RU2816797C2 - System for treating biological eye tissue by microporation - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: system for treating biological tissue of the eye by microporation, comprising: a controller; laser head system, comprising: a housing, a laser subsystem for generating a laser beam along an action axis, and configured to be used in a subsurface ablative treatment process to create a pore pattern, and a lens configured to focus the laser beam on the target tissue; an eye tracking subsystem for tracking identification points and eye movements; a depth control subsystem for controlling the depth of the microporation on the target tissue; wherein the controller is configured to control movements of the laser subsystem, which include a tilt movement, a turn movement and a deflection movement.

EFFECT: restoration of physiological functions of the eye, including restoration of physiological accommodation or physiological pseudo-accommodation due to natural physiological and biomechanical phenomena associated with natural accommodation of the eye.

18 cl, 139 dwg

Description

[0001] This application is a continuation of International Patent Application No. PCT/US20/31392, filed May 5, 2020, which claims priority to U.S. Provisional Application No. 62/843,403, “SYSTEMS AND METHODS FOR OCULAR LASER SURGERY AND THERAPEUTIC TREATMENTS,” filed May 4, 2019, the contents and disclosures of each of which are incorporated herein by reference in their entirety.

[0002] This application relates to the subject matter disclosed in US Application No. 15/942,513 (filed 3/31/2018), International Application No. PCT/US18/25608 (filed 3/31/2018), Taiwan Application No. 108111355 (filed 3/31/2018) /29/2019), US Application No. 11/376,969 (filed 03/15/2006), US Application No. 11/850,407 (filed 05/09/2007), US Application No. 11/938,489 (filed 12/11/2007) , US Application No. 12/958,037 (filed 01/12/2010), US Application No. 13/342,441 (filed 03/01/2012), US Application No. 13/709,890 (filed 10/12/2012), US Application No. 14 /526,426 (filed 10/28/2014), US Application No. 14/861,142 (filed 09/22/2015), US Application No. 15/365,556 (filed 11/30/2016), US Application No. 16/599,096 (filed 10 /10/2019), US Application No. 14/213,492 (filed 14/03/2014), US Application No. 16/258,378 (filed 01/25/2019), US Application No. 15/638,308 (filed 06/29/2017) , US Application No. 16/702,470 (filed 03/12/2019), and US Application No. 15/638,346 (filed 06/29/2017), each of which is incorporated herein by reference in its entirety.

FIELD OF TECHNOLOGY TO WHICH THE INVENTION RELATES

[0002] The subject matter of the invention described herein relates generally to systems, methods, therapies and devices for laser microporation and, in particular, to systems, methods and devices for rejuvenating ocular tissue by laser ocular microporation, especially in connection with the aging of connective tissue, to the rejuvenation of connective tissue through rejuvenation of the eye or sclera.

BACKGROUND OF THE INVENTION

[0004] The eye is a biomechanical structure, a complex sensory organ that contains complex muscular, drainage and fluid mechanisms that perform the functions of vision and biotransport of the eye. The accommodative system is the main driving system in the organ of vision, supporting many physiological and visual functions in the eye. The physiological role of the accommodative system is to move aqueous humor, blood, nutrients, oxygen, carbon dioxide and other cells throughout the organ of vision. In general, the loss of accommodative ability in presbyopia is caused by many lenticular as well as extralenticular and physiological factors that are dependent on aging. Increased rigidity of the eye with age creates a stress-strain state of the mentioned ocular structures and can worsen the accommodative ability, which can affect the eye in the form of a decrease in biomechanical efficiency in relation to physiological processes, including, at a minimum, visual accommodation, aqueous humor hydrodynamics, vitreous hydrodynamics body and pulsating ocular blood flow. Current procedures only affect the optics by some artificial means, such as refractive laser surgery, adaptive optics, or corneal or intraocular implants, which change the optical power in one optical element of the eye and ignore the other optical element and the importance of preserving the physiological functions of the accommodative mechanism.

[0005] In addition, modern scleral implant devices obtain a mechanical accommodation effect. They do not take into account the effects of "pores", "micropores" or creating a matrix of pores with a centered hexagon or circle or polygon in a 3D (3-dimensional) tissue. As such, current procedures and devices are unable to restore normal physiological functions of the eye.

[0006] Accordingly, there is a need for systems and methods for restoring normal physiological functions of the eye that take into account the effects of "pores" or creating a mesh or matrix of pores with a centered hexagon or circle or polygon in three-dimensional (3D) tissue.

SUMMARY OF THE INVENTION

[0007] This application discloses systems, devices and methods for laser microporation for the purpose of rejuvenating ocular tissue, such as those related to connective tissue aging and connective tissue rejuvenation through scleral rejuvenation. The systems, devices and methods disclosed herein restore physiological functions of the eye, including restoration of physiological accommodation or physiological pseudo-accommodation due to natural physiological and biomechanical phenomena associated with natural accommodation of the eye. In some embodiments, the laser system may be configured to target ocular tissue off-axis or in an area of the eye that is not aligned with the visual axis or directed away from the pupil of the eye where the gaze position of the eye is located.

[0008] In some embodiments, the present invention may include a system for performing microporation treatment of biological tissue to improve ocular biomechanics, the system comprising: a controller; a laser head system containing: a housing, a laser subsystem for generating a beam of laser radiation along the axis of influence not aligned with the visual axis of the patient, designed to be used in the process of subsurface ablative treatment to create a pore pattern that improves biomechanics, and a lens (objective) ), configured to focus the laser beam onto the target tissue; an eye tracking subsystem for tracking landmarks and eye movements; a depth control subsystem for controlling the depth of ablation or microporation on the target tissue; and wherein the controller is configured to control movements of the laser subsystem including at least one of a tilt movement, a rotation movement, and a deflection movement.

[0009] In some embodiments, the system may also include a scanning system in communication with the eye tracking subsystem and the depth control subsystem to scan a focal spot over a target tissue area. The system may also include a walk subsystem for identifying biological structures or sites of the eye and one or more diffractive beam splitters.

[0010] In some embodiments, the pore pattern may include pores of uniform size, shape, and depth; or the pore pattern may include pores of different sizes, shapes and depths. The pore pattern may include pores having equal spacing. The pore pattern may include pores having different clearances, and the pore pattern is at least densely packed, i.e. with pores closely spaced to each other or mosaic-shaped, i.e. in the form of a regular, repeating geometric pattern, or placed at intervals.

[0011] The pore depth may be proportional to the total laser energy.

[0012] In some embodiments, the present invention may include a method of treating biological tissue by microporation to improve ocular biomechanics, comprising: the step of generating, by a laser subsystem, a therapeutic beam along an axis of influence not aligned with the patient's visual axis, during a subsurface ablative treatment to create a pore pattern that improves biomechanics; stage of control, subsystem for tracking eye movements, eye position for applying a therapeutic beam; a step of controlling, by the controller, the movement of the laser subsystem, including at least one of a tilt movement, a rotation movement and a deflection movement; and the stage of focusing, with a lens, the therapeutic beam onto the target tissue.

[0013] The method may further include the step of controlling, by a depth control subsystem, the depth of ablation or microporation on the target tissue; and a scanning stage, a scanning system communicating with an eye movement tracking subsystem and a depth control subsystem, a focal spot over the target tissue area.

[0014] Other features and advantages of the present invention are or will be apparent to one skilled in the art upon examination of the following figures and detailed description, which illustrate by way of example the principles of the present invention.

[0015] The systems, devices, and methods described in detail herein for laser ocular microporation are embodiments and should not be considered limiting. One skilled in the art will, upon examination of the following figures and detailed description, recognize other configurations, methods, features and advantages of the subject matter described herein. All such additional configurations, methods, features and advantages are intended to be within the scope of this specification, to fall within the scope of the invention as described herein, and to be protected by the appended claims. The features of the exemplary embodiments should in no way be interpreted as limiting the appended claims unless the claims specifically list those features.

BRIEF DESCRIPTION OF THE FIGURES

[0016] Details of the subject matter presented herein, both in construction and in operation, may be revealed by examination of the accompanying figures, in which like numerals refer to like parts. The components in the figures are not necessarily to scale, but rather the emphasis is on illustrating the principles of the subject matter. Further, all illustrations are intended to convey concepts, but relative sizes, shapes, and other specific features may be shown schematically rather than literally or accurately.

[0017] FIG. 1 - image of the general anatomy of the eye.

[0018] FIG. 2A-2E are images of eye shape and IOP (intraocular pressure), in accordance with some embodiments of the present invention.

[0019] FIG. 3 illustrates an example of posterior treatment zones, in accordance with some embodiments of the present invention.

[0020] FIG. 4, 5A and 5B are views of exemplary tissue being treated with microporation in accordance with some embodiments of the present invention.

[0021] FIG. 6 depicts another exemplary OCT (Optical Coherence Tomography) depth measurement method for monitoring eye movement between ablation pulses, in accordance with some embodiments of the present invention.

[0022] FIG. 7-17 illustrate exemplary laser systems in accordance with some embodiments of the present invention.

[0023] FIG. 18 illustrates an exemplary method of operating a laser system in accordance with some embodiments of the present invention.

[0024] FIG. 19-25 are exemplary flow diagrams of a laser system in accordance with some embodiments of the present invention.

[0025] FIG. 26 illustrates an exemplary operating process for forming a pore matrix, in accordance with some embodiments of the present invention.

[0026] FIG. 27 illustrates another exemplary method of operation for forming a pore matrix, in accordance with some embodiments of the present invention.

[0027] FIG. 28 and 29 illustrate exemplary FPGA (field programmable gate array) laser systems in accordance with some embodiments of the present invention.

[0028] FIG. 30 illustrates another exemplary process for operating a laser system in accordance with some embodiments of the present invention.

[0029] FIG. 31 illustrates an example laser system with a single scanning mirror, in accordance with some embodiments of the present invention.

[0030] FIG. 32 illustrates an exemplary laser system with pulse optimization capability, in accordance with some embodiments of the present invention.

[0031] FIG. 33 illustrates an exemplary OCT imaging/OCT depth control laser system in accordance with some embodiments of the present invention.

[0032] FIG. 34A and 34B are depictions of exemplary OCT depth control signals using a pig's eye, in accordance with some embodiments of the present invention.

[0033] FIG. 35A and 35B illustrate exemplary OCT measurements in accordance with some embodiments of the present invention.

[0034] FIG. 36 is a laser system including an OCT control system for dual OCT depth control (OCT/DC) and scanning OCT imaging subsystems, in accordance with some embodiments of the present invention.

[0035] FIG. 37 is a laser system including an OCT control system with integrated OCT/DC and scanning OCT imaging subsystems, in accordance with some embodiments of the present invention.

[0036] FIG. 38-42 illustrate examples of integrated and/or shared components in an OCT system, in accordance with some embodiments of the present invention.

[0037] FIG. 43A-46 is a laser system for treating scleral tissue, in which the scanning OCT system can provide both 2D cross-sectional and 3D isometric views of the treatment area, in accordance with some embodiments of the present invention.

[0038] FIG. 47-49 depict exemplary eye tracking processes in accordance with some embodiments of the present invention.

[0039] FIG. 50, 51 and 51A illustrate exemplary functions provided to a physician in accordance with some embodiments of the present invention.

[0040] FIG. 52 is a depiction of exemplary treatment zones, in accordance with some embodiments of the present invention.

[0041] FIG. 53 is a laser system including a single scanning mirror that aligns an OCT/DC system beam that is scanned across the surface of the eye to image anatomical features, in accordance with some embodiments of the present invention.

[0042] FIG. 54 is a depiction of other exemplary treatment zones, in accordance with some embodiments of the present invention.

[0043] FIG. 55 is an illustration of the approximate position of the treatment relative to Schlemm's canal and anatomical limbus, in accordance with some embodiments of the present invention.

[0044] FIG. 56 is a video camera system providing images for use in eye tracking, facial feature recognition, and treatment guidance, in accordance with some embodiments of the present invention.

[0045] FIG. 57 is an image of a mirror that can be motorized to move along multiple axes to align the viewing image field with target areas, in accordance with some embodiments of the present invention.

[0046] FIG. 58 illustrates exemplary high magnification microscopic images for inspection of a treatment area, in accordance with some embodiments of the present invention.

[0047] FIG. 59-61B is a laser system including a video camera that can image the treatment area and surrounding elements, in accordance with some embodiments of the present invention.

[0048] FIG. 62-66 depict an exemplary microcut array produced using the systems and methods of the present invention in four oblique quadrants.

[0049] FIG. 67 and 68 are depictions of treatment areas relative to the limbus, in accordance with some embodiments of the present invention.

[0050] FIG. 69 illustrates exemplary microscopic quality video camera images at high magnification for verifying a treatment area relative to the limbus, in accordance with some embodiments of the present invention.

[0051] FIG. 70 is an exemplary 3D image from a TOF (time of flight) camera, in accordance with some embodiments of the present invention.

[0052] FIG. 71 and 72 illustrate an exemplary laser system including a laser head system that provides a fixation point, in accordance with some embodiments of the present invention.

[0053] FIG. 73-85 illustrate an exemplary laser head system in accordance with some embodiments of the present invention.

[0054] FIG. 86 and 87 illustrate an exemplary laser system using diffractive beam splitters (DBS), in accordance with some embodiments of the present invention.

[0055] FIG. 88 and 89 illustrate an exemplary eye interface system in accordance with some embodiments of the present invention.

[0056] FIG. 90 illustrates an exemplary laser system with a laser head system that can be operated by a patient in a seated position, in accordance with some embodiments of the present invention.

[0057] FIG. 91-94 are depictions of a variety of shapes and positions of off-axis treatment zones around the visual axis, in accordance with some embodiments of the present invention.

[0058] FIG. 95 is an exemplary treatment pattern described as 5 critical zones at 5 different distances from the outer edge of the anatomical limbus (AL), in accordance with some embodiments of the present invention.

[0059] FIG. 96 is an example of anterior treatment zones, in accordance with some embodiments of the present invention.

[0060] FIG. 97 is another exemplary treatment pattern described as 5 critical zones at 5 different distances from the outer edge of the anatomical limbus (AL), in accordance with some embodiments of the present invention.

[0061] FIG. 98-100 are other examples of anterior treatment zones, in accordance with some embodiments of the present invention.

[0062] FIG. 101-104 are other examples of posterior treatment zones, in accordance with some embodiments of the present invention.

[0063] FIG. 105-108 are images of round or square pores or other shaped spots, in accordance with some embodiments of the present invention.

[0064] FIG. 109-111 are a variety of patterns, pulses, mosaics, shapes and sizes for both individual micropores and arrays of multiple pores, in accordance with some embodiments of the present invention.

[0065] FIG. 112-115 illustrate exemplary empirical data in accordance with some embodiments of the present invention.

[0066] FIG. 116 is an exemplary histology of micropores, in accordance with some embodiments of the present invention.

[0067] FIG. 117-119 are exemplary views of jointing images in accordance with some embodiments of the present invention.

[0068] FIG. 120 is an exemplary diagram of a hemispherical laser targeting device in accordance with some embodiments of the present invention.

[0069] FIG. 121-125 are illustrations of exemplary optical components in accordance with some embodiments of the present invention.

[0070] FIG. 126A, 126B, and 127 are an exemplary laser system configured to treat scleral tissue, comprising a single scanning mirror that integrates OCT scan control and OCT depth control functions, in accordance with some embodiments of the present invention.

[0071] FIG. 128-132 are illustrations of other exemplary optical components in accordance with some embodiments of the present invention.

[0072] FIG. 133 is a laser system including a patient table or chair, in accordance with some embodiments of the present invention.

[0073] FIG. 134 and 135 illustrate a laser system including a patient headrest, in accordance with some embodiments of the present invention.

[0074] FIG. 136-138 are illustrations of an exemplary eyelid speculum in accordance with some embodiments of the present invention.

[0075] FIG. 139A and 139B are exemplary subsurface images of tissue ablation, in accordance with some embodiments of the present invention.

DETAILED DESCRIPTION

[0076] The following figures illustrate the described invention and method of use in at least one preferred embodiment thereof, which is further explained in detail in the following description. Those skilled in the art will be able to make changes and modifications to the invention as described herein without departing from its spirit and scope. Although the present invention is capable of embodiment in a variety of different forms, the drawings show and further describe in detail a preferred embodiment of the invention, with the understanding that the present disclosure is to be considered an example of the principles of the invention and is not intended to limit the broad aspect of the invention to the illustrated embodiment. All features, elements, components, functions and steps described in relation to any embodiment presented herein are intended to be freely compatible and interchangeable with those of any other embodiment unless otherwise noted. Therefore, it should be understood that what is shown is offered for exemplary purposes only and should not be construed as limiting the scope of the present invention.

[0077] In general, the systems and methods of the present invention take into account a combination of pore filling techniques and creating pore matrices in three dimensions (3D). Pores with specific depth, size and location in the 3D tissue matrix create plastic properties in the tissue matrix. This affects the biomechanical properties of ocular tissue, such as scleral tissue, and makes it more pliable. As you know, connective tissues that contain elastin are “pliable” and must have elasticity. In fact, the sclera has a natural viscoelasticity.

[0078] The systems, devices and methods of the present invention may include laser microporation for ocular tissue rejuvenation, for example, in connection with connective tissue aging, and connective tissue rejuvenation through scleral rejuvenation. The systems, devices and methods disclosed herein restore physiological functions of the eye, including restoration of physiological accommodation or physiological pseudo-accommodation due to natural physiological and biomechanical phenomena associated with natural accommodation of the eye.

[0079] In some embodiments, the system may include a display that is included in the laser module to view the tissue area (clinician display), a control and protection system (see also below) that includes a laser power supply, electronics and motion control platform, as well as secure direct interface to the central terminal. The system may also include a movable table; a translation table to position the laser, optical system, and scanner in a specific area, wherein the laser and optical system may include a 3-μm module and a beamforming optical system; depth control system to prevent ablation from being too deep; eye tracking module; suction and laminarization facilities for operator safety. The system may include beam deflection synchronized with eye tracking to produce multiple micropores. Other components and features may include, for example, a video camera unit for surveillance. The central terminal may be an intelligent movable central terminal, which may include an operator display for control and safety, power distribution to different modules, water cooling of the laser system, an optional foot pedal, communication interface with external devices, troubleshooting facilities, upgrade facilities and other features, and mains power for a wide choice of power supplies, when used in different countries.

[0080] As mentioned above, in some embodiments, the described systems, methods and devices of the invention may include the creation of a finite element model of the accommodative mechanism, which includes seven main paths of the zonular ligaments and three sections of the ciliary muscle, calibration and validation of the model through comparison with previously published experimental measurements of ciliary muscle and lens motion during accommodation, and use of the model to investigate the influence of zonular anatomy and ciliary muscle architecture on normal accommodative function. The model may include the geometry of the lens and extralenticular structures and new accommodation driven by zonular fiber tension and muscle contraction based on numerical simulations.

[0081] In some embodiments, the described systems, methods and devices of the invention may include a method of changing the biomechanical properties of biological tissue using a matrix formation complex consisting of perforations on said tissue, in which the configuration is based on a mathematical algorithm. The change in biomechanical properties of biological tissue depends on the elasticity, shock absorption, resilience, mechanical damping, compliance, stiffness, rigidity, configuration, orientation, deformation, mobility and/or volume of said tissue. Matrix formations of perforations can allow a non-monotonic dependence of the deformation on the force in the said tissue, with the isotropic elastic constant varying within a certain range within the medium. Each matrix formation can form a linear algebraic relationship between row length and column length, with each perforation of said fabric having continuous linear vector spaces with derivatives of order up to N. Where N is an infinite number. The complex may form a total surface area, with each perforation having a proportional relationship to the total surface area of said tissue. The complex can also be positioned to provide a balance of forces, stress and strain and to reduce the shear effect between the matrix formations and the perforation. Each perforation may be a tissue removed volume that forms a dotted pattern on said fabric, the removed volume preferably having a cylindrical shape. The matrix formation consists of tiles with or without repeating patterns, and the tiles are Euclidean, non-Euclidean, regular, semi-regular, hyperbolic, parabolic, spherical or elliptical and any combination thereof. Each perforation may have a linear connection with other perforations within each matrix formation and matrix complex separately. Tessellations directly or indirectly relate to atomic bonds between tissues with stress and shear deformations by calculating a mathematical array of coordinate vectors between perforations. Atomic coupling is the predicted relationship of the volume removed by each perforation with the change in biomechanical properties, observed as an element of a mathematical algorithm. The predicted relationship of volume removed may be mutually exclusive. The tilings can be a square, which can be subdivided into a tiling of equiangular circles or polygons up to a derivative of order n. In some embodiments, a mathematical algorithm uses the coefficient Φ or Phi to find the most effective placement of matrices to change the biomechanical properties of said tissue. The coefficient Φ or Phi can be 1.618 (4 significant figures), representing any fraction of the set of contraction vectors in the grid that have the shortest length compared to the length of all other vectors. In some embodiments, the mathematical relationship of claim 1 includes a nonlinear hyperbolic relationship between planes of biological tissue and at any boundary or separation of adjacent tissues, planes, and spaces within and without the matrix.

[0082] Various embodiments of the laser system are described in US Application No. 15/942,513 (filed 3/31/2018), International Application No. PCT/US18/25608 (filed 3/31/2018), Taiwan Application No. 108111355 (filed 3/ 29/2019), US Application No. 11/376,969 (filed 15/03/2006), US Application No. 11/850,407 (filed 05/09/2007), US Application No. 11/938,489 (filed 12/11/2007), US Application No. 12/958,037 (filed 01/12/2010), US Application No. 13/342,441 (filed 03/01/2012), US Application No. 13/709,890 (filed 10/12/2012), US Application No. 14/ 526,426 (filed 10/28/2014), US Application No. 14/861,142 (filed 09/22/2015), US Application No. 15/365,556 (filed 11/30/2016), US Application No. 16/599,096 (filed 10/ 10/2019), US Application No. 14/213,492 (filed 14/03/2014), US Application No. 16/258,378 (filed 01/25/2019), US Application No. 15/638,308 (filed 06/29/2017), US Application No. 16/702,470 (filed 03/12/2019), and US Application No. 15/638,346 (filed 06/29/2017), which are incorporated herein in their entirety.

[0083] The influence of ocular rigidity and ocular biomechanics on the pathogenesis of age-related presobyopia is an important aspect of the present application. The descriptions in this application are intended to modify the structural stiffness of the connective tissues of the eye, namely, the sclera of the eye, using the systems and methods of the present invention.

[0084] INTRODUCTION

[0085] To better understand the present invention, ocular accommodation, ocular rigidity, ocular biomechanics, and presbyopia are briefly described below. In general, the loss of accommodative ability in presbyopia is caused by many lenticular as well as extralenticular and physiological factors that are dependent on aging. Increased rigidity of the eye with age creates a stressed-strained state of the mentioned ocular structures and can worsen accommodative ability. Overall, the ability to understand the influence of ocular biomechanics, ocular stiffness, and decreased accommodation may build new paradigms for ophthalmic treatment. Treatment of the sclera may serve an important function in the treatment of biomechanical defects in presbyopia by providing at least one means of addressing the actual etiology of the clinical manifestation of the deterioration of accommodation found with age. The effects of accommodation deterioration affect the physiological functions of the eye, including, but not limited to, visual accommodation, aqueous humor hydrodynamics, vitreous hydrodynamics, and pulsatile ocular blood flow. The use of the systems and methods of the present invention to restore greater flexibility in the biomechanical properties of the connective tissue of the eye is a safe procedure and can restore accommodative ability in aging adult patients.

[0086] Accommodation has traditionally been described as the ability of the eye's lens to dynamically change optical power to adjust to different distances. Recently, accommodation has come to be more fully described as a complex biomechanical system containing both lenticular and extralenticular components. These components act simultaneously with many anatomical and physiological structures in the organ of vision to organize not only the visual manifestations that occur during accommodation, but also physiological functions integral to the organ of vision, for example, the hydrodynamics of aqueous humor and ocular biotransport.

[0087] Biomechanics is the science of the origin and actions of forces in biological systems. Biomechanics has not been used sufficiently in ophthalmology. This biomechanical paradigm deserves application to the anatomical connective tissues of the complex organ of vision. The ability to understand the biomechanics of the eye as it relates to accommodation can provide a more complete picture of the role that this primary motor system plays in the function of the visual organ as a whole, while maintaining optical quality for visual tasks.

[0088] The eye is a biomechanical structure, a complex sensory organ that contains complex muscular, drainage and fluid mechanisms that perform the functions of vision and biotransport of the eye. The accommodative system is the main driving system in the organ of vision, supporting many physiological and visual functions in the eye. The physiological role of the accommodative system is to move aqueous humor, blood, nutrients, oxygen, carbon dioxide and other cells throughout the organ of vision. In addition, the accommodative system acts as a neuroreflex circuit that responds to optical information received through the cornea and lens to finely tune the focusing power throughout the visual range, and is essentially the "heart" of the visual organ.

[0089] FIG. 1 depicts the general anatomy of the eye, which will be useful in describing the present application. Fig. 2A-2E depict the eye shape and IOP.

[0090] Additionally, biomechanics (including biomechanics of the eye), its decisive role in the pathophysiology of the organ of vision, physiological accommodation in the eye, scleral surgery, the decisive role of the ciliary muscle in many functions of the organ of vision, including accommodation and hydrodynamics of aqueous humor (outflow/inflow, regulation of pH and IOP) are described in detail in US Application No. 15/942,513, Taiwan Application No. 108111355 and International Application No. PCT/US18/25608, which are incorporated herein in their entirety.

[0091] US Application No. 15/942,513, Taiwan Application No. 108111355 and International Application No. PCT/US18/25608 further describe laser scleral rejuvenation (for example, in Fig. 1A-1-1A-7 and their corresponding descriptions in US Application No. 15/942,513), the role of eye rigidity (including the “stiffness” of the external ocular structures of the eye, including the sclera and cornea) in interfering with the accommodative apparatus. These descriptions are included in this application in their entirety.

[0092] The systems and methods of the present invention take into account a combination of pore filling techniques and creating pore matrices in three dimensions. Pores with special depth, size and location in the 3D tissue matrix create plastic properties in the tissue matrix. This affects the biomechanical properties of ocular tissue, such as scleral tissue, and makes it more pliable. In a 3D matrix scaffold, multiple pores can be created in the form of a matrix structure or mesh(s). Various microporation characteristics can be supported. These characteristics may include volume, depth, density, and so on.

[0093] It should be noted that although the examples in this application describe the treatment of scleral tissue, the system of the invention can also be made to treat other ocular tissues and other tissues.

[0094] FIG. 4, 5A and 5B depict microporation and sclera and examples of tissue being treated in the form of microporation.

[0095] FIG. 62-66 depict an exemplary microcut array produced using the systems and methods of the present invention in four oblique quadrants.

[0096] FIG. 2G in US Application No. 15/942,513 provides an exemplary graphical representation of restored ocular elasticity, reduced scleral drag forces, increased total ciliary ganglion forces, and restored dynamic accommodation after treatment.

[0097] The shape of the matrix (matrix array) can be composed of a variety of sizes, quantities, shapes, geometries, distributions and areas. The matrix shape can be regular or irregular. In some embodiments, it may be advantageous to create a circular, tetrahedral, or centered hexagonal shape. To create a centered hexagon in the matrix, a series of “pores” must be formed with a specific composition, depth, and location relative to other “pores” in the matrix and the tissue located in the space between the pores in the matrix. To obtain the full effect of the matrix as a whole, across all dimensions of the circle or polygon, a significant depth (eg, at least 85%) of the tissue is also necessary. The matrix inside the fabric contains a circle or polygon. The central angle of a circle or polygon remains the same, regardless of the number of points within the matrix. This is an important component of the systems and methods of the present invention because they take advantage of a circular or polygonal matrix that includes the particular relationship and pattern properties of the pores in the matrix or grid.

[0098] The central angle of a circle or polygon is the angle subtended at the center of the circle or polygon by one of its sides. Regardless of the number of sides of a circle or polygon, the central angle of the circle or polygon remains the same.

[0099] Modern implant devices in the sclera receive a mechanical effect during accommodation. No current devices or methods take into account the influence of "pores" or the formation of a matrix of pores with a centered hexagon or circle or polygon in 3D tissue. The systems and methods of the present invention can create a matrix of pores in biological tissue to allow changes in the biomechanical properties of the tissue itself to exert a mechanical influence on the biological functions of the eye. In some embodiments, the primary requirement for the "pores" in the matrix may be circular or polygonal in shape.

[00100] A circle or polygon can, by definition, have any number of sides, and the area, perimeter, and dimensions of the circle or polygon in 3 dimensions can be mathematically measured. In the case of a regular circle or polygon, the central angle is the angle formed at the center of the circle or polygon by any two adjacent vertices of the circle or polygon. If we draw lines from any two adjacent vertices to the center, they would form a central angle. When a circle or polygon is regular, all central angles are equal. It doesn't matter which side is chosen. All central angles will add up to 360° (a full circle), so the value of the central angle is equal to the value of 360 divided by the number of sides. Or given by the formula:

Central angle=360/n degrees, where n is equal to the number of sides.

[00101] Thus, the magnitude of the central angle depends only on the number of sides, and not on the size of the circle or polygon.

[00102] In the context of the present application, circles or polygons are not limited to "regular" or "irregular". Circles or polygons are one of the most comprehensive shapes in geometry. From a simple triangle to squares, rectangles, trapezoids, dodecagons and shapes with many sides.

[00103] Additional descriptions of circles or polygons (including types and properties) are also described, for example, in US application No. 15/942,513 and are included in this application.

[00104] Some embodiments in the present application demonstrate a plurality of circles or polygons in a matrix. Everyone can influence the result of CT (coherence tomography). They may contain enough pores to make a "centered hexagon" possible. The possibility of a square/diamond shape is obvious. The following formula applies to it:

, where: s is the length of any side,

which simplifies to:

, where: s is the length of any side,

[00105] The "time" described in this application may have a special outline, shape, structure and depth. The pore passes through a 3-dimensional tissue through which gases, liquids or microscopic particles can pass. The pores can have any size, shape and can be spaced or mosaic. It should be noted that although some examples in this application refer to a pore in the form of a micropore, the term micropore is not intended to be limiting and may be used interchangeably with the term pore. The "pores" created herein may be circular cylinders or square cylinders to inhibit the formation of scar tissue.

[00106] The creation of pores in the matrix, changing the biomechanical properties of the connective tissue, is a characteristic feature of the present invention. The creation of various sizes of micropores, which are of any size, shape, spaced or mosaic, is also a characteristic feature of the present invention.

[00107] The "pore matrix" of the present application can be used to control wound healing. In some embodiments, this may include filling the pores to inhibit the formation of scar tissue.

[00108] In some embodiments, the pores may have a depth of at least 5%-95% of the depth of the connective tissue and contribute to the creation of an intended change in biomechanical properties. They can have a special structure, location in the matrix and, preferably, mathematically precise characteristics of a circle or polygon. In three-dimensional (3D) space, a planned change in the relative arrangement of pores in a matrix or network is a distinctive characteristic of the present invention (see, for example, FIGS. 1F(a)-1F(c) and the corresponding descriptions thereof in US application 15/942,513). The matrix or lattice may comprise a 2-dimensional (2D) Bravais lattice, a 3D Bravais lattice, or a non-Bravais lattice mesh.

[00109] FIG. 1B-1E in US application 15/942,513 depicts an exemplary pore matrix. The pore matrices in this application are the basic building block from which all continuous matrices can be built. There are many different approaches to arranging pores on connective tissue in a space in which each point will have an identical "atmosphere". That is, each point will be surrounded by the same set of points as any other point, and therefore all points will be indistinguishable from each other. The "pore matrix" can be distinguished by the relationship between the angles between the sides of the "unit pore" and the distance between the pores and the "unit pore". The "elementary pore" is the "first pore created" and, when repeated at regular intervals in three dimensions, will form the matrix grid observed at the surface throughout the depth of the tissue. The “grid parameter” is equal to the length between two points at the corners of the pore. Each of the different mesh parameters is labeled a, b, and c. If two sides are equal, for example in a tetragonal mesh, then the lengths of the two mesh parameters are denoted a and c, with b being omitted. Angles are designated by the Greek letters α, β, and γ such that an angle with a particular Greek letter does not rest on an axis with its equivalent Latin letter. For example, α is the angle subtended between the b and c axes.

[00110] The hexagonal mesh structure may have two angles equal to 90°, with another angle (γ) equal to 120°. For this purpose, the two sides containing the 120° angle must be equal (a=b), and the third side (c) is at an angle of 90° to the other sides and may have a different length.

[00111] The matrix is defined as a specific, repeating arrangement of pores throughout the target connective tissue, such as the sclera. Structure refers to the internal arrangement of the pores rather than the appearance or surface of the matrix. However, they cannot be completely independent, since the appearance of the pore matrix often depends on the internal location. There may be a specific distance between each of the pores in the designated matrix to match the mathematical characteristics and properties of a circle or polygon. The created pores can also interact with the tissue remaining within the matrix, which changes the biomechanical properties of the matrix.

[00112] The spatial relative positions of pores in the matrix can have geometric and mathematical meanings.

[00113] Pore volume fraction, together with bulk density or spatial density, can also have biomechanical, functional, physical, geometric and mathematical meanings, as illustrated in at least FIG. 98 and 99.

[00114] In some embodiments, the laser microporation system of the present invention may generally include at least the following parameters: 1) laser radiation with an integrated fluence of from about 1-3 μJoules/cm ² to, approximately 2 Joules/ ^cm2 ; ≥15.0 J/cm ² on tissue; ≥25.0 J/ ^cm2 on tissue; laser power 0.1-2.5 W to expand treatment options, 2900 nm±200 nm; near the maximum absorption of water in the mid-IR range of the spectrum; The repetition rate and duration of the laser pulses can be adjusted using preset combinations in the range of 100-1000 Hz and 50-225 µs. The range given can be considered a minimum range for ≥15.0 J/cm ² on tissue; ≥25.0 J/ ^cm2 on tissue; to expand treatment options; 2) irradiation using one or more laser pulses or a sequence of pulses having a duration of from about 1 ns to about 20 μs. Some embodiments can, in principle, have a power of up to 50 W; 3) the preferred thermal damage zone (TDZ) range may be less than 20 µm in some embodiments or 20-50 µm in some embodiments; 4) it is also possible to include pulse width parameters from 10 µm to 600 µm.

[00115] Pulse energy of 1-3 microjoules can be provided by femtosecond lasers and picosecond lasers with high pulse repetition rates, for example, from 500 Hz (Zeiss) to several kilohertz (Optimedica). The advantages of femtosecond lasers and picosecond lasers are small spot sizes (eg, 20 micrometers and up to 50 micrometers) and energy densities are high to minimize thermal damage to surrounding tissue. All of the above can lead to effective rejuvenation of the sclera. In some embodiments, lasers can create substantially circular and conical-shaped pores in the sclera with a depth of up to perforation of the sclera and thermal damage from about 25 μm to about 90 μm. The pore depth can be controlled by the pulse energy and the number of pulses. Pore diameter can be altered by motion artifacts and/or defocus. Thermal damage may be related to the number of pulses. The pulse energy can be increased, which can lead to a reduction in the number of pulses and, therefore, to a further reduction in thermal damage. Increasing the pulse energy can also reduce irradiation time. An exemplary design of the described laser system may provide a combination of laser parameters optimized to reduce the thermal damage zone while maintaining treatment time and thereby providing high speed for optimizing treatment time, and a flow chart representing the relationship between the thermal damage zone and the pulse (see for example, Fig. 1E-2 and Fig. 1G-1-1G-4 and their corresponding descriptions in US application 15/942,513).

[00116] In some embodiments, the pulse duration and pulse width can be changed according to the adaptive OCT data, reducing to fine tuning to a target preset depth.

[00117] Nanosecond lasers for microporation or microtunneling, in some embodiments, may include the following specifications: wavelengths in the UV-visible-short-wave infrared regions, typically 350-355 nm; 520-532 nm; 1030-1064 nm; pulse duration 0.1-500 nanoseconds, with passive (or active Q-switching); pulse repetition rates from 10 Hz to 100 kHz; peak energies 0.01-10 milliJoules; maximum peak powers over 10 Megawatts; a beam propagating freely or along a fiber.

[00118] Scleral rejuvenation can be performed using femtosecond or picosecond lasers and the erbium yttrium aluminum garnet (Er:YAG) laser. Other preferred embodiments may include laser energy parameters ideally suited for the 2.94 μm Er:YAG laser, or other laser capabilities with preferred Er:YAG laser energies, or other lasers with different wavelengths with high water absorption .

[00119] MilliJoule energies and energy densities for different spot/pore sizes/shapes may include:

[00120] A spot size of 50 micrometers: a) 0.5 mJoules per pulse is 25 Joules/cm ² ; b) 1.0 mJoules per pulse is 50 Joules/ ^cm2 (possibly with an Er:YAG laser); 3) 2.0 mJoules per pulse is 100 Joules/ ^cm2 .

[00121] Spot size 100 micrometers (all these characteristics are possible with an Er:YAG laser): a) 2.0 mJoules per pulse is 25 Joules/cm ² ; b) 5.0 mJoules per pulse is 62.5 Joules/ ^cm2 ; c) 9.0 mJoules per pulse is 112.5 Joules/cm ² .

[00122] A spot size of 200 micrometers: a) 2.0 mJoules per pulse is 6.8 Joules/cm ² ; b) 9.0 mJoules per pulse is 28.6 Joules/ ^cm2 ; c) 20.0 mJoules per pulse is 63.7 Joules/cm ² .

[00123] 300 micrometer spot size: a) 9.0 mJoules per pulse is 12.8 Joules/cm ² possible with an Er:YAG laser; b) 20.0 mJoules per pulse is 28 Joules/ ^cm2 , possible with a DPM-25/30/40/X laser; c) 30.0 mJoules per pulse is 42.8 Joules/ ^cm2 ; d) 40.0 mJoules per pulse is 57 Joules/ ^cm2 ; e) 50.0 mJoules per pulse is 71 Joules/cm ² .

[00124] 400 micrometer spot size: a) 20 mJoules per pulse is 16 Joules/ ^cm2 , with DPM-25/30/40/50/X laser; b) 30 mJoules per pulse is 24 Joules/ ^cm2 ; c) 40 mJoules per pulse is 32 Joules/ ^cm2 ; d) 50 mJoules per pulse is 40 Joules/ ^cm2 .

[00125] It should be noted that round or square pores or other pore shapes are also possible. See, for example, FIG. 105, 106, 107 and 108. These pores intersecting 3-dimensional connective tissues to a specific desired depth can result in a plurality of cylinders with a variety of shapes, including, but not limited to, circular cylinders, square cylinders, polygonal cylinders or cylinders with a conically varying cross-section. There is evidence that proves that the capabilities for penetration depth, distribution, differentiation and migration of pores depend on the size, shape and geometry of the pores of the framework. Since both viscoelasticity and permeability depend on the porosity, orientation, size, distribution and interconnectivity of the pores, there are some pore sizes that may be superior to other sizes, depending on the clinical purpose of pore formation. The system has the ability to flexibly change the optical design to obtain a variety of pore and matrix parameters. Additionally, the pore bottoms may have conical or flat bottom surfaces depending on the optical design. The additional sides of the pores can form different shapes (e.g., cylinders or cones) depending on the optical design. In some embodiments, as shown in at least FIG. 86 and 87, the system can use diffractive beam splitters (DBS) to change the shape and size of the beam, hence the pores.

[00126] In the case of femto- and picosecond lasers, some available wavelengths include IR wavelength 1030 nm; green wavelength 512 nm and UV wavelength 343 nm. Peak energies can vary from a few nanoJoules (at megahertz pulse repetition rate) to 5-50 microJoules and up to several hundred microJoules in the picosecond region. Femtosecond lasers have pulse durations of 100–900 femtoseconds; peak energies from several nanoJoules to several hundred microJoules, pulse repetition rates from 500 Hz to several Megahertz (the Ziemer LOV Z laser can be used; Ziemer AG, Switzerland: with peak energies equal to several nanoJoules and pulse repetition rates above 5 MHz, with very high quality/density of the beam, focusing into a small spot with a size of 50 micrometers or less).

[00127] The best femtosecond lasers have such high beam quality that, in some embodiments, femtosecond lasers can microtunnel the sclera into micropores using erbium lasers.

[00128] In the context of the present application, nuclear pores can be defined as holes in the nuclear envelope, with a diameter of about 10 nm, through which molecules (for example, nuclear proteins synthesized in the cytoplasm) and RNA must pass (see, for example, Fig. 1H and its corresponding descriptions in US application 15/942,513). The pores are formed by large protein accumulations. Perforations in the nuclear membrane can allow selected materials to flow in and out.

[00129] The formula for porosity in biological tissue can be given as: X(Xa, t)=qT”(X”,t)=x*+u”(X”,t), where qT” is continuously differentiable , an invertible mapping from 0 to a, and u” is the cY component of the displacement. The invertible mapping gradient for the a-component (F”) and its Jacobian (J”) can be specified as J”=detF”, where J” must be strictly positive to prevent each continuum from interpenetrating. The right Cauchy-Green tensor V and its inverse transformation, the Piol strain tensor B for the solid component can be given as V= , B= , where the superscript t denotes transposition.

[00130] Current theoretical and experimental data suggest that creating or maintaining pores in connective tissue accomplishes three important goals. First, the transport of nutrients into cells in the connective tissue matrix. Secondly, the removal of cellular waste. Third, the tissue fluid exerts a force on the wall of the sclera, or the outer layer of the eye, and the force is large enough to be felt by the cells. It is believed that this process is the main mechanism of mechanotransduction in connective tissue, the way the membrane of the eye perceives the mechanical load to which it is exposed and responds to an increase in intraocular pressure. Understanding ocular mechanotransduction is fundamental to understanding how to treat ocular hypertension, glaucoma, and myopia. In addition, the porosity or spatial density of a material or tissue changes its physical and biomechanical properties, such as ductility, elasticity, shear force, tension, stretch, capillary leakage, deformation and shape change). Because the ciliary muscles of accommodation are the primary force agonists in both force and fluid dynamics in the eye, the biomechanics of the ocular outer layer is critical in order to support or inhibit the generation of forces for essential ocular functions, including, but not limited to, restoration. tissues, mechanics of accommodation, regulation of intraocular pressure and hydrodynamics within the eye. Since progressive age-related crosslinking affects the biomechanical stiffness or shock-absorbing properties of the connective tissues of the eye, controlling the porosity or volumetric density of aged ocular tissues may provide an organic solution to restore or rejuvenate the dynamic functions within the eye, without the use of implantable devices or drugs. Changing the biomechanical properties of tissue through microporation can also improve the biomechanical response of tissues to stress and rejuvenate the tissues.

[00131] Inferring the physical properties of a porous medium (e.g., hydraulic conductivity, thermal conductivity, water retention curve) from parameters describing the structure of the medium (e.g., porosity, pore size distribution, specific surface area, bulk density, or spatial pore density) remains a challenge for scientists in the case of soft tissue or bone porosity and their permeability. The system may include the ability to utilize multiple patterns, pulses (see, for example, FIGS. 109, 110 and 111), mosaics, shapes (not necessarily limited to round, rectangular, square) and sizes of both individual micropores and arrays of multiple pores . The pore depth tends to increase with increasing energy, and the pore width is changed not by applying multiple pulses, but by using a diffraction beam splitter (eg, DBS) to obtain a given pore shape, size, and pattern. To test the assumption that porous media have a self-similar scaling characteristic, the fractal dimensions of various features were determined experimentally in vitro for the eyeball of animals and humans and in vivo for human eyes. As shown in FIG. 112, 113, 114 and 115, the mentioned empirical data provide the expected evidence that increasing the density or spatial density (volumetric density) of pores enhances the biomechanical effects of plasticity, capillary fluid leakage and deformation, resulting in improved visual acuity attributed to increased accommodative forces .

[00132] The system may include the ability to provide ablation depth control and warning/control capability that can reliably determine the depth of tissue ablation and ultimately the interface between the sclera and the choroid and effectively prevent ablation beyond the sclera, the system's ergonomic and clinical suitability point of view, as well as for use by the physician, high reliability and controls that guarantee patient safety and reproducibility of the procedure, the ability to scan with an increased working distance for high-speed execution of the procedure.

[00133] In some embodiments, systems of the present invention may use a pulsed solid-state 2.94 μm diode-pumped Q-switched Er:YAG laser (DPSS) in conjunction with a hand-held probe to ablate pores in the sclera to modify plasticity scleral area, in the treatment of presbyopia and other eye dysfunctions.

[00134] SYSTEM ARCHITECTURE

[00135] In some embodiments, the laser system may be configured to target ocular tissue, such as scleral tissue, to present the physician with an augmented reality image of the treatment protocol, a high-resolution video camera image of the patient's eye, proposed micropore treatment sites, and pictures treatments placed around the limbus, vascular bypass and eye tracking, all presented through a graphical user interface (GUI) and artificial intelligence (AI) to facilitate optimal treatment. As shown in FIG. 61A, 61B, 50, 51, 51A and 63 and further described below, the system may offer the physician the ability to shift the treatment location on the patient's eye in the video camera view. The system can allow the physician to rotate the treatment image and view the change. The system may allow the physician to select individual micropores in the treatment pattern that cannot be formed based on the physician's observed image of the vascular structure of the patient's eye. After treatment, the system can provide the clinician with an image that confirms the target micropore depth, also with the ability to view 2D and 3D OCT images (obtained by optical coherence tomography) to verify the correct pores for each treatment protocol. The system can then offer the clinician the opportunity to re-treat individual pores, if necessary, in a second treatment step. The imaging system can collect multiple biometric data and then reconstruct an accurate 3D model of the actual anatomy of each treatment matrix, including each microporation, using OCT and augmented reality (AR) technology. The system can allow the clinician or user to accurately visualize where relevant anatomical structures are located on and below the surface of the eye, through the target tissue, as well as pulse-induced morphological changes in the tissue and within the micropore. The video camera system may be capable of generating an accurate, high-resolution image that accurately measures and clearly visualizes 3D images of the target tissue micropore matrix before and after treatment. Using biometric data measured along the x, y, and z axes, the system may be able to combine treatment layers of augmented reality scenarios for multiple possible treatment impacts. This multimedia platform allows the doctor to make informed treatment decisions and make changes taking into account the individual anatomy of each person.

[00136] FIG. 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and 17 represent exemplary embodiments of the laser system of the present invention. In some embodiments, the laser system may be configured to treat scleral tissue, in which the system may create micropores through multiple pulses of laser light to limit tissue damage, control the final depth of the micropore, and reduce treatment time for each micropore based on thickness variations scleral tissue.

[00137] FIG. 7 shows an exemplary laser system without a mirror galvanometer system, a 5-axis head, and a separate Z-axis movement. FIG. 8 shows an exemplary laser system with laser head control without a mirror galvanometer system, a 5-axis head, and separate Z-axis movement. FIG. 9 shows an exemplary laser system with a headrest, Z-axis movement of the laser head. Fig. 10 shows an exemplary laser system with galvanometric mirrors, a separate visible laser and OCT depth control optical fibers (OCT/DC fibers) aligned on the axis of the treatment laser, and a physician monitoring system for treatment. Fig. 11 depicts an exemplary laser system that combines an OCT/DC system and a visible laser on a single fiber and shared intermediate lenses with a treatment laser and a control and display system. Fig. 12 shows an exemplary laser system that is substantially similar to the system in FIG. 11, but includes an autofocus (AF) lens and a dual-function OCT system. Fig. 13 depicts an exemplary laser system that is substantially similar to the system in FIG. 12, but does not include a mirror galvanometer system, a 5-axis head, or a separate Z-axis movement. FIG. 14 depicts an exemplary laser system that is substantially similar to the system in FIG. 13, but does not contain galvanometric mirrors, contains a 6th axis autofocus lens. Fig. 16 shows an exemplary laser system with an OCT control system that controls depth using an included visible laser. Fig. 15 and 17 represent an exemplary biofeedback (OCT and/or video camera) controlled laser system.

[00138] As shown in FIG. 36, in some embodiments, the laser system may include an OCT control system for dual OCT/DC and scanning OCT subsystems.

[00139] As shown in FIG. 37, in some embodiments, the laser system may include an OCT control system combined with OCT/DC imaging and scanning OCT subsystems.

[00140] As shown in FIG. 84, in some embodiments, the laser system may include a laser treatment laser subsystem in combination with a fiber optic OCT/DC subsystem. This combination can be the central component of a 5-axis motion control device that moves to target the laser beam.

[00141] FIG. 77 and 80A-83 depict an exemplary laser treatment system operating on an off-axis treatment principle.

[00142] Embodiments and features of the laser system are further described in detail in US Application No. 15/942,513, Taiwan Application No. 108111355 and International Application No. PCT/US18/25608, which are incorporated herein in their entirety. For example, as shown in FIG. 6 of US Application No. 15/942,513, the laser system may include a laser, a laser fiber, a laser control system, a control system, and a beam control system. In another example, in FIG. 7 US Application No. 15/942,513, the laser system may also include a depth control subsystem, galvanometric mirrors, a video camera (for example, a CCD camera or a suitable video camera), a microscope for visual observation, a focusing subsystem, and an optical beam delivery system. Fig. 7-1 of US Application No. 15/942,513 depicts an exemplary laser system including on-axis and off-axis imaging capabilities and a depth sensing subsystem. Other exemplary embodiments include a laser system with dichroic optics (see Fig. 3A of US Application No. 15/942,513), a laser system with an eye tracking subsystem located after the galvanometric mirrors (see Fig. 3A of US Application No. 15/942,513) .

[00143] In some embodiments, the present invention may include a method of providing microporation treatment to improve biomechanics. The method may include the step of generating, with a laser, a therapeutic beam along an axis of influence not aligned with the visual axis of the patient, in the process of subsurface laser therapeutic treatment in order to create an ordered set of micropores, which improves biomechanics; the step of controlling, by means of a controller electrically coupled with the laser, the dose of the therapeutic beam to irradiate the target tissue; stage of focusing, with a lens, a therapeutic beam on the target tissue; control stage, through automatic off-axis (laser treatment does not coincide with the pupil or line of sight) tracking and measurement of subsurface anatomical structures and a bypass system, the position of the eye for delivering the therapeutic beam; and wherein the micropore matrix structure has at least one of a radial pattern, a spiral pattern, a phyllotactic pattern, or an asymmetric pattern.

[00144] In some embodiments, the present invention may include a laser eye surgery and therapeutic treatment system that can provide laser therapy to the eye to partially relieve the stress and strain that occurs in the increasingly stiff sclera with age by imparting elasticity to the sclera. tissue using a matrix of micropores formed by the laser in the scleral tissue, either at intervals or in mosaics. The system can promote changes in the biomechanical properties of the sclera, reduce compression of subconsciously reacting connective tissue, fascial tissue and biophysiological structures of the eye, as well as restore impaired accommodative ability and hydrodynamic function of the eye. The system can reduce tension and improve the biomechanical elasticity of the ciliary muscle, accommodative complex, aqueous humor outflow and key physiological anatomical functions that lie directly beneath the scleral tissue. Age-related cross-linking, which causes increased biomechanical stiffness, can be directly or indirectly affected by creating pores that unravel collagen fibrils in the hierarchical tissue structure, creating more flexible and elastic connective tissue after treatment. For example, by using microporation to increase biomechanical elasticity in scleral tissue, it is possible to create a greater force applied to the lens to perform its accommodative function. Fig. 116 represents an approximate histology of micropores. Histological sections stained with hematoxylin and eosin (H and E) (the main tissue stains used in histology) for the laser only (L) and laser plus collagen (L+C) groups at different time points show that in all eyes, inflammatory infiltration and coagulative necrosis (arrows) occurred after 1 month, and these reactions resolved over time. After 9 months, no inflammatory cells or necrosis were observed, and the scleral micropores were still open and filled with fibroblasts. The * denotes scleral micropores. TN stands for Tenon's capsule tissue. The original magnification was 100x. The scale bar is 200 µm.

[00145] In the following, a detailed description of embodiments of the laser system is provided.

[00146] Sequence, performance and safety

[00147] In some embodiments, as shown in FIG. 19 and 20, 21, 22, 23, 24 and 25, the laser system may be configured to treat scleral tissue by performing a sequence of actions that may include pre-acquired patient and surgical data through post-treatment OCT control images (OCT -images).

[00148] In some embodiments, the laser system may be configured to treat scleral tissue by performing an individually selected sequence of actions to form multiple micropores in multiple quadrants in both eyes. Fig. 26, 19 and 20 and 27 represent exemplary processes for forming a pore array.

[00149] In some embodiments, as shown in FIG. 28 and 29, the laser system may include an FPGA (Field Programmable Gate Array) architecture to control the timing of critical processes, safety processes, and image/data processing.

[00150] In some embodiments, the laser system may include a facility for entering a pre-treatment plan to reduce the duration of treatment, for example, by creating an ini.file to load and configure the system before the patient and clinician with the system are ready to begin treatment.

[00151] In some embodiments, the laser system may include means for receiving treatment planning input data based on a variety of sources, for example, previous patient medical records, previous scleral treatment protocols, physician preferences, adjusted treatment optimizations, and scans acquired by the system prior to treatment). As shown in FIG. 28 and 29, the system's acquisition of pre-treatment scanned images may include the use of a video camera, eye tracking, feature recognition, OCT images for the purpose of developing a treatment plan or determining the patient's suitability for scleral treatment.

[00152] In some embodiments, the laser system may include a remote treatment agent. In an example, the system can be controlled by a physician remotely, with a trained technician present at the site of treatment, through a remote GUI session over an Internet connection with or without a Bluetooth device. The physician is located remotely and logs in via a secure Internet connection using a virtual secure network (VPN) and an encrypted password. The control video camera(s) on the laser head, aimed at the patient, are linked by video connection to the technician and physician. The site technician positions the patient and inserts the eyelid speculum (see Figs. 136-138). The technician can enter an individual password from the doctor. The clinician can perform all normal functions, but the clinician may need to turn on the laser feature first. The technician at the treatment site performs normal activation and presses the pedal according to the doctor's commands. The doctor is equipped with an emergency switch. In some embodiments, a technician at the treatment site may perform all of the treatment and the physician views the images remotely.

[00153] In some embodiments, the laser system may include means for remotely monitoring system operation, transferring data files, transferring protocol files, downloading new software, uploading critical treatment protocols to the host system, performing remote maintenance, and calibrations. In some embodiments, these functions may be performed with or without on-site support and through an electronic interface with off-site services.

[00154] OCT/Depth Control (DC)

[00155] FIG. 30, 6 and 18 represent an exemplary method of operation of embodiments of a laser system with biofeedback control.

[00156] In some embodiments, the system may use a single stationary beam from the OCT system to control depth that is collinear with the treatment laser.

[00157] In some embodiments, the depth of a micropore can be estimated using inter-pulse OCT measurements to determine the current depth based on determining the surface at the bottom of each micropore and the undersurface of the sclera. It is also possible to determine the upper surface of the sclera and use it to determine the pore depth. If necessary, the depth of the last pulse and the residual thickness of the sclera are changed and, then, the optimal pulse length (duration) for the next pulse is determined. The above can be done automatically and in real time.

[00158] In some embodiments, as shown in FIG. 27, the adaptive depth adjustment process may generate initial long pulses that can be used to reduce the total number of pulses and the total time required to perform a micropore to a target depth size and reduce the likelihood of the patient's eye moving during the execution of a single micropore. Shortened pulses can be used to ensure that the system is “guided” to the target depth of the target micropore.

[00159] The process shown in FIG. 27 may include a condition for the case where the OCT readout is less than expected, indicating movement of the eye during pore creation. This process is repeated for each pulse to calculate the optimal width for the next pulse. In some embodiments, the pore depth can be compared to an expected range of values, and if the depth is significantly less than expected, it may indicate that the eye has moved, or the system has moved or wobbled, changing the laser alignment. The system can quickly provide an indication of eye movement before the next pulse begins, providing a safety indicator and generating an error transmitted to the system controller. If the movement is small, then the ablation process for the next pore can be continued, but if the movement is determined to be large enough to be considered significant, then the pore formation process can be stopped or suspended until the eye tracking system resets the laser alignment to It is safe to continue the pore formation process. In some embodiments, the system may be capable of combining each pulse of each pore to begin microporation again in the correct pore cell after treatment is re-initiated.

[00160] As shown in FIG. 16, in some embodiments, the laser system may be configured to treat scleral tissue using a depth controlled OCT control system containing a visible laser (also referred to as a pilot beam).

[00161] As shown in FIG. 31, in some embodiments, the laser system may be configured to treat scleral tissue by having a single scanning mirror that aligns the OCT beam that is scanned across the ocular surface to provide imaging of micropores at any point during treatment.

[00162] In some embodiments, the system may use a single stationary beam from the OCT depth control system that is colinear with the treatment laser.

[00163] In some embodiments, as shown in FIG. 109, it can be shown that the pore depth is proportional to the total laser energy, regardless of the number of pulses used to obtain the pore depth.

[00164] In some embodiments, as shown in FIG. 110 and 111, it can be shown that the pore diameter is not affected to any significant extent by the number of pulses used to obtain the pore depth.

[00165] In some embodiments, as shown in FIG. 32, a system (e.g., shown in at least FIGS. 7, 8, 17, and 30) may include the ability to optimize pulse parameters to provide an optical pulse depth between pulses that allows the volume of tissue removal per pulse to be calculated for preliminary planning and achieving target final depth and volume removal. The system can combine OCT and laser beams in one beam, allowing observation of an individual micropore along with depth control. The system may include the ability to use the DC signals of the OCT system to determine the focus position of the treatment laser to obtain optimal micropore characteristics. The system may include an OCT system that is collinear with the ablation laser and serves to identify the air interface with the patient's sclera. The treatment laser can be set to the same focal point on the Z axis as the OCT laser. On this basis, the "focus" of the entire system can be adjusted, and feedback from the OCT system can control that the laser focus is on the patient's sclera.

[00166] In some embodiments, as shown in at least FIGS. 27, the micropore depth can be measured inside the micropore by the DC subsystem of the OCT tilt system; in this case, the measurement can be performed with one beam, collinear to the therapeutic beam, having a slightly smaller beam diameter. The reflected signal can be processed by a signal processing algorithm to determine the depth before and after the laser pulses to ensure the micropore depth, and the system can cancel the next laser pulse if necessary. In some embodiments, the energy of the depth pulse can be calculated directly through the outer layers of the eye and used to assign the energy (width) of the next pulse to complete the process at the desired depth in a minimum number of pulses.

[00167] In some embodiments, depth measurements can be performed on each micropore to ensure ablation does not exceed the limits of the treatment plan and does not exceed the minimum residual scleral thickness for safety purposes, and determine the residual depth of the micropore to be ablated. In some embodiments, as shown in FIG. 33 (and FIGS. 7, 8, 17, and 30), the system may include OCT imaging/OCT depth monitoring using data collected for micropore ablation depth per pulse and total depth provided for final inspection OCT method and verification of the treatment protocol. The system may include an OCT system collinear with the treatment laser that can measure and record values after each pulse before the next pulse during microporation. This is possible by adjusting the OCT beam to a diameter equal to or smaller than the micropore (pore) from the treatment laser, resulting in a clean and reliable signal that allows for rapid use without multiple measurements. A switchable OCT optical system (fixed or variable focal length) can reduce the OCT/DC beam diameter to a value smaller than the micropore diameter so that the OCT system can verify that the treatment laser is focused and the micropore size will then be calculated. The OCT depth sensor can provide a beam diameter small enough to look down into the micropore depth and provide data and analysis between treatment pulses. In some embodiments, the system may use a signal to control the movement of the eye between pulses faster than the applied tracking of eye movement between micropores.

[00168] In some embodiments, as shown in FIG. 17, 18 and 33, the laser system can be configured to treat scleral tissue, and OCT measurement can be performed without scanning the OCT beam, by adjusting the OCT beam diameter to a value less than the diameter of the micropore to view the micropore in depth, without the appearance of false readings or noise in the signal, providing reliable depth measurements for pore depth and residual scleral wall.

[00169] In some embodiments, as shown in FIG. 7, the laser system may be configured to treat scleral tissue, and the visible targeting laser beam may be aligned with the axis of the treatment laser along the OCT depth control beam so that the optimal spot size of the visible targeting laser can be made approximately equal to the diameter of the beam. therapeutic laser and micropores even though said lasers have significantly different wavelengths and focusing distances when projected through optical systems.

[00170] As shown in FIG. 17 and 30, in some embodiments, the laser system may include biofeedback based on video camera images and colorimetric analysis or OCT data, in connection with or without an illumination system, to stop the laser treatment (for safety reasons) or change width of the next pulse to be emitted.

[00171] Linearized tissue depth output from OCT requires extensive data analysis to determine pore depth. The system may include a method for integrating the sum reflection allowing depth determination after an individual pulse. In some embodiments, the method may include the ability to measure micropore depth in real time and between pulses for precise depth control. The depth determination algorithm may vary for many different tissue types. Fig. 34A and 34B depict examples of the OCT depth control signal for a pig eye. As shown in FIG. 32, the system may provide the ability to optimize the parameters of the next pulse to provide an optimal pulse depth. The system can detect pulses to obtain a pre-planned target depth and volume of tissue removal in each pore. As shown in FIG. 35A and 35B, OCT measurement of scleral thickness prior to treatment may enable control of an algorithm to calculate the optimal treatment dose.

[00172] OCT scanner (2D and 3D)

[00173] In some embodiments, as shown in FIG. 8, the laser system may be configured to treat scleral tissue, and a second OCT scanning sensor may be positioned on the axis of the treatment laser to provide a high-quality scan image of the treatment area to provide pre- and post-testing of the effectiveness of the treatment. This can be accomplished using a moving mirror, alternating with the normal application of a treatment laser.

[00174] In some embodiments, an OCT depth monitoring and scanning OCT imaging system may use separate sensors optimized for each task, but share OCT system components to reduce complexity, size, and cost. Figures 38-41 and 42 represent examples of integrated and/or shared components within an OCT system.

[00175] In some embodiments, the OCT scanning function can be positioned collinear with the treatment beam by using a dichroic mirror along the central optical axis, which allows the treatment laser beam to pass the fixed mirror of the OCT scanner to allow more specific scans of the treatment area.

[00176] As shown in FIG. 43A, 43B, 44, 45, and 46, in some embodiments, the laser system may be configured to treat scleral tissue, and the OCT scanning system may produce both 2D cross-sections and 3D isometric images of the treatment area before, during, and after treatment. The system may also provide depth and diameter measurements (or pore cross-sectional shape, ie square or rectangle) for each micropore.

[00177] In some embodiments, the system may also include and provide a function for differentiating layers of fabric from the top surface to the bottom surfaces for all underlying surfaces, using advanced enhanced structural differentiation and digital fabric coloring algorithms.

[00178] TRACKING AND CONTROL

[00179] Eye tracking

[00180] In some operations, micropore formation may be disrupted, for example, if the patient moves the eye, and therefore eye movement tracking is necessary, as described herein. In addition, the system may include a video camera to measure eye movement speed. In some embodiments, the present invention may include a process as shown in FIG. 47, for the case where the velocity is so low that only minor movement can be predicted within the duration of the ablation pulse train. Fig. 48 and 49 also show an example eye tracking process.

[00181] Feature Recognition

[00182] In some embodiments, the laser system may be configured to treat scleral tissue and may employ an eye tracking system to ensure that the laser continues to be aimed at the correct treatment location on the eye during microsurgery, to correct for movement of the eye or other mechanical systems. The system can recognize and track multiple anatomical features of the eye, including the pupil, iris, limbus, and/or vascular (blood vessel) features for off-axis treatment interventions. Feature recognition can provide information for tracking eye movement, vascular bypass (de-selecting individual pore locations), and treatment targeting, for example, to first place the treatment area on the correct anatomical features, as well as to bypass anatomical structures, so-called non-target treatment areas.

[00183] In some embodiments, the laser system may include feature tracking elements for tracking eye movement. Features monitored may include, for example, the pupil, iris, limbus, and vascular structures. The laser system can accept input data from TOF camera, video camera, OCT/DC system, 3D OCT scanner.

[00184] In some embodiments, the system may include recognizing features (which may include facial features, e.g., eyebrows, nose, eyelids) from a TOF camera and a method for applying treatments to correct positions and bypasses. The system may include the ability to position eye features to avoid laser exposure, position the laser for repeated treatment and reposition to target tissue while bypassing non-targeted tissue, and provide fixation points and treatment laser angles. , bypassing blood vessels, positioning therapeutic effects and an AI (artificial intelligence) system. The system can combine multiple coordinate systems from different feature analysis subprocesses (e.g., deep learning, AI) to extract and accumulate relative locations (e.g., pupil, iris, vessels, and other features). See also the exemplary process in FIG. 49 and 50. The system may include an augmented reality overlay to enhance anatomical biometrics and enhance learning (AI-like). Fig. 51 and 51A show exemplary feature recognition images of an anatomical limbus extracted by AI analysis and displayed as an overlay on a video camera image.

[00185] In some embodiments, the system may include recognizing features of subsurface ocular anatomy (eg, ciliary muscles, Schlemm's canal) from OCT images that can be used in positioning a treatment area on the eye. Fig. 54 presents exemplary OCT images (depth control or scanned) for determining the location of the anatomical limbus and Schlemm's canal for the purpose of automating treatment positioning. Images provide OCT biometry and surface anatomy regarding real-time pore placement in the treatment area and individual micropores. Fig. 55 represents the approximate position of the treatment effect relative to Schlemm's canal and the anatomical limbus.

[00186] In some embodiments, the present invention may include a process of summing individual pore volumes for a treatment area as a pore volume fraction and modifying/optimizing the remainder or re-treating. The process may assume a pore shape based on beam characteristics using, but not limited to, OCT depth for an OCT/DC system or an OCT scan, and then calculate the pore volume for each completed pore. This value may be effective after the canceled pore bypass or vascular bypass algorithm removes specific pores from the treatment plan. When this process is performed in real time, modifications to subsequent pore ablation can improve performance to target. Calculations from this process can also be performed prior to any re-exposure to help plan optimal treatment.

[00187] In some embodiments, eye tracking based on feature recognition may provide eye tracking to obtain a treatment home position for repeated treatment or continuous treatment of individual pores.

[00188] Eye tracking video camera

[00189] In some embodiments, the eye tracking system may include a high-definition, high frame rate video camera and appropriate lighting. This backlight can provide adequate illumination of the patient's face/eye area for the clinician and the procedure in general, while the backlight does not interfere with feature tracking (eye tracking) due to introducing artificial reflections on the patient's eye, and proper feature tracking (iris, choroid) is achieved. structure, pilot beam).

[00190] In some embodiments, as shown in FIG. 56, the video camera system can create images for use in eye tracking, facial recognition, treatment guidance, visual images for users to interact with, in connection with AI and augmented reality graphical user interface (GUI) functions.

[00191] In some embodiments, the video camera system may include a movable mirror to modify the field of view manually or automatically. As shown in FIG. 57, the mirror can be electrically driven along several axes in order to combine the field of the observed image with the impact zone.

[00192] In some embodiments, the video camera system may include a video camera with an optical lens system to create high quality, high magnification images, similar to a surgical microscope. Fig. 58 shows exemplary high magnification microscopic images to view the treatment area.

[00193] In some embodiments, as shown in FIG. 59, 60, 61A and 61B, the laser system may include a video camera that can image the treatment area and surrounding features to determine the correct location of the treatment area relative to the limbus and at the correct angular position relative to the visual axis. In some embodiments, these capabilities may also be manually changed by a physician using a GUI.

[00194] Backlight

[00195] Due to the fact that various features in the eye, as well as the pilot beam, can be more accurately detected when using a light source with specified illumination wavelengths (for example, RGB (red/blue/green) and IR (infrared)), the system includes a special lighting system containing mechanics, light sources, electronics, as well as software-implemented connection, evaluation and algorithms. Because the eye-tracking video camera provides the ability to read its individual pixels, it can provide more accurate feature tracking, which is absolutely necessary from a security perspective.

[00196] In some embodiments, the laser system may include an illumination system that can optimize measurements and images for the system's various video cameras and improve facial and eye feature recognition for tracking and positioning. The illumination system may contain lighting components with multiple wavelengths, and the illumination may be modulated based on an active sensor or a camera sensor. The system uses color (RGB) and IR illumination sources. Fig. 75 and 74 are exemplary bottom views of a laser head system including video camera(s), illumination sources, imaging lenses, display, and visible laser alignment crosshairs. The lens assembly may vary depending on the actual optical design used. The display can provide fixation of the eye and points of view.

[00197] Modulation of color (RGB) and IR source illumination can be synchronized with the camera and sensors to recognize features.

[00198] In some embodiments, the laser system may include a backlight and a camera system to optimize eye tracking performance. In some embodiments, the system may emit white light (eg, an RGB LED) every 33 ms and capture a frame for visualization on the surgeon/assistant's screen (to provide a real-time video feed of the patient). Between these 33-ms periods, the system can use different lights in separate colors to detect different features. The duration of individual light pulses can be in the range of 10 ms. The iris may be best detected in blue/IR light. Vascular signs as well as the pilot fascicle may be best detected in red/green light. The pilot beam can also be modulated in brightness, that is, the system can detect and distinguish the pilot beam from the vessel features (since both are red). This will provide the system with important information about the actual state of the complete motion system relative to the patient's eye. In addition, the system can read individual CCD cells of an eye tracking video camera, and the system can select the RGB channels of each cell. It also improves GUI images and augmented reality image-based features.

[00199] Vascular bypass

[00200] In some embodiments, the eye tracking system can visualize the treatment area and can either interpret the images or allow the clinician to review the images and determine locations of micropores that should be avoided, such as during vascular bypass. In some embodiments, micropores that need to be excluded can be “labeled for laser exclusion” either by a physician or through automated image analysis. Fig. 61A-64 are exemplary images in which pores may be marked for exclusion for the purpose of bypassing anatomical structures, such as bypassing a blood vessel. Fig. 65 is an exemplary image to confirm the pore depth, and FIG. 66 provides additional examples.

[00201] In some embodiments, the eye tracking system can analyze the video camera images, recognize vascular features, and determine which pores should be automatically removed from the treatment plan.

[00202] In some embodiments, FIG. 67 and 68 on the GUI represent treatment zones relative to the limbus and provide a diagram on the GUI to assist in targeting treatment. Fig. 69 and 58 show exemplary microscopic video camera images at high magnification to view the position of treatment areas relative to the limbus.

[00203] In some embodiments, the system may include a high-resolution video camera to allow inspection similar to an optical microscope. As described above in FIG. 57, the system may include a movable mirror for designating a target area with manual or automatic zoom and positioning controls based on feature positions in the video camera and TOF camera images.

[00204] FIG. 61A and 61B depict a process, in accordance with some embodiments of the present invention, for positioning treatment and bypassing anatomical structures, which process may be performed manually, semi-automatically or fully automatically, using AI, feature detection, video camera images and OCT scans and using static or dynamic images of the eye obtained by a camera.

[00205] Alignment with face

[00206] In some embodiments, as shown in FIG. 75 and 74, the laser system may include a TOF (time of flight) camera to position the laser head over the patient and detect key facial features. This system can work in conjunction with a pattern (crosshair) projected by a visible laser onto the patient's face as a known feature for position analysis. A TOF camera can be a time-of-flight camera that emits a simulated laser beam and measures the time to reflection. From this information, a 3D image can be constructed as shown in FIG. 70. The TOF camera facilitates locating the face before the eye tracking camera can focus on the eyes and before the OCT/DC beam can focus on the sclera.

[00207] In some embodiments, a TOF camera may provide image data that indicates the eyebrows or nose, a portion of the facial structure that obscures the view of the eye. The angles of fixation and treatment can then be adjusted for the individual patient so that features do not obscure visibility.

[00208] In some embodiments, a TOF camera or image analysis may determine the accessibility of the treatment area and verify that the eyelid and eyelid speculum are cleared from the path of the laser beam.

[00209] Guidance - positioning of therapeutic effects

[00210] In some embodiments, as shown in FIG. 53, the laser system may include a single scanning mirror that aligns the OCT/DC beam that is scanned across the surface of the eye to image anatomical features such as the limbal margin, Schlemm's canal, ciliary muscles, and retinal margin to support treatment positioning and bypass of anatomical structures.

[00211] In some embodiments, the laser system may be configured to treat scleral tissue, and the size, shape, and microporation pattern of the treatment area may be modified based on the treatment plan for the microporation patterns. For example, FIG. J and K of US Application No. 15/942,513 represent an exemplary golden spiral formed from individual treatment patterns, and FIG. L US Application No. 15/942,513 presents an exemplary treatment protocol for 4 quadrants.

[00212] In some embodiments, the laser system may be configured to target ocular tissue and the center of the treatment zone may be modified based on the microporation pattern to be ablated. In some cases, the center of the pattern may be the center of the pupil (or limbus) for golden spiral ablation in multiple treatment segments.

[00213] In some embodiments, the laser system may include means for modifying the positioning of pores in the treatment matrix and normal zones based on the shape of the patient's eye to optimally capture the patient's anatomical features and positional differences. This can be done based on the pretreatment plan and a priori information about the shape of the eye or based on OCT scan data over the extended treatment area.

[00214] Pore volume and pore volume fraction

[00215] Treatment Results - Tissue Removal

[00216] In some embodiments, OCT data and pore shape can be used to calculate tissue volume removal by zone, after bypass exclusions, after pore ablation, based on volume analysis from actual OCT data, or based on a typical pore for the applied optical configuration. Volume analysis will include pore volume fraction as well as spatial density or bulk density. Additional analysis of porosity and porosity of the 3-dimensional framework is a characteristic feature in the present system. A re-treatment plan can be developed for a second treatment or modified during the current treatment to ensure target volume removal, target porosity and maximum porosity.

[00217] In some embodiments, exceptions to the treatment plan can be used to create a new treatment plan that restores tissue removal to provide the same treatment effectiveness.

[00218] The ocular tissue remaining after pore formation can be used in a FMEA (Failure Modes and Effects Assessment) model to evaluate improvements in accommodation, ocular hydrodynamics, and IOP reduction to inform retreatment plans and modify them to improve effectiveness. AI can be used for notification and immediate future treatment.

[00219] In some embodiments, as shown in FIG. 98, the pore volume fraction can be changed to obtain the desired or improved results. There was some evidence suggesting that increasing density and porosity doubled the effectiveness of treatment in some cases, as shown in FIG. 112-115. Porosity or pore volume fraction is defined as the ratio of the total pore volume to the apparent volume of the tissue. The porosity, spatial density, and porosity of the 3D scaffold can be used to create a new retreatment plan. In the case where the pore volume is the size of the void created by the therapeutic effect, and between the pores there is remaining tissue that maintains continuity. In this case, spatial density or volumetric density refers to how densely or closely packed the pores are. This affects both porosity and density, which affects the porosity of a fabric, a property that is the ratio of the volume of pores in a fabric to its total volume. Fabric porosity depends on several factors, including (1) packing density, (2) the breadth of the pore size distribution (the ratio of polydispersity to monodispersity), (3) the shape of the pores, and (4) the interconnectivity of the pores within the matrix. Porosity refers to the proportion of voids or total void space within a tissue wall volume and serves as a useful indicator of the ability to individualize treatment patterns according to the varying thicknesses and biomechanical properties of individual tissues, when age is a dependent variable, to develop a treatment algorithm. Porosity, P (%), of a fabric is calculated using the following equation, in which M denotes the mass per unit area (g/ ^m2 ) of the fabric, h denotes the thickness (µm) of the fabric, and ρ denotes the relative density of the pore matrix (g/ ^cm3 ). The term packing factor provides a relative measure of the overall porosity of a tissue structure. It is calculated by dividing the tissue density by the relative density of the pore matrix and can theoretically have values ranging from 0 (all pores and no continuities) to 1 (no pores and only continuities). Values closer to zero indicate higher porosity. Pore density is calculated by dividing M, the mass per unit area of the fabric, by h, its thickness, and is expressed in units of g/ ^cm3 . P=100 [1-M/1000∙h∙ρ]. The void ratio is also an important metric for optimizing treatment and retreatment, which systems analysis and AI can track in 3D tissue scaffolds between pulses and between pores. The void ratio is the ratio of the volume of voids (pores) in the fabric to the volume of solid tissue remaining at the matrix site in the target tissue.

[00220] e=Vv/Vs

[00221] Where:

e=Void ratio;

Vv=Void Volume (m ³ or cu.ft.);

Vs=Volume of continuities (m ³ or cu.ft.).

[00222] Thus, the void ratio is equal to a ratio, which can be greater than 1. It can also be expressed as a fraction. The void ratio and porosity differ only in the denominator. The void ratio is equal to the ratio of voids to continuities, and porosity is equal to the ratio of voids to the total volume.

[00223] In some embodiments, the laser system may optimize the effectiveness of treatment or re-treatment based on artificial intelligence (AI) programs that collect treatment data for multiple patients, analyze results based on, but are not limited to, sizes, shapes, depths, patterns, pore positions, treated areas, eye shapes. The AI program may be supported by an integrated or stand-alone finite element model (FEM) of the eye, which is described in detail in US Applications 15/638,346 and 16/702,470, incorporated herein. This result can be used to modify the treatment plan automatically or according to the doctor's recommendations.

[00224] LASER HEAD SYSTEM

[00225] In some embodiments, the laser system may be configured to treat scleral tissue off-axis or in an area of the eye that is not aligned with the visual axis or directed away from the pupil of the eye where the gaze position is located. The fixation point on the user display (see, for example, FIG. 75) provides a fixation point to guide and fixate the patient's gaze on a separate axis that is not the visual axis or the pupillary axis for the duration of one treatment area, which can be performed obliquely. quadrant, from the opposite (180 degrees) side. As shown, for example, in FIG. 71 and 72, the laser system may include a laser head system that may provide a fixation point. The laser head can move vertically up and down or rotate over the patient.

[00226] In some embodiments, the laser system may be configured to target ocular tissue, and the laser beam may be oriented off-axis (eg, but above the visual axis of the eye). The laser delivers its treatment effect generally perpendicular or substantially perpendicular to the surface of the eye at the center of the treatment zone. The eye may be positioned at a fixation point that may not be aligned with the axis of treatment, and the eye may also be placed in an extreme position to target the treatment area of ocular tissue, which may be eccentric to the visual axis. In some embodiments, the angle of the laser beam relative to the visual axis may be 51°, or substantially about 51°.

[00227] FIG. 73-85 show an exemplary laser head system of the laser system of the present invention. As shown in FIG. 73, in some embodiments, the laser head may include a housing structure, laser aiming motors and encoders, a laser subsystem, a laser cooling heat exchanger, video camera(s) for use in at least eye tracking, and illumination sources. Fig. 74 and 75 further show a bottom view of the laser head, showing a visible laser alignment crosshair, a display for use with at least eye fixation, and a TOF camera.

[00228] In some embodiments, as shown in FIG. 76, the laser head may include a hose for pumping out treatment waste, which is described in detail herein.

[00229] The laser head and laser subsystem allow flexible movements. For example, FIG. 77-79 represent exemplary movements of the laser head system in a system without a mirror galvanometer system. Fig. 78 (the middle 7800 is a top view) and 79 represent the tilt, swivel and deflection movements of the laser head. Rotation is performed around a vertical axis. The tilt is performed around a horizontal axis. The deflection is performed around a horizontal axis located at 90 degrees to the tilt axis. Fig. 82 and 83 represent approximate focusing positions and angular orientation of the laser beam relative to the top of the eye during off-axis therapeutic interventions, wherein the axis of exposure is shifted relative to the axis of fixation of the eye's gaze. Rotation and translation (x-axis) of the laser head generally provides x- and y-axis motion along with deflection motion. Applying deflection to control x and y motion introduces a change in focus position and, in doing so, requires correction in the z axis by lifting the entire head or, in some cases, perhaps by autofocusing the focusing lens, as shown for example in FIG. 13 and 14.

[00230] FIG. 73, 81, 80A and 80B represent exemplary laser head positions for each quadrant of the eye near facial features.

[00231] In some embodiments, the laser system may use an eye tracking system to assess the patient's ability to hold the eye sufficiently still prior to treatment. The clinician can change the position (angle) of fixation or use an eye interface system to help the patient keep the eye in a stationary position. Fig. 88 and 89 depict an exemplary eye interface system of the present invention.

[00232] The eye fixation system may store basic eye image data to allow repositioning of the treatment area at a later date to complete treatment or complement previous treatments (re-treatment).

[00233] The point of fixation or direction of gaze can be assigned individually relative to the treatment laser beam for each quadrant and for different patients with different facial structures.

[00234] As shown in FIG. 75, the laser system may include a patient display that may also be used to communicate other information to the patient, including instructions and information.

[00235] In some embodiments, the laser system may be configured to treat scleral tissue, wherein the treatment laser beam and associated fixation point and fixation axis are coupled and adjusted for both eyes and quadrants to target facial structures (e.g., nose) . Fig. 73 and 77 represent exemplary laser head positions for each quadrant around facial features. In some embodiments, the treatment laser beam and the visual axis (fixation axis) may form a substantially fixed angle and be 180 degrees opposite to the vertical axis. Some patients may have extreme facial features in some quadrants that may require a reduction in this angle. The system may allow the axis of influence to be slightly non-perpendicular to the scleral surface.

[00236] Example of treatment and fixation angle: (1) The laser treatment angle may, but is not always, 28°. The system aims to “pulse the eye” with the laser at an angle as close to 90° as possible, while taking into account the boundaries of facial geometry (e.g. nose, eyebrows). (2) The fixation point is displayed on the screen and accordingly moves relative to the position of the quadrant currently being treated to bring the patient's "direction of gaze/gaze" into the correct position for pulsing the eye at an angle as close to 90° as possible. (3) The angle between the treatment effect and the fixation point is not always the same. Quadrant-specific fixation points (Q) on the display for each treatment position in the quadrant. The angle depends on the distance to the patient, which in turn depends on the current quadrant being treated. Fig. 81 is an exemplary table containing details of eye position in each quadrant and impact angle (eg, as shown in FIG. 73).

[00237] In some embodiments, the laser system may include a laser head that may have other orientations suitable for multiple patient positions and room configurations. Fig. 90 shows an exemplary laser system with a laser head system in a case where the patient may be in a sitting position.

[00238] Optimization of the speed, direction of motion, and focal distance between individual micropores within the treatment zone can be achieved by one or more elements in the motion control system. To optimize the effectiveness of treatment, the order in which pores are created within the treatment area can be controlled, and an exemplary order is explained in FIG. 91.

[00239] As shown in FIG. 38-41 and 42, in some embodiments, the laser system may include various combinations of OCT system components shared and integrated to simplify, improve reliability, and reduce cost.

[00240] LASER SYSTEM

[00241] The eye is made of connective tissue. Age-related defects in humans are associated with a trend of accelerating deterioration with aging. Cross-links arise from certain classes of metabolic products, such as advanced glycation end products (AGEs). In connective tissue such as the eye, AGEs are caused by the cross-linking of collagen fibrils. Crosslinks increase the biomechanical stiffness of connective tissue. Crosslinking in the sclera causes rigidity of the eye and is associated with loss of visual accommodation, as well as the development of other age-related eye diseases (eg, intraocular hypertension, AMD (age-related macular degeneration), and some forms of cataracts). Disruption of cross-links or “unlinking” of collagen fibrils can reverse the course of AGE and the negative effects of age. Some embodiments of the system may include laser scleral microporation (LSM), which aims to open up scleral microfibrils by creating a matrix of micropores across physiologically important, critical areas to reduce age-related biomechanical stiffness. The main goal is to create the ability for the ciliary muscle complex to move the lens more freely and more effectively restore the operating range of focus (EROF) of the eye in order to see at various distances, especially close and intermediate, which are lost with age. LSM treatment may also slightly improve long-distance focusing for patients with latent farsightedness who have lost some of their distance vision due to loss of accommodative ability. Fig. 117, 118 and 119 show images of approximate jointing.

[00242] In some embodiments, the laser therapy process of the present invention may target specific treatment zones that are located in specific physiological regions encompassing anatomical structures in the eye that are critical to ocular function. Although examples of 3 or 5 physiological zones are described herein, other numbers of physiological zones for treatment may also be considered.

[00243] In some embodiments, the treatment pattern may be described as 5 critical zones at 5 different distances from the outer edge of the anatomical limbus (AL), not in contact with any components or associated corneal tissue, as shown in the figures from FIGS. 2B-1 to FIG. 2B-3 of US Application No. 15/942,513, and FIG. 95 and 97.

[00244] In some embodiments, the laser therapy process of the present invention may provide different laser angles for different quadrants. For example, the laser may be focused relative to the AT (anatomical) limbus. Fig. 80A, 80B, 73 and 81 provide examples of 4 quadrant positions on each eye for treatment. Fig. 91, 92, 93 and 94 represent a variety of off-axis treatment zone shapes and positions around the visual axis. The system can modify the size of the treatment zone or the pattern of pores within the treatment zone on a site-specific basis based on the diameter of the patient's eyeball. The diameter of the eyeball can be measured conventionally before treatment or can be the height of the treatment zone, derived by analyzing OCT scan data, which extends from a point above the AT limb to the limit of the planned treatment zone to ensure that the treatment does not extend beyond the safe zones excluding the retina. See example treatment zones in Fig. 52 and 54.

[00245] Treatment area and patterns

[00246] In some embodiments, the laser system may be configured to treat scleral tissue, and the laser beam may be positioned to provide a full circumferential or 360-degree effect around the eye. Fig. 94 and 93 represent an approximate full circumferential or 360 degree golden spiral formed by individual treatment patterns. The system can change viewing points and multiple treatment zones to ablate a predefined circumferential pattern or spiral.

[00247] In some embodiments, the laser system may be configured to target anterior segment zones (AS zones) of the sclera to produce a desired micropore pattern to produce the desired results. Fig. 96, 67, 68, 97, 98, 99 and 100 provide examples of anterior treatment zones that can be performed using the system of the present invention.

[00248] In some embodiments, the laser system may be configured to target posterior segment zones (PS zones) of the sclera to produce a desired micropore pattern to produce desired results. Fig. 3, 101, 102, 103, 104 and 105 represent examples of posterior treatment zones, for example 5 zones, that can be implemented using the system of the present invention. Fig. 101 describes exemplary critical areas of the posterior segment. Fig. 102 and 103 represent exemplary posterior segment critical areas on the eye. As shown in FIG. 103, an exemplary posterior segment of the eye includes T, temporal, and N, nasal. The figure shows the optic nerve (a) with its central vessels and surrounding meningeal membranes. Its center is located at a distance of about 3 mm towards the nose and 1 mm below the posterior pole of the eyeball. Around it are the posterior short ciliary arteries and nerves. The approximate position of the macula is at x. Along the horizontal meridian, which divides the eye in two, are the posterior long ciliary arteries and nerves (b). The exits of the four vorticose veins are shown, one for each quadrant (c). Curvilinear oblique inputs of the superior oblique (d) and inferior oblique (e) muscles are shown. The cut ends of the four rectus muscles are in f.

[00249] Treatment within a limited treatment area can modify micropores in specific areas. The diamond shape is a simple example pattern, others can more confidently support the optimization of pores in each zone.

[00250] As shown in FIG. 91 and 104, treatment within a limited treatment zone can modify micropores in specific areas. Micropore patterns and the order of micropore formation can be changed as the treatment area changes and for specific areas to optimize treatment effectiveness. For example, FIG. 92 represents one order of micropore formation from 1st to 48th. In fig. 93 and 94 provide further examples of multiple shapes and patterns of treatment zones at multiple locations around the visual axis.

[00251] In some embodiments, the laser system may be configured to treat scleral stiffness of the eye. The system can unravel the age-increasing cross-links of fibrils and microfibrils that occur in connective tissues (FIGS. 5 and 4 represent examples of microporation-treated tissue), including connective tissue in the sclera. The system can reduce biomechanical stiffness by breaking the bonds. Fig. 118 and 119 represent exemplary ablation of individual pores by a therapeutic laser beam, and de-sealing occurs as the rupture of bonds in microfibrils and fibrils. It relaxes the tissue or allows the tissue to become more elastic, i.e. reduces biomechanical stiffness.

[00252] In some embodiments, the micropore matrix structure may be a spiral pattern of an Archimedean spiral, a Cornu spiral, a parabolic spiral, a hyperbolic spiral, a rod spiral, a logarithmic spiral, a Fibonacci spiral, a golden spiral, a Bravais lattice, a non-Bravais lattice mesh, or their combinations.

[00253] In some embodiments, the micropore matrix structure may have a controlled asymmetry that is at least partially rotational asymmetry about the center of the matrix structure. At least partial rotational asymmetry may extend to at least 51 percent of the micropores of the matrix structure. At least partial rotational asymmetry may extend to at least 20 micropores of the matrix structure. In some embodiments, the micropore matrix structure has random asymmetry.

[00254] In some embodiments, the micropore matrix structure has a controlled symmetry that is at least partially rotational symmetry about the center of the matrix structure. At least partial rotational symmetry may extend to at least 51 percent of the micropores of the matrix structure. At least partial rotational symmetry may extend to at least 20 micropores of the matrix structure. In some embodiments, the micropore matrix structure may have random symmetry.

[00255] In some embodiments, the matrix structure contains several clockwise helices and several counterclockwise helices. The number of clockwise spirals and the number of counterclockwise spirals may be Fibonacci numbers or multiples of Fibonacci numbers, or may be in a ratio that converges on the golden ratio.

[00256] Laser system and optical configurations

[00257] In some embodiments, the laser system may be configured to provide a treatment laser within a laser head that can direct the beam in a goniometric manner with movement up to 5 degrees.

[00258] In all cases, the precise angular position and focus position of the treatment laser can be achieved by combining the movement of several elements. In some embodiments, these elements that may be contained in the laser head system are described above and shown in at least FIGS. 78, 73, 80A, 80B and 77.

[00259] As shown in FIG. 10, in some embodiments, the laser system may use galvanometric mirrors, a separate visible laser, and OCT depth control fibers (OCT/DC systems) that are aligned on the axis of the treatment laser and pass through the same focusing optical system, controls the OCT/DC system and laser operations and provides illumination and a video camera with direct line of sight for the physician.

[00260] As shown in FIG. 11, in some embodiments, the laser system may use galvanometric mirrors, a visible laser, and an OCT/DC system that are aligned via a single fiber on the axis of the treatment laser, and pass through the same focusing optical system that controls the operation of the OCT/DC system. and laser operations and providing illumination and a video camera with direct visibility for the doctor.

[00261] As shown in FIG. 12, in some embodiments, the laser system of FIG. 11 may also include an OCT scanning system.

[00262] As shown in FIG. 13, in some embodiments, a laser system similar to that shown in FIG. 12, can work without galvanometric mirrors, 5-axis laser head and separate Z-axis movement.

[00263] As shown in FIG. 14, in some embodiments, a laser system similar to that shown in FIG. 13 may have a configuration that does not include galvanometric mirrors but does include a 6th axis autofocus (AF) lens.

[00264] As shown in FIG. 120, in some embodiments, the laser system may include a laser targeting device circuitry for a hemispherical treatment, with the hemispherical concept being the basic concept for moving the laser head along a hemispherical surface and continuously aiming at the center of the treatment area. The hemisphere is moved along the x, y and z axes to position the center of the hemisphere on the patient's eye, with or without the use of galvanometric mirrors in the design. In its simplest form, a motion control system can move the treatment laser around the patient's eye on the surface of a hemisphere. The hemisphere can be positioned along the x, y and z axes to align with the position of the initial micropore in the treatment protocol and then moved one step along the hemisphere to the position of the next micropore. The x, y and z axes may not change during treatment in one quadrant, but may need to change for another quadrant.

[00265] As shown in FIG. 121-125, and 128-132, in some embodiments, the laser system may be configured to treat scleral tissue by having multiple optical components to modify the size, focal point of the beam (and therefore the pore), with adjustments made manually or automatically under system control. For example, as seen in FIG. 121-125, components may include a CaF ₂ lens, a sapphire combiner, a sapphire hemispherical lens, collimate, focus and defocus the optical beam. The sapphire combiner provides a means for aligning the OCT and visible laser beams into an orientation collinear with the therapy beam. A cylindrical lens made of CaF ₂ serves to round the beam. In fig. 128-132, a pair of lenses is used to change the diameter of the beam in the object plane on the eye instead of the rigidly built-in lens element shown in the previous figures.

[00266] As shown in FIG. 84 and 85, in some embodiments, the laser system may be configured to treat scleral tissue by having multiple optical components contained in a lightweight assembly including another optical system, a diffractive beam splitter (DBS), motors, encoders, laser, laser excitation device, OCT fiber clamp and cooling means.

[00267] In some embodiments, the laser system may include a scanning mirror that can serve as a redundant axis of motion to very quickly make adjustments to the alignment of the beam to the eye. Fig. 126A and 126B present some of the specifications and capabilities of the scanning mirror.

[00268] As shown in FIG. 126A, 126B, and 127, in some embodiments, the laser system may be configured to treat scleral tissue by having a single scanning mirror that combines OCT scanning and OCT depth control functions, wherein the scanning mirror can be adjusted to track the pulse train of the treatment laser. over the surface of the eye during ablation of one pore in such a way as to create a different overall shape and size of the pore and/or a different shape of the bottom of the pore. In some cases, DBS can create an area the size and shape of a micropore. The beam targeting can be translated to shape the shape of a larger micropore using multiple positions and pulses of the system.

[00269] In some embodiments, as shown in FIG. 182, the laser system may include a scanning mirror combining OCT scanning and OCT depth control in a single OCT beam collinear with the treatment laser, wherein the scanning mirror may provide scanning and fixed position functions associated with OCT scanning and OCT depth control . In some embodiments, the laser system may use both functions simultaneously or alternately to combine an OCT scan with a treatment intervention in a quadrant.

[00270] As shown in FIGS. 127, 86, 85, and 57, in some embodiments, the laser system may be configured to treat scleral tissue by having a single scanning mirror that combines the functions of OCT scanning and OCT depth control and diffraction beam splitter (DBS), which shapes and sets the beam size, in the laser head, as shown in FIG. 85. In some embodiments, the beam size and shape can be varied by a plurality of small DBSs. DBS elements of different optical designs can be switched manually or automatically to modify the therapeutic beam profile collinear with the treatment laser beam. In some embodiments, DBS can be used to split a single laser beam into multiple beams, each having the characteristics of the original beam, can be used in a diverging beam, can be used to change the size of the beam, and can be reduced in size when used in front of a beam combiner. DBS designs can result in random spot distributions. The size of one spot may not be related to the distance between spots.

[00271] Headrest system and seat

[00272] In some embodiments, as shown in FIG. 133 and 72, the laser system may include a patient table or chair that can be attached to or positioned relative to the mechanical structure of the laser system and will be secured or remain fixed in position relative to the laser head.

[00273] In some embodiments, the laser system may include a patient chair that allows the patient to lean back and move under the laser system using a non-contact automatic system or manually. A preferred embodiment would position the head exactly centered within the x- and y-axis operating range of the laser head and then provide Z-axis movement to move the patient's face until it is centered within the laser head's operating range. From this position, the motion control system of the TOF camera, laser crosshairs and laser head can be adjusted to the patient for treatment.

[00274] As shown in FIG. 9, 71, 134, and 135, in some embodiments, the laser system may include a patient headrest to hold the patient's head and eye in a stationary position and provide approximate alignment of the eye relative to the laser head during preparation and treatment. The headrest may support the patient's head as required to help keep the eye in a stationary position. The headrest may be attached to the system as shown in FIG. 71, or a chair or treatment table. The headrest can be moved up and down to roughly adjust the patient's eye along the Z axis. The headrest can also serve as a mounting location for an automated optional eye interface mechanism.

[00275] In some embodiments, the headrest may include a helmet mounted to the headrest of a chair or table. Or the headrest can be attached to the laser system and provide positive positional feedback to the system.

[00276] In some embodiments, the headrest may include a tissue waste suction hose (as shown in FIG. 76) or a buffalo filter suction control system for suctioning surgical smoke, located near the eye and appropriately for each zone treatment. In some embodiments, the headrest may include means for aspirating ablation waste in a position adjacent to the quadrant being treated and positionable by a physician.

[00277] In some embodiments, an evacuation control system with a filter for evacuating surgical smoke may be integrated with the system, and the evacuation hose/nozzle(s) may be positioned by the system separately from the headrest, either manually or automatically on a carriage or other device.

[00278] In some embodiments, the headrest may include an automated eye interface system to support positioning of the patient's eye for each quadrant and keeping it stationary. This can be done with or without the help of a doctor.

[00279] FIG. 88 and 89 represent an exemplary ancillary eye attachment component in a laser system that may assist in drawing the eyelids open to target treatment areas, maintaining eye movement, protecting the pupil from stray radiation from the treatment laser, and assisting in directing the patient's gaze to distant off-axis fixation points. .

[00280] PROCEDURE AND MECHANISM OF OPERATION OF THE SYSTEM

[00281] FIG. 19 and 20, and 27 represent exemplary micropore(s) formation processes in some embodiments.

[00282] In some embodiments, a laser therapy procedure may use an erbium yttrium aluminum garnet laser (Er:YAG laser) to create micropores in ocular tissue, such as the sclera. These micropores can form at many depths, with a preferred depth range of, for example, 5%-95% of the scleral thickness, up to the point where the blue coloration of the choroid is almost visible. The micropores can be formed into multiple assemblies including a matrix, for example, 5 mm x 5 mm, 7 mm x 7 mm, or 14 mm x 14 mm. These microporation matrices break the bonds in the fibrils and microfibrils of the sclera, which creates the effect of “unstitching” in the scleral tissue. A direct result of this matrix pattern may be the creation of zones of both positive stiffness (remaining interstitial tissue) and negative stiffness (removed tissue or micropores) in the rigid sclera. These zones of differing stiffness make it possible for the viscoelastic modulus of the sclera after treatment to be more elastic in critical zones when subjected to force or load, such as ciliary muscle contraction. In addition, treated areas of the sclera may create a cushioning effect in the rigid scleral tissue when the ciliary muscles contract due to increased plasticity. This increases the accommodative force by unimpededly directing forces inward and centrally toward the lens or by facilitating inward and upward movement of the accommodative mechanism. This provides an advantage over models that assume an outward net force acting at the equator of the lens. For example, techniques that aim to widen the sclera, such as scleral implants or radial surgical laser ablations such as LAPR, are designed to increase the “gap” or peri-lenticular space to allow the sclera to expand to provide room for the ciliary muscles. The techniques mentioned are based on the theory of “lens constriction” and aim to support outward movement instead of upward and inward movement of the sclera and ciliary mechanism. In general, the creation of micropore matrices in scleral tissue can induce a “unstitching effect” that ruptures the fibrils and microfibrils of the scleral layers and allows a more elastic response to applied stress. Thus, the mechanism of action of the present invention can increase the plasticity and elasticity of scleral tissue within anatomically significant, critical zones by creating said areas of varying stiffness within the ciliary complex, and thereby increase the biomechanical function and efficiency of the accommodative apparatus. Fig. 2C-1 to 2C-4 of US Application No. 15/942,513 explain laser scleral detangling of scleral fibrils and microfibrils and are included in this application.

[00283] In some embodiments, the system's optical design can focus the diverging beam of a treatment laser into a separate converging beam that is directed to a specific pore at a working distance of up to 250 mm. The large working distance, >100 mm, provides the user with a clear line of sight to the eye before, during and after treatment and, for the patient, a more confident, non-contact treatment experience. The requirement of long working distances for the 2.94 µm Er:YAG laser has prevented the use of this wavelength in commercial automated laser systems with greater hands-free operation. Currently, almost all of the commercial 2.94 µm Er:YAG laser systems are either hand-held or articulated arm fed, with the best irradiation working distance being less than 500 mm and an average irradiation working distance of 3-4 mm. In some embodiments, the best irradiation working distance is greater than 100 mm and the average irradiation working distance is 100-200 mm, which allows for non-contact laser treatments without manual intervention.

[00284] In some embodiments, the system can generate beams of a variety of shapes and sizes at the target focal plane by (1) moving optical components along the optical axis, (2) changing the diffractive beam splitter included in the optical path, or a combination of both. .

[00285] The connective tissues of the eye, like all other connective tissues, are affected by age. The sclera makes up 5/6 of the eyeball and is formed by dense, irregular connective tissue. This tissue consists mainly of collagen (50-75%), elastin (2-5%), and proteoglycans. The connective tissues of the eye become stiff with aging, losing their elasticity mainly due to cross-linking that occurs with age. Cross-linking causes “increased biomechanical stiffness” in connective tissues such as the eye. Crosslinks are bonds between polymer chains, such as polymer chains in synthetic biomaterials or proteins in connective tissues. Cross-linking can be caused by free radicals, exposure to ultraviolet light, and aging. In connective tissues, collagen and elastin can crosslink with the continuous formation of fibrils and microfibrils over time. With an increase in the number of fibrils and microfibrils, the sclera becomes inflexible, undergoes “sclerosclerosis”, as well as a concomitant increase in metabolic physiological load. As this pathophysiology progresses, the sclera puts pressure on the underlying structures and causes tension in them from the load, creating biomechanical dysfunction, especially that associated with accommodation. Laser microporation of the sclera breaks up the fibrils and microfibrils of the sclera, effectively “expanding” the bonds and thereby increasing the elasticity of the sclera and “reducing biomechanical stiffness.”

[00286] Biomechanical improvements through treatment can be demonstrated to increase the biomechanical efficiency of the accommodative apparatus. In some embodiments, treatment by forming micropores in a matrix pattern in the four oblique quadrants can restore functional extralenticular forces and restore at least 1-3 diopters of accommodation. Treatment using the system and methods of the present invention can show an average recovery of 1.5 diopters of accommodation after surgery. This significantly increased the patients' visual acuity.

[00287] The use of previously unavailable innovative biometric and imaging technologies has explained that the loss of accommodative ability in presbyopia is due to many constituent lenticular, as well as extralenticular and physiological factors. The lens, lens capsule, choroid, vitreous, sclera, ciliary muscles and zonular ligaments all play a critical role in accommodation and undergo changes with aging. Increased ocular rigidity with age creates tension and strain on these ocular structures and can negatively impact accommodative ability.

[00288] Treatment of the sclera can be of great importance in the treatment of biomechanical defects in presbyopia, providing at least one remedy that takes into account the actual etiology of the clinical manifestation of deterioration of accommodation found with age. Treatment using laser microporation of the sclera to restore more elastic biomechanical properties is a safe procedure and can restore accommodative capacity in aging adult patients. As a result, treatment can expand the dynamic range of accommodation as well as improve aqueous humor outflow. With the advent of improved biometric and imaging techniques and concentrated research efforts, it is possible to obtain information about how the accommodative complex works and how it affects the entire visual organ.

[00289] In some embodiments, a scleral laser microporation procedure may include using the laser described above to perform microablations in the sclera to a partial thickness in a matrix at five critical anatomical zones, for example, 0-7.2 mm from the anatomical limbus (AL ). In some embodiments, the five zones may include: zone 0) 0.0-1.3 mm from AL; distance from AL to the upper border of the ciliary muscle/scleral spur; zone 1) 1.3-2.8 mm from AL; distance from the scleral spur to the lower border of the annular muscle; zone 2) 2.8-4.6 mm from AL; distance from the inferior border of the circular muscle to the inferior border of the radial muscle; zone 3) 4.6-6.5 mm from AL; from the lower border of the radial muscle to the upper border of the posterior zone of the zonular vitreous ligament; and zone 4) 6.5-7.2 mm from AL; from the upper border of the posterior zone of the zonular vitreous ligament to the upper border between the visual and blind parts of the retina.

[00290] As described herein, accommodation of the human eye can occur due to changes or deformations of the lens when the eye refocuses from a far distance to a near distance. This change in the lens can be caused by contraction of the intraocular ciliary muscles (ciliary body), which weakens the tension force of the lens by the supporting zonular fibers and allows an increase in the thickness and curvature of the lens surface. The ciliary muscle may be circular in shape and may consist of three separately oriented groups of ciliary fibers that contract toward the center and anterior aspect of the eye. The three groups of ciliary fibers mentioned are known as longitudinal, radial and annular. Deformation of the ciliary muscle due to contraction of different muscle fibers is converted into or otherwise causes a change in the tension force on the surface of the lens by zonular fibers, whose complex patterns of attachment to the lens and ciliary muscle determine the resulting changes in the lens during accommodation. Contraction of the ciliary muscle also places biomechanical stress on the junction between the ciliary muscle and the sclera of the eye, also known as the white outer layer of the eye. In addition, biomechanical compression, strain, or stress may be generated while accommodation may occur at the junction between the ciliary muscle and the choroid, known as the inner layer of connective tissue between the sclera and the retina. Contraction of the ciliary muscle can also produce biomechanical forces on the trabecular meshwork, lamina cribrosa, retina, optic nerve, and virtually every structure in the eye.

[00291] In some embodiments, application of the methods and models described for various embodiments herein using numerical simulation may result in outputs and results that are within the known ranges of accommodation of a young adult.

[00292] Mathematical 3D models can include mathematical relationships and non-linear neo-Hookean properties to reconstruct the characteristics of structures that have biomechanical, physiological, optical and clinical significance. In addition, 3D FEM (finite element models) models can include data from images, literature, and software related to the human eye.

[00293] Visualization of accommodation structures before and after numerical simulations can be included in addition to means for measuring, estimating and predicting central optical power (COP). They can be used to numerically model and observe characteristic age-related structures, optical systems, and biomechanics of the entire eye. In addition, they can independently model ciliary muscle properties, extralenticular and lenticular lens movements, and lens functions. Individual numerical simulations of anatomical structures and fibers can reveal biomechanical relationships that would otherwise remain unknown and uncertain. Numerical modeling of the patient's eye can be performed using a 3D finite element mesh (FEM) to perform these operations.

[00294] For research, representative 3D geometry of ocular structures at rest can be determined computationally, based on detailed analysis of published measurement data and medical images of young adult ocular anatomy, and through modeling. Special methods implemented in software such as AMPS software (AMPS Technologies, Pittsburgh, PA, USA) can be used to determine the geometric mesh, material properties and boundary conditions and finite element analysis at the modeling stage. The ciliary muscle and zonular ligaments can be thought of as a transversely isotropic material with orientations specified to represent complexly directed fibers. Additionally, CFD simulations can be performed to generate fiber trajectories that can then be displayed on a geometric model.

[00295] Initially, the lens simulation may include the lens in a relaxed configuration, before pre-stretching the zonular fibers into an unaccommodated position and shape. A non-accommodated position of the lens can be achieved when the zonular ligaments are shortened, for example, to 75% and 80% of their original length, and more specifically, to approximately 77% of their original length. The accommodative movement can then be simulated by performing active contractions of various fibers of the ciliary muscle. In some embodiments, this can be accomplished using prior skeletal muscle models that are modified to represent dynamics characteristic or otherwise specific to ciliary muscle. The model results representing the movement of the lens and the anterior section of the ciliary muscle and the thickness of the deformed lens at the midline and apex can be checked or otherwise confirmed by comparing them with available accommodation measurements published in the medical literature. In order to study the contribution of different groups of ciliary fibers to the overall action of the ciliary muscle, numerical simulations can be performed for each group of fibers by activating each group separately while others remain passive or otherwise unchanged.

[00296] Various useful aspects of the following embodiments are described taking into account numerical simulations using zonular ligament pretension models and ciliary muscle contraction models.

[00297] With respect to zonular ligament pretension, modeling may include: 1) forming thin layers of 3D material oriented between the measured attachment points of the zonular fiber inserts on the lens and the origin on the ciliary body/choroid; 2) a given direction of the fibers in the plane of the thin layer (for example, fibers directed from the beginning to the insert); and 3) a transversely isotropic forming material with tension in the preferred direction. In addition, and especially related to 3), the following advantages are obtained: a) the introduction of a time-varying tension parameter regulates the stress developed in the material; b) the input of time-varying tension can be adjusted to create the desired deformation in the lens consistent with measurements of the unaccommodated configuration; c) age-related changes in properties and geometric characteristics to obtain the influence of age; and d) others. US Applications 15/638,346 and 16/702,470, incorporated herein, detail full FEM simulations of human eye accommodation.

[00298] With respect to models of contracting ciliary muscles, the modeling may include: 1) a modified structural model to represent the smooth and structural aspects of the mechanical response of the ciliary body; 2) a set, for example 3, of sets of specified fiber directions to represent the physiological orientation of muscle cells and the lines of action of the generated force; and 3) a transversely isotropic forming material with the creation of an effective force in the preferred direction. Additionally, with respect to 3) specifically, the benefits obtained include: a) activation parameter inputs regulate the active stress generated in the material; b) activation inputs can be tuned to generate a suitable accommodation response consistent with measured data in the literature; c) the activation of individual groups of muscle fibers can be varied individually to assess their contribution to lens deformation/strain; d) the activation of individual groups of muscle fibers can be changed separately in order to assess the proportional participation in the deformation/tension of the sclera of the eye; e) the activation of individual groups of muscle fibers can be varied individually to assess their contribution to choroidal strain/strain; and f) others.

[00299] In various embodiments, simulation results may be due to changes in tensions and activations applied to the zonular and ciliary materials, as opposed to creating a displacement applied to the outer mesh node(s).

[00300] Systems, methods and devices are further disclosed for providing a predictive output in the form of a 3D computer model with built-in artificial intelligence (AI) that can be used to find the best predictive instructions for therapeutic vision correction, regulation or correction of a patient's vision defect, eye disease or age-related dysfunction. The best predictive instructions can be obtained from the input of physical structures, numerical modeling of neural networks and the expected influence on the therapeutic effect. To provide various useful results, new information can be analyzed in connection with optimized retrospective information on therapeutic effects. The concepts of this application can be used to perform a variety of numerical simulation operations and enable a knowledge base-based platform so that the system can improve its response instructions as the database expands. The concepts of the present application can also use AI to create progressive age-specific numerical models of targeted tissues and clinical manifestations of disease states to link treatment planning to outcomes.

[00301] In some embodiments, the stored candidate instructions may preferably be an optimized custom microporation algorithm for controlling the microperiod laser. Instructions can be provided with the AI processor through direct integration, self-import, or remotely, such as via Bluetooth or another application or wireless connection. These instructions can be followed before or during surgery.

[00302] In some embodiments, the stored inferred instructions may preferably be an optimized custom lens numerical simulation algorithm used to simulate manipulation of an implantable intraocular lens for the purpose of improving medical procedures and performance.

[00303] The instructions may also be structured as an "atomous" system, whereby the instructions may be presented with independent inputs and outputs of a study design to test various ocular conditions and responses to surgical procedures, implantable devices, or other therapeutic interventions on the eye to optimize the calculated and the resulting characteristics.

[00304] In addition, these instructions may also include one or more of: an algorithm for interpreting image processing, enhancing ophthalmology imaging processing platforms, and related diagnostics for the imaging device.

[00305] As described herein, methods for improving treatments, surgeries or pharmacological interventions in ophthalmology may include obtaining topological, topographical, structural, physiological, morphological, biomechanical properties, material characteristics and optical data for the human eye, together with applied physical processes and analysis using mathematical modeling using extensive artificial intelligence systems.

[00306] In some embodiments, applications using numerical simulation may include methods performed by devices, systems, and methods for automated planning of an ophthalmic surgical procedure, including obtaining physical measurement data and applied physical processes of a patient's entire eye. Methods known in the art can be used to obtain measurement data. The information obtained from the measurements can be interpolated and extrapolated to select nodes of a finite element model (FEM) of the human eye for analysis, which can then be analyzed to predict the initial stress state of the eye and obtain preoperative states of the cornea, lens and other structures. The finite element analysis model can include the incision data that constitutes the “initial” surgical plan. New analyzes can then be performed to model the resulting deformations, biomechanical effects, stresses, strains, ocular curvature values, and dynamic movements of the eye, particularly the ciliary muscles, lens, and accommodative structures. These can be compared with baseline values and vision targets. If necessary, the surgical plan can be modified and the new ablation data obtained can be entered into FEM and the analysis repeated. This procedure can be repeated as desired or necessary until vision goals are achieved.

[00307] Artificial Intelligence and Numerical Modeling

[00308] In some embodiments, artificial intelligence (AI) software may use a learning machine, such as an artificial neural network, to conduct machine learning, whereby the system can learn from data and therefore includes a learning component based on continuous expansion of the database . This can be used to improve reliability when the database is created and updated, which was previously unknown in previous predictive systems, 3D modeling methods and devices.

[00309] Numerical modeling may include numerical modeling of the age-related development of a patient's eye, having the predictive ability to model the results of ophthalmic surgery, determine remission rates from treatment, and perform predictive algorithms for future surgical or therapeutic improvements that have heretofore been unknown in previous predictive systems, methods and devices of 3D modeling.

[00310] In some embodiments, systems of the present invention may include a virtual ocular simulation analyzer, which may include integrating information related to all structures of the eye into a computer program for the purpose of numerically simulating the biomechanical and optical functioning of the eye, as well as numerically simulating age-related changes for use in clinical practice. Additional details regarding the virtual eye simulation analyzer are provided in US Application No. 15/942,513 and are incorporated herein.

[00311] The simulator can combine mathematical relationships and nonlinear neo-Hookean properties to reconstruct the characteristics of biomechanically, physiologically, and optically significant structures and other structures that may be important or otherwise of clinical significance. The simulator may use methods known in the art to input data included in the 3D FEM with patient specific data based on analysis of the patient's own eye(s). In addition, the simulator can use methods known in the art to input data and create a numerical model of the patient's eye using a 3D FEM mesh, i.e. essentially creating a customized dynamic “virtual eye” in real time, something that has been previously unknown in previous predictive systems, 3D modeling methods and devices.

[00312] In some embodiments, the AI may have the ability to learn through predictive numerical modeling and the functionality to improve model prediction results for ocular surgical or therapeutic interventions through a learning machine, such as artificial neural networks, such as in ABACUS. The program may also present instructions directly to a communications processor or data processing system for the purpose of creating and applying algorithms, mathematical ordering, formulating, data profiling, surgical decisions, and more. It may also present instructions directly to a workstation, imaging system, robotic system controller, or other execution device. In addition, it may also present instructions indirectly, via Bluetooth or other remote connection, to a robotic systems controller, imaging system, or other workstation.

[00313] The models of this application may find various applications in clinical, research and surgical practice, including: 1) the use of preliminary assessment and numerical modeling of the accommodative functions of the eye (examples include the calculation and application of IOL (intraocular lens) for presbyopia, extralenticular medications and their use); 2) the use of preliminary assessment and numerical modeling of the circulation of intraocular fluid, for example, to detect glaucoma; 3) construction of virtual numerical models and numerical models of IOL efficiency, therapeutic treatment and various biomechanical aspects; 4) virtual numerical simulation using AI and machine intelligence (MI) to reproduce the individualized effects of aging on the biomechanical and physiological functions of the patient's eye that are clinically relevant; 5) planning a surgical operation; 6) import and numerical simulation of a computational model (for example, FEM), for example, for IOLs and other structures; 7) virtual clinical trials and analysis; 8) real-time intraoperative analysis, planning and execution of surgery; 9) the action of the lens of the eye as it relates to optical and biomechanical dysfunction, cataract formation, and the like; and 10) other.

[00314] In some embodiments of the invention, a dual-axis closed-loop galvanometer optical system assembly may be used.

[00315] In some embodiments, the laser system may include a galvanometric mirror camera correction system, which is further explained in detail in FIG. 3C of US Application No. 15/942,513, which is incorporated herein. Fig. 3D US Application No. 15/942,513 presents an exemplary flow diagram of the operation of a video camera-based eye sensor in accordance with some embodiments of the present invention.

[00316] In some embodiments, as further explained in detail in FIG. 4A in US Application No. 15/942.51, incorporated herein, the laser system may include a treatment laser emitting a laser beam that passes through an intermediate lens to a dichroic mirror or is specularly reflected.

[00317] FIG. 4B-1 in US Application No. 15/942,513, incorporated herein, shows an exemplary laser treatment system forming pore depth in accordance with some embodiments of the present invention. Fig. 4B-1 generally shows the treatment laser beam passing to the dichroic mirror before passing to the first galvanometric mirror, then to the second galvanometric mirror, through the focusing optical system and to the patient's eye. Fig. 4A-1-4A-10 in US Application No. 15/942,513 show how microporation/nanoporation can be used to remove superficial, subsurface and interstitial tissue and affect superficial, interstitial, biomechanical characteristics (e.g., planarity, surface porosity, tissue geometry, tissue viscoelasticity and other biomechanical and biorheological characteristics) of the target surface or target tissue being ablated.

[00318] In some embodiments, an optical coherence tomography (OCT) system may be used to obtain subsurface images of the eye. Essentially, by communicating with a computer that is connected to a video monitor, the system allows the user or operator to view subsurface images of tissue ablation. As noted herein, a pore can have a depth from 5% to 95% of the scleral thickness in 3-dimensional space, with an average scleral thickness of 700 μm representing a typical pore depth. Laser microporation can be performed to a depth greater than refractive surface ablation surgery, performed at depths of 200 µm to 300 µm, and several orders of magnitude deeper than other refractive surface ablative surgeries that have been performed on corneal tissue and typically to depth from 10 µm to 45 µm on average and, in general, >120 µm (see Figs. 139A and 139B).

[00319] In at least some embodiments, the system may provide a real-time intraoperative view of tissue depth levels. The system may include image segmentation to identify the inner border of the sclera for improved depth control.

[00320] FIG. 4A-5 and 4B-2 of US Application No. 15/942,513 present exemplary simplified diagrams of an ablation pore in the sclera, showing an example of the depth of ablation relative to the inner border of the sclera, and are included herein.

[00321] FIG. 5 of US Application No. 15/942,513 presents an exemplary flow chart of a depth control process in accordance with some embodiments of the present invention and is included herein.

[00322] In general, a depth control system, such as an OCT system, performs repetitive B-mode scanning synchronized with a laser. A B-mode scan can show the superior surface of the conjunctiva and/or sclera, the boundaries of the ablated pore, and the inferior interface between the sclera and the choroid or ciliary body. Automatic image segmentation algorithms can be used to identify the upper and lower surfaces of the sclera (eg, 400-1000 micrometers thick) and the boundaries of the ablated pore. The distance from the upper surface of the sclera to the lower surface of the pore can be automatically calculated and compared with the local scleral thickness. In some embodiments, this occurs in real time. When the pore depth reaches a predetermined size or fraction of the scleral thickness, ablation can be stopped and the scanning system is discretely advanced to the next target ablation site. In some embodiments, the images may be segmented to identify the internal boundaries of the sclera.

[00323] As shown in the steps of FIG. 5 (US Application No. 15/942,513), in an exemplary embodiment, an initial or initialization sequence of steps may be performed first. This initial sequence of steps begins with setting the pore coordinates at step 412. At step 414, an AB mode scan of the target area is performed. This scan produces an image that is processed at step 416 to segment and identify the scleral boundary. Next, at step 418, the distance between the conjunctival surface and the scleral boundary is calculated.

[00324] After completion of this initial sequence of steps, ablation may begin at step 420. The laser beam is excited and a B-mode scan is performed at step 422. This B-scan produces an image that can then be segmented at step 426 and the pore depth and ablation rate are calculated from the image. The pore depth and ablation rate data are compared to the target depth at step 430. If the target depth is not achieved, then the process returns to step 422 and repeats. Once the target depth is reached, step 432 stops the ablation process and step 434 begins the initial process again by setting the coordinates of the next pore. In some embodiments, the depth control system may monitor the ablation depth within a single pulse and may stop the ablation to reduce risk, and there may also be other internal processes occurring that may stop the ablation if the process is out of a predetermined range; the operating limits of eye tracking are exceeded, the maximum preset number of pulses is exceeded, the controlled laser power is outside the specified limits. All of the above serve as risk reduction measures.

[00325] In some embodiments of the present invention, arrays of laser spots may be used to simultaneously ablate multiple pores. These laser spot matrices can, in some cases, be formed by microlenses and also be determined by the characteristics of the laser. Increasing the wavelength can lead to a decrease in the number of laser spots, with an increase in spot diameter.

[00326] With respect to certain other aspects of the present invention, in many embodiments it is advantageous to preoperatively measure ocular characteristics and individualize treatment according to the needs of the individual patient. Preoperative measurement of ocular characteristics may include measurements of intraocular pressure (IOP), scleral thickness, scleral stress/strain, anterior segment vasculature, accommodative response, and refractive error. Measuring scleral thickness may involve the use of optical coherence tomography (OCT). Scleral stress/strain measurements may include Brillouin scattering, OCT elastography, and photoacoustics (light plus ultrasound). Measurement of anterior segment vasculature may involve the use of OCT or Doppler OCT. Measuring refractive error may involve the use of equipment such as the iTrace trademarked product from Tracey Technologies Corp.. Those of ordinary skill in the art will recognize that other measurements, methods, and systems are also applicable.

[00327] During the treatment procedure, intraoperative biofeedback loops can be of great importance to keep the physician informed regarding the progress of the operation. Such feedback loops may include the use of topographic measurements and control of bypass areas such as the anterior ciliary arteries.

[00328] Biofeedback loops may include a feedback sensor to correct nonlinearities in the piezo scanning mechanism. The sensor in some embodiments may provide real-time position feedback, for example, within a few milliseconds, and use capacitive sensors for real-time position feedback. A real-time positional feedback loop can be coupled to the controller and, when certain biological signatures are identified based on tissue characteristics, can stop the laser during surgery.

[00329] The sensor feedback device may also perform biological or chemical "intelligent sensing" to allow ablation of target tissue and protect or bypass surrounding tissue. In some cases, smart sensing can be accomplished by embedding a biochip in a mask that is activated by low irradiation and detects the location, depth, size, shape, or other parameters of the ablation profile. Some embodiments contemplate the applicability of galvanometric optical systems that can be used to measure numerous laser beam control parameters and special functions.

[00330] Those of ordinary skill in the art will appreciate that other feedback methods and systems may also be employed.

[00331] In some embodiments, the systems, methods, and devices of the present invention may include on-screen display capabilities in a GUI, which may include receiving each image frame and transmitting information to a video display after each ablation within a 3- to 7-dimensional micropore before and after the laser pulse in real time, and image the surface. The GUI can contain a built-in system for simultaneously viewing 7 views of recorded images, including: surface, internal pore, external pore, micropore bottom, whole eyeball image, target matrix area.

[00332] In some embodiments, the preferred projection for the microprocessor may be a 7-hypercube, but there are other examples in 3D spherical form included in the GUI and the microprocessor. Orthogonal projections may include examples such as those shown in FIG. 8 US Application No. 15/942,513.

[00333] In some embodiments, a support vector machine-based pattern recognition capability may be included in a microprocessor-based AI system. For a nonlinear classification problem, SVM can transform the input space into a high-dimensional space through the nonlinear transformation K(X). Therefore, a nonlinear problem can be transformed into a linear problem, and then the optimal separating hyperplane will be calculated in the new multidimensional space, for example, using the integrated software tools Matlab or Mathematica. For additional information, see US Application No. 15/942,513.

[00334] Some embodiments may use Serre layering or weak layering. They are capable of creating an image of each cylindrical micropore in the matrix and the entire matrix on a 3D surface and an interstitial image of pore matrices in cross section. An exemplary 3D display 900 is shown in FIG. 9 US Application No. 15/942,513.

[00335] FIG. 10 of US Application No. 15/942,513 depicts, in accordance with some embodiments of the present invention, exemplary design schemes that can be carried out as follows. Step 1001: Treatment design/planning may begin with a tissue hierarchy that is established using a mathematical projection of the 7-sphere onto the entire sphere to create a congruent treatment platform based on the 7-dimensional shape and hyperbolic planar tessellation. Step 1002: The off-axis mathematical algorithm derived from the tissue hierarchy and Fibonacci pattern formation is displayed as a mathematical image. Step 1003: Algorithmic code is then implemented to design custom microporation patterns that reflect the biorheology of the tissues, including all inputs of stiffness, viscoelastic modulus, topology, topography, biometry, and the like. Step 1004 (not shown): Anatomical traversal software may be executed to erase or eliminate non-target fields, matrices, regions. Step 1005 (not shown): The surgeon/user may also manipulate target or non-target areas via a touch screen interface.

[00336] In some embodiments, the described systems, methods and devices of the present invention may include the following capabilities for issuing treatment algorithms by a laser user interface system. Real-time math is included and represented as 3D math files, which can also be animated GIFs to display a priori information related to matrix performance. The workstation/algorithm works in conjunction with the VESA system to provide the user/surgeon with a mathematical representation of the ideal 3D array configuration on the eye. The topological representation of the image is stereographically projected on the display. The matrix is expressed by predefined formulas and can further be modeled as a Fibonacci series using a variety of densities, spot sizes, geometric characteristics, and micro- and nanopore configurations. The benefit of the Fibonacci series is to create the most balanced matrix formula that matches the body's own natural tissue hierarchy on both the macro and micro scales.

[00337] The matrix may also correspond to a model of hyperbolic geometry or a homogeneous (regular, quasi-regular or semi-regular) hyperbolic tiling, which is a jointed tiling of a hyperbolic plane that contains regular circles or polygons as faces and is vertex-transitive (transitive at its vertices , isogonal, i.e., there is an isometric mapping of any vertex to any other vertex). Examples are shown in FIGS. 10 and 11 of US Application No. 15/942,513 and are incorporated into this application. It follows that all vertices are congruent, and the mosaic has a high order of rotational and translational symmetry.

[00338] Uniform tessellations can be identified by the configuration of their vertices, a sequence of numbers representing the number of sides of circles or polygons around each vertex. One example below represents a heptagonal tiling that contains 3 heptagons around each vertex. It is also regular, since all circles or polygons are the same size, and can therefore be assigned the Schläfli symbol.

[00339] Uniform tilings can be regular (if they are also face-transitive and edge-transitive), quasi-regular (if they are edge-transitive but not face-transitive), or semi-regular (if they are neither edge-transitive nor face-transitive) . For right triangles ( pq 2), there are two regular tilings represented by the Schläfli symbol { p, q } and { q, p }.

[00340] In some embodiments, the described systems, methods and devices of the present invention may include a mechanism for creating a micropore matrix, in which the pattern of multiple micropores may have a controlled uneven distribution or a uniform distribution or a random distribution and may be one of radial pattern, spiral pattern, phyllotactic pattern, asymmetric pattern, or a combination thereof. The phyllotactic spiral pattern may have clockwise and counterclockwise parastichy in accordance with the present invention. Fig. 12 of US Application No. 15/942,513 depicts an exemplary schematic representation of the creation of an asymmetrically controlled distribution of an algorithmic matrix pattern on the eye with helical phyllotaxis in which each micropore matrix appears sequentially.

[00341] In some embodiments, the micropore array pattern may be any one of an Archimedean spiral, a Cornu spiral, a parabolic spiral, a hyperbolic spiral, a rod spiral, a logarithmic spiral, a Fibonacci spiral, a golden spiral, or combinations thereof.

[00342] In some embodiments, the described systems, methods and devices of the present invention may include creating a 3D model of microporation on a spherical surface.

[00343] In some embodiments, the described systems, methods and devices of the present invention may include the use of Fibonacci parameters and mathematical parameters to optimize the performance, results and safety of surgery in a laser microporation treatment matrix having a pore pattern, e.g. micropores or nanopores, in which the pattern is a pattern of uneven distribution, which is realized in multi-profile tissue in accordance with the existing tissue hierarchy at the macro level and micro level in such a way that the treatment gives a congruent rejuvenation effect. The treatment matrix or mesh containing a plurality of micropores/nanopores/ablations/cuts/targets may be arranged in an unevenly distributed pattern, the pattern being helical or phyllotactic. The patterns can be described by the Vogel equation. In addition, there are many other geometries/densities/depths and shapes that have spiral or phyllotactic patterns of flow paths, such as open channels or pores. The micropores/nanopores may be specifically designed to fit any given contact lens, mask, or other model material or design having a non-uniform distribution pattern. Alternatively, microporation can be used in connection with conventional coated or uncoated perforated polymers, for example, hydrophilic or hydrophobic types. The matrix structure having a pattern of unevenly distributed micropores and the lens or mask can be used together as a therapy system.

[00344] Figures 4A-1 to 4A-10 and 26-3A of US Application No. 15/942,513 show how microporation/nanoporation can be used to remove superficial, subsurface and interstitial tissue and affect superficial, interstitial, biomechanical characteristics (eg, planarity, surface porosity, tissue geometry, tissue viscoelasticity, and other biomechanical and biorheological characteristics) of the target surface or target tissue being ablated. In addition, the present invention may include a variety of automated data processing systems for processing micro-shot execution data in various compositions and configurations.

[00345] Characteristics of the exposed fabric include, but are not limited to, porosity, texture, viscoelasticity, void ratio, surface roughness height, and uniformity. Surface characteristics, such as surface roughness height and reflectivity, are measured to determine condition. This microporation can also affect the deformation, compliance and flexibility of the tissue and has an orange peel texture. Therefore, the properties of microporated/nanoporated tissue will generally influence and/or enhance tissue health by restoring or rejuvenating the tissue's biomechanical compliance at rest and under stress/strain, as well as tissue permeability.

[00346] In some embodiments, a microporation may include a plurality of micropore traces arranged in a pattern. The pattern of micropore traces may comprise regular circles or polygons, irregular circles or polygons, ellipsoids, arcs, spirals, phyllotactic patterns, or combinations thereof. The pattern of micropore traces may comprise radial arcuate traces, radial spiral traces, or combinations thereof. The micropore trace pattern may comprise a combination of inner radial helical traces and outer radial helical traces. The pattern of air flow paths may comprise a combination of clockwise radial helical paths and counterclockwise radial helical paths. Micropore tracks may be separated or discontinuous from each other. Alternatively, one or more micropore routes may be fluidly coupled. The number of radial arcuate traces (“arcs”), radial spiral traces, or combinations thereof may vary.

[00347] In some embodiments, the microporation may comprise a pattern that is a controlled nonlinear distribution pattern, a controlled linear distribution pattern, or a random pattern. In some embodiments, the ocular contact lens/eye mask may comprise a micropore trace pattern, wherein the micropore trace pattern is constructed from x and y coordinates of the pattern with a controlled non-uniform distribution. The controlled non-uniform distribution pattern used to create the microporation pattern in the ocular contact lens/eye mask may be the same as or different than the matrix structure of the laser microporation algorithm used with the ocular contact lens/eye mask. In an embodiment, the pattern with controlled non-uniform distribution is the same as the matrix structure of the laser microporation algorithm used with the ocular contact lens/eye mask. In some embodiments, the controlled non-uniform distribution pattern is different from the matrix structure of the laser microporation algorithm used.

[00348] In some embodiments, the laser microporation system may have phyllotactic patterns in accordance with embodiments of the laser microporation algorithms described herein. The eye contact lens/eye mask works in coordination with the laser microporation system creating phyllotactic patterns, where the laser microporation system creates multiple micropores, multiple holes, multiple cavities, multiple channels, multiple passages or combinations thereof that are formed into a pattern designed to promote improvement natural biological functions such as fluid flow, blood flow, muscle movement, as well as static and dynamic biological functions, with the participation of the ocular contact lens/eye mask and tissue having a phyllotactic pattern. Micropores, holes, cavities, channels, passages, or combinations thereof may form biological duct pathways that extend along, within, or through the load-bearing soft pad, or in combination. In one embodiment, the pattern of micropores, holes, cavities, channels, passages, or combinations thereof may be in the form of regular circles or polygons, irregular circles or polygons, ellipsoids, arcs, spirals, phyllotactic patterns, or combinations thereof. In another embodiment, the air flow paths may be in the shape of regular circles or polygons, irregular circles or polygons, ellipsoids, arcs, spirals, phyllotactic patterns, or combinations thereof.

[00349] In some embodiments, a suitable spiral or phyllotactic pattern can be created along the x and y coordinates of any phyllotactic matrix of the microporation system embodiments described above. In an embodiment, the x and y coordinates of the spiral or phyllotactic pattern are translated and rotated to define the x′ and y′ coordinates of the spiral or phyllotactic pattern of the accessory airways, where Ɵ is equal to π/n in radians, and n is equal to any integer. The coordinates (x′ and y′) can be plotted, for example, using computer aided drafting (CAD) software, to form a suitable pattern, such as a spiral or phyllotactic pattern.

[00350] Patterns can then be used to define radial arcuate and spiral channels, as well as annular channels that may intersect arcuate and spiral channels, or combinations thereof. Annular, arcuate, helical, or combination channels may cause shape deformation, such as the formation of grooves, cavities, holes, passages, or other paths. Exemplary embodiments of groove patterns that are based on transferred phyllotactic patterns are also shown in FIG. 10, 13 and 16 in US application 15/942,513. Additional exemplary embodiments based on transferred phyllotactic patterns are shown in FIG. 14A-14D, 15A-15F and 41 in US application 15/942,513.

[00351] As shown below, the microporation pattern may have a number of clockwise spirals and a number of counterclockwise spirals, wherein the number of clockwise spirals and the number of counterclockwise spirals are Fibonacci numbers or multiples of Fibonacci numbers.

[00352] FIG. 14A in US application 15/942,513 depicts an exemplary embodiment of a micropore pattern that can be implemented directly on a target tissue or, alternatively, on a contact lens, mask or other similar model having a micropore pattern with a controlled uneven distribution of micropores in a Fibonacci series distribution. in accordance with some embodiments of the present invention.

[00353] FIG. 14B in US application 15/942,513 is an exemplary illustration of a phyllotactic spiral pattern containing clockwise and counterclockwise parastichy, in accordance with some embodiments of the present invention.

[00354] FIG. 14C in US application 15/942,513 is another exemplary illustration of a phyllotactic spiral pattern containing clockwise and counterclockwise parastichy, in accordance with some embodiments of the present invention.

[00355] FIG. 14D-15F in US application 15/942,513 are exemplary illustrations of the Vogel model, in accordance with some embodiments of the present invention.

[00356] FIG. 16A-16N in US application 15/942,513 are exemplary illustrations of exemplary embodiments of microporations derived from icosahedral pattern shapes in accordance with some embodiments of the present invention

[00357] FIG. 17A-17B and 2K-18 and 2K-19 in US application 15/942,513 depict exemplary microporation patterns derived from icosahedral pattern shapes representing fractal spherical and icosahedral/tetrahedral tilings, in accordance with some embodiments of the present invention.

[00358] Surface Area : The total surface area of the target tissue affects the amount of total tissue material removed. Typically, as the total surface area of the fabric increases, the amount of surface material removed increases. In some embodiments, the total surface area of the target tissue microporations may be equal to the total potential surface area of the microporation system (i.e., the target microporation area if there were no micropores in it), minus the total micropore area (i.e., the sum of the areas of all micropores ). Thus, the amount of total micropore surface area can range from 1% to approximately 99.5% of the total potential surface area, depending on the micropore area sought. See fig. 30 in US application 15/942,513 for exemplary surface areas, in accordance with some embodiments of the present invention.

[00359] Depth : figures from FIG. 4A-5 to 4A-10 in US application 15/942,513 show that the overall depth of the target tissue can influence the amount of total tissue material removed. Typically, as the amount of total tissue depth increases, the amount of intervening or subsurface tissue removed increases. In some embodiments, the depth of tissue microporation removed is equivalent to the total potential subsurface and intermediate tissue of the microporation system (i.e., the total intermediate and subsurface tissue if it did not contain micropores), minus the total micropore volume (i.e., the sum of the areas of all micropores). Thus, the value of the total microporation volume can range from 1% to approximately 95% of the total potential subsurface and intermediate microporation tissue volume, depending on the size of the desired micropore volume.

[00360] Pore Density : The density of the pore matrix, eg, a plurality of micropores, can influence the total amount of micropore area and the total amount of surface, subsurface, and interstitial volume removed. The total number of micropores and the distribution of micropores may also have an influence. A variety of exemplary configurations of densities, micropore size, and micropore distribution are shown in the figures from FIGS. 2K-1-A to 2K-1-C and to fig. 2K-17 in US application 15/942,513. It should be noted that micropores can be created randomly, uniformly or individually. The spatial density or bulk density of multiple micropores can also influence biomechanical properties.

[00361] Number of Pores : The number of pores, such as micropores, can influence the total amount of micropore area and the amount of total surface, subsurface, and interstitial volume removed. In addition, the number of micropores can influence the density and distribution of the micropore coating on the surface of the microporation, which, in turn, can directly affect the total pore volume fraction of the microporation. In some embodiments, the number of micropores may be at least about 3, at least about 5, at least about 8, at least about 12, or at least about 15. In some other embodiments In an embodiment, the number of micropores may be at least about 45, at least about 96, at least about 151, or at least about 257. Additional exemplary parameters are also presented in FIG. 31-34B, 37, 38 and 39 in US application 15/942,513.

[00362] In some embodiments, the number of pores may be 9-10,000 according to the spot size, which may vary from 1 nm to 600 μm. The number of micropores may be in a range containing any pair of the above-mentioned upper and lower limits.

[00363] The microporation of the present invention can be influenced by various parameters and factors, which are presented in FIG. 31-35 in US application 15/942,513 and are discussed further below.

[00364] Deflection Angle : When applying a laser pulse to target tissue, increasing or decreasing the deflection angle α can affect how the micropores are placed within the pattern and the shape of the clockwise and counterclockwise spirals. The angle of deflection is equal to the quotient of 360° divided by a constant or variable value, and therefore the angle of deflection can be constant or variable. In some embodiments, the pattern may have a polar deviation angle that ranges from about 100° to about 170°. Small changes in deflection angle can significantly alter the matrix structure and may show phyllotactic patterns that differ only in deflection angle value. The approximate deflection angle can be 137.3°. The deflection angle can also be 137.5° or 137.6°. In some embodiments, the deflection angle is at least about 30°, at least about 45°, at least about 60°; at least about 90° or at least about 120°. In other embodiments, the deflection angle is less than 180°, for example, no more than about 150°. The deflection angle may be within a range containing any pair of the above-mentioned upper and lower limits. In some other embodiments, the deflection angle ranges from about 90° to about 179°, from 120° to about 150°, from about 130° to about 140°, or from about 135° to about 139°. In some embodiments, the angle of deflection is determined by dividing 360° by an irrational number. In some embodiments, the deflection angle is determined by dividing 360° by the golden ratio. In some embodiments, the deflection angle is in the range of about 137° to about 138°, such as about 137.5° to about 137.6°, such as about 137.50° to about 137.51°. In some embodiments, the deflection angle is 137.508°.

[00365] Microporation matrix edge distance : In some embodiments, the overall dimensions of the matrix structure may be determined based on the microporation geometry and intended use. The distance from the center of the pattern to the outermost micropores may extend to a distance bordering the edge of the micropore. Thus, the edges of the outermost micropores may extend to or intersect with the edge of the micropore. Alternatively, the distance from the center of the pattern to the outermost micropores may extend to a distance that allows some portion of the space between the edges of the outermost micropores and the edge of the micropore to be free of micropores. The minimum distance from the edges of the outermost micropores can be set as required. In some embodiments, the minimum distance from the edges of the outermost micropores to the outer edge of the microporation is a predetermined distance, identified as the latent length or the percentage of the length of the front surface of the microporation from which the matrix structure arises. Micropores can be widely or narrowly spaced, or arranged in a mosaic pattern.

[00366] Pore size : In some embodiments, the size of the pores, such as micropores, may be determined, at least in part, by the total matrix area desired for the microporation. The size of the micropores may be constant throughout the pattern or may vary within the pattern. In some embodiments, the micropore size is constant. In some embodiments, the size of the micropores varies with the distance of the micropores from the center of the pattern. There are many sizes allowed in the system. The pore size can vary from 1 nm to 600 µm. In some other embodiments, the size is 50 microns, 100 microns, 125 microns, 200 microns, 250 microns, 325 microns, 425 microns, or 600 microns.

[00367] Pore Shape : There are a variety of pores allowed in a system. The shape of pores, such as micropores created in connective tissue by electromagnetic radiation, can correspondingly influence tissue response and wound healing. Square shapes may heal more slowly than round shapes. The microporation system is capable of creating a variety of customized micropore geometries. In some embodiments, the ideal shape is square.

[00368] The form may also provide the effective result of a plurality of micropores. The amount of coverage may depend on the shape of the micropores. The shape of micropores can be regular or irregular. In some embodiments, the shape of the micropores may be in the form of slits, regular circles or polygons, irregular circles or polygons, ellipsoids, circles, arcs, spirals, channels, other suitable shapes, or combinations thereof. In some embodiments, the plurality of micropores are shaped like circles. In some embodiments, the matrix shape may be in the form of one or more geometric patterns, such as icosahedral or tetrahedral tilings, with multiple circles or polygons (or other shapes) intersecting. The shape may also influence unwanted or undesirable wound healing and can be changed depending on the intended function of the micropore.

[00369] FIG. 16A-N in US application 15/942,513 provide examples of multiple micropores with such pores. The plurality of micropores are configured in such a way that the patterns resemble circles or polygons, which may have slightly arcuate edges. Removal of tissue in such configurations affects biomechanical properties in a mathematically and geometrically balanced manner, creating microporation stability.

[00370] Design Parameter : A design parameter may influence the overall placement of the microporation matrix or mesh within the 3D tissue and relative to the edges of the microporation, taking into account the "atmosphere" within the tissue. The microporation pattern can be adjusted depending on the natural shape of the tissue itself or based on the intended physiological anatomy or desired effect. This can be a self-dual (infinite) regular Euclidean honeycomb, a dual polyhedron, a 7 cube, a 7 orthoplex, or, similarly, a simple mesh, a Bravais lattice, or a non-Bravais lattice mesh.

[00371] Scaling factor : The scaling factor can affect the overall size and dimensions of the multi-micropore pattern. The scaling factor can be adjusted so that the edges of the outermost micropores are within the required distance of the outer edge of the micropore. In addition, the scaling factor can be adjusted so that the inner edges of the innermost micropores are within the desired distance of the inner edge of the micropore. The principle of duality can be generalized to n-dimensional space and dual polyhedra; in two dimensions, these figures are called dual circles or polytopes, or three dimensions or multiple dimensions containing vertices, matrices, or similarly containing isotropic and/or anisotropic tilings.

[00372] Distance between nearest adjacent pores : Together with factor analysis of the number and size of pores, for example micropores, the distance between the centers of the nearest neighboring micropores can be determined. The distance between the centers of any two micropores may depend on matrix design factors. In some embodiments, the shortest distance between the centers of any two micropores is never repeated (ie, the distance between the pores is never the same exact distance). This type of gap is also an example of controlled asymmetry. In some other embodiments, the shortest distance between the centers of any two micropores is always repeated (ie, the distance between the pores is always the same exact distance). This type is also an example of controlled symmetry. In some embodiments, the distance between two micropores is randomized (ie, the spacing between the pores is random). Thus, the system can provide controlled asymmetry, which is at least partial rotational asymmetry about the center of the pattern or matrix pattern, random asymmetry, which is at least partial rotational random asymmetry about the center of the pattern or matrix pattern, and controlled symmetry , which is at least partial rotational symmetry about the center of the pattern or matrix pattern, and random symmetry, which is at least partial rotational random symmetry about the center of the pattern or matrix pattern.

[00373] In some embodiments, the rotational asymmetry may extend to at least 51% of the micropores of the matrix pattern. In some embodiments, the rotational asymmetry may extend across at least 20 micropores of the matrix structure design. In some embodiments, rotational symmetry may extend to at least 51% of the micropores of the matrix pattern. In some embodiments, rotational symmetry may extend across at least 20 micropores of the matrix pattern. In some embodiments, the rotational random pattern may extend over at least 51% of the micropores of the matrix pattern. In some embodiments, the rotational random pattern may extend across at least 20 micropores of the matrix pattern.

[00374] In some embodiments, 51% of the pattern of holes can be described in polar coordinates by the Vogel model equation: φ= n × α , r = c√n , as described above.

[00375] Matched ocular contact lens/eye mask

[00376] The matched ocular contact lens/eye mask (see, for example, Fig. 27A, element 2700, and Fig. 40 in US application 15/942,513) can be flexible or rigid, soft or hard. It can be made from any number of different materials, including materials commonly used in contact lenses or eye masks, such as both hydrophilic and hydrophobic polymers or soft gel, or collagen, or soluble materials, or special metals. An exemplary flexible lens/mask may include a pliable hydrophilic (“water-loving”) plastic.

[00377] In some embodiments, the described systems, methods and devices of the present invention may include a method and device for treating the sclera and adjacent ocular structures and fractional microporation and surface restoration, laser microporation of the eye for rejuvenation or restoration of physiological function of the eye and/or alleviating dysfunction or disease. In various embodiments, the matrices can have a variety of geometries, densities, configurations, distributions, and spot sizes and depths. They can also be pre-scheduled and executed at different points in time. The matrix can also penetrate the episclera, the scleral substance or the dark lamina of the sclera to any percentage of the required portion. Electromagnetic energy input values may also be suitable.

[00378] A hydrophobic scleral lens, individually adjustable in thickness in nanometers, microns, etc. : In various embodiments, the customizable hydrophobic scleral lens may have different dimensions, generally measured in millimeters, micrometers, or nanometers. In general, a given scleral contact lens may be one that may incorporate a computer-generated special algorithm for laser treatment of a patient's sclera. First, it is possible to combine spots that are reprocessable and the spots can be made into a specific shape through a mask or lens. The mask can be made from a variety of materials, including one or more hydrophobic polymers or a mixture of polymers that are impermeable to the laser. This can provide an additional level of protection for surrounding tissue that is not intended to be affected, in addition to intelligent mapping techniques. The central corneal contact lens can be shaded to protect the cornea from the microscope illumination and from the laser beam itself. In various embodiments, said lens may be disposable rather than reusable while the pattern is on the eye. In addition, said lens may be supplied pre-packaged in sterilized containers.

[00379] Said lens can be created by measuring biometry, morphology, anatomy, topography, keratotomy, scleral thickness, properties, refraction, light scattering of materials and other features and characteristics that can be imported, loaded or otherwise entered into a three-dimensional (3D) dynamic model finite element modeling (FEM), which can be a platform for the “virtual eye”. The system of the invention can process both corneal and lens information and can perform a variety of algorithmic tests after the optical design and all information have been entered. The system can apply mathematical and physical scenarios designed to increase accommodative optical power by manipulating the sclera, and can also shape the cornea into a desired Zernike polynomial profile that will produce maximum accommodative optical power in the case where laser vision correction (LVC) and accommodation are planned . Once completed, the pattern can be created, for example, using ISIS (eye imaging and mapping software to analyze and reproduce mapping in the visible spectrum of the refractive state of the eye, the refractive state of the cornea, for example, both the refractive state of the lens and the refractive state of the cornea, or "dual optics") by using a virtual eye, and the said pattern is visualized. In some embodiments, the ISIS may be a servo mechanism.

[00380] The plate may also include marked coordinates of the 12 and 6 o'clock meridians for orientation by the physician on the eye. The plate may also include a marked specific and different 10/2/4/7 meridian coordinate to orient the treatment quadrants for the clinician. The plate/contact lens can be produced by a suitable 3D printer that is linked to the ISIS motherboard. Once completed, the lens can be sterilized before being placed on the patient's eye.

[00381] In some exemplary steps, the laser, which may be coupled to or comprise an eye motion sensor in some embodiments, may first be calibrated or turned on, and the lens is installed by the physician. The plate can act as a mask and simultaneously direct the laser beam.

[00382] The lens design is called "semi-scleral contact" (SEQ). This lens has, as its starting position, the load-bearing edge of the sclera, on the 2.0-mm portion of the sclera, and consists of three curves. The SEQ lens features 10 fenestrations that prevent the lens from sticking. Uneven corneal surfaces can be corrected using rigid gas permeable (RGP) contact lenses, corneal lenses with diameters ranging from 8.0 mm to 12.0 mm. Scleral lenses can have diameters ranging from 22.0 mm to 25.0 mm.

[00383] Lens design and manufacturing formulas can be used to construct and final fit the lens. To narrow the entire row, you can start with a trial set to select a sagittal size from 2.70 mm to 4.10 mm. The differences in the trial set are the same as in the trial set for RGP lenses with a normal pitch of 0.05 mm between different radii.

[00384] The SEQ lens fitting kit ends with a sagittal height difference of 0.1 mm. Regardless of an oxygen permeability (DK) value of 90 and 10 SEQ lens fenestrations, an oxygen supply problem may persist. Fitted lenses with diameters greater than 12.0 mm have more support so that the lens is immobile and therefore tear exchange cannot occur.

[00385] In some exemplary steps, 1) when the laser contains an eye motion sensor, the lens is positioned by a physician. The plate acts as a mask and simultaneously directs the laser beam. 2) This guide plate system is laser specific; the pattern is placed on the eye and through the lens itself, which is perforated in a process that creates a treatment plan map and aligns all the spots from the scanner before and after the treatment. 3) ISIS stores this information for that particular patient's eye, 4) In the event that a treatment needs to be repeated, all information (topographic, etc.) is imported back into the patient profile for ISIS to recalculate and reconfigure "from start to finish" existing stains to further maximize results. 5) ISIS calculates the central optical power (COP) before and the predicted COP after the simulation, which can inform the patient and surgeon regarding the magnitude of the possible COP for any given patient with and without additional LVC. 6) ISIS also demonstrates, using a virtual eye obtained through FEM, biomechanical functions, optical functions, and numerical simulations of vision at all distances. 7) ISIS also demonstrates post-operative COP, optical axis of the eye (AA), refractive values, Zernike profile changes, etc., and, as a result, continues to collect all the database information to create promising, more complex and optimizing algorithms. 8) ISIS can also profile various algorithms to promote understanding of the dual optical system and suggest changing scenarios based on changes in scleral thickness and other biometrics, geometry, optical system, etc. with age. The benefit of this is great, but a specific embodiment is that ISIS can generate an age-based treatment plan based on an initial assessment of the patient's cataract age. Therefore, ISIS can predict in advance how many spots and what pattern to use, and therefore potential retreatment zones will be “pre-determined” by ISIS based on the first plate. This means that, at subsequent visits, the ISIS can alert the physician when a critical decline in COP occurs, and re-treatment can be initiated at any time (this will be determined by the physician, the patient, and the ISIS results). 9) ISIS can also provide audio interaction and can alert the clinician during treatment if there is a need for intervention when it is completed, and direct the clinician to such examination data that should be assessed for accuracy or given more attention. ISIS may make recommendations to the physician, but the physician directs the selection of programs that ISIS will perform. 10) ISIS also contains a reference list and can search for articles, knowledge, and the latest trends. 11) ISIS can act as an intelligent voice assistant, such as Apple Siri.

[00386] Laser design features for some embodiments may include, a 2.94 μm Er:YAG laser based on an Er:YAG active material for ophthalmic lasers; with duration. pulse about 250 μs; The pulse repetition rate can be 3, 10, 15, 20, 25, 30, 40, 50 pulses/s.

[00387] The different total absorption curves of different tissue components can be important. At a wavelength of 2.94 µm, the laser can have a near-infrared wavelength closest to 3.00 µm, the wavelength of maximum absorption of _H2O . This allows the laser to effectively evaporate _H2O from tissue (ablative mechanism), with little thermal effect. Laser beam-tissue interaction at 2.94 µm: 2.94 µm can be a very important wavelength for tissue ablation; 10-20 times more absorbed by water than CO ₂ at 10.6 µm; 3 times more absorbed by water than by the active medium Er:YSGG at 2.79 µm; The ablation threshold for water at 2.94 µm is about 1 J/cm ² . Ablation occurs instantly and may only be a superficial effect. This allows for very precise ablation with little associated tissue damage.

[00388] Applications of the Er:YAG ophthalmic system may include extended 510K resolution for excision, cutting, evaporation of ocular soft tissue, and therefore expanded applications are foreseeable once the system is approved, including: pterygium surgery; surgical treatment of glaucoma; with infringement of the optic nerve head (posterior sclera); intraocular capsulotomy; extraocular soft tissue surgery; for age-related macular degeneration (AMD); and in other aspects.

[00389] Methods and devices are also provided for treating the sclera and adjacent ocular structures and fractional microporation and surface restoration.

[00390] This application provides a system and method for performing fractional resurfacing of a target area of the eye, such as the sclera, using electromagnetic radiation. Electromagnetic radiation is generated by an electromagnetic radiation source. Electromagnetic radiation is directed to a specific area of the target area of the eye, preferably the sclera. Electromagnetic radiation can be blocked from affecting another part of the target area of the eye by a mask or scleral lens. Alternatively, electromagnetic radiation may be applied to areas of the target area of the sclera other than the specific area.

[00391] This application further describes a method for modifying tissue using a quasi-continuous laser beam, which is designed to change the optical properties of the eye and includes controlled adjustment of the volumetric power density of the beam and assignment of the desired wavelength of the beam. Tissue modification can be achieved by focusing the beam to a preselected starting point in the tissue and moving the focal point of the beam in a predetermined manner relative to the starting point through a given volume of tissue or along a given path in the tissue. Depending on the assigned volumetric power density, the tissue targeted by the focal point can be modified either by photoablation or by changing the viscoelastic properties of the tissue.

[00392] Ophthalmic laser system

[00393] In various embodiments, the ophthalmic laser system of the present invention may include a laser beam delivery system and an eye motion sensor responsive to eye movement and operating in conjunction with the laser beam delivery system to ablate scleral material of the eye in the anterior and/or posterior regions by directing a laser beam pulse to a selected area of the sclera of the eye. The pulses are fired in such a sequence and pattern that no laser pulses hit consecutive locations and no consecutive pulses overlap. The pattern moves in response to movement of the eye. Since the sclera of the eye is “off-axis,” the scanning mechanism is new in that it does not work by fixing the beam on the visual axis of the eye. As shown in FIG. 20 and fig. 20A-20D in US application 15/942,513, in contrast, the "off-axis" scanning mechanism may include an eye interface system using a goniometric mirror or guidance system to ablate opposing quadrants of the sclera off the visual axis. A closed loop feedback system is located within the scanner itself, as well as between the eye interface and the scanner, in the form of a magnetic sensing mechanism that ties the laser head to the eye interface and, through eye positioning via biofeedback, enables both motion tracking eyes and beam delivery.

[00394] In some embodiments, the laser system may include means for selecting and adjusting the shape and size of the area irradiated by each pulse of laser energy without changing the energy density of the beam. By changing the size of the irradiated zone between pulses, some areas of the surface can be eroded more than others, and therefore the surface can be repurposed. The method and system are suitable, among other things, for removing corneal ulcers and repurposing the cornea to remove refractive errors, as well as repurposing optical elements. In some embodiments, the laser beam may enter an optical system housed in an articulating arm and terminating in an eyepiece having a suction cup for attachment to the eye. The optical system may include a beam shaping device to correct any asymmetry in the beam cross-section, a first intermediate telescopic system, a beam size control system, and a second intermediate telescopic system. The beam size control system may contain a diaphragm having a window of a certain shape or a section of the diaphragm of a certain shape and axially moved along the converging or diverging section of the beam. An alternative beam size control system contains a diaphragm having a window of a certain shape and located between coupled systems with variable focal lengths. It is also possible to use mirrors, adjustable slits and refractive systems. In some embodiments, the laser may preferably be an Er:YAG laser. The system may include a measuring device for measuring the surface profile and a feedback control system for controlling the operation of the laser in accordance with the measured and desired profiles.

[00395] In some embodiments, the method, apparatus and system for precision model-guided laser interventions described herein improves the accuracy, speed range, reliability, adaptability, safety and effectiveness of interventions, such as laser microsurgery, especially ophthalmic surgery, including the possibility of performing such laser surgery outside the visual axis. Fig. 19 in US application 15/942,513 presents an exemplary diagram of an instrument and system in accordance with some embodiments of the present invention, which are applicable to those areas of medicine where precision positioning of the laser treatment is critical, in any case where precise limitation of the spatial extent of the laser treatment is desired. impact, and/or in any case where it is necessary to influence the accuracy of operations on a target or group of targets subject to movement during a procedure. Therefore, the system may include the following key components: 1) a user interface consisting of a video display, a microprocessor and controls, a GUI (graphical user interface), 2) an imaging system, which may include a zoomable surgical video microscope, 3) an automated 3D target sensing, locating and tracking system that can follow the movements of a subject's tissue, such as an eye, during surgery, allowing the surgeon to pre-determine a radiation treatment based on an image that is automatically stabilized over an extended period of time, 4 ) a laser that can be focused so that only the precision treatment effects described by the user interface are affected, 5) a diagnostic system including mapping and topography, numerical data, mathematical data, geometric data, imaging data, by measuring precise surfaces and 3D shapes before, during and after the procedure, wherein said measurements must be performed online within periods of time not limited by human reaction times and can be performed in real time, and 6) a fast-acting reliable means of protection by automatically interrupting laser excitation if any conditions justifying such an interruption of the procedure, such as safety concerns.

[00396] FIG. 20(E-G) in US application 15/942,513 further explains the off-axis characteristics of a laser system in accordance with some embodiments of the present invention. As shown, beta(β) is the visual axis in all cases, and alpha(α) is the angle between the visual axis and the impact axis. The axis of rotational symmetry is the vertical axis. Laser treatment areas are preferably not obscured by the patient's eyelids and other facial features. The eye fixation axis and the laser beam axis are at a fixed angle relative to each other to create pores in the specified treatment areas. The supplied laser beam can be rotated around the vertical axis β. In some embodiments, the main features may be that: the laser beam and the scanning area (eg, the OCT area) are on the same centerline, and the scanning area and focal length are consistent with the laser spot size and focal length. The video camera is located slightly away from the axis of the laser beam. The eye fixation point may be at a predetermined angle to the delivered laser beam, rotating 180° around the β axis from the delivered laser beam.

[00397] FIG. 20I in US application 15/942,513 presents another example of off-axis scanning, in accordance with some embodiments of the present invention. As shown, the therapeutic effect can be carried out at an angle.

[00398] In some embodiments, the system can be used for diagnostic and analysis purposes in ophthalmology and eye surgery support and may include 3D to 7D mapping capability for detecting locations, shapes and landmarks on and in a patient's eye in three dimensions and for generating data and signals representing such locations, shapes and eye landmarks, a display means receiving signals from the 3D-7D mapping means, for presenting to the user images representing said locations, shapes and eye landmarks at target locations, including the means display controls to allow the user to select a target location and display a cross-section of areas of the eye in real time both during ablation and after each laser pulse, a position analysis tool associated with the 3D mapping tool and receiving its signals to recognize the occurrence of changes in the position of the signs - eye landmarks, a target tracking means coupled to a position analyzing means for searching for a target tissue landmark feature and finding a new position of said landmark feature after such a change in position and for generating a signal indicating the new position, and a tracking data positioning means for receiving said signal from the target tracking means and for making a change in targeting of the three-dimensional mapping means to a new position of said target tissue landmark feature, thereby following the landmark feature and stabilizing the images on the display means.

[00399] The display means described in various embodiments of the present invention may be a video display and further include a surgical microscope or digital monitor or smart device-based means directed at the patient's eye to obtain real-time microscopic video images of target areas ocular tissue and for inputting video image information into the video image display means to provide such microscopic video images to be displayed and support the user for diagnosis and analysis, with the ability to display different sections of patient tissue selected by the user in real time.

[00400] The tracking means may include a rotating mirror with automatic control, robotic control, Bluetooth control, and the system may include an objective lens arrangement associated with the mapping means and containing a final focusing lens, wherein the rotating the mirror is located within the objective lens arrangement, movable relative to the final focusing lens, in one embodiment.

[00401] In some embodiments, the system may include a laser pulse source for generating a laser beam with a wavelength in the range of infrared to near-infrared light and a power capable of performing the type of ocular surgery required, laser excitation control means for providing the surgeon with the user can control the aiming, depth and excitation time of the laser in order to perform the required surgical operation, a 3D-7D mapping tool aimed at the patient's eye to obtain data representing the location and shape of landmarks on and inside the eye(s), a microprocessor-based tool for receiving data from the three-dimensional mapping means and for converting the data into a format presentable on a screen and suitable for a surgeon/user to accurately determine the location of eye landmarks and the targeting location and depth of the laser beam within said landmarks, and the display means for displaying microprocessor-generated images presenting to the surgeon/user the topography of the eye and the target location and depth of the laser beam before the next laser pulse is initiated, during preparation for and during surgery, wherein the display control allows the surgeon/user to select areas of the eye for display, including cross-sectional images of sections of the eye.

[00402] A source of infrared and near-infrared laser energy operating in a free-running, continuous-wave or Q-switched mode can generate a laser beam capable of performing the desired laser surgery on patient tissue, including within transparent patient tissue. The system may include optical path means for receiving the laser beam and redirecting the laser beam and focusing it, if necessary, on a desired target in the tissue on which the operation is to be performed.

[00403] The system may include a laser housing disposed to enclose and guide the optical path means to obtain images of said target along the optical path means and to provide video image information to the video image display means, and to track movements of tissue of a subject to which the system is aimed. , without causing damage to the subject's tissue before the next laser pulse is initiated, and a corresponding shift in the optical path before the next laser pulse is initiated, so that the 3D mapping tool and the surgical microscope tool generate information and images, as well as the target setting and position laser beam after changes in tissue position. Each captured image frame and information is sent to the video display after each pulse inside the 3D-7D micropore before and after excitation of the laser pulse in a dynamic form of real-time image of the surface. The GUI interface may include an integrated system for simultaneously viewing 7 views of recorded images, including: surface, internal pore, external pore, micropore bottom, whole eyeball image, target matrix area.

[00404] In some embodiments, the preferred projection for a microprocessor may be a 7-hypercube, but other examples exist in spherical volumetric space that can be embedded in a GUI and microprocessor. Orthogonal projections may include examples such as those shown in FIG. 8 US Application No. 15/942,513.

[00405] The system may include multidimensional scaling, linear discriminant analysis and linear dimensionality reduction processing, as well as local linear embedding and isometric maps (ISOMAP). It is also possible to include non-linear dimensionality reduction techniques.

[00406] In some embodiments, the system may allow 1D, 2D, 3D, or 4D transformation, up to and including 7D transformation of topological images or fiber formation. Fibrous formation is a generalization of the concept of a bundle of fibers. A fiber bundle precisely defines the idea of one topological space, called a fiber, parameterized by another topological space, called a base. A fibrous formation is similar to a bundle of fibers, except that the fibers need not be the same space nor homeomorphic; more precisely, they are homotopy equivalent. When filaments are equivalent to the technical properties of topological space in 3-, 4-, 5-, 6-, and 7-dimensional spherical spaces, then the continuous map p:E→B satisfies the homotopy lifting property with respect to any space. Fiber bundles (on paracompact bases) constitute important examples. In homotopy theory, any mapping is “as accurate as” the filament, i.e. any map can be decomposed as a homotopy equivalence in the "space of mapping trajectories" followed by the fiber formation into homotopy layers.

[00407] The laser workstation can be equipped with three programmable axes (X, Y, Z; extendable to 5 axes), contains an automatic rotary table mechanism programmable in the X, Y, Z axes, and a 2-position rotary table. The station can include a human machine interface (HMI) with a level of user access protection, diagnostics and data logging for validated processes and ease of operation, as well as a software sorting module adaptable for uniquely identifiable pulse modulation, with: pore diameter: 0.1 µm - 1000 microns; maximum ablation depth: 0.1 µm - 2000 µm; Pore size tolerance: >±1-20 µm.

[00408] Operational characteristics may also include computer networking, iPad operation, joystick control, touch screen operation, iPhone operation, remote or Bluetooth operation, built-in digital video camera operation, operation with built-in video capabilities and so on.

[00409] SYSTEM AND METHODS FOR DELIVERY OF EYE DRUGS USING LASER

[00410] In some embodiments, the described systems, methods and devices of the present invention can be used to deliver ophthalmic drugs using a laser, for example, methods and devices for phototherapeutic treatment, for example, through ablation, coagulation and/or phototherapeutic modulation of target tissue, for example, scleral tissue and other intraocular tissues such as the choroid, subchoroidal space, neuroretina or other tissues. This application discloses a method of creating an initial penetration surface (A) in a biological membrane (1), comprising the following steps: a) creating a plurality of individual micropores (2 i ) in the biological membrane (1), wherein each individual micropore (2 i ) has a separate penetration surface (Ai); and b) creating such a number of individual micropores ( 2i ) and with such shapes that the initial penetration space (A), which is the sum of the individual penetration surfaces (Ai) of all individual micropores ( 2i ), has the required value. A microporator performing the method is also disclosed. In this case, the biological surface could be an eye. In the case of the eye: the scleral zone is irradiated in such a way that the therapeutic agent passes through the opened zone created by the laser radiation and, thereby, is delivered to the intraocular target tissues in the anterior or posterior parts of the eyeball, for example, the choroid, neuroretina, retinal epithelium, choroid membrane, vitreous humor or aqueous humor.

[00411] US application 15/942,513, incorporated herein, discloses additional embodiments of drug delivery systems, devices and methods that may also be used in and/or intended for use with the system of the present invention.

[00412] In some embodiments, the described systems, methods and devices of the present invention can be used, but are not limited to, for the delivery of drugs, nutrients, grape seed extract, stem cells, protein enriched plasma, photoactivated smart polymer carriers and matrix metalloproteinases. Fig. 20P-1-20P-3 in US application 15/942,513 represent, in some embodiments, exemplary choroid plexus drug targets and nutrient delivery.

[00413] The drug delivery system can be used in a preoperative/intraoperative/postoperative setting to deliver any drug needed in a variety of ocular surgeries for prophylactic or postoperative use.

[00414] In some embodiments, the laser system may include an eye interface setup, such as shown in FIG. 20, 20A-20B in US application 15/942,513. The eye pairing unit may be positioned above the eye during medical surgery. The eye pairing can provide a four quadrant view.

[00415] In some embodiments, the laser system may include a nozzle safety device depicted in FIG. 21A-21B in US application 15/942,513. In some exemplary actions, the nozzle guard may be secured to the nozzle.

[00416] In some embodiments, the laser system may include a workstation depicted in FIG. 21A-21B in US application 15/942,513. The workstation may include a method, apparatus, and system for the above-described model-guided precision laser interventions. The workstation may include a GUI interface, an articulating arm, a laser housing assembly, a CCD video camera, a galvanometric mirror scanner capable of off-axis scanning, a pilot beam, a three-dimensional mapping facility, at least one communications-enabled microprocessor, a power supply and display means, including means for presenting images to the surgeon/user indicating the precise current location of the laser target and depth on computer images that typically include a plan view and selected sections of the eye representing landmark features of the eye at different depths, an imaging system, coupled to video image display means, including three to seven dimensional mapping means for generating, reading and interpreting data to obtain information relating to the seven dimensional location of significant landmark features of the tissue to be operated on, and including microprocessor means for interpreting the data and presenting data to the video display in a format suitable for the surgeon/user, and is equipped with three programmable axes (X, Y, Z; can be extended to 5 axes), contains an automatic rotary table mechanism, programmable in the X, Y, Z axes, and a 2-position rotary table. Contains a human machine interface (HMI) with secure user access. Additional workstation details are provided in US Application No. 15/942,513 and are included herein.

[00417] In some embodiments, the mechanical or physical requirements of the system described herein may be incorporated into a "mobile" workstation with locking wheels and an articulated arm with a counterweight to prevent the cart from tilting during use or transport (see, for example, FIG. 24 and 26-5 of US Application No. 15/942,513). Accessories may include: applicator part (consumable part): The consumable part for collecting ablated tissue creates a hygienic interface between the device and the tissue. Eye attachment (optional): The applicator is reusable, easy to clean, biocompatible and sterilizable. Footswitch: Footswitch control for standard laser delivery.

[00418] Depth control

[00419] In most tissues, disease progression is accompanied by changes in mechanical properties. Laser Speckle Rheology (LSR) is a new method we have developed to measure the mechanical properties of tissue. By illuminating a sample with coherent laser light and calculating speckle intensity modulations from the reflected laser speckle patterns, the LSR method calculates τ, the decay time constant of the intensity decorrelation, which is closely related to the mechanical properties of the tissue. The application of LSR technology can be confirmed by measuring the mechanical properties of the fabric. LSR measurements of τ were performed using a variety of different phantoms and tissue samples and compared with the complex shear modulus G* measured using a rheometer. In all cases, there is a strong correlation between τ and G* (r=0.95, p<0.002). These results demonstrate the effectiveness of the LSR method as a non-invasive and non-contact technology for assessing the mechanical properties of biological samples.

[00420] As is known, disease progression under the influence of the most serious mortality factors, such as cancer and atherosclerosis, and a number of other severe diseases, including neurodegenerative disease and osteoarthritis, is accompanied by changes in the mechanical properties of tissues. The most reliable evidence of the relevance of biomechanical properties to disease assessment can be obtained using traditional ex vivo mechanical testing, which involves staining, stretching, or manipulating the specimen. To meet the need for in situ mechanical characterization, a new optical technique, LSR, can be applied.

[00421] When a cloudy sample, such as tissue, is illuminated with a coherent laser beam, the beams interact with the tissue particles and travel along paths of different lengths due to multiple scattering events. Self-interference creates a pattern of dark and light spots called a laser speckle pattern. Due to the thermal Brownian motion of scattering particles, the paths of light rays can continuously change, and the speckle structure fluctuates over time intervals corresponding to the mechanical properties of the medium surrounding the scattering centers.

[00422] In various embodiments, open-loop biofeedback may be used during intraoperative procedures using chromophore and other biofeedback processes. In chromophore-based embodiments, color saturation can be measured with sensitivity down to micrometric levels of accuracy to determine tissues suitable and unsuitable for surgical procedures. Pulse emission decisions can be made based on various preset color saturation levels. This approach contrasts with current systems, which may only use color or other metrics to provide feedback to imaging equipment rather than to the actual laser delivery devices that perform the treatment. Likewise, crawling subsurface anatomy for predictive depth calibration can leverage real-time depth calculations to determine how close extraction or other treatment procedures are to completion, while supporting active monitoring for unwanted and unexpected anatomical structures. As such, the control of hydrodynamic and other parameters differs from that of previous systems, which can monitor surface levels for reflection but cannot effectively measure depth in tissue or other biological matter.

[00423] The LSR method takes this concept and analyzes the decorrelation of backscattered ray intensity to obtain an estimate of tissue biomechanics. To this end, the LSR method calculates the speckle sequence intensity decorrelation function, g2(t), and derives its decay time constant, τ, as an indicator of biomechanical properties.

[00424] Laser Speckle Rheology Test Bed

[00425] In some exemplary steps, the volumetric mechanical properties of fabric and substrates are measured using an LSR bench setup. This installation includes a laser with multiple coherence lengths of laser radiation, after which a linear polarizer and a beam expander are installed. A focusing lens and a plane mirror are used to focus the illuminated spot onto a location on the target tissue. Laser speckle patterns are imaged using a high-speed CMOS video camera. Additional details regarding LSR measurements are described in US Application No. 15/942,513 and are included herein.

[00426] The systems and methods of the present application can be used to measure the path length differential of photons in a scattering medium using the spectral absorption characteristics of water. Determination of the path length differential is a prerequisite for quantifying chromophore concentration changes measured by near-infrared spectroscopy (NIRS) techniques. Quantitative measurements of chromophore concentration in tissue serve to quantify ablation rates in depth using absorption in water and time-resolved measurements across different layers of scleral tissue as it depends on the ablation rate of absorption, pulse width, and laser beam energy. Quantitative measurements of chromophore concentration in tissue are further described in US Application No. 15/942,513 and are included herein.

[00427] Additional embodiments herein may include the use of a probe design that is configured as multiple source-detector pairs such that it can operate with a white light source to produce continuous absorption spectra and reduced scattering coefficients. The advantages of such a probe with multiple separated sources and detectors are further described in US application No. 15/942,513 and are included in this application.

[00428] In some embodiments, the laser system of the present invention may also include an exemplary multi-layer imaging platform. The platform may include: HL - halogen lamp; MS - mirror system; DD - digital excitation device; L2 - projection lens; L3 - video camera lens; LCTF - liquid crystal tunable filter; and a CCD VC - CCD video camera, or other suitable video camera. Other suitable video cameras can be used. Additional details of the multilayer imaging platform are described in US Application No. 15/942,513 and are included herein.

[00429] Applications of Fluorescence: Fluorescence spectroscopy is a technique used to distinguish between target and non-target tissues based on the profile of the emission spectra of endogenous fluorophores. In the present embodiment, the laser system may include real-time fluorescence spectroscopy-based techniques to discriminate various connective tissue constituents to distinguish ocular scleral connective tissue from adjacent non-target tissue. This anatomical traversal system can be applied again using real-time imaging, such as OCT imaging sensors, as well as chromophore sensors (aqueous, color, etc.) or non-fluorescence spectroscopy.

[00430] Systems of the present invention may include a biofeedback sensor, a scanner including a galvanometer, and a video camera that provide biofeedback that serves to distinguish target and non-target tissues, in addition to transitions within tissues from one chromophore to to the next chromophore, in the form of a sensitive biofeedback loop. Such transitions are relatively high-energy and therefore absorb ultraviolet, visible and near-infrared wavelengths. On the other hand, systems known in the art use simple image-based feedback to a laser module that detects it. Because many biological molecules can absorb light through electronic transitions, their detection and control can be a useful general imaging capability.

[00431] It should be noted that chromophore detection and control, which involves using color differences based on the characteristic light absorption of different materials, as a method of detecting, monitoring and defining boundaries within tissue, is a useful improvement.

[00432] Some exemplary activities may perform numerical simulations of zonal treatments, including: a base model with scleral stiffness and fixation tension varied in individual complete zones: combinations of zonal treatments (with and without changes in fixation): e.g. , separate impacts: 0, 1, 2, 3, 4; combined effects: 1+2+3, 1+2+3+4, 0+1+2+3+4; effective stiffness: elastic modulus (E)=1.61 MPa, equivalent to age ~30 years; weakening of fixation between the sclera and the ciliary body/choroid when using the values in the original accommodation model.

[00433] The effect of zonal treatment on ciliary body deformation during accommodation may include scleral stiffness and scleral stiffness + fixation.

[00434] In some embodiments, different shapes of treatment areas may be applied within a single quadrant of the sclera, based on a basic numerical modeling for multiple (e.g., 3 or 5) critical zones: a basic accommodation model of a healthy eye with aged sclera: starting with stiff sclera: elastic modulus (E)=2.85 MPa, equivalent to age ~50 years; tense fixation between the sclera and the ciliary body/choroid, all other parameters changed (degree of excitation of the ciliary body, stiffness of other components, etc.).

[00435] In some exemplary steps, a numerical treatment simulation of a complex shape may include: a base model with regionally “treated” scleral stiffness: shapes with different treatment areas (without changing fixation), resulting in a treated stiffness: modulus of elasticity ( E)=1.61 MPa, equivalent to age ~30 years; The effective stiffness in each zone can be determined from the shape area in each zone and the values in the original accommodation model.

[00436] The effect of complex shape treatment on ciliary body deformation during accommodation may involve only scleral stiffness.

[00437] Therapeutic hardness may depend on: the volume fraction of pores in the area of treatment, i.e. % of scleral volume removed by treatment; in this case, the volume fraction of the pores changes by changing the parameters of the ablation pores; and other indicators. The resulting stiffness was assessed by a combination of microscale metrics: pores were assumed to be parallel and uniformly spaced/size within volume=volume fraction (% of total scleral volume); the residual volume is “aged” sclera (E=2.85 MPa); ~43.5% of volume required to be removed to change scleral stiffness in the treated area from aged (eg, 50-year-old) to young (eg, 30-year-old); protocols (combinations of % density and depth) allow a maximum volume fraction of 13.7%, which is equivalent to a new stiffness of 2.46 MPa; matrix size = side length of the square treatment zone (mm).

[00438] In some embodiments, the parameters taken into account include the parameters shown in FIG. 26-3A, 26-3A1, 26-3A2 and 36 in US application 15/942,513.

[00439] FIG. 107 examines and shows the following parameters.

[00440] Treatment surface area = treated scleral surface area (mm ² ), wherein treated surface area = matrix square.

[00441] Thickness=thickness of the sclera in the treatment area (mm), assumed to be uniform.

[00442] Treatment volume = volume of sclera that is treated (mm ² ), .

[00443] Density %=percentage of treated surface area occupied by pores (%).

[00444] Spot size=surface area of one pore (mm ² ).

[00445] Number of pores=number of pores in the treatment area.

[00446] *round to the nearest whole number.

[00447] Total pore surface area = total area within the treated surface area occupied by pores:

.

[00448] Depth=depth of one pore (mm); depends on the momentum in each pore (ppp).

[00449] Depth %=percentage of thickness extending inward at a time.

[00450] .

[00451] Total pore volume = the total volume within the treated surface area occupied by pores.

[00452] Volume fraction = percentage of treatment volume occupied by pores (%), i.e. percentage of scleral volume removed by laser.

[00453]

[00454] Relationships between treatment parameters include: laser treatment input parameters; properties of the sclera; input data to calculate the new stiffness.

[00455] Calculate the new scleral stiffness in the treatment area.

[00456] Volume fraction = percentage of treatment volume occupied by pores (%), i.e. percentage of scleral volume removed by laser.

[00457]

[00458] Stiffness=modulus of elasticity of the sclera before treatment (MPa).

[00459] Stiffness after treatment=modulus of elasticity of the sclera after treatment, (MPa); as assessed by a microscale coupled model.

[00460]

[00461] Laser treatment input parameters: scleral properties, input data for calculating new stiffness input into finite element model of treated zones, effect of volume fraction on ciliary body deformation only during accommodation: scleral stiffness only, total area of treated zone (area share=1).

[00462] Protocols=range of possible combinations of density % and depth, sclera in all zones modified to post-treatment stiffness corresponding to pore volume fraction.

[00463] The influence of volume fraction on the deformation of the ciliary body during accommodation:

scleral stiffness + fixation, total area of the zone affected (proportion of area = 1), in a healthy state = calculation results on the initial accommodation model.

[00464] Protocols = range of possible combinations of density % and depth, sclera in all zones, changed to stiffness after treatment, corresponding to the volume fraction of the pores, the effect of volume fraction on the deformation of the ciliary body during accommodation: sclera stiffness + shape of the treatment zone.

[00465] Protocols = range of possible combinations of density % and depth, sclera in all zones, modified to post-treatment stiffness corresponding to pore volume fraction and treatment zone fraction in the area.

[00466] Calculation of J/cm ² : J/cm ² × Hz (1/s) × Pore Size (cm ² )=W; J/cm ² = W/Hz/pore size. Example: the spot is actually “square”, so the area will be calculated as the area of a square: 7.2 J/cm ² = 1.1 W/300 Hz/ (225 µm × 10 ^-4 ) ² .

[00467] Factors that can affect the % ablation depth during surgery on a living eye include: moisture content on the surface and within the tissue, layer of Tenon's fascia or conjunctiva, laser beam angle, thermal damage, possible use of water irrigation, cryoirrigation /cooled eye drops, cryohydrogel cartridge in laser dispensing system (intraoperative medications such as antibiotics/steroids).

[00468] In some embodiments, the described systems, methods, and devices of the invention may further include the following features.

[00469] Adjustable micropore density: Dose and inflammation control can be achieved by varying the number of micropores created in each treatment zone. Adjustable micropore size; dose and flexible variation of microporation pattern. Adjustable micropore thermal profile: The system can create micropores with adjustable thermal profiles that minimize the risk of coagulation zone formation. Adjustable Depth with Depth Sensing: The system creates controllable micropores and prevents ablation from being too deep. Recognize anatomical structures to bypass blood vessels. Laser Safety: The device is a Class 1c laser device, the system detects contact with the eye, and the eye attachment covers the cornea. Integrated smoke evacuation and filtration: Fractional ablation can be performed without the unnecessary need for a smoke evacuation system, since smoke, vapor and tissue particles will be sucked directly by the integrated system. The laser system will contain an integrated real-time video camera (eg, endoscopic video camera, CCD video camera) with a biofeedback loop coupled to the laser guidance system integrated with a GUI display for depth control/limit control.

[00470] In some embodiments, the described systems, methods and devices of the invention may provide: A laser system biofeedback loop integrating chromophore color change recognition using melanin content (computer integration of various stages of micropore creation when color changes; a priori depth information in 3 thickness zones; a laser system capable of integrating a priori scleral thickness mapping for transmission to the laser targeting tool and scleral microporation tool; application of OCT or ultrasonic biomicroscopy (UBM) or 3D tomography; laser system programming code with pulse control for each procedure; electronic communication channel for transmitting data to the report (calibration data and service data, statistical data, etc.). The components of the laser system can have a modular layout for convenient maintenance and repair. Possible inclusion in a self-testing circuit, as well as a calibration procedure in real time before the treatment, after the treatment and before the next treatment. All calibrations can be recorded in a database. Other specific capabilities may include a communications port for online communications (e.g., service troubleshooting using WIFI, report generation and server communication, WIFI access to diagnostic information (error code/parts requests), and either repair and maintenance reporting for troubleshooting, or issuing a service order by a service employee). Some embodiments may include a service kit of spare parts for on-site service and repair; key card of the laser system along with programming of controlled pulses, including a time limit; a pilot beam with a flexible shape for setting boundary conditions, as well as for switching on, if a chemical laser nozzle is on the axis, alignment and positioning; a pilot beam that coincides with the setting fixation beam to start the system according to the pass-fail principle in order to begin therapeutic ablation; requirements for a laser system containing an eye tracking system and an associated eye fixation system for safe ablation with eye movement control; requirements for a laser system containing the ability to perform "axial" energy delivery through a goniometric mirror system to produce microporation on the sclera, or through the use of a slit lamp, or with propagation in a free volume. These solutions may require high power, high beam quality, and integration of a fixation point and/or eye tracking system. High beam quality can mean: focusing the laser system into a spot from 50 µm all the way up to 425 µm. The laser system can perform a high-speed 360-degree treatment by scanning galvanometric mirrors and using robotics to change quadrant treatments within 40-45 seconds for the entire eye (e.g., 4 quadrants in each eye, approximately 10 seconds per quadrant; switching laser position to the next quadrant for 1-2 seconds). The laser system can be a workstation with a built-in foot switch, a computer monitor; OCT system; CCD video camera and/or microscopic system. The laser system may include a table/chair module for patient positioning that can be adjusted from a supine position; with adjustable angle; or in a sitting position; and a power chair.

[00471] In some exemplary steps, the described systems, methods and devices of the invention may include the following medical procedure: 1) A user manual may provide information regarding handling of the system. 2) Place the ophthalmic applicator on the treatment area and place the applicator block on the ophthalmic applicator. 3) The user can set the parameters of the therapeutic effect. 4) The user begins the treatment procedure. 5) The user can be provided with information about the current treatment status. 6) The user may be provided with information regarding calibration of the energy supplied to the eye, before and after treatment. 7) To eliminate unwanted odors, dispersion of ablation smoke can be prevented. 8) The user can be provided with information about eye imaging during treatment, between quadrants and after treatment.

[00472] Microporations - Approximate parameters

Designation Description Procedure Whole eye - 4 quadrants Place and size of treatment effect Procedure: average area 300 cm ² (= average value), partial treatment effects: average area 50 cm ² Scenarios Maximum use case Expected use case Number of therapeutic effects per day Matrix size 5 mm (variable in the range 2 mm - 14 mm) 5 mm (variable in the range 2 mm - 14 mm) “Standard” microporation (MP) parameters; based on preliminary experiments: MP1 Pulse repetition rate 300 Hz, pulse duration 125 µs, 5 pulses per pore, 5% MP2 Pulse repetition rate 200 Hz, pulse duration 175 µs, 5 pulses per pore, 7% MP3 Pulse repetition rate 100 Hz, pulse duration 225 µs, 7 pulses per pore, 8% MP4 Pulse repetition rate 200 Hz, pulse duration 225 µs, 5 pulses per pore, 6%

[00473] The system may be operated using a pre-approved electronic key card. Visualization required during surgery: Illumination of the eye to assist in providing visualization, a light source, either external or built into the fixation device of the laser adapter, video camera, and GUI interface to the computer monitor may be a required module. The patient may be in a horizontal or inclined, or sitting position. A guard may be required to protect the patient's eye during procedures. Operation: The system can allow the laser to turn on when the applicator and applicator part are attached, with proper tissue contact and verified user access. Pore depth control: maximum depth controlled by a limit switch (with optical or equivalent control). Control of eye movement during the procedure: For a completely non-contact procedure on the eye, eye tracking technology can be enabled, with appropriate eye fixation points. Vascular Bypass: Scanning/identification of the ocular vasculature may be provided to avoid microporation in the area. See fig. 4A-1-4A-10 in US application 15/942,513, which show how microporation/nanoporation can be used to remove superficial, subsurface and intermediate tissue and change superficial, intermediate biomechanical characteristics (e.g., planarity, surface porosity, tissue geometry, viscoelasticity tissue and other biomechanical and biorheological characteristics) of the target surface or target tissue being ablated.

[00474] Performance requirements may include: Variable pore size, pore matrix size, and pore location. Approximate preparation time: 5 minutes from the moment the device is turned on until the start of the microporation process (average user reaction time is assumed). Robotics built into quadrants to meet treatment time requirements. The therapeutic effect time can be <60 s, 45 s per procedure. Micropore diameter: Adjustable between 50 µm - 600 µm. Tissue ablation rate: adjustable in the range of 1-15%. Microporation matrix size: Area adjustable from 1 mm × 1 mm to 14 × 14 mm, square matrix shape with specially shaped pores. Possibility of obtaining multiple ablation patterns. Short press to turn the laser on and off: The actual microporation process can be started by just briefly pressing the foot switch, instead of pressing it throughout the entire microporation. Turning off the laser can be done in the same way. Ablated pore depth: from 5% to 95% of the scleral thickness. Biocompatibility: All tissue contact parts must be made of materials that meet medical device requirements.

[00475] In some embodiments, the system may include: a laser with a wavelength wavelength of: 2900 nm +/- 200 nm; near the maximum absorption of water in the mid-IR range of the spectrum. Maximum laser energy density: ≥15.0 J/cm ² on tissue, ≥25.0 J/cm ² on tissue; to expand treatment options 2900 nm +/- 200 nm; near the maximum absorption of water in the mid-IR range of the spectrum. Laser Setting Combinations: Laser repetition rate and pulse width can be adjusted using preset combinations in the range of 100-500 Hz and 50-225 µs. Said range may be a minimum range, for example, ≥15.0 J/cm ² tissue, or ≥25.0 J/cm ² tissue, to expand treatment options. Number of pulses per pore with aggressive treatment strategy: For the formation of deep micropores in the dermis, for example, with a depth of >1 mm, you can also select the settings for “aggressive” treatment tactics. Since the depth is regulated mainly by the integral flux density, a large number of pulses per pore should automatically lead to an increase in depth values. Therefore, the pulses per pore (PPP) values can be adjusted in the range of 1-15 PPP. Shock and vibration protection:

[00476] In some embodiments, the described systems, methods, and devices of the invention may include a protective lens, as shown in FIG. 27A-27C in US application 15/942,513.

[00477] In some embodiments, the described systems, methods, and devices of the invention may include an eyelid speculum, as shown in various embodiments in FIGS. 136-138 and figs. 28A-29B in US application 15/942,513.

[00478] One or more of the components, processes, features and/or functions presented in the figures may be differently arranged and/or combined in a single component, block, feature or function, or implemented as multiple components, steps or functions . Additional elements, components, processes and/or functions may be introduced without departing from the invention. The devices and/or components depicted in the figures may be configured to implement one or more of the methods, features or processes shown in the figures. The algorithms described in this application can also be effectively implemented in software and/or embedded in hardware.

[00479] It should be noted that aspects of the present invention may be described herein in the form of a process that is represented by a flowchart, route diagram, block diagram, or block diagram. Although a flowchart may describe activities as a sequential process, many of the activities may be performed in parallel or simultaneously. In addition, the order of operations can be rearranged. The process ends when the operations are completed. A process may correspond to a method, function, procedure, routine, subroutine, or the like. When a process matches a function, its termination corresponds to the function returning to the calling function or main function.

[00480] In various embodiments, the algorithms and other software used to implement the systems and methods disclosed herein are typically stored in non-volatile computer-readable memory and typically contain instructions that, when executed by one or more processors or processor systems associated with said memory perform the steps to implement the subject matter of the invention described in this application. The implementation of imaging, machine learning, prediction, automatic correction and other aspects of the invention described herein can be used with current and future medical systems and devices to perform medical procedures that provide benefits not currently known in the field.

[00481] In some embodiments, the described systems, methods, and devices are performed prior to or concurrently with various medical procedures. In some embodiments, they may be implemented as stand-alone systems, methods and devices, together with any required components, to achieve the respective purposes, as will be understood by those skilled in the art. It should be understood that medical procedures that benefit from the information provided in this application are not limited to implementations using the following information, but may also benefit from other procedures previously known, currently performed, and developed in the future.

[00482] The above-described implementations are considered innovative compared to the prior art and are considered critical to the practice of at least one aspect of the invention and to achieving the above-described objects. The language used in the specification to present the present embodiments is to be understood not only in terms of their generally stated meanings, but to include special interpretation within the structure of the present specification, material, or acts beyond the scope of their generally stated meanings. Thus, while an element may be understood in the context of the present specification to include more than one meaning, its application should be understood to be generalized to all possible meanings supported by the description and the language and statements describing the element.

[00483] Interpretations of the above-described statements or elements of the drawings are intended to include not only the combination of elements that are expressly described, but all equivalent structure, material or action to perform substantially the same function, in substantially the same manner, to obtain , essentially the same result. Therefore, in this sense, it is contemplated that any one of the described elements and various embodiments thereof can be equivalently replaced by two or more elements or that two or more elements can be replaced by a single element in a claim.

[00484] Variations of the claimed subject matter discovered by one of ordinary skill in the art, not known or later developed, are definitely considered equivalents within the intended scope of the invention and various embodiments thereof. Therefore, obvious substitutions now or later known to one of ordinary skill in the art are stated to be within the scope of the elements described. Thus, the present disclosure is intended to be understood to include everything specifically illustrated and described above that is conceptually equivalent, that is obviously interchangeable, and that includes the basic ideas.

[00485] In the above description and in the figures, like elements are designated by like numerals. The use of “for example,” “etc.,” and “or” indicates non-exclusive alternatives without limitation unless otherwise noted. The use of “including” or “includes” means “including but without limitation” or “includes but without limitation” unless otherwise stated.

[00486] The above expression "and/or" placed between the first object and the second object means one of the following (1) the first object, (2) the second object, and (3) the first object and the second object. Several objects listed through “and/or” should be treated in the same way, i.e. "one or more" objects connected in this way. In addition to the objects specifically designated by “and/or,” other objects may be present, whether related or unrelated to the specifically designated objects. Thus, by way of non-limiting example, the reference to "A and/or B", when used in connection with an open-ended expression such as "comprising", may refer, in one embodiment, to A only (optionally including other entities, except B); in another embodiment, to B only (optionally including objects other than A); in yet another embodiment, to both A and B (optionally including other objects). These objects can be elements, actions, constructs, processes, operations, values, and the like.

[00487] It should be noted that where a single value or range of values is given in this application (for example, 5, 6, 10, 100, etc.), it should be remembered that the value or range of values may be broader than a single number or range of numbers unless otherwise noted. Any specific values mentioned in this application are presented merely as examples.

[00488] Various terms used above and throughout the present invention may have the same meanings set forth in US Application No. 15/942,513, US Provisional Application No. 62/843,403, Taiwan Application No. 108111355, and International Application No. PCT/US18/25608 , which are fully included in this application.

Claims (26)

1. A system for treating biological tissue of the eye by microporation, wherein the system contains: controller; laser head system containing: frame, a laser subsystem for generating a beam of laser radiation along the axis of influence not aligned with the visual axis of the patient, and configured to be used in the process of subsurface ablative treatment to create a pore pattern, and a lens configured to focus the laser beam onto the target tissue; an eye tracking subsystem for tracking landmarks and eye movements; a depth control subsystem for controlling the depth of microporation on the target tissue; And wherein the controller is configured to control movements of the laser subsystem, including a tilt movement, a rotation movement, and a deflection movement. 2. The system as claimed in claim 1, further comprising a scanning system communicated with an eye tracking subsystem and a depth control subsystem for scanning with a focal spot over the target tissue area. 3. The system of claim 1, further comprising a bypass subsystem for identifying biological structures or locations of the eye. 4. The system according to claim 1, additionally containing one or more diffraction beam splitters. 5. The system of claim 1, wherein the pore pattern includes pores of uniform size, shape and depth. 6. The system of claim 1, wherein the pore pattern includes pores of different sizes, shapes and depths. 7. The system of claim 1, wherein the pore pattern includes pores having equal spacing. 8. The system according to claim 1, in which the pore pattern includes pores having different spacing, and wherein the pore pattern is at least a pattern made with the pores closely spaced to each other or the pattern is made in the form of a regular, repeating geometric pattern, or placed at intervals. 9. The system according to claim 1, in which the pore depth is proportional to the total laser energy. 10. The system according to claim 1, in which the depth control subsystem is additionally configured to measure and estimate the pore depth. 11. The system according to claim 10, in which the pore depth is measured between pulses. 12. The system of claim 10, wherein the pore depth is measured and estimated between pulses. 13. The system according to claim 1, wherein the pore pattern is a spiral pattern. 14. The system of claim 13, wherein the pore pattern is a spiral pattern of an Archimedean spiral, a Cornu spiral, a parabolic spiral, a hyperbolic spiral, a rod spiral, a logarithmic spiral, a Fibonacci spiral, a golden spiral, or combinations thereof. 15. The system according to claim 1, in which the pore pattern is made in the form of a matrix array. 16. The system of claim 1, wherein the laser head system further comprises a display for providing eye fixation. 17. The system according to claim 1, wherein the laser head system further comprises illumination sources. 18. The system of claim 1, wherein the laser head system further comprises a video camera system configured to track eye movement.

Images