A personalized corneal cross-linking system and a method for processing corneal intermediate results

Abstract

The present invention claims a personalized corneal cross-linking system and a method for processing corneal intermediate results. The corneal cross-linking system includes a corneal information acquisition module and a personalized solution generation module; the corneal information acquisition module is used to acquire and process the patient's preoperative information and obtain the biomechanical constitutive parameter α of the cornea before CXL surgery; the personalized solution generation module is used to automatically convert the CXL parameters according to the target corneal biomechanical constitutive parameter α after CXL surgery and the preoperative α. In summary, the above technical scheme has the following beneficial effects: the corneal information acquisition module in the scheme can acquire the patient's preoperative corneal information and obtain the corneal biomechanical constitutive parameter α, and the target corneal biomechanical constitutive parameter α of the patient is converted into a CXL parameter through the personalized solution generation module, thereby providing the CXL surgery with intermediate parameters suitable for the patient, and the CXL parameters include a combination of different irradiances and different total energies during ultraviolet irradiation.

Description

Technical Field

[0001] The present invention relates to the technical field of corneal cross-linking, and more particularly to a personalized corneal cross-linking system and a method for processing corneal intermediate results thereof. Background Art

[0002] Keratoconus (KC) is the most common ectatic corneal disease, with a prevalence of about 1 / 2000, and is one of the most common reasons for corneal transplantation. The common clinical manifestations of KC are highly irregular myopic astigmatism and varying degrees of visual impairment, which seriously affect the patient's vision and quality of life. Existing studies have shown that in some areas of the KC stroma, there are phenomena such as reduced collagen fiber cross-linking, disordered fiber arrangement, and degradation of the extracellular matrix, which weakens the local mechanical properties. Under the action of intraocular pressure, the cornea gradually bulges outward, resulting in local thinning and steepening, which is an important cause of the deterioration of KC. The occurrence and development of KC is closely related to changes in the biomechanical properties of the cornea.

[0003] Corneal cross-linking (CXL) is a procedure that uses ultraviolet light (ultraviolet A, UVA) to induce new covalent bonds between amino groups / groups within and between collagen fibers in the corneal stroma, thereby improving the biomechanical properties of the cornea, slowing down or even preventing the progression of KC at a pathological level, and effectively reducing the proportion of KC patients requiring corneal transplantation. It is currently the most popular treatment for KC.

[0004] Due to the large difference between the improvement of corneal biomechanical properties and the physiological state, a series of problems have arisen: the existing CXL surgery leads to an increase in the overall stiffness of the cornea, which causes the corneal compliance to decrease too much, significantly increasing the risk of glaucoma; this is similar to the principle that the overall corneal compliance decreases significantly after Boston Type 1 artificial cornea (containing a metal stent, with high material mechanical properties) transplantation, causing a significant increase in the incidence of glaucoma. Secondly, the distribution of biomechanical properties and physiological state of KC after CXL surgery are quite different. When the biomechanical properties of the cornea are excessively improved after CXL surgery, obvious stress concentration will occur at the boundary between the cross-linked and non-cross-linked areas; over time, the biomechanical properties of the boundary area will decrease, resulting in local corneal thinning or expansion, causing KC to continue to progress. It has been reported that up to 23% of KC cases relapse and worsen after CXL surgery, requiring a second surgery.

[0005] In addition, because the exact relationship between the improvement of corneal biomechanical properties and CXL parameters is unknown, most of the CXL currently performed is based on the physician's personal experience or the standard model provided by the manufacturer to select CXL parameters, and it is impossible to quantitatively predict the improvement of corneal biomechanical properties after CXL. The evaluation of the effect of CXL surgery currently mainly relies on corneal topography, medical optometry and visual acuity results for indirect evaluation, and there is a lack of technical solutions based on the pathological reduction of biomechanical properties and the quantitative improvement of personalized CXL.

[0006] For example, the patent with publication number CN110314035A discloses a corneal cross-linking device with controllable shape and depth, which provides a solution for irradiation with different wavelengths, different shapes or different orientations, solving the technical problem of the single spot shape associated with the cornea; the patent with publication number CN113240711A discloses a real-time personalized cross-linking system, which provides a solution for adjusting the ultraviolet irradiation position in real time, so as to irradiate the pre-specified real position of the cornea, and obtains results that are far better than the method for characterizing corneal collagen cross-linking. None of the above-disclosed inventions have achieved the possibility of providing personalized selection of CXL parameters based on the purpose of quantitatively improving the biomechanical properties of the cornea.

[0007] Therefore, how to achieve personalized selection of CXL parameters to achieve quantitative improvement of corneal biomechanical properties is the technical problem to be solved by this application. Summary of the invention

[0008] According to one aspect of the present invention, a personalized corneal cross-linking system is provided. The system utilizes a scheme that can measure corneal biomechanical properties in vivo, and an originally discovered CXL parameter, namely, a mathematical relationship between UVA irradiance and total energy and the extent of improvement in corneal biomechanical properties, to design a personalized CXL system to achieve quantitative improvement in corneal biomechanical properties.

[0009] In order to achieve the above purpose, the following technical solutions are provided:

[0010] A personalized corneal cross-linking system includes a corneal information acquisition module and a personalized scheme generation module; the corneal information acquisition module is used to obtain and process the patient's preoperative information and obtain the corneal biomechanical constitutive parameter α; the personalized scheme generation module is used to automatically convert the corneal biomechanical constitutive parameter α to obtain CXL parameters.

[0011] According to a second aspect of the present invention, a personalized corneal intermediate result processing method is provided, which includes the following process:

[0012] St10, control the corneal information acquisition module to collect the patient's corneal morphological data and dynamic eyeball deformation parameters.

[0013] St20. The lesion area is selected based on the maximum curvature, the thinnest point and the thickness of the posterior surface. The center of the triangle formed by the three points is used as the center point of the subsequent CXL spot.

[0014] St30, controlling the corneal information acquisition module to construct a personalized whole eyeball geometric model.

[0015] St40, based on the personalized whole eyeball geometric model, finite element analysis combined with dynamic mesh technology simulated the measurement process of Corvis ST, and the corneal biomechanical constitutive parameter α was obtained through reverse modeling and iterative calculation.

[0016] St50, based on the comparison between the corneal biomechanical constitutive parameter α and the target value of α after surgery, the patient's personalized corneal biomechanical constitutive parameter α improvement ratio is obtained.

[0017] In summary, the above technical solution has the following beneficial effects: the corneal information acquisition module in this solution can collect the patient's preoperative corneal information and calculate the in vivo corneal biomechanical constitutive parameter α, and convert the target corneal biomechanical constitutive parameter α to be achieved by the patient after CXL surgery into CXL parameters through a personalized solution, thereby providing the CXL surgery with intermediate parameters suitable for the patient, and the CXL parameters mainly include a combination of different irradiances and different total energies during ultraviolet irradiation. The personalized solution generation module provides different personalized CXL parameters for different patients, so that the improvement of corneal biomechanical properties after surgery in different patients can be quantitatively predicted, thereby solving the problem of precise treatment of KC using CXL. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 A schematic diagram of the module relationship of a personalized corneal cross-linking system;

[0019] Figure 2 A schematic diagram of a personalized full-eye first-person perspective three-dimensional image model;

[0020] Figure 3 A schematic diagram of a personalized full-eye second-view three-dimensional image model;

[0021] Figure 4 Schematic diagram of the finite element simulation Corvis ST measurement process;

[0022] Figure 5 This is a schematic diagram of the air-solid coupling model between air and cornea;

[0023] Figure 6 A schematic diagram of the process relationship of a personalized corneal cross-linking system;

[0024] Figure 7 Schematic diagram of a scaffold structure 33 of a personalized corneal cross-linking system.

[0025] Attached figure numbers: 10, corneal information acquisition module; 20, personalized plan generation module; 30, personalized light spot implementation module; 31, light emitting structure; 32, LCD device; 33, bracket structure; 331, base; 322, horizontal rod; 333, vertical rod; 34, camera. DETAILED DESCRIPTION

[0026] The present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. The same parts are represented by the same reference numerals. It should be noted that the words "front", "rear", "left", "right", "upper" and "lower" used in the following description refer to directions in the accompanying drawings, and the words "bottom surface" and "top surface", "inner" and "outer" refer to directions toward or away from the geometric center of a specific component, respectively.

[0027] like Figure 1 As shown, a personalized corneal cross-linking system includes a corneal information acquisition module 10 and a personalized solution generation module 20; the corneal information acquisition module 10 is used to acquire and process the patient's preoperative information and obtain the corneal biomechanical constitutive parameter α; the personalized solution generation module 20 is used to automatically convert the corneal biomechanical constitutive parameter α (preoperative value and postoperative target value) to obtain the CXL parameter. The corneal information acquisition module 10 in this solution can collect the patient's preoperative corneal information and calculate the in vivo corneal biomechanical constitutive parameter α, and the target corneal biomechanical constitutive parameter α to be achieved by the patient after CXL surgery is converted into a personalized CXL parameter by the personalized solution generation module 20, thereby providing the CXL surgery with an intermediate parameter suitable for the patient, and the CXL parameter mainly includes a combination of different irradiances and different total energies during ultraviolet irradiation. The personalized solution generation module 20 provides different personalized CXL parameters for different patients, so that the improvement of corneal biomechanical properties of different patients after surgery can be quantitatively predicted, thereby solving the problem of accurate treatment of KC using CXL.

[0028] like Figure 2 and Figure 3As shown, the corneal information acquisition module 10 includes an anterior segment analyzer and a corneal biomechanical analyzer. The existing commercial equipment anterior segment analyzer (Pentacam) and corneal biomechanical analyzer (Corvis ST) are used to collect patient morphological data and dynamic eye deformation parameters, and the lesion area is selected according to the three points of the maximum corneal curvature (Kmax), the thinnest point (MCT) and the highest point of the back surface. The center of the triangle formed by the three points is used as the center point of the subsequent CXL spot, and the distance between the two points is used as the radius of the subsequent CXL spot. In addition, the original corneal height data is derived from the corneal topography of the anterior segment analyzer and combined with the axial data to adjust on the basis of the standardized eyeball geometry model to construct a personalized whole eyeball geometry model.

[0029] like Figure 4 and Figure 5 As shown, Figure 4 Spring-damper boundary conditions were added to the equatorial part of the middle sclera. The initial material properties of the model were set according to the mechanical properties parameters of the human cornea and sclera obtained in vitro (α and μ data matrices). The intraocular pressure was corrected using the biomechanical data provided by CorvisST to set the pressure inside the eyeball model. The model used a 15-node triangular prism unit (C3D15H) and divided the grid into two layers. The spring-damper system (k, c) was used to set the boundary conditions of the entire eyeball. The stress-free state of the corneal model was obtained through repeated iterative calculations. On this basis, the finite element simulation was performed again to load the intraocular pressure to obtain the initial stress of the entire eyeball.

[0030] Figure 5 is the air velocity and stress distribution of the whole eyeball at a certain moment. Finite element analysis combined with dynamic mesh technology simulates the gas-solid coupling between gas and cornea during Corvis ST measurement, and accurately calculates the gas pressure on the corneal surface that changes with time and space; inverse modeling obtains the optimal spring-damper parameter combination as boundary conditions. Iterative calculations are performed on the basis of the model, and inverse modeling analysis is performed to obtain the in vivo corneal biomechanical constitutive parameters α and μ. The corneal biomechanical constitutive parameter α of the patient is compared with the postoperative α target value (the standard corneal α value of the same age group is used as the benchmark value), and the patient's personalized corneal biomechanical constitutive parameter α improvement ratio is obtained, among which the relationship between μ and CXL parameters is not so obvious.

[0031] The CXL parameters obtained by the personalized solution generation module 20 include UVA irradiance and UVA total energy.

[0032] The calculation of UVA irradiance is obtained through the following process: by comparing the corneal biomechanical constitutive parameter α of the patient with the postoperative α target value, the improvement ratio Y of the corneal biomechanical constitutive parameter α personalized for the patient is obtained;

[0033] The relationship between UVA irradiance and the target improvement Y of corneal biomechanical properties is:

[0034]

[0035] In formula (1.1), X1 is the UVA irradiance, and Y is the increase ratio of the corneal biomechanical constitutive parameter α.

[0036] The calculation of the total UVA energy is obtained through the following process: by comparing the patient's corneal biomechanical constitutive parameter α with the postoperative α target value, the improvement ratio Y of the patient's personalized corneal biomechanical constitutive parameter α is obtained;

[0037] The relationship between the total UVA energy and the target improvement Y of corneal biomechanical performance is:

[0038] Y=18.538lnX2+8.245 (1.2)

[0039] In formula (1.2), X2 is the total UVA energy, and Y is the increase ratio of the corneal biomechanical constitutive parameter α.

[0040] The personalized spot implementation module 30 is also included, and the personalized spot implementation module 30 is used to irradiate according to the CXL parameters obtained by the personalized scheme generation module 20. The personalized spot implementation module 30 is based on the location of the center of the lesion and generates a corresponding personalized cross-linking scheme, and outputs it in the form of a proposed cross-linked spot map according to the CXL parameters. The CXL parameters of the personalized cross-linking scheme include the center position of the cross-linking, UVA irradiance and total energy.

[0041] like Figure 6 As shown, the personalized light spot implementation module 30 includes a light emitting structure 31, an LCD device 32 and a bracket structure 33; the personalized solution generation module 20, the light emitting structure 31 and the LCD device 32 are all arranged on the bracket structure 33, and the light emitting structure 31 and the LCD device 32 are respectively coupled to the personalized solution generation module 20; the personalized solution generation module 20 controls the LCD device 32 to change the light spot emitted by the light emitting structure 31 according to the CXL parameters.

[0042] like Figure 7As shown, the support structure 33 includes a base 331, a horizontal rod 332 and a vertical rod 333. The two ends of the vertical rod 333 are respectively connected to the base 331 and the horizontal rod 332. The personalized solution generation module 20, the light emitting structure 31 and the LCD device 32 are all arranged on the horizontal rod 332. Specifically, the horizontal rod 332 and the vertical rod 333 are hollow rods. The two ends of the vertical rod 333 are respectively connected to the base 331 and the horizontal rod 332. The personalized solution generation module 20 can be fixed on the horizontal rod 332 for easy viewing. The front end of the horizontal rod 332 is provided with a cover body, and the light emitting structure 31 and the LCD device 32 are fixed in the cover. Further, the horizontal rod 332 can rotate around the vertical rod 333, and the hollow rod can accommodate the required circuit. The main body of the personalized solution generation module 20 is a control computer.

[0043] The light emitting structure 31 includes a light source module, a concave mirror and a light modifier arranged on a support structure 33; the light source module is arranged at the focus of the concave mirror, and the light emitted by the light source module is converted into parallel light after passing through the concave mirror, and the light modifier is used to change the line of the parallel light. Specifically, the light source module includes an ultraviolet light source and a power supply; the luminous power of the ultraviolet light source is adjustable, not more than 5W, and stably emits ultraviolet light (UVA) with a wavelength of 370nm, and the power supply is used to provide a continuously adjustable current of 0 to 5A to change the illumination intensity of the ultraviolet light. The light source module is placed at the focus of the concave mirror, and the emitted light is converted into parallel light after passing through the concave mirror. The light modifier is a light homogenizer or a focusing lens, and the parallel light can be converted into surface light through the light homogenizer, and the light radiation can be focused through the focusing lens.

[0044] The LCD device 32 includes an LCD chip and polarizers located on both sides of the LCD chip. The LCD chip can be a liquid crystal panel of a commercial projector, such as a liquid crystal screen with a model number of L3D07U-81G00. The polarizer can convert light into linear polarized light to reduce the absorption of UVA by the liquid crystal. The control computer provides an image signal according to the pseudo-crosslinking light spot diagram, selectively displays a transparent pattern on the liquid crystal screen, and allows UVA to pass through to achieve crosslinking. The control computer controls the light intensity and illumination time of the light source module to change the UVA irradiance and UVA total energy, and controls the LCD device 32 to adjust the center position and diameter of the light spot. The center position and diameter of the target light spot are determined by the pseudo-crosslinking light spot diagram obtained by the personalized solution generation module 20. The control computer can use wired and wireless data connections to obtain or store data from the server.

[0045] The personalized spot implementation module 30 also includes a camera 34 disposed on the support structure 33. The camera 34 is coupled to the personalized solution generation module 20 and is used to collect corneal images and display them on a control computer. Specifically, the camera 34 uses a camera 34 with an eye tracking function. During the operation, the corneal image is collected and displayed on the computer, so as to achieve real-time tracking of eye movements, reduce the loss of cross-linking energy, and accurately implement the personalized solution. At the same time, it is also convenient for medical staff to observe the corneal state and perform other treatments.

[0046] According to a second aspect of the present invention, a personalized corneal intermediate result processing method is provided, which includes the following process:

[0047] St10, control the corneal information acquisition module 10 to acquire the patient's corneal morphology data and dynamic eyeball deformation parameters.

[0048] St20. The lesion area is selected based on the maximum curvature, the thinnest point and the thickness of the posterior surface. The center of the triangle formed by the three points is used as the center point of the subsequent CXL spot.

[0049] St30, controlling the corneal information acquisition module 10 to construct a personalized whole eyeball geometric model.

[0050] St40, based on the personalized whole eyeball geometric model, finite element analysis combined with dynamic mesh technology simulated the measurement process of Corvis ST, and the corneal biomechanical constitutive parameter α was obtained through reverse modeling and iterative calculation.

[0051] St50, based on the comparison between the corneal biomechanical constitutive parameter α and the target value of α after surgery, the patient's personalized corneal biomechanical constitutive parameter α improvement ratio is obtained.

[0052] Example:

[0053] Before the operation, the Pentacam anterior segment analyzer and the Corvis corneal biomechanical analyzer in the corneal information acquisition module 10 collect the patient's morphological data and dynamic eyeball deformation parameters to locate the center of the lesion area. In addition, the above data are used to construct a geometric model of the entire eyeball: finite element analysis combined with dynamic mesh technology simulates the gas-solid coupling between the gas and the cornea during the Corvis measurement process, and accurately calculates the gas pressure on the corneal surface that changes with time and space; reverse modeling is used to obtain the optimal spring damper parameter combination as a boundary condition. Iterative calculations are performed on the basis of the model, and reverse modeling analysis is used to obtain the patient's in vivo corneal biomechanical constitutive parameters α and μ. Finally, the patient's corneal biomechanical constitutive parameter α is compared with the target value of α after surgery (with the standard corneal value of the same age group as the benchmark value), and the personalized corneal biomechanical performance improvement recommendation is obtained, and it is transmitted to the control computer.

[0054] The control computer calculates the required UVA irradiance and total energy according to the relationship (1.1) and (1.2), and adjusts the control light source accordingly; in addition, based on the positioning of the center of the lesion, the diameter of the cross-linking area is set, and a corresponding personalized cross-linking scheme is generated, including the center position of the cross-linking, UVA irradiance and total energy, to form a simulated cross-linking spot diagram. Subsequently, the light emitted by the light source module is reflected by a concave mirror and converted into parallel light. The parallel light can be converted into surface light and focused light radiation through a homogenizing plate or a focusing lens, and finally the personalized treatment spot is imaged on the cornea through the LCD device 32, so as to achieve personalized quantitative enhancement of corneal biomechanical properties.

[0055] The camera 34 collects corneal images during the operation and displays them on the control computer, so as to achieve real-time tracking of eye movements, reduce the loss of cross-linking energy and accurately implement personalized plans. It also allows medical staff to observe the corneal status and perform other treatments.

[0056] The above are only preferred embodiments of the present invention. The protection scope of the present invention is not limited to the above embodiments. All technical solutions under the concept of the present invention belong to the protection scope of the present invention. It should be pointed out that for ordinary technicians in this technical field, some improvements and modifications without departing from the principle of the present invention should also be regarded as the protection scope of the present invention.

Claims

1. A personalized corneal cross-linking system, characterized in that: It includes a corneal information collection module (10) and a personalized solution generation module (20); The corneal information acquisition module (10) is used to acquire and process the patient's preoperative information and obtain the corneal biomechanical constitutive parameter α; The personalized solution generation module (20) is used to automatically convert the CXL parameters according to the corneal biomechanical constitutive parameter α; The CXL parameters obtained by the personalized solution generation module (20) include UVA irradiance and UVA total energy; The calculation of the UVA irradiance is obtained by the following process: By comparing the patient's corneal biomechanical constitutive parameter α with the postoperative α target value, the improvement ratio Y of the patient's personalized corneal biomechanical constitutive parameter α is obtained; The relationship between UVA irradiance and the target improvement Y of corneal biomechanical properties is: In formula (1.1), X1 is the UVA irradiance, and Y is the increase ratio of the corneal biomechanical constitutive parameter α.

2. The personalized corneal cross-linking system according to claim 1, characterized in that: The corneal information acquisition module (10) comprises an anterior segment analyzer and a corneal biomechanics analyzer.

3. The personalized corneal cross-linking system according to claim 1, characterized in that: The calculation of the total UVA energy is obtained by the following process: By comparing the patient's corneal biomechanical constitutive parameter α with the postoperative α target value, the improvement ratio Y of the patient's personalized corneal biomechanical constitutive parameter α is obtained; The relationship between the total UVA energy and the target improvement Y of corneal biomechanical performance is: Y=18.538lnX2+8.245(1.2) In formula (1.2), X2 is the total UVA energy, and Y is the increase ratio of the corneal biomechanical constitutive parameter α.

4. The personalized corneal cross-linking system according to any one of claims 1 to 3, characterized in that: It also includes a personalized light spot implementation module (30), which is used to perform irradiation according to the CXL parameters obtained by the personalized solution generation module (20).

5. The personalized corneal cross-linking system according to claim 4, characterized in that: The personalized light spot implementation module (30) comprises a light emitting structure (31), an LCD device (32) and a support structure (33); The personalized solution generation module (20), the light emitting structure (31) and the LCD device (32) are all arranged on a support structure (33), and the light emitting structure (31) and the LCD device (32) are respectively coupled to the personalized solution generation module (20); The personalized solution generation module (20) controls the LCD device (32) to change the light spot emitted by the light emitting structure (31) according to the CXL parameters.

6. The personalized corneal cross-linking system according to claim 5, characterized in that: The support structure (33) comprises a base (331), a horizontal rod (332) and a vertical rod (333), the two ends of the vertical rod (333) are respectively connected to the base (331) and the horizontal rod (332), and the personalized solution generation module (20), the light emitting structure (31) and the LCD device (32) are all arranged on the horizontal rod (332).

7. The personalized corneal cross-linking system according to claim 5, characterized in that: The personalized light spot implementation module (30) also includes a camera arranged on a support structure (33), the camera being coupled to the personalized solution generation module (20) and being used for collecting corneal images.

8. A personalized corneal intermediate result processing method, applied to the corneal cross-linking system according to any one of claims 1 to 3, characterized in that: The process includes: Controlling the corneal information collection module (10) to collect the patient's corneal morphology data and dynamic eyeball deformation parameters; The lesion area is selected based on the maximum curvature, thinnest point and posterior surface thickness. The center of the triangle formed by the three points is used as the center point of the subsequent CXL spot. Controlling the corneal information acquisition module (10) to construct a personalized full eyeball geometric model; Based on the personalized whole eyeball geometric model, finite element analysis combined with dynamic mesh technology simulated the measurement process of Corvis ST, and the corneal biomechanical constitutive parameter α was obtained through reverse modeling and iterative calculation. By comparing the target value of corneal biomechanical constitutive parameter α and postoperative α, the patient's personalized corneal biomechanical constitutive parameter α improvement ratio is obtained.

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