Femtosecond laser-assisted personalized transepithelial corneal crosslinking device and method, electronic equipment and storage medium

Abstract

The invention discloses a femtosecond laser assisted personalized transepithelial cornea crosslinking device and method, electronic equipment and a storage medium. The cross-epithelium cornea crosslinking device comprises a femtosecond laser source, an energy adjusting assembly, an axial focusing assembly, a light beam two-dimensional scanning assembly, a light beam converging assembly, a sample interface assembly, an imaging observation assembly, a control assembly and an operation planning assembly. The femtosecond laser source, the energy adjusting assembly and the axial focusing assembly are sequentially connected, the axial focusing assembly, the light beam two-dimensional scanning assembly and the light beam converging assembly are sequentially connected, and the light beam converging assembly and the sample interface assembly are oppositely arranged; the imaging observation assembly is arranged close to the light beam convergence assembly and the sample interface assembly. Accurate drug delivery and personalized crosslinking are achieved in a minimally invasive mode, the crosslinking area is selected in a personalized mode according to the corneal morphology characteristics, riboflavin can be promoted to cross the corneal epithelium to enter the corneal stroma layer, and meanwhile the unnecessary injury area of the corneal epithelium is reduced.

Description

Technical Field

[0001] The present invention belongs to the technical field of ophthalmic surgical instruments and relates to a cross-linking device, and in particular to a femtosecond laser-assisted personalized transepithelial corneal cross-linking device, method, electronic equipment and storage medium. Background Art

[0002] Keratoconus is a bilateral, progressive corneal ectasia that typically begins during adolescence. Its incidence is approximately 1 in 2,000, and it is increasing annually. Characterized by progressive thinning of the corneal stroma and a localized conical convexity of the cornea, it presents clinically with myopia, irregular astigmatism, and scarring, leading to visual impairments such as blurred vision, double vision, and glare, with the risk of blindness.

[0003] Keratoconus has become one of the main reasons for corneal transplantation, and some patients eventually require corneal transplantation. Currently, corneal cross-linking is an effective surgical method to slow down or even stop the progression of keratoconus, especially for severe or rapidly progressive cases. Riboflavin is a photosensitizer (or cross-linker) for corneal cross-linking. It is a hydrophilic molecule that cannot penetrate the hydrophobic corneal epithelium. Corneal cross-linking refers to the process of cross-linking between collagen monomers mediated by riboflavin under ultraviolet irradiation by producing singlet oxygen and superoxide radicals. Corneal cross-linking can increase the hardness of collagen, thereby maintaining the biomechanical stability and hardness of the cornea.

[0004] The current standard clinical approach for corneal cross-linking is epithelial-free corneal cross-linking (Epi-off). Because the corneal epithelial barrier is highly hydrophobic and tightly connected, riboflavin is less efficient in penetrating the corneal stroma. Therefore, an epithelial area with a diameter of 7-9 mm in the center of the cornea needs to be removed before riboflavin administration. The thickness of the removed epithelium is approximately 50-70 μm. However, this method of corneal epithelial removal may lead to persistent corneal epithelial defects, subepithelial corneal opacity, and eye infections.

[0005] Since the delivery of riboflavin in traditional corneal cross-linking relies on the epithelial removal (Epi-off) step, this process is prone to postoperative infection and delayed healing. Although transepithelial cross-linking (Epi-on) does not require epithelial removal, the riboflavin penetration effect is poor, resulting in insufficient cross-linking depth and failure to achieve the ideal therapeutic effect. How to optimize the ocular administration route of riboflavin has always been a clinical problem that needs to be solved urgently. Therefore, it is particularly critical to develop a riboflavin corneal delivery technology that can deliver drugs in a targeted, precise and minimally invasive manner.

[0006] In recent years, there have been many studies to promote the penetration of riboflavin, such as chemical reagent release, iontophoresis, ultrasound introduction and other auxiliary delivery methods, but these schemes have limitations such as low effectiveness and lack of long-term efficacy. The current clinical problems encountered in the background technology of riboflavin delivery include but are not limited to: (1) Postoperative complications: Riboflavin delivery in traditional corneal cross-linking depends on the epithelial removal step, which is prone to cause postoperative infection and delayed healing; (2) Poor transepithelial cross-linking effect: Although transepithelial cross-linking (Epi-on) does not require epithelial removal, the riboflavin penetration effect is poor, resulting in insufficient cross-linking depth and failure to achieve the ideal therapeutic effect; (3) Lack of personalized delivery: Keratoconus is not a weakening of the overall biomechanics, but a weakening of the local biomechanics, which leads to the bulging of the corneal position at the cone point. Therefore, strengthening the corneal biomechanics at the cone point (local corneal cross-linking) can reduce the endothelial damage caused by large-area light exposure during ultraviolet cross-linking.

[0007] In view of this, there is an urgent need to design a new corneal collagen cross-linking method to overcome at least some of the above-mentioned defects of the existing corneal collagen cross-linking method.

[0008] The disclosure of the above background technology content is only used to assist in understanding the inventive concept and technical solution of the present invention. It does not necessarily belong to the prior art of this patent application. In the absence of clear evidence that the above content has been disclosed on the filing date of this patent application, the above background technology should not be used to evaluate the novelty and creativity of this application. Summary of the Invention

[0009] The present invention provides a femtosecond laser-assisted personalized trans-epithelial corneal cross-linking device, method, electronic equipment and storage medium, which can promote riboflavin to cross the corneal epithelium and enter the corneal stroma, while reducing the unnecessary damage area of the corneal epithelium.

[0010] In order to solve the above technical problems, according to one aspect of the present invention, the following technical solution is adopted:

[0011] A femtosecond laser-assisted personalized transepithelial corneal cross-linking device, comprising: a femtosecond laser source, an energy regulation component, an axial focusing component, a two-dimensional light beam scanning component, a light beam convergence component, a sample interface component, an imaging observation component, a control component, and a surgical planning component;

[0012] The control component is respectively connected to the femtosecond laser source, the energy adjustment component, the axial focusing component, the beam two-dimensional scanning component, the imaging observation component and the surgical planning component;

[0013] The femtosecond laser source, energy regulation component, and axial focusing component are connected in sequence, the axial focusing component, two-dimensional beam scanning component, and beam converging component are connected in sequence, the beam converging component and the sample interface component are arranged opposite to each other; the imaging observation component is arranged close to the beam converging component and the sample interface component;

[0014] The femtosecond laser source is used to generate a femtosecond laser beam with a specific repetition frequency and emission wavelength;

[0015] The energy adjustment component is used to adjust the femtosecond laser pulse energy and focal length in a personalized manner;

[0016] The axial focusing assembly is used to control the penetration depth of the light spot in the sample by adjusting the focus position of the femtosecond laser beam;

[0017] The two-dimensional light beam scanning component is used to scan the light beam within the field of view with personalized circle center size and interval;

[0018] The beam converging component is used to focus the scanning beam to generate an axially elongated femtosecond laser focused spot;

[0019] The sample interface assembly is used to connect to the upper surface of the sample when the laser is applied;

[0020] The imaging observation component is used to observe and record the femtosecond laser scanning process within the field of view;

[0021] The control component is used to control the laser scanning trajectory to generate personalized cross-linking area size and array density;

[0022] The surgical planning component is used to set scanning parameters based on corneal topography images and corneal mechanical properties information, thereby personalizing the surgical area, hole array depth, and hole array density; set laser energy parameters, use the photocavitation effect to scan the surface of the corneal tissue epithelium to produce a microchannel array, or use the photochemical effect to scan inside the corneal stroma to produce collagen fiber cross-linking.

[0023] As an embodiment of the present invention, the energy adjustment component is used in conjunction with a femtosecond laser source to adjust the effective focal length of the femtosecond laser pulse, so that specific energy adjustment can be achieved through the control component under the laser energy parameter conditions designed by the surgical planning component;

[0024] The generated effective focal length changes with the focused energy density and can vary within 1-200 μm, which is sufficient to penetrate the corneal epithelium and elastic layer and form microchannels at the depth of the corneal stroma.

[0025] As an embodiment of the present invention, the axial focusing assembly moves along the optical axis under the settings of the control assembly and the surgical planning assembly, thereby causing the absolute position of the light spot to move axially, and ultimately causing the lower edge of the focused light spot to move below the sample interface assembly, thereby inducing nonlinear multiphoton cross-linking or photocavitation in the corneal tissue for selective direct or auxiliary cross-linking, with depth selectivity of the action position.

[0026] The scanning area of the two-dimensional light beam scanning component is determined based on the thickness, curvature, and stiffness characteristics of the cornea. The internal components of the two-dimensional light beam scanning component move to form a scan. The horizontal arrangement spacing of the microchannel array formed after scanning can be adjusted within 1-500μm, and the action position of each light pulse can be distributed separately or overlappingly.

[0027] As an embodiment of the present invention, the beam converging component cooperates with the movable axial focusing component to focus the femtosecond laser pulse spot. During the movement of the axial focusing component and the movement of the two-dimensional beam scanning component, the beam converging component ensures that the lateral effective size of the focused spot is no more than 10 μm.

[0028] The sample interface component is used to dock and fix the sample;

[0029] The beam converging assembly, sample interface assembly, and imaging observation assembly cooperate with each other, with two assemblies remaining coaxial and the other being perpendicular to the coaxial assembly. A dichroic mirror placed at a 45-degree angle is passed between the beam converging assembly and the sample interface assembly, so that the diffusely reflected light from the sample and the plasma glow generated by the laser are diverted to enter the imaging observation assembly, while the outgoing light beam from the femtosecond laser source is filtered by the dichroic mirror and does not enter the imaging observation assembly.

[0030] As an embodiment of the present invention, the surgical planning component includes an image acquisition unit and a cross-linking area planning unit; the image acquisition unit is used to acquire and analyze corneal topography and iris images, and the cross-linking area planning unit further combines mechanical properties to generate a unique femtosecond laser scanning array trajectory.

[0031] According to another aspect of the present invention, the following technical solution is adopted: a transepithelial corneal cross-linking method using the above-mentioned femtosecond laser-assisted personalized transepithelial corneal cross-linking device, the method comprising the following steps:

[0032] Step S1, collecting patient corneal topography data, collecting and analyzing the patient's corneal topography image through an image acquisition unit;

[0033] Step S2, establishing a reference coordinate system based on the biometric features of the eye image, acquiring the patient's iris image through the image acquisition unit, and registering the iris texture and corneal topography within the same coordinate system by coordinate transformation;

[0034] Step S3, selecting a personalized trans-epithelial cross-linking region, and selecting a trans-epithelial cross-linking region;

[0035] Step S4, extracting the personalized cross-linking area in the reference coordinate system, and transmitting the selected personalized cross-linking area coordinate data to the surgical planning component for confirmation;

[0036] Step S5: generating a femtosecond laser scanning trajectory in combination with the coordinate information, converting the confirmed personalized cross-linking area coordinate data, generating a scanning device control signal, and transmitting it to the control component.

[0037] Step S6: The femtosecond laser scans the corneal epithelium to form a transepithelial microchannel array. The control component sequentially transmits signals to the axial focusing component to adjust the focal plane position. The beam two-dimensional scanning component is then controlled to move the focus spot position within the focal plane. The energy adjustment component determines the intensity of the focus spot and the length of the microchannel at each moment.

[0038] Step S7: The crosslinking agent is infiltrated through the micropore array and cross-epithelially cross-linked by ultraviolet light. The corneal crosslinking agent is dripped from the outside of the cornea. Without removing the corneal epithelium, the crosslinking agent diffuses inward through the microchannel array to the corneal stroma. The fibers in the corneal stroma are cross-linked by single-photon linear absorption of ultraviolet light or multi-photon absorption of near-infrared light.

[0039] Step S8, postoperative effect evaluation, assessing corneal biomechanical strength, safety, riboflavin penetration depth and healing condition.

[0040] As an embodiment of the present invention, step S7 is replaced by: under the premise of personalized selection of areas, no cross-linking agent is used at all, no photocavitation effect is triggered at all, and no microchannel array is generated at all. Only a femtosecond laser beam is tightly scanned within the corneal stroma to induce photochemical or photothermal effects to achieve trans-epithelial corneal nonlinear cross-linking.

[0041] As an embodiment of the present invention, in step S2, after the feature points are extracted, registration is achieved through rigid body coordinate transformation;

[0042]

[0043] Where R is the three-dimensional rotation matrix, θ represents the rotation angle around each axis, and t is the translation vector;

[0044] In step S5, the set of all vertices in the surgical area polygon is calculated as V = {v i =(x i ,y i )|i=1,2,...,n}, and get the coordinates of the center point

[0045] Generates concentric circles with equal or gradual spacing, and generates the maximum circumcircle arc of a polygon, which has a maximum radius.

[0046] Generate a set of scanning radius based on parameters For each concentric circle C = {p∈R 2 |||pc||=r j}, find the intersection arc segment with the polygonal surgical area P, let θ be the extreme angle, then the inner arc segment is where [α jk ,β jk ] is the angle interval, which satisfies that all points on the corresponding arc are inside the polygon P, K j is the number of arc segments; then, the arc segment is determined to be inside the polygon according to the arc detection algorithm, and the intersection points on the concentric circles are sorted by polar angle to form an arc segment AB. Take any point p in the arc segment = (C x +r k cosθ,C y +r k sinθ), construct a single-ended ray and calculate the number of intersections N with the polygon edge. If a single-ended ray intersects a non-end point of the j-th edge, the intersection indicator function δ j (p) is 1, otherwise it is 0;

[0047] When the number of intersection points N is an odd number, the arc segment of the scanning trajectory is within the polygonal surgical area, and the laser emits femtosecond laser pulses; when N is an even number, the arc segment of the scanning trajectory is outside the polygonal surgical area, and the laser does not emit laser light;

[0048] In step S6, the axial length of the generated microchannel can be expressed as Where n is the refractive index of the cornea, NA is the effective numerical aperture of the femtosecond laser scanning system, and λ is the wavelength of the femtosecond laser;

[0049] In step S7, at the penetration depth z, the light intensity reached can be expressed as I(z)=I0·e -μ·z ; Where I0 is the initial light intensity at the surface, and μ is the light attenuation coefficient corresponding to the overall medium system of cornea and riboflavin solution.

[0050] According to another aspect of the present invention, the following technical solution is adopted: an electronic device includes a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor implements the steps of the above method when executing the computer program.

[0051] According to another aspect of the present invention, the following technical solution is adopted: a storage medium stores computer program instructions, and the computer program instructions implement the steps of the above method when executed by a processor.

[0052] The beneficial effects of the present invention are as follows: the femtosecond laser-assisted personalized transepithelial corneal cross-linking device, method, electronic device and storage medium proposed in the present invention can achieve precise drug delivery and personalized cross-linking in a minimally invasive manner, and can personalize the cross-linking area according to the corneal morphological characteristics, thereby promoting riboflavin to cross the corneal epithelium and enter the corneal stroma, while reducing the unnecessary damage area of the corneal epithelium. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 Schematic diagram of the composition of a femtosecond laser-assisted personalized transepithelial corneal cross-linking device in one embodiment of the present invention.

[0054] Figure 2 Schematic diagram of the composition of a femtosecond laser-assisted personalized transepithelial corneal cross-linking device in one embodiment of the present invention.

[0055] Figure 3 Schematic diagram of the use of a femtosecond laser-assisted personalized transepithelial corneal cross-linking method in one embodiment of the present invention.

[0056] Figure 4 Flowchart of a femtosecond laser-assisted personalized transepithelial corneal cross-linking method according to one embodiment of the present invention.

[0057] Figure 5 Schematic diagram of the laser action of a femtosecond laser-assisted personalized transepithelial corneal cross-linking device in one embodiment of the present invention.

[0058] Figure 6 This is a top-down microscopic image of the microchannel array actually processed in the trans-epithelial corneal cross-linking device in one embodiment of the present invention.

[0059] Figure 7 This is an axial microscopic grayscale image of a microchannel generated by a transepithelial corneal cross-linking device according to an embodiment of the present invention.

[0060] Figure 8 FIG. 1 is a schematic diagram of the composition of an electronic device in one embodiment of the present invention.

[0061] The reference numerals are as follows:

[0062] 1-Femtosecond laser source; 2-Energy adjustment component; 3-Axial focusing component; 4-Two-dimensional beam scanning component; 5-Beam convergence component; 6-Sample interface component; 7-Imaging observation component; 8-Control component; 9-Surgery planning component; 10-Operation interface; 11-Corneal topography; 12-Iris image; 13-Femtosecond laser scanning array trajectory; 14-Femtosecond laser beam; 15-Laser focusing area; 16-Corneal epithelium; 17-Descemet's layer; 18-Corneal stroma; 1 9-riboflavin; 20-cross-linker permeation microchannel; 21-microchannel length; 22-energy level; 23-XY direction / horizontal plane / focal plane microchannel array; 24-XZ direction / vertical section / axial microchannel morphology; 2a-half-wave plate; 2b-polarization beam splitter; 2c-photodetector; 7a-dichroic mirror; 7b-collimating mirror; 7c-short-pass filter; 7d-tube lens; 7e-imaging sensor; 9a-image acquisition unit; 9b-cross-linking area planning unit. DETAILED DESCRIPTION

[0063] The preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0064] In order to further understand the present invention, preferred embodiments of the present invention are described below in conjunction with examples. However, it should be understood that these descriptions are only for further illustrating the features and advantages of the present invention, rather than limiting the claims of the present invention.

[0065] The description in this section is only for several typical embodiments, and the present invention is not limited to the scope of the embodiments described. The same or similar existing technical means and some technical features of the embodiments are mutually replaced within the scope of the description and protection of the present invention.

[0066] The description of the steps in each embodiment in the specification is only for the convenience of explanation, and the implementation method of this application is not limited by the order of implementation of the steps.

[0067] The term "connection" as used in this specification includes both direct connection and indirect connection, such as connection through active devices, passive devices or electrically conductive media; it may also include connection through other active devices or passive devices that are well known to those skilled in the art and can achieve the same or similar functional purposes, such as connection through circuits or components such as switches and follower circuits.

[0068] The present invention discloses a femtosecond laser-assisted personalized transepithelial corneal cross-linking device. Figure 1 、 Figure 2 This is a schematic diagram of the composition of a femtosecond laser-assisted personalized transepithelial corneal cross-linking device according to one embodiment of the present invention; Figure 1 、 Figure 2The trans-epithelial corneal cross-linking device includes: a femtosecond laser source 1, an energy adjustment component 2, an axial focusing component 3, a two-dimensional beam scanning component 4, a beam convergence component 5, a sample interface component 6, an imaging observation component 7, a control component 8 and a surgical planning component 9.

[0069] The control component 8 is respectively connected to the femtosecond laser source 1, the energy adjustment component 2, the axial focusing component 3, the two-dimensional beam scanning component 4, the imaging observation component 7 and the surgical planning component 9.

[0070] The femtosecond laser source 1, energy regulation component 2, and axial focusing component 3 are connected in sequence, the axial focusing component 3, two-dimensional beam scanning component 4, and beam converging component 5 are connected in sequence, and the beam converging component 5 and the sample interface component 6 are arranged opposite to each other; the imaging observation component 7 is arranged close to the beam converging component 5 and the sample interface component 6.

[0071] The femtosecond laser source 1 is used to generate a femtosecond laser beam 14 with a specific repetition frequency and emission wavelength; the energy adjustment component 2 is used to adjust the femtosecond laser pulse energy and focal length in a personalized manner.

[0072] The axial focusing assembly 3 is used to control the penetration depth of the light spot in the sample by adjusting the focal position of the femtosecond laser beam. In one embodiment, the sample includes but is not limited to a tissue phantom, an isolated animal eye, a living animal or a patient eye, and in one embodiment, it can be the epithelial layer of the cornea.

[0073] The two-dimensional beam scanning component 4 is used to scan the beam with personalized circle center size and interval within the field of view; the beam converging component 5 is used to focus the scanning beam to produce an axially elongated femtosecond laser focus spot; the sample interface component 6 is used to dock with the upper surface of the sample when the laser is applied; the imaging observation component 7 is used to observe and record the femtosecond laser scanning process within the field of view; the control component 8 is used to control the laser scanning trajectory to generate personalized cross-linking area size and array density.

[0074] The surgical planning component 9 is used to set scanning parameters based on the corneal topography image and corneal mechanical properties information, thereby personalizing the surgical area, hole array depth, and hole array density; set laser energy parameters, use the photocavitation effect to scan the surface of the corneal tissue epithelium to produce a microchannel array, or use the photochemical effect to scan inside the corneal stroma to produce collagen fiber cross-linking.

[0075] In one embodiment of the present invention, the energy modulation component 2 is used in conjunction with the femtosecond laser source 1 to regulate the effective focal length of the femtosecond laser pulse, enabling specific energy adjustments to be achieved through the control component 8 under the laser energy parameters designed by the surgical planning component 9. The resulting effective focal length varies with the focused energy density and can range from 1 to 200 μm, sufficient to penetrate the corneal epithelium and Descemet's membrane, forming microchannels deep within the corneal stroma.

[0076] In one embodiment of the present invention, the axial focusing component 4 moves along the optical axis under the settings of the control component 8 and the surgical planning component 9, thereby causing the absolute position of the light spot to move axially, and finally causing the lower edge of the focused light spot to move below the sample interface component 6, causing nonlinear multiphoton cross-linking or photocavitation in the corneal tissue to perform selective direct or auxiliary cross-linking, and the action position has depth selectivity.

[0077] The scanning area of the two-dimensional light beam scanning component 4 is determined based on the thickness, curvature, and stiffness characteristics of the cornea. The internal components of the two-dimensional light beam scanning component 4 move to form a scan. The horizontal arrangement spacing of the microchannel array formed after scanning can be adjusted within 1-500μm, and the action position of each light pulse can be distributed separately or overlappingly.

[0078] In one embodiment of the present invention, the beam converging component 5 cooperates with the movable axial focusing component 3 to focus the femtosecond laser pulse spot. During the movement of the axial focusing component 3 and the movement of the two-dimensional beam scanning component 4, the beam converging component 5 ensures that the lateral effective size of the focused spot is no more than 10 μm.

[0079] The lower end surface of the sample interface component 6 can be a solid plane, a solid arc surface, a hollow circular surface, or other shapes; the sample interface component 6 is used to dock and fix samples, where the samples include but are not limited to tissue phantoms, isolated animal eyes, living animals or patient eyes.

[0080] The beam converging component 5, the sample interface component 6 and the imaging observation component 7 cooperate with each other, two of which remain coaxial and the other component is perpendicular to it; a dichroic mirror placed at 45° is passed between the beam converging component 5 and the sample interface component 6, and the diffusely reflected light of the sample and the plasma glow generated by the laser are both diverted to enter the imaging observation component 7. The outgoing light beam of the femtosecond laser source 1 is filtered by the dichroic mirror and does not enter the imaging observation component 7.

[0081] In one embodiment of the present invention, the surgical planning component 9 includes an image acquisition unit 9a and a cross-linking area planning unit 9b; the image acquisition unit 9a is used to acquire and analyze the corneal topography 11 and the iris image 12, and the cross-linking area planning unit 9b further combines the mechanical properties to generate a unique femtosecond laser scanning array trajectory 13.

[0082] The present invention also discloses a trans-epithelial corneal cross-linking method using the femtosecond laser-assisted personalized trans-epithelial corneal cross-linking device, the method comprising the following steps:

[0083] [Step S1] Acquisition of patient corneal topography data: collecting and analyzing the patient's corneal topography image through the image acquisition unit 9a;

[0084] [Step S2] establishing a reference coordinate system based on the biometric features of the eye image, acquiring the patient's iris image through the image acquisition unit, and registering the iris texture and corneal topography within the same coordinate system by coordinate transformation;

[0085] In one embodiment, after feature point extraction, registration is achieved through rigid coordinate transformation.

[0086]

[0087] Where R is the three-dimensional rotation matrix, θ represents the rotation angle around each axis, and t is the translation vector.

[0088] [Step S3] Personalized transepithelial cross-linking region selection: Select the transepithelial cross-linking region (selection can be done interactively through the operation interface 10 or automatically);

[0089] [Step S4] Extracting the personalized cross-linking area in the reference coordinate system, and transferring the selected personalized cross-linking area coordinate data to the surgical planning component (9) for confirmation (which can be operated through the operation interface 10);

[0090] [Step S5] generating a femtosecond laser scanning trajectory based on the coordinate information, converting the confirmed personalized cross-linking area coordinate data, generating a scanning device control signal, and transmitting it to the control component 8;

[0091] In one embodiment, step S5 includes: calculating the set of all vertices V in the surgical area polygon = {v i =(x i ,y i )|i=1,2,...,n}, and get the coordinates of the center point

[0092] Generates concentric circles with equal or gradual spacing, and generates the maximum circumcircle arc of a polygon, which has a maximum radius.

[0093] Generate a set of scanning radius based on parameters For each concentric circle C = {p∈R 2 |||pc||=r j}, find the intersection arc segment with the polygonal surgical area P, let θ be the extreme angle, then the inner arc segment is where [α jk ,β jk ] is the angle interval, which satisfies that all points on the corresponding arc are inside the polygon P, K j is the number of arc segments. Then, the arc detection algorithm is used to determine whether the arc segment is inside the polygon. The intersection points on the concentric circles are sorted by polar angle to form an arc segment AB. Take any point p in the arc segment = (C x +r k cosθ,C y +r k sinθ), construct a single-ended ray and calculate the number of intersections N with the polygon edge. If a single-ended ray intersects a non-end point of the j-th edge, the intersection indicator function δ j (p) is 1, otherwise it is 0.

[0094] When the number of intersection points N is an odd number, the arc segment of the scanning trajectory is within the polygonal surgical area, and the laser emits femtosecond laser pulses; when N is an even number, the arc segment of the scanning trajectory is outside the polygonal surgical area, and the laser does not emit laser.

[0095] [Step S6] The femtosecond laser scans the corneal epithelium to form a trans-epithelial microchannel array. The control component 8 transmits signals to the axial focusing component 3 in sequence to adjust the focal plane position, and then controls the two-dimensional beam scanning component 4 to move the focal spot position within the focal plane. The energy adjustment component 2 determines the intensity of the focal spot action position and the microchannel length at each moment.

[0096] In one embodiment, the resulting microchannel axial length can be expressed as Where n is the refractive index of the cornea, NA is the effective numerical aperture of the femtosecond laser scanning system, and λ is the wavelength of the femtosecond laser.

[0097] [Step S7] The cross-linking agent penetrates through the microporous array and is cross-linked across the epithelium by ultraviolet light. The corneal cross-linking agent (such as riboflavin, or other corneal cross-linking agents) is dripped into the outside of the cornea. Without removing the corneal epithelium, the cross-linking agent diffuses inward through the microchannel array to the corneal stroma. The fibers in the corneal stroma are cross-linked by the single-photon linear absorption of ultraviolet light or the multi-photon absorption of near-infrared light.

[0098] In one embodiment, at the penetration depth z, the light intensity reached can be expressed as I(z)=I0·e -μ·z; Where I0 is the initial light intensity at the surface, and μ is the light attenuation coefficient corresponding to the overall medium system of cornea and riboflavin solution.

[0099] [Step S8] Postoperative effect evaluation, assessing corneal biomechanical strength, safety, riboflavin penetration depth, and healing status.

[0100] In one embodiment of the present invention, step S7 can be replaced by: under the premise of personalized selection of areas, no cross-linking agent is used at all, no photocavitation effect is triggered at all, and no microchannel array is generated at all. Only a femtosecond laser beam is tightly scanned within the corneal stroma to induce photochemical or photothermal effects to achieve trans-epithelial corneal nonlinear cross-linking.

[0101] See Figures 1 to 5 The present invention provides a femtosecond laser-assisted personalized transepithelial corneal cross-linking device, which combines the corneal morphology and mechanical properties to personalize the treatment area and cross-linking density, and generates a micropore array through femtosecond laser to assist in the delivery of cross-linking agents, or directly generates a multi-photon nonlinear cross-linking effect through femtosecond laser to achieve the purpose of precise drug delivery and personalized treatment.

[0102] During operation, the femtosecond laser source is used to generate a femtosecond laser beam with a specific repetition frequency and wavelength, the energy regulation component personalizes the femtosecond laser pulse energy and focal length, the axial focusing component changes the focal position of the femtosecond laser beam, the axial condition component also controls the penetration depth of the microchannel array in the sample, the two-dimensional beam scanning component performs array scanning with adjustable size and interval according to the selected center of the circle in the field of view, the beam convergence component focuses the scanning beam to generate an axially elongated femtosecond laser focused spot, the sample interface component docks with the upper surface of the sample when the laser acts, the imaging observation component is used to observe and record the femtosecond laser scanning process within the field of view, the control component is used to control the laser scanning trajectory and change the cross-linking area size and array density, and the surgical planning component sets the hole array position and characteristics according to the corneal topography image information.

[0103] In one embodiment of the present invention, the femtosecond laser focused spot is configured to form a microchannel or a cross-linked region by setting different single pulse energies from 0.0 to 1.5; the femtosecond laser source, the energy adjustment component, the control component, and the surgical planning component can all independently or in conjunction with each other to adjust the energy level 22, such as Figure 7 shown.

[0104] The energy level 22 includes at least two or more optional energy levels, each energy level has a specific value adjustable within 0.01-50 μJ, and controls the axial length of the focused light spot and the microchannel length 21 to be adjustable within 10-300 μm, so as to directly or indirectly promote the cross-linking of the corneal stroma.

[0105] The axial focusing assembly can control the movement of internal components by stepping or pulsed electrical signals, and remotely adjust the axial position of the laser focusing area 15 away from the sample. The laser focusing area 15 is spindle-shaped. Preferably, the focusing assembly can make the lower end of the spindle-shaped volume of the laser focusing area be located in the corneal epithelium, elastic layer, and stroma.

[0106] When the laser focusing area 15 is at the same specific position inside the cornea, only the femtosecond laser source or energy adjustment device forms cross-linking agent permeation microchannels 20 of different lengths; the riboflavin 19 solution above the cross-linking agent permeation microchannel 20 penetrates into the cornea through the microchannel.

[0107] The beam two-dimensional scanning component performs spiral line scanning with a diameter of 0.2-20mm in a circle with a maximum scanning field of 20×20mm at the center of the cross-linked surgical area determined by the surgical planning component. 2 ,Preferably, the spacing between adjacent points and the spacing between lines in the ,scanning trajectory can be adjusted to equal values, for example Figure 6 The microchannel arrays are formed by scanning at equal intervals of 50 and 100 μm. Figure 6 Also disclosed are the XY direction / horizontal plane / focal plane microchannel array 23 and the XZ direction / vertical cross section / axial microchannel morphology 24.

[0108] Advantages of the embodiments of the present invention include:

[0109] a. Possessing personalized delivery capabilities: Compared to traditional and existing epithelial de-crosslinking solutions, the present invention can introduce riboflavin into the corneal stroma by means of a microchannel array generated by a femtosecond laser without removing corneal epithelial cells; or utilize the femtosecond laser spot itself to induce photochemical crosslinking.

[0110] b. Minimally invasive treatment of corneal epithelial cells: The single lateral size of the femtosecond laser spot described in the present invention does not exceed 10 μm, which is much smaller than the mm-level wound size of existing epithelial removal methods, and the risk of postoperative infection can be reduced.

[0111] c. The auxiliary cross-linking area can be selected according to the corneal morphology: Compared with the existing transepithelial corneal cross-linking schemes (such as iontophoresis, ultrasound introduction, etc.), the existing technologies have a larger delivery area and require hand-held and no imaging monitoring device. The femtosecond laser-assisted method described in the present invention can be monitored by the imaging system, combined with corneal topography alignment and guidance, to personalize and accurately point to the tiny area that needs auxiliary cross-linking.

[0112] The background section of the present invention may contain background information on the problem or environment of the present invention, but does not necessarily describe the prior art. Therefore, the inclusion of content in the background section is not an admission by the applicant that the prior art is present.

[0113] The present invention also discloses an electronic device, Figure 8 This is a schematic diagram of the composition of an electronic device according to an embodiment of the present invention; Figure 8 At the hardware level, the electronic device includes a memory, a processor, and at least one network interface. The processor may be a microprocessor, and the memory may include internal memory, such as random access memory (RAM) or non-volatile memory. Of course, the electronic device may also include other hardware as needed.

[0114] The processor, network interface, and memory may be interconnected via an internal bus. The memory is used to store programs (which may include operating system programs and application programs); the programs may include program code, which may include computer operating instructions. The memory may include internal memory and non-volatile memory, and provides instructions and data to the processor.

[0115] In one embodiment, the processor can read the corresponding program from the non-volatile memory into the memory and then run it; the processor can execute the program stored in the memory and is specifically used to perform the following operations (such as Figure 4 shown):

[0116] [Step S1] Acquiring corneal topography data of the patient, and collecting and analyzing the patient's corneal topography image through the image acquisition unit (9a);

[0117] [Step S2] establishing a reference coordinate system based on the biometric features of the eye image, acquiring the patient's iris image through the image acquisition unit, and registering the iris texture and corneal topography within the same coordinate system by coordinate transformation;

[0118] [Step S3] Personalized transepithelial cross-linking region selection: select the transepithelial cross-linking region (selection can be done interactively via the operation interface (10) or automatically);

[0119] [Step S4] Extracting the personalized cross-linking area in the reference coordinate system, and transferring the selected personalized cross-linking area coordinate data to the surgical planning component (9) for confirmation (which can be operated through the operation interface 10);

[0120] [Step S5] generating a femtosecond laser scanning trajectory in combination with the coordinate information, converting the confirmed personalized cross-linking area coordinate data, generating a scanning device control signal, and transmitting it to the control component (8);

[0121] [Step S6] The femtosecond laser scans the corneal epithelium to form a trans-epithelial microchannel array. The control component (8) sequentially transmits signals to the axial focusing component (3) to adjust the focal plane position, and then controls the two-dimensional beam scanning component (4) to move the focal spot position within the focal plane. The energy adjustment component (2) determines the intensity of the focal spot action position and the length of the microchannel at each moment.

[0122] [Step S7] The cross-linking agent penetrates through the microporous array and is cross-linked across the epithelium by ultraviolet light. Riboflavin and other corneal cross-linking agents are dripped into the outside of the cornea. Without removing the corneal epithelium, the cross-linking agent diffuses inward through the microchannel array to the corneal stroma. The fibers in the corneal stroma are cross-linked by the single-photon linear absorption of ultraviolet light or the multi-photon absorption of near-infrared light.

[0123] [Step S8] Postoperative effect evaluation, assessing corneal biomechanical strength, safety, riboflavin penetration depth, and healing status.

[0124] The present invention further discloses a storage medium having computer program instructions stored thereon, which, when executed by a processor, implements the following steps of the method of the present invention (eg Figure 4 shown):

[0125] [Step S1] Acquiring corneal topography data of the patient, and collecting and analyzing the patient's corneal topography image through the image acquisition unit (9a);

[0126] [Step S2] establishing a reference coordinate system based on the biometric features of the eye image, acquiring the patient's iris image through the image acquisition unit, and registering the iris texture and corneal topography within the same coordinate system by coordinate transformation;

[0127] [Step S3] Personalized transepithelial cross-linking region selection: select the transepithelial cross-linking region (selection can be done interactively via the operation interface (10) or automatically);

[0128] [Step S4] Extracting the personalized cross-linking area in the reference coordinate system, and transferring the selected personalized cross-linking area coordinate data to the surgical planning component (9) for confirmation (which can be operated through the operation interface 10);

[0129] [Step S5] generating a femtosecond laser scanning trajectory in combination with the coordinate information, converting the confirmed personalized cross-linking area coordinate data, generating a scanning device control signal, and transmitting it to the control component (8);

[0130] [Step S6] The femtosecond laser scans the corneal epithelium to form a trans-epithelial microchannel array. The control component (8) sequentially transmits signals to the axial focusing component (3) to adjust the focal plane position, and then controls the two-dimensional beam scanning component (4) to move the focal spot position within the focal plane. The energy adjustment component (2) determines the intensity of the focal spot action position and the length of the microchannel at each moment.

[0131] [Step S7] The cross-linking agent penetrates through the microporous array and is cross-linked across the epithelium by ultraviolet light. Riboflavin and other corneal cross-linking agents are dripped into the outside of the cornea. Without removing the corneal epithelium, the cross-linking agent diffuses inward through the microchannel array to the corneal stroma. The fibers in the corneal stroma are cross-linked by the single-photon linear absorption of ultraviolet light or the multi-photon absorption of near-infrared light.

[0132] [Step S8] Postoperative effect evaluation, assessing corneal biomechanical strength, safety, riboflavin penetration depth, and healing status.

[0133] In summary, the femtosecond laser-assisted personalized transepithelial corneal cross-linking device proposed in the present invention achieves precise drug delivery and personalized cross-linking in a minimally invasive manner. The cross-linking area is personalized according to the corneal morphological characteristics, which can promote riboflavin to cross the corneal epithelium and enter the corneal stroma, while reducing the unnecessary damage area of the corneal epithelium.

[0134] It should be noted that the present application can be implemented in software and / or a combination of software and hardware; for example, it can be implemented using an application-specific integrated circuit (ASIC), a general-purpose computer, or any other similar hardware device. In some embodiments, the software program of the present application can be executed by a processor to implement the above steps or functions. Similarly, the software program of the present application (including related data structures) can be stored in a computer-readable recording medium; for example, a RAM memory, a magnetic or optical drive, or a floppy disk and the like. In addition, some steps or functions of the present application can be implemented in hardware; for example, as a circuit that cooperates with a processor to perform various steps or functions.

[0135] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0136] The description and application of the present invention here are illustrative and are not intended to limit the scope of the present invention to the above-described embodiments. The effects or advantages involved in the embodiments may not be embodied in the embodiments due to interference from various factors, and the description of the effects or advantages is not used to limit the embodiments. Variations and changes to the embodiments disclosed here are possible, and the replacement of the embodiments and various equivalent components are well known to those of ordinary skill in the art. It should be clear to those skilled in the art that the present invention can be implemented in other forms, structures, arrangements, proportions, and with other components, materials, and parts without departing from the spirit or essential characteristics of the present invention. Other variations and changes can be made to the embodiments disclosed here without departing from the scope and spirit of the present invention.

Claims

1. A femtosecond laser-assisted personalized transepithelial corneal cross-linking device, characterized in that: The trans-epithelial corneal cross-linking device comprises: a femtosecond laser source (1), an energy adjustment component (2), an axial focusing component (3), a two-dimensional light beam scanning component (4), a light beam convergence component (5), a sample interface component (6), an imaging observation component (7), a control component (8) and a surgical planning component (9); The control component (8) is respectively connected to the femtosecond laser source (1), the energy adjustment component (2), the axial focusing component (3), the two-dimensional light beam scanning component (4), the imaging observation component (7) and the surgical planning component (9); The femtosecond laser source (1), the energy adjustment component (2), and the axial focusing component (3) are connected in sequence; the axial focusing component (3), the two-dimensional light beam scanning component (4), and the light beam converging component (5) are connected in sequence; the light beam converging component (5) and the sample interface component (6) are arranged relative to each other; and the imaging observation component (7) is arranged close to the light beam converging component (5) and the sample interface component (6); The femtosecond laser source (1) is used to generate a femtosecond laser beam (14) with a specific repetition frequency and emission wavelength; The energy adjustment component (2) is used to adjust the femtosecond laser pulse energy and focal length in a personalized manner; The axial focusing assembly (3) is used to control the penetration depth of the light spot in the sample by adjusting the focus position of the femtosecond laser beam; The light beam two-dimensional scanning component (4) is used to perform light beam scanning within the field of view with personalized circle center size and interval; The beam converging component (5) is used to focus the scanning beam to generate an axially elongated femtosecond laser focused spot; The sample interface component (6) is used to connect to the upper surface of the sample when the laser is applied; The imaging observation component (7) is used to observe and record the femtosecond laser scanning process within the field of view; The control component (8) is used to control the laser scanning trajectory to generate personalized cross-linking area size and array density; The surgical planning component (9) is used to set scanning parameters according to the corneal topography image and corneal mechanical property information, thereby individually changing the surgical area, hole array depth, and hole array density; setting laser energy parameters, using the photocavitation effect to scan the surface of the corneal tissue epithelium to generate a microchannel array, or using the photochemical effect to scan the interior of the corneal stroma to generate collagen fiber cross-linking.

2. The femtosecond laser-assisted personalized transepithelial corneal cross-linking device according to claim 1, characterized in that: The energy adjustment component (2) is used in conjunction with the femtosecond laser source (1) to adjust the effective focal length of the femtosecond laser pulse, so that specific energy adjustment can be achieved through the control component (8) under the laser energy parameter conditions designed by the surgical planning component (9); The generated effective focal length changes with the focused energy density and can vary within 1-200 μm, which is sufficient to penetrate the corneal epithelium and elastic layer and form microchannels at the depth of the corneal stroma.

3. The femtosecond laser-assisted personalized transepithelial corneal cross-linking device according to claim 1, characterized in that: The axial focusing component (4) moves along the optical axis under the settings of the control component (8) and the surgical planning component (9), thereby causing the absolute position of the light spot to move axially, and finally causing the lower edge of the focused light spot to move below the sample interface component (6), thereby causing nonlinear multi-photon cross-linking or photo-induced cavitation in the corneal tissue, so as to perform selective direct or auxiliary cross-linking, and the action position has depth selectivity; The scanning area of the two-dimensional light beam scanning component (4) is determined according to the thickness, curvature and rigidity characteristics of the cornea. The internal components of the two-dimensional light beam scanning component (4) move to form a scan. The arrangement spacing distance of the microchannel array formed after scanning can be adjusted within 1-500 μm in the horizontal direction. The action position of each light pulse can be distributed in a separated or overlapping manner.

4. The femtosecond laser-assisted personalized transepithelial corneal cross-linking device according to claim 1, characterized in that: The beam converging component (5) cooperates with the movable axial focusing component (3) to focus the femtosecond laser pulse spot. During the movement of the axial focusing component (3) and the movement of the two-dimensional beam scanning component (4), the beam converging component (5) ensures that the transverse effective size of the focused spot is no greater than 10 μm. The sample interface component (6) is used to dock and fix the sample; The beam converging component (5), the sample interface component (6) and the imaging observation component (7) cooperate with each other, wherein two components are kept coaxial and the other component is perpendicular to the beam converging component (5) and a dichroic mirror is placed at 45 degrees between the beam converging component (5) and the sample interface component (6), so that the diffusely reflected light of the sample and the plasma glow generated by the laser action are both diverted to enter the imaging observation component (7), and the outgoing light beam of the femtosecond laser source (1) is filtered by the dichroic mirror and does not enter the imaging observation component (7).

5. The femtosecond laser-assisted personalized transepithelial corneal cross-linking device according to claim 1, characterized in that: The surgical planning component (9) includes an image acquisition unit (9a) and a cross-linking area planning unit (9b); the image acquisition unit (9a) is used to acquire and analyze a corneal topography (11) and an iris image (12), and the cross-linking area planning unit (9b) further combines mechanical properties to generate a unique femtosecond laser scanning array trajectory (13).

6. A transepithelial corneal cross-linking method using the femtosecond laser-assisted personalized transepithelial corneal cross-linking device according to any one of claims 1 to 5, characterized in that: The method comprises the following steps: Step S1, collecting patient corneal topography data, collecting and analyzing the patient's corneal topography image through the image acquisition unit (9a); Step S2, establishing a reference coordinate system based on the biometric features of the eye image, acquiring the patient's iris image through the image acquisition unit, and registering the iris texture and corneal topography within the same coordinate system by coordinate transformation; Step S3, selecting a personalized trans-epithelial cross-linking region, and selecting a trans-epithelial cross-linking region; Step S4, extracting the personalized cross-linking area in the reference coordinate system, and transferring the selected personalized cross-linking area coordinate data to the surgical planning component (9) for confirmation; Step S5, generating a femtosecond laser scanning trajectory in combination with the coordinate information, converting the confirmed personalized cross-linking area coordinate data, generating a scanning device control signal, and transmitting it to the control component (8); Step S6, the femtosecond laser scans the corneal epithelium to form a trans-epithelial microchannel array, the control component (8) sequentially transmits signals to the axial focusing component (3) to adjust the focal plane position, and then controls the two-dimensional beam scanning component (4) to move the focus spot position within the focal plane, and the energy adjustment component (2) determines the action intensity and microchannel length of the focus spot action position at each moment; Step S7: The crosslinking agent is infiltrated through the micropore array and cross-epithelially cross-linked by ultraviolet light. The corneal crosslinking agent is dripped from the outside of the cornea. Without removing the corneal epithelium, the crosslinking agent diffuses inward through the microchannel array to the corneal stroma. The fibers in the corneal stroma are cross-linked by single-photon linear absorption of ultraviolet light or multi-photon absorption of near-infrared light. Step S8, postoperative effect evaluation, assessing corneal biomechanical strength, safety, riboflavin penetration depth and healing condition.

7. The transepithelial corneal cross-linking method according to claim 6, wherein: The step S7 is replaced by: under the premise of personalized selection of areas, no cross-linking agent is used at all, no photocavitation effect is triggered at all, and no microchannel array is generated at all. Only the femtosecond laser beam is tightly scanned in the corneal stroma to induce photochemical or photothermal effects to achieve trans-epithelial corneal nonlinear cross-linking.

8. The transepithelial corneal cross-linking method according to claim 6, wherein: In step S2, after feature point extraction, registration is achieved through rigid body coordinate transformation; Where R is the three-dimensional rotation matrix, θ represents the rotation angle around each axis, and t is the translation vector; In step S5, the set of all vertices in the surgical area polygon is calculated as V = {v i =(x i ,y i )|i=1,2,...,n}, and get the coordinates of the center point Generates concentric circles with equal or gradual spacing, and generates the maximum circumcircle arc of a polygon, which has a maximum radius. Generate a set of scanning radius based on parameters For each concentric circle Find the intersection arc segment with the polygonal surgical area P, let θ be the extreme angle, then the inner arc segment is where [α jk ,β jk ] is the angle interval, which satisfies that all points on the corresponding arc are inside the polygon P, K j is the number of arc segments; then, the arc segment is determined to be inside the polygon according to the arc detection algorithm, and the intersection points on the concentric circles are sorted by polar angle to form an arc segment AB. Take any point p in the arc segment = (C x +r k cosθ,C y +r k sinθ), construct a single-ended ray and calculate the number of intersections N with the polygon edge. If a single-ended ray intersects a non-end point of the j-th edge, the intersection indicator function δ j (p) is 1, otherwise it is 0; When the number of intersection points N is an odd number, the arc segment of the scanning trajectory is within the polygonal surgical area, and the laser emits femtosecond laser pulses; when N is an even number, the arc segment of the scanning trajectory is outside the polygonal surgical area, and the laser does not emit laser light; In step S6, the axial length of the generated microchannel can be expressed as Where n is the refractive index of the cornea, NA is the effective numerical aperture of the femtosecond laser scanning system, and λ is the wavelength of the femtosecond laser; In step S7, at the penetration depth z, the light intensity reached can be expressed as I(z)=I0·e -μ·z ; Where I0 is the initial light intensity at the surface, and μ is the light attenuation coefficient corresponding to the overall medium system of cornea and riboflavin solution.

9. An electronic device comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein: When the processor executes the computer program, the steps of the method according to any one of claims 5 to 8 are implemented.

10. A storage medium having computer program instructions stored thereon, characterized in that: When the computer program instructions are executed by a processor, the steps of the method according to any one of claims 5 to 8 are implemented.

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