A cross-linking operation simulation optimization method based on a multi-physical field coupling cornea constitutive model

Abstract

The application discloses a cross-linking operation simulation optimization method based on a multi-physical field coupling cornea constitutive model, and comprises the following steps: firstly, a multi-physical field coupling cornea constitutive theoretical model is constructed, the influence of operation parameters on photochemical reaction is integrated, a positive correlation mapping between cross-linking density and mechanical properties is established, and a theoretical framework covering multiple physical fields is formed; secondly, based on the theoretical model, a three-dimensional geometric model is combined with clinical data to establish a cornea cross-linking numerical simulation model; thirdly, the numerical model is applied to perform full cornea dynamic simulation, analyze the characteristics of a lesion area and optimize parameters; and finally, measured and animal experiment data are fused to verify the parameter change trend, and the operation parameters are compared and optimized to calibrate the model. The method can accurately simulate the cross-linking process, provides a basis for individualized optimization of operation parameters and efficacy prediction, solves the problems of poor efficacy and lack of individualized adaptation in a traditional scheme, and promotes precise treatment.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedical engineering, biomechanics, photochemical reaction kinetics and computer science, in particular to a cross-linking operation simulation optimization method based on a multi-physical field coupling corneal constitutive model. BACKGROUND

[0002] Keratoconus is a progressive corneal ectatic disease characterized by progressive thinning and conical protrusion of the central or para-central cornea, ultimately leading to irregular astigmatism and decreased vision. The core mechanism is the abnormal structure of collagen fibers in the corneal stroma: normal corneal collagen forms a stable network through covalent cross-linking to maintain biomechanical strength; while patients due to genetic, enzymatic imbalance or metabolic disorders, leading to disordered arrangement of collagen fibers, which cannot withstand intraocular pressure. When the local elastic modulus of the cornea decreases, the intraocular pressure and corneal stress balance is broken, and the weak area gradually expands and thins, with a decrease in the radius of curvature. The cornea initiates a compensatory mechanism to adjust the stress distribution, but this in turn exacerbates the deterioration of the weak area, forming a vicious cycle that ultimately drives disease progression.

[0003] Corneal cross-linking is an effective means of treating keratoconus and other corneal ectatic diseases, its principle is to use ultraviolet light to irradiate corneal tissue infiltrated with riboflavin, to form new covalent bonds between collagen fibers, thereby enhancing the mechanical strength and stability of the cornea. However, the current technology still has significant limitations in clinical application.

[0004] From the type of scheme, traditional corneal cross-linking is mainly divided into three steps: first, remove the epithelial layer in the central 7-9mm area of the cornea, then soak in 0.1% riboflavin solution for 30 minutes, during which the drip is replenished every 2-3 minutes, and finally use ultraviolet light with a wavelength of 370nm and an irradiance of 3mW / cm² for continuous irradiation for 30 minutes. This scheme has the problems of long operation process, difficulty in precise control of cross-linking depth, and complications such as infection and pain caused by epithelial removal operation; at the same time, the standardized operation mode is difficult to match the biomechanical differences between individual patients, leading to uneven treatment effect.

[0005] To solve the above problems, clinical medicine has developed improved techniques such as rapid cross-linking and low-osmolar riboflavin cross-linking. For example, rapid cross-linking shortens the treatment time by increasing the intensity of ultraviolet irradiation, but has problems such as insufficient cross-linking depth and unstable long-term efficacy; low-osmolar riboflavin thin corneal cross-linking effectively protects the corneal endothelial layer of patients with thin corneas, but the penetration efficiency of riboflavin is low and the cross-linking effect is difficult to guarantee. These technologies have not fundamentally broken through the core difficulties: first, the setting of surgical parameters such as light intensity, irradiation time, and riboflavin concentration lacks scientific basis, resulting in significant differences in clinical efficacy of different schemes; second, the cross-linking process is affected by multiple factors such as corneal thickness, riboflavin permeability, drug diffusion kinetics, oxygen consumption and supply efficiency, and existing technologies cannot systematically quantify the contribution of each factor to the treatment effect, making it impossible to establish a reliable efficacy prediction model.

[0006] Based on the above analysis, the key challenge facing current corneal cross-linking surgery is the lack of scientific research methods. On the one hand, there is a lack of quantitative analysis models that can integrate multiple factors, making it impossible to accurately reveal the internal relationship between surgical parameters and the evolution of corneal mechanical properties; on the other hand, there is no standardized surgical outcome evaluation system, resulting in a lack of underlying technical support for technological innovation, making it difficult to make the leap from "empirical treatment" to "precision medicine".

[0007] Current corneal cross-linking surgery urgently needs precise models that integrate multiple physical field factors in terms of treatment effect optimization, individualized scheme development, and accurate prediction of postoperative mechanical response. Although existing corneal constitutive models have formed a system of hyperelasticity, viscoelasticity, and super-viscoelasticity, there is still a lack of coupled models that integrate multiple physical field factors such as light energy distribution, riboflavin concentration gradient, and oxygen diffusion behavior, making it impossible to dynamically describe the spatio-temporal evolution of corneal mechanical properties during the cross-linking process. The highly nonlinear multi-field strong coupling phenomena involved in corneal cross-linking, such as photochemical cross-linking, mass transport, and biomechanical response, far exceed the conventional processing capabilities of traditional finite element simulation platforms.

[0008] Specifically, there are three major gaps in existing technology: first, there is a lack of systematic mechanism modeling tools that integrate mechanical-optical-chemical reaction processes, making it difficult to reveal the essence of mechanical property evolution from the molecular cross-linking mechanism level; second, there is a lack of multi-field coupled simulation models that can simulate the dynamic evolution of corneal mechanics during the cross-linking process, making it impossible to quantify the nonlinear relationship between surgical parameters and mechanical enhancement; third, there is a lack of customized treatment scheme design methods based on individual biomechanical parameters and dynamic response to changes in surgical parameters, making it difficult to meet the needs of clinical precision medicine.

[0009] It should be noted that the information disclosed in the above background section is only for understanding the background of the present application, and therefore can include information that does not constitute prior art known to those of ordinary skill in the art. SUMMARY

[0010] The main purpose of the present application is to overcome the defects existing in the background art, provide a cross-linking operation simulation optimization method based on a multi-physical field coupling corneal constitutive model, to assist in realizing the precision and individualization of corneal cross-linking operation, and overcoming the uncertainty problem of treatment effect caused by individual differences and complex multi-physical field coupling.

[0011] In order to achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0012] A cross-linking operation simulation optimization method based on a multi-physical field coupling corneal constitutive model, comprising the following steps:

[0013] S1, constructing a multi-physical field coupling corneal constitutive theory model: integrating the influence mechanism of cross-linking operation parameters on the covalent bond generation rate in photochemical reaction, establishing a positive correlation mapping relationship between cross-linking density and corneal mechanical properties, forming a multi-physical field coupling theoretical framework covering rare substance transfer, light field distribution, photochemical reaction and mechanical response;

[0014] S2, establishing a corneal cross-linking numerical simulation model: based on the theoretical model, combining clinical measurement data and corneal three-dimensional geometric model, through grid division and boundary condition setting, realizing parameter transmission and nonlinear coupling calculation of rare substance transfer, light field distribution, photochemical reaction and mechanical response, generating a numerical simulation model of dynamic evolution of corneal mechanical properties;

[0015] S3, full corneal simulation analysis and parameter optimization: applying the numerical simulation model to simulate the full corneal cross-linking, quantitatively analyzing the biomechanical properties of the lesion area, and optimizing the key parameters of the model based on the simulation results;

[0016] S4, experimental verification and model iteration: integrating the measured data of corneal biomechanical measurement equipment and animal experiment data, verifying the trend of corneal biomechanical parameter changes for different operation parameter combinations, and optimizing the operation parameters and calibrating the model through comparison between experiment and simulation.

[0017] Further, step S1 specifically comprises:

[0018] Establishing a photochemical reaction kinetics model: based on the optical properties of the cornea, constructing an ultraviolet propagation path and energy distribution model, quantifying the influence of riboflavin concentration and oxygen content on the depth of light energy absorption; based on the substance non-steady-state diffusion equation, introducing a photo-degradation term and a reaction consumption term in riboflavin diffusion, and introducing an oxidation reaction consumption term and an anterior chamber supply term in oxygen diffusion, to generate a light energy absorption spatial distribution model;

[0019] Constructing a cross-linking density-mechanical property coupling constitutive model: defining the space-time distribution function of cross-linking density according to the output of photochemical reaction, and integrating cross-linking density as a material parameter adjustment factor into the hyperelastic constitutive model;

[0020] Setting up multi-physical field coupling interface: defining the two-way coupling equation of photochemical reaction and mechanical response, combining physiological boundary conditions to establish multi-field synergistic mechanism.

[0021] Further, the construction of the photochemical reaction kinetics model in step S1 specifically includes:

[0022] Based on the modified Beer-Lambert law, an attenuation model of ultraviolet light in the cornea is constructed, and by describing the attenuation law of light intensity with depth, the concentration gradient of riboflavin, light intensity and oxygen diffusion behavior are dynamically coupled;

[0023] Through the photochemical reaction kinetics equation, the nonlinear coupling relationship among ultraviolet intensity, riboflavin concentration and oxygen partial pressure is introduced into the covalent bond generation process, the depth-dependent characteristics of covalent bond generation are established, and the spatiotemporal distribution function of crosslinking density changing with time and depth is generated;

[0024] Taking the crosslinking density distribution as input, the relationship between mechanical parameters and crosslinking density is established through the hyperelastic constitutive model, and the time-varying evolution of the mechanical properties of the cornea is represented.

[0025] Further, step S2 specifically includes:

[0026] Parameterized three-dimensional corneal modeling: extracting corneal geometric parameters from OCT images to construct an adjustable three-dimensional corneal model;

[0027] Meshing and boundary condition setting: using a differentiated encryption meshing strategy, setting the ultraviolet light field, riboflavin diffusion boundary and physiological load conditions based on surgical equipment parameters;

[0028] Multi-physical field coupling solution: coupling the diffusion equation and the photochemical reaction kinetics equation, establishing the nonlinear mapping relationship between crosslinking density and elastic modulus, using the iterative method to solve the multi-physical field equation set, and quantifying the influence mechanism of the surgical parameters through parameter scanning and response surface modeling.

[0029] Further, the multi-physical field coupling solution specifically includes:

[0030] Equation coupling and relationship modeling: coupling riboflavin diffusion equation, light transmission equation, oxygen consumption equation and photochemical reaction kinetics equation, constructing covalent bond generation rate expression and crosslinking density-elastic modulus mapping function;

[0031] Numerical solution of equation set: using Newton iteration method to solve the multi-physical field nonlinear equation set in space and time, outputting the mechanical property parameters of different regions and time nodes, and reflecting the step-by-step influence of diffusion field, light field and chemical reaction field on mechanical parameters in the solving process;

[0032] Surgical parameter influence analysis: Through multi-group parameter combination scanning design and response surface modeling, the system quantifies the effect of each parameter on the biomechanical properties of the cornea, especially focusing on the gradient influence of light intensity distribution and material diffusion characteristics on cross-linking effect.

[0033] Further, the numerical simulation in step S2 adopts a sequential coupling strategy:

[0034] Solve the diffusion equations of riboflavin and oxygen, where riboflavin diffusion considers light-induced degradation and reaction consumption, and oxygen diffusion needs to include reaction consumption and anterior chamber supply, output the spatial and temporal distribution of riboflavin and oxygen concentrations;

[0035] With the riboflavin concentration distribution as input, solve the light field transmission equation by describing the law of light intensity decay with depth to obtain the internal light intensity distribution of the cornea, which affects the reaction rate in the material diffusion process;

[0036] According to the light intensity distribution and active oxygen concentration, update the mechanical parameters through the mapping relationship between cross-linking density and mechanical parameters, solve the mechanical response field and obtain the stress-strain distribution.

[0037] Further, step S3 specifically includes:

[0038] Multi-module integration and full corneal modeling: integrate theoretical models and numerical simulation models to build a three-dimensional dynamic simulation model covering the full cornea;

[0039] Quantitative analysis of lesion area: apply pathological intraocular pressure to specific areas of the cornea to simulate pathological conditions, and quantify the repair effect of different surgical parameters on the lesion area through simulation;

[0040] Model parameter calibration: optimize key parameters such as photochemical reaction rate constant and elastic modulus mapping coefficient based on clinical data.

[0041] Further, step S4 specifically includes:

[0042] Measure the stress-strain response of the cornea under the preset parameter grid through equivalent axis tensile experiments to verify the simulation accuracy of the model for isotropic mechanical behavior;

[0043] Apply asymmetric load through non-equivalent axis tensile experiments to verify the ability of the model to describe anisotropic mechanical behavior;

[0044] Based on the comparative analysis of experimental data and simulation results, optimize the surgical parameters and calibrate the model.

[0045] Further, step S4 also includes:

[0046] Fusion of CorvisST measured data and animal experiment biaxial tensile data to build a multi-source data collaborative closed-loop mechanism;

[0047] Iterative optimization of simulation model parameters through experimental data feedback forms a data-driven model calibration process;

[0048] Based on the verified model output personalized operation parameter combination, the cross-linking curative effect is accurately predicted.

[0049] A computer program product comprising a computer program which, when executed by a processor, implements the cross-linking operation simulation optimization method based on the multi-physical field coupled cornea constitutive model.

[0050] The present application has the following beneficial effects:

[0051] The present application proposes a cross-linking operation simulation optimization method based on a multi-physical field coupled cornea constitutive model, which realizes the precision and individualization of corneal cross-linking operation by fusing multi-physical field factors. First, the influence of cross-linking operation parameters on photochemical reaction and the relationship between cross-linking density and mechanical properties are integrated to build a multi-physical field coupled cornea constitutive theoretical model. Then, the numerical simulation model is constructed by combining the corneal lenticule geometric model with the above theoretical model, realizing the parameter transmission and coupling calculation between the multi-physical fields of rare substance transmission, light field distribution, photochemical reaction and mechanical response. Subsequently, the biomechanical properties of the conical keratopathy area in the cross-linking process are quantitatively analyzed and dynamically simulated by using full corneal cross-linking simulation, and the key parameters of the model are optimized. Finally, the measured data of the corneal biomechanics measuring equipment (such as Corvis ST) and the animal experiment data are fused to systematically obtain the variation trend and magnitude characteristics of the corneal biomechanics parameters under different operation parameter combinations. Through these series of steps, the corneal cross-linking process can be accurately simulated, providing a scientific basis for the individualized optimization and curative effect prediction of operation parameters, effectively solving the technical problems of poor curative effect and lack of individualized adaptation of traditional operation schemes, and promoting the precision treatment of conical keratopathy and other diseases.

[0052] The important innovation and significant advantages of the present application mainly lie in three aspects.

[0053] Firstly, in the construction of the multi-physical field coupled cornea constitutive model, the ultraviolet light field transmission law, riboflavin transcorneal penetration kinetics, oxygen consumption transmission process, and corneal mechanical reconstruction effect are innovatively integrated to form a multi-physical process coupling system covering rare substance transmission-light field distribution-photochemical reaction-mechanical response. This model breaks through the limitation of traditional single physical field modeling, sets the constitutive relationship as a binary function of time and depth, and can accurately depict the dynamic evolution process of corneal mechanical properties in cross-linking operation, and quantitatively reveal the influence mechanism of operation parameters such as ultraviolet dose and photosensitizer concentration on cross-linking degree spatial distribution and corneal biomechanics, laying a theoretical foundation for operation parameter optimization and postoperative effect evaluation.

[0054] Secondly, in the numerical simulation of multi-physical field coupling corneal crosslinking, the system uses partial differential mathematical field to fit special reaction kinetics, including the illumination field affected by the local riboflavin concentration and the photochemical reaction field affected by the riboflavin concentration, illumination intensity and oxygen concentration; through the self-defined coupling relationship between physical fields and the series connection of multi-physical field parameter transmission relationship, a runnable numerical simulation model is built. At the same time, the geometric model is processed in layers and probes are set to realize the detection of the mechanical properties of the cornea at multiple time nodes, as well as the comprehensive detection of the change trend of riboflavin concentration, oxygen content, illumination intensity and mechanical performance index in each depth space, filling the gap of crosslinking operation parameter change process and detection index setting.

[0055] Thirdly, in the model optimization driven by data, a model parameter calibration algorithm based on simulation and experimental data fusion is proposed. By integrating the corneal geometric model and the multi-physical field coupling model, a high-precision three-dimensional simulation model is constructed to realize the quantitative analysis and dynamic simulation of the biomechanical properties of the lesion area; by fusing the Corvis ST measured data and the biaxial tensile test data of animal experiments, the system obtains the change trend and magnitude characteristics of the corneal biomechanical parameters for different crosslinking operation parameter combinations, realizes the iterative optimization of the model parameters and the experimental verification of the anisotropy characteristics of the cornea. This multi-source data collaborative fusion method breaks through the limitations of traditional single data calibration and improves the mapping accuracy of the corneal constitutive model to the real physiological environment, providing a solid data support for the individualized scheme design of crosslinking operation.

[0056] In summary, by constructing the corneal constitutive model integrating the photochemical crosslinking kinetics, biomechanical response and material transport characteristics, the cross-scale simulation from the molecular crosslinking mechanism to the macroscopic mechanical properties is realized, which provides scientific support for solving the bottleneck problems such as efficacy optimization and individualized scheme formulation in corneal crosslinking operation, and promotes the technology to move towards "precision medicine".

[0057] Other beneficial effects of the embodiments of the present application will be further described below. BRIEF DESCRIPTION OF DRAWINGS

[0058] Figure 1 It is a personalized operation parameter driven corneal crosslinking effect visualization schematic diagram of the embodiments of the present application.

[0059] Figure 2 It is a corneal crosslinking effect simulation schematic diagram of the personalized lesion area of the keratoconus of the embodiments of the present application.

[0060] Figure 3 It is a general flowchart of the corneal crosslinking operation simulation optimization system of the embodiments of the present application. DETAILED DESCRIPTION

[0061] The embodiments of the present application will be described in detail below. It should be emphasized that the following description is only exemplary and is not intended to limit the scope of the present application and its applications.

[0062] The present application aims to solve the problems of poor efficacy and lack of individual adaptation in traditional corneal crosslinking surgery, proposes to construct a multi-physical field coupled corneal constitutive model, integrates multi-field factors such as photochemical reaction, mass transfer and mechanical response, and realizes individual optimization of surgical parameters and accurate prediction of efficacy. The method of the present application breaks through the limitation of single physical field modeling, forms a model iteration mechanism driven by multi-source data, and provides scientific support for the precision treatment of diseases such as keratoconus.

[0063] Referring to Figure 3 The embodiment of the present application provides a crosslinking surgery simulation optimization method based on a multi-physical field coupled corneal constitutive model, comprising the following steps:

[0064] Step S1, constructing a multi-physical field coupled corneal constitutive theory model: integrating the influence mechanism of crosslinking surgery parameters on the covalent bond generation rate in photochemical reaction, establishing a positive correlation mapping relationship between crosslinking density and corneal mechanical properties, and forming a multi-physical field coupled theoretical framework covering rare substance transfer, light field distribution, photochemical reaction and mechanical response.

[0065] In some embodiments, step S1 specifically comprises:

[0066] Establishing a photochemical reaction kinetics model: based on the optical properties of the cornea, constructing an ultraviolet propagation path and energy distribution model, quantifying the influence of riboflavin concentration and oxygen content on the depth of light energy absorption; based on the substance non-steady-state diffusion equation, introducing a photo-degradation term and a reaction consumption term in riboflavin diffusion, and introducing an oxidation reaction consumption term and an anterior chamber supply term in oxygen diffusion, generating a light energy absorption spatial distribution model;

[0067] Constructing a crosslinking density-mechanical property coupled constitutive model: defining the space-time distribution function of crosslinking density according to the output of photochemical reaction, and integrating crosslinking density as a material parameter adjustment factor into the hyperelastic constitutive model;

[0068] Setting up a multi-physical field coupling interface: defining a two-way coupling equation of photochemical reaction and mechanical response, and establishing a multi-field synergistic mechanism combined with physiological boundary conditions.

[0069] In some embodiments, the photochemical reaction kinetics model in step S1 specifically comprises: constructing an ultraviolet attenuation model in the cornea based on the modified Beer-Lambert law, dynamically coupling the riboflavin concentration gradient, light intensity and oxygen diffusion behavior by describing the attenuation law of light intensity with depth; introducing the nonlinear coupling relationship among ultraviolet intensity, riboflavin concentration and oxygen partial pressure into the covalent bond generation process through the photochemical reaction kinetics equation, establishing the depth-dependent characteristics of covalent bond generation, and generating the spatiotemporal distribution function of crosslinking density changing with time and depth; taking the crosslinking density distribution as input, establishing the relationship between mechanical parameters and crosslinking density through the hyperelastic constitutive model, and representing the time-varying evolution of the mechanical properties of the cornea.

[0070] Step S2, establishing a numerical simulation model of corneal crosslinking: based on the theoretical model, combining clinical measurement data and a three-dimensional geometric model of the cornea, realizing parameter transfer and nonlinear coupling calculation of substance transfer, light field distribution, photochemical reaction and mechanical response through grid division and boundary condition setting, and generating a numerical simulation model of dynamic evolution of the mechanical properties of the cornea.

[0071] In some embodiments, step S2 specifically comprises:

[0072] Parameterized three-dimensional corneal modeling: extracting corneal geometric parameters from OCT images to construct an adjustable three-dimensional corneal model;

[0073] Grid division and boundary condition setting: using a differentiated encryption grid strategy, setting the ultraviolet light field, riboflavin diffusion boundary and physiological load conditions based on surgical equipment parameters;

[0074] Multi-physical field coupling solution: coupling the diffusion equation and the photochemical reaction kinetics equation, establishing a nonlinear mapping relationship between crosslinking density and elastic modulus, solving the multi-physical field equation set by iteration method, and quantifying the influence mechanism of surgical parameters by parameter scanning and response surface modeling.

[0075] In some embodiments, the multi-physical field coupling solution specifically comprises:

[0076] Equation coupling and relationship modeling: coupling the riboflavin diffusion equation, the light transmission equation, the oxygen consumption equation and the photochemical reaction kinetics equation, constructing the covalent bond generation rate expression and the crosslinking density-elastic modulus mapping function;

[0077] Numerical solution of equation set: using Newton iteration method to solve the multi-physical field nonlinear equation set in space and time, outputting the mechanical property parameters at different regions and time nodes, and reflecting the step-by-step influence of diffusion field, light field and chemical reaction field on mechanical parameters in the solving process;

[0078] Surgical parameter influence analysis: Through scanning design and response surface modeling with multiple parameter combinations, the effects of each parameter on corneal biomechanical properties are systematically quantified, with particular attention paid to the gradient influence of light intensity distribution and material diffusion characteristics on cross-linking effect.

[0079] In some embodiments, the numerical simulation in step S2 employs a sequential coupling strategy: solving the diffusion equations for riboflavin and oxygen, where riboflavin diffusion considers photoinduced degradation and reaction consumption, and oxygen diffusion needs to incorporate reaction consumption and anterior chamber supply, outputting the spatiotemporal distribution of riboflavin and oxygen concentrations; using the riboflavin concentration distribution as input, solving the light field transmission equation by describing the law of light intensity attenuation with depth to obtain the light intensity distribution inside the cornea, which in turn affects the reaction rate in the material diffusion process; based on the light intensity distribution and reactive oxygen concentration, updating the mechanical parameters through the mapping relationship between crosslinking density and mechanical parameters, solving the mechanical response field, and obtaining the stress-strain distribution.

[0080] Step S3, Full Corneal Simulation Analysis and Parameter Optimization: Apply the numerical simulation model to perform dynamic simulation of full corneal crosslinking, quantitatively analyze the biomechanical characteristics of the lesion area, and optimize the key parameters of the model based on the simulation results.

[0081] In some embodiments, step S3 specifically includes:

[0082] Multi-module integration and full corneal modeling: Integrating theoretical models and numerical simulation models to construct a three-dimensional dynamic simulation model covering the entire cornea;

[0083] Quantitative analysis of lesion areas: Pathological-grade intraocular pressure is applied to specific areas of the cornea to simulate the lesion state, and the repair effect of different surgical parameters on the lesion area is quantified through simulation.

[0084] Model parameter calibration: Optimize key parameters such as photochemical reaction rate constant and elastic modulus mapping coefficient based on clinical data.

[0085] Step S4, Experimental Verification and Model Iteration: Integrate corneal biomechanical measurement data, such as CorvisST, with animal experimental data, and systematically verify the changing trends of corneal biomechanical parameters for different combinations of surgical parameters. Optimize surgical parameters and calibrate the model through experimental and simulation comparisons.

[0086] In some embodiments, the experimental verification in step S4 specifically includes: measuring the stress-strain response of the cornea under a preset parameter grid through an equivalent axial tensile test to verify the model's simulation accuracy for isotropic mechanical behavior; applying an asymmetric load through an unequal axial tensile test to verify the model's ability to characterize anisotropic mechanical behavior; and optimizing surgical parameters and calibrating the model based on a comparative analysis of experimental data and simulation results. The experimental data can be divided into a calibration group and a verification group, used for parameter fine-tuning and model accuracy evaluation respectively, to ensure verification independence.

[0087] In some embodiments, step S4 further comprises: fusing the CorvisST measured data and the animal experiment biaxial tensile data to construct a multi-source data collaborative closed-loop mechanism; iteratively optimizing the simulation model parameters through experimental data feedback to form a data-driven model calibration process; and outputting individualized surgical parameter combinations based on the verified model to realize precise prediction of crosslinking efficacy.

[0088] The specific embodiments of the present application, algorithm examples and experimental verification are further described below.

[0089] A corneal crosslinking surgery simulation optimization method, comprising: integrating the influence of crosslinking surgery parameters on photochemical reaction and the relationship between crosslinking density and mechanical properties to build a multi-physical field coupled corneal constitutive theory model; combining the corneal lenticule geometric model with the multi-physical field coupled corneal constitutive theory model to build a numerical simulation model, realizing parameter transmission and coupled calculation between multi-physical fields of rare substance transmission, light field distribution, photochemical reaction and mechanical response; using full corneal crosslinking simulation to realize quantitative analysis and dynamic simulation of the biomechanical properties of the keratoconus lesion area during the crosslinking process, and optimizing the key parameters of the model; and fusing the CorvisST measured data and the animal experiment data to systematically obtain the variation trend and magnitude characteristics of the corneal biomechanical parameters under different surgical parameter combinations.

[0090] The method can accurately simulate the corneal crosslinking process, provide a scientific basis for individualized optimization of surgical parameters and efficacy prediction, effectively solve the technical problems of poor efficacy and lack of individualized adaptation of traditional surgical schemes, and promote the precision treatment of keratoconus and other diseases.

[0091] As shown in Figure 3 A corneal crosslinking surgery simulation optimization method, comprising the following steps:

[0092] S1, building a multi-physical field coupled corneal constitutive theory model: systematically analyzing the influence mechanism of crosslinking surgery parameters on the covalent bond generation rate in photochemical reaction, combining the positive correlation between crosslinking density and corneal mechanical properties, and establishing a multi-physical field coupled corneal constitutive theory model;

[0093] S2, building a corneal crosslinking numerical simulation model: based on the theoretical model constructed in step S1, fusing the clinical measured data, and integrating the three-dimensional geometric model of the corneal lenticule. Grid division and boundary conditions are implemented on the model, and parameter transmission and nonlinear coupling calculation between multi-physical fields such as rare substance transmission, light field distribution, photochemical reaction and mechanical response are realized to establish a numerical simulation model that can accurately reflect the dynamic evolution of corneal mechanical properties during the crosslinking surgery process;

[0094] S3, full cornea simulation analysis: the cross-linking mechanism simulation model integrated in steps S1 and S2 is applied to full cornea cross-linking simulation, and the quantitative analysis and dynamic simulation of the biomechanical properties of the lesion area are realized through simulation. In the simulation process, the key parameters of the model are optimized and adjusted to improve the accuracy and practicality of the model, so that it is more suitable for clinical actual needs;

[0095] S4, experimental verification: based on the full cornea cross-linking mechanism model established in step S3, the Corvis ST measured data and animal experiment data are fused, and the change trend and magnitude characteristics of the corneal biomechanical parameters are systematically obtained for different cross-linking operation parameter combinations. Through comparative analysis of experimental data and simulation results, the reliability and effectiveness of the model are verified.

[0096] Further, step S1 specifically includes the following sub-steps:

[0097] S11: Establishing a photochemical reaction kinetics model: based on the optical properties of the cornea, a model of the propagation path and energy distribution of ultraviolet (UV) in the cornea is constructed, and key influencing factors such as riboflavin concentration and oxygen content are considered to quantify the influence of operation parameters on light energy absorption depth and density, and then a spatial distribution model of light energy absorption is established;

[0098] S12: Constructing a cross-linking density and mechanical property coupling constitutive model: based on the output of the photochemical reaction model, define the spatial distribution function of the cross-linking density in the corneal tissue, consider the time dependence of the cross-linking reaction, and dynamically calculate the cross-linking density in different regions; based on the theory of biomechanics and experimental data, the cross-linking density is taken as a material parameter adjustment factor and is integrated into the Holzapfel Gasser Ogden hyperelastic constitutive model;

[0099] S13: Setting up multi-physics coupling interface and boundary conditions: defining the coupling equation of photochemical reaction and mechanical response; combining the physiological boundary conditions of the cornea, establishing a bidirectional coupling mechanism of photochemical reaction and mechanical response, and setting up boundary conditions that meet the physiological environment.

[0100] Further, step S2 specifically includes the following sub-steps:

[0101] S21, parameterized three-dimensional cornea model construction: extract the geometric parameters such as corneal thickness, curvature, and microlens shape from OCT images, use image processing software for segmentation and reconstruction, combine with clinical data to construct a parameterized three-dimensional cornea model, and realize flexible adjustment of geometric characteristics;

[0102] S22, meshing and boundary condition setting: adopt a mixed mesh strategy to differentially encrypt different regions of the cornea, set the UV light field and riboflavin diffusion boundary conditions based on the parameters of the surgical equipment, and simulate the physiological load such as intraocular pressure and the corneal constraint conditions.

[0103] S23, multi-physics coupling solving and parameter analysis: coupling the diffusion equation of each surgical parameter, the propagation equation and the photochemical reaction kinetics equation; establishing the mapping relationship between the crosslinking density and the elastic modulus; using Newton iteration method to solve the multi-physics equation set, and based on parameter scanning design and response surface modeling, quantitatively analyzing the influence mechanism of surgical parameters on the biomechanical properties of cornea.

[0104] Further, in step S23, the multi-physics coupling solving and parameter analysis mainly includes the following sub-steps:

[0105] S231, equation coupling and relationship modeling: coupling the diffusion equation of riboflavin, light and oxygen and the photochemical reaction kinetics equation, constructing the covalent bond generation rate expression in the crosslinking surgery process, establishing the nonlinear mapping function between the crosslinking density and the elastic modulus, and laying the mathematical model foundation for multi-physics coupling;

[0106] S232, numerical solution of equation set: using Newton iteration method to numerically solve the coupled multi-physics nonlinear equation set, and obtaining the mechanical property parameters of cornea in different regions and at different times;

[0107] S233, analysis of influence of surgical parameters: through parameter scanning design of multiple groups of surgical parameter combinations, combining with the response surface modeling method, systematically quantitatively analyzing the influence law and mechanism of each parameter on the biomechanical properties of cornea.

[0108] Further, step S3 specifically includes the following sub-steps:

[0109] S31, multi-module integration and full cornea modeling: integrating the crosslinking mechanism model of S1 and S2, and constructing a three-dimensional simulation model covering the full cornea;

[0110] S32, quantitative analysis and dynamic simulation of biomechanical properties: simulating the keratoconus lesion area by additionally applying intraocular pressure in part of the cornea, and using simulation to quantitatively analyze the optimal surgical parameters for different degrees of lesions;

[0111] S33, model parameter optimization and clinical fitness: based on clinical data, calibrating key parameters such as photochemical reaction rate constant and elastic modulus mapping function coefficient in the model. The initial value of the parameter can be obtained by fitting in vitro experiment and mechanical stretching experiment.

[0112] Further, in step S4, by equal biaxial and unequal biaxial stretching experiments, the stress-strain response of the cornea is measured under the preset parameter grid, and the simulation data are compared to verify the simulation accuracy of the model on isotropic and anisotropic mechanical behavior and optimize the operation parameters; with the help of experimental and simulation closed-loop and the fusion of Corvis ST measured data and animal experiment data, a data-driven model iteration mechanism is formed to provide experimental and model support for the precision and individualization of corneal cross-linking surgery.

[0113] The specific algorithm implementation of each step is further described in detail below.

[0114] 1. Establish a multi-physical field coupled corneal constitutive theory model

[0115] The multi-physical field coupling effect in the process of corneal collagen cross-linking treatment can be systematically described by establishing a comprehensive theoretical model. This model integrates four key physical processes of rare substance diffusion, light field transmission, photochemical reaction and mechanical property evolution, and builds a complete theoretical framework. The core of this framework is: first, to clarify the interaction relationship between riboflavin diffusion dynamics, oxygen transmission mechanism and ultraviolet absorption characteristics from the microscale; second, to reveal the influence law of these physical processes on the covalent bond generation rate and distribution in photochemical reaction; finally, to establish the quantitative relationship between the cross-linking density and the macroscopic mechanical properties, so as to accurately predict the stiffness enhancement effect of the cornea after cross-linking treatment. This multi-scale modeling method not only can deeply analyze the physical and chemical nature of corneal cross-linking, but also can provide a theoretical basis for the optimization of clinical treatment parameters.

[0116] In the modeling of chemical diffusion process, Fick's second law is used to describe the non-steady-state diffusion behavior of riboflavin and oxygen in the cornea tissue. The diffusion equation of this law is shown in the following formula (1):

[0117] c is the concentration of the substance, t is the time, is the vector gradient operator, is the diffusion coefficient, is the source term, this equation not only describes the diffusion process of the substance under the driving of the concentration gradient, but also quantitatively characterizes the riboflavin photodegradation effect induced by ultraviolet irradiation and the consumption of riboflavin in photochemical reaction through the source term S. At the same time, the transmission of oxygen also follows Fick's second diffusion law, but its kinetic behavior is also affected by the consumption in photochemical reaction, and its source term includes the consumption of oxidation reaction and the supply of anterior chamber oxygen. The spatiotemporal concentration distribution of these two key chemical components determines the kinetic characteristics and final effect of the photo-crosslinking reaction.

[0118] In the modeling of the light field transport part, the modified Beer-Lambert law is adopted to describe the propagation and attenuation characteristics of ultraviolet light in the corneal tissue containing riboflavin. The differential form of the law can be expressed as formula (2):

[0119] The analytical expression (3) can be obtained by integral operation:

[0120] where I(z) represents the local light intensity at the corneal depth z, is the initial light intensity at the incident surface (z=0), is the molar absorption coefficient of riboflavin at a specific wavelength, and C(z) represents the riboflavin concentration distribution at the corneal depth z. This part of the model systematically characterizes the attenuation law of ultraviolet light in the corneal tissue, revealing the influence of the initial incident light intensity, riboflavin concentration gradient, and tissue penetration depth on the light intensity. The light field transport model part not only characterizes the spatial selectivity of photochemical reactions, making the crosslinking degree at different corneal depths present a gradient change, but also through the dynamic coupling of light field characteristics and chemical components (riboflavin and oxygen), ultimately regulates the crosslinking density of collagen fiber network in the corneal stroma, significantly affecting the law of macroscopic mechanical properties of the tissue evolving over time.

[0121] In the corneal crosslinking treatment, the generation of covalent bonds is a typical photochemical kinetic process, and its generation efficiency presents a nonlinear coupling relationship with ultraviolet light intensity, riboflavin concentration, and oxygen partial pressure. Specifically, the ultraviolet light intensity I(z) forms a gradient distribution at the corneal depth z through the Beer-Lambert law, directly determining the generation rate of the excited state of riboflavin molecules , while the excited state riboflavin reacts with ground state oxygen molecules to generate highly active singlet oxygen through energy transfer. This active oxygen species then attacks the amino side chain on the collagen fiber, promoting the formation of stable carbon-nitrogen covalent crosslinking bonds between adjacent collagen molecules. Among them, the light intensity gradient regulates the reactive region through spatial selectivity, the riboflavin concentration distribution simultaneously affects the light absorption efficiency and reactant supply, while the oxygen diffusion becomes a limiting factor for deep crosslinking is the oxygen diffusion coefficient, is the oxygen concentration), which are dynamically coupled through the photochemical reaction kinetic equation, ultimately forming a crosslinking density distribution with depth-dependent characteristics in the corneal stroma. t , the corneal shear modulus z at time The constitutive relation of the cornea (Gij) G0is the initial shear modulus of the cornea, G0is the initial shear modulus of the cornea,

[0122] The mechanical property evolution is the core output of the model. By establishing the function of the shear modulus and other mechanical parameters changing with time and space, the model can quantitatively describe the enhancement effect of photo-crosslinking reaction on the stiffness of the cornea. This function couples the three key parameters of riboflavin concentration, oxygen concentration, and light intensity through the integral form, accurately reflecting the dependence of the crosslinking degree on each physical quantity. Based on this, the modified Holzapfel-Gasser-Ogden hyperelastic constitutive model is used to characterize the anisotropic mechanical behavior of the cornea after crosslinking.

[0123] 2. Numerical simulation of corneal crosslinking based on multi-physical field coupling

[0124] To accurately simulate the corneal crosslinking surgery process, a numerical simulation model needs to be built based on the theoretical model. The boundary conditions and initial conditions of the model need to be fully considered in the actual treatment scenario. The initial state corresponds to the characteristics of the cornea without medication, while the boundary conditions need to reasonably describe the riboflavin concentration distribution on the surface of the cornea after medication, the light conditions, and the oxygen exchange process with the anterior chamber.

[0125] The finite element method is used to discretely solve the multi-physical field model. The corneal geometric structure is meshed, and the grid density is adjusted according to the characteristics of each physical field. In the solving process, the sequential coupling strategy is adopted, and the specific parameter transfer order is as follows:

[0126] (1) Chemical diffusion field is solved first: based on the set boundary conditions, the concentration distribution of riboflavin and oxygen in the cornea changes with time and space. This step provides key input parameters for the subsequent light field and mechanical field, such as the riboflavin concentration directly affecting the light absorption efficiency, and the oxygen concentration determining the amount of reactive oxygen species generated.

[0127] (2) Light field distribution calculation: the beam envelope electromagnetic wave field is used to describe the light field, and the riboflavin concentration distribution obtained from the chemical diffusion field is used as the input of the light absorption coefficient. The radiation transfer equation is solved to obtain the light intensity distribution inside the cornea. The light intensity distribution further affects the photochemical reaction rate in the chemical field, forming a two-way coupling relationship.

[0128] (3)Mechanical parameter updating and mechanical response solving: According to the active oxygen species concentration calculated by the chemical field and the light field distribution, the amount of covalent bond generated between collagen fibers is calculated through the preset cross-linking reaction kinetics model. The number of covalent bonds is associated with the mechanical parameters, and the mechanical parameters in the corneal constitutive model are updated to solve the mechanical response field and obtain the stress and strain distribution of the cornea.

[0129] According to the above sequence, the coupled solving and related calculation of chemical diffusion field, light field and mechanical field are realized.

[0130] 3. Data-driven model parameter optimization

[0131] To accurately verify the multi-physical field coupled corneal cross-linking constitutive model, a two-way driven research system of "simulation optimization-experiment verification" is constructed to ensure the accurate description of the model to the corneal cross-linking process from the dimensions of mechanical response simulation and actual measurement verification. The specific experimental methods are as follows:

[0132] (1) Simulation optimization

[0133] Based on the multi-physical field coupled corneal constitutive model, the corneal geometric model is first constructed and embedded with multiple physical field characteristics such as chemical diffusion, light transmission, photochemical reaction and mechanical response. According to the pathological characteristics of keratoconus, the "15mmHg intraocular pressure applied in the keratoconus lesion area" is used to simulate the pathological state of reduced regional stiffness of keratoconus. Then, the "ultraviolet intensity and irradiation time" are used as the core adjustment parameters to drive the model operation. On the one hand, the correlation between "local stiffness increment and corneal protrusion improvement" is quantitatively analyzed to optimize the key model parameters such as cross-linking reaction rate constant (determining the covalent bond generation rate) and cross-linking efficiency coefficient (affecting the change of corneal mechanical properties), and to clarify the role of cross-linking strengthening in the repair of corneal morphology. On the other hand, parameter sensitivity analysis is carried out to identify the influence weight of ultraviolet intensity and irradiation time on the cross-linking effect. At the same time, the quantitative relationship between "local lesion improvement and irradiation time" is established to provide a theoretical basis for parameter optimization.

[0134] (2) Experimental verification

[0135] Firstly, the equibiaxial tension experiment is carried out. The equibiaxial tension device is used to apply symmetric mechanical load to the corneal samples before and after cross-linking. The parameter grid of "light intensity and irradiation time" is set in advance. By measuring the stress-strain response of the corneal samples under different parameters, the change rule of the mechanical parameters such as elastic modulus and stiffness of the cornea after cross-linking is obtained. The experimental data are compared with the mechanical response output by the simulation model to verify the simulation accuracy of the model for the cross-linking effect of the isotropic region of the cornea. At the same time, based on the test results of the parameter grid, the important surgical parameters such as light intensity and irradiation time are optimized in reverse.

[0136] At the same time, unequal biaxial stretching experiments are carried out, and the anisotropy of the whole cornea is designed for unequal biaxial stretching experiments: the asymmetric load is applied to the cornea sample to simulate the complex mechanical environment of the cornea in the physiological or pathological state. By observing the deformation mode and stress distribution difference of the corneal microlens region, the ability of the model to describe the anisotropic mechanical behavior of the cornea is verified. The mechanical response prediction value of the corneal microlens region in the simulation is compared with the experimental measured data, the assumption of the anisotropic constitutive relation in the model is corrected, and the applicability of the model to the complex mechanical environment of the cornea is ensured.

[0137] (3) Multi-source data fusion

[0138] Firstly, the collaborative closed loop of experiment and simulation is realized, and through the combination of equal biaxial and unequal biaxial stretching experiments, on the one hand, the simulation accuracy of the multi-physical field coupling model to the mechanical response of the cornea is verified, the model parameters are corrected, and the personalized optimal operation parameter combination is found; on the other hand, based on the correlation between the light parameters and the mechanical properties obtained by the experiment, the system parameters such as light intensity in the simulation link are optimized in reverse, forming a collaborative closed loop of “simulation guiding experiment design and experiment feeding back model optimization”, and finally providing reliable experimental support and model basis for the parameter precise regulation of corneal crosslinking operation and pathological repair effect prediction, and promoting the development of corneal crosslinking technology from experience to precision and individualization.

[0139] Secondly, the Corvis ST measured data and the biaxial stretching experimental data of animal experiments are fused. On the one hand, the addition of the Corvis ST measured data makes the model better fit the real human cornea; on the other hand, the biaxial stretching experimental data of animal experiments provides mechanical parameters under precise control, which complement each other.

[0140] By fusing these multi-source data, the biomechanical property changes of the cornea during the crosslinking operation can be more comprehensively and accurately reflected, providing rich and reliable data basis for the iterative optimization of model parameters, and realizing effective experimental verification of the anisotropy of the cornea, thereby improving the mapping accuracy of the corneal constitutive model to the real physiological environment, and building a solid data support for the personalized scheme design of the crosslinking operation.

[0141] Experimental results

[0142] Figure 1 The personalized operation parameter driven corneal crosslinking effect visualization schematic diagram of the embodiment of the application is shown in FIG. 6. Figure 1It can be seen that the "time iteration number" can correspond to the time course of corneal crosslinking, the z-axis represents the depth of the corneal stroma, and the data in the right color column reflect the size of the Young's modulus. Therefore, each raw data point in the figure can present the change of the biomechanical properties of the cornea at different depths as the crosslinking time advances, that is, the performance of the crosslinking effect at different times and depths, and thus can provide a basis for selecting a suitable personalized surgical plan for the patient. Figure 2 The present application is a simulation diagram of the corneal crosslinking effect of the personalized pathological region of keratoconus. Figure 2 It can be seen that, on the constructed corneal lenticule geometric model, the pressure in the x-axis direction simulating the gas pulse is applied to the middle region of the lenticule. By obtaining the stress and strain information of the keratoconus region at different crosslinking degrees, it can be known from the displacement in the x-axis direction that the greater the change in corneal hardness, the smaller the displacement, and the more significant the crosslinking effect. Based on the simulation data obtained, the real parameter data obtained by Corvis ST can be compared, the personalized crosslinking parameters can be associated with the measured values of the crosslinking effect, and the reliability of the present application can be verified to provide a reliable basis for setting personalized surgical parameters.

[0143] The present application breaks through the limitation of traditional single physical field modeling by constructing a multi-physical field coupled corneal constitutive model integrating ultraviolet light field transmission, riboflavin penetration kinetics, oxygen consumption transmission and biomechanical response, realizes cross-scale simulation from molecular crosslinking mechanism to macroscopic mechanical properties, innovatively establishes a time-space dynamic evolution constitutive relationship, accurately quantifies the influence of surgical parameters on the spatial distribution of crosslinking degree and biomechanical properties, provides technical support for individualized scheme, develops a multi-field coupled numerical simulation platform based on partial differential equations, realizes dynamic monitoring of riboflavin concentration, oxygen content, light intensity and mechanical properties through layered probe detection, fills the gap of dynamic tracking of surgical parameters, integrates Corvis ST clinical data and animal experiment biaxial tensile data, constructs a simulation-experiment closed-loop optimization mechanism, significantly improves the mapping accuracy of the model to the real physiological environment, systematically solves the core technical bottlenecks of lack of basis for parameter setting, inaccurate treatment effect prediction and insufficient individual adaptation in traditional surgery, and promotes the leap of corneal crosslinking from empirical treatment to precision medicine.

[0144] The important innovations and significant advantages of the present application are:

[0145] 1) Construction of a multi-physical field coupled corneal constitutive model

[0146] The innovative integration of ultraviolet light field transmission law, riboflavin transcorneal penetration kinetics, oxygen consumption delivery process, corneal mechanical reconstruction effect and other processes constructs a multi-physical process coupling system covering the processes of rare substance delivery, light field distribution, photochemical reaction and mechanical response; the traditional single physical field modeling limitation is broken through, the constitutive relation is set as a binary function of time and depth, the dynamic evolution process of the mechanical properties of the cornea in the crosslinking operation is accurately described, and the influence mechanism of the operation parameters such as ultraviolet dose and photosensitizer concentration on the spatial distribution of crosslinking degree and the biomechanical properties of the cornea is quantitatively revealed, thereby providing a theoretical basis for operation parameter optimization and postoperative effect evaluation.

[0147] 2) Numerical simulation of multi-physical field coupled corneal crosslinking:

[0148] The partial differential mathematics field is used to fit special reaction kinetics, including the illumination field affected by the local riboflavin concentration and the photochemical reaction field affected by the riboflavin concentration, illumination intensity and oxygen concentration; the coupling relationship between the physical fields is self-defined, the multi-physical field parameter delivery relationship is connected in series, and a runnable numerical simulation model is built; the geometric model is processed in layers and probes are set, the mechanical properties of the cornea at multiple time nodes are detected, and the change trends of the riboflavin concentration, oxygen content, illumination intensity and mechanical performance index in each depth space are comprehensively detected, thereby filling the blank of crosslinking operation parameter change history and detection index setting.

[0149] 3) Data-driven model optimization:

[0150] A model parameter calibration algorithm based on simulation and experimental data fusion is proposed; by integrating the corneal geometric model and the multi-physical field coupling model, a high-precision three-dimensional simulation model is built, the quantitative analysis and dynamic simulation of the biomechanical properties of the lesion area are realized, the Corvis ST measured data and the biaxial tensile test data of animal experiments are fused, the change trend and magnitude characteristics of the corneal biomechanical parameters are systematically obtained for different crosslinking operation parameter combinations, the model parameter iterative optimization and experimental verification of the anisotropic properties of the cornea are realized, the traditional single data calibration limitation is broken through, the mapping precision of the corneal constitutive model to the real physiological environment is improved through multi-source data collaborative fusion, and data support is provided for the individualized scheme design of the crosslinking operation.

[0151] The embodiment of the present application also provides a storage medium for storing a computer program, which is executed to perform at least the method described above.

[0152] The embodiment of the present application also provides a control device comprising a processor and a storage medium for storing a computer program; wherein the processor is used to execute the computer program to perform at least the method described above.

[0153] The embodiment of the present application also provides a processor which executes a computer program to perform at least the method described above.

[0154] The storage medium can be implemented by any type of nonvolatile storage device, or a combination thereof. The nonvolatile memory can be a Read Only Memory (ROM), a Programmable Read-Only Memory (PROM), an Erasable Programmable Read-Only Memory (EPROM), an Electrically Erasable Programmable Read-Only Memory (EEPROM), a Ferromagnetic Random Access Memory (FRAM), a Flash Memory, a magnetic surface storage, an optical disc or a Compact Disc Read-Only Memory (CD-ROM). The magnetic surface storage can be a magnetic disc memory or a magnetic tape memory. The storage medium described in the embodiments of the present application is intended to include, but is not limited to, these and any other suitable type of memory.

[0155] In several embodiments provided by the present application, it should be understood that the disclosed system and method can be implemented in other manners. The described device embodiments are merely schematic, and the division of the units is merely a logical function division. For example, a plurality of units or components can be combined or integrated into another system, or some features can be ignored or not executed. In addition, the displayed or discussed coupling between the components can be indirect coupling or direct coupling through some interface, electrically, mechanically or other forms.

[0156] The units described as separated components can or can not be physically separated, and the components displayed as units can or can not be physical units, i.e., can be located in one place or distributed on a plurality of network units; some or all of the units can be selected according to actual needs to achieve the purposes of the embodiments of the present application.

[0157] In addition, each functional unit in the embodiments of the present application can be integrated in one processing unit, or each unit can be a separate physical unit, or two or more units can be integrated in one unit; the integrated unit can be implemented in the form of hardware, or in the form of hardware plus software function unit.

[0158] Those skilled in the art can understand that all or part of the steps of the above-mentioned method embodiments can be completed by program instruction related hardware, and the foregoing program can be stored in a computer readable storage medium, and the program performs the steps of the above-mentioned method embodiments when executed; and the foregoing storage medium includes a mobile storage device, a read-only memory (ROM), a random access memory (RAM), a magnetic disc or an optical disc and various storage medium capable of storing program codes.

[0159] Alternatively, the integrated unit of the present application can be stored in a computer readable storage medium if it is realized in the form of a software function module and sold or used as an independent product. Based on such understanding, the technical solutions of the embodiments of the present application can be embodied in the form of a software product, and the computer software product is stored in a storage medium, includes several instructions to make a computer device (which can be a personal computer, a server, or a network device, etc.) execute all or part of the methods described in the embodiments of the present application. The foregoing storage medium includes a mobile storage device, a ROM, a RAM, a magnetic disc or an optical disc and various storage medium capable of storing program codes.

[0160] The methods disclosed in the several method embodiments of the present application can be combined arbitrarily without conflict to obtain new method embodiments.

[0161] The features disclosed in the several product embodiments of the present application can be combined arbitrarily without conflict to obtain new product embodiments.

[0162] The features disclosed in the several method or device embodiments of the present application can be combined arbitrarily without conflict to obtain new method or device embodiments.

[0163] The above is a further detailed description of the present application in combination with specific preferred embodiments, and the specific implementation of the present application cannot be limited to these descriptions. For those skilled in the art, without departing from the concept of the present application, a number of equivalent substitutions or obvious modifications can be made, and the performance or use is the same, which should be regarded as belonging to the protection scope of the present application.

Claims

1. A cross-linking surgical simulation optimization method based on a multi-physics field coupled corneal constitutive model, characterized in that, Includes the following steps: S1. Constructing a Multi-Physics-Coupled Corneal Constitutive Theory Model: Integrating the influence mechanism of cross-linking surgical parameters on the covalent bond formation rate of photochemical reactions, establishing a positive correlation between cross-linking density and corneal mechanical properties, and forming a multi-physics-coupled theoretical framework covering rare substance transport, light field distribution, photochemical reactions, and mechanical responses; specifically including: establishing a photochemical reaction kinetic model: constructing an ultraviolet propagation path and energy distribution model based on corneal optical properties, quantifying the influence of riboflavin concentration and oxygen content on the depth of light energy absorption; based on the unsteady diffusion equation of matter, introducing photodegradation and reaction consumption terms in riboflavin diffusion, and introducing oxidation reaction consumption and anterior chamber supply terms in oxygen diffusion, generating a spatial distribution model of light energy absorption; constructing a cross-linking density-mechanical property coupled constitutive model: defining the spatiotemporal distribution function of cross-linking density based on the output of photochemical reactions, and incorporating cross-linking density as a material parameter adjustment factor into the hyperelastic constitutive model; setting a multi-physics coupling interface: defining a bidirectional coupling equation between photochemical reactions and mechanical responses, and establishing a multi-field synergistic mechanism in conjunction with physiological boundary conditions; S2. Establish a numerical simulation model for corneal crosslinking: Based on the theoretical model, combined with clinical measured data and a three-dimensional geometric model of the cornea, through mesh generation and boundary condition setting, the parameter transfer and nonlinear coupling calculation of rare substance transfer, light field distribution, photochemical reaction and mechanical response are realized, and a numerical simulation model of the dynamic evolution of corneal mechanical properties is generated. S3. Full corneal simulation analysis and parameter optimization: Apply the numerical simulation model to perform dynamic simulation of full corneal cross-linking, quantitatively analyze the biomechanical properties of the lesion area, and optimize the key parameters of the model based on the simulation results; S4. Experimental Verification and Model Iteration: By integrating measured data from corneal biomechanical measurement equipment with animal experimental data, the system verifies the changing trends of corneal biomechanical parameters for different combinations of surgical parameters. The surgical parameters are optimized and the model is calibrated through comparison of experiments and simulations.

2. The cross-linking surgical simulation optimization method based on a multi-physics field coupled corneal constitutive model as described in claim 1, characterized in that, The construction of the photochemical reaction kinetic model in step S1 specifically includes: A model for the attenuation of ultraviolet light in the cornea is constructed based on the modified Beer-Lambert law. By describing the attenuation of light intensity with depth, the model dynamically couples the riboflavin concentration gradient, light intensity, and oxygen diffusion behavior. By incorporating the nonlinear coupling relationship between ultraviolet intensity, riboflavin concentration and oxygen partial pressure into the covalent bond formation process through photochemical reaction kinetic equations, the depth-dependent characteristics of covalent bond formation are established, and a spatiotemporal distribution function of crosslinking density as a function of time and depth is generated. Using the crosslinking density distribution as input, a hyperelastic constitutive model is used to establish the relationship between mechanical parameters and crosslinking density, thus characterizing the time-varying evolution of corneal mechanical properties.

3. The cross-linking surgical simulation optimization method based on a multi-physics field coupled corneal constitutive model as described in any one of claims 1 to 2, characterized in that, Step S2 specifically includes: Parametric 3D corneal modeling: Extracting corneal geometric parameters from OCT images to construct an adjustable 3D corneal model; Mesh generation and boundary condition setting: A differentiated meshing strategy was adopted, and the ultraviolet light field, riboflavin diffusion boundary and physiological load conditions were set based on the surgical equipment parameters; Multiphysics coupling solution: Couple the surgical parameter diffusion equation with the photochemical reaction kinetic equation, establish the nonlinear mapping relationship between crosslinking density and elastic modulus, solve the multiphysics equation set by iterative method, and quantify the influence mechanism of surgical parameters through parameter scanning and response surface modeling.

4. The cross-linking surgical simulation optimization method based on a multi-physics field coupled corneal constitutive model as described in claim 3, characterized in that, The multiphysics coupling solution specifically includes: Equation coupling and relation modeling: Couple the riboflavin diffusion equation, light transport equation, oxygen consumption equation and photochemical reaction kinetic equation to construct the covalent bond formation rate expression and the crosslink density-elastic modulus mapping function; Numerical solution of the equations: The Newton-Raphson iteration method is used to solve the nonlinear equations of the multiphysics field in a time-space discretization manner, and the mechanical performance parameters of different regions and time nodes are output. The solution process reflects the stepwise influence of the diffusion field, light field and chemical reaction field on the mechanical parameters. Surgical parameter influence analysis: Through scanning design and response surface modeling with multiple parameter combinations, the system quantifies the effect of each parameter on corneal biomechanical properties, focusing on the gradient influence of light intensity distribution and material diffusion characteristics on cross-linking effect.

5. The cross-linking surgical simulation optimization method based on a multi-physics field coupled corneal constitutive model as described in any one of claims 1 to 2, characterized in that, In step S2, the numerical simulation adopts a sequential coupling strategy: Solve the diffusion equations for riboflavin and oxygen, where riboflavin diffusion takes into account photo-induced degradation and reaction consumption, and oxygen diffusion needs to take into account reaction consumption and anterior chamber supply, outputting the spatiotemporal distribution of riboflavin and oxygen concentrations. Using the riboflavin concentration distribution as input, the light field transmission equation is solved by describing the law of light intensity decay with depth to obtain the light intensity distribution inside the cornea. This light intensity distribution has a reaction effect on the reaction rate in the material diffusion process. Based on the light intensity distribution and reactive oxygen concentration, the mechanical parameters are updated through the mapping relationship between crosslinking density and mechanical parameters, and the mechanical response field is solved to obtain the stress-strain distribution.

6. The cross-linking surgical simulation optimization method based on a multi-physics field coupled corneal constitutive model as described in any one of claims 1 to 2, characterized in that, Step S3 specifically includes: Multi-module integration and full corneal modeling: Integrating theoretical models and numerical simulation models to construct a three-dimensional dynamic simulation model covering the entire cornea; Quantitative analysis of lesion areas: Pathological-grade intraocular pressure is applied to specific areas of the cornea to simulate the lesion state, and the repair effect of different surgical parameters on the lesion area is quantified through simulation. Model parameter calibration: Optimize key parameters such as photochemical reaction rate constant and elastic modulus mapping coefficient based on clinical data.

7. The cross-linking surgical simulation optimization method based on a multi-physics field coupled corneal constitutive model as described in any one of claims 1 to 2, characterized in that, Step S4 The experimental verification specifically includes: The stress-strain response of the cornea under a pre-defined parameter grid was measured by equivalent axial tensile test to verify the model's accuracy in simulating isotropic mechanical behavior. The model's ability to characterize anisotropic mechanical behavior was verified by applying an asymmetric load through unequal shaft tension experiments. Based on the comparative analysis of experimental data and simulation results, surgical parameters were optimized and the model was calibrated.

8. The cross-linking surgical simulation optimization method based on a multi-physics field coupled corneal constitutive model as described in claim 7, characterized in that, Step S4 also includes: By integrating CorvisST measured data with biaxial stretching data from animal experiments, a multi-source data collaborative closed-loop mechanism is constructed. The simulation model parameters are iteratively optimized by feedback from experimental data, forming a data-driven model calibration process; Based on the validated model, personalized surgical parameter combinations are output to achieve accurate prediction of cross-linking efficacy.

9. A computer program product, comprising a computer program, characterized in that, When the computer program is executed by the processor, it implements the cross-linking surgery simulation optimization method based on the multi-physics field coupled corneal constitutive model as described in any one of claims 1 to 8.

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