to glaucomatous and non-glaucomatous optic neuropathy. A higher T–N strain gradient may therefore indicate early biomechanical susceptibility of the ONH before irreversible rim thinning occurs. This metric could thus complement structural parameters in identifying eyes at risk of myopic optic neuropathy. Several limitations warrant consideration. First, this study did not include eyes with pathologic myopia, which may partly explain the absence of a significant difference in BMO-MRW between groups. Future studies incorporating a broader spectrum of myopic severity could help clarify this relationship. Second, the cross-sectional design can demonstrate associations but not causation. Longitudinal follow-up is needed to determine whether eyes exhibiting greater baseline regional asymmetry are more likely to undergo progressive structural remodeling. Third, the DVC calculations were constrained to the visible ONH tissues captured by OCT, and strain normalization was based on an assumed linear relationship beyond baseline IOP. While we provided error estimates to account for measurement uncertainty, future studies employing more advanced tissue models or extended imaging depths could improve strain quantification. Finally, although our sample size was sufficient to detect significant associations, it limited further subgroup analyses. Fourth, the effective Young’s modulus derived in this study represents a relative, IOP-normalized biomechanical parameter rather than an intrinsic material constant. Fifth, although IOP elevation was monitored and achieved globally, the eyelid-based loading paradigm may introduce subtle directional constraints. Therefore, the reported temporal–nasal strain asymmetry should be interpreted as a relative deformation metric under a standardized, clinically feasible loading condition rather than a pure pressure-only perturbation. Despite these limitations, the present study substantially advances current understanding by shifting the conceptual framework from “global strain” to “regional asymmetry.” Quantitative assessment of the T–N strain gradient represents a novel, clinically applicable biomechanical biomarker. In the future, a simplified, rapid version of this test may enable early identification of highly myopic eyes at greatest risk for optic nerve head remodeling, facilitating targeted monitoring and timely intervention. In conclusion, this study identifies regional mechanical asymmetry as a key biomechanical feature of myopic ONHs. The temporal–nasal strain gradient was independently associated with multiple structural parameters. These findings provide new insight into the biomechanical pathogenesis of myopic optic neuropathy and suggest that the T–N strain gradient may serve as a potential clinical biomarker for early risk detection. Declarations Equal Contribution Statement: * These authors contributed equally to this work and shared the first authorship. # These authors contributed equally to this research and shared corresponding authorship. Meeting Presentation: This material has not been presented at any meetings. Funding Support: This research was supported by the National Natural Science Foundation of China (82171016) and the National Natural Science Foundation of China (U22A201722). Disclosure statement: The authors declare no conflict of interest. Ethics approval and consent to participate This study was approved by the Ethics Committee of Wenzhou Medical University (Approval No. H2025-025-K-24) and adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained from all participants included in the study. Consent for publication Not applicable. References Morgan IG, Ohno-Matsui K, Saw S-M. Myopia. Lancet. 2012;379(9827):1739-1748. Huh MG, Jeong Y, Shin YI, Park KH, Jeoung JW. 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Swept-Source OCT for Evaluating the Lamina Cribrosa: A Report by the American Academy of Ophthalmology. Ophthalmology. 2019;126(9):1315-1323. Chuangsuwanich T, Tun TA, Braeu FA, et al. How Myopia and Glaucoma Influence the Biomechanical Susceptibility of the Optic Nerve Head. Invest Ophthalmol Vis Sci. 2023;64(11):12. Wang YX, Panda-Jonas S, Jonas JB. Optic nerve head anatomy in myopia and glaucoma, including parapapillary zones alpha, beta, gamma and delta: Histology and clinical features. Prog Retin Eye Res. 2020;83:100933. Jonas JB, Jonas RA, Panda-Jonas S. Clinical and histological aspects of the anatomy of myopia, myopic macular degeneration and myopia-associated optic neuropathy. Prog Retin Eye Res. 2025;109:101402. Jonas RA, Wang YX, Yang H, et al. Optic Disc-Fovea Distance, Axial Length and Parapapillary Zones. The Beijing Eye Study 2011. PLoS One. 2015;10(9):e0138701. Tun TA, Wang X, Baskaran M, et al. Determinants of lamina cribrosa depth in healthy Asian eyes: the Singapore Epidemiology Eye Study. Br J Ophthalmol. 2020;105(3):367-373. Rebolleda G, García-Montesinos J, De Dompablo E, Oblanca N, Muñoz-Negrete FJ, González-López JJ. Bruch's membrane opening changes and lamina cribrosa displacement in non-arteritic anterior ischaemic optic neuropathy. Br J Ophthalmol. 2016;101(2):143-149. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 09 Feb, 2026 Reviewers agreed at journal 09 Feb, 2026 Reviewers invited by journal 09 Feb, 2026 Editor assigned by journal 09 Feb, 2026 Submission checks completed at journal 06 Feb, 2026 First submitted to journal 05 Feb, 2026 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. 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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-8797848","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":590353475,"identity":"e0d22789-7833-4726-be8a-7fa31a767f34","order_by":0,"name":"Kaiming Ruan","email":"","orcid":"","institution":"National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.","correspondingAuthor":false,"prefix":"","firstName":"Kaiming","middleName":"","lastName":"Ruan","suffix":""},{"id":590353476,"identity":"4f3a4fed-1fd8-49ff-a17e-c02a5c417c60","order_by":1,"name":"Zhengxi Zhang","email":"","orcid":"","institution":"National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.","correspondingAuthor":false,"prefix":"","firstName":"Zhengxi","middleName":"","lastName":"Zhang","suffix":""},{"id":590353477,"identity":"e7d39158-f93f-4b23-ae84-d0de40d81c3c","order_by":2,"name":"Zihao Zou","email":"","orcid":"","institution":"National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.","correspondingAuthor":false,"prefix":"","firstName":"Zihao","middleName":"","lastName":"Zou","suffix":""},{"id":590353478,"identity":"4b0f7fd7-1372-448b-9ec9-0ce9f4ba83b4","order_by":3,"name":"Dan Cheng","email":"","orcid":"","institution":"National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.","correspondingAuthor":false,"prefix":"","firstName":"Dan","middleName":"","lastName":"Cheng","suffix":""},{"id":590353479,"identity":"71c44e1f-32bc-4220-9d68-e83bf05625b8","order_by":4,"name":"Yuchen Wang","email":"","orcid":"","institution":"National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.","correspondingAuthor":false,"prefix":"","firstName":"Yuchen","middleName":"","lastName":"Wang","suffix":""},{"id":590353480,"identity":"2bf1c189-b43c-45b7-920d-13d1fc60fa68","order_by":5,"name":"Ye Yang","email":"","orcid":"","institution":"National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.","correspondingAuthor":false,"prefix":"","firstName":"Ye","middleName":"","lastName":"Yang","suffix":""},{"id":590353481,"identity":"caa29d75-774c-4df5-99f0-891ecba75158","order_by":6,"name":"Yufeng Ye","email":"","orcid":"","institution":"National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.","correspondingAuthor":false,"prefix":"","firstName":"Yufeng","middleName":"","lastName":"Ye","suffix":""},{"id":590353482,"identity":"35276564-f30a-433d-9e06-9889340eb1f0","order_by":7,"name":"Meixiao Shen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYHAC9t9/KhgY2NhJ0SPBcwaohZkkLbxtQJJoLfLTzhgYSM7bJs/HzMD4mKeCQZ6/gfnZA3xaDG6nJSQYbrtt2MbMwGwMdKHhjANs5gZ4tUgnHziQuO02I1ALmzTQhYwbGHjYJPA6bHZiY8PBObftgVrYf/P+Y7AnqIXhdvJhxsaG24kgW5h5GxgSCWoB+iWNmeHY7eQ2ZsZmyTnHJJJnHGYzI+CwHDNmhprbtvPbmw9+eFNjY9vf3vwMv8MQgLGBiYdBgoQIAmv6QYrqUTAKRsEoGDEAADm1PUUWg/7VAAAAAElFTkSuQmCC","orcid":"","institution":"National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.","correspondingAuthor":true,"prefix":"","firstName":"Meixiao","middleName":"","lastName":"Shen","suffix":""}],"badges":[],"createdAt":"2026-02-05 13:53:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8797848/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8797848/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102875103,"identity":"31028af7-7078-485c-8045-682f114efe6e","added_by":"auto","created_at":"2026-02-17 19:24:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":853230,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAcquisition and biomechanical analysis pipeline.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Setup of acute intraocular pressure (IOP) elevation during swept-source OCT imaging. A calibrated digital pressure gauge (SH-II-10) applied a controlled 0.65 N force to the lower eyelid to elevate IOP, monitored by an iCare tonometer.\u003c/p\u003e\n\u003cp\u003e(B) Schematic illustration of the digital volume correlation (DVC) analysis. A total of 512 B-scans were acquired to reconstruct the 3D optic nerve head (ONH) volume, from which displacement fields between baseline and loaded states were computed.\u003c/p\u003e\n\u003cp\u003e(C) Visualization of the DVC computation grid showing 3D sub-volume tracking points (orange dots) used for local strain estimation within the ONH.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8797848/v1/782fff6321e54592d3801378.png"},{"id":102875136,"identity":"870d724c-2d81-458d-aaf1-03e75fbcd4cd","added_by":"auto","created_at":"2026-02-17 19:24:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":802706,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRepresentative visualization of ONH biomechanics and structural remodeling in normal control (NC) and high myopia (HM) groups.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLeft panel (Mechanical Assessment): Acute IOP-induced strain maps and temporal–nasal (T–N) strain gradients derived from DVC analysis. Highly myopic eyes show elevated overall strain and increased T–N mechanical asymmetry compared to controls.\u003c/p\u003e\n\u003cp\u003eRight panel (ONH Structural Remodeling): Corresponding structural metrics obtained from OCT, including Bruch’s membrane opening area (BMOA), gamma zone area, lamina cribrosa depth (LCD), and BMO–minimum rim width (BMO–MRW). HM eyes exhibit enlarged BMOA and gamma zone and deeper LCD compared to NC eyes.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8797848/v1/28ca5b0b204df6a478c779e8.png"},{"id":102875108,"identity":"181dc77b-150e-4324-9e12-9cb275135aac","added_by":"auto","created_at":"2026-02-17 19:24:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":73659,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRepeatability and reproducibility of acute IOP-induced ONH strain measurements.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBland–Altman plots comparing mean strain values between repeated measurements.\u003c/p\u003e\n\u003cp\u003eThe mean bias was near zero with \u0026gt;95% of data points within the limits of agreement, confirming good measurement reliability.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8797848/v1/2f787513dae773a4015590ab.png"},{"id":102875105,"identity":"b791ab35-12f4-46b3-9c5d-c47e98a6c9c8","added_by":"auto","created_at":"2026-02-17 19:24:38","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":71267,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of biomechanical parameters between groups.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Acute IOP-induced ONH strain (von Mises, %).\u003c/p\u003e\n\u003cp\u003e(B) Temporal–nasal (T–N) strain gradient (%).\u003c/p\u003e\n\u003cp\u003eHighly myopic eyes (HM, red) exhibited significantly greater global strain and T–N strain gradient compared with normal controls (NC, blue).\u003c/p\u003e\n\u003cp\u003e(C) Regional effective Young’s modulus of ONH.\u003c/p\u003e\n\u003cp\u003eEffective Young’s modulus was derived from the linear relationship between intraocular pressure elevation and the temporal–nasal strain gradient under quasi-static loading conditions (10 s sustained IOP elevation, target ΔIOP = 18 mmHg).\u003c/p\u003e\n\u003cp\u003eError bars indicate standard deviation. P \u0026lt; 0.05, P \u0026lt; 0.01.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8797848/v1/1ad9017dfe699407cc675b0e.png"},{"id":102875138,"identity":"6207fa7b-2bc5-46f6-9159-7fafb6157a62","added_by":"auto","created_at":"2026-02-17 19:24:49","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":199200,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAssociations between ONH biomechanical parameters and structural remodeling metrics.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eScatterplots showing correlations between key mechanical indices (IOP-induced ONH strain and T–N strain gradient) and structural parameters.\u003c/p\u003e\n\u003cp\u003eLinear regression lines and coefficients (R², P-values) demonstrate significant positive associations between regional mechanical asymmetry and ONH structural remodeling across both NC (blue) and HM (red) eyes.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8797848/v1/7d0dbc76f055f89f4f8c6495.png"},{"id":102875139,"identity":"e4085b48-ba3c-41aa-a76f-9c45871fa0cb","added_by":"auto","created_at":"2026-02-17 19:24:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3091150,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8797848/v1/3adae3df-ff66-48b4-a412-1a439261d5bc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Regional Mechanical Asymmetry: A Key Feature of the Optic Nerve Head in High Myopia Associated with Structural Remodeling","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePathologic myopia is a leading cause of irreversible vision impairment worldwide, primarily driven by profound structural alterations in the posterior segment of the eye.\u003csup\u003e1\u003c/sup\u003e Among these changes, remodeling of the optic nerve head (ONH) is of particular concern due to its strong association with an increased risk of myopic optic neuropathy and glaucoma.\u003csup\u003e2\u0026ndash;7\u003c/sup\u003e Although morphological changes such as enlargement of the Bruch\u0026rsquo;s membrane opening (BMO), development of parapapillary gamma zone atrophy, and posterior bowing of the lamina cribrosa have been widely reported in myopic eyes\u003csup\u003e8\u003c/sup\u003e, the fundamental biomechanical mechanisms driving this remodeling remain incompletely characterized.\u003c/p\u003e \u003cp\u003eWhile intraocular pressure (IOP) is the principal mechanical stressor, the ONH itself serves as the primary load-bearing structure within its anatomical region.\u003csup\u003e9\u0026ndash;11\u003c/sup\u003e In high myopia, structural weakening of ONH tissues may compromises this integrity, creating a permissive environment for stress concentration and tissue deformation. Recent advances in optical coherence tomography (OCT) biomechanics, particularly digital volume correlation (DVC), now enable in vivo quantification of three-dimensional tissue strain in response to controlled IOP elevation.\u003csup\u003e12\u0026ndash;14\u003c/sup\u003e Our prior work has revealed a consistent nasotemporal asymmetry of structural remodeling in highly myopic eyes.\u003csup\u003e15\u0026ndash;18\u003c/sup\u003e Recent longitudinal studies have demonstrated that in highly myopic glaucoma, temporal visual field deterioration and papillomacular bundle damage occur earlier and progress more rapidly than in non-myopic glaucoma, highlighting a distinct pattern of regional vulnerability.\u003csup\u003e19\u003c/sup\u003e However, the local biomechanical mechanisms underlying this preferential temporal susceptibility of the optic nerve head remain poorly understood, as most existing studies have focused primarily on structural\u0026ndash;functional associations rather than region-specific mechanical behavior. We therefore hypothesized that regional mechanical asymmetry, particularly along the temporal\u0026ndash;nasal (T\u0026ndash;N) axis, is linked to the characteristic structural remodeling observed in myopic eyes. To test this hypothesis, the present study introduces the concept of a T\u0026ndash;N strain gradient to characterize spatial mechanical asymmetry within the ONH.\u003c/p\u003e \u003cp\u003eWe conducted a biomechanical investigation integrating ONH strain responses to acute IOP elevation with multi-parametric structural analysis. The specific objectives were: (1) to quantify and compare both global and regional strain patterns between highly myopic and control eyes under standardized IOP elevation; and (2) to determine whether these mechanical parameters\u0026mdash;especially the T\u0026ndash;N strain gradient\u0026mdash;are independently associated with key structural remodeling metrics, including BMO area, gamma zone area, lamina cribrosa depth, and BMO-minimum rim width.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis prospective, cross-sectional study was approved by the Ethics Committee of Wenzhou Medical University and adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants (H2025-025-K-24).\u003c/p\u003e\n\u003cp\u003eA total of 45 subjects were recruited, and the right eye of each participant was selected for analysis. The cohort consisted of 25 eyes with high myopia (HM) and 20 normal control (NC) eyes. All subjects underwent a comprehensive ophthalmic examination. The HM group was defined by an axial length (AL) \u0026ge; 26.0 mm. The NC group comprised eyes with AL between 22.0 and 26.0 mm.\u003c/p\u003e\n\u003cp\u003eExclusion criteria were as follows: visual field defects; glaucomatous optic neuropathy; pathologic myopia as defined by the META-PM classification\u003csup\u003e20\u003c/sup\u003e; prior intraocular surgery or ocular trauma; contact lens wear within one month; and any systemic disease that may affect the eye, such as diabetic retinopathy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSS-OCT Image Acquisition and Loading Paradigms\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll eyes were imaged using a commercial swept-source OCT system (VG200S; SVision Imaging, Henan, China). A three-dimensional raster scanning protocol was employed to acquire volumes centered on the optic nerve head (ONH), covering a 3 \u0026times; 3 mm area. Each volume consisted of 512 horizontal B-scans, and each B-scan contained 512 A-scans.\u0026nbsp;To optimize image quality, each B-scan was averaged 8 times to reduce speckle noise.\u003c/p\u003e\n\u003cp\u003eAll imaging was performed under cycloplegia. Each eye underwent swept-source OCT scanning of the ONH under two standardized mechanical loading conditions: a baseline state and an acute IOP-induced state (Figure 1A). At baseline, two reference volumes were acquired in the primary gaze position. For the IOP-induced condition, a calibrated pressure gauge (SH-II-10, Nanjing NSCING Co., Ltd) applied a gentle, perpendicular force of 0.65 N to the temporal lower eyelid, producing an acute IOP elevation monitored with an iCare tonometer (iCare Pro, Finland) before and during the loading. A second OCT volume was then obtained under sustained pressure. The acquisition workflow and mechanical loading paradigm are illustrated schematically in Figure\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eDigital Volume Correlation and Strain Calculation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe three-dimensional displacement field within the ONH between the baseline and loaded states was computed using the digital volume correlation (DVC) module in Amira 2024 (Thermo Fisher Scientific).\u0026nbsp;Prior to DVC computation, the ONH region was segmented and extracted from the full volumetric dataset to isolate the region of interest\u0026nbsp;(Figure 1B).\u0026nbsp;A rigid registration algorithm was then applied to the extracted volumes to correct for any potential\u0026nbsp;global motion\u0026nbsp;between the acquisition of the reference and deformed states.\u003c/p\u003e\n\u003cp\u003eDVC analysis was performed with the following optimized parameters: a subvolume size of 100 \u0026mu;m isotropic cube was selected to provide an optimal balance between spatial resolution and computational stability.\u0026nbsp;(Figure 1C)\u0026nbsp;The iterative calculation was set to run for a maximum of 200 cycles or until a convergence criterion of u = 0.001 was met, whichever occurred first. The raw strain values obtained from DVC were normalized to account for interindividual variations in the actual achieved IOP elevation. The final corrected strain was calculated as: corrected strain = raw strain \u0026times; (18 / \u0026Delta;IOP), where 18 mmHg represents the target IOP elevation used for standardization across all subjects.\u003c/p\u003e\n\u003cp\u003eThe resulting displacement vector field was subsequently used to compute the Lagrangian finite strain tensor. From this tensor, the scalar von Mises strain (a measure of total deformation magnitude) and the principal strains (E1: maximum tensile strain, E2: intermediate strain, E3: maximum compressive strain) were derived for quantitative comparative analysis. Regional mechanical asymmetry was quantified by the\u0026nbsp;temporal-nasal (T-N) strain gradient, defined as the absolute difference in sectoral von Mises strain between the temporal and nasal quadrants. (Figure 2, mechanical assessment)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQuantification of ONH Structural Parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Four key parameters of ONH structural remodeling were analyzed from the baseline OCT volumes obtained before mechanical loading, using previously established methods from our laboratory.\u003csup\u003e15,17\u003c/sup\u003e All measurements were performed using 18 radial B-scans covering a 6\u0026times;6 mm area centered on the ONH. \u0026nbsp;(Figure 2,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eONH structural remodeling).Briefly, Bruch\u0026rsquo;s membrane opening area (BMOA) was derived from manually identified BMO points and calculated as the area enclosed by their projection onto a best-fit plane; the parapapillary gamma zone area was defined as the region between the BMO boundary and the optic disc margin on the scanning laser ophthalmoscopy image; lamina cribrosa depth (LCD) was obtained as the mean perpendicular distance from the BMO plane to the anterior lamina cribrosa across predefined sampling locations; and BMO\u0026ndash;minimum rim width (BMO\u0026ndash;MRW) was defined as the smallest distance from the BMO point to the internal limiting membrane across all radial scans.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConceptual Interpretation of Acute IOP-Induced Deformation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo provide theoretical support for the experimentally observed strain\u0026ndash;IOP relationships, the optic nerve head (ONH) tissue was modeled as a linear viscoelastic material. The ONH and lamina cribrosa are primarily composed of collagen-rich connective tissues, which are known to exhibit time-dependent deformation under sustained mechanical loading. However, in the present study, intraocular pressure (IOP) elevation was applied over a short duration and maintained at a constant level prior to image acquisition, thereby approximating a quasi-static loading condition.\u003c/p\u003e\n\u003cp\u003eSpecifically, the elevated IOP was sustained for approximately 10 seconds before swept-source OCT imaging. This interval was sufficient to allow transient viscoelastic responses to largely dissipate, enabling strain measurements to reflect a mechanically stabilized state. Under these experimental conditions, the constitutive behavior of ONH tissues was described using a Kelvin\u0026ndash;Voigt viscoelastic model:\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003eThis simplification permits direct interpretation of the experimentally observed linear relationship between applied loading and measured strain as an effective elastic response.\u003c/p\u003e\n\u003cp\u003eIn vivo quantification of absolute ONH tissue stress is not feasible due to geometric complexity and material heterogeneity. Accordingly, IOP was treated as a normalized surrogate for the applied mechanical load, consistent with prior in vivo biomechanical studies of the ONH. The target IOP elevation was set to approximately 18 mmHg, a magnitude commonly used to induce measurable ONH deformation while remaining within a physiologically safe range and a near-linear mechanical response regime.\u003c/p\u003e\n\u003cp\u003eBased on this framework, an effective Young\u0026rsquo;s modulus was defined as the proportional coefficient relating IOP elevation to the regional strain response:\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"data:image/png;base64,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\"\u003e\u003c/p\u003e\n\u003cp\u003eThe effective Young\u0026rsquo;s modulus reported in this study therefore represents an apparent, IOP-normalized biomechanical parameter, reflecting relative regional stiffness rather than an intrinsic material constant. This formulation enables direct comparison of biomechanical behavior between normal control and high myopia eyes, as well as between nasal and temporal regions of the ONH.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using SPSS Statistics (Version 26; IBM Corp., USA). Independent samples t-tests and chi-square tests were used to compare continuous and categorical demographic variables between groups, respectively. Linear regression analyses (both univariate and multivariate) were employed to identify factors associated with the structural remodeling parameters. The multivariate models were adjusted for potential confounders. A p-value of less than 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eSubject Characteristics\u003c/h2\u003e \u003cp\u003eA total of 45 subjects were included in the final analysis. Baseline characteristics and structural parameters of the high myopia (HM) and normal control (NC) groups are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The two groups showed no significant differences in age, sex distribution, baseline intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, or radial peripapillary capillary (RPC) density (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The HM group had a significantly longer axial length than the NC group (27.44\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82 mm vs. 24.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01 mm; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The HM group exhibited a significantly larger Bruch's membrane opening area (BMOA) (3.44\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10 mm\u0026sup2; vs. 2.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54 mm\u0026sup2;; p\u0026thinsp;=\u0026thinsp;0.01) and a larger gamma zone area (1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80 mm\u0026sup2; vs. 0.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39 mm\u0026sup2;; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) compared to the NC group. No significant inter-group differences were found in lamina cribrosa depth (LCD) or BMO-minimum rim width (BMO-MRW) (p\u0026thinsp;=\u0026thinsp;0.22 and p\u0026thinsp;=\u0026thinsp;0.57, respectively).\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\u003eComparison of Parameters Between High Myopia and Normal Contral\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\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\u003eNC\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;20\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHM\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;25\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCLINICAL PARAMETER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.80\u0026thinsp;\u0026plusmn;\u0026thinsp;3.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.20\u0026thinsp;\u0026plusmn;\u0026thinsp;5.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, male/female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAxial length, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.44\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline IOP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.41\u0026thinsp;\u0026plusmn;\u0026thinsp;2.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.66\u0026thinsp;\u0026plusmn;\u0026thinsp;2.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRNFL, \u0026micro;m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e123.20\u0026thinsp;\u0026plusmn;\u0026thinsp;13.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e121.50\u0026thinsp;\u0026plusmn;\u0026thinsp;16.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPC, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.55\u0026thinsp;\u0026plusmn;\u0026thinsp;4.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.50\u0026thinsp;\u0026plusmn;\u0026thinsp;5.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eONH STRUCTURAL REMODELING\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMOA, mm\u0026sup2;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.44\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLCD, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e431.30\u0026thinsp;\u0026plusmn;\u0026thinsp;70.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e455.82\u0026thinsp;\u0026plusmn;\u0026thinsp;61.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGAMA Area, mm\u0026sup2;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMO-MRW, um\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e229.86\u0026thinsp;\u0026plusmn;\u0026thinsp;32.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e235.23\u0026thinsp;\u0026plusmn;\u0026thinsp;30.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eIOP, intraocular pressure; RNFL, retinal nerve fiber layer; RPC, radial peripapillary capillary; BMOA, Bruch membrane opening area; LCD, lamina cribrosa depth; BMO-MRW, Bruch membrane opening-minimum rim width.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eONH Biomechanical Measurements\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStrain Measurements\u003c/h2\u003e \u003cp\u003eThe biomechanical responses of the ONH under acute IOP elevation are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;4. The HM group demonstrated a significantly higher global mechanical response, represented by von Mises strain, than the NC group (5.84\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47% vs. 4.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96%; p\u0026thinsp;=\u0026thinsp;0.01). This increased strain in HM eyes was primarily manifested as significantly greater compression (E3: -5.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42% vs. -4.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Furthermore, the HM group exhibited significant regional mechanical asymmetry, evidenced by a higher temporal-nasal (T-N) strain gradient (0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38 vs. 0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\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 ONH Biomechanical Measurements between Normal Control and High Myopia Groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\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\u003eNC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute IOP-Induced Strain, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evon Mise\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.84\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.65\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-4.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-5.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eONH Biomechanical Imbalance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT-N Strain Gradient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eIOP, intraocular pressure; T-N, temporal-nasal.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe accuracy of the DVC method was characterized by a baseline noise level of 2.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74% strain, calculated from two repeated OCT acquisitions under baseline conditions (NC: 1.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56%; HM: 2.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.86%; p\u0026thinsp;=\u0026thinsp;0.19). The reliability of the acute IOP-induced strain measurement protocol, evaluated in a subset of 10 healthy eyes, demonstrated good intraoperator repeatability (ICC\u0026thinsp;=\u0026thinsp;0.83) and intersession reproducibility (ICC\u0026thinsp;=\u0026thinsp;0.76), while interoperator reproducibility was moderate (ICC\u0026thinsp;=\u0026thinsp;0.67). Bland-Altman analysis (Fig.\u0026nbsp;3) corroborated these findings, showing no systematic bias with the majority of data points within the limits of agreement.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eEstimation of Regional Effective Young\u0026rsquo;s Modulus\u003c/h2\u003e \u003cp\u003eLinear regression analysis revealed a strong linear relationship between intraocular pressure and the regional strain gradient across all groups and regions. Based on the constitutive framework described above, the slope of this relationship was directly interpreted as the effective Young\u0026rsquo;s modulus. The estimated effective Young\u0026rsquo;s moduli were as follows: NC\u0026ndash;Nasal: 0.0542 MPa, NC\u0026ndash;Temporal: 0.0492 MPa, HM\u0026ndash;Nasal: 0.0479 MPa, HM\u0026ndash;Temporal: 0.0403 MPa. These findings indicate that both myopia-related changes and regional differences in material behavior contribute to the observed strain distribution within the ONH.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eFactors Associated with Structural Remodeling Parameters\u003c/h2\u003e \u003cp\u003eThe factors associated with key structural remodeling parameters are detailed in Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. For BMOA (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e): In the multivariate analysis of all subjects, both a higher global strain (von Mises) (β\u0026thinsp;=\u0026thinsp;0.27, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and a larger T-N Strain Gradient (β\u0026thinsp;=\u0026thinsp;0.85, p\u0026thinsp;=\u0026thinsp;0.01) were identified as independent factors associated with a larger BMOA, after adjusting for axial length. For gamma zone area (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), in the multivariate model, larger T\u0026ndash;N strain gradient was independently associated with larger gamma zone area (β\u0026thinsp;=\u0026thinsp;0.63, p\u0026thinsp;=\u0026thinsp;0.02). For LCD (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e), univariate analysis revealed that a larger T-N Strain Gradient was significantly associated with a deeper LCD (β\u0026thinsp;=\u0026thinsp;59.85, p\u0026thinsp;=\u0026thinsp;0.02). No other biomechanical factors showed a significant association. For BMO-MRW (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e), no significant associations were found between the biomechanical parameters (global strain or T-N Gradient) and BMO-MRW.\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\u003eFactors Associated with Bruch Membrane Opening Area\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIndicators\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eMultivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAxial length, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline IOP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute IOP-Induced Strain, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT-N Strain Gradient, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eIOP, intraocular pressure; T-N, temporal-nasal.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFactors Associated with lamina cribrosa depth\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIndicators\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAxial length, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline IOP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-4.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute IOP-Induced Strain, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT-N Strain Gradient, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eIOP, intraocular pressure; T-N, temporal-nasal.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFactors Associated with Gamma Area\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIndicators\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eMultivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAxial length, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline IOP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute IOP-Induced Strain, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT-N Strain Gradient, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eIOP, intraocular pressure; T-N, temporal-nasal.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFactors Associated with BMO-MRW\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIndicators\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariate Analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAxial length, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline IOP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute IOP-Induced Strain, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT-N Strain Gradient, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-14.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eBMO-MRW, Bruch membrane opening-minimum rim width; IOP, intraocular pressure; T-N, temporal-nasal.\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\u003eThe significant relationships identified through linear regression analyses are visually demonstrated in Fig.\u0026nbsp;5, which presents scatterplots illustrating the associations between the key biomechanical factors and ONH structural remodeling parameters.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study provides, to our knowledge, the first in vivo evidence linking regional mechanical asymmetry within the ONH to multifaceted structural remodeling in high myopia. First, we validated acute IOP-induced ONH strain measurements, demonstrating good repeatability and reproducibility of von Mises strain. Second, highly myopic eyes exhibited not only elevated global strain but, more importantly, a significantly larger T-N strain gradient than controls. Third, regional mechanical asymmetry was independently associated with structural remodeling in myopic discs. Collectively, these findings indicate that the mechanical vulnerability of the myopic ONH is not merely a matter of generalized weakening but is characterized by distinct spatial heterogeneity, which appears to be a key driver of asymmetric structural remodeling.\u003c/p\u003e\n\u003cp\u003eSwept-source OCT (SS-OCT) offers distinct advantages, including higher acquisition rates and enhanced penetration depth, enabling more reliable visualization of deep ONH structures, particularly the lamina cribrosa, under dynamic loading conditions.\u003csup\u003e15,17,21,22\u003c/sup\u003eThe accuracy of our DVC methodology was first verified by calculating baseline noise from repeated OCT acquisitions under identical conditions, yielding a strain value of 2.04 ± 0.74% (NC: 1.87 ± 0.56%; HM: 2.18 ± 0.86%; p = 0.19), which is consistent with previous reports\u003csup\u003e13,23\u003c/sup\u003e Building upon this validation, we further evaluated measurement reliability across multiple dimensions. The demonstrated reliability of acute IOP-induced strain measurements (intraoperator:ICC=0.83; intersession:ICC=0.76; interoperator ICC=0.67) represents the first validation accounting for both temporal variations and observer-dependent factors in a clinical setting. Our implementation of sectoral DVC analysis represents a technical advancement, enabling, to our knowledge, the first in vivo quantification of regional ONH strain heterogeneity. The linear strain correction based on individual IOP elevation (ΔIOP) was justified by previous studies confirming minimal nonlinear effects beyond 18 mmHg, ensuring accurate inter-subject comparisons.\u003csup\u003e13\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eThe morphological remodeling of the ONH in myopia has been well characterized both histologically and clinically.\u003csup\u003e8,24\u003c/sup\u003e In moderately myopic eyes, the Bruch’s membrane opening (BMO) typically shifts toward the temporal or inferotemporal direction, producing a nasal overhang of Bruch’s membrane and its temporal absence, which defines the parapapillary gamma zone.\u003csup\u003e25\u003c/sup\u003e This shift contributes to optic disc ovalization, elongation of the fovea–disc distance, and stretching of papillomacular vessels and nerve fiber bundles.\u003csup\u003e8,15,26\u003c/sup\u003e In highly myopic eyes, further expansion and thinning of the lamina cribrosa and the peripapillary scleral flange occur, accompanied by the development of circular gamma and delta zones.\u003csup\u003e27,28\u003c/sup\u003e These features reflect progressive remodeling of both superficial and deep ONH structures under mechanical loading in myopic eyes.\u003c/p\u003e\n\u003cp\u003eIn our cohort, highly myopic eyes demonstrated significant enlargement in BMOA and gamma zone area, while showing no significant differences in LCD or BMO-MRW compared with controls. Our study extends these structural observations by revealing a fundamental biomechanical disparity: highly myopic eyes exhibited not only greater overall deformation (von Mises strain: 5.84 ± 1.47% vs. 4.84 ± 0.96%; p = 0.01) but also more pronounced regional mechanical asymmetry (T–N strain gradient: 0.54 ± 0.38 vs. 0.19 ± 0.32; p \u0026lt; 0.01). The concurrent increase in global strain and T–N asymmetry suggests that highly myopic eyes experience both amplified and spatially uneven mechanical loading across the ONH, with the temporal region being particularly susceptible to deformation.\u003cbr\u003e\u0026nbsp;To further elucidate the biomechanical basis of this regional asymmetry, we introduced a constitutive modeling framework and derived an effective Young’s modulus from the linear relationship between IOP elevation and regional strain gradient. Under a quasi-static loading condition (10 s sustained IOP elevation), the ONH response was approximated using a Kelvin–Voigt viscoelastic model, allowing the slope of the IOP–strain relationship to be interpreted as an apparent, IOP-normalized Young’s modulus.\u003c/p\u003e\n\u003cp\u003eUsing this approach, highly myopic eyes exhibited lower effective Young’s moduli than normal controls in both nasal and temporal regions, indicating increased mechanical compliance. Moreover, the temporal ONH consistently demonstrated a lower effective modulus than the nasal ONH, with this nasal–temporal difference being more pronounced in HM.(Figure 4) These findings provide direct biomechanical evidence that regional differences in tissue compliance contribute to asymmetric ONH deformation.\u003c/p\u003e\n\u003cp\u003eThe strong independent associations between the T–N strain gradient and multiple structural parameters (BMOA: β=0.85, p=0.01; gamma zone: β=0.63, p=0.02) support regional mechanical asymmetry as a fundamental driver of myopic ONH remodeling. The observed spatial variation in effective Young’s modulus provides a plausible mechanical explanation for this relationship, whereby regions with lower stiffness undergo greater deformation under equivalent IOP loading. These relationships persisted after adjustment for axial length, indicating that mechanical factors provide additional information beyond geometric elongation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInterestingly, although lamina cribrosa depth (LCD) did not differ significantly between the HM and NC groups, its significant correlation with the T–N strain gradient (β=59.85, p=0.02) suggests that posterior bowing of the lamina cribrosa is more closely governed by localized mechanical asymmetry than by axial elongation per se. This observation implies that subtle mechanical asymmetry may precede overt morphological changes detectable by conventional structural measures.\u003c/p\u003e\n\u003cp\u003eTogether, these findings suggest that an asymmetric mechanical environment—arising from regional heterogeneity in effective tissue stiffness—may initiate a cascade of remodeling events, from superficial BMO displacement and gamma zone formation to deeper lamina cribrosa bowing. This sequential remodeling may underlie the increased susceptibility of highly myopic eyes to glaucomatous and non-glaucomatous optic neuropathy. A higher T–N strain gradient may therefore indicate early biomechanical susceptibility of the ONH before irreversible rim thinning occurs. This metric could thus complement structural parameters in identifying eyes at risk of myopic optic neuropathy.\u003c/p\u003e\n\u003cp\u003eSeveral limitations warrant consideration. First, this study did not include eyes with pathologic myopia, which may partly explain the absence of a significant difference in BMO-MRW between groups. Future studies incorporating a broader spectrum of myopic severity could help clarify this relationship. Second, the cross-sectional design can demonstrate associations but not causation. Longitudinal follow-up is needed to determine whether eyes exhibiting greater baseline regional asymmetry are more likely to undergo progressive structural remodeling. Third, the DVC calculations were constrained to the visible ONH tissues captured by OCT, and strain normalization was based on an assumed linear relationship beyond baseline IOP. While we provided error estimates to account for measurement uncertainty, future studies employing more advanced tissue models or extended imaging depths could improve strain quantification. Finally, although our sample size was sufficient to detect significant associations, it limited further subgroup analyses. Fourth, the effective Young’s modulus derived in this study represents a relative, IOP-normalized biomechanical parameter rather than an intrinsic material constant. Fifth, although IOP elevation was monitored and achieved globally, the eyelid-based loading paradigm may introduce subtle directional constraints. Therefore, the reported temporal–nasal strain asymmetry should be interpreted as a relative deformation metric under a standardized, clinically feasible loading condition rather than a pure pressure-only perturbation. Despite these limitations, the present study substantially advances current understanding by shifting the conceptual framework from “global strain” to “regional asymmetry.” Quantitative assessment of the T–N strain gradient represents a novel, clinically applicable biomechanical biomarker. In the future, a simplified, rapid version of this test may enable early identification of highly myopic eyes at greatest risk for optic nerve head remodeling, facilitating targeted monitoring and timely intervention.\u003c/p\u003e\n\u003cp\u003eIn conclusion, this study identifies regional mechanical asymmetry as a key biomechanical feature of myopic ONHs. The temporal–nasal strain gradient was independently associated with multiple structural parameters. These findings provide new insight into the biomechanical pathogenesis of myopic optic neuropathy and suggest that the T–N strain gradient may serve as a potential clinical biomarker for early risk detection.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEqual Contribution Statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e*\u003c/strong\u003e These authors contributed equally to this work and shared the\u0026nbsp;first authorship.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u0026nbsp;\u003c/sup\u003eThese authors contributed equally to this research and shared corresponding authorship.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeeting Presentation:\u0026nbsp;\u003c/strong\u003eThis material has not been presented at any meetings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Support:\u0026nbsp;\u003c/strong\u003eThis research was supported by the National Natural Science Foundation of China (82171016) and the National Natural Science Foundation of China (U22A201722).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure statement:\u0026nbsp;\u003c/strong\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Wenzhou Medical University (Approval No. H2025-025-K-24) and adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained from all participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eMorgan IG, Ohno-Matsui K, Saw S-M. Myopia. \u003cem\u003eLancet.\u0026nbsp;\u003c/em\u003e2012;379(9827):1739-1748.\u003c/li\u003e\n \u003cli\u003eHuh MG, Jeong Y, Shin YI, Park KH, Jeoung JW. Can Baseline Parapapillary Atrophy Morphology Predict Future Glaucoma Progression?- An OCT Glaucoma Imaging Study. \u003cem\u003eAm J Ophthalmol.\u0026nbsp;\u003c/em\u003e2024.\u003c/li\u003e\n \u003cli\u003eLatif K, Nishida T, Moghimi S, Micheletti E, Du K, Weinreb RN. 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Determinants of lamina cribrosa depth in healthy Asian eyes: the Singapore Epidemiology Eye Study. \u003cem\u003eBr J Ophthalmol.\u0026nbsp;\u003c/em\u003e2020;105(3):367-373.\u003c/li\u003e\n \u003cli\u003eRebolleda G, Garc\u0026iacute;a-Montesinos J, De Dompablo E, Oblanca N, Mu\u0026ntilde;oz-Negrete FJ, Gonz\u0026aacute;lez-L\u0026oacute;pez JJ. Bruch\u0026apos;s membrane opening changes and lamina cribrosa displacement in non-arteritic anterior ischaemic optic neuropathy. \u003cem\u003eBr J Ophthalmol.\u0026nbsp;\u003c/em\u003e2016;101(2):143-149.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"ophthalmic-and-physiological-optics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Ophthalmic and Physiological Optics](https://link.springer.com/journal/44402)","snPcode":"44402","submissionUrl":"https://submission.springernature.com/new-submission/44402/3?","title":"Ophthalmic and Physiological Optics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8797848/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8797848/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo investigate regional mechanical asymmetry of the optic nerve head (ONH) in high myopia.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eSwept-source OCT imaging was performed before and during controlled acute intraocular pressure (IOP) elevation. Three-dimensional strain was calculated using digital volume correlation, from which global strain (von Mises) and regional mechanical asymmetry (temporal\u0026ndash;nasal strain gradient) were derived. Based on the measured strain response to IOP elevation, an effective, IOP-normalized Young\u0026rsquo;s modulus was estimated to characterize relative regional ONH tissue stiffness. Structural parameters included Bruch\u0026rsquo;s membrane opening area (BMOA), lamina cribrosa depth (LCD), gamma zone area, and BMO-minimum rim width.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThis study included 25 highly myopic eyes and 20 normal control eyes. The high myopia group exhibited larger BMOA and gamma zone area, as well as greater global strain (5.84\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47% vs. 4.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96%; p\u0026thinsp;=\u0026thinsp;0.01) and T\u0026ndash;N strain gradient (0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38 vs. 0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Temporal ONH stiffness was significantly reduced relative to the nasal region. Multivariate analyses showed that the T-N strain gradient was independently associated with larger BMOA and gamma zone area, while global strain was associated with BMOA. A higher T-N strain gradient was also associated with greater LCD in univariate analysis.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eRegional mechanical asymmetry is a key biomechanical feature of the highly myopic ONH and is independently linked to multiple aspects of structural remodeling. These findings highlight the role of regional mechanical asymmetry and suggest a potential biomechanical biomarker for early risk assessment in high myopia.\u003c/p\u003e","manuscriptTitle":"Regional Mechanical Asymmetry: A Key Feature of the Optic Nerve Head in High Myopia Associated with Structural Remodeling","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-17 19:24:27","doi":"10.21203/rs.3.rs-8797848/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-10T04:06:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"28653407208205232744897204149940740121","date":"2026-02-09T23:23:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-09T20:08:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-09T20:04:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-06T07:36:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"Ophthalmic and Physiological Optics","date":"2026-02-05T13:26:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"ophthalmic-and-physiological-optics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Ophthalmic and Physiological Optics](https://link.springer.com/journal/44402)","snPcode":"44402","submissionUrl":"https://submission.springernature.com/new-submission/44402/3?","title":"Ophthalmic and Physiological Optics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c6c46f44-c87d-4fcd-b0aa-5929e570a75f","owner":[],"postedDate":"February 17th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-17T19:24:29+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-17 19:24:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8797848","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8797848","identity":"rs-8797848","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}