Systems and Methods for Ocular Laser Surgery and Therapeutic Procedures

Abstract

To provide systems and methods for restoring normal ocular physiological functions taking into account effects of pores or creating a lattice or matrix array of pores with a central hexagon or polygon in three-dimensional (3D) tissue.SOLUTION: Systems, devices, and methods are provided to deliver microporation medical treatments to improve biomechanics, wherein the system includes a laser for generating a beam of laser radiation on a treatment-axis not aligned with a patients visual-axis, operable for use in subsurface ablative medical treatments to create an array pattern of micropores that improves biomechanics. The array pattern of micropores is at least one of a radial pattern, a spiral pattern, a phyllotactic pattern, or an asymmetric pattern.SELECTED DRAWING: Figure 41

Description

Technical Field

[0001] Field of the Invention

[0001] The subject matter described herein generally relates to systems, methods, treatments, and devices for laser scleral micro-poration, and more particularly to systems, methods, and devices for rejuvenation of ocular tissue by laser scleral micro-poration, specifically for rejuvenation of connective tissue related to aging of the connective tissue or rejuvenation of the eye or sclera.

Background Art

[0002] Background of the Invention

[0002] The eye is a biomechanical structure, a complex sensory organ that includes complex muscle, drainage, and body fluid mechanisms involved in visual function and ocular biotransport. The accommodation system is the main movable system in the eye organ and facilitates many physiological and visual functions of the eye. The physiological role of the accommodation system is to move water, blood, nutrients, oxygen, carbon dioxide, and other cells around the eye organ. Generally, the loss of accommodation ability in presbyopic eyes is caused by various lens factors affected by aging, as well as extra-lenticular and physiological factors. The increase in ocular rigidity with aging causes stress and strain on these eye structures and may also affect the accommodation ability, which can affect the eye in the form of reduced biomechanical efficiency of physiological processes, including, for example, visual accommodation, aqueous humor hydrodynamics, vitreous humor hydrodynamics, and ocular pulsatile blood flow. Current techniques only manipulate the optical system by some artificial means that exchange the refractive power of one optical system of the eye, such as by refractive corrective laser surgery, adaptive optics, or corneal or intraocular implants, and the importance of maintaining the physiological functions of other optical systems and the accommodative mechanism is ignored.

[0003] In addition, implant devices in current scleras achieve a mechanical effect during adjustment. Such devices do not consider the effect of creating a matrix array of pores in a hexagonal or polygonal shape centered on "pores", "micro-pores", or 3D tissue. Therefore, current techniques and devices cannot restore normal physiological eye functions. Summary of the Invention Problems to be Solved by the Invention

[0004]

[0004] Therefore, there is a need for a system and method for restoring normal physiological eye functions that takes into account creating a lattice or matrix array of pores in a hexagonal or polygonal shape centered on "pores" or three-dimensional (3D) tissue. Means for Solving the Problems

[0005] Summary of the Invention

[0005] A system, device, and method for laser scleral micro-poration for rejuvenation of eye tissue, specifically for rejuvenation of connective tissue related to aging of the sclera, are disclosed. The systems, devices, and methods disclosed herein restore the physiological functions of the eye, including restoring physiological regulation or physiological pseudoregulation through natural physiological and biomechanical phenomena related to the natural accommodation of the eye.

[0006]

[0006] In some embodiments, a system is provided for delivering a medical treatment by micro-poration to improve biomechanics, where the system includes a laser operable to generate a laser radiation beam on a treatment axis that is not aligned with the patient's line of sight for use in a medical treatment by subsurface ablation to create an array or lattice pattern of micro-pores that improve biomechanics. The system includes a housing and a controller within the housing that communicates with the laser and is operable to control the dosimetry of the laser radiation beam upon application to a target tissue. The system also includes a lens operable to focus the laser radiation beam onto the target tissue and an automated off-axis subsurface anatomical structure tracking, measurement, and avoidance system. The array pattern of micro-pores is at least one of a radial pattern, a spiral pattern, a phyllotaxis pattern, or an asymmetric pattern.

[0007]

[0007] In some embodiments, the array pattern of micro-pores is a spiral pattern of an Archimedes spiral, an Euler spiral, a Fermat spiral, a hyperbolic spiral, a lituus, a logarithmic spiral, a Fibonacci spiral, a golden spiral, a Bravais lattice, a non-Bravais lattice, or a combination thereof.

[0008]

[0008] In some embodiments, the array pattern of micro-pores has a controlled asymmetry that is at least partial rotational asymmetry about the center of the array pattern. The at least partial rotational asymmetry can extend to at least 51 percent of the micro-pores of the array pattern. The at least partial rotational asymmetry can extend to at least 20 micro-pores of the array pattern. In some embodiments, the array pattern of micro-pores has a random asymmetry.

[0009]

[0009] In some embodiments, the array pattern of micro - pores has a controlled symmetry that is at least partially rotationally symmetric about the center of the array pattern. The at least partial rotational symmetry can extend to at least 51 percent of the micro - pores of the array pattern. The at least partial rotational symmetry can extend to at least 20 micro - pores of the array pattern. In some embodiments, the array pattern of micro - pores can have random symmetry.

[0010]

[0010] In some embodiments, the array pattern has a plurality of clockwise spirals and a plurality of counter - clockwise spirals. The number of clockwise spirals and the number of counter - clockwise spirals can be Fibonacci numbers or multiples of Fibonacci numbers, or they can be ratios that converge to the golden ratio.

[0011]

[0011] In some embodiments, a method is provided for delivering a medical treatment by microporation to improve biomechanics. The method includes generating a treatment beam on a treatment axis that is not aligned with the patient's visual axis in a medical treatment by subsurface ablation using a laser to create an array of micro - pores for improving biomechanics; controlling the dosimetry of the treatment beam upon application to the target tissue by a controller in electrical communication with the laser; focusing the treatment beam on the target tissue by a lens; monitoring the eye position at which the treatment beam is applied by an automated off - axis subsurface anatomical structure tracking, measuring, and avoidance system; and wherein the array pattern of micro - pores is at least one of a radial pattern, a spiral pattern, a phyllotaxis pattern, or an asymmetric pattern.

[0012] Brief Description of the Drawings

[0012] Details of the subject matter shown in this specification can become apparent by considering the accompanying drawings with respect to both its structure and operation. In the figures, like reference numerals refer to like parts. The components in the figures are not necessarily to scale; rather, emphasis has been placed on illustrating the principles of the subject matter. Further, all illustrations are intended to convey concepts, and here, relevant sizes, shapes, and other detailed attributes may be illustrated schematically rather than literally or precisely. Illustrated in the accompanying drawings is at least one of the best modes of the present invention.

Brief Description of the Drawings

[0013]

Figure 1A-1

[0013] An exemplary strong membrane laser rejuvenation method for viscoelasticity according to an embodiment of the present disclosure is shown.

Figure 1A-2

[0013] An exemplary strong membrane laser rejuvenation method for viscoelasticity according to an embodiment of the present disclosure is shown.

Figure 1A-3

[0013] An exemplary strong membrane laser rejuvenation method for viscoelasticity according to an embodiment of the present disclosure is shown.

Figure 1A-4

[0014] An exemplary posterior scleral rejuvenation method and optic nerve head decompression according to an embodiment of the present disclosure are shown.

Figure 1A-5

[0014] An exemplary posterior scleral rejuvenation method and optic nerve head decompression according to an embodiment of the present disclosure are shown.

Figure 1A-6

[0014] An exemplary posterior scleral rejuvenation method and optic nerve head decompression according to an embodiment of the present disclosure are shown.

Figure 1A-7

[0014] An exemplary posterior scleral rejuvenation method and optic nerve head decompression according to an embodiment of the present disclosure are shown.

Figure 1B

[0015] An exemplary pore matrix array according to an embodiment of the present disclosure is shown.

Figure 1C

[0015] An exemplary pore matrix array according to an embodiment of the present disclosure is shown.

Figure 1D

[0015] Shows an exemplary pore matrix array according to an embodiment of the present disclosure.

Figure 1E

[0015] Shows an exemplary pore matrix array according to an embodiment of the present disclosure.

Figure 1E-1

[0016] Shows an exemplary pattern velocity calculation according to an embodiment of the present disclosure.

Figure 1E-2

[0017] Shows an exemplary solidification zone according to an embodiment of the present disclosure.

Figure 1F

[0018] Shows an exemplary schematic projection view of the bottom surface of the hep unit cell on the closest-packed layer according to an embodiment of the present disclosure.

Figure 1G-1

[0019] Shows an exemplary laser profile according to an embodiment of the present disclosure.

Figure 1G-2

[0019] Shows an exemplary laser profile according to an embodiment of the present disclosure.

Figure 1G-3

[0019] Shows an exemplary laser profile according to an embodiment of the present disclosure.

Figure 1G-4

[0019] Shows an exemplary laser profile according to an embodiment of the present disclosure.

Figure 1H

[0020] Shows an exemplary pore structure feature according to an embodiment of the present disclosure.

Figure 2A-1

[0021] Shows an exemplary treatment pattern having three critical zones according to an embodiment of the present disclosure.

Figure 2A-2

[0021] Shows an exemplary treatment pattern having three critical zones according to an embodiment of the present disclosure.

Figure 2B-1

[0022] Shows an exemplary treatment pattern having five critical zones according to an embodiment of the present disclosure.

Figure 2B-2

[0022] Shows an exemplary treatment pattern having five critical zones according to an embodiment of the present disclosure.

Figure 2B-3

[0022] Exemplary treatment patterns having five critical zones according to an embodiment of the present disclosure are shown.

Figure 2C-1

[0023] Exemplary laser scleral de-crosslinking of scleral thick fibers and fine fibers according to an embodiment of the present disclosure is shown.

Figure 2C-2

[0023] Exemplary laser scleral de-crosslinking of scleral thick fibers and fine fibers according to an embodiment of the present disclosure is shown.

Figure 2C-3

[0023] Exemplary laser scleral de-crosslinking of scleral thick fibers and fine fibers according to an embodiment of the present disclosure is shown.

Figure 2C-4

[0023] Exemplary laser scleral de-crosslinking of scleral thick fibers and fine fibers according to an embodiment of the present disclosure is shown.

Figure 2D-1

[0024] Exemplary treatment effects on ocular rigidity according to an embodiment of the present disclosure are shown.

Figure 2D-2-4

[0024] Exemplary treatment effects on ocular rigidity according to an embodiment of the present disclosure are shown.

Figure 2E

[0025] Another exemplary three critical significant zones according to an embodiment of the present disclosure are shown.

Figure 2F

[0026] Exemplary matrix arrays of micro-incisions in four inclined quadrants according to an embodiment of the present disclosure are shown.

Figure 2G

[0027] Exemplary graphic displays of treatment results according to an embodiment of the present disclosure are shown.

Figure 2H

[0028] Exemplary box plots of ocular rigidity according to an embodiment of the present disclosure are shown.

Figure 2I

[0029] Exemplary box plots of pre-operative and post-operative intraocular pressures according to an embodiment of the present disclosure are shown.

Figure 2J

[0030] Exemplary graphs showing uncorrected visual acuity and corrected distance visual acuity according to an embodiment of the present disclosure are shown.

Figure 2K-1

[0031] Illustrates an exemplary protocol execution according to an embodiment of the present disclosure.

Figure 2K-1-A

[0032] Illustrates exemplary protocol parameters for three critical zones according to an embodiment of the present disclosure.

Figure 2K-1-B

[0032] Illustrates exemplary protocol parameters for three critical zones according to an embodiment of the present disclosure.

Figure 2K-1-C

[0032] Illustrates exemplary protocol parameters for three critical zones according to an embodiment of the present disclosure.

Figure 2K-2

[0033] Illustrates exemplary diagrams of various protocols and their results according to an embodiment of the present disclosure.

Figure 2K-3

[0033] Illustrates exemplary diagrams of various protocols and their results according to an embodiment of the present disclosure.

Figure 2K-4

[0033] Illustrates exemplary diagrams of various protocols and their results according to an embodiment of the present disclosure.

Figure 2K-5

[0033] Illustrates exemplary diagrams of various protocols and their results according to an embodiment of the present disclosure.

Figure 2K-6

[0033] Illustrates exemplary diagrams of various protocols and their results according to an embodiment of the present disclosure.

Figure 2K-7

[0033] Illustrates exemplary diagrams of various protocols and their results according to an embodiment of the present disclosure.

Figure 2K-8

[0033] Illustrates exemplary diagrams of various protocols and their results according to an embodiment of the present disclosure.

Figure 2K-9

[0033] Illustrates exemplary diagrams of various protocols and their results according to an embodiment of the present disclosure.

Figure 2K-10

[0033] Illustrates exemplary diagrams of various protocols and their results according to an embodiment of the present disclosure.

Figure 2K-11

[0033] Illustrates exemplary diagrams of various protocols and their results according to an embodiment of the present disclosure.

Figure 2K-12

[0033] Illustrative diagrams of various protocols and their results according to an embodiment of the present disclosure are shown.

Figure 2K-13

[0033] Illustrative diagrams of various protocols and their results according to an embodiment of the present disclosure are shown.

Figure 2K-14

[0033] Illustrative diagrams of various protocols and their results according to an embodiment of the present disclosure are shown.

Figure 2K-15

[0033] Illustrative diagrams of various protocols and their results according to an embodiment of the present disclosure are shown.

Figure 2K-16

[0033] Illustrative diagrams of various protocols and their results according to an embodiment of the present disclosure are shown.

Figure 2K-17

[0033] Illustrative diagrams of various protocols and their results according to an embodiment of the present disclosure are shown.

Figure 2K-18

[0034] An illustrative electroporation pattern according to an embodiment of the present disclosure is shown.

Figure 2K-19

[0034] An illustrative electroporation pattern according to an embodiment of the present disclosure is shown.

Figure 2K-20

[0035] Another illustrative pattern according to an embodiment of the present disclosure is shown.

[0036] Another illustrative protocol and its result according to an embodiment of the present disclosure are shown.

Figure 3A

[0037] An illustrative laser treatment system according to an embodiment of the present disclosure is shown.

Figure 3B

[0038] Another illustrative laser treatment system according to an embodiment of the present disclosure is shown.

Figure 3C

[0039] An illustrative camera correction system according to an embodiment of the present disclosure is shown.

Figure 3D

[0040] An illustrative flowchart according to an embodiment of the present disclosure is shown.

Figure 4A

[0041] Another exemplary laser treatment system according to an embodiment of the present disclosure is shown.

Figure 4A-1

[0042] Shows how microporation / nanoporation can be used according to an embodiment of the present disclosure.

Figure 4A-2

[0042] Shows how microporation / nanoporation can be used according to an embodiment of the present disclosure.

Figure 4A-3

[0042] Shows how microporation / nanoporation can be used according to an embodiment of the present disclosure.

Figure 4A-4

[0042] Shows how microporation / nanoporation can be used according to an embodiment of the present disclosure.

Figure 4A-5

[0042] Shows how microporation / nanoporation can be used according to an embodiment of the present disclosure.

Figure 4A-6

[0042] Shows how microporation / nanoporation can be used according to an embodiment of the present disclosure.

Figure 4A-7

[0042] Shows how microporation / nanoporation can be used according to an embodiment of the present disclosure.

Figure 4A-8

[0042] Shows how microporation / nanoporation can be used according to an embodiment of the present disclosure.

Figure 4A-9

[0042] Shows how microporation / nanoporation can be used according to an embodiment of the present disclosure.

Figure 4A-10

[0042] Shows how microporation / nanoporation can be used according to an embodiment of the present disclosure.

Figure 4B-1

[0043] Another exemplary laser treatment system according to an embodiment of the present disclosure is shown.

Figure 4B-2

[0043] Another exemplary laser treatment system according to an embodiment of the present disclosure is shown.

Figure 5

[0044] Shows an exemplary flowchart of OCT-based depth control according to an embodiment of the present disclosure.

Figure 6

[0045] Shows an exemplary laser treatment system component map according to an embodiment of the present disclosure.

Figure 7

[0046] Shows another exemplary laser treatment system according to an embodiment of the present disclosure.

Figure 7-1

[0047] Shows another exemplary laser treatment system according to an embodiment of the present disclosure.

Figure 8

[0048] Shows an exemplary orthographic projection according to an embodiment of the present disclosure.

Figure 9

[0049] Shows an exemplary 3D map according to an embodiment of the present disclosure.

Figure 10

[0050] Shows an exemplary design pattern according to an embodiment of the present disclosure.

Figure 11

[0051] Shows an exemplary model according to an embodiment of the present disclosure.

Figure 12

[0052] Shows an exemplary schematic representation according to an embodiment of the present disclosure.

Figure 13

[0053] Shows an exemplary graphic image according to an embodiment of the present disclosure.

Figure 14A

[0055] Shows an exemplary microporation pattern according to an embodiment of the present disclosure.

Figure 14B

[0056] Is an exemplary explanatory diagram of a phyllotaxis spiral pattern according to an embodiment of the present disclosure.

Figure 14C

[0057] Is another exemplary explanatory diagram of a phyllotaxis spiral pattern according to an embodiment of the present disclosure.

Figure 14D

[0058] Is an exemplary explanatory diagram of the Vogel model according to an embodiment of the present disclosure.

Figure 14E

[0058] Exemplary explanatory diagram of the Vogel model according to an embodiment of the present disclosure.

Figure 15A

[0059] Exemplary explanatory diagram of the phyllotaxis spiral pattern according to an embodiment of the present disclosure.

Figure 15B

[0059] Exemplary explanatory diagram of the phyllotaxis spiral pattern according to an embodiment of the present disclosure.

Figure 15C

[0059] Exemplary explanatory diagram of the phyllotaxis spiral pattern according to an embodiment of the present disclosure.

Figure 15D

[0059] Exemplary explanatory diagram of the phyllotaxis spiral pattern according to an embodiment of the present disclosure.

Figure 15E

[0059] Exemplary explanatory diagram of the phyllotaxis spiral pattern according to an embodiment of the present disclosure.

Figure 15F

[0059] Exemplary explanatory diagram of the phyllotaxis spiral pattern according to an embodiment of the present disclosure.

Figure 16A

[0060] Exemplary explanatory diagram of exemplary micro - poration derived from the icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16B

[0060] Exemplary explanatory diagram of exemplary micro - poration derived from the icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16C

[0060] Exemplary explanatory diagram of exemplary micro - poration derived from the icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16D

[0060] Exemplary explanatory diagram of exemplary micro - poration derived from the icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16E

[0060] Exemplary explanatory diagram of exemplary micro - poration derived from the icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16F

[0060] Exemplary explanatory diagram of exemplary micro - poration derived from the icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16G

[0060] Exemplary explanatory diagram of an exemplary micro-poration derived from an icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16H

[0060] Exemplary explanatory diagram of an exemplary micro-poration derived from an icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16I

[0060] Exemplary explanatory diagram of an exemplary micro-poration derived from an icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16J

[0060] Exemplary explanatory diagram of an exemplary micro-poration derived from an icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16K

[0060] Exemplary explanatory diagram of an exemplary micro-poration derived from an icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16L

[0060] Exemplary explanatory diagram of an exemplary micro-poration derived from an icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16M

[0060] Exemplary explanatory diagram of an exemplary micro-poration derived from an icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 16N

[0060] Exemplary explanatory diagram of an exemplary micro-poration derived from an icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 17A

[0061] Exemplary explanatory diagram of a micro-poration pattern derived from an icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 17B

[0061] Exemplary explanatory diagram of a micro-poration pattern derived from an icosahedron pattern shape according to an embodiment of the present disclosure.

Figure 18

[0062] Exemplary lens design according to an embodiment of the present disclosure.

Figure 19

[0063] Exemplary devices and systems according to certain embodiments of the present disclosure are shown.

Figure 20

[0064] Exemplary "off-axis" scanning mechanisms according to certain embodiments of the present disclosure are shown.

Figure 20A

[0064] Exemplary "off-axis" scanning mechanisms according to certain embodiments of the present disclosure are shown.

Figure 20B

[0064] Exemplary "off-axis" scanning mechanisms according to certain embodiments of the present disclosure are shown.

Figure 20C

[0064] Exemplary "off-axis" scanning mechanisms according to certain embodiments of the present disclosure are shown.

Figure 20D

[0065] Exemplary strong film fixing components according to certain embodiments of the present disclosure are shown.

Figure 20E

[0066] Furthermore, off-axis features of a laser system according to certain embodiments of the present disclosure are shown.

Figure 20F

[0066] Furthermore, off-axis features of a laser system according to certain embodiments of the present disclosure are shown.

Figure 20G

[0067] Another exemplary off-axis scanning type according to certain embodiments of the present disclosure is shown.

Figure 20H

[0067] Another exemplary off-axis scanning type according to certain embodiments of the present disclosure is shown.

Figure 20I

[0067] Another exemplary off-axis scanning type according to certain embodiments of the present disclosure is shown.

Figure 20J

[0068] The aqueous humor flow path in the eye is shown.

Figure 20K

[0069] How the present system can increase the outflow of the vitreous membrane according to certain embodiments of the present disclosure is shown.

Figure 20L

[0069] How the present system can increase the outflow of the vitreous membrane according to certain embodiments of the present disclosure is shown.

Figure 20M

[0070] An exemplary handpiece delivery system versus an articulated arm according to certain embodiments of the present disclosure is shown.

Figure 20N

[0071] Shows treatment zones in the anterior and posterior eye balls according to an embodiment of the present disclosure.

Figure 20O

[0071] Shows treatment zones in the anterior and posterior eye balls according to an embodiment of the present disclosure.

Figure 20P-1

[0072] Shows choroid plexus drug and neutraceuticals delivery according to an embodiment of the present disclosure.

Figure 20P-2

[0072] Shows choroid plexus drug and neutraceuticals delivery according to an embodiment of the present disclosure.

Figure 20P-3

[0072] Shows choroid plexus drug and neutraceuticals delivery according to an embodiment of the present disclosure.

Figure 20Q-1

[0073] Shows how the present system can potentially be used for transcleral drug delivery according to an embodiment of the present disclosure.

Figure 20Q-2

[0073] Shows how the present system can potentially be used for transcleral drug delivery according to an embodiment of the present disclosure.

Figure 20Q-3

[0073] Shows how the present system can potentially be used for transcleral drug delivery according to an embodiment of the present disclosure.

Figure 20R

[0074] Shows an exemplary optthacoil.

Figure 20S

[0075] Shows a drug delivery carrier in some embodiments according to an embodiment of the present disclosure.

Figure 20T-1

[0076] Shows an exemplary scleral wafer according to an embodiment of the present disclosure.

Figure 20T-2

[0076] Shows an exemplary scleral wafer according to an embodiment of the present disclosure.

Figure 20T-3

[0076] Shows an exemplary scleral wafer according to an embodiment of the present disclosure.

Figure 21A

[0077] Shows an exemplary nozzle guard according to an embodiment of the present disclosure.

Figure 21B

[0077] Shows an exemplary nozzle guard according to an embodiment of the present disclosure.

Figure 22

[0078] Shows an exemplary nozzle guard attached to a nozzle according to an embodiment of the present disclosure.

Figure 23

[0079] Shows a nozzle with a disposable insert and filter attached according to an embodiment of the present disclosure.

Figure 24

[0080] Shows an exemplary workstation according to an embodiment of the present disclosure.

Figure 25A

[0081] Shows an exemplary housing according to an embodiment of the present disclosure.

[0082] Figure 25A shows a 360-degree rotatable housing unit according to an embodiment of the present disclosure.

Figure 25B

[0082] Figure 25B shows a 360-degree rotatable housing unit according to an embodiment of the present disclosure.

Figure 26-A

[0083] Shows an exemplary multi-layer imaging platform according to an embodiment of the present disclosure.

Figure 26-B-C

[0084] Shows an exemplary CCD camera according to an embodiment of the present disclosure.

Figure 26-D

[0085] Shows an exemplary camera view using a CCD camera according to an embodiment of the present disclosure.

Figure 26-1

[0086] Shows an exemplary procedure according to an embodiment of the present disclosure.

Figure 26-2

[0087] Shows exemplary wavelengths at high water absorption according to an embodiment of the present disclosure.

Figure 26-3A

[0089] Shows exemplary parameters according to an embodiment of the present disclosure.

Figure 26-3A1

[0089] Shows exemplary parameters according to an embodiment of the present disclosure.

Figure 26-3A2

[0089] Shows exemplary parameters according to an embodiment of the present disclosure.

Figure 26-4

[0090] Shows anatomical structure recognition according to an embodiment of the present disclosure.

Figure 26-4-1

[0091] Shows an exemplary treatment density effect according to an embodiment of the present disclosure.

Figure 26-5

[0092] Shows another exemplary workstation according to an embodiment of the present disclosure.

Figure 27A-C

[0093] Shows an exemplary lens / mask according to an embodiment of the present disclosure.

Figure 28A-C

[0094] Shows an exemplary operation using an eyelid retractor according to an embodiment of the present disclosure.

Figure 29A-B

[0094] Shows an exemplary operation using an eyelid retractor according to an embodiment of the present disclosure.

Figure 30

[0095] Shows an exemplary test and anatomical structure avoidance in a laser section according to an embodiment of the present disclosure.

Figure 31

[0096] Shows exemplary further treatment parameters according to an embodiment of the present disclosure.

Figure 32

[0096] Shows exemplary further treatment parameters according to an embodiment of the present disclosure.

Figure 33

[0097] Shows exemplary various treatment area shapes according to an embodiment of the present disclosure.

Figure 34

[0098] Shows an exemplary shape treatment effect according to an embodiment of the present disclosure.

Figure 35

[0100] Shows an exemplary treatment simulation method according to an embodiment of the present disclosure.

Figure 36

[0100] Shows an exemplary treatment simulation method according to an embodiment of the present disclosure.

Figure 37

[0101] Shows an exemplary treatment effect according to an embodiment of the present disclosure.

Figure 38

[0101] Shows an exemplary treatment effect according to an embodiment of the present disclosure.

Figure 39

[0101] Shows an exemplary treatment effect according to an embodiment of the present disclosure.

Figure 40

[0102] Another exemplary nozzle according to an embodiment of the present disclosure is shown.

Figure 41

[0103] A further exemplary treatment pattern according to an embodiment of the present disclosure is shown.

Mode for Carrying Out the Invention

[0014] Detailed Description

[0105] The figures described below show at least one usage method of the described invention and its preferred best mode, and the best mode will be defined in more detail in the following description. Those skilled in the art may make modifications and improvements to what is described herein without departing from its spirit and scope. Although the present invention can be implemented in many different forms, the present disclosure should be regarded as an exemplification of the principles of the present invention, and it is not intended to limit the broad aspects of the present invention to the exemplary embodiments. Under the understanding that the preferred embodiments of the present invention are shown in the drawings and will be described in detail herein. All features, elements, components, functions, and steps described in connection with any embodiment provided herein can be freely combined and are intended to be substitutable with those from any other embodiment unless otherwise specified. Therefore, it should be understood that the examples are described for illustrative purposes only and should not be construed as limiting the scope of the present invention.

[0015]

[0106] FIGS. 1-29 show exemplary embodiments of a system and method for laser scleral microporation for rejuvenation of ocular tissue, specifically for rejuvenation of connective tissue related to aging of connective tissue by scleral rejuvenation.

[0016]

[0107] Generally, the systems and methods of the present disclosure take into account a combination of pore filling techniques and creating a three-dimensional (3D) matrix of pores. Pores of specific depths, sizes, and arrangements within a tissue matrix 3D scaffold create plastic behavior within the tissue matrix. This affects the biomechanical properties of the scleral tissue, making it more compliant. Connective tissues containing elastin are known to be "compliant," i.e., elastic. In fact, the sclera has natural viscoelasticity.

[0017]

[0108] The influence of ocular rigidity and ocular biomechanics on the etiology of presbyopia associated with aging is an important aspect here. This specification describes modifying the structural rigidity of the ocular connective tissue, i.e., the sclera of the eye, using the systems and methods of the present disclosure.

[0018]

[0109] To better understand the present disclosure, a brief description of accommodation, ocular rigidity, ocular biomechanics, and presbyopia is provided. Generally, the loss of accommodation ability in presbyopic individuals is caused by various lens factors affected by aging, as well as extra-lenticular and physiological factors. The increase in ocular rigidity associated with aging causes stress and strain in these eye structures, and the accommodation ability can be affected. Overall, if ocular biomechanics, ocular rigidity, and loss of accommodation are understood, a new ophthalmic treatment paradigm may be created. Scleral treatment may play an important role in treating biomechanical deficits in presbyopic individuals by providing at least one means of addressing the true etiology of the clinical symptoms of accommodation loss seen with aging. The effects of accommodation loss can affect the physiological functions of the eye, including but not limited to visual accommodation, aqueous humor hydrodynamics, vitreous humor hydrodynamics, and ocular pulsatile blood flow. Restoration of the more compliant biomechanical properties of the ocular connective tissue using the systems and methods of the present disclosure is a safe procedure and can restore the accommodation ability of the elderly.

[0019]

[0110] Accommodation has traditionally been described as the ability of the eye's lens to dynamically change its refractive power to adapt to various distances. More recently, accommodation has been better described as a complex biomechanical system having both intra-lenticular and extra-lenticular components. The synchronous operation of these components with many of the anatomical and physiological structures of the eye organ results in the organization of not only the visual findings associated with accommodation, but also the physiological functions essential to the eye organ, such as aqueous humor hydrodynamics and ocular biotransport.

[0020]

[0111] Biomechanics is the study of the origin and effects of forces in biological systems. In ophthalmology, biomechanics has not yet been fully utilized. This biomechanical paradigm is worthy of being extended to the anatomical connective tissues of the complex eye organ. As ocular biomechanics relates to accommodation, understanding it may enable a more detailed overall picture of the role this major motility system plays in the overall eye organ function while maintaining the optical quality for visual tasks.

[0021]

[0112] The eye is a biomechanical structure, a complex sensory organ that includes complex muscle, drainage, and humoral mechanisms involved in visual function and ocular biotransport. The accommodation system is the major motility system in the eye organ and facilitates many of the physiological and visual functions of the eye. The physiological role of the accommodation system is to move water, blood, nutrients, oxygen, carbon dioxide, and other cells around the eye organ. Additionally, it acts as a neural reflex loop, finely adjusting the focusing ability over the full range of vision in response to optical information received through the cornea and lens, and is essentially the "heart" of the eye organ.

[0022]

[0113] Biomechanics is particularly important for the complexity of regulatory functions and the dysfunctions associated with age-related eye diseases (e.g., presbyopia, glaucoma, age-related macular degeneration (AMD), and myopia). The age-related changes in the lens have been elucidated and reported for a long time. Recent attempts have demonstrated how the stiffening of eye tissues manifests as presbyopia. Ocular rigidity has been correlated with clinically significant age-related loss of accommodation, age-related macular degeneration, increased intraocular pressure (IOP), decreased ocular pulsatile blood flow, and certain forms of glaucoma and cataracts. The stiffening of the ciliary body and the loss of elasticity of the choroid can also contribute to accommodation.

[0023]

[0114] Biomechanics plays a decisive role in the pathophysiology of the eye organ. In healthy young eyes, this mechanism is biomechanically efficient and accurately achieves focusing on objects at a specific distance. However, with aging, this biomechanical mechanism is affected by changes in material properties, anatomical relationships, and the breakdown of healthy connective tissue matrix structure relationships due to the aging process. These biomechanical dysfunctions not only disrupt the function of the regulatory mechanism and affect the ability to dynamically adjust the focus of the lens to achieve ideal optical quality, but also disrupt the functions of other physiological mechanisms that are crucial for the eye organ, such as ocular hydrodynamics, ocular blood flow, and metabolic homeostasis. Therefore, biomechanics plays an important role in the pathophysiology associated with aging, including glaucoma and AMD.

[0024]

[0115] Presbyopia is a vision disorder conventionally defined as the progressive loss of accommodation ability associated with aging. However, the decrease in the ability to adjust the refractive power of the lens for various distances is only one consequence of this complex disorder. With the aging of the eye, there are changes in the connective tissues of the eye organ or "oculus", which have a significant but reversible impact on the biomechanical efficiency of eye function. Studies using ultrasound biomicroscopy (UBM), endoscopy, optical coherence tomography (OCT), and magnetic resonance imaging (MRI) have shown age-related changes in the vitreous membrane, peripheral choroid, ciliary muscle, and zonules. Age-related changes cause biomechanical alterations, which also appear in the sclera that bends inward with aging.

[0025]

[0116] According to one model, during accommodation, the ciliary muscle contracts, removing the tension on the zonules, thereby reducing the tension on the lens and allowing the lens to curve and increase its refractive power. The age-related decline in lens elasticity hinders lens deformation and the lens refractive power does not increase sufficiently to view nearby objects. Current techniques for eliminating the presbyopic symptom of reduced near vision typically include glasses, multifocal or monovision contact lenses, corneal procedures that produce monovision or multifocality, lens implants using multifocal lenses, corneal inlays, aphakic inlays, and accommodative intraocular lenses. However, none of these techniques restore true accommodation. Instead, these techniques attempt to improve near and intermediate vision by manipulating the optical system of either the cornea or the lens.

[0026]

[0117] For true physiological accommodation to occur, when the eye changes focus from far to near, or from near to far, its focal length must be modified so that objects are seen clearly. Generally, this is thought to be mainly caused by the ciliary muscle, which contracts to make the lens assume a more convex shape. However, this accommodation process is much more complex. Accommodation is also affected by corneal abnormalities, and thus, for clear vision, the lens must deform and undulate to match the corneal abnormalities to create an optical balance between the lens and the cornea before exerting a focal response to the accommodative stimulus. In addition, the tension of the zonules on the lens and the elastic choroid contribute to the accommodation range and biomechanical function of the entire accommodation complex. Dysfunction of these complex components can lead to dysfunction of the biomechanical relationship, which can affect the accommodation amplitude, lens deformation, and the central refractive power resulting from the dynamic accommodation force.

[0027]

[0118] For example, in scleral surgery as a presbyopia treatment, myopia has been treated using corneal incisions, which is known as radial keratotomy (RK). An anterior ciliary sclerotomy (ACS) technique that utilizes radial incisions of the scleral portion covering the ciliary muscle has been developed. This incision was thought to increase the distance between the ciliary muscle and the lens, and by increasing the "operating distance" of the muscle and tightening of the zonules, it was considered possible to restore the accommodation ability in presbyopic patients. The long-term results of ACS suggest that this technique has been almost unsuccessful in restoring accommodation, and the effect completely disappeared with the extremely rapid healing of the scleral wound. After ACS, laser presbyopia reversal (LAPR), which performs radial sclerotomy using a laser, followed. However, the results of LAPR have been inconsistent. Scleral implants attempt to restore the accommodation ability by lifting the ciliary muscle and sclera and tensioning the zonules that hold the lens. The discussion about its effectiveness remains divided.

[0028]

[0119] Loss of accommodation is used synonymously with presbyopia. However, it must be emphasized that loss of accommodation is merely one clinical symptom as a result of an aged (or presbyopic) eye. With aging, numerous changes occur in the lens and surrounding tissues, which can contribute to loss of accommodation. Studies have shown hardening of the lens substance with aging, a decrease in the ability (and refractive power) to change its shape during accommodation, and a decrease in accommodation ability. Softening of the lens capsule, flattening of the lens, and anterior movement of the lens with aging may also contribute to loss of accommodation ability. However, accommodation is a complex mechanism. Many lens-based models cannot incorporate the effects from the extra-lenticular structures. To fully understand accommodation, it is necessary to consider both the lens and extra-lenticular components together.

[0029]

[0120] The magnitude of accommodation lost with aging is related to extracapsular factors (mainly zonules, choroid, and sclera) and has only been investigated relatively recently. The space around the lens decreases with aging. The ciliary body has been shown to contract during accommodation, with a decrease in the distance from the scleral spur to the ora serrata. Using UBM, the attachment areas of the posterior zonules adjacent to the ora serrata have been identified, and the contraction of these zonules is thought to be the cause of the distance decrease seen with accommodation. This complex action of the zonules is suspected to be antagonistic. While the anterior zonules relax, the tension exerted on the lens by them decreases, the lens changes its shape anteriorly, the posterior zonules contract, and the posterior capsule recedes. This vitreous - zonule complex stiffens with aging and loses its elasticity. Also, currently, it is known that the deformability of the sclera during accommodation decreases with aging in the nasal region. The vitreous has also been suggested as an important factor in the lens shape change during accommodation and may play a role in presbyopia. The new model suggests that the extracapsular structures may contribute up to 3 diopters. These age - related changes in the structures and their biomechanical interactions in the ciliary body - lens complex may contribute to presbyopia.

[0030]

[0121] The ciliary muscle plays a decisive role in many functions of the eye organ, including accommodation and aqueous humor hydrodynamics (outflow / inflow, pH regulation, and IOP). The optically important role of the ciliary muscle is to dynamically adjust the lens to focus at various distances (near point, intermediate point, and far point). During accommodation, the ciliary muscle contracts, changing the shape of the lens and basically moving the lens forward and inward. This shape deformation is caused by the relaxation of the tension on the anterior zonular fibers and the movement of aqueous humor into the posterior chamber. This enables the lens to change from a relatively aspherical shape to a more spherical shape, and thus its refractive power increases for near vision. The contraction of the ciliary muscle is also important for the expansion of the trabecular meshwork and aqueous humor drainage. Inappropriate drainage or disruption of the normal flow of aqueous humor through either the uveoscleral outflow pathway or the Schlemm's canal can increase IOP and contribute to the development of certain types of ocular hypertension or glaucoma. Ciliary muscle contraction during accommodation decreases intraocular pressure (IOP). This is probably due to a decrease in aqueous humor outflow resistance caused by the expansion of the Schlemm's canal and the opening of the trabecular meshwork when the ciliary muscle moves forward and inward during accommodation.

[0031]

[0122] FIGS. 1A-(1-3) show an exemplary scleral laser viscoelastic rejuvenation method for realizing the extensibility of the ciliary muscle in some embodiments. The ciliary muscle and its components include meridional or longitudinal (1), radial or oblique (2), and circular or sphincter (3) muscle fiber layers as they appear by sequential removal towards the interior of the eye. The cornea and sclera have been removed, and the Schlemm's canal (a), collecting venules (b), and scleral spur (c) remain. The meridional fibers (1) often exhibit acute-angled junctions (d) and terminate at the epichoroidal stars (e). The radial fibers intersect at obtuse angles (f), and similar junctions are present in the circular ciliary muscle at a larger angle (g).

[0032]

[0123] The rigidity of the structure describes its resistance to deformation in the case of a confined structure containing non-compressible contents. Ocular rigidity refers to the resistance of the eye to stress. An increase in ocular rigidity has been correlated with aging, supporting the idea that presbyopia and ocular rigidity share common biomechanical factors. In addition to affecting accommodation, ocular rigidity can also impede the return of the accommodator to the unaccommodated state after being adjusted by weakening the elastic recoil of the choroid backward.

[0033]

[0124] Ocular rigidity has been correlated with a decrease in ocular pulsatile blood flow. The blood vessels that support the overall health of the eye pass through the sclera. If ocular rigidity increases, the resistance of the sclera to venous outflow increases, and the flow through the choroidal blood vessels may decrease.

[0034]

[0125] Ocular rigidity has been correlated with the etiology of macular degeneration. If ocular rigidity increases, the resistance of the sclera to venous outflow increases, and the flow through the choroidal blood vessels may decrease. This can damage Bruch's membrane and lead to choroidal neovascularization. Since a decrease in the flow through the choroidal blood vessels can also lead to a decrease in perfusion, this may lead to hypoxia and choroidal neovascularization.

[0035]

[0126] Ocular rigidity has been correlated with certain forms of glaucoma. Recent models suggest that ocular rigidity affects the scleral response to increased intraocular pressure. If ocular rigidity decreases, the mechanical strain transmitted to the optic nerve head associated with age-related changes and increased intraocular pressure due to ocular rigidity in both the anterior and posterior segments of the eye may decrease. During normal accommodation, when the ciliary muscle contracts, the retina and choroid are pulled forward near the optic nerve head. The ciliary muscle retains its contractile force with aging, however, since an increase in the rigidity of the sclera can affect the motility of the ciliary muscle, the tension applied to the optic nerve head during ciliary muscle contraction may increase.

[0036]

[0127] Figures 1A-(4 - 7) show the posterior scleral rejuvenation method and optic nerve head decompression in some embodiments.

[0037]

[0128] The ocular rigidity or "stiffness" of the external eye structures, including the sclera and cornea, occurs with aging of the eye and affects all the biomechanical functions of the internal anatomical structures such as the extra-lenticular and lenticular anatomy of the accommodative complex and the trabecular meshwork, choroid, and retina. In addition, ocular rigidity has a significant impact on the physiological functions of the eye organ, such as changes in the dynamics of aqueous humor and the efficiency of ocular pulsatile blood flow. The increase in ocular rigidity affects other tissues, including ocular blood flow through the sclera and optic nerve. Ocular rigidity has been correlated with the etiology of many age-related eye diseases. Therefore, ocular rigidity not only affects the decline of visual accommodation but may also have broader clinical significance.

[0038]

[0129] Ocular biomechanics is the study of the origin and effects of forces in the eye. All eye tissues contain collagen, which imparts viscoelastic properties to the eye tissues. Viscoelastic materials include the properties of both fluids and elastic materials. Fluids tend to take the shape of their container, while elastic materials deform under stress and can return to their original shape. When stress is applied to a viscoelastic material, the molecules rearrange to accept the stress, which is called creep. This rearrangement also creates a reverse stress in the material, which allows the material to return to its original shape when the stress is removed. Therefore, viscoelasticity is an important property that enables tissues to respond to stress.

[0039]

[0130] Chronic stress that exceeds the healing capacity of tissues can lead to chronic inflammation and ultimately cell death, which technically describes the pathophysiology of aging. Like all other connective tissues, the ocular connective tissues are affected by age. The sclera occupies five-sixths of the eye and constitutes dense and irregular connective tissue. The sclera mainly contains collagen (50 - 75%), elastin (2 - 5%), and proteoglycans. The ocular connective tissues stiffen with age, and cross-linking that occurs with aging is the main cause of the loss of their elasticity. Cross-linking is the bond between polymer chains, such as those in synthetic biomaterials or proteins in connective tissues. Cross-linking can be caused by free radicals, ultraviolet exposure, and aging. In connective tissues, collagen and elastin may continue to cross-link over time to form fibrils and microfibrils. As the amount of fibrils and microfibrils increases, the sclera stiffens, resulting in "sclerosclerosis" and an accompanying increase in metabolic physiological stress. As described above, the basis for the change in scleral material properties that leads to the loss of extensibility of scleral tissue when stress is applied may include an age- and ethnicity-related increase in collagen cross-linking, along with the loss of elastin-driven recoil and / or microstructural changes in collagen. With the progression of this pathophysiology, the sclera exerts compressive and load stresses on the underlying structures, resulting in biomechanical dysfunction, specifically dysfunction related to accommodation.

[0040]

[0131] Age-related ocular hardening also affects the biomechanics of the ciliary muscle and the accommodation mechanism. For example, although the contractile force of the ciliary muscle does not decrease with age, it is known that the ciliary muscle may have a reduced ability to contract or exert substantial force on the lens to produce the same refractive changes as in a younger system. A further explanation may be that ocular hardness affects the biomechanical contribution of the ciliary muscle by relaxing the zonular tension and reducing the accommodation ability.

[0041]

[0132] Age-related changes in the material properties within the sclera affect the mobility of the connective tissue of the scleral fibers and directly lead to a loss of extensibility. This causes a decrease in the normal maintenance and metabolic turnover of proteoglycans (PGs) in the sclera, leading to the loss of PGs and ultimately tissue atrophy. However, if the extensibility and mobility of the scleral connective tissue are restored, this PG loss can be reversed.

[0042]

[0133] As described above, the systems and methods of the present disclosure take into account the combination of pore filling techniques and creating a three-dimensional matrix of pores. Pores of specific depths, sizes, and arrangements in the tissue matrix 3D scaffold cause plastic behavior within the tissue matrix. This affects the biomechanical properties of the scleral tissue, making it more flexible. Multiple pores can be created in the matrix 3D scaffold in an array pattern or lattice. Various microporation features can be supported, including volume, depth, density, etc.

[0043]

[0134] It is advantageous to create a tetrahedral or central hexagonal shape. To create a central hexagon within the matrix, there must be a series of "pores" with a specific composition, depth, and relationship to other "pores" in the spatial organization between the matrix and the pores within the matrix. A significant depth of the tissue (e.g., at least 85%) is also required to obtain the full effect of the entire matrix across the dimensions of the polygon. The matrix within the tissue contains a polygon. The central angle of the polygon remains the same even if there are multiple spots within the matrix. This is an essential component of the systems and methods of the present disclosure for utilizing a polygonal matrix containing a matrix-like or lattice-like pore pattern with unique relationships and properties.

[0044]

[0135] The central angle of a polygon is the angle defined at the center of the polygon by one of its sides. Regardless of the number of sides of the polygon, the central angle of the polygon remains the same.

[0045]

[0136] Current implant devices in the sclera achieve mechanical effects during adjustment. There is no current device or method that utilizes the effect of "pores" or the effect of creating a matrix array of centrally hexagonal or polygonal pores in three-dimensional tissue. The systems and methods of the present disclosure can create a pore matrix array in biological tissue, enabling changes in the biomechanical properties of the tissue itself to create a mechanical effect on the biological function of the eye. The basic requirement for the matrix-shaped "pores" is that they are polygonal.

[0046]

[0137] A polygon, by definition, can have any number of sides, area, and perimeter, and the dimensions of a polygon in 3D can be mathematically measured. In the case of a regular polygon, the central angle is the angle created at the center of the polygon by any two adjacent vertices of the polygon. If lines are drawn from any two adjacent vertices to the center, they will create the central angle. Since this polygon is a regular polygon, all central angles are equal. It doesn't matter which side is chosen. The sum of all central angles should be 360° (a complete circle), so the size of the central angle is 360 divided by the number of sides. Or, as an equation, it is as follows: Central angle = 360 / n degrees (where n is the number of sides).

[0047]

[0138] Therefore, the size of the central angle depends only on the number of sides and not on the size of the polygon.

[0048]

[0139] As used herein, whether the polygon is a "regular" polygon or an "irregular" polygon is not limited. A polygon is one of the shapes that geometrically encompasses almost everything. From simple triangles to squares, rectangles, trapezoids, through dodecagons and beyond.

[0049]

[0140] The types of polygons include regular polygons and irregular polygons, convex polygons and concave polygons, self-intersecting polygons and orthogonal polygons. A regular polygon has all sides and interior angles equal. A regular polygon is always convex. Irregular polygons may have sides of different lengths and angles of different magnitudes, and are the opposite of regular polygons. Convex means that all interior angles are less than 180° and all vertices point "outward" away from the interior. The opposite of this is concave. Regular polygons are convex. Concave means that one or more interior angles are greater than 180°. Some vertices are pushed "inward" towards the interior of the polygon. A polygon can have one or more sides that create multiple small polygons by crossing back over another side. It is best to consider them as several separate polygons. A polygon that does not self-intersect in this way is called a simple polygon.

[0050]

[0141] The properties of all polygons (regular and irregular) include the interior angle at each vertex inside the polygon and the angle between an extended side and an adjacent side outside the polygon. A diagonal of a polygon is a line connecting any two non-adjacent vertices. For regular polygons, there are various methods for calculating the area. For irregular polygons, there is no general formula. The perimeter is the distance around the polygon or the sum of its side lengths.

[0051]

[0142] The properties of a regular polygon include the apothem (inradius), which is the line from the center of the polygon to the midpoint of a side. This is also the radius of the inscribed circle. The radius (circumradius) of a regular polygon is the line from the center to any vertex. This is also the radius of the circumscribed circle of the polygon. The inscribed circle is the largest circle that fits inside the regular polygon. The circumscribed circle is a circle that passes through all the vertices of the regular polygon. Its radius is the radius of the polygon.

[0052]

[0143] Some embodiments herein show a plurality of polygons within a matrix array. Each can affect CT (Computed Tomography). They contain pores sufficient to enable a "central hexagon". A square / rhombus shape may be evident. The formula is as follows:

Number

Number

[0053]

[0144] The "pores" described herein can have a specific morphology, shape, composition, and depth. Creating pores within the matrix array that change the biomechanical properties of connective tissue is a unique feature of this disclosure.

[0054]

[0145] The "pore matrix" used herein can be used for the control of wound healing. In some embodiments, this can include filling the pores to inhibit scar tissue.

[0055]

[0146] In some embodiments, the pores may have a depth of at least 5% - 95% through the connective tissue and can help create the intended change in biomechanical properties. The pores may have a specific composition, arrangement in the matrix, and desirably, mathematical properties of polygons. In three-dimensional (3D) space, the intended change in the relationship between the matrix or lattice of pores is a unique feature of this disclosure (see Figure 1F). The matrix or array can include a 2D Bravais lattice, 3D Bravais lattice, or non-Bravais lattice.

[0056]

[0147] Referring to FIGS. 1(B - E), an exemplary pore matrix array is shown. The pore matrix array herein is a basic component from which all continuous arrays can be constructed. There can be multiple different ways to arrange pores on CT in a space where each point can have the same "atmosphere". That is, since each point can be surrounded by the same set of points as any other point, all points can become indistinguishable from each other. A "pore matrix array" can be identified by the relationship between the angles between the sides of a "unit pore" and the distances between pores and "unit pores". A "unit pore" is the first "created pore" which, when repeated at regular intervals in three dimensions, gives rise to the lattice of the matrix array seen over the depth from the surface of the tissue. The "lattice constant" is the length between two position points at the corners of a pore. Each of the various lattice constants is denoted by the letters a, b, and c. When two sides are equal, as in a cubic lattice, the lengths of those two lattice constants are denoted by a and c, and b is omitted. The angles are denoted by the Greek letters α, β, and γ, and the angle for a particular Greek letter is defined by the axis of its Roman equivalent. For example, α is the angle included between the b - axis and the c - axis.

[0057]

[0148] A hexagonal lattice structure can have two angles equal to 90° and the remaining angle (γ) equal to 120°. For this to occur, the two sides surrounding the 120° angle must be equal (a = b), while the third side (c) is 90° to the other sides and can be of any length.

[0058]

[0149] Referring to FIG. 1F, an exemplary schematic projection view of the bottom surface of the hcp unit cell on the closest-packed layer is shown. The matrix array is defined as a specific repeating arrangement of pores over the target connective tissue, such as the dura mater. Structure refers to the internal arrangement of pores and not to the appearance or surface of the matrix. However, since the appearance of the pore matrix is often related to the internal arrangement, it is not completely independent. There may be a specific distance between each of the pores in the specified matrix to satisfy the polygonal mathematical features and properties. The pores created also have a relationship with the remaining tissue within the matrix and can thus change the biomechanical properties of the matrix.

[0059]

[0150] The spatial relationships of the pores within the matrix have geometric and mathematical meanings.

[0060]

[0151] In some embodiments, the laser microporation system of the present disclosure (see FIG. 3) generally includes at least these parameters: 1) laser radiation having a fluence of about 1 to 3 μJoules / cm2 and about 2 Joules / cm2; ≧ 15.0 J / cm 2 On tissue; ≧ 25.0 J / cm 2 On tissue; 2900 nm ± 200 nm to broaden the treatability; approximately the absorption maximum of water in the mid-infrared region; the laser repetition rate and pulse duration may be adjustable by using a predefined combination in the range of 100 to 500 Hz and 50 to 225 μs. This range is the minimum range ≧ 15.0 J / cm 2 Visibly on tissue ≧ 25.0 J / cm 2Organizationally, to increase disposability, it is irradiated with one or more laser pulses or a series of pulses having a duration of about 1 ns to about 20 μs. Some embodiments may have a maximum 50 W version; 3) The range of the Thermal Damage Zone (TDZ) may be less than 20 μm in some embodiments, or 20 - 50 μm in some embodiments; 4) The parameter of the pulse width of 10 μm - 600 μm may also be included (see Figure 1E-1).

[0061]

[0152] The energy per pulse of 1 - 3 microjoules may be associated with femtosecond lasers and picosecond lasers with high repetition rates ranging from, for example, 500 Hz (Zeiss) to several kilohertz (Optimedica). The benefits of femtosecond lasers and picosecond lasers are a small spot size (e.g., 20 microns and a maximum of 50 microns), with minimal thermal issues for the surrounding tissue while having a high energy density. All of this can lead to effective strengthening of the sclera. In some embodiments, the laser may create a substantially round conical hole in the sclera with a maximum depth of penetration and thermal damage of about 25 μm to a maximum of about 90 μm. The depth of the hole can be controlled by the pulse energy and the number of pulses. The hole diameter can vary due to movement artifacts and / or defocusing. Thermal damage can be correlated with the number of pulses. The pulse energy may be increased, which can lead to a decrease in the number of pulses and a further decrease in the associated thermal damage. An increase in pulse energy can also shorten the irradiation time. An exemplary design of the described laser system enables a laser profile optimized for a low thermal damage zone while maintaining the irradiation time and thus high speed for the optimal treatment time, and a graph showing the correlation between the thermal damage zone and the pulses (see Figures 1E-2 and 1G-(1 - 4)).

[0062]

[0153] Nanosecond lasers for micro poring or micro tunneling include the following specifications in some embodiments: wavelength, ultraviolet - visible - short infrared 350 - 355nm; 520 - 532nm; 1030 - 1064nm typical; - pulse length 0.1 - 500 nanoseconds, passive (or active Q - switching); pulse repetition rate 10Hz - 100kHz; peak energy 0.01 - 10 millijoules; peak power maximum over 10 megawatts; free - beam or fiber delivery.

[0063]

[0154] The intense film rejuvenation method can be implemented with femtosecond or picosecond lasers and er:YAG lasers. Other preferred embodiments of ideal laser energy parameters for 2.94 ER:YAG lasers or other laser possibilities of preferred ER:YAG laser energy or other lasers of different wavelengths with high water absorption.

[0064]

[0155] Examples of millijoules and energy density for different spot sizes / shapes / pores can be as follows:

[0065]

[0156] Spot size 50 microns: a) 0.5 mJ pp is equal to 25 J / cm2; b) 1.0 mJ pp is equal to 50 J / cm2 (possible with Er:YAG); 3) 2.0 mJ pp is equal to 100 J / cm2.

[0066]

[0157] Spot size 100 microns (all possible with ER:YAG): a) 2.0 mJ pp is equal to 25 J / cm2; b) 5.0 mJ pp is equal to 62.5 J / cn2; c) 9.0 mJ pp is equal to 112.5 J / cm2.

[0067]

[0158] Spot size 200 microns: a) 2.0 m joules pp is equal to 6.8 joules / cm2; b) 9.0 m joules pp is equal to 28.6 joules / cm2; c) 20.0 m joules pp is equal to 63.7 joules / cm2.

[0068]

[0159] Spot size 300 microns: a) 9.0 m joules pp is equal to 12.8 joules / cm2 - possible with ER:YAG; b) 20.0 m joules pp is equal to 28 joules / cm2 - possible with DPM-25 / 30 / 40 / X; c) 30.0 m joules pp is equal to 42.8 joules / cm2; d) 40.0 m joules pp is equal to 57 joules / cm2; e) 50.0 m joules pp is equal to 71 joules / cm2.

[0069]

[0160] Spot size 400 microns: a) 20 m joules pp is equal to 16 joules / cm2 - with DPM-25 / 30 / 40 / 50 / X; b) 30 m joules pp is equal to 24 joules / cm2; c) 40 m joules pp is equal to 32 joules / cm2; d) 50 m joules pp is equal to 40 joules / cm2.

[0070]

[0161] It is noted that circular or square pores or spots are similarly possible.

[0071]

[0162] Regarding femtosecond and picosecond lasers, some available wavelengths include infrared 1030 nm; green 512 nm and ultraviolet 343 nm. The peak energy can vary from nanojoules (at MHz repetition rate) of 5 - 50 microjoules to several hundred microjoules in the picosecond regime at most. Pulse lengths are 100 - 900 femtoseconds; peak energy from nanojoules to several hundred microjoules, and femtosecond lasers having a pulse repetition rate of 500 Hz to several megahertz (Ziemer LOV Z; Ziemer AG, Switzerland: nanojoule peak energy at a repetition rate exceeding 5 MHz, beam quality / density is extremely good - small spot - a focus of 50 microns or less is possible).

[0072]

[0163] In some embodiments, due to the extremely accurate beam quality of the best femtosecond lasers, femtosecond laser microtunneling of the strong film can be achieved as micro - pores using erbium lasers.

[0073]

[0164] As used herein, a nuclear pore can be defined as an opening in the nuclear envelope with a diameter of about 10 nm through which molecules (such as nuclear proteins synthesized in the cytoplasm) and RNA are supposed to pass (see Figure 1H). The pores are generated by large protein assemblies. The perforation of the nuclear envelope allows selected materials to flow in and out.

[0074]

[0165] Equation for porosity in biological tissue: X(Xa,t)=qT”(X”,t)=x *+u”(X”,t),(1) [where qU is a continuously differentiable invertible mapping from 0; a up to, and u” is the cY element displacement]. The invertible deformation gradient F” for the a element, and its Jacobian I” are defined as J” = detF” (3) [where J” must be strictly positive to prevent self-interpenetration of each continuum]. The right Cauchy–Green tensor % and its inverse, the Piola deformation tensor B for the solid element, are defined as V = F‘IF‘ (4) B = F’-‘F’+ [where the subscript t indicates transpose].

[0075]

[0166] Current theoretical and experimental evidence suggests that by creating or maintaining pores in connective tissue, three important issues are achieved. First, pores transport nutrients to cells in the connective tissue matrix. Second, pores carry out cell waste. Third, the tissue fluid exerts a force on the wall of the strong membrane or the outer eye coat, and the force is large enough for the cell to detect. This is considered to be a basic mechano-transduction mechanism in connective tissue, a way for the eye coat to detect the mechanical load applied thereto and the increase in intraocular pressure. Understanding mechano-transduction in the eye is essential for understanding how to treat glaucoma, glaucoma and myopia.

[0076]

[0167] Deriving the physical properties of a porous medium (e.g., hydraulic conductivity, thermal conductivity, water retention curve) from parameters that describe the structure of the medium (e.g., porosity, pore size distribution, specific surface area) is a continuing challenge for scientists, whether in soft tissue or for the porosity and permeability of bone tissue. To confirm the hypothesis that a porous medium has self-similar scaling behavior, the fractal dimensions of various features have been determined experimentally.

[0077] System procedures and mechanisms of action

[0168] In current accommodation theories, some claim that the crystalline lens is mainly involved in the refractive changes that enable us to read, but it has been found that all elements of the ciliary body are involved. Elucidating the role of the extracapsular process in accommodation supports the theory that scleral therapy, which modifies biomechanical properties by restoring extensibility to originally rigid tissues, can affect the accommodation ability of the elderly.

[0078]

[0169] The VisioDynamics theory, in particular, argues that presbyopia is not a refractive disorder or simply a loss of the ability to focus on near-point objects. Rather, presbyopia is an age-related consequence that occurs in the eye organ or the connective tissue of the eye, just as it does throughout the body. This produces a significant but reversible impact on the biomechanical efficiency of eye function, specifically accommodation, which may also improve not only the dynamic visual focusing ability but also eye biotransport and eye metabolic efficiency. The VisioDynamics theory examines, based on fundamental and natural biological events that occur with aging, specifically the effect of eye rigidity on the accommodation structure beneath the major outer coating or sclera of the eye. The sclera undergoes a progressive "scleral hardening" with aging, which corresponds to a normal and progressive irreversible change that occurs in all connective tissues. During this hardening process, the compression of the sclera increases, thereby imposing surprisingly large loads, stresses, and strains on the underlying and related eye structures and intraocular structures. The stress and strain experienced by this eye rigidity or the related structures that control the ciliary body and dynamic accommodation affect the biomechanics of the eye and impair the eye's ability to perform its core organ functions.

[0079]

[0170] In some embodiments, an eye laser surgery and treatment system provides eye laser treatment designed to reduce the stress and strain that occur in the sclera, which gradually hardens with age, by creating extensibility in the scleral tissue using a laser-generated micropore matrix in the scleral tissue. This system aims to facilitate changes in the biomechanical properties of the sclera, reduce compression of the eye's subliminal connective tissue, facial tissue, and biophysiological structures, and restore regulatory capabilities. Specifically, this system is designed to reduce stress across the ciliary muscle, accommodation complex, and important physiological biostructures directly beneath the aging scleral tissue and increase biomechanical extensibility.

[0080]

[0171] Laser treatment targets specific treatment areas within distinct physiological zones that include critical anatomical structures within the eye related to eye function. Examples of three or five physiological zones are described herein, but other numbers of physiological zones may also be considered for treatment.

[0081]

[0172] In some embodiments, the treatment pattern can be described as three critical zones at three different distances from the outer edge of the anatomical limbus (AL) that do not contact any component or associated tissue of the cornea. These zones are shown in FIGS. 2A-(1-2). In some embodiments, the treatment pattern can be described as five critical zones at five different distances from the outer edge of the anatomical limbus (AL) that do not contact any component or associated tissue of the cornea, as shown in FIGS. 2B-(1-3).

[0082]

[0173] Laser treatment may create microspores in the sclera using an erbium:yttrium-aluminum-garnet (Er:YAG) laser. These microspores can be created at a plurality of depths in a preferred depth range, such as 5% to 95% of the sclera, up to the point where the bluish tint of the choroid is just visible. The microspores can be created in a plurality of array forms, including a matrix array, such as a 5 mm × 5 mm, 7 mm × 7 mm, or 14 mm × 14 mm matrix array. These micro-poration matrices disrupt the bonds of the scleral fibrils and microfibrils, exerting a "decrosslinking" effect on the scleral tissue. As a direct result of this matrix pattern, both a range of positive stiffness (remaining stromal tissue) and negative stiffness (removed tissue or microspores) are created in the rigid sclera. Due to these ranges with differences in stiffness, the viscoelastic coefficient of the treated sclera can become highly progressive across the critical zone when subjected to forces or stresses, such as the contraction of the ciliary muscle. In addition, the treated area of the sclera can produce a damping effect in the rigid scleral tissue during the contraction of the ciliary muscle due to increased plasticity. This results in an unresisted force moving inward and centrally towards the lens, or promoting the upward and inward movement of the accommodation mechanism, thus enhancing the accommodation effort. This is an advantage over models that assume a net outward force at the lens equator. For example, techniques aimed at expanding the sclera, such as surgical laser radial ablation like scleral implants or LAPR, all aim to increase the "space" or the periphakic cavity by making room for the ciliary muscle to expand the sclera. These techniques are based on the "lens crowding" theory and aim to produce an outward movement rather than an upward and inward movement of the sclera and ciliary mechanism. Overall, creating a microspore matrix in the scleral tissue causes a "decrosslinking effect" and severs the fibrils and microfibrils of the scleral layer, enabling a more progressive response to applied stress.Accordingly, the proposed mechanism of action for the present system is to increase the plasticity and extensibility of the scleral tissue covering the anatomically important critical zone by creating these regions of different stiffnesses covering the ciliary complex, thereby improving the biomechanical function and efficiency of the accommodator. Figures 2C-(1 - 4) show the laser scleral de-crosslinking of scleral fibrils and microfibrils in some embodiments.

[0083]

[0174] Referring to FIGS. 2D(1 - 4), the effect of this procedure on ocular rigidity has been investigated using the novel model. Like all other connective tissues, ocular connective tissues are affected by age. The sclera occupies five-sixths of the eye and constitutes a dense and irregular connective tissue. The sclera mainly contains collagen (50 - 75%), elastin (2 - 5%), and proteoglycans. The ocular connective tissues stiffen with aging, and the loss of their elasticity is mainly due to cross-linking that occurs with aging. Cross-linking causes an "increase in biomechanical rigidity" in connective tissues such as those in the eye. Cross-links are bonds between polymer chains, such as those in synthetic biomaterials or proteins in connective tissues. Cross-linking can be caused by free radicals, ultraviolet exposure, and aging. In connective tissues, collagen and elastin can continue to cross-link over time to form fibrils and microfibrils. As the amount of fibrils and microfibrils increases, the sclera stiffens, resulting in "scleral sclerosis" and an associated increase in metabolic physiological stress. With the progression of this pathophysiology, the sclera exerts compressive and load stresses on the underlying structures, causing biomechanical dysfunction, specifically accommodation-related dysfunctions. Laser scleral microporation destroys scleral fibrils and microfibrils to effectively "de-crosslink" the bonds, thereby increasing the extensibility of the sclera and "decreasing the biomechanical rigidity".

[0084]

[0175] In one exemplary surgery, six freshly enucleated porcine eyes were modified by crosslinking (with 0.8 ml of 2% glutaraldehyde for 10 minutes) to reproduce the ocular rigidity of an aged human eye (60 years old) based on the ocular rigidity coefficient model of Pallikaris et al. Seven freshly enucleated porcine eyes were left unmodified to reproduce the ocular rigidity of a young human eye (30 years old). Three eyes from each group were treated, while the remaining eyes were used as controls. Briefly, for this study, an intraocular pressure (IOP) versus injection volume curve was created for each eye using a pressure transducer (up to 5 psi), a dosing syringe controller, a data computer reader, and a tissue holding frame that fixed each porcine eye. Next, the ocular rigidity coefficient (K = d ln(P) / dV [in mmHg / μl units]) was calculated as the slope of ln(IOP) versus injection volume (from an IOP of 30 - 50 mmHg). In the young eyes, rigidity decreased by 10.8% with treatment. In the aged eyes, rigidity decreased by 30.1% with treatment. Using analysis of variance (ANOVA) and Tukey's honestly significant difference (Tukey HSD) test, it was found from this study that this system significantly reduced ocular rigidity in aged eyes and overall (p = 0.0009; p = 0.0004). This reduction in ocular rigidity could be caused by "decrosslinking" of the aged tissue.

[0085]

[0176] In one exemplary surgery, 26 subjects were treated and 21 completed 24 months of postoperative care. Five patients dropped out due to overlapping business trips. Preoperative (month 0) IOP and postoperative IOP (determined by pneumatic tonometry) are shown. For these patient eyes, there is an immediate 5% drop in IOP compared to preoperative IOP. Over the two years after treatment, the patient IOP remained approximately 15% lower than the preoperative IOP. The immediate and sustained IOP decrease could demonstrate an improvement in aqueous humor outflow after treatment. Using ANOVA and Tukey HSD test, these differences became statistically significant from the third month postoperatively and continued throughout all subsequent months (p = 0.000063 at the 24 - month postoperative time point). This IOP decrease could indicate an improvement in ocular motility and a reduction in ocular rigidity after treatment.

[0086]

[0177] Biomechanical improvement by treatment may be found to increase the biomechanical efficiency of the accommodator. In some embodiments, by creating micropores across four tilted quadrants of the matrix, the treatment can restore extraocular functional forces and restore at least 1 to 3 diopters of accommodation. The inventors have reported that the results show an average of 1.5 diopters of accommodation postoperatively. This significantly improved the vision of the inventors' patients. The data of the 24-month postoperative follow-up of this clinical trial were published in 2015 and showed promising results. Vision was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, and statistical analysis was performed using ANOVA and Tukey HSD tests. The patients' uncorrected monocular near visual acuity was 0.25 ± 0.18 logMAR (mean ± standard deviation) at 24 months postoperatively, compared with 0.36 ± 0.20 logMAR (mean ± standard deviation) preoperatively (p < 0.00005).

[0087]

[0178] In summary, by using innovative biometric and imaging technologies that were not previously available, it has been elucidated that there are many lens factors, extraocular factors, and physiological factors that cause the loss of accommodation ability in the presbyopic eye. All of the lens, lens capsule, choroid, vitreous, sclera, ciliary muscle, and zonule play a decisive role in accommodation and are affected by aging. The increase in ocular rigidity with aging causes stress and distortion in these ocular structures, which can affect the accommodation ability.

[0088]

[0179] Scleral therapy can play an important role in the treatment of biomechanical deficits in presbyopic eyes by providing at least one means of addressing the true etiology of the clinical symptoms of the loss of accommodation seen with aging. Treatments that utilize laser microporation of the sclera to restore more compliant biomechanical properties are a safe procedure and can restore the accommodation ability of the elderly. As a result, this treatment improves the dynamic range of accommodation as well as aqueous humor outflow. The emergence of improved biometry, imaging, and research focus allows for obtaining information on how the accommodative complex works and what effects it has on the entire eye organ.

[0089]

[0180] Referring to FIG. 2E, three exemplary critical significant zones as measured from the anatomical limbus (AL) are shown. Zone 1) extends from 0.5 to 1.1 mm from the AL, across the scleral spur at the origin of the ciliary muscle; Zone 2) extends from 1.1 to 4.9 mm from the AL, across the center of the ciliary muscle body; Zone 3) extends from 4.9 to 5.5 mm from the AL, across the attachment point of the longitudinal muscle fibers of the ciliary body immediately anterior to the ora serrata at the attachment point of the posterior zonular fibers. FIG. 2E(b) shows exemplary restoration of mechanical efficiency and improvement in biomechanical mobility.

[0090]

[0181] In some embodiments, the laser scleral microporation procedure may involve performing partial thickness microablation of the matrix sclera at five critical anatomical zones from 0 to 7.2 mm from the anatomical limbus (AL) using the lasers described above. The five zones can include the following: Zone 0) from 0.0 to 1.3 mm from the AL; the distance from the AL to the upper boundary of the ciliary muscle / scleral spur; Zone 1) from 1.3 to 2.8 mm from the AL; the distance from the scleral spur to the lower boundary of the circular muscle; Zone 2) from 2.8 to 4.6 mm from the AL; the distance from the lower boundary of the circular muscle to the lower boundary of the radial muscle; Zone 3) from 4.6 to 6.5 mm from the AL; from the lower boundary of the radial muscle to the upper boundary of the posterior zonular zone; and Zone 4) from 6.5 to 7.2 mm from the AL; from the upper boundary of the posterior zonular zone to the lower boundary of the ora serrata.

[0091]

[0182] Figure 2F shows an exemplary matrix array of micro-incisions in four tilted quadrants.

[0092]

[0183] Figure 2G shows an exemplary graphical display of the restored extensibility of the treated eye, decreased scleral resistance, increased ciliary body resultant force, and restored dynamic accommodation.

[0093]

[0184] Figure 2H shows an exemplary box-and-whisker plot of the ocular rigidity of control (black) and treated (gray) porcine eyes. The upper and lower limits of the box represent the 75th and 25th percentiles, the bar within the box represents the median, and the whiskers represent the full extent of the data range.

[0094]

[0185] Figure 2I shows an exemplary box-and-whisker plot of the preoperative and postoperative intraocular pressure (IOP) of patient eyes. The star indicates a significant difference from the preoperative IOP. The upper and lower limits of the box represent the 75th and 25th percentiles, the bar within the box represents the median, the whiskers represent the full extent of the data range, and the white circles represent outliers.

[0095]

[0186] Figure 2J shows an exemplary graph showing the uncorrected and corrected distance visual acuity at 4 m, intermediate distance (60 cm), and near distance (40 cm) for a) monocular and b) binocular patient eyes. Error bars represent mean ± SD.

[0096]

[0187] As described herein, accommodation of the human eye occurs through changes or deformations of the eye lens when the eye shifts from far - point focus to near - point focus. These changes in the lens are caused by the contraction of the ciliary muscle (ciliary body) within the eye, which relaxes the tension exerted on the lens via the zonular fibers, increasing the thickness and surface curvature of the lens. The ciliary muscle can be composed of three unique orientations of ciliary muscle fiber groups that are ring - shaped and contract towards the center and front of the eye. These three ciliary muscle fiber groups are known as longitudinal, radial, and circular. The deformation of the ciliary muscle resulting from the contraction of different muscle fibers leads to or otherwise causes a change in the tension on the surface of the eye lens via the zonular fibers, and its complex attachment pattern to the lens and ciliary muscle influences the resulting changes in the lens during accommodation. The muscle contraction of the ciliary body also applies biomechanical strain to the connection location between the ciliary muscle and the sclera, which is known as the white outer coating of the eye. Additionally, biomechanical compression, strain, or stress that can be induced during accommodation can occur at the connection location between the ciliary muscle and the choroid, which is known as the inner connective tissue layer between the sclera and the retina. Ciliary muscle contraction can also cause biomechanical forces on the trabecular meshwork, lamina cribrosa, retina, optic nerve, and virtually every structure of the eye.

[0097]

[0188] Applying the techniques and models described herein in connection with various embodiments using simulations can lead to outputs and results that fall within the known accommodation range of young adult humans.

[0098]

[0189] 3D mathematical models can incorporate mathematics and non - linear neo - Hookean properties to reproduce the behavior of structures of biomechanical, physiological, optical, and clinical importance. Additionally, 3D (finite element model) FEM models can incorporate data from imaging, literature, and software regarding the human eye.

[0099]

[0190] In addition to means for measuring, evaluating, and predicting the Central Optical Power (COP), visualization of the accommodative structure during and after simulation may be included. Using these, the overall eye structure, optics, function, and biomechanics by age can be simulated and viewed. Furthermore, these can independently simulate the ciliary muscle, extra-lenticular and lenticular movement of the eye lens, and the characteristics of the functions on the eye lens. From individual simulations of anatomical structures and fibers, biomechanical relationships that would otherwise be unknown and undefined can be revealed. Numerical simulation of a patient's eye can be created by achieving these operations using 3D FEM mesh generation.

[0100]

[0191] For refinement, a representative 3D geometry of the resting eye structure can be computationally defined based on a detailed review of literature measurements and medical images of the anatomy of young adult eyes, and through modeling. Using specialized methods implemented in software such as AMPS software (AMPS Technologies, Pittsburgh, PA), geometric mesh generation, material property and boundary condition definition, and finite element analysis can be performed during the modeling stage. The ciliary muscle and zonules can be represented as transversely isotropic materials with orientations specified to represent complex fiber directions. In addition, computational fluid dynamic simulations can be performed to create fiber trajectories, which can then be mapped to the geometric model.

[0101]

[0192] Initially, the modeling of the lens can include a relaxed configuration of the lens before it is stretched to its unaccommodated position and shape by the pre - tensioned zonular fibers. The zonular can reach the unaccommodated lens position when it contracts, for example, to 75% - 80% of its starting length, more specifically, to about 77% of its starting length. Next, the accommodation movement can be simulated by actively contracting various fibers of the ciliary muscle. In some embodiments, this can be achieved using a previous skeletal muscle model that has been modified to represent the mechanics specific or unique to the ciliary muscle in a special or other form. The model results representing the forward movement and deformation of the lens and ciliary body at the midline and apex and the deformed lens thickness can be verified by comparing it with the existing medical literature measurements regarding accommodation or confirmed by other means. To examine the contribution of various ciliary fiber groups to the overall function of the ciliary muscle, simulations can be performed by independently activating each fiber group while keeping the others passive or unchanged in other ways.

[0102]

[0193] Various beneficial aspects of the embodiments described below are described in relation to simulations that apply a pre - tensioned zonular model and contract the ciliary muscle model.

[0103]

[0194] In relation to the pre - tensioned zonular, the modeling can include the following: 1) creating a 3D material sheet oriented between the measured zonular attachment points on the lens and the origin points on the ciliary body / choroid; 2) a specific fiber direction in the sheet plane (i.e., the fiber oriented from the origin point to the attachment point); and 3) a transversely isotropic constitutive material with preferred - orientation tension generation. Further, particularly in relation to 3), a) the stress generated in the material by the time - varying tension parameter input is adjusted; b) the time - varying tension input is adjusted so as to produce the required strain in the lens that conforms to the measurements of the unaccommodated configuration; c) the age - related changes in the material properties and geometry that cause the effects of aging; and d) other aspects, including advantages, are realized.

[0104]

[0195] In connection with a contracting ciliary muscle model, the modeling can include the following: 1) a constitutive model modified to represent the smooth muscle and skeletal muscle aspects of the mechanical response of the ciliary body; 2) three sets of specified fiber directions for representing the physiological orientation of muscle cells and the lines of action of force generation; and 3) a transversely isotropic constitutive material with active force generation in a preferred direction. Further, particularly in connection with 3), a) the activity parameter input adjusts the active stress generated in the material; b) the activity input is adjusted to produce an appropriate regulatory response that conforms to literature measurements; c) the activity of individual muscle fiber groups can vary independently to evaluate their contribution to lens strain / stress; d) the activity of individual muscle fiber groups can vary independently to evaluate their contribution to scleral strain / stress; e) the activity of individual muscle fiber groups can vary independently to evaluate their contribution to choroid plexus strain / stress; and f) advantages are realized, including others.

[0105]

[0196] In various embodiments, the simulation results can depend on modifications to the tension and activity inputs to the zonule and ciliary body materials, as opposed to applying displacements to the external nodes of the mesh.

[0106]

[0197] Thereafter, a system, method, and apparatus are disclosed for finding predictive best orders for the therapeutic ophthalmic correction, surgery, or rehabilitation of a patient's vision abnormality, eye disease, or age-related dysfunction, using a 3D computer model incorporating artificial intelligence (AI) to provide prediction results. The predictive best orders can be derived from physical structure inputs, neural network simulations, and prospective treatment outcome influences. For bringing various benefits, the new information can be analyzed in conjunction with optimized historical treatment outcome information. The concepts herein can be used in the implementation of a number of simulations and, having a knowledge-based platform, this system can improve its order response as the database expands.

[0107]

[0198] In some embodiments, the contemplated stored instructions may preferably be an optimized custom photoablation algorithm for driving a photothermal laser for photoablation. The instructions may be provided with the AI processor either by direct incorporation, imported stand-alone, or remotely via a Bluetooth-enabled application or connection. These instructions can be executed either preoperatively or intraoperatively.

[0108]

[0199] In some embodiments, the contemplated stored instructions may preferably be an optimized custom intraocular lens simulation algorithm used for the simulation of implantable intraocular lens surgery to improve medical procedures and understanding.

[0109]

[0200] The instructions can also be set up as a "stand-alone" system for use as a virtual clinical trial system or research and development system, whereby the instructions can be provided with independent research design inputs and outputs for testing various conditions and responses of the eye to ophthalmic surgical procedures, implant devices, or other therapeutic procedures to optimize the design and resulting responses.

[0110]

[0201] In addition, these instructions can also include one or more of an image processing understanding interpretation algorithm, an extension of an ophthalmic imaging data platform, and companion diagnostics for an imaging device.

[0111]

[0202] A method of improving ophthalmic treatment, surgery, or pharmacological intervention as described herein may include obtaining data regarding the topology, topography, structure, physiology, morphology, biomechanics, material properties, and optics of the human eye, along with analysis through mathematical simulation using applied physics and artificial intelligence networks.

[0112]

[0203] Virtual clinical applications using simulations can include techniques performed by devices, systems, and methods for the automated design of ophthalmic surgical procedures, including obtaining physical measurements of a patient's entire eye and applied physics. These measurements can be obtained using prior art. The measured information can be interpolated and extrapolated to fit the nodes of a finite element model (FEM) of the human eye for analysis, which can then be analyzed to predict the initial state of the eye's stress and obtain preoperative conditions of the cornea, lens, and other structures. Incision data constituting an "initial" surgical plan can be incorporated into the finite element analysis model. New analysis can then be performed to simulate the resulting eye deformation, biomechanical effects, stress, strain, curvature, and more specifically, the mechanical movement of the ciliary muscle, lens, and accommodation structures of the eye. These can be compared to their original values and vision goals. If necessary, the surgical plan can be modified, and the obtained new ablation data can be input into the FEM, and the analysis can be repeated. This procedure can be repeated as desired or necessary until the vision goal is achieved.

[0113]

[0204] Artificial intelligence (AI) software can perform machine learning using artificial neural networks, whereby the system can learn from data and thus has a learning component based on an ongoing database expansion. This may be operable to improve reliability as the database is created and updated, which has not been known in the prior art of 3D prediction modeling systems, methods, and devices.

[0114]

[0205] The simulation can include a predictive ability to simulate ophthalmic surgical outcomes for further surgery or treatment enhancement, determine the rate of regression after treatment, and execute a prediction algorithm, which has not been known in the prior art of 3D prediction modeling systems, methods, and devices.

[0115]

[0206] A virtual eye simulation analyzer may include integrating information on all structures of the eye into a computer program for simulating the biomechanical and optical functions of the eye, as well as aging simulation for clinical application purposes.

[0116]

[0207] A virtual eye simulation analyzer system, apparatus, and method may include an output display that a user can view as a stand-alone or integrated display system, along with other devices.

[0117]

[0208] The information used as input to the simulator may include biometric imaging information (such as UBM, OCT, etc.). Dynamic imaging can be performed using UBM, OCT, etc. Anatomical information may include geometry, histology, etc. Physiological function information may include dynamic regulation, aqueous humor pathway, intraocular pressure, pulsatile ocular blood flow, retinal performance or disorders, etc. Physical and biomechanical information regarding the material properties of the eye tissues and related biomechanics may also be used.

[0118]

[0209] The simulator may incorporate mathematical and non-linear neo-Hookean properties to reproduce structural behaviors such as biomechanics, physiology, and optics that may be valuable or otherwise clinically important. The simulator can input data that is incorporated into 3D FEM, along with unique patient data based on the analysis of one or more individual eyes of the patient using conventional methods. Further, the simulator can input data using conventional methods and create a numerical simulation of the patient's eye using 3D FEM mesh generation - essentially creating a custom dynamic real-time "Virtual Eye" that has not been known in the prior art of 3D prediction modeling systems, methods, and apparatuses until now.

[0119]

[0210] In some embodiments, the AI may have the ability to learn by predictive simulation and, for example, may be operable to improve simulation predictions for eye surgery or therapeutic procedures through the artificial neural network of the "ABACUS" program. ABACUS may also have the ability to directly provide instructions to processors or processing systems coupled to communicate to create and apply algorithms, sequences, formula generation, data profiling, surgical selections, etc. This may also have the ability to directly provide instructions to workstations, image processing systems, robotic controllers, or other implementation devices. Additionally, this may also have the ability to indirectly provide instructions to robotic controllers, image systems, or other workstations through Bluetooth or other remote connections.

[0120]

[0211] The models herein include: 1) the use of previous evaluations and simulations of the eye's accommodation function (examples include presbyopia applications - IOL design and use, extracapsular lens therapy and its use); 2) the use of previous evaluations and simulations of the eye's aqueous humor outflow pathway, such as for glaucoma applications; 3) virtual and real-time simulations of the effectiveness of IOLs, treatment procedures, and various biomechanical implications; 4) virtual simulations using AI and CI to reproduce customized aging effects on the individual biomechanical and physiological functions of the eye with clinical significance; 5) surgical planning; 6) import and simulation of design models (such as FEM) for IOLs, etc.; 7) virtual clinical trials and analysis; 8) real-time intraoperative surgical analysis, planning, and execution; 9) the performance of the eye's lens when it is related to optical and biomechanical dysfunctions, cataract formation, etc.; and 10) various applications to clinical, research, and surgical uses, including others.

[0121]

[0212] As further components of the simulator, the following can be mentioned: 1) eye scanning; 2) optical inputs such as the following, a) corneal optics, wavefront, elastography, hysteresis, visual acuity, topography, connective tissue macro and microstructures, and b) lens optics, for example, wavefront, visual acuity, topography, lens turbidity, light scattering, central refractive power (COP) during accommodation and non-accommodation, elastography, viscoelastic properties, etc.; 3) scleral biomechanics, viscoelasticity, material properties, stress, strain mapping, connective tissue macro / microstructures; 4) trabecular meshwork material, viscoelasticity, connective tissue macro and microstructures; 5) cribriform plate material properties, stress, strain, viscoelasticity, connective tissue macro and microstructure; 6) physiological inputs including the following, a) aqueous humor outflow and inflow, b) intraocular pressure (IOP), c) ocular pulsatile blood flow, d) retinal activity, etc.; 7) surface spectroscopy; 8) collagen fibril characteristics of the cornea, sclera, lens, etc.; and 9) others.

[0122]

[0213] The benefits of the simulator in the accommodation embodiments can include the following: 1) measuring, analyzing, and simulating eye accommodation in real time; 2) demonstrating accommodation biomechanics in real time; 3) evaluating accommodation biomechanics; 4) visualizing the accommodation structure; 5) measuring, evaluating, and predicting the central refractive power; 6) simulating age-related changes in the overall eye structure, function, and biomechanics; and 7) others.

[0123]

[0214] The main structural component inputs can be based on the sclera, cornea, lens, trabecular meshwork, lamina cribrosa, retina, etc. For the sclera, the inputs can include the following: scleral rigidity, viscoelasticity, scleral thickness, scleral depth, 3D surface topology, upper surface spectral dimension, 3D spectroscopy, etc. For the cornea, the inputs can include the following: corneal wavefront, viscoelasticity, topography, corneal incision, corneal thickness, 3D topology, K value, corneal rigidity, 3D spectroscopy, etc. For the lens, the inputs can include the following: lens wavefront, central refractive power, accommodation range, light scattering, turbidity, etc. For the trabecular meshwork, the inputs can include the following: elasticity, outflow, inflow, etc. For the lamina cribrosa, the inputs can include the following: porosity, mechanical dependence, perfusion, porous elasticity, cup floor depth, etc.

[0124]

[0215] Some of the various main optical profiles, characteristics, information, and vision information outputs for the cornea can include the following: overall aberration, visual streak ratio, depth of focus, MRSE, vision, lens scattering, etc. Some of the various main optical profiles, characteristics, information, and vision information outputs for the lens can include the following: overall aberration, VSOF, depth of focus, etc.

[0125]

[0216] Also, exemplary embodiments of creating a 3D microporation model on a spherical surface are described.

[0126]

[0217] Also, exemplary embodiments of Pantec protocol modified Fibonacci MatLab pore calculations for the whole-eye pattern are described.

[0127]

[0218] Referring to FIG. 2K-1, an example of protocol execution is described here: Protocol 1.1: 225um (total of 169 holes @ 3% = 42.25 holes / quadrant). Examples of Matlab code used for Protocol 1.1 can include the following: >> fibonacci_spiral_connected_Pantec (‘r’,0.225,3,6.62,9.78). The breakdown of Matlab code parameters may include the following: Parameter 1, ‘r’ = pore shape: Enter ‘r’ for rectangular pore shape or ‘c’ for circular. Use ‘r’ for ‘please’ and ‘c’ for ‘DPM25’ * ; Parameter 2, 225um (0.225) = r_shape: Length of rectangular pore shape or radius of circular pore shape [mm] unit; Parameter 3, 3% = D: Pore density [percent] unit; Parameter 4, 6.62mm (radius of the zone excluded from pore calculation). This applies when there are no pores calculated in the corneal / limbus range (6.62mm) = r_b: Radius for the start of the circle [mm] unit; Parameter 5, 9.78mm (radius to the end of the pore calculation zone). The 6.62mm radius will be subtracted from the pore calculation process, so it is possible to set the radius from 6.62mm to 9.78mm as the only calculation range containing pores = r_e: Radius for the end of the circle [mm] unit. When the code (‘r’,0.225,3,6.62,9.78) is input into Matlab, Matlab will output a figure specially generated for that pore protocol. The total number of pores in the title is obtained in this way.

[0128]

[0219] Treatment operation protocol: The following is an exemplary protocol for treatment operations, and there are two operations per protocol: a) The first operation for the entire quadrant range; b) The second operation for the “patch” range of a 5×5mm rhombus. i) The diagonal length of this rhombus is = 5×√(2)=7.07mm. ii) The 5×5 matrix can be placed on the sphere updated by the inventors so that the Fibonacci spiral can fit the model.

[0129]

[0220] Ball comparison: The "patch" of the present inventors is 5×5 in some embodiments, and thus dimensions are used. Er:Yag laser with an optical fiber probe; 600 μm spot size; 9 micro-incisions in 4 inclined quadrants; treatment time of 10 minutes / eye; micro-pores in the critical zone (e.g., 3 or 5 zones) across the ciliary body complex; creating a compliant matrix zone in the sclera.

[0130]

[0221] The purposes of the procedure can include the following: 1) improving the extensibility of the sclera covering the critical anatomical structure of the ciliary muscle complex; 2) restoring the mechanical efficiency of the natural accommodation mechanism; 3) improving biomechanical mobility to achieve accommodation force, etc.

[0131]

[0222] An exemplary Fibonacci treatment pattern was generated two-dimensionally through Matlab or other programs. When having a patch of the correct size, such as 5×5 mm, it can perform actual treatments that may not fit the critical zone (e.g., zones 1 - 3, or 1 - 5). There is a method to obtain an actual estimation from a 3D model to a 2D model. As shown in Figure 2K-1, the parameters can include the following:

[0132]

[0223] Baseline: 600 μm (total 92 holes @ 16% = 23 holes / quadrant).

[0133]

[0224] Spot size: 600um; depth: 80%; density: 16%; removal volume: 1.16 mm 3 ; total number of holes overall: 92; total number of holes / quadrant: 23.

[0134]

[0225] Protocol 1.1: 225 μm (total 169 holes @ 3% = 42.25 holes / 5.5 mm patch: effective) total number of holes / 5.5 mm patch.

[0135]

[0226] Figures 2K-1-A to 2K-1-C show exemplary protocol parameters creating a rhombus pattern for three critical zones.

[0136]

[0227] In some embodiments, this can be important for knowing how many pores are in a 5×5 patch on the 3D model in response to density changes and spot size changes in each protocol. If this is known, patch operations can be performed. FIGS. 2K-(2~17) show exemplary diagrams of various protocols used and their results. These protocols include the following:

[0228] Protocol 1.1: 225 μm (total 96 holes @ 3% = 24 holes / quadrant: valid)

[0229] Spot size: 225 um; Depth: 80%; Density: 3%; Removed volume: 0.91 mm 3 ; Total number of pores: 96; Number of pores / quadrant: 24

[0230] Protocol 1.2: 225 μm (total 161 holes @ 5% = 40.25 holes / quadrant: valid)

[0231] Spot size: 225 um; Depth: 80%; Density: 5%; Removed volume: 1.52 mm 3 ; Total number of pores: 161; Number of pores / quadrant: 40.25

[0232] Protocol 1.3: 225 μm (total 257 holes @ 8% = 64.25 holes / quadrant: valid)

[0233] Spot size: 225 um; Depth: 80%; Density: 8%; Removed volume: 2.43 mm 3 ; Total number of pores: 257; Number of pores / quadrant: 64.25

[0234] Protocol 1.4: 225 μm (total 565 holes @ 10% = 141.25 holes / quadrant: valid)

[0235] Spot size: 225 um; Depth: 80%; Density: 10%; Removed volume: 3.04 mm 3 ; Total number of pores: 565; Number of pores / quadrant: 141.25

[0236] Protocol 2.1: 250 μm (total 100 holes @ 3% = 25 holes / quadrant: valid)

[0237] Spot size: 250 um; Depth: 80%; Density: 3%; Removed volume: 0.91 mm 3; Total number of pores: 100; Number of pores per quadrant: 25

[0238] Protocol 2.2: 250μm (Total 166 holes @ 5% = 41.5 holes / quadrant: effective)

[0239] Spot size: 250um; Depth: 80%; Density: 5%; Removed volume: 1.52mm 3 ; Total number of pores: 166; Number of pores per quadrant: 41.5

[0240] Protocol 2.3: 250μm (Total 265 holes @ 8% = 66.25 holes / quadrant: effective)

[0241] Spot size: 250um; Depth: 80%; Density: 8%; Removed volume: 2.43mm 3 ; Total number of pores: 265; Number of pores per quadrant: 66.25

[0242] Protocol 2.4: 250μm (Total 332 holes @ 10% = 83 holes / quadrant: effective)

[0243] Spot size: 250um; Depth: 80%; Density: 10%; Removed volume: 3.04mm 3 ; Total number of pores: 332; Number of pores per quadrant: 83

[0244] Protocol 3.1: 325μm (Total 59 holes @ 3% = 14.75 holes / quadrant: effective)

[0245] Spot size: 325um; Depth: 80%; Density: 3%; Removed volume: 0.91mm 3 ; Total number of pores: 59; Number of pores per quadrant: 14.75

[0246] Protocol 3.2: 325μm (Total 98 holes @ 5% = 24.5 holes / quadrant: effective)

[0247] Spot size: 325um; Depth: 80%; Density: 5%; Removed volume: 1.52mm 3 ; Total number of pores: 98; Number of pores per quadrant: 24.5

[0248] Protocol 3.3: 325μm (Total 157 holes @ 8% = 39.25 holes / quadrant: effective)

[0249] Spot size: 325um; Depth: 80%; Density: 8%; Removed volume: 2.43mm 3; Total number of pores: 157; Number of pores per quadrant: 39.25

[0250] Protocol 3.4: 325μm (Total 196 holes @ 10% = 49 holes / quadrant: Valid)

[0251] Spot size: 325um; Depth: 80%; Density: 10%; Removed volume: 3.04mm 3 ; Total number of pores: 196; Number of pores per quadrant: 49

[0252] Protocol 4.1: 425μm (Total 34 holes @ 3% = 8.5 holes / quadrant: Valid)

[0253] Spot size: 425um; Depth: 80%; Density: 3%; Removed volume: 0.91mm 3 ; Total number of pores: 34; Number of pores per quadrant: 8.5;

[0254] Protocol 4.2: 425μm (Total 57 holes @ 5% = 14.25 holes / quadrant: Valid)

[0255] Spot size: 425um; Depth: 80%; Density: 5%; Removed volume: 1.52mm 3 ; Total number of pores: 57; Number of pores per quadrant: 14.25

[0256] Protocol 4.3: 425μm (Total 92 holes @ 8% = 23 holes / quadrant: Valid)

[0257] Spot size: 425um; Depth: 80%; Density: 8%; Removed volume: 2.43mm 3 ; Total number of pores: 92; Number of pores per quadrant: 23

[0258] Protocol 4.4: 425μm (Total 115 holes @ 10% = 28.75 holes / quadrant: Valid)

[0259] Spot size: 425um; Depth: 80%; Density: 10%; Removed volume: 3.04mm 3 ; Total number of pores: 115; Number of pores per quadrant: 28.75

[0137] The following are exemplary code references for the protocol:

[0260] fibonacci_spiral_connected_Pantec(‘r’,0.225,3,6.62,9.78)>>1.1

[0261] fibonacci_spiral_connected_Pantec('r', 0.225, 5, 6.62, 9.78) >> 1.2

[0262] fibonacci_spiral_connected_Pantec('r', 0.225, 8, 6.62, 9.78) >> 1.3

[0263] fibonacci_spiral_connected_Pantec('r', 0.225, 10, 6.62, 9.78) >> 1.4

[0264] fibonacci_spiral_connected_Pantec('c', 0.125, 3, 6.62, 9.78) >> 2.1

[0265] fibonacci_spiral_connected_Pantec('c', 0.125, 5, 6.62, 9.78) >> 2.2

[0266] fibonacci_spiral_connected_Pantec('c', 0.125, 8, 6.62, 9.78) >> 2.3

[0267] fibonacci_spiral_connected_Pantec('c', 0.125, 10, 6.62, 9.78) >> 2.4

[0268] fibonacci_spiral_connected_Pantec('c', 0.1625, 3, 6.62, 9.78) >> 3.1

[0269] fibonacci_spiral_connected_Pantec('c', 0.1625, 5, 6.62, 9.78) >> 3.2

[0270] fibonacci_spiral_connected_Pantec('c', 0.1625, 8, 6.62, 9.78) >> 3.3

[0271] fibonacci_spiral_connected_Pantec('c', 0.1625, 10, 6.62, 9.78) >> 3.4

[0272] fibonacci_spiral_connected_Pantec('c', 0.2125, 3, 6.62, 9.78) >> 4.1

[0273] fibonacci_spiral_connected_Pantec('c', 0.2125, 5, 6.62, 9.78) >> 4.2

[0274] fibonacci_spiral_connected_Pantec('c', 0.2125, 8, 6.62, 9.78) >> 4.3

[0275] fibonacci_spiral_connected_Pantec('c', 0.2125, 10, 6.62, 9.78) >> 4.4

[0138]

[0276] As pointed out, the input includes the following: pore diameter (μm); pore depth (μm); number of pores; pore density; angle of the pore zone; position of the laser beam from the surface and others, as desired or required.

[0139]

[0277] Various inputs can be used for proper and accurate modeling. The input may include pore diameter in μm, which is for actually varying the parameters not only of the spot number ratio and pattern but also of the pore diameter. Density should also be included, as well as the number of pores related to the pore diameter according to the formula of surface area, Power Calculation, the angle and long arc in each zone of the eyeball where each spot or row of spots will be placed, and the angle where there will be a laser spot for each zone using eye parameter inputs and the like.

[0140]

[0278] In some embodiments, the depth is fixed and at least two tests can be simulated, such as 50% depth = 454 μm or 80% depth = 700 μm.

[0141]

[0279] The protocol requirements for each treatment pattern may include the following: spot size; depth; total number of eye pores in all quadrants; number of pores / quadrant; number of pores / 5.5 mm patch; removal volume; density (number of spots). The implementation of the treatment operation may include the following: total quadrant vs. patch (surface area), where the specific corneal diameter of the shape-changing eye may be important.

[0142]

[0280] Exemplary embodiments of the application and field application of artificial intelligence and simulation can include the following: 1) Use in eye research and development to realize various modelings; 2) Virtual clinical trials; 3) Laser integration as a diagnostic companion or robotic controller; 4) Implementation of virtual surgery on the eye for a "smart surgery" plan; 5) Integration into an imaging device improves image interpretation; 6) Integration into a surgical microscope for "real-time" correction of surgery / treatment (e.g., for IOL surgery); and 7) Others.

[0143]

[0281] The functions of simulation can include the following: 1) Simulation of ideal biomechanics to optimize the best central refractive power regarding overall visual function and accommodation; 2) Simulation of ideal biomechanics to optimize the best refractive power of the overall visual function and the cornea; 3) Simulation of ideal biomechanics to optimize the reduction of aqueous humor outflow from the trabecular meshwork; 4) Simulation of ideal biomechanics to optimize the retinal decompression of the cribriform plate and peripapillary sclera; 5) Simulation to optimize scleral rejuvenation; 5) Simulation to optimize the surgical results of intraocular lens surgery; 6) Simulation to optimize the surgical or treatment results regarding corneal surgery; 7) Aging change simulation to evaluate the long-term effects of aging on eye function; 8) Aging change simulation to evaluate the long-term stability of the eye and the results of various surgical techniques; 9) Simulation to analyze tests of eye applications, treatments, surgical procedures, implant devices, and pharmacological treatments by virtual clinical trials; and 10) Others.

[0144]

[0282] The algorithms and other software used in implementing the systems and methods disclosed herein are generally stored in non-transitory computer-readable memory and generally include instructions for performing steps that implement the subject matter described herein by one or more processors or a processing system coupled thereto. Implementations of imaging, machine learning, prediction, automatic correction, and other subject matter described herein can be used in performing medical procedures that provide benefits not heretofore known in the art, along with current and future-developed medical systems and devices.

[0145]

[0283] In some embodiments, the systems, methods, and devices described are implemented before or concurrently with various medical procedures. In some embodiments, a medical procedure may be implemented with its own systems, methods, and devices, along with any components necessary to achieve its respective goals, as would be understood by one of ordinary skill in the art. It should be understood that medical procedures that benefit from the materials described herein are not limited to implementations using the materials described below, but may similarly benefit other past, currently practiced, and future-developed procedures.

[0146]

[0284] FIG. 3A shows an exemplary laser treatment system according to some embodiments of the present disclosure. In some embodiments, the treatment laser beam travels to dichroic 208. At dichroic 208, the laser beam travels to galvo setup 320, which consists of galvo 1 210 and galvo 2 212. Next, the beam passes from galvo setup 320 through focusing optics 216 and ultimately reaches patient eye 140.

[0147]

[0285] Also in this embodiment, a control and monitoring system is provided, which generally consists of a computer 310, a video monitor 312, and a camera 308. The camera 308 provides monitoring of the laser beam at the dichroic 208 via the lens 306. The camera 308 sends its feed to the computer 310. The computer 310 can also be operated to monitor and control the galvo setup 320. The computer 310 is also coupled to the video monitor 312 to provide a live feed from the camera 308 to the user or operator.

[0148]

[0286] In some embodiments of the present invention, a biaxial closed-loop galvano optical assembly is used.

[0149]

[0287] Since multiple laser systems may be used for the treatment in some embodiments, additional laser systems will be described here.

[0150]

[0288] The laser system may include a mount assembly with a cage-mounted galvano having a servo controller, an intelligent sensor, a feedback system, and an optical camera. Some embodiments may include the use of a cage-mounted galvano optical assembly. Some embodiments include an ultra-high resolution nanopositioner and can achieve a resolution below nanometers.

[0151]

[0289] For spreading, FIG. 3A shows further exemplary details of a CCD (or CMOS) camera-based visual target tracking subsystem. When using a dichroic 208 beam splitter, visible light can be picked off while the IR treatment beam can be transmitted. The beam splitter 208 is located here in front of a steering element shown as a galvo mirror 320. A lens 306 images the tissue plane (eye) onto the camera. Features in the image field (such as blood vessels, iris edges, etc.) are identified by image processing, and their coordinates in the camera pixel field are calculated. When the eye moves frame-to-frame within the pixel field, the change in the position of the reference feature can be calculated. An error function is calculated from the change in the reference feature position, and the galvo mirror 320 is commanded to minimize the error function. In this configuration, the center of the optical line of sight is always the treatment spot located on the fixed coordinates of the camera pixel field. The apparent movement by repositioning the galvo 320 can be to move the image of the eye relative to the fixed treatment spot.

[0152]

[0290] FIG. 3B shows an exemplary laser treatment system 303 according to an embodiment of the present disclosure. The laser treatment system 303 is similar to FIG. 3A, except that the visual target tracking subsystem is located behind the galvo mirror 320.

[0153]

[0291] In this embodiment, the treatment laser beam proceeds to a galvo setup 320 consisting of galvo 1 210 and galvo 2 212. Next, the beam passes from the galvo setup 320 to the dichroic 208. At the dichroic 208, the laser beam passes through the focusing optics 216 and finally reaches the patient's eye 140.

[0154]

[0292] Also, in this embodiment, a control and monitoring system is provided, which generally consists of a computer 310, a video monitor 312, and a camera 308. The camera 308 provides monitoring of the laser beam at the dichroic 208 via the lens 306. The camera 308 sends its feed to the computer 310. The computer 310 can also be operated to monitor and control the galvo setup 320. The computer 310 is also coupled to the video monitor 312 to provide a live feed from the camera 308 to the user or operator.

[0155]

[0293] Here, the eye image is shown at the center of the pixel field. When eye movement is detected within the pixel field, the galvo 320 is repositioned to move the treatment spot to a new position within the pixel field corresponding to the eye movement and to a desired fixed position relative to the reference features of the eye.

[0156]

[0294] In connection with the aforementioned biofeedback loop, in some embodiments, visual target tracking involves the use of a light source that generates an infrared illumination beam projected onto an artificial reference attached to the eye. The infrared illumination beam is projected near the visual axis of the eye and has a spot size that is larger than the reference on the eye and encompasses the range as the reference moves with the eye.

[0157]

[0295] In some embodiments, the reference has a retroreflective surface that produces a retroreflection order that will be stronger than the backscatter from the eye. An optical condenser may be configured and positioned away from the eye to collect this backscattered infrared light to form a reference bright spot image spot at a selected image position.

[0158]

[0296] The bright spot image spot is visible on a dark background with a single element positioning detector positioned at the image position selected to receive the bright spot image spot and configured to measure the two-dimensional position of a reference bright spot image spot on the positioning detector. An electrical circuit may be coupled to the positioning detector to generate a positioning signal indicative of the reference position of the center of gravity of the bright spot image spot based on the measured two-dimensional position of the bright spot image spot on the positioning detector.

[0159]

[0297] FIG. 3C shows an exemplary camera correction system according to an embodiment of the present disclosure. In this exemplary embodiment, the upper portion shows the camera focus position after galvanometer use, and the lower portion shows the camera focus position before the galvanometer. In this exemplary embodiment, various landmarks 392 can be seen, including capillaries, iris, pupil, etc. A treatment spot 394 can also be seen in each embodiment.

[0160]

[0298] As shown in the exemplary embodiment, the upper portions of the focus before the galvanometer each show the pupil as the center pixel of each image. With the lower post-galvanometer compensation, the treatment spot 394 can remain in the focus of the camera in each image, thereby enabling the system to remain in an appropriate position for the associated procedure.

[0161]

[0299] FIG. 3D shows an exemplary flow diagram 330 of a camera-based visual target tracker process according to an embodiment of the present disclosure.

[0162]

[0300] Broadly speaking, this figure represents the acquisition of an eye image using a CCD or CMOS camera. The image data is sent to a computer where important features are segmented / extracted (e.g., blood vessels, iris features, pupil edges). This image is saved as a reference frame. Subsequently, subsequent images are compared to the reference frame. After comparing the reference features in pixel coordinates, a shift is calculated. Next, after converting from pixel coordinates to scanning system coordinates, the scanning system is commanded to shift the treatment beam line of site to restore the relationship to the reference features. If the shift is too large or outside the range of the scanning system, the procedure is stopped and means are taken to reacquire the target image field.

[0163]

[0301] As a more detailed explanation referring to each step, for some embodiments, the initialization or start procedure needs to acquire an image frame in step 332 before processing the image frame acquired in step 334 to extract features. Next, using this acquired frame containing the features to be extracted, a reference frame is set in step 336.

[0164]

[0302] After the reference frame is set, step 338 consists of acquiring an additional image frame called the current frame. This image or current frame is processed in step 340 to extract features. Step 342 consists of comparing the current frame with the reference frame set in step 336. The image shift between the current frame and the reference frame is calculated and the difference between these frames is determined. From the comparison with a preset threshold, the system can determine whether the image shift exceeds the preset threshold, and at this point, the procedure is stopped by proceeding to step 352.

[0165]

[0303] If the image shift does not exceed a preset threshold and thus is not too large, the system calculates, at step 346, a compensation level for compensating for the change or shift between the current frame and the reference frame. This compensation level is calculated on the physical coordinates used by the scanner at step 348. Next, at step 350, the scanner is instructed to compensate using the coordinates. After this compensation step 338 is performed, another current image frame is acquired and the cycle continues.

[0166]

[0304] FIG. 4A shows an exemplary laser treatment system 400 according to an embodiment of the present disclosure. In this exemplary embodiment, the laser treatment system 400 consists of a treatment laser 202 that emits a laser beam that travels through a relay lens 204 to a dichroic or flip-in 208. A visible spotting laser 206 similarly emits a laser beam that travels to the dichroic or flip-in 208. In some embodiments, the beams from the treatment laser 202 and the visible spotting laser 206 can merge simultaneously at a first dichroic or flip-in 208. In other embodiments, these beams can reach the first dichroic or flip-in 208 at different times.

[0167]

[0305] One or more beams travel to a second dichroic 208 after leaving the first dichroic or flip-in 208. One or more beams travel to a galvo 210 after leaving the second dichroic 208. Galvo 1 210 can consist of a mirror that rotates through a galvanometer setup to move the laser beam. One or more beams travel to galvo 2 212 after leaving galvo 210, which can have a setup similar to galvo 1 210. One or more beams travel to a dichroic (visible / IR) 214 after leaving galvo 2 212. The operator 160 can monitor one or more beams at the dichroic (visible / IR) 214 by using a surgical microscope 150. One or more beams travel from the dichroic (visible / IR) 214 through a focusing optical system 216 and reach the patient's eye 140.

[0168]

[0306] Figure 4A provides additional monitoring elements used by the operator 160 to assist in medical procedures. The depth control subsystem 302 aids in controlling the depth of the ablation procedure in the present invention and receives input from the second dichroic 208. FIGS. 4A-(1-10) show how micro-poration / nano-poration can be used to remove the target surface or the surface, subsurface, and interstitial tissue of the target tissue to be ablated and affect surface, interstitial, and biomechanical characteristics (e.g., flatness, surface porosity, tissue geometry, tissue viscoelasticity, and other biomechanical and rheological characteristics).

[0169]

[0307] Similarly, the eye tracker 304 aids in tracking landmarks on the patient's eye 140 during the medical procedure in the present invention and receives input from the second dichroic 208. This exemplary embodiment shows another dichroic 208 that splits the beam and outputs it to the eye tracker 304 and the depth control subsystem 302.

[0170]

[0308] FIG. 4B shows an exemplary laser treatment system including ablation pore depth according to an embodiment of the present disclosure. FIG. 4B generally shows the treatment laser beam that travels to the galvo 1 210 after reaching the dichroic 208, then to the galvo 2 212, and then through the focusing optics 216 to the patient's eye 140. As shown above, FIGS. 4A-(1-10) show how micro-poration / nano-poration can be used to remove the target surface or the surface, subsurface, and interstitial tissue of the target tissue to be ablated and affect surface, interstitial, and biomechanical characteristics (e.g., flatness, surface porosity, tissue geometry, tissue viscoelasticity, and other biomechanical and rheological characteristics).

[0171]

[0309] The OCT system 404 is an optical coherence tomography system used to obtain an image under the surface of the eye. Therefore, when the OCT system 404 is coupled to a computer 310 that is coupled to a video monitor 312, it provides the user or operator with the ability to view an image under the surface of the tissue ablation; the pore ablation may be 5% - 95% of the scleral thickness, the average scleral thickness is 700μm, and the typical pore depth may be on the order deeper than the refractive surface ablation at a depth of about 200um - 300um. This is a significantly deeper depth compared to other surface refractive ablation techniques that are typically on the order of an average depth of 10um - 45umμm and generally >120um.

[0172]

[0310] In at least some embodiments, OCT provides a real-time intraoperative view of depth levels in the tissue. OCT may provide image segmentation to help identify the inner boundary of the sclera for better controlled depth. As shown above, FIGS. 4A-(1 - 10) show how micro-poration / nano-poration can be used to remove the surface, subsurface, and interstitial tissue of the target surface or target tissue being ablated and affect the surface, interstitial, biomechanical characteristics (e.g., planarity, surface porosity, tissue geometry, tissue viscoelasticity, and other biomechanical and rheological characteristics).

[0173]

[0311] In some embodiments, the OCT system 404 uses an OCT measurement beam that is incident on the treatment beam line of sight via a dichroic beam splitter 208 located in front of the scanning system. In this way, the center of the OCT system line of sight is always the pore being ablated. The OCT system is connected to a computer 310 for image processing and laser control.

[0174]

[0312] In some embodiments of the present invention, an anatomical structure avoidance subsystem is provided that identifies critical biological obstacles or locations (such as blood vessels, etc.) during a procedure. To that end, subsurface visualization may be provided that identifies obstacles such as blood vessels or anatomical structures that are desirable to avoid during the procedure.

[0175]

[0313] FIGS. 4A-5 and 4B show exemplary simple ablation pore diagrams in the sclera showing an example of ablation depth relative to the inner boundary of the sclera.

[0176]

[0314] FIG. 5 shows an exemplary flow diagram 410 of OCT-based depth control according to an embodiment of the present disclosure.

[0177]

[0315] Generally, an OCT system performs repeated B-scans synchronized with a laser. The B-scan shows the upper surface of the conjunctiva and / or sclera, the boundary of the pores to be ablated, and the lower interface between the sclera and the choroid or ciliary body. The upper and lower surfaces of the sclera (typically 400-1000 microns thick) and the boundaries of the ablated pores are identified using an automatic image segmentation algorithm. The distance from the upper surface of the sclera to the bottom of the pore is automatically calculated and compared to the local thickness of the sclera. In some embodiments, this is done in real time. When the pore depth reaches a predefined value or percentage of the sclera thickness, ablation is stopped and the scanning system is sent to the next target ablation position. In some embodiments, the image may be segmented to identify the inner scleral boundary.

[0178]

[0316] In connection with the steps in this figure, in an exemplary embodiment, first a set of start or initialization steps are performed. This set of start steps begins with positioning at the pore coordinates in step 412. A B-scan of the target area is performed in step 414. An image is created by this scan and the scleral boundary is segmented and identified by processing it in step 416. Next, the distance between the conjunctival surface and the scleral boundary is calculated in step 418.

[0179]

[0317] After completion of this set of start steps, ablation is initiated at step 420. A laser beam pulse is emitted at step 422, followed by a B-scan at step 424. This B-scan creates an image, which is then segmented at step 426 to calculate the pore depth and ablation rate from the image. This pore depth and ablation rate are compared with the target depth at step 430. If the target depth has not been reached, the process then loops back to step 422 and repeats. When the target depth is reached, the ablation process stops at step 432 and the positioning to the next pore coordinates at step 434 starts the start process again. In some embodiments, the OCT system can monitor the ablation depth during a single pulse, can stop ablation as a risk mitigation means, and other internal processes that can end ablation if the process is out of range; if the visual target tracking operating limit is exceeded; if the preset maximum number of pulses is exceeded; or if the laser output monitoring is out of limits may also be performed. These are all risk mitigation means.

[0180]

[0318] FIG. 6 shows an exemplary laser treatment system component map 600 showing the relationships of related subsystems according to an embodiment of the present disclosure.

[0181]

[0319] Generally, the laser treatment system component map 600 shows a laser 602, a laser delivery fiber 120, a laser control system 604, a monitoring system 608, and a beam control system 606.

[0182]

[0320] Laser 602 generally consists of several subsystems. In this exemplary embodiment, these subsystems include system control electronics 104, an Er:YAG laser head 612, a laser cooling system 108, an HV power supply 110, and a system power supply 112. A foot pedal 114 provides some control to the system user. Laser 602 sends a laser beam to beam control system 606 via a laser delivery fiber 120.

[0183]

[0321] Beam control system 606 generally consists of beam transport optics 624, a red spotting laser 626, galvo mirrors 628, beam delivery optics 630, and an active focus 632.

[0184]

[0322] Laser control system 604 maintains a link with laser 602 through laser synchronization and maintains a link with beam control system 606 through an output control position state. Laser control system 604 generally consists of a user interface 614, a power supply 616, a galvo controller 618, a galvo controller 620, and a microcontroller 622. Laser control system 604 can also be operated by a joystick 610.

[0185]

[0323] Monitoring system 608 generally consists of a CCD camera 634 and a visible microscope 636.

[0186]

[0324] In some embodiments, a fiber laser made of a high refractive index undoped cladding and a doped core is used. The laser beam travels through a fiber guided within the fiber core and undergoes high amplification due to the interaction length. Fiber lasers are considered advantageous over other laser systems because they are low cost, require little maintenance, are highly reliable, have no mirror or beam path alignment, and among other qualities, have simple thermal management characteristics, high beam quality, high electrical efficiency, high optical efficiency, high peak energy, and are lightweight and generally compact.

[0187]

[0325] In some embodiments of the present invention, a spot array may be used to ablate multiple pores simultaneously. Such spot arrays may in some cases be created using microlenses and may also be affected by the characteristics of the laser. The larger the wavelength, the larger the spot diameter may be and the fewer the number of spots.

[0188]

[0326] Referring to FIG. 7, an exemplary laser treatment system 700 according to an embodiment of the present invention is shown. The laser treatment system 700 generally comprises a control system 702, an optical system, and beam control.

[0189]

[0327] The control system 702 includes a monitor 704 and a monitor 2 706, as well as a keyboard 708 and a mouse 710, to give the user the ability to interact with and control a host computer 724 that executes a computer program. In many embodiments, the computer program executed on the host computer 724 includes a control program that controls a visible spotting laser 712, a laser head 714, a laser cooling system 716, a system power supply 718, a laser power supply 720, and a beam transport optical system 722.

[0190]

[0328] Also, in this embodiment, a depth control subsystem 726, a galvo mirror 728, a CCD camera 730, a visible microscope 732, a focus subsystem 734, and a beam delivery optical system 736 are also provided.

[0191]

[0329] FIG. 7-1 shows another exemplary laser treatment system.

[0192]

[0330] Pre-operative measurement of eye characteristics and customization of treatment according to the needs of individual patients are beneficial in many embodiments. Pre-operative measurement of eye characteristics may include measurement of intraocular pressure (IOP), scleral thickness, scleral stress / strain, anterior vasculature, accommodative response, and refractive anomalies. Measurement of scleral thickness may include using optical coherence tomography (OCT). Measurement of scleral stress / strain may include using Brillouin scattering, OCT elastography, photoacoustics (light + ultrasound). Measurement of anterior vasculature may include using OCT or Doppler OCT. Measurement of refractive anomalies may include using products such as the trademarked product iTrace from Tracey Technologies Corp.

[0193]

[0331] An intraoperative biofeedback loop can be important in a procedure to continuously provide the physician with information regarding the progress of the procedure. Such a feedback loop may include using topography measurements and monitoring "keep away" zones such as the anterior ciliary arteries.

[0194]

[0332] The biofeedback loop may include a closed-loop sensor that corrects for non-linearity in a piezoelectric scanning mechanism. In some embodiments, this sensor may provide real-time position feedback in a few milliseconds and utilize a capacitive sensor for real-time position feedback. The real-time position feedback may communicate with a controller and may abort laser activation when certain biological characteristics based on tissue characteristics are identified during the procedure.

[0195]

[0333] The sensor / feedback device may also perform biological or chemical "smart sensing" that enables ablation of the target tissue while protecting or avoiding surrounding tissue. In some examples, this smart sensing may be achieved by using the incorporation of biochips in a mask that is activated by light irradiation and detects position, depth, size, shape, or other ablation profile parameters. A galvo-optical system assembly is also contemplated in some embodiments and can be used for laser steering and gauging a number of parameters of special functions.

[0196]

[0334] In some embodiments, the systems, methods, and devices described can include image display transmission and GUI interface features that can send information including each captured image frame to a video display before and after laser emission in dynamic real-time and surface view, and after each emission inside 3D to 7D micropores. The GUI can have a 7-directional integrated multi-view system for image acquisition, including surface, internal pores, external pores, bottom of micropores, global spherical eye view, target array range.

[0197]

[0335] In some embodiments, a 7-cube may be a preferred projection for the microprocessor, but there are other examples for the dimensional spherical shape integrated with the GUI and microprocessor. The orthographic projection may include examples as shown in FIG. 8.

[0198]

[0336] SVM pattern recognition is integrated into the AI (Artificial Intelligence) network for the microprocessor path. For non-linear classification problems, SVM will change the input space to a high-dimensional space by the non-linear mapping K(X). Therefore, the non-linear problem becomes a linear problem, and then the optimal separation hyperplane will be calculated in the new high-dimensional space using the programming incorporated in Matlab or Mathematica. Since the optimization function and the classification function only include the inner product (xi - xe) between samples, the transformed high-dimensional space is also only the inner product (k(xi) - k(xe)). When the kernel function (k(xi_-k(xe) satisfies the Mercer condition, it corresponds to the transformed space of the inner product K(xi, x=(k(xi)-k(x)). General kernel functions include linear kernel, polynomial kernel, and radial bias kernel functions. The use of an appropriate kernel function can be an alternative to the non-linear mapping (aping) of the high-dimensional space that will achieve linear classification after non-linear transformation. The corresponding classification and discrimination function can be obtained as follows:

Number

[0199]

[0337] In some examples, the following can be cited as the mapping and optimization formulas of machine learning:

Number

[0200]

[0338] The devices of the GUI interface and the code can include multi-dimensional scaling, and linear discriminant analysis and linear dimensionality reduction processing, as well as local linear embedding and isometric mapping (ISOMAP), are also non-linear dimensionality reduction methods included in the same way.

[0201]

[0339] A continuous mapping p: E → B that satisfies the homotopy lifting property for any space may be used. Fiber bundles (with paracompact bases) form an important example. In homotopy theory, any mapping is "as good as" a fibration - that is, any mapping can be decomposed as a homotopy equivalence into the "mapping path space", and subsequently the fibration can be decomposed into homotopy fibers.

[0202]

[0340] The fiber, by definition, is the subspace of E that is the preimage of a point b in B. If the base space B is path-connected, it is a consequence of the definition that the fibers over two different points b1 and b2 in B are homotopy equivalent. Thus, one usually speaks of "the fiber".

[0203]

[0341] Some embodiments can utilize Serre fibrations or weak fibrations. These are capable of generating mappings over arrays and 3D surfaces of each cylindrical micropore of the entire array and interstitial mapping of the pore array in cross-section. An exemplary 3D mapping 900 is shown in FIG. 9.

[0204]

[0342] Figure 10 shows an exemplary design pattern that can be implemented as follows. Step 1001: The treatment design / planning starts from the organizational hierarchy constructed using a 7-sphere mathematical projection across the entire sphere to construct a congruent treatment platform built on a 7D shape and a hyperbolic plane tessellation. Step 1002: The off-axis mathematical algorithm derived from the organizational hierarchy and the Fibonacci pattern formation is displayed as a mathematical image. Step 1003: Next, the algorithm code is executed to develop a customized microporation pattern that reflects the tissue bioreology including all inputs such as stiffness, viscoelastic coefficient, topology, topography, biometrics, etc. Step 1004 (not shown): The anatomical structure avoidance software is executed to erase or remove off-target fields, arrays, regions. Step 1005 (not shown): The surgeon / user can also manipulate the target or off-target range with a touch screen interface.

[0205]

[0343] In some embodiments, the described systems, methods, and devices may include the following features for laser user interface system delivery of treatment algorithms. Real-time mathematical images are captured and displayed in both a 3D mathematical file format that can also be executed in a GIF animation format to display prior information regarding array effectiveness. The workstation / algorithm works with a VESA system to generate a mathematical image for the user / surgeon regarding the optimal configuration of an above-eye 3D array. The topological representation of the image is projected in a stereoscopic rendering on the display. The array is of a pre-fixed type and can additionally be simulated in a Fibonacci sequence having multiple densities, spot sizes, micro- and nano-pore geometries, and arrangements. The advantage of the Fibonacci sequence is that the most balanced array type corresponding to the natural tissue hierarchy of the body at both the macroscale and microscale is created.

[0206]

[0344] The array can also follow a hyperbolic geometry model or a uniform (regular, quasiregular, or semiregular) hyperbolic tiling that has a regular polygon as a face and is vertex-transitive (transitive with respect to its vertices, equiangular, i.e., there is an isometry that maps any vertex to any other). Examples are shown in FIGS. 10 and 11. Thus, all vertices are congruent, and the tiling has a high degree of rotational and translational symmetry.

[0207]

[0345] A uniform tiling can be specified by its vertex configuration, a sequence representing the number of sides of the polygons surrounding each vertex. The following example represents a heptagonal tiling with three heptagons surrounding each vertex. This is also regular since all polygons are the same size, and thus it can also be given a Schläfli symbol.

[0208]

[0346] A uniform tiling can be regular (when face-transitive and edge-transitive), quasiregular (when edge-transitive but not face-transitive), or semiregular (when neither edge-transitive nor face-transitive). Right triangles (p q 2) have two regular tilings represented by the Schläfli symbols {p,q} and {q,p}.

[0209]

[0347] An exemplary model is shown in FIG. 11.

[0210]

[0348] In some embodiments, the systems, methods, and apparatuses described may include a mechanism for creating an array of micropores, where the micropore array pattern has a controlled non-uniform distribution, or a uniform distribution, or a random distribution, and is at least one of a radiation pattern, a spiral pattern, a phyllotaxis pattern, an asymmetric pattern, or a combination thereof. The phyllotaxis spiral pattern may have right-handed and left-handed diagonals according to the present disclosure: FIG. 12 shows an exemplary schematic representation 1200 creating an array algorithm pattern of a non-uniform distribution controlled by phyllotaxis spirals on the eye, where each micropore array appears continuously. R0 is the radius of the region corresponding to the center of the meristem around which micropores are created. The large vertical arrow symbolically represents the expansion of the vertical micro-poration in the array, while the arrow drawn horizontally indicates the spatial expansion of the new micropore system, and i and j are pairs of consecutive Fibonacci numbers, i.e., such a pair of consecutive Fibonacci numbers is denoted as (i,j). The symbols n, n - i, n - j, n - i - j represent numbers indicating the order in which micropores appear along the spiral formed during the expansion of the array. However, in some cases, it may be better to represent them with the symbols n, n + i, n + j, n + i + j. The same secondary spiral family has consecutive numbers with a certain difference between them. Thus, for the left-handed family: (n + i) - n = i [which is a Fibonacci number], (n + i + j) - (n + j) = i [which is the same Fibonacci number]. For the right-handed family: (n + j) - n = j [which is the second Fibonacci number], (n + i + j) - (n + i) = j [which is the same Fibonacci number]. Thus, here we have the case of (i,j) phyllotaxis.

[0211]

[0349] In some embodiments, the micropore array pattern is one of an Archimedean spiral, an Euler spiral, a Fermat spiral, a hyperbolic spiral, a lituus, a logarithmic spiral, a Fibonacci spiral, a golden spiral, or a combination thereof.

[0212]

[0350] In some embodiments, the systems, methods, and devices described may include creating a 3D microporation model on a spherical surface. FIG. 13 shows an exemplary graphic image 1300 created on a CAD program of an exemplary embodiment of microporation having a mechanism for radially and laterally expanding a microporation array by creating a microhole array and utilizing an o phyllactic spiral that expands the array between faces and between sides while maintaining a non-uniform distribution through the aperture in accordance with the Vogel model and Fibonacci array, where X number of microholes in a plurality of densities, diameters, and geometric shapes are created by the present invention. These exemplary embodiments are the anterior or posterior sclera of the eye, but may also be the cornea).

[0213]

[0351] In some embodiments, the systems, methods, and devices described may include optimizing the performance, outcomes, and safety of a surgical procedure in a laser-assisted microporation treatment array having a pattern of microholes / nanoholes utilizing Fibonacci and mathematical parameters, where the pattern is a non-uniform distribution pattern that aligns with existing tissue hierarchies at the macroscale and microscale to deliver a rejuvenating effect of the procedure uniformly to cross-sectional tissue. A treatment array or grid having a plurality of microholes / nanoholes / ablations / incisions / targeting may be arranged in a non-uniform distribution pattern, where the pattern is a spiral or phyllotaxis. The pattern may be described by Vogel's formula. Also included are a plurality of other geometries / densities / depths, and shapes having flow paths of spiral or phyllotaxis patterns, such as the morphology of the aperture channels or pores. The microholes / nanoholes can be specifically adapted to correspond to a given contact lens, mask, or other template material or design having a non-uniform distribution pattern. Alternatively, the microporation can be used in conjunction with conventional porous coated or uncoated polymers, such as hydrophilic or hydrophobic types. An array pattern having microholes in a non-uniform distribution pattern and a lens or mask can be used together as a treatment system.

[0214]

[0352] As shown above, FIGS. 4A-(1-10) and 26-3A show how micro-poration / nano-poration can be used to remove the surface, subsurface, and interstitial tissue of the ablation target surface or target tissue, and affect the surface, interstitial, and biomechanical characteristics (e.g., planarity, surface porosity, tissue geometry, tissue viscoelasticity, and other biomechanical and rheological characteristics). In addition, the present disclosure includes various automated processing systems for handling the delivery of micro-porations of various compositions and configurations.

[0215]

[0353] Effective tissue characteristics include, among others, porosity, texture, viscoelasticity, surface roughness, and uniformity. The quality is determined by measuring surface characteristics such as roughness and gloss. Such micro-porations also cause tissue deformation, flexibility, and flexibility, and can have a "tangerine peel" texture. Therefore, the characteristics of the tissue treated with micro-poration / nano-poration generally affect and / or enhance the tissue quality by the recovery or rejuvenation of the biomechanical flexibility of the tissue at rest and under stress / strain.

[0216]

[0354] As shown below, the micro-poration pattern may have a plurality of right-handed helices and a plurality of left-handed helices, where the number of right-handed helices and the number of left-handed helices are Fibonacci numbers or multiples of Fibonacci numbers.

[0217]

[0355] FIG. 14A shows an exemplary embodiment of a micro-poration pattern, which can be realized directly on the target tissue or on a contact lens, mask, or other such template, and has a controlled non-uniform distribution of micro-pores of the Fibonacci array distribution according to the present disclosure.

[0218]

[0356] FIG. 14B is an exemplary explanatory diagram of a phyllotaxis spiral pattern having right-handed and left-handed diagonals according to the present disclosure.

[0219]

[0357] Figure 14C is another exemplary explanatory diagram of a phyllotaxis spiral pattern having clockwise and counterclockwise diagonal rows according to the present disclosure.

[0220]

[0358] Figure 14D is an exemplary explanatory diagram of the Vogel model in the present disclosure. The Vogel model includes a pattern of florets. Briefly, each floret faces the next floret at an angle of 137.5°. The number of left-handed spirals and the number of right-handed spirals are Fibonacci numbers. In a typical sunflower, there are 34 in one direction and 55 in the other.

[0221]

[0359] Figures 15A to 15F are exemplary explanatory diagrams of phyllotaxis spiral patterns according to the Vogel model having various apertures according to the present disclosure.

[0222]

[0360] Figures 16A to 16N are exemplary explanatory diagrams of exemplary embodiments of micro-poration derived from an icosahedron pattern shape according to the present disclosure.

[0223]

[0361] Figures 17A to 17B, Figures 2K-(18 to 19) are exemplary explanatory diagrams of micro-poration patterns derived from an icosahedron pattern shape representing a fractal sphere and an icosahedron / tetrahedron tessellation according to the present disclosure.

[0224]

[0362] In some embodiments, the exemplary micro-poration patterns shown in FIGS. 14A to 17B above may be pre-punched in a contact lens or a mask. Disclosure of FIG. 18 of a contact lens / ocular mask cooperating with the micro-poration pattern of FIG. 18.

[0225]

[0363] Figures 2K1 to 2K17; Plus 3D eyes 2 slides show exemplary embodiments of the present invention of micro-poration patterns of multiple micropores of multiple densities and multiple spot sizes.

[0226]

[0364] Figure 2K-20 is an exemplary graphic image of an exemplary embodiment of micro-poration of a pattern having 41 micro-pores according to the present invention.

[0227]

[0365] FIGS. 14A to 14D are exemplary explanatory views of an exemplary embodiment according to the present invention. A sunflower pattern, which is a kind of "Fibonacci spiral", or a spiral with a constant Fibonacci angle approaching the golden angle where the opening between consecutive points is equal to 137.508°, is described by Vogel's model.

[0228]

[0366] The Vogel model as described is φ = n * α, r = c√n [where: n is the serial number of the floret counted from the center to the outside; φ is the angle formed by the reference direction and the position vector of the nth floret in a polar coordinate system with the center of the inflorescence as the origin, such that the opening α between the position vectors of any two consecutive florets is constant and is 137.508° for the sunflower pattern; r is the distance from the center of the inflorescence to the center of the nth floret; and c is a constant scaling factor]. Refer to FIG. 41.

[0229]

[0367] In some embodiments, the micro-pore pattern is described by the Vogel model or a modification of the Vogel model. In some embodiments, the micro-pore pattern may be described by the Vogel model, where: n is the serial number of the micro-pore counted from the center to the outside of the micro-pore pattern; φ is the angle formed by the reference direction and the position vector of the nth micro-pore in a polar coordinate system with the center of the micro-pore pattern as the origin, such that the opening between the position vectors of any two consecutive micro-pores is a constant angle α; r is the distance from the center of the micro-pore pattern to the center of the nth micro-pore; and c is a constant scaling factor.

[0230]

[0368] In some embodiments, all, substantially all, or some of the micropores of the micropore pattern will be described by (i.e., will follow) the Vogel model. In some embodiments, all of the micropores of the micropore pattern may be described by the Vogel model. In some other embodiments, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% of the micropores may be described by the Vogel model.

[0231]

[0369] Surface area: The total target tissue surface area affects the total amount of tissue material removed. Typically, as the total tissue surface area increases, the amount of surface material removed increases. In some embodiments, the total microporation surface area of the target tissue is equal to the potential total surface of the microporation system (i.e., the microporation target area if there were no micropores) minus the total micropore area (i.e., the sum of the areas of all the micropores). Thus, the size of the total microporation surface area can range from 1% to about 99.5% of the potential total surface area depending on the desired size of the micropore area. See FIG. 30.

[0232]

[0370] Depth: Referring again to FIGS. 4A-(5-10), these figures show that the total target tissue depth affects the total amount of tissue material removed. Typically, as the total tissue depth increases, the amount of interstitial or subsurface tissue removed increases. In some embodiments, the depth of the tissue microporation being removed is equal to the potential total subsurface and interstitial tissue of the microporation system (i.e., the total interstitial and subsurface tissue if there were no micropores) minus the total micropore cubic volume (i.e., the sum of the areas of all the micropores). Thus, the size of the total microporation cubic volume can range from 1% to about 95% of the potential total subsurface and interstitial cubic volume of the microporation tissue depending on the desired amount of the micropore cubic volume.

[0233]

[0371] Density of micropores: The density of the micropore array affects the total amount of micropore area and the total amounts of surface, subsurface, and interstitial removal volumes. This also affects the total number of micropores and the micropore distribution. Multiple density configurations, micropore diameters, and micropore distributions are illustrative of the present invention. The micropores may be delivered randomly, uniformly, or individually. Refer to FIGS. 2K-1-(A to C) to FIGS. 2K-17.

[0234]

[0372] Number of micropores: The number of micropores affects the total amount of micropore area and the amounts of total surface, subsurface, and interstitial removal volumes. In addition, the number of micropores affects the density and distribution of the micropore coating on the surface of the micro-poration system, which in turn directly affects the total volume extraction of the micro-poration system. In certain embodiments, the number of micropores is at least about 3, at least about 5, at least about 8; at least about 12, or at least about 15. In another embodiment, the number of micropores is at least about 45, at least about 96, at least about 151, and at least about 257. Also refer to FIGS. 31 to 34, FIGS. 37, FIGS. 38, FIGS. 39 for the above and following parameters.

[0235]

[0373] In some embodiments, the number of pores can range from 36 to 10,000 depending on the size of the spot that can range from 1 nm to 600 um. The number of micropores can be within a range including any pair of the above upper and lower limits. Refer to FIG. 41.

[0236]

[0374] Aperture: In a method of a micro-poration system for delivering a laser pulse to a target tissue, an increase or decrease in the aperture affects how the micropores are placed within the pattern and the shape of clockwise and counterclockwise spirals. The aperture is equal to 360° divided by a constant value or a variable value. Thus, the aperture may be a constant value or it may vary. In some embodiments, the pattern has an aperture in the range of about 100° to about 170° in polar coordinates. It has been observed that a small change in the aperture can greatly change the array pattern and that phyllotaxis patterns with only different aperture values can be shown. The aperture may be 137.3°. The aperture may also be 137.5°, 137.6°. In some embodiments, the aperture 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 aperture is less than 180°, such as about 150° or less. The aperture can be within a range including any pair of the above upper and lower limits. In some other embodiments, the aperture is in the range of about 90° to about 179°, about 120° to about 150°, about 130° to about 140°, or about 135° to about 139°. In some embodiments, the aperture is determined by dividing 360° by an irrational number. In some embodiments, the aperture is determined by dividing 360° by the golden ratio. In some embodiments, the aperture is in the range of about 137° to about 138°, for example about 137.5° to about 137.6°, for example about 137.50° to about 137.51°. In some embodiments, the aperture is 137.508°. Refer to FIGS. 31 to 34.

[0237]

[0375] Distance to the edge of the micro - pore array: In some embodiments, the overall dimensions of the array pattern can be determined based on the geometry and intended use of the micro - poration system. The distance from the center of the pattern to the outermost micro - pore can extend to a distance that shares a boundary with the edge of the micro - poration system. Thus, the edge of the outermost micro - pore can extend to or intersect with the edge of the micro - poration system. Alternatively, the distance from the center of the pattern to the outermost micro - pore can extend to a distance that allows for a certain size of gap between the edge of the outermost micro - pore and the edge of the micro - poration system that does not include the micro - pores. The minimum distance from the edge of the outermost micro - pore can be specified as desired. In some embodiments, the minimum distance from the edge of the outermost micro - pore to the outer edge of the micro - poration system is a specific distance specified as an individual length or as a ratio to the length of the micro - poration system surface on which the array pattern appears.

[0238]

[0376] Size of the micro - pores: In some embodiments, the size of the micro - pores is determined, at least in part, by the total array area desired for the micro - poration system. The size of the micro - pores may be constant throughout the pattern or it may vary within the pattern. In some embodiments, the size of the micro - pores is constant. In some embodiments, the size of the micro - pores varies with the distance of the micro - pores from the center of the pattern. The size of the pores can range from 1 nm to 600 μm. In some other embodiments, the sizes are 50 μm, 100 μm, 125 μm, 200 μm, 250 μm, 325 μm, 425 μm, and 600 μm.

[0239]

[0377] Shape of micropores: The shape of the micropores themselves created in connective tissue by electromagnetic irradiation affects the tissue response and the resulting healing relative to wound healing. Square shapes heal more slowly compared to circular shapes. The microporation system has the ability to create multiple geometrically distinct micropore shapes. In some embodiments, the ideal shape is square.

[0240]

[0378] Shape also has an impact on the micropore array. The magnitude of the coverage rate can be affected by the shape of the micropores. The shape of the micropores may be regular or irregular. In some embodiments, the shape of the micropores may be in the form of slits, regular polygons, irregular polygons, ellipsoids, circles, arcs, spirals, channels, or combinations thereof. In some embodiments, the micropore array has a circular shape. In some embodiments, the shape of the array may be in the form of one or more geometric patterns, preferably icosahedron or tetrahedron tessellation, where multiple polygons intersect.

[0241]

[0379] FIGS. 16A - 16N show examples of such shaped micropore arrays. The micropore array is configured to resemble a pattern in a polygon that may have somewhat precise edges. Removal of tissue in these configurations results in biomechanical properties being achieved in a mathematically and geometrically balanced way that gives stability to the system.

[0242]

[0380] See also FIGS. 31 - 35 for various factors.

[0243]

[0381] Design Factor: The design factor affects the overall arrangement of the microporation array or lattice in a three-dimensional organization regarding the "atmosphere" within the organization and at the edge of the microporation. The design of the microporation can be adjusted according to the unique shape or desired influence around the physiological anatomical structure of the organization itself or as intended. This can be a self-dual (infinite) Euclidean regular honeycomb structure, dual polyhedron, 7-cube, 7-orthoplex, or similar simple lattice, Bravais lattice, or non-Bravais lattice;

[0244]

[0382] Scaling Factor: The scaling factor affects the overall size and dimensions of the micropore array pattern. The scaling factor can be adjusted such that the edge of the outermost micropore is within a desired distance from the outer edge of the microporation system. Additionally, the scaling factor can be adjusted such that the inner edge of the innermost micropore is within a desired distance from the inner edge of the microporation system. Duality can be generalized to three dimensions or multiple dimensions including vertices, arrays, etc. that include n-dimensional space and dual polyhedra; in two dimensions this is called a dual polygon, or includes tessellations, both isotropic and anisotropic.

[0245]

[0383] Distance between nearest neighboring micro - pores: Considering the number and size of micro - pores, the distance between the centers of the nearest neighboring micro - pores can be determined. The distance between the centers of any two micro - pores varies according to the considerations of the outer array design. In some embodiments, the shortest distance between the centers of any two micro - pores is never repeated (i.e., the spacing between pores is never exactly the same distance). This type of spacing is also an example of controlled asymmetry. In another embodiment, the shortest distance between the centers of any two micro - pores is always repeated (i.e., the spacing between pores is always exactly the same distance). This type of spacing is also an example of controlled symmetry. In some embodiments, the distance between two micro - pores is randomly arranged (i.e., the spacing between pores is random). Thus, the system can provide controlled asymmetry that is at least partially rotationally asymmetric with respect to the center of the array design or pattern, random asymmetry that is at least partially rotationally random with respect to the center of the array design or pattern, and controlled symmetry that is at least partially rotational with respect to the center of the array design or pattern, and random symmetry that is at least partially rotationally random with respect to the center of the array design or pattern.

[0246]

[0384] In some embodiments, the rotational asymmetry extends to at least 51% of the micro - pores in the pattern design. In some embodiments, the rotational asymmetry extends to at least 20 micro - pores in the array pattern design. In some embodiments, the rotational symmetry extends to at least 51% of the micro - pores in the pattern design. In some embodiments, the rotational symmetry extends to at least 20 micro - pores in the pattern design. In some embodiments, the rotationally random pattern extends to at least 51% of the micro - pores in the pattern design. In some embodiments, the rotationally random pattern extends to at least 20 micro - pores in the pattern design.

[0247]

[0385] In some embodiments, 51% of the aperture pattern may be described in polar coordinates by the following formula: φ = n * α, r = c√n [where n is the serial number of the aperture counted from the center of the aperture pattern outward; φ is the angle between the reference direction and the position vector of the nth aperture in a polar coordinate system with the center of the aperture pattern as the origin, such that the opening between the position vectors of any two consecutive apertures is a constant angle α; r is the distance from the center of the aperture pattern to the center of the nth aperture; and c is a constant scaling factor].

[0248]

[0386] Collaborative ophthalmic contact lens / ophthalmic mask: The collaborative ophthalmic contact lens / ophthalmic mask (see FIGS. 27A, 2700 and 40) can be flexible or rigid, soft or hard. It can be made of a wide variety of materials, including those conventionally used as contact lenses or ophthalmic masks, such as hydrophilic, hydrophobic polymers, or soft gels or collagen or soluble materials or special metals. Exemplary flexible lenses / masks include supple hydrophilic (“water-loving”) plastics.

[0249]

[0387] In some embodiments, the micro-poration may include a plurality of micropore pathways arranged in a pattern. The pattern of micropore pathways can include regular polygons, irregular polygons, ellipsoids, arcs, spirals, phyllotaxis patterns, or combinations thereof. The pattern of micropore pathways can include radially arcuate pathways, radially spiral pathways, or combinations thereof. The pattern of micropore pathways can include a combination of inwardly radially spiral pathways and outwardly radially spiral pathways. The pattern of air flow pathways can include a combination of clockwise radially spiral pathways and counterclockwise radially spiral pathways. The micropore pathways may be separated from each other or discontinuous. Alternatively, one or more of the micropore pathways may be in fluid communication. The number of radially arcuate pathways (“arcs”), radially spiral pathways, or combinations thereof can vary.

[0250]

[0388] In some embodiments, the micro-poration can include a pattern that is a controlled non-linear distribution pattern, a controlled linear distribution pattern, or a random pattern. In some embodiments, the ophthalmic contact lens / ophthalmic mask can include a pattern of micro-pore pathways, where the pattern of micro-pore pathways is generated from the x and y coordinates of a controlled non-uniform distribution pattern. The controlled non-uniform distribution pattern used to generate the micro-pore pathways of the ophthalmic lens / ophthalmic mask can be the same as, or different from, the array pattern of the laser micro-poration algorithm used in the ophthalmic lens / ophthalmic mask. In certain embodiments, the controlled non-uniform distribution pattern is the same as the array pattern of the laser micro-poration algorithm used in the ophthalmic lens / ophthalmic mask. In some embodiments, the controlled non-uniform distribution pattern is different from the array pattern of the laser micro-poration algorithm used.

[0251]

[0389] In some embodiments, a laser microporation system may have a phyllotaxis pattern according to an embodiment of the laser microporation algorithm described herein. When the laser microporation system is configured with a plurality of micropores, apertures, cavities, channels, passages, or combinations thereof in a pattern that promotes the improvement of natural biological functions such as fluid flow, blood flow, muscle movement, and static and dynamic biological functions through an ophthalmic lens / ophthalmic mask and tissue having a phyllotaxis pattern, the ophthalmic lens / ophthalmic mask cooperates with the laser microporation system having the phyllotaxis pattern. The micropores, apertures, cavities, channels, passages, or combinations thereof, together with a backup pad, can define a biological flow path within, through, or a combination thereof. In certain embodiments, the pattern of micropores, apertures, cavities, channels, passages, or combinations thereof may be in the form of regular polygons, irregular polygons, ellipsoids, arcs, spirals, phyllotaxis patterns, or combinations thereof. In another embodiment, the air flow path may be in the form of regular polygons, irregular polygons, ellipsoids, arcs, spirals, phyllotaxis patterns, or combinations thereof.

[0252]

[0390] In some embodiments, a suitable spiral or phyllotaxis pattern can be generated from the x and y coordinates of any phyllotaxis array pattern of the microporation system embodiments described above. In certain embodiments, the x and y coordinates of the spiral or phyllotaxis pattern are transposed and rotated to determine the x' and y' coordinates of the spiral or phyllotaxis backup air flow pattern, where θ is equal to π / n in radians and n is any integer. A suitable pattern such as a spiral or phyllotaxis pattern can be generated by plotting (x' and y') using, for example, the use of computer-aided drafting (CAD) software.

[0253]

[0391] Next, the pattern can be used to define radially arcuate and helical channels, and annular channels that can intersect the arcuate and helical channels, or combinations thereof. The annular, arcuate, helical, or combined channels can be formed by causing a shape deformation such as in the form of a groove, cavity, orifice, passageway, or other pathway. Detailed embodiments of channel patterns based on the phyllotaxis pattern are shown in FIGS. 10, 13, and 16. Additional embodiments based on the phyllotaxis pattern are shown in FIGS. 14A-14D, FIGS. 15A-15F, and FIG. 41.

[0254]

[0392] In some embodiments, the systems, methods, and devices described can include treatment of the sclera and adjacent eye structures, and fractional microporation and resurfacing, methods and apparatus for laser eye microporation, for rejuvenation or restoration of physiological eye function and / or reduction of dysfunction or disease. In various embodiments, the array can exhibit a plurality of geometries, densities, configurations, distributions, densities, and spot sizes and depths. The array can also be pre-planned and implemented at various times. The array can also penetrate the episclera, scleral stroma, or choroid at any percentage of the required poration. Application of electromagnetic energy is also suitable.

[0255]

[0393] Myeyes Hydrophobic Strong Membrane Lens Customizable Wafer, Nano, μm, etc.: In various embodiments, the hydrophobic strong membrane lens customizable wafer can have various sizes generally measured in millimeters, micrometers or nanometers. Generally, this is a scleral contact lens that can include a computer-generated custom algorithm for laser treatment of a patient's sclera. First, a reusable spot may be stored, and the spot may be profiled by a mask or a lens. The mask may be made of various materials through which the laser can pass, including one or more hydrophobic polymers or polymer blends. This can provide an additional level of protection to the surrounding tissue to be treated in addition to smart mapping technology. The corneal center contact lens may be colored to protect the cornea from the light of the microscope and the laser beam itself. In various embodiments, this may be disposable and not reusable after a pattern is placed on the eye. Additionally, this may be delivered in a pre-packaged sterile container.

[0256]

[0394] This can be created by measuring biometrics, morphology, anatomy, topography, keratotomy, scleral thickness, material properties, refraction, light scattering, and other characteristics, and the quality is imported, uploaded, or otherwise input into a three-dimensional (3D) dynamic FEM module, which is a platform for the "Virtual Eye". The system of the present disclosure processes information on both the cornea and the lens for the purpose of enhancing the accommodation power through the operation of the sclera, and executes a plurality of algorithm inspections where all the optics and information are applied to mathematical and physical scenarios, which also provides the desired Zernike profiling of the cornea that can produce the maximum accommodation power when there is an accommodation plan in addition to LVC. When a complete pattern is generated using the virtual eye by ISIS, there is visualization of the pattern.

[0257]

[0395] The Myeyes wafer also stamps coordinates on the 12 o'clock and 6 o'clock meridians so that the doctor can orient it on the eye. The Myeyes wafer also stamps unique different coordinates on the 10 / 2 / 4 / 7 meridians so that the doctor can orient the treatment quadrant. The My Eyes wafer / contact lens is fabricated by a corresponding 3D printer connected to the ISIS motherboard. Once completed, the lens is sterilized and then fitted onto the patient's eye.

[0258]

[0396] In some exemplary operations, first, a laser that can be combined with a visual target tracker or, in some embodiments, incorporated therein, is calibrated or initialized, and the lens is placed in position by the doctor. The wafer serves as both a mask and a laser guide.

[0259]

[0397] As shown in FIG. 18, this lens design is called "semiscleral-contact" (SEQ). This lens has a scleral bearing edge at the 2.0 mm portion of the cornea as its starting point and consists of three curves. The SEQ lens features 10 openings, which prevent the lens from becoming irreversibly adhered. An irregular corneal surface is corrected using an RGP contact lens, and the corneal lens ranges from 8.0 mm to 12.0 mm in diameter. (Regardless of whether it is double or not) The scleral lens varies in diameter from 22.0 mm to 25.0 mm.

[0260]

[0398] For lens construction and final fitting, equations are used for lens calculation and manufacturing. To narrow down the entire range, start with a sagittal fitting set that extends from 2.70 mm to 4.10 mm. The difference in the fitting set is similar to that of an RGP lens fitting set with different radii of 0.05 mm between normal steps.

[0261]

[0399] The SEQ compliant set ends with a 0.1 mm height difference in the sagittal direction. Despite a DK value of 90 (125 when required) and ten times the open window of the SEQ lens, the oxygen supply problem persists. There is much evidence that for adjusted lenses with a diameter greater than 12.0 mm, it does not move and thus tear exchange cannot occur.

[0262]

[0400] In one exemplary operation: 1) Since the laser includes a visual target tracker, the lens is placed in position by the physician. The wafer serves as both a mask and a laser guide. 2) This wafer-guided system is unique to the laser; a pattern is placed over the eye through the lens itself that is being drilled during the process, a map receipt of the procedure is created, and all spots are recorded by a scanner before and after the treatment. 3) ISIS retains this information for this particular patient's eye. 4) If a retreatment is required, all information (such as topography) is imported again into the patient's ISIS profile, and the "surroundings" of the existing spots are recalculated and reconfigured for further maximization. 5) ISIS always calculates the COP before applying the simulation and a predictable COP after application, so that the patient and the surgeon can obtain information on the possible amount of COP for any particular patient with and without additional LVC. 6) ISIS also demonstrates both biomechanical and optical functions, as well as visual simulations at all distances, by using a FEM virtual eye. 7) ISIS also demonstrates postoperative COP, AA, refraction, Zernike profile changes, etc., and continues to obtain all database information at the backend to find more sophisticated optimization algorithms. 8) ISIS can also promote the understanding of dual optics by profiling various algorithms and provide scenarios that change based on age-related changes in scleral thickness and other biometric, geometric, optical, etc. Although the usefulness of this is infinite, a specific embodiment is that ISIS can generate an aging treatment map from the patient's initial examination to cataract age. Thus, ISIS can predict how many spots there are and which patterns should be used beforehand so that the range of possible retreatment at the time of the first wafer is "predetermined" by ISIS. This means that ISIS can warn the physician if there is a critical COP loss at a subsequent visit, and a retreatment can be started at any time (which can be determined by the physician, the patient, and the ISIS output).9) ISIS also has acoustic interaction, can warn the doctor during treatment whether intervention is needed, and at the end of it, can give the doctor guidelines on which tests should be evaluated for accuracy or for further attention. ISIS can make suggestions to the doctor, but the doctor has the initiative in choosing the program to be implemented by ISIS. 10) ISIS also has a literature list and can similarly search for papers, knowledge, and recent trends. 11) ISIS works like SirI and searches for literature.

[0263]

[0401] For some embodiments containing an Er:Yag ophthalmic laser laser medium, the laser characteristics can include an Er:YAG laser with a wavelength of 2.94 μm; a pulse duration of about 250 μs; and repetition rates of 3, 10, 15, 20, 25, 30, 40, 50 pps.

[0264]

[0402] The various net absorption curves of the various tissue components can be important. The 2.94-μm wavelength laser can be the wavelength closest to the peak absorption of H20 at 3.00 μm in the near-infrared spectrum. This enables it to effectively evaporate H20 from the tissue with little thermal effect (ablation mechanism). Laser-tissue interaction @ 2.94 μm: Early researchers found that for 2.94 μm, it is a large wavelength for tissue ablation; the absorption by water is 10 - 20 times better than that of CO2 at 10.6 μm; the absorption by water is 3 times better than that of Er:YSGG at 2.79 μm; and the ablation threshold of water at 2.94 μm is about 1 J / cm 2 was understood. Ablation occurs instantaneously and can be only a surface effect. This provides extremely accurate ablation with little accompanying tissue damage.

[0265]

[0403] As an application of the Er:Yag ophthalmic system, a wide range of 510K for excision, incision, and evaporation of the soft tissues of the eye can be cited. Therefore, after its adoption, the use will inevitably expand, including pterygium surgery; glaucoma surgery; optic nerve head entrapment (posterior sclera); intracapsular cataract extraction; extraocular soft tissue surgery; AMD, etc.

[0266]

[0404] Also contemplated are methods and devices for the treatment of the sclera and adjacent eye structures and for fractional microporation and resurfacing.

[0267]

[0405] As described herein, a system and method are provided for performing fractional resurfacing of a target area of the eye, such as the sclera, using electromagnetic radiation. The electromagnetic radiation is generated by an electromagnetic radiation source. The electromagnetic radiation is caused to be applied to a particular portion of the target area of the eye, preferably the sclera. The electromagnetic radiation may be prevented from affecting another portion of the target area of the eye by a mask or a scleral lens. Alternatively, the electromagnetic radiation may be applied to a portion of the target area of the sclera other than a particular portion.

[0268]

[0406] In addition, this specification describes a method of modifying tissue with a quasi - continuous laser beam to change the optical properties of the eye, which includes controllably setting the volumetric output density of the beam and selecting a desired beam wavelength. Tissue modification is achieved by focusing the beam at a pre - selected starting point in the tissue and moving the focus of the beam relative to the starting point in a predetermined manner throughout a specified volume of the tissue or along a specified path in the tissue. Depending on the selected volumetric output density, the tissue where the focus impinges can be modified by photoablation or by a change in the viscoelastic properties of the tissue.

[0269]

[0407] Ophthalmic laser system

[0408] In various embodiments, an ophthalmic laser system includes a laser beam delivery system and a target tracker operable with the laser beam delivery system to respond to movement of the eye, and ablates scleral material of both the anterior and / or posterior eye by applying laser beam shots to a selected area of the sclera of the eye. The shots are fired in a pattern in sequence such that laser shots are not fired at consecutive positions and such that consecutive shots do not overlap. The pattern is moved in response to movement of the eye. Since the sclera of the eye is "off-axis", this scanning mechanism is novel in that it does not operate by fixing the beam to the visual axis of the eye. Referring to FIGS. 20, 20(A-C), rather, the "off-axis" scanning mechanism requires an ophthalmic docking system 2000 that utilizes a goniometric mirror or guidance system to ablate the opposite quadrant of the sclera that is off the visual axis. A closed-loop feedback system is located in the form of a magnetic sensor mechanism inside the scanner and also between the ophthalmic docking system and the scanner, both of which lock the laser head to the ophthalmic docking system and, thanks to the biofeedback, position the eye such that both target tracking and beam delivery operate.

[0270]

[0409] In some embodiments, a laser device for rejuvenating a surface includes means for selecting and controlling 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 irradiation area between pulses, a portion of the surface can be eroded more than others, so that the surface can be reprofiled. This method and device are particularly suitable for the removal of corneal ulcers and refractive abnormalities by corneal reprofiling, and also for the reprofiling of optical elements. In one embodiment, the beam from the laser enters an optical system housed in an articulated arm and terminates at an eyepiece having a suction cup for attachment to the eye. The optical system includes a beam forming device for correcting the asymmetric beam cross-section, a first relay telescope, a beam size control system and a second relay telescope. The beam size control system has a stopper with a profiled window or a profiled stopper portion and is axially movable along the converging or diverging beam portion. Another beam size control system has a stopper with a profiled window and is positioned between the combined zoom systems. Mirrors, adjustable slits and refractive systems may also be used. The laser may preferably be an ER:YAg laser in some embodiments. This device may include a measuring device for measuring the surface profile and a feedback control system for controlling the laser operation according to the measured desired profile.

[0271]

[0410] In some embodiments, the methods, devices, and systems for template-controlled precision laser intervention described herein improve the accuracy speed range, reliability, versatility, safety, and effectiveness of laser microsurgery, particularly interventions such as ophthalmic surgery, including the ability to perform such laser surgery off-axis. Returning again to FIG. 19, FIG. 19 shows an exemplary device and system 1900 applicable to specialized fields where the positioning accuracy of laser treatment is critically important whenever it is desirable to precisely limit the spatial spread of the laser treatment, and / or whenever precise movement on or over a target or series of targets that are subject to movement during the procedure would be affected. Thus, system 1900 includes the following key components: 1) a user interface consisting of a video display, microprocessor, and control device, a GUI interface; 2) an imaging system that may include a surgical video microscope with zoom capabilities; 3) an automatic 3D target capture and tracking system capable of tracking a subject matter, e.g., and eye movement during surgery, such that a surgeon user can pre-determine its emission pattern based on an image that automatically stabilizes over time; 4) a laser that can be focused, such that only the precise treatment described by the user interface is affected; 5) a diagnostic system incorporating mapping and topography, numerical data, mathematical data, geometric data, imaging data by means for measuring precise surfaces and 3D shapes before, during, and after the procedure, said measurements being performed online within a time scale not limited to the human response time and may be in real-time; and 6) a high-speed and highly reliable safety means whereby laser emission is automatically interrupted if any condition that would justify interruption of the procedure, e.g., a safety concern, arises.

[0272]

[0411] Figures 20(E - I) further illustrate off-axis features of the laser system. In some embodiments, the system may provide 360-degree scanning. Laser delivery may be nominally positioned perpendicular to the surface of the eye being treated. The axis of rotational symmetry is the fixation point of the eye. The treatment area of the laser is preferably not obscured by the patient's eyelids and other features. The eye fixation axis and the laser beam axis form a fixed angle, exposing the pores in a defined zone. The laser beam delivery can be rotated around the eye, β. In some embodiments, important elements may include: the laser beam and the OCT scan range are on the same centerline, and the OCT scan range and focal length are adapted to the laser spot size and focal length. The camera is positioned immediately beside the laser centerline. Zoom capabilities are provided to view the entire eye or the bottom of the pores. The image provides features off-axis for the visual target tracking system to lock onto. A color image may be provided to detect depth by tissue coloring. The fixation point of the eye has a fixed angular relationship to the 180° laser delivery beam from the laser delivery beam around β. Figures 20(G - I) show another exemplary off-axis scanning type.

[0273]

[0412] In some embodiments, a system for use in ophthalmic diagnosis and analysis and / or assistance in ophthalmic surgery includes 3D-7D mapping means for three-dimensionally detecting the position, shape, and features in and on a patient's eye, and for generating data and signals representing such position, shape, and features; display means for receiving signals from the 3D-7D mapping means and presenting an image at a target position representative of the position, shape, and features of the eye, enabling a user to select a target position and to display in real time a cross-section of a portion of the eye both during ablation and after each laser pulse; display control means for enabling real-time display of cross-sections of different portions of the patient's tissue as selected by the user for diagnosis and analysis and for assisting the user; position analysis means associated with and receiving signals from the three-dimensional mapping means for recognizing the occurrence of a change in the position of a feature of the eye; target tracking means associated with the position analysis means for searching for features of the target tissue and finding a new position of such features after such a position change and for generating a signal indicative of the new position; and tracking positioning means for receiving the signal from the target tracking means and performing a change for the purpose of the three-dimensional mapping means to the new position of the feature of the target tissue, thereby stabilizing the image on the display means by tracking the feature.

[0274]

[0413] The display means may be a video display, and further includes a surgical microscope or digital monitor or smart device means directed at the patient's eye for taking in real time a video microscopic image of a target area of the eye tissue and feeding video image information to the video display means to display such video microscopic image, assisting the user in diagnosis and analysis and enabling real-time display of different cross-sections of the patient's tissue as selected by the user.

[0275]

[0414] An embodiment is a system in which the tracking positioning means includes a turning mirror under automatic control, under robotic control, or under Bluetooth control, the system including an objective lens assembly associated with the mapping means and having a final focusing lens, where the turning mirror is positioned within the objective lens assembly and is movable relative to the final focusing lens.

[0276]

[0415] Devices and systems for high-precision ophthalmic laser surgery at the surgical site include a laser pulse source for generating an infrared to near-infrared laser beam having a power capable of achieving a desired type of surgery in the eye, laser emission control means for enabling the achievement of the desired surgery by allowing the surgeon / user to control the aiming, depth, and timing of the laser emission, 3D to 7D mapping means directed at the patient's eye for obtaining data representing the position and shape of features on and inside the eye, microprocessor means for receiving data from the three-dimensional mapping means and converting the data into a format useful for precisely locating the features of the eye and the aiming and depth of the laser beam within those features for presentation on a screen and for the surgeon / user, and display means for displaying, prior to and during surgery and before the next pulse of the laser is emitted, a microprocessor-generated image representing the topography of the eye and the aiming and depth of the laser beam for the surgeon / user, including a cross-sectional image of a portion of the eye and including display control means for enabling the surgeon / user to select the range of the eye to be displayed.

[0277]

[0416] An infrared or near-infrared pulse, self-running, or continuous or Q-switched optical laser power source for generating a laser beam capable of achieving a desired laser surgery in the patient's tissue, including within the patient's transparent tissue, optical path means for receiving the laser beam, redirecting the laser beam, and appropriately focusing it towards a desired target within the tissue where the surgery is to be performed.

[0278]

[0417] A laser housing positioned to obstruct and direct an optical path means for taking an image of the target along the optical path means, and feeding video image information to video display means, and tracking the movement of the target tissue targeted by the system without damaging the target tissue before the next pulse of the laser is emitted, and shifting the optical path accordingly before the next pulse of the laser is emitted, whereby the three-dimensional mapping means and the surgical microscope means, and the information and images generated by the aiming and positioning of the laser beam follow the change in the position of the tissue. Each image frame acquires information inside the 3D-7D micropores before and after the emission of the laser in dynamic real-time and surface view and sends it to the video display. The GUI has a 7-directional integrated multi-view system for image acquisition including the surface, internal pores, external pores, bottom of the micropores, global spherical eye view, target array range.

[0279]

[0418] In some embodiments, a 7-cube is a preferred projection for the microprocessor: However, other examples exist in a dimensional spherical shape and the space is integrated into the GUI and the microprocessor. The orthographic projection may include the example shown in FIG. 8 above.

[0280]

[0419] The device can include multi-dimensional scaling, linear discriminant analysis, and linear dimensionality reduction processing, and locally linear embedding and isometric mapping (ISOMAP) are non-linear dimensionality reduction methods that are similarly included.

[0281]

[0420] In some embodiments, the device may be capable of topological imaging or 1D, 2D, 3D, or 4D, and up to 7D transformations of the phasings. The phasing is a generalization of the concept of a fiber bundle. A fiber bundle refines the idea that one topological space, called a fiber, is "parameterized" by another topological space, called the base. A phasing is similar to a fiber bundle, except that the fibers need not be the same space, nor need they be homeomorphic; rather, the fibers are merely homotopy equivalent. When the phasing is equivalent to the technical properties of a topological space in 3, 4, 5, 6, and 7 dimensional sphere spaces, the continuous mapping p: E → B satisfies the homotopy lifting property for any space. Fiber bundles (with paracompact bases) form an important example. In homotopy theory, any mapping is "as good as" a phasing - that is, any mapping can be decomposed as a homotopy equivalence into the "mapping path space", and subsequently the phasing can be decomposed into homotopy fibers.

[0282]

[0421] The laser workstation may have three programmable axes (X, Y, Z; extensible up to 5 axes), and have an automatic rotary table machine, programmable X, Y, Z axes and a 2 - station rotary table. This can include a human - machine interface (HMI) with security user access levels, diagnosis and data logging for validated processes and user - friendly operation, and a sorter module adaptable to unique pulse modulation, where: hole diameter: 1μm to 1000μm; maximum drill depth 0.1μm to 2000μm; hole tolerance: > ±1 to 20μm.

[0283]

[0422] The operational features may also include network computer connection, iPad operation, joystick operation, touch - screen operation, iPhone operation, remote or Bluetooth operation, digital camera integration operation, video integration operation, etc.

[0284]

[0423] Laser-Assisted Ocular Drug Delivery System and Method

[0424] FIG. 20J shows the aqueous humor outflow pathway within the eye. Aqueous humor outflow can be regulated by the active contraction of the ciliary muscle and trabecular meshwork cells. When the ciliary muscle contracts, the trabecular meshwork expands, outflow increases, and IOP decreases. When the trabecular meshwork cells contract, outflow decreases and IOP increases. In some embodiments, the described system can result in an improvement in the dynamics of the ciliary muscle and improve the hydrodynamics of aqueous humor drainage.

[0285]

[0425] The uveoscleral pathway is an alternative route of aqueous humor drainage and can account for 10 - 30% of total aqueous humor outflow. For the uveoscleral pathway, aqueous humor enters the ciliary body and passes through the ciliary muscle fibers into the suprachoroidal and suprachoroidal spaces. FIGS. 20(K - L) show how the described system in some embodiments can increase uveoscleral outflow.

[0286]

[0426] The sclera is 10 times more permeable than the cornea and about half as permeable as the conjunctiva. Thus, permeate can diffuse and enter the posterior portion via the transcleral route. In conventional drug delivery (such as eye drops), approximately 90% of the drug is lost due to nasolacrimal duct drainage, tear dilution, and tear turnover metabolism, leading to low ocular bioavailability, and less than 5% of the topical drug has ever reached the aqueous humor.

[0287]

[0427] In some embodiments, the systems, methods, and apparatuses described in this disclosure can be used for laser-assisted eye drug delivery, such as methods and devices for treating target tissues, such as scleral tissue and other intraocular tissues, such as choroid, subchoroid space, neural retina, etc., by ablation, coagulation, and / or adjustment by phototherapy. A method of creating an initial permeable surface (A) on a biological membrane (1) is disclosed, the method comprising: a) creating a plurality of individual micropores (2i) in the biological membrane (1), each individual micropore (2i) having an individual permeable surface (Ai); and b) creating a number and shape of individual micropores (2i) such that the initial permeable surface (A), which is the sum of the individual permeable surfaces (Ai) of all the individual micropores (2i), has a desired value. A microporator for implementing this method is also disclosed. In this case, the biological surface can be the eye. In the case of the eye: irradiating the scleral area so that a therapeutic agent passes through the opening range created by the laser radiation and is thereby delivered to an intraocular target tissue in the anterior or posterior eye, such as choroid, neural retina, retinal epithelium, uvea, vitreous, or aqueous humor.

[0288]

[0428] In some embodiments, the systems, methods, and apparatuses described in this disclosure may be used for laser-assisted eye drug delivery, such as methods and devices for a smart-activated polymer carrier, which may be a photoactivated, photo-modified poly(acrylamide), or may be used to finely manipulate the pore size of a nano / microporous material, demonstrating its application to the reversible color adjustment of a porous polymer photonic crystal based on humidity condensation.

[0289]

[0429] In addition, in some embodiments, the systems described herein may include one or more of an ophthalmic docking station, a scleral mask / nozzle guard, a nozzle, a novel 360-degree articulated arm, novel off-axis scanning, a drug delivery system, depth control, accessories, a Fibonacci algorithm, and the like. Some options include a portable wand, an optical fiber handpiece, a scanning automatic laser applicator, a workstation, remote control such as Bluetooth, and a portable tonometer for pre- and post-operative intraocular pressure measurement, and the like.

[0290]

[0430] FIG. 20M shows an exemplary handpiece delivery system and an articulated arm therefor.

[0291]

[0431] For the purpose of delivery, the eye can be considered to consist of two segments. The anterior part includes the cornea, conjunctiva, sclera and anterior uvea, while the posterior part includes the retina, vitreous and choroid. There are three main routes for drug delivery to the eye: topical, systemic, and intravitreal injection. For the treatment of conditions occurring in the anterior part of the eye, controlled delivery systems such as eye inserts, minitablets and disposable lenses can be applied to the outer surface of the eye. The long residence time after topical application may improve the bioavailability of the administered drug, and in addition, various strategies, including cyclodextrins, liposomes and nanoparticles, are being tested for improving permeation. Drug delivery strategies for treating diseases in the posterior part of the eye will be considered herein. The development of therapeutic agents requiring long-term repeated administration strongly drives the development of sustained release drug delivery systems so as to result in less frequent administration and less invasive techniques.

[0292]

[0432] Drug delivery to the eye often serves two main purposes. First, treating the outer eye for periorbital conditions such as conjunctivitis, blepharitis, and dry eye, and second, treating eye disorders such as glaucoma, diabetic retinopathy, uveitis, and age-related macular degeneration (AMD), retinopathy, and biomechanical compression, restriction, or interference with the normal physiological functions of blood vessels, nerves, or connective tissue beneath the surface of eye tissues. Under normal conditions, drugs administered to the eye as eye drops in aqueous solution are rapidly diluted and washed away from the eye surface by the continuous flow of tears. Drug dilution on the eye surface also reduces the drug flowing from the surface into the eye. As a result, eye drops have to be administered frequently at high concentrations to reach therapeutic levels. The success of delivering lipophilic drugs in aqueous eye suspensions has led to the development of delivery systems intended to increase the residence time of the drug on the eye surface. By maintaining high levels of the drug in the tears for an extended period, it may be possible to increase uptake into the eye. This can also be combined with strategies to improve eye penetration. Beyond the use of conventional systems such as solutions, suspensions, creams, and gels, developments have been made using devices such as inserts and viscoelastic solutions.

[0293]

[0433] In some embodiments, the systems, methods, and devices described in this disclosure can be used for posterior eye drug delivery in the posterior sclera, including but not limited to the peripapillary sclera and the lamina cribrosa. Currently, the treatment of diseases in the posterior eye is hampered by the low effectiveness of topical drugs and the lack of minimally invasive methods to reach or treat the posterior eye.

[0294]

[0434] Figures 20(N - O) show treatment zones in the anterior and posterior eyes in some embodiments.

[0295]

[0435] In some embodiments, the systems, methods, and devices described in this disclosure can be used for the delivery of, but not limited to, drugs, nutraceuticals, grape seed extract, stem cells, plasma rich protein, photoactivated smart polymer carriers, and matrix metalloproteases. FIG. 20P shows choroid plexus drug and nutraceutical delivery in some embodiments.

[0296]

[0436] It is difficult to reach and maintain an effective drug concentration at the site of action. Only about 5% of the applied dose from eye drops permeates through the cornea and reaches the eye tissue, and the residence time is about 2 to 5 minutes. Attempts to improve ocular bioavailability include extending the drug residence time in the conjunctival sac and improving drug permeation across the cornea, which is the main route of drug entry into the eye. Local delivery systems include suspensions, gels, erodible and non-erodible inserts, and rods.

[0297]

[0437] Increasing the viscosity of topical formulations can improve residence in the eye, and it can be seen that the combined use of viscosity modifiers is synergistic. Such formulations are particularly useful as artificial tears, and ophthalmic lubricants may also be utilized for topical drug delivery to the eye. Celluloses such as polyvinyl alcohol (PVA) and hydroxypropylmethylcellulose have a wide range of molecular weights and are often used as viscosity-modifying substances because they are compatible with many of the topically applied active agents. Selecting a specific combination of polymers can achieve specific viscosities or gelling properties. In-situ gelling systems undergo a phase transition from a liquid phase to a solid phase in response to triggers such as changes in pH, temperature, or the presence of ions, forming viscoelastic gels. Poloxamers, block copolymers of poly(oxyethylene) and poly(oxypropylene), form thermoreversible gels in the range of 25 - 35 °C and are generally well tolerated. Cellulose acetate phthalate (CAP) undergoes a phase transition caused by a change in pH [8]. However, such systems require high polymer concentrations, which can cause discomfort to the user. Gellan gum is an anionic polysaccharide that forms transparent gels in the presence of monovalent or divalent cations. Once gelled, the first controlled-release ophthalmic delivery device was launched by Alza in the mid-1970s. This contains active pilocarpine and alginic acid enclosed in a reservoir surrounded by two release-control membranes made of ethylene vinyl acetate copolymer and surrounded by a white lining. Similar to liposomes, polymer microparticle delivery systems such as microspheres and nanospheres are being studied for topical delivery to the eye. Particles in the micrometer size range are referred to as microspheres, while nanoparticles have a submicron diameter. Figure 20Q shows, in some embodiments, how the described system might be used for transcleral drug delivery and improvement of drug intracellular release and permeation. This system can be manufactured using several techniques, including milling and homogenization, spray drying, supercritical fluid technology, and emulsion solvent evaporation.If microparticles are incorporated into viscous droplets and gels, easier administration can be promoted compared to aqueous suspension formulations for intravitreal drug delivery via the scleral vasculature and aqueous humor. A smart-activated polymer carrier may be incorporated, and it may be a photo-activated light-modified poly(acrylamide), or it may be used to finely manipulate the pore size of nano / micro-porous materials, and its application to the reversible color adjustment of porous polymer photonic crystals based on humidity condensation is demonstrated. To improve permeability.

[0298]

[0438] As a result, therefore, for anterior targets, local eye sites and subconjunctival sites are used, while for posterior targets, intravitreal administration is desirable. According to local administration of drugs, especially for powerful molecules with severe side effects such as immunosuppressive drugs, the possibility of side effects is reduced. These may be useful, either alone or in combination, for alleviating the conditions associated with dry eye. Due to the effective blood-retinal barrier, most systemically administered drugs cannot achieve therapeutic levels in the vitreoretinal cavity, and side effects occur after systemic administration of such powerful molecules, so the usefulness of this route is limited. Sustained release can extend the duration of the effective concentration at the site of action, as demonstrated by current delivery systems. Controlled release formulations proposed for sustained intravitreal delivery include liposome formulations, biodegradable microspheres, biodegradable and non-biodegradable implants. Encapsulating the drug in nanoparticles before incorporation into contact lenses is a strategy that can be used to sustain release. If the size and loading of the nanoparticles are low, then the lens should remain transparent. Delivery of particulate polymers can include microspheres or nanospheres that can be manufactured in several ways, including spray drying, emulsification, and solvent evaporation and precipitation.

[0299]

[0439] Microspheres can be useful for delivery to the front part for attachment to the surface of the eye to extend release, but also useful as sustained release injection formulations. Figure 20R shows an exemplary optthacoil, which consists of a drug-loaded hydrogel embedded in a coiled wire designed to be placed on the conjunctival lid. After injecting the nanoparticles into the vitreous, the optional targeting of drug-loaded sustained release microspheres in the eye has also been explored by modifying the surface of the particles so that their distribution in the eye changes. Figure 20S shows a drug delivery carrier in some embodiments. Figures 20T(1-3) show a 360+ scleral wafer in some embodiments.

[0300]

[0440] In some embodiments, the drug delivery system includes a drug and a lens disposed on the eye having a back surface that includes: a central portion (cornea), and a scleral portion having an outer edge and an inner edge, and a treatment portion consisting of an outer edge, an inner margin, and an interlocking carrier depot (which has a plurality of tissue array sizes, shapes, and variants). The corneal portion may be made of silicon carbide to protect the cornea and / or may be metal. Silicon carbide may be a preferred one. It is also opaque. The lens may be a scleral lens that covers a diameter of at least 18 mm. The scleral portion of the lens may contact only the sclera. The treatment portion of the lens may contact only the sclera and the corneal periphery including the corneoscleral envelope and the limbus.

[0301]

[0441] In some embodiments, the haptic portion of the scleral lens further defines a channel that extends radially along at least a portion of the distance between the outer and inner edges. The drug may be selected from the group consisting of antibiotics, antivirals, antifungals, antiparasitics, corticosteroids, non-steroidal anti-inflammatory drugs, mydriatics, cycloplegics, biologics, drugs that modify angiogenesis, drugs that increase aqueous humor outflow, drugs that decrease aqueous humor secretion, antihistamines, secretagogues, mast cell stabilizers, tear supplements, antimetabolites, and immunomodulators, VEGF, and other posterior segment drugs such as timoline, etc.

[0302]

[0442] In some embodiments, the diseases to be treated can include bacterial infections, viral infections, fungal infections, parasitic infections, inflammation, angiogenesis, ocular surface diseases, glaucoma, allergies, dry eye, dysplasia, neoplasms, and AMD.

[0303]

[0443] In some embodiments, the treatment portion of the lens is made of mesoporous silica. A photoactivatable mobile part based on the photoisomerization of azobenzene derivatives is used in combination with mesoporous silica. It has been demonstrated that the back-and-forth rocking motion serves as a molecular propellant that regulates the release of molecules from the pores of silica nanoparticles under "remote control" upon photoexcitation. Unlike that regulated by many other nanomachines, azobenzene-driven release can occur in an aqueous environment. Using photoactivated mesostructured silica (LAMS) nanoparticles, the luminescent dye and the ophthalmic drug are released only inside the target tissue array (e.g., the sclera), and when it is irradiated at a specific wavelength, the propellant is activated. The amount of molecular release depends on the light intensity and irradiation time. The irradiated target tissue array is exposed to the particle suspension, and the particles are taken up by the cells. Cells containing particles loaded with a specific drug are released from the particles inside the cells only when the propellant is photoexcited by a specific wavelength. The selected ophthalmic drugs are loaded into the particles and released therefrom inside the cells under photoexcitation, and apoptosis is induced. The intracellular release of molecules is highly sensitive to control by light intensity, irradiation time, and wavelength, and the delivery of anticancer drugs inside the cells is regulated under external control.

[0304]

[0444] The drug delivery system can be used for the transscleral delivery of any drug required for multiple eye surgeries for prophylactic use or postoperative use in the preoperative / pre- and post-operative / postoperative state.

[0305]

[0445] In some embodiments, a transcleral delivery system for treating a patient's eye includes a device for facilitating the transcleral delivery of a drug through a range of the device, an ablator configured to generate microperforations in the region of the sclera of the patient's eye, and a drug, where the drug causes at least one of the biological modulations of the target tissue. The drug may be administered transclerally or into the sclera at a laser poration site having a predetermined permeation surface that changes over time, where the predetermined permeation surface that changes over time achieves a predetermined accumulation concentration of at least one drug, thereby being effective in treating an eye disease, and further where the laser poration site includes a plurality of pores having different geometries. The drug may be administered transclerally or into the sclera at a first position, and a plurality of drugs may be administered transclerally or into the sclera at different positions. The drug may also be administered into the suprachoroidal space. The drug may be delivered either after or during the irradiation of the target tissue array.

[0306]

[0446] Returning again to FIGS. 20-20B, the system of the present disclosure may include an ophthalmic docking station 2000. The ophthalmic docking station 2000 may be positioned over the eye 2010 during a medical procedure. FIG. 20C shows an exemplary top view of the ophthalmic docking station 2000. This ophthalmic docking station 2000 may provide a four-quadrant view. FIG. 20D shows an exemplary scleral fixation component 2020 attachable to the ophthalmic docking station 2000.

[0307]

[0447] Referring to FIGS. 21A - 21B, embodiments of nozzle guards 2100 and 2110 are shown. FIG. 22 shows the nozzle guard 2110 attached to the nozzle 2200 in some exemplary operations. FIG. 23 shows the disposable insert and filter 2310 attached to the nozzle 2200.

[0308]

[0448] FIG. 24 shows an exemplary workstation 2400 for laser microporation, as well as a handpiece and related equipment 2420 for laser surgery of the eye. The workstation 2400 can include methods, devices, and systems for template - controlled precision laser intervention, as described above. As described above, the methods, devices, and systems improve the accuracy, speed range, reliability, versatility, safety, and effectiveness of laser microsurgery, particularly interventions such as ophthalmic surgery, including the ability to perform such laser surgery off - axis.

[0309]

[0449] The system can include a touch screen or a remotely controlled GUI interface. A graphical user interface (GUI) is a type of user interface that enables a user to interact with an electronics device via graphic icons and visual indicators such as secondary notation instead of a text - based user interface, typed command labels, or text navigation.

[0310]

[0450] The instrumentation workstation 2400 can include an articulated arm 2410; a laser housing unit 2500 (FIG. 25) including a CCD video camera, a galvo scanner capable of off - axis scanning, and a built - in laser housing unit including an aiming beam, etc.

[0311]

[0451] FIGS. 25A - 25B show a 360 - degree rotatable housing unit 2500.

[0312]

[0452] This device and system can include three-dimensional mapping means, at least one communicatively coupled microprocessor, a power source, and display means, the display means including means for presenting to the surgeon / user an image indicating the current exact laser aiming position and depth on a computer-generated view including a plan view and a selective cross-sectional view of the eye generally representing eye features at different depths.

[0313]

[0453] This device and system can also include an optical path including a focusing lens having the ability to control the focus of the laser beam on the eye tissue and thus the effective depth of the laser beam, within about 5 microns, by depth control means for the surgeon to vary the focus of the lens to control the effective depth of the laser beam.

[0314]

[0454] This device and system can further include system programming means for enabling the surgeon / user to pre-program the pattern of lesions in the eye tissue along three axes in three dimensions and for operating the laser to automatically follow a pre-selected programmed surgical path.

[0315]

[0455] This device and system user interface may include provisions for presenting information to the surgeon / user and for enabling control of the surgical procedure by the surgeon / user, including three to seven-dimensional topography and characteristic contours of the target tissue including imaging of cross-sections of the tissue, scanning of surfaces and extents, and real-time dynamic control of the emission of the surgical laser beam by the user, and video display means for presenting to the surgeon / user accurate arrays of information, patterns, and meridians regarding the position of the tissue of the patient targeted by the system.

[0316]

[0456] This device and system may include or comprise an imaging system connected to a video display means, including three-dimensional to seven-dimensional mapping means for generating, reading, and interpreting data to obtain information about the location of significant features of the tissue to be manipulated in seven dimensions, and microprocessor means for interpreting the data and presenting the data in a format useful to the surgeon / user on the video display means. This may also include an anatomical structure locator having a chromophore sensor for detecting color changes, dimensions, water content, shape, spectral characteristics, optical characteristics, and a reverse scanning biofeedback feature capable of outlining accurate 3D to 7D images of blood vessels, veins, and any other non-target anatomical structures. This is capable of sending a signal to the laser to avoid non-target anatomical structures. There is also a laser feature that can guide the laser to avoid erased areas / arrays / spots / regions by manual specification by the user / surgeon on the touch screen GUI interface.

[0317]

[0457] The laser workstation may comprise three programmable axes (X, Y, Z; expandable up to five axes), which have an automatic rotary table machine, programmable X, Y, Z axes and a two-station rotary table, a human machine interface (HMI) with security user access levels, diagnosis and data logging for validated processes, and user-friendly operation. Sorter module with compatible operating characteristics: unique pulse modulation; hole diameter: -1μm to 800μm; maximum drill depth 0.1μm to 2000μm; hole tolerance: >±1μm to 20μm.

[0318] Depth control

[0458] In virtually all tissues, disease progression is accompanied by changes in mechanical properties. Laser speckle rheology (LSR) is a new technique developed by the inventors to measure the mechanical properties of tissues. By irradiating a sample with a coherent laser beam and calculating the speckle brightness modulation from the reflected laser speckle pattern, LSR calculates the decay time constant τ of intensity decorrelation, which is closely related to the mechanical properties of the tissue. The use of LSR technology can be validated by measuring the mechanical properties of tissues. LSR measurements of τ were performed on various phantom and tissue samples and compared with the complex shear modulus G * measured using a rheometer. In both cases, a strong correlation was observed between τ and G * (r = 0.95, p < 0.002). These results demonstrate the effectiveness of LSR as a non-invasive and non-contact technique for the mechanical evaluation of biological samples.

[0319]

[0459] Disease progression in major causes of death such as cancer and atherosclerosis, as well as several other debilitating disorders including neurodegenerative diseases and osteoarthritis, are known to be accompanied by changes in tissue mechanical properties. The most accessible evidence regarding the importance of biomechanical properties in disease assessment is obtained using conventional ex vivo mechanical examinations involving strain, extensibility, or manipulation of the sample. To address the need for in situ mechanical characterization, novel optical tools may include LSR.

[0320]

[0460] When an opaque sample such as tissue is irradiated with a coherent laser beam, the light rays interact with tissue particles and travel along paths of different lengths due to multiple scattering. The self-interference of the returning light creates a pattern of bright and dark spots known as laser speckles. The optical path can change continuously due to the thermal Brownian motion of the scattering particles, and the speckle pattern fluctuates on a time scale corresponding to the mechanical properties of the medium around the scattering centers.

[0321]

[0461] In various embodiments, an open biofeedback loop can be used during the intraoperative procedure using a chromophore and other biofeedback processes. In embodiments of the chromophore, color saturation is measured with a sensitivity that reaches micron-level accuracy, and tissue that is appropriate and inappropriate for the surgical procedure can be determined. Pulse determination can be made based on various preset color saturation levels. This is in contrast to prior art systems that may use color or other metrics only for feedback to the imaging device and not for the actual laser application device applying the treatment. Similarly, subsurface anatomical structure avoidance for predictive depth calibration can use a tool to determine depth calculations in real time and maintain active monitoring regarding unwanted and unexpected anatomical structures while determining how close an extraction or other treatment procedure is to completion. Thus, monitoring of water or other features is different from legacy systems that can monitor surface reflection levels but cannot effectively measure depth in tissue or other biological materials.

[0322]

[0462] LSR utilizes this concept and analyzes the intensity decorrelation of the backscattered light to generate an estimate of tissue biomechanics. For this purpose, LSR calculates the intensity decorrelation function g2(t) of the speckle train and extracts its decay time constant τ as a measure of the biomechanical properties. The aim of this paper is to investigate the relationship between the measurement of τ by LSR and the measurement of the complex shear modulus G * by conventional bulk mechanical tests.

[0323] Laser Speckle Rheology Bench

[0463] The bulk mechanical properties of the tissue and matrix are measured using a desktop LSR setup. This setup includes lasers of multiple coherence laser lengths, followed by a linear polarizer and a beam expander. A focusing lens and a plane mirror are used to focus the irradiation spot on the target tissue area. A high-speed CMOS camera is used to image the laser speckle pattern. An image series is processed, and the intensity incoherence function g2(t) is determined by calculating the correlation between every two frames. Temporal and spatial averaging is applied to the image series pixels to reduce statistical errors. A single exponential function is fitted to the obtained g2(t) curve, and the time constant τ is extracted.

[0324]

[0464] The sclera is a viscoelastic tissue, and its complex shear modulus can be accurately adjusted by modifying the viscoelastic coefficient by laser reshaping or selective fiber and / or fibril ablation to reduce biomechanical stiffness. By measuring the mechanical properties through a biofeedback loop during the laser procedure, the LSR sensitivity to slight progressive changes in the mechanical properties can be evaluated, and thus the desired effect can be titrated. Further, a preferred embodiment of the present invention is a simulation by FEM (VESA) of the change in the viscoelastic coefficient through artificial intelligence algorithm prediction of the desired pattern of reshaping and / or fiber / fibril selective ablation.

[0325]

[0465] Changes in scleral transparency or turbidity / transparency can create scattering features. The final volume fraction is measured, and a strong backscattering signal is well identified. LSR measurements are required, followed by a conventional mechanical frequency sweep over a specified duration. The final point measurement is performed using both LSR and AR-G2 devices for the treated sclera.

[0326]

[0466] As used herein, a chromophore relates to the water absorption spectrum for quantifying tissue chromophore concentration changes in near-infrared spectroscopy.

[0327]

[0467] The systems and methods herein can be used to measure the path length differences of photons in a scattering medium by utilizing the spectral absorption characteristics of water. The determination of this path length difference is a prerequisite for quantifying the chromophore concentration changes measured by near-infrared spectroscopy (NIRS). Using the quantification of tissue chromophore concentration measurements, the depth of the ablation rate caused by water absorption, as well as the time-resolved measurements through various strong membrane tissue layers when related to the ablation rate of laser beam absorption, pulse width, and energy, are quantified.

[0328]

[0468] In some embodiments, the laser docking station may include a female end for the laser housing unit and can be achieved using magnetic sensors between the laser head and the female and male parts in a closed feedback loop state. These sensors will detect the spectral reflection of tissue that is differently absorbed by Er:YAg due to the nature of the ER:Yag wavelength.

[0329]

[0469] The number of pulses can be detected by the laser as well as a CCD video camera, which can detect the reflected light that reflects differently in different colors.

[0330]

[0470] Since the strong membrane is made up of 99% water, water can also be used as a chromophore. Therefore, the number of pulses per pore in the strong membrane tissue that has been laser-treated is fed back to the laser system, and it can be used to determine how many pulses per pore and at which tissue level the strong membrane is because there are tissue layers in the strong membrane.

[0331]

[0471] Electrical oscillations can provide biofeedback. Quantification of tissue chromophore concentration measurements is performed with a galvanometer or optical system, and the different path estimates obtained by water absorption and time-resolved measurements, and the number of pulses per pore, are compared. The sensor can also transmit and quantify the dynamic change of the absorption coefficient of water as a function of the incident fluence at 2.94 μm.

[0332]

[0472] The reduction of chromophore concentration, absorption and scattering characteristics of human in vivo scleral absorption, and the scattering coefficient of in vivo human connective tissue such as the sclera of the eye provide crucial information regarding non-invasive connective tissue (sclera) diagnosis for surgical and clinical purposes. To date, in vivo scleral optical properties have rarely been reported. As described above, the absorption and scattering characteristics of in vivo skin in the wavelength range of 650 - 1000 nm using a diffusion probe in "modified two-layer geometry". As disclosed herein, the continuous determination of the spectrum of scleral optical properties in the range of 500 - 1000 nm. The concentrations of chromophores such as oxyhemoglobin, deoxyhemoglobin, and melanin calculated based on the absorption spectra of 18 subjects at wavelengths above and below 600 nm were found to vary due to the inherent differences in the regions examined. The scattering ability related to the average size of the scatterers shows a clear contrast among scleral phototypes, scleral sites, and wavelengths. The present invention uses the oxy- and deoxyhemoglobin concentrations evaluated at wavelengths above and below 600 nm to distinguish between the target tissue (sclera) and the anatomical structure (artery / vein) adjacent to it. For example, the sclera is not vascularized and can show a deoxyhemoglobin response, while adjacent blood vessels can show an oxy-hemoglobin response. Using the diffuse reflectance method with visible and near-infrared light sources, the hemodynamics and optical properties of the upper and lower dermis can be examined.

[0333]

[0473] The absorption coefficient μ of the sclera a , the scattering coefficient μ s ’, and the chromophore concentration are fundamental properties of tissues that can provide information essential for many surgical, therapeutic, and diagnostic applications, such as monitoring skin blood oxygenation, melanin concentration, detection of hydration by fluorescence, laser surgery, and photodynamic therapy.

[0334]

[0474] Generally, the photon diffusion theory derived from the radiative transport equation is used as the forward model, and the optical properties of in vivo samples at a source-detector separation longer than 5 mean free paths are determined, where the mean free path is 1 / (μ a +μ sIt is defined as ‘)’. Since this cannot satisfy the boundary conditions and the assumptions of multiple scattering in a turbid medium, it has been found to be an insufficient model for source-detector separations longer than 5 mean free paths. To examine it limited to superficial tissue volumes such as the sclera, a source-detector separation shorter than 5 mean free paths is incorporated. In vivo techniques can determine the optical properties of the sclera using an alternative forward model. To determine the optical properties of the in vivo sclera, the inventors use visible reflectance spectroscopy together with a multilayer sclera model and an optimization algorithm predetermined by the use of OCT, UBM or CCD video camera guidance integrated with artificial intelligence FEM. A multilayer skin model, as well as several fitting parameters such as layer thickness, chromophores, and the scattering characteristics of each layer, and their corresponding ranges must be carefully selected in advance to avoid non-uniqueness in the solution space.

[0335]

[0475] The system model used extracts optical properties from the diffuse reflection spectrum collected from the sclera in vivo. In this technique, in order to separate the absorption and reduced scattering coefficients from the measured reflectance, all chromophores contributing to the measured signal must be known in advance, and the reduced scattering coefficient must be linearly related to the wavelength. Next, all constituent chromophores are determined and the absorption spectrum is recovered. In addition, the reduced scattering coefficient exhibits a linear dependence on the wavelength, and the empirical mathematical model will appropriately recover the tissue optical properties.

[0336]

[0476] Further embodiments herein include the use of a probe design adjusted to be a plurality of light source-detector pairs, so that a continuous spectrum of absorption and reduced scattering coefficients can be obtained using a white light source. Advantages of this multi-light source-detector separated probe include relatively low equipment cost and in vivo real-time self-calibration regarding equipment response (by normalizing the reflectance of one light source pair using it as a reference and the reflectance of other light source-detector separated pairs with respect to the reference). The normalized reflectance and light source-detector separation are then fitted to a diffusion model by a least squares minimization algorithm, and the absorption and reduced scattering spectra are determined. The chromophore concentration is extracted by linearly fitting the recovered absorption spectrum with a known chromophore absorption spectrum, and the reduced scattering spectrum is fitted to the scattering power law to obtain the scattering ability. The skin optical properties of the sclera are determined using the probe, and the chromophore concentration and scattering ability of the sclera are also extracted. It can be seen that implementing "two-region chromophore fitting" for the absorption spectrum will result in the best fit with a minimum residual. By two-region chromophore fitting, the inventors mean that the sclera absorption spectrum fits a set of known chromophore absorption spectra at wavelengths from 500 nm to 600 nm and separately fits again from 600 nm to 1000 nm. The logical basis for implementing two-region fitting is that the sclera has very different optical properties in the visible and NIR wavelength regions, and thus the sampling volumes in these two regions are completely different. Similarly, the best fit to the reduced scattering coefficient of the skin was obtained when the reduced scattering spectrum was fitted separately in the region below 600 nm and the region above. The scattering ability depends not only on the anatomical position but also on the position on the scleral layer. These systems and methods have the ability to simultaneously examine in vivo superficial tissues at different depths. Also disclosed in various embodiments are hemoglobin concentrations with significant differences in the target scleral tissue and non-target adjacent anatomical structures.

[0337]

[0477] Machine use may include a diffusion probe used with multimodal fibers for both transmission and detectors. Reflectance can be measured by multiple layers, multiple depths, and simultaneous depth capabilities. Diffuse reflectance spectroscopy as a tool for measuring absorption coefficients in the sclera, along with hemoglobin concentration for integrated tissue absorption scattering in vivo imaging and depth control and anatomical structure avoidance guidance means for laser surgery injury prevention, and in vivo micropore biometry and observation of ongoing wound healing changes in tissue.

[0338]

[0478] In laser treatment, optical properties (absorption and scattering coefficients) are important parameters. The melanin content of tissue affects the absorption of light in the skin. A diffuse reflectance probe consisting of a ring of six light delivery fibers and a central collection fiber system has been proposed for measuring diffuse reflected light from the sclera. Absorption coefficients were calculated from these measurements. This system has the ability of a real-time in vivo method to determine the absorption coefficients of the desired target tissue in the sclera over multiple layers at multiple depths. The three signal sources that affect the intensity of the diffuse reflected light are due to the characteristics of the connective tissue. (1) Light scattering changes, both fast (milliseconds exceeding 10 s) and slow (i.e., > about 0.5 s), (2) fast (about 0.5 - 2.5 s) absorption changes from changes in the redox state of the chromophore, i.e., the oxy / deoxyhemoglobin ratio (known as the "initial dip" period), and (3) slower (about 2 - 10 s) absorption changes (correlated with the fMRI BOLD signal) due to an increase in blood volume. The light scattering changes are thought to be caused by changes in the interstitial volume due to cell hydration, water content, water movement, and capillary dilation.

[0339]

[0479] Quantitative diffuse light methods such as spatial resolved reflectance, diffuse optical spectroscopy (DOS), and tomography (DOT), and diffuse correlation spectroscopy (DCS) handle the exquisite sensitivity to functional and structural changes in connective tissue. Some embodiments utilize the near-infrared spectral region (600 - 1000 nm) for multispectral absorption (μ a ) and reduced scattering coefficient (μ s’) can be separated and quantified, providing quantification of several important biological chromophores such as deoxyhemoglobin (HbR), oxyhemoglobin (HbO2), water (H2O), and lipids. The concentrations of these chromophores represent direct metrics of tissue function such as blood volume fraction, tissue oxygenation, and hydration. Additionally, the scattering coefficient contains important structural information regarding the size and density of scatterers and can be used for the evaluation of tissue composition (extracellular matrix proteins, cell nuclei, mitochondria) and for tracking tissue remodeling processes (such as wound healing). This system utilizes a limited number of optical wavelengths (e.g., 2 - 6) and a narrow temporal bandwidth, but forms a high-resolution image of the subsurface structure by sampling a large number of light source-detector “views”. For an ideal DOT design, thousands of light source-detector pairs and wavelengths can be used to achieve the maximum spatial resolution. This system further uses a non-contact quantitative optical imaging technique, modulation imaging, which is capable of both separating and spatially resolving optical absorption and scattering parameters, enabling wide-field quantitative mapping of tissue optical properties. This uses spatially modulated illumination for imaging tissue components. Periodic illumination patterns of various spatial frequencies are projected over a large area of the sample. Due to sample turbidity, the diffuse reflectance image is modified from the illumination pattern. Typically, sinusoidal illumination patterns are used. Demodulation of these spatially modulated waves characterizes the modulation transfer function (MTF) of the material and embodies the optical property information of the sample. By incorporating color coding into the software, it becomes possible to assign colors and view overlays on the displayed 3D transformed image. Artificial intelligence recognition of color-assigned anatomical features is incorporated, thereby enabling real-time identification of tissue differences between the target tissue and adjacent anatomical structures and capturing a 3D integrated transformed display with colors assigned to the image samples. Anatomical structure avoidance techniques mainly focused on blood vessels and subsurface tissues by using the optical properties of tissues using reflectance spectroscopy, a biofeedback loop, and a CCD video camera.

[0340]

[0480] Referring to FIG. 26-A, a multi-layer imaging platform 2600 according to some embodiments is shown. The platform 2600 may include an HL - halogen lamp; an MS - mirror system; a DD - digital driver; an L2 - projection lens; an L3 - camera lens; an LCTF - liquid crystal tunable filter; and a CCD VC - CCD video camera. FIGS. 26-B and 26-C show an exemplary CCD camera with a nozzle. FIG. 26-D shows an exemplary camera view using a CCD camera. In some embodiments, this platform may include a solid - state laser wavelength Er:Yag 2.94μm, a self - propelled system with a scanning and long - working - distance platform, a procedure performed in a sitting position under a slit lamp, doctor control / software - dependence, a procedure time of several minutes for both eyes, etc.

[0341]

[0481] In some embodiments, a method for quantitative mapping of tissue absorption and scattering characteristics is provided, whereby it is possible to use local sampling of the in - vivo concentrations of oxy - and deoxy - hemoglobin for the selective identification and discrimination of target and non - target tissues for surgical planning and laser guidance for laser surgery of the sclera. The dynamic changes that coincide in both scattering and absorption emphasize the importance of optical property separation for the quantitative assessment of tissue hemodynamics. Such systems and methods integrate a general platform of spatially modulated structured illumination using speckle correlation and fluorescence. The systems and methods are then used in an in - vivo real - time intraoperative setting to provide feedback and guidance to the surgeon. The 3D transformation of the reconstructed image can be simultaneously displayed by a CCD video camera in color - coding assignment and utilized for anatomical structure avoidance software and target procedures that can be modified during the operation. Further use of this system post - operatively to display in - vivo measurements, physiology, wound healing, and morphology under the tissue surface where microporation has been performed for further guidance and procedure - related matters.

[0342]

[0482] Use of Fluorescence: The sclera has only about 25% of the total GAGs present in the cornea. Since GAGs attract water, the sclera is less hydrated than the cornea (but not by more than 75%; due to several structures that carefully maintain the low hydration level of the cornea). The large variation in fibril size and the irregular spacing between scleral components lead to light scattering and turbidity. The color of the sclera is white in a healthy state but can change over time or due to disease (such as hepatitis). Internally, the sclera merges with the choroid tissue at the suprachoroid lamina. The innermost scleral layer is called the brown lamina as described herein. All of these have specific fluorescence, spectral characteristics, and water content.

[0343]

[0483] Fluorescence and diffuse reflectance spectroscopy are powerful tools for distinguishing one connective tissue from another based on the emission from endogenous fluorophores and the diffuse reflection of absorbers such as hemoglobin, melanin, water, and protein content. However, separate analytical methods are used for the identification of fluorophores and hemoglobin. Simultaneous estimation of fluorophores and hemoglobin can be performed using a single autofluorescence spectroscopy technique. Diagnostic real-time treatment selection for target and non-target in vivo tissues is an important technical feature herein. The emission from prominent fluorophores, collagen, flavin adenine dinucleotide, phospholipids, and GAGS, proteoglycans has been analyzed empirically and this can also assign color tags. The water concentration can also be calculated from the ratio of fluorescence emission at 500 and 570 nm. When using a diagnostic algorithm based on linear discriminant analysis, for 410 nm excitation, better classification between normal and tumor tissues is obtained compared to 320 nm. Using fluorescence spectroscopy as a single entity, the prominent fluorophores and water concentration within gradient tissues and isolated tissue structures and components can be evaluated.

[0344]

[0484] Fluorescence spectroscopy is a tool used to distinguish target tissues from non-target tissues based on the emission spectrum profile from endogenous fluorophores. Fluorescence is used to estimate the concentration of fluorophores for use in autofluorescence spectroscopy and for its diagnostic input regarding clinically important in vivo tissues, and for using such information as a laser guidance software code platform via a real-time biofeedback loop. Fluorescence emission of the scleral tissue is recorded at excitation wavelengths of 320 and 410 nm. The emission characteristics of fluorophores such as collagen, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), phospholipids and porphyrins, proteoglycans, GAG, extracellular matrix of collagen and melanocytes are elicited from the scleral tissue and adjacent anatomical tissues such as blood vessels, veins, nerves, etc. Next, accurate tissue classification is performed using the spectral intensity ratio (SIR) and multivariate principal component analysis - linear discriminant analysis (PCA - LDA). The diagnostic algorithm based on PCA - LDA has provided better classification efficiency than SIR. Furthermore, it is found that using PCA - LDA, spectral data based especially on excitation wavelengths from 100 nm to 700 nm is more efficient in classification than 320 nm excitation. The higher effectiveness of PCA - LDA in tissue classification was further confirmed by the receiver operating characteristic (ROC) curve method. The results of this initial data acquisition represent a system and method for discrimination of various connective tissue components from adjacent non-target tissues in this preferred embodiment of the scleral connective tissue of the eye using a fluorescence spectroscopy-based real-time tool (which can present a major challenge). This anatomical structure avoidance system can be repeated using a real-time OCT imaging sensor and a chromophore sensor (water, color, etc.) or spectroscopy without fluorescence.

[0345]

[0485] There are many biomolecules that can absorb light by electronic transitions. Such transitions are relatively high in energy and are thus related to the absorption of ultraviolet, visible, and near-infrared wavelengths. Molecules generally have double-bond chains, and their π-orbital electrons act in a similar manner to electrons in metals in that they act as small antennas that can "receive" the electromagnetic waves of photons that they collectively pass through. If the resonance of the π-orbital structure matches the wavelength of the photon, then photon absorption becomes possible. The systems herein utilize this electrical oscillation to provide biofeedback to a laser module, thereby not only distinguishing between target and non-target tissues, but also distinguishing the actual transitions of tissue from one chromophore to the next, creating an ultra-sensitive super feedback loop. Additionally, in the field of infrared spectroscopy research, there are various bonds that resonate or twist resonantly in response to infrared wavelengths and thereby can absorb such photons. Perhaps the most dominant chromophore that absorbs by vibrational transitions in biology is water. In the infrared, the absorption of water is the most powerful contributing factor to tissue absorption and is described in the present invention. All other tissues having chromophores of color such as blood vessels, veins, or melanin are also described as providing biofeedback in their own specific absorption or vibrational transitions and are further defined as tissue characteristics detected by these laser modules and other systems and combinations described herein.

[0346]

[0486] In some embodiments, color and chromophore detection can be used to track blood vessels and other subsurface features in the sclera and other eye sites. Similarly, hydration detection can also be used. Specifically, the corrective claim includes a biofeedback sensor and a scanner including a galvanometer and a CCD camera, which provide biofeedback used to distinguish target tissue from non-target tissue in addition to the transition from one chromophore to the next within the tissue in the form of a high-sensitivity biofeedback loop. Such transitions are relatively high in energy and are thus related to absorption at ultraviolet, visible, and near-infrared wavelengths. These concepts are not disclosed or taught in the prior art that uses simple image-enhanced feedback for the laser modules it discloses. Since many biomolecules can absorb light by electronic transitions, their detection and monitoring can provide useful general imaging capabilities.

[0347]

[0487] It should be noted that the detection and monitoring of chromophores is the use of color differences based on the intrinsic light absorption of different materials as a method of detecting, monitoring, and determining boundaries within tissues, which is an advantageous improvement of the present disclosure. The detection and monitoring of color can identify slight differences in tissue composition and then provide the advantage that it can be used to improve the accuracy in position-based avoidance and targeting only the desired tissue sites.

[0348]

[0488] The features of the laser system can include the following: a flash lamp or a solid laser wavelength of Er:Yag 2.94μm, or other wavelengths having a high water absorption quasi-peak shown in FIGS. 26-2; an optical fiber delivery system, including a fiber core of 50um to 600um, with a portable probe and eye contact type; flash lamp excitation type; doctor-dependent; without visual target tracking; a procedure time of about 10 minutes per eye; doctor / manual depth control.

[0349]

[0489] An exemplary system functional diagram for the laser system of the present disclosure is shown in FIG. 3B.

[0350]

[0490] In some embodiments, the features may include: a solid-state laser wavelength of Er:Yag at 2.94 μm; an optical delivery system with a free space, short focal length, and portable laser head, for eye contact; a solid-state laser wavelength of Er:Yag at 2.94 μm diode, or other wavelengths having a high water absorption quasi-peak as shown in FIG. 26-2; diode excitation; manual positioning; a 2D scanning micropore arrangement; a spot size of 50 μm to 425 μm, with a strong film nozzle guard; with physician / manual depth control; performed in a semi-reclining position; software control / foot pedal; monitor visualization. Exemplary system functional diagrams are shown in FIGS. 3A and 27(A-C).

[0351]

[0491] Engineering advantages may include: components being lightweight, having a larger "space" in the handpiece compared to previous systems, etc. Engineering challenges may include: a solid-state laser source based on a base station, miniaturization of all components, sufficient power / energy, etc. Clinical advantages may include: easy to use, simple, not technically complex, etc. Clinical challenges may include: patient eye movement, still being surgeon-dependent, extra pieces for the eye, no visual target tracking, depth control, means to keep the eyelids open (FIGS. 28(A-C) and FIGS. 29(A-B).

[0352]

[0492] In some embodiments, the features may include: solid state laser wavelength Er:Yag 2.94μm; free space, short focal length, manually controlled optical delivery system, eye contact type; solid state laser wavelength Er:Yag 2.94μm diode, or other wavelengths having a high water absorption quasi-peak as shown in FIG. 26-2; diode excitation type; manual positioning; 2D scanning micropore arrangement; spot 50μm to 425μm, strong film nozzle guard and foot pedal; with physician / manual depth control; performed in a semi-reclining position; software control / foot pedal; with visualization camera, articulated arm and camera and monitor visualization with handpiece holder as shown in FIGS. 26A and 24.

[0353]

[0493] The engineering advantages may include: components are lightweight, there is more "space" in the handpiece compared to previous systems, etc. The engineering challenges may include: solid laser source based on a base station, miniaturization of all components, sufficient power / energy, stability of the articulated arm, CCD camera image zoom and resolution, etc. The clinical advantages may include: easy to use, simple, not technically complex, etc. The clinical challenges may include: patient eye movement, still surgeon-dependent, extra piece for the eye, no visual target tracking, depth control.

[0354]

[0494] In some embodiments, the features may include the following: solid-state laser wavelength Er:Yag 2.94μm; a long focal length optical delivery system with free space and automatic control, non-contact with the patient; solid-state laser wavelength Er:Yag 2.94μm, or other wavelengths with high water absorption quasi-peaks shown in Figure 26-2; diode-pumped; 6-axis positioning by a robot; 2D scanning micro-pore arrangement; operating distance of 15 - 20 cm with active depth control; laser output monitoring sensor and control system; performed in a semi-reclining position; hands-free / software control / foot pedal; visual target tracking; spot size 50μm - 425μm; eye fixation light source or LED array, ablation debris removal system and camera / monitor visualization; procedure time for both eyes is about several minutes as shown in Figure 26.1.

[0355]

[0495] The engineering advantages may include the following: automation of 6-axis laser positioning, depth control, visual target tracking, eye fixation point, multiple treatment patterns, ablation material removal, shortening of treatment time, hands-free operation for the surgeon, etc. The clinical advantages may include the following: easy to use, simple, fast, no contact with the patient's eye, improvement of pore reproducibility, etc. The clinical challenges may include the following: automation, high-precision beam deflection scanner, patient visual target tracking, and depth control.

[0356]

[0496] In some embodiments, the features may combine the above features of the free space optical delivery system with the features of a fiber optic delivery system as an additional subsystem.

[0357]

[0497] The engineering advantages may include the following: integration of various subsystems, control systems, displays, etc. The clinical advantages may include the following: improvement of camera and visualization, OCT and depth verification, expansion of treatment capabilities using the advantages of multiple beam delivery systems, etc. The clinical challenges may include the following: expansion of control and functions in the control system and software.

[0358]

[0498] In some embodiments, the 2.94 μm Er:Yag laser may be substituted with other wavelengths having high water absorption as shown in the wavelength vs. water absorption plot (see FIG. 26-2), i.e., 2.0 μm, etc.

[0359]

[0499] In some embodiments, the 2.94 μm Er:Yag laser may be substituted with other types of diode-pumped solid (DPSS) lasers that can produce circular, square, or rectangular spots and have higher beam quality, such as single-mode emission.

[0360]

[0500] In some embodiments, the 2.94 μm Er:Yag laser may be substituted with other types of diode-pumped solid (DPSS) lasers that combine multiple light sources to achieve an equivalent fluence.

[0361]

[0501] In some embodiments, the 2.94 μm Er:Yag solid laser may be substituted with other types of lasers having an equivalent fluence specification that use shorter pulse lengths. In some embodiments, the features may include the following: a camera that will provide both high resolution and color images; a zoom range for the surgeon to view the entire eye or the bottom of the pores, and the surgeon can monitor the treatment protocol and has the opportunity to terminate and block the laser if necessary; an electronic signal interface that enables the system to acquire image data. The camera will also provide system control when used with internal image processing, as well as analysis for providing the eye position and automatic centering of the patient's eye for treatment, input for the visual target tracking software, and a background image for overlaying the treatment area on the image of the patient's eye. The camera may be positioned off the laser axis (see FIG. 20F), enabling the field of view to see the treatment area, the entire eye, and the features of the patient's eye on which the visual target tracking locks on.

[0362]

[0502] Engineering advantages can include the following: integration of CCD camera images and analysis by visual target tracking, and a laser beam delivery system and control software. These features will reduce potential risks; the procedure is under the control of the physician. Clinical advantages can include the following: improved visualization and overall control of the procedure by the surgeon, reduced risk of eye movement, etc.

[0363]

[0503] In some embodiments, features can include the following: depth control can be monitored by OCT and other techniques, ensuring that the depth limit of the pore is not exceeded and controlling the remaining scleral thickness below the bottom of the pore without interrupting the procedure. Since the OCT sensor will converge on the laser beam axis and the optical system will match the focal length to the laser beam delivery system, the OCT system will act as a focus sensor for both the OCT and the laser system. OCT will continuously sample the depth of the sample pore, and the sampling rate will provide confirmation of laser emission that should be terminated immediately between laser pulses or while the laser pulse is effective (see again FIG. 4B for an exemplary OCT system).

[0364]

[0504] Engineering advantages can include the following: integration of the OCT system with the laser beam delivery system and control software. Clinical advantages can include the following: reduced surgeon dependence, reduced risk of scleral penetration, improved pore depth and reproducibility, etc.

[0365]

[0505] In some embodiments, a long working distance system is preferred because: 1) it offers improved: visual target tracking, depth control, positioning accuracy, illumination and visualization, plume removal, cost effectiveness; 2) minimally invasive, non-contact - ultra minimally invasive; 3) automated control / high reliability, predictable results; 4) user and patient safety; 5) it provides higher engineering flexibility to fully characterize the procedure, including "non-contact" techniques, etc.

[0366]

[0506] In some embodiments, the features can include the following: robotics that positions the centerline of the laser beam delivery system at the 6-axis position and positions the centerline of the laser at the center of the eye at a distance where the focus of the beam spot is on the surface of the strong membrane; means for rotating the laser beam delivery system 360° around the eye to implement all of the treatment patterns including the individual pores to be ablated (see the examples shown in FIGS. 20(E, G, H)).

[0367]

[0507] In some embodiments, the features of the robotics for positioning the laser beam delivery system can include the following: long focal length optics, 10 - 20 cm, galvanometer scanners for positioning x and y, angular motion control of the x-step after scanning only in y, automatic focus control for z correction, focusing for individual patients, moving in combinations of x and y in sub-quadrant sections of the quadrants, and means for reducing the movement of the xy scanner beam motion for ablation. The robot may be able to control 6 axes similar to a coordinate measuring machine; the laser beam delivery system may be attached to a rotary mechanism on the symmetry axis of the patient's eye that controls various axes with an x, y scanner and a focusing mechanism, etc. (see the example shown in FIG. 20I).

[0368]

[0508] Other features include stability, speed, fineness of angular accuracy in the x, y scanners, and a large number of movable systems. Clinical advantages include no need for manual operation, limited training and manual dexterity of the surgeon, shortened treatment time, and non-contact with the patient, etc.

[0369]

[0509] In some embodiments, the patient can still move the eye to the required position. The fixation target may be shifted to each of the four quadrants or to a sub-treatment range within a quadrant (Figure 2B-2), and the robot or joystick position needs to track the eye position, including the superonasal; superotemporal; inferonasal; inferotemporal. Images of each quadrant and initial tests by the visualization / portable system of laser ablation may be provided. The fixation position of the eye may be essential for positioning the treatment range on the eye based on the patient's details. By being able to shift the fixation point of the eye, means for avoiding blood vessels can be provided in the shift of the treatment range. By moving the fixation point, means for moving the center of the treatment position on the eye are provided. Also, means for dividing a large treatment pattern into smaller ablation ranges, a mosaic of the entire treatment range, reducing the incident angle of the beam on the surface of the eye at any point, and eliminating the need to move the laser beam delivery system.

[0370]

[0510] In some embodiments, the fixation point may include a single or multiple illumination light sources; and is selectively illuminated based on its position relative to the laser beam. The illumination light source may also move with the laser delivery system, or there may be multiple light sources at predefined positions. The illumination light source may be an LED or an array of individually specifiable LEDs. The fixation point position may be fixed or may be controlled as part of a visual target tracking system in combination with laser beam positioning.

[0371]

[0511] Consider multiple treatment simulations. Zone treatment simulation: Baseline model with varying scleral stiffness and adhesion tightness in each individual zone: Treated combined zones (with and without changes in adhesion): Individually: 0, 1, 2, 3, 4; Combined: 1+2+3, 1+2+3+4, 0+1+2+3+4; Effective stiffness: Elastic modulus (E) = 1.61 MPa, equivalent to about 30 years old*; Loose adhesion between the sclera and the ciliary body / choroid, using the values in the original accommodation model here. Refer to Figure 35.

[0372]

[0512] The effects of zonular treatment on ciliary body deformation during accommodation may include scleral rigidity, scleral rigidity + adhesion.

[0373]

[0513] Different treatment area shapes may be applied to one scleral quadrant in relation to five critical zone baseline simulations: the original model of normal accommodation with an "aged" sclera; the sclera where stiffening has begun: elastic modulus (E) = 2.85 MPa, equivalent to about 50 years old; close adhesion between the sclera and the ciliary body / choroid, with all other parameters varied (ciliary body activity, rigidity of other components, etc.).

[0374]

[0514] Shape treatment simulation: baseline model with locally "treated" scleral rigidity: different range shapes were treated (adhesion not varied) → treatment rigidity: elastic modulus (E) = 1.61 MPa, equivalent to about 30 years old; the effective rigidity of each zone can be determined by the size of the shape range in each zone and the values in the original accommodation model.

[0375]

[0515] The effects of shape treatment on ciliary body deformation during accommodation may include only scleral rigidity.

[0376]

[0516] Treatment rigidity may depend on the following: pore volume fraction in the treatment area → % scleral removal volume by treatment; the pore volume fraction varies by changing the parameters of the ablation holes; and others. The composite rigidity is estimated as microscale mixing: the holes are assumed to be parallel with equal spacing / size within the volume = volume fraction (% of the total scleral volume); the remaining volume is the "aged" sclera (E = 2.85 MPa); to change the scleral rigidity of the treatment area from aged (50 years) to young (30 years), it is necessary to remove about 43.5% of the volume; a maximum volume fraction of 13.7% is possible with a protocol (combination of density % and depth), which corresponds to a new rigidity of 2.46 MPa; array size = side length (mm) of the square treatment area.

[0377]

[0517] The following parameters are considered (see FIGS. 26 - 3A, 26 - 3A1, 26 - 3A2, 36).

[0378]

[0518] An exemplary model result is shown in FIG. 42. Treatment surface area = surface area of the hardened film treated (mm^2), where treatment surface area = square of the array. Thickness = thickness of the hardened film in the treatment range (mm), assumed to be uniform Treatment volume = volume of the hardened film treated (mm^2) Treatment volume = treatment surface area × thickness = array 2 × thickness Density % = ratio of pores in the treatment surface area (%) Spot size = surface area of one pore (mm^2) # Pores = number of pores in the treatment area

Number

Number

Number

Number

Number

[0379]

[0530] The relationships between treatment parameters include the following: input parameters of laser treatment; properties of the hardened film; input for calculation of new stiffness.

[0380]

[0531] Calculate the new stiffness of the sclera in the treatment zone Volume fraction = the ratio of the pore volume in the treatment volume (%), that is, the ratio of the sclera volume removed by the laser. [Number] Stiffness = elastic modulus of the sclera before treatment (MPa) Treatment stiffness = elastic modulus of the sclera after treatment (MPa); estimated from the microscale mixing model [Number]

[0381]

[0535] Laser treatment input parameters: sclera characteristics, input to the finite element model of the treatment zone for calculating new stiffness, effect of volume fraction on the deformation of the ciliary body in regulation: Sclera stiffness only ** All treated zone areas (area fraction = 1) Protocol = range of combinations of possible density % and depth, sclera of all zones changed to treatment stiffness according to pore volume fraction Effect of volume fraction on the deformation of the ciliary body in regulation: sclera stiffness + adhesion ** All treated zone areas (area fraction = 1) *** Healthy = original regulation model results Protocol = range of combinations of possible density % and depth, sclera of all zones changed to treatment stiffness according to pore volume fraction Effect of volume fraction on the deformation of the ciliary body in regulation: sclera stiffness + treatment range shape Protocol = range of combinations of possible density % and depth, sclera of all zones changed to treatment stiffness according to pore volume fraction and area fraction of the treatment area

[0382]

[0540] J / cm2 calculation: J / cm2 × Hz (1 / sec) × pore diameter (cm2) = W; J / cm2 = W / Hz / pore diameter. Example: The PLEASE spot is actually "square", so the area can be calculated based on the square: 7.2 J / cm2 = 1.1 w / 300 Hz / (225 μm 10 -4 ) 2 .

[0383]

[0541] Factors affecting the ablation depth % of the living eye under surgery: water content on the surface and inside the tissue, the Tenon's or conjunctiva layer, laser emission angle, thermal damage, water spray, cryo-spray / refrigerated eye drops, cryo-hydrogel cartridge in the laser disposable system (intraoperative drug administration such as antibiotics / steroids) can be considered.

[0384]

[0542] In some embodiments, the systems, methods, and apparatuses described in this disclosure may include the following features.

[0385]

[0543] Adjustable micro pore density: Dose and inflammation control can be achieved due to the variable of micro pores created per unit of applied area. Adjustable micro pore diameter; Dose of micro poration and flexible patterning. Adjustable micro pore thermal profile: The system can create micro pores with an adjustable thermal profile that minimizes the creation of a coagulation zone. Adjustable depth by depth recognition: The system creates micro pores in a controlled manner, preventing over ablation (anatomical structure recognition) and avoiding blood vessels. Figure 26-4 shows anatomical structure recognition. Laser safety level: The device is a laser class 1c device, and the system detects contact with the eye and the eye pod covers the cornea. Integrated smoke exhaust and filtration: Smoke, vapor, and tissue particles will be directly aspirated by the integrated system, so fractional ablation can be performed without any extra need to introduce a smoke exhaust system. The laser system will have an integrated CCD real-time video camera (e.g., an internal camera) that includes a biofeedback loop to a laser guidance system integrated with a GUI display for depth control / limit control. Refer to Figure 26-4-1.

[0386]

[0544] In some embodiments, the systems, methods, and apparatuses described in this disclosure may provide the following: A laser system biofeedback loop incorporating chromophore-based discoloration recognition using melanin content (computer integration of various micropore discoloration gradings. Empirical (a prior) depth information in three thickness zones). A laser system capable of integrating a laser guidance plan and an empirical scleral thickness mapping for communication with scleral microporation. Use of OCT or UBM or 3D tomography. Laser system programming release code with controlled pulses per procedure. Electronically linked to reporting to Ace Vision. Complete data reports (calibration data, and service data, statistics, etc.). The laser system components are constructed in a modular fashion for easy service maintenance and repair maintenance. Self-calibration type setup before, after, and prior to subsequent procedures and real-time procedure calibration. All calibrations are recorded in a database. (Plug-and-play service) Laser communication port for online (WIFI service troubleshooting, report generation, and communication with the company (AVG). WIFI access to diagnostic information (error codes / parts requirements) and either exemption from repair and maintenance troubleshooting or ordering of service by a service provider. A maintenance service for on-site repair and a repair spare parts service kit are created. Integration of the laser system key card with controlled pulse programming including time limits. A flexible-shaped aiming beam for setting boundary conditions and also for triggering level and positioning when the laser nozzle is on-axis. A system Go No Go for starting treatment ablation is triggered by the aiming beam that coincides with the alignment fixed beam. Laser system requirements including a visual target tracking system and a corresponding eye fixation system for the safety of ablation to control eye movement. The laser system requirements must have the ability to deliver microporation to the sclera by going through the gonioscope system for "on-axis" delivery or through slit lamp application or free space application.These may require higher power, good beam quality and the incorporation of a fixation target and / or a visual target tracking system. Good beam quality means the following: the laser system requires focusing between 50 μm and 425 μm. A laser system having the ability to perform rapid 360-degree maneuvers by galvanometer scanning and to change quadrant treatments within 40 - 45 seconds per eye using robotics (4 quadrants per eye, approximately 10 seconds per quadrant; repositioning to the next quadrant with the laser on for 1 - 2 seconds). The laser system is a workstation integrated with a foot pedal, a computer monitor; an OCT; a CCD video camera and / or a microscope system (as required). The laser system patient positioning table / chair module is movable freely from the supine position; variable angle; or a seat. An electric chair (see Figure 26 - 4, which shows the recognition of anatomical structures).

[0387]

[0545] In some exemplary operations, the systems, methods, and devices described in this disclosure may include the following medical procedures: 1) The user manual may provide information regarding the correct handling of the system. 2) Place the eye applicator in the treatment area and position the applicator unit on the eye applicator. 3) The user can set the treatment parameters. 4) The user starts the treatment procedure. 5) The user may receive information regarding the status during the treatment. 6) The user may receive information regarding the calibration of the energy for the eye before and after the treatment. 7) To prevent an unwanted odor, the spread of ablation smoke can be prevented. 8) The user may receive information regarding the visualization of the eye during, between quadrants, and after the treatment.

[0388]

[0546] Generally, the system can be relatively easy to maintain. If necessary, system services can be performed as quickly as possible, which can lead to minimizing downtime. Furthermore, the service cost can be lower than that of a general laser system. The applicator unit, the eye applicator, and the disposable insert can be particularly easy to handle and hygienic, especially during attachment and detachment. Software can enable data exchange between the device and the PC.

[0389]

Table 1

[0390]

[0548] The service requirements can be listed as follows: whichever occurs first, either up to once a year or after 1,000 procedures; whichever occurs first, either up to once a year or after 2,000 procedures; whichever occurs first, either up to once a year or after 3,000 procedures, etc. Overall product life: For all components, it can be evaluated to withstand a product life of at least 5 years. Cleaning: Wipe the entire system clean with a damp soft cloth that has not been immersed in standard hand disinfectant. System operation: By means of a pre-approved electronic key card. Patient position: The patient can be in a supine position. Visualization required during surgery: Illuminating the eye and assisting with the provided visualization - either an external light source or a laser adapter-fixed device CCD video camera incorporated - and a GUI interface with a computer monitor is a necessary module. The patient can be in a supine position or a tilted position or a seated position. Shielding for the safety of the patient's eyes during the procedure. Operation: The system can be such that it can activate the laser only when the applicator and the insert are attached, there is appropriate tissue contact, and it is confirmed that the user can access it. Pore depth monitor: The maximum depth monitored by an end switch (optically or equally monitored) incorporated depth monitor / depth control. Intraocular movement management internal procedure: Visual target tracking technology with a corresponding eye fixation target for a completely non-contact intraocular procedure. Vascular system avoidance: Scan / define the eye's vascular system to avoid microporation in this area. Refer to Figure 4A(1 - 10) showing how microporation / nanoporation can be used to remove the surface, subsurface, and interstitial tissues of the ablation target surface or target tissue and affect the surface, interstitial, biomechanical characteristics (e.g., planarity, surface porosity, tissue geometry, tissue viscoelasticity, and other biomechanical and rheological characteristics).

[0391]

[0549] Performance requirements may include the following: variable pore diameter, pore array size, and pore position. Preparation time: 5 minutes from powering on the device to the start of the microporation process (assuming an average user response time). Robot capture by quadrant to meet the treatment time requirement. Treatment time: <60 45s for one procedure. Robot capture by quadrant to meet the treatment time requirement. Micro pore diameter: adjustable from 50μm to 600μm. Tissue ablation rate: adjustable from 1% to 15%. Microporation array size: area adjustable from 1mm×1mm to a maximum of 14×14mm, square-shaped pore custom-shaped array. Multiple ablation pattern capabilities. To activate and stop the laser, press briefly: The actual microporation process can be started by pressing the footswitch for a short time instead of pressing the footswitch throughout the entire microporation. The laser can be stopped in the same way. Depth of the ablated hole: 5% to 95% of the strong film thickness. Biocompatibility: All tissue contact parts should be made of materials that comply with medical device requirements.

[0392]

[0550] In some embodiments, the system may include the following: Laser wavelength: 2900nm ± 200nm; approximate mid-infrared absorption maximum of water. Maximum laser fluence: ≧15.0J / cm 2 On tissue ≧25.0J / cm 2 On tissue; 2900nm ± 200nm to expand the treatment possibility; approximate mid-infrared absorption maximum of water. Laser setting combinations: The laser repetition rate and pulse duration may be adjustable by using predefined combinations in the range of 100 - 500Hz and 50 - 225μs. The said range can be regarded as the minimum range ≧15.0J / cm 2 On tissue ≧25.0J / cm 2Organizationally, to increase disposability. Pulse number per pore for aggressive treatment: “Aggressive” settings may also be selectable to create micro-pores deep into the dermis, e.g., with a depth > 1 mm. Since depth is mainly fluence-controlled, a high pulse number per pore should automatically lead to a greater depth value. Thus, the pulse per pore (PPP) value may be adjustable between: 1 - 15 PPP. Laser repetition rate and pulse duration may be adjustable by using predefined combinations in the range of 100 - 500 Hz and 50 - 225 μs. The said range may be seen as a minimum range. Shock and vibration: The device should withstand large truck transportation within the provided single-use packaging or multi-use packaging (in case of service or repair). “Aggressive” settings may also be selectable to create micro-pores deep into the dermis, e.g., with a depth > 1 mm. Since depth is mainly fluence-controlled, a high pulse number per pore should automatically lead to a greater depth value. Thus, the pulse per pore (PPP) value may be adjustable between: 1 - 15 PPP. Prevention of odor diffusion: A system may be implemented to minimize the spread of unpleasant odors. GUI: The user interface may be assisted by a reasonable display size. Audible noise: The maximum noise generated by the system (with the cooling and exhaust system at 100%) may not exceed 70 dBA or 50 Dba. Impact absorbance of the unit: The unit should withstand a drop from a certain height without suffering major damage that would cause system failure. System connectivity with one or more of USB, LAN, WLAN, Bluetooth, Zigbee.

[0393]

[0551] Physical requirements can be listed as follows: The laser system can be incorporated into a "cart" type workstation unit equipped with lockable wheels and a counterbalanced / articulated arm to prevent the cart from tipping over during use or transportation (see Figures 24 and 26-5). No tilting requirement. Weight: Weight (cart + counterbalanced / articulated arm): < 100 kg. Auxiliary equipment: Used in conjunction with a video monitoring system, such as a standard eyepiece, etc. Temperature and relative humidity specifications for shipping and use: Humidity: < 70% RH, no condensation; Operating temperature: 18 - 35 °C; Humidity: < 70% RH, no condensation; Storage and transportation temperature: -10 - 60 °C.

[0394]

[0552] Design and usability: The usability of this design meets the general needs of the target user group, including the primary users, physicians, and medical staff. Weight balance: The weight balance of the unit can achieve market acceptance. Shape of the applicator unit: The shape of the unit may be optimized. Operating radius: The connection between the desktop unit and the handheld unit can enable an operating radius of at least 1.2 m. Eye: With a good view to see the proper positioning of the user, it is possible to confirm the proper positioning of the laser with respect to the eye tissue. Convenience of handling the applicator and insert: The applicator and insert can be easily attachable and detachable.

[0395]

[0553] Allowable application area for the human body: Generally, this device can be applied to the eye. Biocompatibility: All tissue contact parts should be made of materials that comply with medical device requirements.

[0396]

[0554] Accessories can be listed as follows: Applicator insert (disposable part): A disposable part that collects the ablated tissue, which establishes a hygienic interface between the device and the tissue. iPod (optional): The applicator can be reusable, easy to clean, biocompatible, and sterilizable. Foot switch: Operates with a standard foot switch for laser emission.

[0397]

[0555] Some embodiments described in the present application include a construction of a system that uses a pulsed 2.94 μm Er:YAG laser with a hand-held probe for ablating holes in the sclera, modifying the plasticity of a region of the sclera, and treating presbyopia and other eye dysfunctions.

[0398]

[0556] In some embodiments, the system includes parts of the PLEASE™ platform and additionally the 3mikron™ Class IV Er:YAG fractional laser system. The main parts are as follows: the iGalaxy module, a spherical application (e.g., Saucer) module that includes the following: 3mikron™ DPM-2 (Er:YAG), a scanning unit and visual target tracking, a robotic stage for positioning, a touch screen control display, a camera system, a microscope, a suction system, a depth detection system, illumination and laminar flow, an aiming beam. The portable cart module may include the following: a power supply, a touch screen control display for non-surgical personnel, a control and cooling unit, the DriCon™ platform, a wireless foot pedal, etc.

[0399]

[0557] In some embodiments, part or all of the system can be easily positioned on the patient's face. The iGalaxy module (see also FIG. 26-1) enables the establishment of a local aseptic environment by utilizing laminar flow inside. The iGalaxy module includes all relevant parts of the treatment procedure, such as a mechatronics motion system that moves the laser with high precision to a selected treatment area on the sclera.

[0400]

[0558] This system may include the ability to ensure control of ablation depth and to detect with high reliability the depth of tissue ablation and ultimately the interface between the sclera and the choroid, and warning / control features that can effectively prevent ablation beyond the sclera, the ability for the system to be ergonomically and clinically practical and acceptable for use by a physician, high reliability and control to ensure patient safety and procedure reproducibility, and the ability to scan at a greater working distance to produce faster procedures.

[0401]

[0559] In some embodiments, the system includes a display (physician's display) included in an iGalaxy module for viewing the tissue area, a laser supply, electronics and an operation control platform, and control and safety including safety (also refer to below), a direct interface with an iBase station. The system may also include a motion stage: a translation stage for positioning the laser and optical systems and scanner within a specific range, laser and optics: a 3mikron module and beam forming optics, a depth control system for avoiding over-ablation, a visual target tracking module, suction and laminar flow for operator safety. Beam deflection synchronized with visual target tracking for micro-pore array generation. Other components and features include: a camera unit for imaging, an iBase intelligent movable base station, an operator display for control and safety, power distribution to different modules, water cooling of the laser system, an optional foot pedal, a communication interface with the external world, debugging, updates, and other features, and a main power supply for a wide range of power supplies for international operation.

[0402]

[0560] As described above, in some embodiments, the systems, methods, and apparatuses described in this disclosure may include creating a finite element model of an accommodation mechanism that includes seven major zonular pathways and three ciliary muscle sections, calibrating and validating the model by comparing it to published experimental measurements of ciliary muscle and lens movement during accommodation, and using the model to investigate the effects of zonular anatomy and ciliary muscle composition on healthy accommodation function. The model may include accommodation caused by novel zonular tension and muscle contraction that utilizes the geometry and simulation of the lens and extra-lenticular structures.

[0403]

[0561] In some embodiments, the systems, methods, and apparatuses described in the present disclosure may include a method of changing the biomechanical properties of biological tissue using a matrix-forming composite consisting of perforations in the tissue, where the configuration is based on a mathematical algorithm. The change in the biomechanical properties of the biological tissue relates to the elasticity, shock absorption, resilience, mechanical relaxation, flexibility, stiffness, hardness, composition, alignment, deformation, mobility, and / or volume of the tissue. The formation of the perforation matrix enables a non-monotonic force-deformation relationship on the tissue having various isotropic elastic constants across the medium. With each matrix formation, a linear algebraic relationship is created between the row length and the column length, where each perforation of the tissue has a continuous linear vector space with up to the nth derivative. When N is an infinite number. This composite creates a total surface area, where each perforation has a proportional relationship with the total surface area of the tissue. The composite may also be arranged to achieve an equilibrium of force, stress, and strain, reducing the shear effect between matrix formation and perforation. Each perforation may be the excised volume of the tissue that defines a point lattice on the tissue, where the preferred shape of the excised volume is cylindrical. The matrix formation consists of a tessellation with or without a repeating pattern, where the tessellation is Euclidean, non-Euclidean, regular, semi-regular, hyperbolic, parabolic, spherical, or elliptical and any variations thereof. Each perforation may have a linear relationship with other perforations individually within each matrix formation and the matrix composite. The tessellation is directly or indirectly related to the stress and shear strain atomic relationships between tissues by calculating a mathematical array of position vectors between the perforations. The atomic relationship is a predictable relationship between the removed volume by each perforation and the change in biomechanical properties seen as elements of the mathematical algorithm. The predictable relationships of the removed volume may be mutually exclusive. The tessellation may be a square that can be further divided into a tessellation of equiangular polygons up to the nth derivative. In some embodiments, the mathematical algorithm uses the factor Φ or phi to find the most efficient matrix arrangement for changing the biomechanical properties of the tissue.The factor Φ or phi may be 1.618 (4 significant digits), which corresponds to any ratio of the set of global vectors in the lattice that have the shortest length relative to the lengths of all other vectors. In some embodiments, the mathematical algorithm of claim 1 includes a non-linear hyperbolic relationship between the planes of biological tissue and any boundary or separation of adjacent tissue, planes, and spaces within and outside the matrix.

[0404]

[0562] In some embodiments, the systems, methods, and apparatuses described in this disclosure may include a protective lens 2700 as shown in FIGS. 27A - 27C.

[0405]

[0563] In some embodiments, the systems, methods, and apparatuses described in this disclosure may include eyelid retractors 2810 / 2820 / 2830 as shown in various embodiments of FIGS. 28A - 28C. FIGS. 29A - 29B show exemplary operations using the eyelid retractor 2830.

[0406]

[0564] One or more of the components, processes, features, and / or functions shown in these figures may be rearranged and / or combined into a single component, block, feature, or function, or may be embodied in several components, steps, or functions. Additional elements, components, processes, and / or functions may also be added without departing from the disclosure. The devices, apparatuses, and / or components shown in these figures may be configured to perform one or more of the methods, features, or processes described in these figures. The algorithms described herein may also be efficiently implemented in software and / or embedded in hardware.

[0407]

[0565] Aspects of the present disclosure are noted to be described herein as processes depicted as flowcharts, flow diagrams, structural diagrams, or block diagrams. Although a flowchart may describe operations as a sequential process, many of the operations can be performed in parallel or simultaneously. Additionally, the order of the operations may be rearranged. A process ends when its operations are completed. A process may correspond to a method, function, procedure, subroutine, subprogram, etc. When a process corresponds to a certain function, its end corresponds to the function returning to a function call or the main function.

[0408]

[0566] The practicability described above is considered novel compared to the prior art and is considered critically important for the implementation of at least one aspect of the present disclosure and for the achievement of the above-described objectives. The terms used herein to describe this embodiment should be understood to include not only their generally defined meanings, but also structures, materials, or operations that exceed the scope of the generally defined meanings in terms of the special definitions herein. Thus, if an element can be understood to include two or more meanings in the context of this specification, then by extension its use must be understood to be general to all possible meanings supported by this specification and by one or more of the terms that describe that element.

[0409]

[0567] The definitions of the terms or elements of the drawings described above are intended to include not only combinations of elements explicitly recited, but also equivalent structures, materials, or operations for performing substantially the same function in substantially the same way to obtain substantially the same result. Thus, in this sense, it is contemplated that equivalent substitutions of two or more elements may be made with respect to any one of the elements described and its various embodiments, or that a single element may be substituted for two or more elements in a certain claim.

[0410]

[0568] Changes from the claimed subject matter that would be apparent to one of ordinary skill in the art, now known or later devised, are expressly contemplated to be equivalents within the intended scope and their various embodiments. Thus, obvious substitutions now or later known to one of ordinary skill in the art are defined to be within the scope of the defined elements. Accordingly, it is intended that this disclosure be understood to include what is specifically illustrated and described above, what is conceptually equivalent, what can be obviously substituted, and also what incorporates the essential ideas.

[0411]

[0569] In the foregoing description and drawings, like elements are identified by like reference numerals. The use of "for example", "etc.", and "or" indicates non-exclusive alternatives without limitation, unless otherwise noted. The use of "including" or "comprising" means "including but not limited to" or "comprising but not limited to" unless otherwise noted.

[0412]

[0570] As used above, the term "and / or" placed between a first entity and a second entity means (1) the first entity, (2) the second entity, and (3) one of the first entity and the second entity. Multiple entities listed using "and / or" are to be construed in the same way, i.e., as "one or more" of the entities so joined. Optionally, other entities may exist, whether or not related to the specifically identified entities, in addition to the entities specifically identified by the "and / or" clause. Thus, by way of non-limiting example, the expression "A and / or B", when used in conjunction with an open-ended phrase such as "comprising", may, in one embodiment, refer to only A (optionally including entities other than B); in another embodiment, only B (optionally including entities other than A); and in yet another embodiment, both A and B (optionally including other entities). These entities can refer to elements, operations, structures, processes, acts, values, etc.

[0413]

[0571] When individual values or ranges of values are specified in this specification (e.g., 5, 6, 10, 100, etc.), it should be noted that, unless otherwise indicated, the values or ranges of values may be claimed more broadly as individual numbers or ranges of numbers. Any individual value mentioned in this specification is provided merely as an example.

[0414] 【0...

Claims

1. A system for delivering a medical treatment by micro-poration to improve biomechanics, a laser for generating a laser radiation beam on a treatment axis that is not aligned with the patient's visual axis, operable for use in a medical treatment by subsurface ablation to create an array pattern of micro-pores for improving biomechanics; a housing; a controller within the housing, in communication with the laser, and operable to control the dosimetry of the laser radiation beam upon application to a target tissue; a lens operable to focus the laser radiation beam onto the target tissue; an automated off-axis subsurface anatomical structure tracking, measurement, and avoidance system comprising; and wherein the array pattern of the micro-pores is at least one of a radiation pattern, a spiral pattern, a phyllotaxis pattern, or an asymmetric pattern, and wherein the array pattern of the micro-pores has at least a partial rotational asymmetry with respect to the center of the array pattern and has a controlled asymmetry extending to at least 51 percent of the micro-pores of the array pattern, a system.

2. The system of claim 1, wherein the array pattern of the micro-pores is a spiral pattern of Archimedes' spiral, Euler's spiral, Fermat's spiral, hyperbolic spiral, lituus, logarithmic spiral, Fibonacci's spiral, golden spiral, or a combination thereof.

3. The system of claim 1, wherein the array pattern has a plurality of right-handed spirals and a plurality of left-handed spirals.

4. The system of claim 3, wherein the number of right-handed spirals and the number of left-handed spirals are Fibonacci numbers or multiples of Fibonacci numbers.

5. The system of claim 3, wherein the number of right-handed spirals and the number of left-handed spirals are ratios that converge to the golden ratio.

6. The system according to claim 1, wherein the at least partial rotational asymmetry extends to at least 20 micropores of the array pattern.

7. The system according to claim 1, wherein the array pattern of the micropores further has random asymmetry.

8. The system according to claim 1, wherein the array pattern of the micropores further has random symmetry.

9. A method for delivering a medical treatment by micro-poration to improve biomechanics, comprising: generating a treatment beam on a treatment axis that is not aligned with the visual axis of a patient in a medical treatment by subsurface ablation using a laser to create a micropore array for improving biomechanics; controlling the dosimetry of the treatment beam upon application to a target tissue by a controller in electrical communication with the laser; focusing the treatment beam on the target tissue with a lens; monitoring the eye position to which the treatment beam is applied by an automated off-axis subsurface anatomical structure tracking, measuring, and avoidance system and; wherein the array pattern of the micropores is at least one of a radiation pattern, a spiral pattern, a phyllotaxis pattern, or an asymmetric pattern, and wherein the array pattern of the micropores is at least partial rotational asymmetry with respect to the center of the array pattern, having a controlled asymmetry extending to at least 51 percent of the micropores of the array pattern.

10. The method according to claim 9, wherein the array pattern of the micropores is a spiral pattern of Archimedes' spiral, Euler's spiral, Fermat's spiral, hyperbolic spiral, lituus, logarithmic spiral, Fibonacci's spiral, golden spiral, or a combination thereof.

11. The method according to claim 9, wherein the array pattern has a plurality of right-handed spirals and a plurality of left-handed spirals. **Claim 12** The method according to claim 11, wherein the number of right-handed spirals and the number of left-handed spirals are Fibonacci numbers or multiples of Fibonacci numbers. **Claim 13** The method according to claim 11, wherein the number of right-handed spirals and the number of left-handed spirals are ratios that converge to the golden ratio. **Claim 14** The method according to claim 9, wherein the at least partial rotational asymmetry extends to at least 20 micropores of the array pattern. **Claim 15** The method according to claim 9, wherein the array pattern of the micropores further has random asymmetry.

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