HK40016651A - Systems and methods for ocular laser surgery and therapeutic treatments - Google Patents

Description

Systems and methods for ophthalmic laser surgery and therapy treatment

Technical Field

The subject matter described herein relates generally to systems, methods, therapies, and devices for laser scleral microperforations, and more particularly, to systems, methods, and devices for laser scleral microperforations to rejuvenate tissue of the eye, particularly with respect to aging of connective tissue, rejuvenation of connective tissue by eye or sclera rejuvenation.

Background

The eye is a biomechanical structure, a complex sensing organ that contains complex muscle, drainage and fluid mechanisms responsible for visual function and ocular biological transport. The regulatory system is the primary mobile system in the organs of the eye that promotes many physiological and visual functions in the eye. The physiological role of the regulatory system is to move aqueous humor, blood, nutrients, oxygen, carbon dioxide and other cells around the organs of the eye. In general, the loss of accommodation in presbyopia has many functional lenses and extra-lens and physiological factors that are affected by increasing age. Eye stiffness, which increases with age, creates stress and strain on these ocular structures and may affect accommodative ability, which may affect the eye in the form of reduced biomechanical efficiency of physiological processes including visual accommodation, aqueous humor dynamics, vitreous hydrodynamics, and ocular pulsatile blood flow, to name a few. Current procedures manipulate optics only by some manual means (such as by refractive laser surgery, adaptive optics, or corneal or intraocular implants), which exchange power in one optic of the eye, while ignoring the importance of the other optic and maintaining the physiological function of the accommodation mechanism.

Furthermore, current implanted devices in the sclera achieve a mechanical effect when adjusted. They do not take into account the effects of 'holes', 'micropores' or the creation of a matrix array of holes with a central hexagon or polygon in 3D tissue. Thus, current procedures and devices fail to restore normal ocular physiology.

Therefore, there is a need for a system and method for restoring normal ocular physiology that considers the effects of 'holes' or creates a lattice or matrix array of holes with central hexagons or polygons in three-dimensional (3D) tissue.

Disclosure of Invention

Systems, devices and methods for laser scleral microperforation for rejuvenation of tissue of the eye, particularly connective tissue rejuvenation by scleral rejuvenation with respect to the aging of connective tissue, are disclosed. The systems, devices, and methods disclosed herein restore physiological function of the eye, including restoring physiological accommodation or physiological pseudo-accommodation through natural physiological and biomechanical phenomena associated with natural accommodation of the eye.

In some embodiments, a system for providing microporous medical treatment to improve biomechanics is provided, wherein the system comprises: a laser for producing a beam of laser radiation on a treatment axis that is not aligned with the patient's visual axis, operable for use in a subcutaneous ablation medical treatment to produce an array or lattice pattern of biomechanically improved micro-pores. The system comprises: a housing; a controller within the housing in communication with the laser and operable to control dosimetry of the beam of laser radiation as applied to target tissue. The system further comprises: a lens operable to focus a beam of laser radiation onto target tissue; and an automated off-axis subcutaneous anatomy tracking, measurement, and avoidance system. The array pattern of micropores is at least one of a radial pattern, a spiral pattern, a leaf pattern, or an asymmetric pattern.

In some embodiments, the array pattern of microwells is a spiral pattern of an archimedean spiral, an euler spiral, a fermat spiral, a hyperbolic spiral, a lituus (lituus), a logarithmic spiral, a Fibonacci spiral, a golden spiral, a Bravais lattice, a non-Bravais lattice, or a combination thereof.

In some embodiments, the array pattern of microwells has a controlled asymmetry that is at least a partial rotational asymmetry about the center of the array pattern. The at least partial rotational asymmetry may extend to at least 51% of the microwells of the array pattern. The at least partial rotational asymmetry may extend to at least 20 microwells of the array pattern. In some embodiments, the pattern of the array of microwells has random asymmetry.

In some embodiments, the array pattern of microwells has controlled symmetry that is at least partial rotational symmetry about the center of the array pattern. The at least partial rotational symmetry may extend to at least 51% of the microwells of the array pattern. The at least partial rotational symmetry may extend to at least 20 microwells of the array pattern. In some embodiments, the array pattern of microwells may have random symmetry.

In some embodiments, the array pattern has a plurality of clockwise spirals and a plurality of counterclockwise spirals. The number of clockwise spirals and the number of counter-clockwise spirals may be the Fibonacci number or a multiple of the Fibonacci number, or they may be in a ratio that converges on the golden ratio.

In some embodiments, a method for providing microporous medical therapy to improve biomechanics is provided. The method comprises the following steps: in a subcutaneous ablation medical treatment, a treatment beam is generated by a laser on a treatment axis that is not aligned with the patient's visual axis to produce an array of biomechanically improved microwells; controlling dosimetry of the treatment beam while applied to the target tissue by a controller in electrical communication with the laser; focusing the therapeutic light beam through a lens onto the target tissue; monitoring the eye position for applying the treatment beam by an automated off-axis subcutaneous anatomy tracking, measurement, and avoidance system; and wherein the array pattern of micropores is at least one of a radial pattern, a spiral pattern, a leaf pattern, or an asymmetric pattern.

Drawings

The details of the subject matter set forth herein, both as to its structure and operation, may be apparent by study of the accompanying drawings, in which like reference numerals refer to like parts. The components in the drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the subject matter. Moreover, all illustrations are intended to convey concepts, where relative sizes, shapes and other detailed attributes may be illustrated schematically rather than literally or precisely. Illustrated in the drawing(s) is at least one of the best mode embodiments of the invention.

Fig. 1A-1 through 1A-3 illustrate exemplary viscoelastic scleral laser rejuvenation according to embodiments of the present disclosure.

Fig. 1A-4 through 1A-7 illustrate exemplary posterior scleral rejuvenation and cranial decompression according to embodiments of the present disclosure.

Fig. 1B-1E illustrate an exemplary aperture matrix array in accordance with an embodiment of the present disclosure.

1E-1 illustrates an exemplary pattern velocity calculation according to embodiments of the present disclosure.

Fig. 1E-2 illustrate an exemplary condensation zone according to embodiments of the present disclosure.

FIG. 1F illustrates an exemplary schematic projection of a basal plane of an hcp unit cell on a tightly packed layer, according to an embodiment of the disclosure.

Fig. 1G-1 through 1G-4 illustrate exemplary laser profiles according to embodiments of the present disclosure.

Fig. 1H illustrates exemplary pore structure characteristics according to embodiments of the present disclosure.

Fig. 2A-1 to 2A-2 illustrate exemplary treatment patterns with three critical zones according to embodiments of the present disclosure.

Fig. 2B-1 to 2B-3 illustrate exemplary treatment patterns with five critical zones according to embodiments of the present disclosure.

Fig. 2C-1 through 2C-4 illustrate exemplary laser scleral uncrosslinking of scleral fibrils and microfibers according to embodiments of the present disclosure.

Fig. 2D-1 through 2D-4 illustrate exemplary effects of treatment on eye stiffness according to embodiments of the present disclosure.

Fig. 2E illustrates another exemplary three important critical regions according to an embodiment of the present disclosure.

Fig. 2F illustrates an exemplary matrix array of micro-ablations in four oblique quadrants according to embodiments of the present disclosure.

Fig. 2G illustrates an exemplary graphical representation of a treatment result according to an embodiment of the present disclosure.

Fig. 2H illustrates an exemplary box and whisker plot of eye stiffness according to an embodiment of the disclosure.

Fig. 2I illustrates an exemplary box and whisker plot of intraocular pressure pre-and post-surgery according to an embodiment of the disclosure.

Fig. 2J illustrates an example chart showing uncorrected and distance-corrected visual acuity in accordance with an embodiment of the present disclosure.

Fig. 2K-1 illustrates an exemplary scheme implementation according to an embodiment of the present disclosure.

Fig. 2K-1-a to 2K-1-C illustrate exemplary scheme parameters for three key regions according to embodiments of the present disclosure.

Fig. 2K-2 to 2K-17 illustrate exemplary views of various schemes and their results according to embodiments of the present disclosure.

Fig. 2K-18 to 2K-19 illustrate exemplary micro-hole patterns according to embodiments of the present disclosure.

Fig. 2K-20 illustrate another exemplary pattern according to an embodiment of the present disclosure.

Fig. 2K-21 illustrate another exemplary scheme and their results according to embodiments of the present disclosure.

Fig. 3A illustrates an exemplary laser treatment system according to an embodiment of the present disclosure.

Fig. 3B illustrates another exemplary laser treatment system according to an embodiment of the present disclosure.

Fig. 3C illustrates an exemplary camera correction system according to an embodiment of the present disclosure.

Fig. 3D illustrates an exemplary flow diagram according to an embodiment of the disclosure.

Fig. 4A illustrates another exemplary laser treatment system according to an embodiment of the present disclosure.

Fig. 4A- (1-10) illustrate how micro/nanopores may be used according to embodiments of the present disclosure.

Fig. 4B illustrates another exemplary laser treatment system according to an embodiment of the present disclosure.

Figure 5 illustrates an exemplary flow diagram for OCT-based depth control according to an embodiment of the present disclosure.

Fig. 6 illustrates an exemplary laser therapy system component diagram in accordance with an embodiment of the present disclosure.

Fig. 7 illustrates another exemplary laser treatment system according to an embodiment of the present disclosure.

Fig. 7 illustrates another exemplary laser treatment system according to an embodiment of the present disclosure.

Fig. 8 illustrates an exemplary orthographic projection according to an embodiment of the disclosure.

Fig. 9 illustrates an example 3D mapping in accordance with an embodiment of the present disclosure.

Fig. 10 illustrates an exemplary design pattern in accordance with an embodiment of the present disclosure.

Fig. 11 illustrates an exemplary model according to an embodiment of the present disclosure.

Fig. 12 illustrates an exemplary schematic representation according to an embodiment of the present disclosure.

Fig. 13 illustrates an exemplary graphical image according to an embodiment of the present disclosure.

Fig. 4A- (1-10) illustrate how micro/nanopores may also be used in accordance with embodiments of the present disclosure.

Fig. 14A illustrates an exemplary micro-pore pattern according to embodiments of the present disclosure.

Fig. 14B is an exemplary illustration of a lobed spiral pattern, according to an embodiment of the present disclosure.

Fig. 14C is another exemplary illustration of a lobed spiral pattern, according to an embodiment of the present disclosure.

Fig. 14D is an exemplary illustration of a Vogel model according to an embodiment of the disclosure.

Fig. 15A-15F are exemplary illustrations of lobed spiral patterns, according to embodiments of the present disclosure.

Fig. 16A-16N are exemplary illustrations of exemplary micro-pores derived from icosahedron pattern shapes, according to embodiments of the present disclosure.

17A-17B are exemplary illustrations of microwell patterns derived from icosahedron pattern shapes, according to embodiments of the present disclosure.

Fig. 18 is an exemplary lens design according to an embodiment of the present disclosure.

Fig. 19 illustrates an exemplary instrument and system according to an embodiment of the present disclosure.

Fig. 20, 20 (a-C) illustrate an exemplary 'off-axis' scanning mechanism in accordance with embodiments of the present disclosure.

Fig. 20D illustrates an exemplary scleral fixation assembly, in accordance with embodiments of the present disclosure.

Fig. 20 (E-I) further illustrates the off-axis features of the laser system according to embodiments of the present disclosure.

Fig. 20 (G-I) illustrates different exemplary types of off-axis scanning according to embodiments of the present disclosure.

Fig. 20J illustrates the aqueous flow within the eye.

Fig. 20 (K-L) illustrates how a system according to an embodiment of the present disclosure will increase uveal outflow.

Fig. 20M illustrates an exemplary handpiece transport system and articulated arm in accordance with embodiments of the disclosure.

Fig. 20 (N-O) illustrates treatment zones in the anterior and posterior spheres according to embodiments of the disclosure.

Fig. 20P illustrates choroid plexus drug and nutraceutical delivery according to embodiments of the present disclosure.

Fig. 20Q illustrates how the system may be used for transscleral drug delivery, according to an embodiment of the present disclosure.

Fig. 20R illustrates an exemplary ophthalmic oil (opthacil).

Fig. 20S illustrates a drug delivery carrier in some embodiments according to embodiments of the present disclosure.

Fig. 20T (1-3) illustrate an exemplary scleral wafer, according to embodiments of the present disclosure.

21A-21B illustrate an example nozzle guard according to an embodiment of the present disclosure.

Fig. 22 illustrates an example nozzle guard attached to a nozzle in accordance with an embodiment of the present disclosure.

FIG. 23 illustrates a nozzle fitted with a disposable insert and filter in accordance with an embodiment of the present disclosure.

Fig. 24 illustrates an exemplary workstation according to an embodiment of the present disclosure.

Fig. 25 illustrates an example housing according to an embodiment of the present disclosure.

Fig. 25A-25B illustrate a housing unit that can rotate 360 degrees according to an embodiment of the present disclosure.

Fig. 26-a illustrates an exemplary multi-layer imaging platform according to embodiments of the present disclosure.

26-B and 26-C illustrate an exemplary CCD camera according to embodiments of the present disclosure.

Fig. 26-D illustrates an exemplary camera view using a CCD camera according to an embodiment of the disclosure.

Fig. 26-1 illustrates an exemplary process according to an embodiment of the present disclosure.

Fig. 26-2 illustrates an exemplary wavelength with high water absorption according to embodiments of the present disclosure.

26-3 illustrate exemplary off-axis scanning according to embodiments of the disclosure: and (5) treating the angle.

26-3A through 26-3A2 illustrate exemplary parameters according to embodiments of the present disclosure.

Fig. 26-4 illustrate anatomical recognition according to embodiments of the present disclosure.

FIG. 26-4-1 illustrates exemplary effects of treating density according to embodiments of the present disclosure

26-5 illustrate another exemplary workstation according to an embodiment of the present disclosure.

Fig. 27 (a-C) illustrate an exemplary lens/cover according to embodiments of the present disclosure.

28A-C and 29A-B illustrate exemplary operations using a speculum according to embodiments of the present disclosure.

FIG. 30 illustrates exemplary testing and anatomical structure avoidance in a laser section according to embodiments of the present disclosure.

Fig. 31-32 illustrate exemplary additional treatment parameters according to embodiments of the present disclosure.

Fig. 33 illustrates exemplary different treatment region shapes according to embodiments of the present disclosure.

Fig. 34 illustrates an exemplary effect of shape therapy according to an embodiment of the present disclosure.

Fig. 35 illustrates an exemplary effect of shape therapy according to an embodiment of the present disclosure.

Fig. 35-36 illustrate an exemplary treatment simulation method according to an embodiment of the present disclosure.

Fig. 37-39 illustrate exemplary therapeutic effects according to embodiments of the present disclosure.

Fig. 40 illustrates another example nozzle in accordance with an embodiment of the present disclosure.

Fig. 41 illustrates a further exemplary treatment pattern according to an embodiment of the present disclosure.

FIG. 42 illustrates example model results according to an embodiment of the present disclosure.

Detailed Description

The drawings described below illustrate the described invention and the method used in at least one of its preferred best mode embodiments, which are defined in further detail in the following description. Those of ordinary skill in the art may be able to make changes and modifications to what is described herein without departing from its spirit and scope. While this invention is susceptible of embodiment in many different forms, there is shown in the drawings and will herein be described in detail preferred embodiments of the invention with the understanding that the present disclosure is to be considered as an exemplification of the principles of the invention and is not intended to limit the broad aspect of the invention to the embodiments illustrated. Unless otherwise specified, all features, elements, components, functions, and steps described with respect to any embodiment provided herein are intended to be freely combinable and replaceable with those features, elements, components, functions, and steps from any other embodiment. Accordingly, it is to be understood that the description is set forth only for the purposes of example and that it is not intended to limit the scope of the invention.

Fig. 1-29 illustrate exemplary embodiments of laser scleral microperforation systems and methods for rejuvenation of tissue of the eye, particularly connective tissue rejuvenation by scleral rejuvenation with respect to aging of connective tissue.

In general, the systems and methods of the present disclosure contemplate a combination of hole filling techniques and creating a matrix of holes in three dimensions (3D). Pores of a particular depth, size and arrangement in a matrix 3D scaffold of tissue produce plastic behavior in the tissue matrix. This affects the biomechanical properties of the scleral tissue, allowing it to be more flexible. It is well known that elastin containing connective tissue is 'flexible' and is meant to be elastic. In fact, the sclera has natural viscoelastic properties.

The effects of ocular stiffness and ocular biomechanics on the pathogenesis of age-related presbyopia are important aspects herein. The description herein is such that the structural stiffness of the ocular connective tissue (i.e., the sclera of the eye) is altered using the systems and methods of the present disclosure.

In order to better appreciate the present disclosure, ocular accommodation, ocular stiffness, ocular biomechanics, and presbyopia will be briefly described. In general, the loss of accommodation in presbyopia has many functional lenses and extra-lens and physiological factors that are affected by increasing age. Eye stiffness, which increases with age, creates stress and strain on these ocular structures and may affect accommodative ability. In general, understanding the effects of ocular biomechanics, ocular stiffness, and loss of accommodation can lead to new ophthalmic treatment paradigms. Scleral therapy may have an important role in treating biomechanical deficiencies in presbyopia by providing at least one means of addressing the true cause of the clinical manifestations of loss of accommodation seen with age. The effects of loss of accommodation have had an effect on the physiological functions of the eye including, but not limited to, visual accommodation, aqueous humor dynamics, vitreous hydrodynamics, and ocular pulsatile blood flow. Restoring the more flexible biomechanical properties of ocular connective tissue using the systems and methods of the present disclosure is a safe procedure and can restore accommodation in the elderly.

Accommodation has traditionally been described as the ability of the lens of the eye to dynamically change diopters to accommodate various distances. More recently, accommodation has been better described as a complex biomechanical system having both a lens and an extra-lens assembly. These components act in synchrony with many anatomical and physiological structures in the ocular organs to coordinate not only the visual performance that occurs with accommodation, but also the physiological functions necessary for the ocular organs, such as aqueous humor dynamics and ocular biological transport.

Biomechanics is the study of the origin and effect of forces in biological systems. Biomechanics has not been fully exploited in ophthalmology. This biomechanical paradigm deserves expansion into the anatomical connective tissue of complex ocular organs. Because ocular biomechanics are related to accommodation, understanding ocular biomechanics may allow a more complete understanding of the role this primary movement system has on the overall ocular organ function, while maintaining the optical quality of the visual task.

The eye is a biomechanical structure, a complex sensing organ that contains complex muscle, drainage and fluid mechanisms responsible for visual function and ocular biological transport. The regulatory system is the primary mobile system in the organs of the eye that promotes many physiological and visual functions in the eye. The physiological role of the regulatory system is to move aqueous humor, blood, nutrients, oxygen, carbon dioxide and other cells around the organs of the eye. In addition, it acts as a neuro-reflex loop, reacting to the optical information received through the cornea and lens to fine-tune the focusing power throughout the range of vision, and is essentially the "heart" of the eye's organs.

Biomechanics is particularly important for the complexity of regulatory functions and dysfunctions that occur with age-related eye diseases such as presbyopia, glaucoma, age-related macular degeneration (AMD) and myopia. Age-related changes in the lens have long been understood and reported. Recent efforts have demonstrated how the hardened ocular tissue behaves as presbyopia. Ocular stiffness has been associated with clinically significant loss of accommodation with age, age-related macular degeneration, elevated intraocular pressure (IOP), reduced pulsatile blood flow in the eye, and certain forms of glaucoma and cataracts. Stiffening of the zonule device and loss of elasticity of the choroid may also affect regulation.

Biomechanics play a crucial role in the pathophysiology of ocular organs. In healthy young eyes, this mechanism is biomechanically efficient and accurately achieves focus on objects at a particular distance. However, as we age, this biomechanical mechanism is affected by changes in material properties, anatomical relationships, and degradation of healthy connective tissue infrastructure relationships due to aging processes. These biomechanical dysfunctions not only result in disruption of the function of the accommodation mechanism, which affects the ability of the dynamically focusing lens to achieve the desired optical image quality, but also affect the function of other physiological mechanisms critical to the eye organs, such as ocular biofluids, ocular blood flow, and metabolic homeostasis. Thus, biomechanics play a key role in the pathophysiology that occurs with aging (including glaucoma and AMD).

Presbyopia is a disease of vision traditionally defined as the gradual loss of accommodation with age. However, the loss of power to accommodate the diopters of the lens for various distances is only a result of this complex disease. As the eye ages, there are connective tissue changes in the eye organs or "eye", which have a significant but reversible effect on the biomechanical efficiency of eye function. Studies using Ultrasound Biomicroscopy (UBM) and endoscopy, Optical Coherence Tomography (OCT), and Magnetic Resonance Imaging (MRI) have shown age-related changes in the vitreous membrane, the surrounding choroid, ciliary muscle, and zonules. Age-related changes cause biomechanical changes that are also manifested in the sclera, which curves inward with age.

According to one model, during accommodation, the ciliary muscle contracts, releasing tension on the zonules, which reduces tension on the lens and allows the lens to bend and increase its refractive power. The decrease in lens elasticity with age impedes the deformation of the lens and the refractive power of the lens will not increase enough to see nearby objects. Current methods of addressing the loss of myopic symptoms of presbyopia typically include spectacles, multifocal or single vision contact lenses, corneal surgery to induce single vision or multifocal, lens implants using multifocal lenses, corneal inlays, onlays and accommodating intraocular lenses. However, none of these procedures restore true accommodation. Instead, these procedures attempt to improve myopia and mesopic vision by manipulating the optics in the cornea or in the lens.

In order for true physiologic accommodation to occur, when the focus changes from far to near or too far from near, the eye must modify its focal length to see the object clearly. Typically, this is believed to be caused primarily by the ciliary muscle, which contracts and forces the lens into a more convex shape. However, the adjustment process is much more complex. Accommodation is also affected by corneal aberrations, and so to be clearly seen, the lens must be shaped and contoured (with) corneal aberrations to create an optical equilibrium between the lens and the cornea prior to the application of a focusing response to the accommodation stimulus. In addition, zonular tension on the lens and elastic choroid affects the range of accommodation and biomechanical function of the entire regulatory complex. Failure of these complex components results in a biomechanical relationship dysfunction that may affect the amplitude of accommodation, lens deformation, and central refractive power generated from dynamic accommodation forces.

Scleral surgery, for example as a treatment of presbyopia, has used corneal incisions to treat myopia, a treatment known as Radial Keratotomy (RK). An Anterior Ciliary Sclerotomy (ACS) was developed that utilized a radial incision in the portion of the sclera overlying the ciliary muscle. The incision is believed to increase the space between the ciliary muscle and the lens, allowing for increased muscle 'working distance' and tightening of the zonules to restore accommodation in presbyopia. Long-term results of ACS indicate that this procedure was largely unsuccessful in restoring accommodation, and the effect was completely eliminated because scleral wounds healed very quickly. ACS is followed by laser presbyopia reversal (LAPR), which uses a laser to perform a radial sclerectomy. However, the results of LAPR are bad. Scleral implants attempt to lift the ciliary muscles and sclera, tighten the zonules supporting the lens, and restore accommodation. Their effectiveness is still controversial.

Loss of accommodation and presbyopia have been used interchangeably. However, it should be emphasized that loss of accommodation is only one clinical manifestation of the consequences of aging (or presbyopia) eyes. With age, there are many changes to the lens and surrounding tissue that may contribute to loss of accommodation. Studies have shown that lens material hardens with age, its ability to change shape (and optical power) during accommodation is reduced, and accommodation is reduced. Softening of the lens capsule, flattening of the lens, and forward movement of the lens with age may also contribute to loss of accommodation, however, accommodation is a complex mechanism. Many lens-based models fail to combine effects from the extra-lens structure. To fully understand accommodation, the lens and lens assembly need to be considered together.

The amount of accommodation loss associated with extra-crystalline factors (mainly zonules, choroid and sclera) with age has only recently been investigated. The peripheral lens space (circumlentil space) decreases with age. The ciliary body has been shown to contract during accommodation and there is a decrease in the distance from the scleral spur to the serration. With UBM, the attachment zones of the trailing zonules of adjacent jagged edges have been identified, and the contraction of these zonules is believed to be the cause of the decrease in distance found with respect to accommodation. This complex role of the zonules is suspected to be reciprocal. When the anterior zonules relax, their tension on the lens is reduced, causing the lens to change shape forward and the posterior zonules contract, moving the posterior capsule in reverse. This vitreous-zonule complex hardens with age, losing its elasticity. It is also now known that with age, the sclera becomes less deformable during accommodation in the nasal region. The vitreous has also been considered to be an important factor in the change of lens shape during accommodation and may play a role in presbyopia. New models show that up to 3 diopters may be affected by the extra-lens structure. Age-related changes in these structures and their biomechanical interactions with the ciliary body-lens complex may contribute to presbyopia.

The ciliary muscle plays a key role in many functions of the eye organs, including regulation and aqueous humor dynamics (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, medium and far). During accommodation, the ciliary muscle contracts to change the shape of the lens and move the lens substantially forward and inward. This shape deformation is caused by the release of tension on the anterior zonules and the moving aqueous humor fluid in the posterior chamber. This allows the lens to change from a relatively aspherical shape to a more spherical shape, thereby increasing its near vision refractive power. Contraction of the ciliary muscle is also important for dilating the trabecular meshwork and for aqueous humor drainage. Inadequate drainage or interference with the normal flow of aqueous humor drainage by the uveal outflow pathway or Schlemm's canal can increase IOP and contribute to the development of certain types of ocular hypertension or glaucoma. Contraction of the ciliary muscle during accommodation lowers intraocular pressure (IOP). This may be due to a decrease in resistance to aqueous outflow during accommodation caused by inward and forward movement of the ciliary muscles, which dilates the Schlemm's canal and opens the trabecular meshwork.

In some embodiments, fig. 1A- (1-3) illustrate exemplary scleral laser rejuvenation allowing for compliance viscoelasticity in ciliary muscles. The ciliary muscle and its components include the meridional or longitudinal (1), radial or oblique (2) and circular or sphincter (3) layers of muscle fibers, as shown by the continuous removal into the eye. The cornea and sclera have been removed, leaving Schlemm's canal (a), and venules (b) and scleral spur (c) collected. Warp fibers (1) typically exhibit sharp junctions (d) and terminate in choroidal stars (e). The radial fibers meet at an obtuse angle (f) and similar connections occur at even wider angles (g) in the annular ciliary muscle.

The stiffness of a structure describes its resistance to deformation and, in the case of a constrained structure with incompressible contents, the stiffness is related to the volume of the structure and the pressure of the contents. Ocular rigidity (Ocular rigidity) refers to the resistance of the eyeball to pressure. An increase in ocular stiffness has been associated with an increase in age, which supports the notion that presbyopia and ocular stiffness share a common biomechanical factor. In addition to affecting accommodation, ocular stiffness may also hinder the return of the accommodation device to an uncoordinated state after the accommodation state by inhibiting elastic recoil of the posterior choroid.

Ocular stiffness has been associated with a reduction in pulsatile blood flow to the eye. Blood vessels that support the health of the entire eye pass through the sclera. An increase in ocular stiffness may increase the resistance of the sclera to venous outflow and reduce flow through the choroidal vessels.

Ocular stiffness has been associated with the pathogenesis of macular degeneration. An increase in ocular stiffness may increase the resistance of the sclera to venous outflow and reduce flow through the choroidal vessels. This may damage Bruch's membrane and lead to choroidal neovascularization. Reducing flow through choroidal vessels may also reduce perfusion, which may lead to the induction of hypoxia and choroidal neovascularization.

Ocular stiffness has been associated with certain forms of glaucoma. Recent models indicate that ocular stiffness affects the sclera response to increased intraocular pressure. Due to age-related changes and eye stiffness in both the anterior and posterior spheres, reducing eye stiffness may reduce the mechanical strain transmitted to the optic nerve head with elevated intraocular pressure. During normal accommodation, when the ciliary muscle contracts, the retina and choroid are pulled forward near the optic nerve head. The ciliary muscle maintains its contractile force with age, however the increased stiffness of the sclera may affect ciliary muscle motility, which may increase the tension on the optic nerve head during ciliary muscle contraction.

In some embodiments, fig. 1A- (4-7) illustrates posterior scleral rejuvenation and cranial decompression.

The ocular stiffness or "rigidity" of the outer ocular structures of the eye, including the sclera and cornea, that appear in the eye with age affects the biomechanical functions of all internal anatomical structures, such as the extracrystalline and phaco-anatomical structures of the regulatory complex, as well as the trabecular meshwork, choroid, and retina. In addition, ocular stiffness has a significant impact on the physiological function of the ocular organs, such as changes in aqueous humor dynamics and the efficiency of ocular pulsatile blood flow. Increased ocular stiffness also affects other tissues, including ocular blood flow through the sclera and optic nerve. Ocular stiffness has been associated with the pathogenesis of many age-related ocular diseases. Thus, ocular stiffness may not only affect the loss of visual accommodation, but also have broader clinical implications.

Ocular biomechanics are a study of the source and effect of intraocular forces. All ocular tissues contain collagen, which provides them with viscoelastic properties. Viscoelastic substances comprise properties of both fluids and elastic materials. Fluids tend to take the shape of their containers, while elastic materials may deform under stress and return to their original shape. When stress is applied to a viscoelastic material, the molecules will rearrange to accommodate the stress, which is known as creep (creep). This rearrangement also creates an opposing stress in the material, allowing the material to return to its original shape when the stress is removed. Therefore, viscoelasticity is an important property that allows tissues to react to stress.

Chronic stress beyond the healing capacity of the tissue may lead to chronic inflammation and ultimately cell death, which technically describes the pathophysiology of aging. Like all other connective tissues, ocular connective tissue is affected by age. The sclera constitutes 5/6 of the eye and is composed of dense irregular connective tissue. It is mainly composed of collagen (50-75%), elastin (2-5%) and proteoglycan. The connective tissues of the eye harden with age, losing their elasticity, primarily due to cross-linking that occurs with age. Crosslinks are bonds between polymer chains, such as those in synthetic biomaterials or proteins in connective tissue. Crosslinking may be caused by free radicals, uv irradiation and aging. In connective tissue, collagen and elastin can be cross-linked to continuously form fibrils and microfibrils over time. As the number of fibrils and microfibers increases, the sclera hardens, undergoing 'sclerosis', and the concomitant increase in metabolic physiological stress. As previously mentioned, the increase in collagen cross-linking associated with age and ethnicity, as well as the loss of elastin-driven recoil and/or collagen microarchitectural changes, may underlie changes in the properties of the scleral material, resulting in a loss of compliance of the scleral tissues when stress is applied. As this pathophysiology develops, the sclera exerts compressive and loading stresses on underlying structures, creating biomechanical dysfunctions, particularly those associated with regulation.

Age-related increased ocular stiffness also has an effect on the biomechanics of the ciliary muscle and the accommodative mechanism. For example, it is known that the contractile force of the ciliary muscle does not decrease with age, however, it may have a reduced ability to contract or apply considerable force on the lens to produce the same diopter change as those in the young system. A further explanation may be that ocular stiffness affects the biomechanical contribution of the ciliary muscle by relaxing zonular tension and reducing accommodation.

Age-related material property changes within the sclera affect the mobility of the connective tissue of the scleral fibers, directly resulting in loss of compliance. This results in a reduction in the normal maintenance and turnover of Proteoglycans (PGs) in the sclera, resulting in loss of PG and ultimately tissue atrophy. However, this loss of PG can be reversed if the compliance and motility of the scleral connective tissue is restored.

As described above, the systems and methods of the present disclosure contemplate a combination of hole filling techniques and creating a matrix of holes in three dimensions. Pores of a particular depth, size and arrangement in a matrix 3D scaffold of tissue produce plastic behavior within the tissue matrix. This affects the biomechanical properties of the scleral tissue, allowing it to be more flexible. Multiple holes can be created in a matrix 3D scaffold, in an array pattern or lattice(s). Various microporous properties can be supported. These may include volume, depth, density, etc.

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 'holes' of a particular composition, depth, and relationship to the other 'holes' in the matrix and the spatial organization between the holes in the matrix. A large amount of tissue depth (e.g., at least 85%) is also required to obtain the full effect of the entire matrix over the entire size of the polygon. The matrix within the tissue contains polygons. The central angle of the polygon remains constant regardless of the number of blobs in the matrix. This is an essential component of the systems and methods of the present disclosure, as they utilize matrices having polygons that include the unique relationships and properties of the hole patterns in the matrix or lattice.

The center angle of a polygon is the angle subtended by one of the sides of the polygon at the center of the polygon. The central angle of the polygon remains constant regardless of the number of sides of the polygon.

Current implanted devices in the sclera achieve a mechanical effect when adjusted. The present device or method does not take into account the effects of 'holes' or create a matrix array of holes with a central hexagon or polygon in 3D tissue. The systems and methods of the present disclosure may create a matrix array of holes in biological tissue to allow for changes in the biomechanical properties of the tissue itself to produce a mechanical effect on the biological function of the eye. The main requirement for 'holes' in the matrix is a polygon.

By definition, a polygon may have any number of sides, and the area, perimeter, and size of the polygon in 3D may be mathematically measured. In the case of a regular polygon, the central angle is the angle formed by any two adjacent vertices of the polygon at the center of the polygon. If lines are to be drawn from any two adjacent vertices to the center, they will form a center angle. Since the polygon is regular, all central angles are equal. It does not matter which edge is chosen. All central angles will add up to 360 ° (a complete circle) and thus the central angle is measured as 360 divided by the number of edges. Alternatively, as in the formula:

center angle =360/n degrees, where n is the number of edges.

Thus, the measurement of the center angle depends only on the number of edges, and not on the size of the polygon.

As used herein, a polygon is not limited to being "regular" or "irregular. A polygon is one of the most ubiquitous shapes in geometry. From simple triangles up to squares, rectangles, trapezoids, to dodecagons, and even more.

Types of polygons include regular and irregular, convex and concave, self-intersecting and intersecting. Regular polygons have all sides and interior angles that are the same. Regular polygons are always convex. Irregular polygons include those polygons in which each edge may have a different length, each corner may have a different measurement, and are the inverse of regular polygons. Convex is understood to mean that all internal angles are less than 180 ° and all vertices point 'outwards' away from the inside. Its opposite is concave. The regular polygon is convex. Concave is understood to mean that one or more internal angles are greater than 180 °. Some vertices are pushed "inward" towards the inside of the polygon. The polygon may have one or more edges that cross back onto another edge, thereby creating a plurality of smaller polygons. It is best viewed as a number of individual polygons. Polygons that do not self-intersect in this manner are referred to as simple polygons.

The properties of all polygons (regular and irregular) include the internal angle at each vertex on the inside of the polygon and the angle on the outside of the polygon between an edge and an extended adjacent edge. A diagonal of a polygon is a line linking any two non-adjacent vertices. For regular polygons, there are a number of ways to calculate the area. For irregular polygons, there is no general formula. The perimeter is the sum of the distances around the polygon or its side lengths.

Properties of a regular polygon include edge-to-center distance (inside diameter), which is a line from the center of the polygon to the midpoint of the edge. This is also the inner diameter-the radius of the inner circle. The radius of a regular polygon (the radius of the circumference) is a line from the center to any vertex. It is also the radius of the circumscribed circle of the polygon. The inner circle is the largest circle that will fit within a regular polygon. A circumscribed circle is a circle passing through all the vertices of a regular polygon. Its radius is the radius of the polygon.

Some embodiments herein illustrate a plurality of polygons within a matrix array. Each of which may affect CT (coherence tomography). They contain enough holes to allow a 'central hexagon'. The square/diamond shape may be evident. Such as the formula:

diagonal line =Wherein:sis the length of any of the sides and,

it is simplified as follows:

diagonal line =Wherein:sis the length of any edge.

The 'pores' described herein may have a particular form, shape, composition and depth. The creation of pores within a matrix array that alter the biomechanical properties of connective tissue is a unique feature of the present disclosure.

As used herein, an "aperture matrix" may be used to control wound healing. In some embodiments, it may include a fill hole to inhibit scar tissue.

In some embodiments, the pores may have a depth of at least 5% -95% through the connective tissue and help produce the desired biomechanical property change. They may have a specific composition, arrangement in a matrix, and desirably have the mathematical properties of a polygon. In three-dimensional (3D) space, the expected variation in the relationship between the pores in a matrix or lattice is a unique feature of the present disclosure (see fig. 1F). The matrix or array may include a 2D Bravais lattice, a 3D Bravais lattice, or a non-Bravais lattice.

Referring to fig. 1 (B-E), an exemplary matrix array of holes is illustrated, herein the matrix array of holes is the basic building block from which all successive arrays can be built, there may be many different ways to arrange the holes on a CT in space, where each point will have the same "environment (atmosphere)". that is, each point will be surrounded by the same set of points as any other point, so that all points will not be distinguishable from each other.

The hexagonal lattice structure may have two angles equal to 90 deg., wherein the other angle (gamma) is equal to 120 deg.. To achieve this, two sides around the 120 ° angle must be equal (a = b), while the third side (c) is 90 ° to the other sides and can have any length.

Referring to FIG. 1F, an exemplary schematic projection of the basal planes of an hcp unit cell onto a tightly packed layer is illustrated. A matrix array is defined as an arrangement of specific, repeating pores that extend through a target connective tissue (e.g., the sclera). Texture refers to the internal arrangement of pores, rather than the appearance or surface of a matrix. However, these are not completely independent, as the appearance of the matrix of holes is usually related to the internal arrangement. There may be a certain distance between each of the holes in the given matrix to satisfy the mathematical properties and properties of the polygon. The resulting pores may also be correlated with the remaining tissue within the matrix, thus altering the biomechanical properties of the matrix.

The spatial relationship of the holes within the matrix has geometric and mathematical significance.

In some embodiments, the laser microperforation system of the present disclosure (see fig. 3) generally includes at least these parameters: 1) laser radiation having a fluence of between about 1-3 microjoules/cm 2 and about 2 joules/cm 2; the texture is more than or equal to 15.0J/cm; more than or equal to 25.0J/cm on the organization; extended therapeutic possibilities of 2900nm +/-200 nm; near the middle IR absorption maximum of water; the laser repetition rate and pulse duration may be adjusted by using a predefined combination in the range of 100-. The range can be regarded as the smallest range that is organically ≧ 15.0J/cm or more and that is organically ≧ 25.0J/cm or more; expanding the treatment possibilities; 2) the irradiation is performed using one or more laser pulses or a series of pulses having a duration between about 1 ns and about 20 μ s. Some embodiments may potentially have versions up to 50W; 3) in some embodiments, the extent of the Thermal Damage Zone (TDZ) may be less than 20 μm, or in some embodiments, between 20-50 μm; 4) parameters of pulse width from 10 μm to 600 μm may also be included. (see FIG. 1E-1).

An energy of 1-3 microjoules per pulse can be linked to femtosecond and picosecond lasers with high repetition rates (e.g. 500hz (zeiss) up to several kilohertz (optimatica)). The benefits of femtosecond and picosecond lasers are small spot sizes (e.g., 20 microns and up to 50 microns) and high energy density in order to minimize thermal problems to surrounding tissue. All of which can lead to effective scleral rejuvenation. In some embodiments, the laser may create a substantially circular and conical hole in the sclera, with a depth up to the perforation of the sclera, and thermal damage from about 25 μm up to about 90 μm. The hole depth can be controlled by the pulse energy and the number of pulses. The aperture may vary due to motion artifacts and/or defocus. Thermal damage may be related to the number of pulses. The pulse energy may be increased, which may result in a reduction of the number of pulses and thus a further reduction of thermal damage. The increase in pulse energy may also reduce the exposure time. The described exemplary design of the laser system allows for an optimized laser profile for lower thermal damage regions while maintaining the irradiation time, thereby maintaining a fast speed for optimal treatment time, and a graph showing the correlation between thermal damage regions and pulses (see fig. 1E-2 and fig. 1G- (1-4)).

In some embodiments, nanosecond lasers used for microperforation or micro-tunneling include the following specifications: wavelength UV-visible-short infrared 350 and 355 nm; 520-532 nm; typically 1030-; pulse length 0.1-500 nanoseconds, passive (or active Q-switched); the pulse repetition rate is 10Hz-100 kHz; peak energy of 0.01-10 mJ; the peak power is more than 10 megawatts at most; free beam or fiber optic transmission.

Femtosecond or picosecond lasers and er can be used: YAG laser to perform scleral rejuvenation. Other preferred embodiments of laser energy parameters for a 2.94 ER: YAG laser or with ER: other laser possibilities of YAG preferred laser energy or other lasers of different wavelengths with high water absorption are desirable.

The millijoules and energy density for different spot sizes/shapes/holes may include:

spot size 50 micron: a) 0.5 mJ pp equals 25J/cm 2; b) 1.0 mJoule pp equals 50 joules/cm 2 (for Er: YAG is possible); 3) 2.0 mJ pp equals 100J/cm 2.

Spot size 100 microns (for ER: YAG, all these are possible): a) 2.0 mJ pp equals 25J/cm 2; b) 5.0 mJ pp equals 62.5J/cn 2; c) the 9.0 mJ pp is equal to 112.5J/cm 2.

Spot size 200 micron: a) 2.0 mJ pp equals 6.8J/cm 2; b) 9.0 mJ pp equals 28.6J/cm 2; c) 20.0 mJ pp equals 63.7J/cm 2.

Spot size 300 microns: a) 9.0 mJoule pp equals 12.8 joules/cm 2 — for ER: YAG is possible; b) 20.0 mJ pp equals 28J/cm 2-possible for DPM-25/30/40/X; c) 30.0 mJ pp equals 42.8J/cm 2; d) 40.0 mJoule pp equals 57 joules/cm 2; e) 50.0 mJoule pp equals 71 joules/cm 2.

Spot size 400 micron: a) 20 mJ pp equals 16J/cm 2-D PM-25/30/40/50/X; b) 30 mJ pp equals 24J/cm 2; c) 40 mJ pp equals 32J/cm 2; d) the 50 mJoule pp equals 40 joules/cm 2.

Note that circular or square holes or spots are also possible.

With respect to femtosecond and picosecond lasers, some useful wavelengths include IR 1030 nm; green 512nm and UV 343 nm. The peak energy can vary from nanojoules (at MHz repetition rates) through 5-50 microjoules up to several hundred microjoules in the picosecond range. A femtosecond laser with a pulse length of 100-; peak energy from nanojoules to hundreds of microjoules, pulse repetition rate from 500Hz to several megahertz (Ziemer LOV Z; Ziemer AG, switzerland: nanojoule peak energy at repetition rates exceeding 5 MHz, beam quality/density is very good — it is possible to concentrate in small spots of 50 microns and below).

In the best femtosecond laser, the beam quality is so accurate that in some embodiments, femtosecond laser micro-tunneling as a microperforated sclera using an Erbium laser can be achieved.

As used herein, nuclear pore can be defined as an opening in the nuclear envelope of about 10 nm in diameter through which molecules (such as nucleoproteins synthesized in the cytoplasm) and rna must pass (see fig. 1H). The pores are created by large protein modules. Perforations in the nuclear membrane allow for the selection of materials for inflow and outflow.

The formula for the porosity in biological tissue can be defined as: x (Xa, t) = qT "(X", t) = X + u "(X", t), (1), where qU is a continuous differentiable reversible mapping from 0 to a, and u "is the cY-component shift. The reversible deformation gradient of the a-component F "and its jacobi" can be defined as J "= det F" (3), where J "must be strictly positive to inhibit self-penetration of each continuum. The% of the right cauchy-green tensor and its inverse (Piola deformation tensor B for solid components) are defined as V = F ' IF ' (4) B = F ' - ' F ' +, where the superscript t denotes the transpose.

Current theoretical and experimental evidence suggests that creating or maintaining pores in connective tissue accomplishes three important tasks. First, it transports nutrients to cells in the connective tissue matrix. Secondly, it carries away cellular waste. Third, the interstitial fluid exerts a force on the wall of the sclera or outer eye membrane that is large enough for cellular perception. This is considered to be the basic mechanical transduction mechanism in connective tissue, i.e. the way the eye membrane senses the mechanical load it is subjected to and responds to the elevation in intraocular pressure. Understanding ocular mechanical transduction is the basis for understanding how to treat ocular hypertension, glaucoma and myopia,

deriving the physical properties of porous media (e.g., water conductivity, thermal conductivity, water retention curve) from parameters describing the structure of the media (e.g., porosity, pore size distribution, specific surface area) is a continuing challenge for scientists, both as to the porosity and its permeability in soft tissue and to bone tissue. To validate the hypothesis of porous media with self-similar scale behavior, the fractal dimensions of various features have been experimentally determined.

Mechanism of system processes and actions

While some current theory of accommodation indicates that the lens is the primary cause of refractive change that allows us to read, it has been found that all of the elements of the zonule device are involved. The elucidation of the role played by the extra-crystalline processes in accommodation supports the theory of scleral therapy, which alters biomechanical properties by restoring compliance to otherwise hard tissues, potentially affecting accommodation in presbyopia.

In particular, VisioDynamics theory states that presbyopia is not ametropia, nor is the loss in the ability to simply focus on near objects. Instead, it is an age-related result on the ocular organs or connective tissue of the eye as if they occurred systemically. This has a significant but reversible impact on the biomechanical efficiency of ocular function (particularly accommodation), which potentially improves not only dynamic visual focusing capabilities, but also ocular biological transport and ocular metabolic efficiency. The visio dynamics theory is based on fundamental and natural biological phenomena that occur with age and in particular cause the influence of eye stiffness on the accommodative structure under the main outer layer of the eye or sclera. The sclera undergoes a gradual "hardening" with age, which represents a normal and gradual irreversible change that occurs in all connective tissues. This hardening process increases scleral compression, which places surprisingly significant loads, stresses and strains on the underlying and related ocular and intraocular structures. Controlling this ocular stiffness or stress and strain on the dynamically-accommodating ciliary body and associated structures affects the biomechanics of the eye and impairs the ability of the eye to perform its core organ functions.

In some embodiments, the ophthalmic laser surgery and therapy treatment system provides an ophthalmic laser treatment procedure designed to relieve stress and strain that occurs with increasingly stiff sclera with age by creating compliance in the scleral tissue using a laser generating matrix of micropores in the scleral tissue. The system is intended to promote biomechanical property changes in the sclera to reduce compression of sub-threshold (supraspinal) connective tissue, facial tissue and biophysical structures of the eye and restore accommodation. The system is specifically designed to relieve stress and increase biomechanical compliance in the ciliary muscle, the accommodation complex and critical physiological anatomy directly beneath aged scleral tissue.

The laser treatment process is directed to specific treatment areas located in different physiological regions that cover critical anatomical structures within the eye relative to eye function. Although examples of 3 or 5 physiological regions are described herein, other numbers of physiological regions are contemplated for treatment.

In some embodiments, the treatment pattern can be described as 3 critical regions in 3 different distances from the outer edge of the Anatomical Limbus (AL) without contacting any component of the cornea or related tissue. These regions are illustrated in FIG. 2A- (1-2). In some embodiments, the treatment pattern may be described as 5 critical regions in 5 different distances from the outer edge of the Anatomical Limbus (AL) without contacting any components of the cornea or related tissue, as illustrated in fig. 2B- (1-3).

Laser treatment procedures may use erbium: an yttrium-aluminum-garnet (Er: YAG) laser creates pores in the sclera. These micropores may be created at a variety of depths having a preferred range of depths (e.g., from 5% -95% of the sclera up to the point where the blue tone of the choroid is just visible). Microwells can be created in a plurality of arrays including matrix arrays (e.g., 5mm x5mm, 7mm x 7mm, or 14mm x 14mm matrix arrays). These microporous matrices disrupt the bonds in the scleral fibrils and microfibers that have an "uncrosslinked" effect in the scleral tissue. The direct result of this matrix pattern is a region in the rigid sclera that produces both positive stiffness (remaining interstitial tissue) and negative stiffness (removed tissue or microvoids). These regions of different stiffness allow the viscoelastic modulus of the treated sclera to be more compliant over critical areas when subjected to forces or stresses, such as contraction of the ciliary muscle. In addition, due to the increased plasticity, the treated region of the sclera can create a damping effect in the hard scleral tissue when the ciliary muscle contracts. This enhances the accommodation effort by directing the uncompressible forces inward and centrally towards the lens or facilitating the inward upward movement of the accommodation mechanism. This is an advantage over models that assume a net outward force at the lens equator. For example, techniques directed to scleral expansion (such as scleral implants) or surgical laser radial ablation, (such as LAPR), are directed to increasing the 'space' or periphakic space to allow scleral expansion to intentionally give ciliary muscle space. These techniques are based on the theory of 'lens crowding' and aim to induce outward movement of the sclera and ciliary body mechanism, rather than upward and inward movement. In general, the formation of a matrix of micropores in the scleral tissue induces an "uncrosslinked effect", cutting the fibrils and microfibers of the scleral layers, allowing a more compliant response to the applied stress. The mechanism of the proposed action of this system is therefore to increase the plasticity and compliance of the scleral tissues on the anatomically important critical areas by creating these areas of different stiffness on the ciliary complex and thus improve the biomechanical function and efficiency of the accommodation device. Fig. 2C- (1-4) illustrates laser scleral decrosslinking of scleral fibrils and microfibers in some embodiments.

With reference to fig. 2D (1-4), the effect of this process on eye stiffness has been studied using a novel model. Like all other connective tissues, ocular connective tissue is affected by age. The sclera constitutes 5/6 of the eye and is composed of dense irregular connective tissue. It is mainly composed of collagen (50-75%), elastin (2-5%) and proteoglycan. The connective tissues of the eye harden with age, losing their elasticity, primarily due to cross-linking that occurs with age. Crosslinking produces an "increase in biomechanical stiffness" in connective tissue such as those in the eye. Crosslinks are bonds between polymer chains, such as those in synthetic biomaterials or proteins in connective tissue. Crosslinking may be caused by free radicals, uv irradiation and aging. In connective tissue, collagen and elastin can be cross-linked to continuously form fibrils and microfibrils over time. As the number of fibrils and microfibers increases, the sclera hardens, undergoing 'sclerosis', and the concomitant increase in metabolic physiological stress. As this pathophysiology develops, the sclera exerts compressive and loading stresses on underlying structures, creating biomechanical dysfunctions, particularly those associated with regulation. The laser scleral micropores effectively disrupt scleral fibrils and microfiber "uncrosslinked" bonds, thereby increasing scleral compliance and "reducing biomechanical stiffness".

In some exemplary procedures, six freshly harvested pig eyes were altered by cross-linking (0.8 ml of 2% glutaraldehyde for 10 minutes) to mimic the eye stiffness of an older human eye (60 years), based on the Pallikaris et al eye stiffness coefficient model. Seven newly harvested pig eyes were left unchanged to mimic the eye hardness of a young human eye (30 years old). Three of the eyes in each group received treatment, while the remaining eyes were used as controls. Briefly, the study used a pressure sensor (up to 5 psi), a dosage injector controller, a data computerized reader, and a tissue holding frame to which each pig eye was fixed to generate IOP versus injection volume curves for each eye. The ocular hardness coefficient (K = d ln (P)/dV [ in mmHg/μ l ]) was then calculated as ln (IOP) (from IOP between 30-50 mmHg) slope of the injection volume. In young eyes, treatment resulted in a 10.8% reduction in stiffness. In older eyes, treatment resulted in a 30.1% reduction in hardness. Using analysis of variance (ANOVA) and Tukey honesty significant difference (TukeyHSD) tests, this study found that this system significantly reduced eye stiffness in both the old eye and the whole (p = 0.0009; p = 0.0004). This decrease in ocular hardness may be due to "uncrosslinked" aged tissue.

In some exemplary procedures, twenty-six subjects underwent treatment and 21 completed 24 months of post-operative care. Five patients exited due to professional travel conflicts. Data for pre-operative (month 0) and post-operative IOP (as measured by tonometer) are shown. There was an immediate 5% decrease in IOP of the patient's eye compared to preoperative IOP. Within two years after treatment, patients' IOP remains about 15% lower than preoperative IOP. Immediate and sustained reduction in IOP may show improvement in aqueous outflow after treatment. These differences were statistically significant starting at month 3 post-surgery and continuing through all subsequent months (p =0.000063 at 24 months post-surgery) using ANOVA and TukeyHSD tests. This reduction in IOP may indicate increased ocular motility and a reduction in ocular stiffness after treatment.

Biomechanical improvements via therapy may demonstrate increased biomechanical efficiency of the modulation device. In some embodiments, the treatment can restore functional extraocular lens force and restore a minimum of 1-3 diopters of accommodation by creating micro-holes in the matrix on four oblique quadrants. Our reported results show an average post-operative 1.5 diopter accommodation. This significantly improves the vision of our patients. Data from the 24-month post-operative follow-up from this clinical study was presented in 2015 and showed promising results. Visual acuity was measured using a standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart and statistically analyzed using ANOVA and TukeyHSD tests. Uncorrected monocular myopic acuity in patients at 24 months post-surgery was 0.25 ± 0.18 logMAR (mean ± standard deviation) compared to pre-operative 0.36 ± 0.20 logMAR (p < 0.00005).

In summary, the loss of accommodation in presbyopia has been demonstrated to have many contributing lenses and extra-lens and physiological factors using innovative biometric and imaging techniques not previously available. The lens, lens capsule, choroid, vitreous, sclera, ciliary muscle, and zonules all play a key role in accommodation and are affected by increasing age. Increasing eye stiffness with age creates stress and strain on these ocular structures and may affect accommodative ability.

Scleral therapy can address the real cause of the clinical manifestations of loss of accommodation experienced with age by providing at least one means to address, with an important role in the treatment of biomechanical deficiencies in presbyopia. Treatment with laser microholes of the sclera to restore more flexible biomechanics is a safe process and can restore accommodation in aging adults. As a result, the treatment improves dynamic range of regulation and aqueous outflow. With the advent of improved biometric, imaging, and research focus, information can be obtained on how the regulatory complex works and how it affects the entire eye organ.

Referring to fig. 2E, exemplary three key important regions as measured from the Anatomical Limbus (AL) are shown. Zone 1) 0.5-1.1mm from AL, above the scleral spur at the origin of the ciliary muscle; zone 2), 1.1-4.9mm from AL, above the middle ciliary body; zone 3), 4.9-5.5mm from AL, above the insertion of the longitudinal muscle fibers of the ciliary body, just anterior to the serration rim upon insertion of the posterior vitreous zonules. Fig. 2e (b) illustrates exemplary restored mechanical efficiency and improved biomechanical activity.

In some embodiments, the laser scleral microperforation procedure may involve the use of the above-described laser to perform partial thickness micro-ablation in the sclera in a matrix in five key anatomical regions (0-7.2 mm from the Anatomical Limbus (AL)). The five regions may include: zone 0) 0.0-1.3mm from AL; the distance from AL to the upper boundary of the ciliary muscle/scleral spur; zone 1) distance AL1.3-2.8 mm; the distance from the scleral spur to the inferior border of the orbicular muscle; zone 2) 2.8-4.6mm from AL; the distance from the inferior border of the circular muscle to the inferior border of the radial muscle; zone 3) 4.6-6.5mm from AL; the lower boundary of the radial muscle to the upper boundary of the posterior vitreal zonule region; and zone 4) 6.5-7.2mm from AL; the upper boundary of the posterior vitreal small band region to the upper boundary of the serrated edge.

Fig. 2F illustrates an exemplary matrix array of micro-ablations in four oblique quadrants.

Fig. 2G illustrates an exemplary graphical representation of restored ocular compliance, decreased scleral resistance, increased ciliary resultant force, and restored dynamic accommodation after treatment.

Fig. 2H illustrates exemplary box and whisker plots of eye hardness for control (black) and treatment (gray) porcine eyes. The upper and lower ends of the box represent the 75 th and 25 th percentiles, the bars within the box represent the median and must represent the entire range of the data range.

Fig. 2I illustrates exemplary box and whisker plots of pre-and post-operative intraocular pressure (IOP) of a patient's eye. Stars indicate significant differences from preoperative IOP. The upper and lower ends of the box represent the 75 th and 25 th percentiles, the bars within the box represent the median, the whole range of the data range must be represented, and the white circles represent outliers.

Fig. 2J illustrates an exemplary chart showing uncorrected and distance-corrected visual acuity at, intermediate (60 cm), and near (40 cm) distance 4m for a) a single eye and b) a double eye patient's eye. Error bars represent mean ± SD.

As described herein, accommodation of the human eye occurs through a change or deformation of the lens of the eye as the eye transitions from a far focus to a near focus. This lens change is caused by the contraction of the ciliary muscle (ciliary body) in the eye, which relieves tension on the lens by the zonular fibers hanging, and allows the thickness and surface curvature of the lens to increase. The ciliary muscle may have an annular shape and may consist of three uniquely oriented groups of ciliary fibers that contract towards the center and front of the eye. These three ciliary fiber groups are referred to as longitudinal, radial and circular. The deformation of the ciliary muscle due to contraction of the different muscle fibers translates into or otherwise causes a change in tension on the surface of the lens of the eye by the zonular fibers, the pattern of complex attachment of the zonular fibers to the lens and ciliary muscle determining the resultant change in the lens during accommodation. Ciliary muscle contraction also applies a biomechanical strain at the junction between the ciliary muscle, referred to as the white outer layer of the eye, and the sclera of the eye. In addition, biomechanical compression, strain or stress may be induced during accommodation that may occur at the junction between the ciliary muscle and the choroid, referred to as the inner connective tissue layer between the sclera and the retina of the eye. Ciliary muscle contraction can also induce biomechanical forces on nearly every structure in the trabecular meshwork, lamina cribrosa, retina, optic nerve, and eye.

Applying the techniques and models described with respect to various embodiments herein using simulations may result in outputs and results that fall within the range of known adjustments for young adults.

The 3D mathematical model may combine mathematical and nonlinear Neohookean properties to reconstruct the behavior of structures of biomechanical, physiological, optical and clinical importance. Furthermore, a 3D (finite element model) FEM model may incorporate data from imaging, literature and software related to the human eye.

In addition to the means for measuring, evaluating and predicting the Central Optical Power (COP), visualization of the adjustment structure during and after the simulation may be included. These can be used to simulate and view the structure, optics, function and biomechanics of the whole eye at a particular age. Furthermore, they can independently mimic the properties of the ciliary muscle, the extra-and lens movements of the eye lens and the function on the eye lens. Separate simulations of anatomical structures and fibers can reveal biomechanical relationships that would otherwise be unknown and ambiguous. A numerical simulation of the patient's eyes may be created using the 3D FEM mesh to achieve these operations.

To elaborate, a representative 3D geometry of a static eye structure may be computationally defined by modeling based on literature measurements and extensive review of medical images and anatomical structures of young adult eyes. During the modeling phase, specialized methods implemented in software, such as AMPS software (AMPS technology, pittsburgh, pennsylvania), may be used to perform geometric meshing, material property and boundary condition definition, and finite element analysis. The ciliary muscle and zonules can be represented as transversely isotropic materials with orientation designated to represent complex fiber directions. Additionally, computational fluid dynamics simulations may be performed to generate fiber trajectories, which may then be mapped to a geometric model.

Initially, the lens mold may include the lens in a relaxed configuration prior to pre-stretching to an unaccommodated position and shape by the zonule fibers. The unadjusted lens position may be reached when the zonules are shortened, for example, to between 75% and 80% of their starting length, and more particularly to about 77% of their starting length. The accommodative movement can then be simulated by performing an active contraction of the various fibers of the ciliary muscle. In some embodiments, this may be accomplished using a previous model of skeletal muscle modified to represent dynamics that are specific or otherwise specific or unique to the ciliary muscle. The model results representing the lens and ciliary body anterior movement and the thickness of the ocular lens deformed at the midline and apex can be confirmed or otherwise validated by comparing the model results to existing medical literature measurements for accommodation. To study the contribution of the various ciliary fiber groups to the overall action of the ciliary muscle, simulations may be performed for each fiber group by activating each fiber group individually while the other fiber groups remain passive or otherwise unchanged.

Various beneficial aspects of the embodiments described below are described with respect to simulations that apply a pre-tensioned zonule model and a contracted ciliary muscle model.

With respect to pre-stretched small ribbons, the modeling may include: 1) creating a sheet of 3D material oriented between the attachment point of the measuring zonules inserted on the lens and the origin of the ciliary body/choroid; 2) a specified fiber direction in the plane of the sheet (i.e., from the starting point to the inserted fiber); and 3) a laterally isotropic, constitutive material having a tensile force generation in a preferred direction. Furthermore, particularly with respect to 3), advantages have been achieved, including: a) inputting time-varying tension parameters to adjust stress generated in the material; b) the time-varying tension input is tuned to produce a desired strain in the lens to match the measurement of the unadjusted configuration; c) age changes in material properties and geometry to produce age-related effects; and d) others.

With respect to the contracted ciliary muscle model, the modeling may include: 1) improved constitutive models for representing smooth and skeletal aspects of ciliary body mechanical response; 2) a set of specified fiber directions representing a physiological orientation of muscle cells and lines of action of force generation; and 3) a transversely isotropic constitutive material having active force generation in a preferred direction. Furthermore, particularly with respect to 3), advantages have been achieved, including: a) the activation parameter input adjusts the activation stress generated in the material; b) the activation input is tuned to produce an appropriate adjustment response to match the document measurement; c) the activation of individual muscle fiber groups can be varied individually to assess the contribution to lens strain/stress; d) the activation of individual muscle fiber groups can be varied individually to assess the contribution to eye-sclera strain/stress; e) activation of individual muscle fiber groups can be varied individually to assess the contribution of choroidal strain/stress; and f) others.

In various embodiments, the simulation results may be controlled by modification of the stretching and activation inputs to the zonule and ciliary body material, rather than performing the applied displacement on the external node(s) of the mesh.

Thereafter, systems, methods and devices are disclosed for providing predictive outcomes in the form of 3D computer models with integrated Artificial Intelligence (AI) that may be used to find predictive best instructions for therapeutic ophthalmic correction, manipulation or rehabilitation of a patient's vision defects, eye diseases or age-related dysfunctions. The predictive best instruction may be derived from physical structure inputs, neural network simulations, and prospective treatment outcome effects. The new information may be analyzed in conjunction with optimized historical treatment outcome information to provide various benefits. The concepts herein can be used to perform a large number of simulations and have a knowledge-based platform that enables the system to improve its instruction response as the database is expanded.

In some embodiments, the contemplated stored instructions may preferably be an optimized, customized photoablation algorithm for driving a photoablation photothermal laser. The instructions may be provided with the AI processor via direct integration, independent import, or remotely (via a bluetooth enabled application or connection). These instructions may be executed in advance or intraoperatively.

In some embodiments, the contemplated stored instructions may preferably be an optimized customized intraocular lens simulation algorithm for simulating manipulation of an implantable intraocular lens in order to improve medical procedures and understanding.

The instructions may also be provided as a 'stand-alone' system to function as a virtual clinical trial system or development system, whereby the instructions may be provided with independent study design inputs and outputs to test the eye for various conditions and responses to surgical manipulations, implant devices, or other therapeutic manipulations of the eye in order to optimize the design and outcome response.

Further, the instructions may also include one or more of: algorithms for image processing interpretation, extensions of ophthalmic imaging data platforms, and concomitant diagnostics of imaging devices.

As described herein, methods for improving ophthalmic therapy, surgery, or pharmacological intervention can include obtaining topological, topographic (topographical), structural, physiological, morphological, biomechanical, material properties, and optical data of the human eye, as well as applying physics, and analyzing by mathematical simulation using an artificial intelligence network.

Virtual clinical applications using simulations may include techniques performed via automatically designed devices, systems, and methods for ophthalmic surgical procedures that include obtaining physical measurements and applying physics of the entire eye of a patient. These measurements may be obtained using conventional techniques. 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 state of the initial stress of the eye and obtain the preoperative condition of the cornea, lens and other structures. The incision data that make up the "initial" surgical plan may be incorporated into the finite element analysis model. New analyses can then be performed to simulate the resulting deformations, biomechanical effects, stresses, strains, curvature of the eye and dynamic movements of the eye, more particularly the ciliary muscles, lens and accommodative structures. These can be compared to their original values and to the visual target. If necessary, the surgical plan can be modified and the resulting new ablation data can be entered into the FEM and analyzed repeatedly. This process can be repeated as needed or necessary until the visual goal is met.

Artificial Intelligence (AI) software can use artificial neural networks for machine learning, whereby the system can learn from data and therefore have a learning component based on continuous database extensions. When the database is expressed and updated, it may be operable to improve reliability, which has heretofore been unknown in the prior art of 3D predictive modeling systems, methods and apparatus.

The simulation may include an age progression simulation of the patient's eye with predictive capabilities to simulate ophthalmic surgical outcomes, determine regression rates for treatments, and execute predictive algorithms for future surgical or treatment enhancements heretofore unknown in the prior art of 3D predictive modeling systems, methods, and devices.

The virtual eye simulation analyzer may comprise integrating information related to all structures of the eye into a computer program for the purpose of simulating biomechanical and optical functions of the eye, as well as age-related simulations for clinical application purposes.

Virtual eye simulation analyzer systems, devices, and methods may include an output display that may be viewed by a user as a stand-alone or integrated display system, among other devices.

The information used as input to the simulator may include biometric imaging information (UBM, OCT, and others). Dynamic imaging can be performed using UBM, OCT, and others. Anatomical information may include geometry, histology, and others. Physiological functional information may include dynamic regulation, aqueous humor flow, intraocular pressure, pulsatile eye blood flow, retinal performance or damage, and others. Material properties of the tissues of the eye, physical and biomechanical information related to relative biomechanics may also be used.

The simulator may combine mathematical and nonlinear Neohookean properties in order to reconstruct the behavior of biomechanical, physiological, optical and other structures that may be of value or otherwise of clinical importance. The simulator may use conventional methods to input the data incorporated into the 3D FEM along with the patient's unique data based on analysis of their own eye or eyes. Furthermore, the simulator can use conventional methods to input data and use 3D FEM meshing to create numerical simulations of the patient's eyes-essentially creating customized dynamic real-time "virtual eyes" that have heretofore been unknown in the prior art of 3D predictive modeling systems, methods and devices.

In some embodiments, the AI may be able to learn via predictive simulation and may be operable to improve simulated prediction of surgical or therapeutic manipulation of the eye by, for example, an artificial neural network in the "ABACUS" procedure. The ABACUS may also be capable of providing instructions directly to a communicatively coupled processor or processing system to create and apply algorithms, mathematical sequencing, formula generation, data profiling, surgical selection, and others. It may also be capable of providing instructions directly to a workstation, image processing system, robot controller, or other device for implementation. Further, it may be able to provide instructions indirectly through bluetooth or other remote connections to a robot controller, vision system, or other workstation.

The models herein may have various applications for clinical, research, and surgical use, including: 1) use of previous assessments and simulations of the eye's accommodative function (examples include presbyopic indications-IOL design and use, extra-lens therapy and use thereof); 2) the use of previous assessments and simulations of the aqueous humor flow of the eye, such as for glaucoma indications; 3) virtual and real-time simulation of the efficacy, therapeutic treatment, and various biomechanical implications of IOLs; 4) virtual simulation using AI and CI to reproduce customized aging effects on the individual's biomechanics and physiological functions of the individual's eyes, which is of clinical importance; 5) planning the operation; 6) such as for IOL and other design model (such as FEM) introductions and simulations; 7) virtual clinical trials and analyses; 8) real-time intra-operative surgical analysis, planning and execution; 9) such as its performance in the lens of the eye in relation to optical and biomechanical dysfunction, cataract formation and the like; and 10) others.

Additional components of the simulator may include: 1) eye scanning; 2) optical inputs such as a) corneal optics, wavefronts, elastography, hysteresis, visual acuity topography, connective tissue macro-and microstructures, and b) lens optics such as wavefronts, visual acuity, topography, lens opacity, light scattering, Central Optical Power (COP) during accommodation and disorders, elastography, viscoelastic properties, and others; 3) sclera biomechanics, viscoelasticity, material properties, stress, strain mapping, connective tissue macro/microstructure; 4) trabecular mesh materials, viscoelasticity, connective tissue macrostructures and microstructures; 5) sieve material properties, stress, strain viscoelasticity, connective tissue macro and micro structure; 6) a physiological input comprising: a) aqueous outflow and inflow, b) intraocular pressure (IOP), c) ocular pulsating blood flow, d) retinal activity and others; 7) surface spectroscopy; 8) corneal, scleral, lens and other collagen fibril characterizations; and 9) others.

Benefits of the simulator in the tuning embodiment may include: 1) measuring, analyzing and simulating accommodation of the eye in real time; 2) displaying and adjusting biomechanics in real time; 3) assessing regulatory biomechanics; 4) visualization of the adjustment structure; 5) measuring, evaluating and predicting central power; 6) simulating the age progression of the whole eye structure, function and biomechanics; and 7) others.

The primary structural component inputs may be based on the sclera, cornea, lens, trabecular meshwork, lamina cribrosa, retina, and others. For the sclera，These may include: scleral hardness, viscoelasticity, scleral thickness, scleral depth, 3D surface topology, top surface spectral dimensions, 3D spectra, and others. For cornea，These may include: corneal wavefront, viscoelasticity, topography, keratotomy, corneal thickness, 3D topography, K-reading, corneal hardness, 3D spectroscopy, and others. For crystalline lens，These may include: lens wavefront, central power, accommodative amplitude, light scatter, opacity, and others. For trabecular meshwork, these may include: elasticity, outflow, inflow, and others. For a screen deck, this may include: porosity, mechanical dependency, perfusion, pore elasticity, cup bottom depth, and others.

Some of the various primary optical profiles, properties, information and visual acuity information outputs of the cornea may include: total aberrations, visual strehl ratio, depth of focus, MRSE, visual acuity, lens scatter, and others. Some of the various primary optical profiles, properties, information and visual acuity information outputs of the lens may include: total aberration, VSOF, depth of focus, and others.

Also described are example embodiments of creating a 3D micro-pore model on a spherical surface.

Also described is an example embodiment of Fibonacci MatLab well calculations for a full-eye pattern revised by the Patec protocol.

With reference to FIG. 2K-1, an example of implementation of the scheme is now described: scheme 1.1: 225um (169 total holes @ 3% =42.25 holes/quadrant). Examples of Matlab code for scenario 1.1 may include: > > fibonacci _ spiral _ connected _ patch ('r', 0.225, 3, 6.62, 9.78). The Matlab code parameter decomposition may include: parameter 1, 'r' = pore shape: for rectangular shapes, ` r ` is keyed, or for circular hole shapes, ` c ` is keyed. For 'please (please)' use 'r', and for 'DPM 25'; parameter 2, 225um (0.225) = r _ shape: the length of the rectangular hole shape or the radius of the circular hole in [ mm ]; parameter 3, 3% = D: pore density in [% ] units; parameter 4, 6.62mm (radius of area subtracted from hole calculation). Therefore, no hole was calculated in the cornea/limbus region (6.62 mm) = r _ b: the radius of the origin of the circle, in [ mm ]; parameter 5, 9.78mm (radius to the end of the area where the hole is calculated). The 6.62mm radius will be subtracted from the hole calculation process, allowing the 6.62mm to 9.78mm radius to be the only calculated area with hole = r _ e: the radius of the end of the circle is in [ mm ]. Once the code (('r', 0.225, 3, 6.62, 9.78)) is entered in Matlab, it will output a map specifically generated for this hole pattern. This is how the header gets its total number of holes.

Treatment management scheme: the following are exemplary protocols for therapeutic manipulation, which are 2 manipulations per protocol: a) a first manipulation of the entire quadrant region; b) second manipulation of the "Patch" area 5x5mm rhombus i) having the length of its diagonalmm, ii) we have updated the 5x5 matrix placed on the sphere, the Fibonacci helix can satisfy the model.

Ball comparison: in some embodiments, our "patch" is 5x5, so this size is used. Er with fiber probe: a Yag laser; spot size of 600 μm; nine micro-ablations in 4 oblique quadrants; 10 minutes/eye treatment time; micropores in critical regions (e.g., 3 or 5 regions) on the ciliary complex; creation of a flexible matrix region in the sclera.

The surgical target may include: 1) increasing the compliance of the sclera with the critical anatomical structures of the ciliary muscle complex; 2) restoring the mechanical efficiency of the natural regulation mechanism; 3) improving biomechanical mobility to achieve regulatory capability; and others.

Exemplary Fibonacci treatment patterns are generated by Matlab or other procedures in two dimensions. When having the correct size patch (such as 5x5 mm), it may perform actual treatments that may not be appropriate in the critical area (e.g., areas 1-3 or 1-5). There are methods to get the actual estimate from the 3D model to the 2D model. As shown in fig. 2K-1, the parameters may include:

baseline: 600 μm (92 total wells @ 16% =23 wells/quadrant).

Spot size: 600 um; depth: 80 percent; density: 16 percent; volume removed: 1.16mm³(ii) a Overall hole: 92; total aperture/quadrant: 23.

scheme 1.1: 225 μm (169 total wells @ 3% =42.25 wells/5.5 mm patch: validation) total wells/5.5 mm patch.

Fig. 2K-1-a to 2K-1-C illustrate exemplary recipe parameters for generating diamond patterns for 3 critical areas.

In some embodiments, it may be important to know how many holes there are in the 5x5 patch on the 3D model in each scenario, based on varying density and varying spot size. Once known, patch manipulation may be performed. Fig. 2K- (2-17) illustrates exemplary views of the various schemes used and their results. These solutions include:

scheme 1.1: 225 μm (96 total wells @ 3% =24 total wells/quadrant: confirmed)

Spot size: 225 um; depth: 80 percent; density: 3 percent; volume removed: 0.91mm³(ii) a Overall hole: 96; total aperture/quadrant: 24

Scheme 1.2: 225 μm (161 total wells @ 5% =40.25 wells/quadrant: confirmed)

Spot size: 225 um; depth: 80 percent; density: 5 percent; volume removed: 1.52mm³(ii) a Overall hole: 161; total aperture/quadrant: 40.25

Scheme 1.3: 225 μm (257 total wells @ 8% =64.25 wells/quadrant: confirmed)

Spot size: 225 um; depth: 80 percent; density: 8 percent; volume removed: 2.43mm³(ii) a Overall hole: 257; total aperture/quadrant: 64.25

Scheme 1.4: 225 μm (565 total wells @ 10% =141.25 wells/quadrant: confirmation)

Spot size: 225 um; depth: 80 percent; density: 10 percent; volume removed: 3.04mm³(ii) a Overall hole: 565; total aperture/quadrant: 141.25

Scheme 2.1: 250 μm (100 total wells @ 3% =25 wells/quadrant: confirmation)

Spot size: 250 um; depth: 80 percent; density: 3 percent; volume removed: 0.91mm³(ii) a Overall hole: 100, respectively; total aperture/quadrant: 25

Scheme 2.2: 250 μm (166 total wells @ 5% =41.5 wells/quadrant: confirmed)

Spot size: 250 um; depth: 80% density: 5 percent; volume removed: 1.52mm³(ii) a Overall hole: 166, a water-soluble polymer; total aperture/quadrant: 41.5

Scheme 2.3: 250 μm (265 total wells @ 8% =66.25 total wells/quadrant: confirmation)

Spot size: 250 um; depth: 80 percent; density: 8 percent; volume removed: 2.43mm³(ii) a Overall hole: 265 of a nitrogen-containing gas; total aperture/quadrant: 66.25

Scheme 2.4: 250 μm (332 total wells @ 10% =83 wells/quadrant: confirmation)

Spot size: 250 um; depth: 80 percent; density: 10 percent; volume removed: 3.04mm³(ii) a Overall hole: 332; total aperture/quadrant: 83

Scheme 3.1: 325 μm (59 total wells @ 3% =14.75 total wells/quadrant: confirmed)

Spot size: 325 um; depth: 80 percent; density: 3 percent; volume removed: 0.91mm³(ii) a Overall hole: 59; total aperture/quadrant: 14.75

Scheme 3.2: 325 μm (98 total wells @ 5% =24.5 total wells/quadrant: confirmation)

Spot size: 325 um; depth: 80 percent; density: 5 percent; volume removed: 1.52mm³(ii) a Overall hole: 98, respectively; general hole/elephantLimiting: 24.5

Scheme 3.3: 325 μm (157 total wells @ 8% =39.25 total wells/quadrant: confirmation)

Spot size: 325 um; depth: 80 percent; density: 8 percent; volume removed: 2.43mm³(ii) a Overall hole: 157; total aperture/quadrant: 39.25

Scheme 3.4: 325 μm (196 total wells @ 10% =49 wells/quadrant: confirmed)

Spot size: 325 um; depth: 80 percent; density: 10 percent; volume removed: 3.04mm³(ii) a Overall hole: 196 parts by weight; total aperture/quadrant: 49

Scheme 4.1: 425 μm (34 total wells @ 3% =8.5 wells/quadrant: confirmed)

Spot size: 425 um; depth: 80 percent; density: 3 percent; volume removed: 0.91mm³(ii) a Overall hole: 34; total aperture/quadrant: 8.5

Scheme 4.2: 425 μm (57 total wells @ 5% =14.25 total wells/quadrant: confirmation)

Spot size: 425 um; depth: 80 percent; density: 5 percent; volume removed: 1.52mm³(ii) a Overall hole: 57; total aperture/quadrant: 14.25

Scheme 4.3: 425 μm (92 total wells @ 8% =23 wells/quadrant: confirmation)

Spot size: 425 um; depth: 80 percent; density: 8 percent; volume removed: 2.43mm³(ii) a Overall hole: 92; total aperture/quadrant: 23

Scheme 4.4: 425 μm (115 total wells @ 10% =28.75 wells/quadrant: confirmed)

Spot size: 425 um; depth: 80 percent; density: 10 percent; volume removed: 3.04mm³(ii) a Overall hole: 115, 115; total aperture/quadrant: 28.75

The following are exemplary code references for the scheme:

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

fibonacci_spiral_connected_Pantec（‘r’，0.225，5，6.62，9.78）>>1.2

fibonacci_spiral_connected_Pantec（‘r’，0.225，8，6.62，9.78）>>1.3

fibonacci_spiral_connected_Pantec（‘r’，0.225，10，6.62，9.78）>>1.4

fibonacci_spiral_connected_Pantec（‘c’，0.125，3，6.62，9.78）>>2.1

fibonacci_spiral_connected_Pantec（‘c’，0.125，5，6.62，9.78）>>2.2

fibonacci_spiral_connected_Pantec（‘c’，0.125，8，6.62，9.78）>>2.3

fibonacci_spiral_connected_Pantec（‘c’，0.125，10，6.62，9.78）>>2.4

fibonacci_spiral_connected_Pantec（‘c’，0.1625，3，6.62，9.78）>>3.1

fibonacci_spiral_connected_Pantec（‘c’，0.1625，5，6.62，9.78）>>3.2

fibonacci_spiral_connected_Pantec（‘c’，0.1625，8，6.62，9.78）>>3.3

fibonacci_spiral_connected_Pantec（‘c’，0.1625，10，6.62，9.78）>>3.4

fibonacci_spiral_connected_Pantec（‘c’，0.2125，3，6.62，9.78）>>4.1

fibonacci_spiral_connected_Pantec（‘c’，0.2125，5，6.62，9.78）>>4.2

fibonacci_spiral_connected_Pantec（‘c’，0.2125，8，6.62，9.78）>>4.3

fibonacci_spiral_connected_Pantec（‘c’，0.2125，10，6.62，9.78）>>4.4

as noted, the inputs include: pore size (mum); depth of hole (mum); #, of the hole; the density of the pores; the angle of the area of the hole; the location of the laser beam from the surface, and other, if needed or desired.

Various inputs can be used for sufficient and accurate modeling. These may include pore sizes in mum, as pore sizes actually change parameters, not just the scale of # spots and patterns. Density should also be taken into account, as well as surface area formulas, number of holes as related to hole size calculated from power, angle and long arc in each area of the eyeball where each spot or row of spots needs to be placed, angle at which the laser spot will be located for each area that is being entered using eye parameters, and others.

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

The protocol requirements for each treatment mode may include: spot size; depth; the number of whole ball holes in all quadrants; number of holes/quadrant; number of holes/5.5 mm patch; the volume removed; density- (number of blobs). Performing a therapeutic maneuver may include: the entire quadrant and patch (surface area) where shape variation of a particular corneal diameter of the eye may be important.

Exemplary embodiments of applications for artificial intelligence, simulation and field applications may include: 1) use the R & D of the eye for various modeling implementations; 2) virtual clinical trials; 3) laser integration as a diagnostic partner or robot controller; 4) performing a virtual surgical procedure on the eye for the "smart surgical" plan; 5) integration into an imaging device to improve image interpretation; 6) integrated into a surgical microscope for "real-time" modification of surgery/treatment (e.g., for IOL surgery); and 7) others.

The simulated functions may include: 1) simulating ideal biomechanics for optimizing overall visual function and optimal central power for accommodation; 2) simulating ideal biomechanics for optimizing the total visual function and optimal optical power of the cornea; 3) simulating ideal biomechanics for optimizing reduced aqueous outflow from the trabecular meshwork; 4) simulating ideal biomechanics for optimizing retinal decompression of the lamina cribosa and peripapillary sclera; 5) simulation for optimizing scleral rejuvenation; 5) a simulation for optimizing surgical outcome of intraocular lens surgery; 6) simulation of surgical or treatment outcomes for optimizing corneal surgery; 7) age progression simulation to assess the long-term effects of aging on eye function; 8) age progression simulations to assess the long-term stability and outcome of various surgical procedures of the eye; 9) simulation of tests for analyzing applications, treatments, surgical manipulations, implant devices, and medication of the eye via virtual clinical trials; and 10) others.

Algorithms and other software for implementing the systems and methods disclosed herein are typically stored in a non-transitory computer-readable memory and typically contain instructions that, when executed by one or more processors or processing systems coupled thereto, perform steps to perform the subject matter described herein. Implementations of imaging, machine learning, prediction, auto-correction, and other subject matter described herein may be used with currently and future developed medical systems and devices to perform medical procedures that provide benefits heretofore unknown to the art.

In some embodiments, the described systems, methods, and devices are performed prior to or concurrently with various medical procedures. In some embodiments, they may be implemented in their own systems, methods and devices, as well as any required components to achieve their respective goals, as will be appreciated by those skilled in the art. It should be understood that medical procedures benefiting from the materials described herein are not limited to implementations using the materials described below, but that other procedures previously, currently performed, and developed in the future may also benefit.

Fig. 3A illustrates an exemplary laser therapy system according to some embodiments of the present disclosure. In some embodiments, the treatment laser beam travels to the color separator 208. At the color separator 208, the laser beam travels to a galvanometer arrangement 320 comprised of a galvanometer 1210 and a galvanometer 2212. The light beam then passes from the galvanometer device 320 to the focusing optics 216 and ultimately to the patient's eye 140.

Also provided in this embodiment is a control and monitoring system that is generally comprised of a computer 310, a video monitor 312, and a camera 308. Camera 308 provides monitoring of the laser beam at color separator 208 via lens 306. Camera 308 transmits its feed to computer 310. The computer 310 is also operable to monitor and control the galvanometer device 320. The computer 310 is also coupled to a video monitor 312 to provide a user or operator with a real-time feed from the camera 308.

In some embodiments of the invention, a two-axis closed-loop galvanometer optical assembly is used.

Since multiple laser systems may be used for treatment in some embodiments, additional laser systems will now be described.

The laser system may include a cage mount galvanometer including a servo controller, a smart sensor, a feedback system, and a mounting assembly having an optical camera. Some embodiments may include the use of a cage mounted galvanometer optical assembly. Some embodiments may include ultra-high resolution nanopositioners to achieve sub-nanometer resolution.

For expansion, fig. 3A shows more exemplary details of a CCD (or CMOS) camera based eye tracker subsystem. The color separator 208 beam splitter is used to pick up visible light while allowing transmission of the IR therapy beam. The beam splitter 208 is located in front of a turning element, here shown as galvanometer 320. Lens 306 images the tissue plane (eye) onto the camera. Features in the image field (e.g., blood vessels, edges of the iris, etc.) are identified by image processing and their coordinates in the camera pixel field are calculated. If the eye moves from frame to frame in the pixel field, the change in the position of the reference feature can be calculated. An error function is calculated based on the change in the reference feature position and the command to galvanometer 320 to minimize the error function. In this configuration, the optical line of sight is always centered on the treatment spot, which is located at fixed coordinates in the camera pixel field. The apparent motion from repositioning galvanometer 320 would be to move the eye image relative to the fixed treatment spot.

Fig. 3B illustrates 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 eye tracking subsystem is located behind the galvanometer 320.

In this embodiment, the treatment laser beam travels to a galvanometer arrangement 320 comprised of galvanometer 1210 and galvanometer 2212. The light beam then passes from the galvanometer device 320 to the color separator 208. At the color separator 208, the laser beam travels to focusing optics 216 and ultimately to the patient's eye 140.

Also provided in this embodiment is a control and monitoring system that is generally comprised of a computer 310, a video monitor 312, and a camera 308. Camera 308 provides monitoring of the laser beam at color separator 208 via lens 306. Camera 308 transmits its feed to computer 310. The computer 310 is also operable to monitor and control the galvanometer device 320. The computer 310 is also coupled to a video monitor 312 to provide a user or operator with a real-time feed from the camera 308.

Here, the eye image is shown centered on the pixel field. When eye motion is detected in the pixel field, the galvanometer 320 is repositioned to move the treatment spot to a new position in the pixel field corresponding to the movement of the eye, and a desired fixed position relative to the eye reference feature.

With reference to the aforementioned biofeedback loop, in some embodiments, eye tracking includes using a light source to generate an infrared illumination beam that is projected onto an artificial reference affixed to the eye. The infrared illumination beam is projected near the visual axis of the eye and has a spot size on the eye greater than the reference and covers an area as the reference moves with the eye.

In some embodiments, the reference has a retro-reflective surface that produces an order of magnitude stronger backscatter than would be produced from the eye. The optical collector can be configured and positioned at a distance from the eye to collect this backscattered infrared light to form a reference bright image spot at a selected image location.

The bright image spots appear on a dark background, with a single element positioning detector located at a selected image position to receive the bright image spots, and configured to measure a two-dimensional position of a reference bright image spot on the positioning detector. The circuitry may be coupled to the positioning detector to generate a positioning signal indicative of a position of the reference from a centroid of the bright image spot based on a two-dimensional position of the measured bright image spot on the positioning detector.

Fig. 3C illustrates an exemplary camera correction system according to an embodiment of the present disclosure. In an example embodiment, the top row illustrates the camera focus position after the galvanometer has been used, and the bottom row illustrates the camera focus position before the galvanometer. Various landmarks (landmark) 392 can be seen in the exemplary embodiment, including capillaries, irises, pupils, etc. Treatment spots 394 are also seen in each example.

As shown in the exemplary embodiment, the top rows of focus before the galvanometers each show the pupil as the center pixel of each image. Compensation after the galvanometers in the bottom row allows the treatment spot 394 to maintain a focus of the camera's attention in each image and thereby allow the system to remain in place during the associated procedure.

Fig. 3D illustrates an exemplary flowchart 330 of a camera-based eye tracker process according to an embodiment of the present disclosure.

In general terms, the figure represents the use of a CCD or CMOS camera to capture an image of the eye. The image data is transmitted to a computer where key features are segmented/extracted (e.g., blood vessels, iris features, edges of the pupil). The image is stored as a reference frame. Subsequent images are then compared to the reference frame. After comparing the reference features in the pixel coordinates, a shift is calculated. Conversion of the pixel coordinates to the scanning system coordinates then occurs before commanding the scanning system to deviate the treatment beam line from the site to restore the relationship with respect to the reference feature. If the shift is too large or out of range of the scanning system, the process is stopped and steps are taken to reacquire the target image field.

As explained in more detail with reference to each step, according to some embodiments, an initialization or start sequence entails capturing image frames in step 332 before processing the captured image frames in order to extract features in step 334. The captured frame with the extracted features is then used to set the reference frame in step 336.

After setting the reference frame, step 338 includes capturing an additional image frame referred to as the current frame. The image or current frame is processed in step 340 to extract features. Step 342 includes comparing the current frame with the reference frame set in step 336. Image shifts between the current frame and the reference frame are calculated to determine differences between the frames. Comparison with the preset threshold allows the system to determine if the image shift exceeds the preset threshold and stop the process at this point by going to step 352.

If the image shift does not exceed the preset threshold and is therefore not too large, the system calculates a compensation level in step 346 in order to compensate for the change or shift between the current frame and the reference frame. In step 348, the compensation level is calculated as physical coordinates used by the scanner. The scanner is then commanded to compensate using the coordinates in step 350. After this compensation step 338 occurs and another current image frame is captured, and the loop continues.

Fig. 4A illustrates an exemplary laser treatment system 400 according to an embodiment of the present disclosure. In the exemplary embodiment, laser treatment system 400 includes a treatment laser 202 that emits a laser beam that travels through a relay lens 204 to a color separator or inverter (flip-in) 208. The visible deposition laser 206 emits a laser beam that also travels to a color separator or inverter 208. In some embodiments, the beams from the treatment laser 202 and the visible deposition laser 206 may meet at the first color separator or inverter 208 simultaneously. In other embodiments, the light beams may arrive at the first color separator or flipper 208 at staggered times.

The one or more light beams exit the first color separator or flipper 208 and travel to the second color separator 208. One or more light beams exit the second color separator 208 and travel to the galvanometer 210. Galvanometer 1210 may include a mirror that rotates through a galvanometer device to move the laser beam. One or more beams of light exit the galvanometer 210 and travel to the galvanometer 2212, and the galvanometer 2212 may be a similar device as the galvanometer 1210. One or more beams of light exit the galvanometer 2212 and travel to the color separator (visible/IR) 214. The operator 160 may monitor one or more light beams at the color separator (visible/IR) 214 by using the surgical microscope 150. One or more light beams travel from a color separator (visible/IR) 214 through focusing optics 216 to the patient's eye 140.

In fig. 4A, additional monitoring elements are provided for use by an operator 160 to assist in a medical procedure. In accordance with the present invention, the depth control subsystem 302 assists in controlling the depth of the ablation process and receives input from the second color separator 208. Fig. 4A- (1-10) illustrate how micro/nanopores may be used to remove surface, subcutaneous, and interstitial tissue and affect ablated target surface or surface, interstitial, biomechanical properties (e.g., planarity, surface porosity, tissue geometry, tissue viscoelasticity, and other biomechanical and biorheological properties) of the target tissue.

Similarly, in accordance with the present invention, the eye tracker 304 helps track landmarks on the patient's eye 140 during medical procedures and receives input from the second color separator 208. In the example embodiment shown, another color separator 208, the color separator 208 separates the light beam, with the output going to an eye tracker 304 and a depth control subsystem 302.

Fig. 4B illustrates an exemplary laser treatment system including an ablation hole depth in accordance with an embodiment of the present disclosure. Fig. 4B-1 generally shows that the treatment laser beam travels to the color separator 208 before traveling to the galvanometer 1210, then through the focusing optics 216 to the galvanometer 2212, and to the patient's eye 140. As indicated above, fig. 4A- (1-10) illustrate how micro/nanopores may be used to remove surface, subcutaneous, and interstitial tissue and affect the surface, interstitial, biomechanical properties (e.g., planarity, surface porosity, tissue geometry, tissue viscoelasticity, and other biomechanical and biorheological properties) of an ablated target surface or target tissue.

OCT system 404 is an optical coherence tomography system for obtaining subcutaneous images of the eye. As such, when coupled to computer 310 (which computer 310 is coupled to video monitor 312), OCT system 404 provides the user or operator with the ability to see a subcutaneous image of tissue ablation; the hole ablation may be between 5% and 95% of the sclera thickness, with an average sclera thickness of 700 μm, and typical hole depths may be orders of magnitude greater than refractive surface ablations that are about 200-300 um deep. This is a significantly greater depth than other surface refractive ablation procedures, which are typically between 10 um-45 um and typically >120 um on average depth.

In at least some embodiments, OCT provides a real-time intra-operative view of the depth level in tissue. OCT can provide image segmentation to identify the scleral internal boundaries to help better control depth. As indicated above, fig. 4A- (1-10) illustrate how micro/nanopores may be used to remove surface, subcutaneous, and interstitial tissue and affect surface, interstitial, biomechanical properties (e.g., planarity, surface porosity, tissue geometry, tissue viscoelasticity, and other biomechanical and biorheological properties) of an ablation target surface or tissue.

In some embodiments, the OCT system 404 uses an OCT measurement beam that is injected into the treatment beam line of sight via a dichroic beam splitter 208 located before the scanning system. In this manner, the OCT system line of sight is always centered on the hole being ablated. The OCT system is connected to a computer 310 for processing the image and for controlling the laser.

In some embodiments of the invention, an anatomical avoidance subsystem is provided to identify key biological obstacles or locations (e.g., blood vessels and others) during surgery. In this way, subcutaneous visualization may be provided to identify obstacles in the procedure that are desired to be avoided, such as blood vessels or anatomical structures.

Fig. 4A-5 and 4B illustrate exemplary simplified views of ablation holes in the sclera, showing examples of depths of ablation associated with the inner boundary of the sclera.

Figure 5 illustrates an exemplary flow diagram of OCT-based depth control 410 according to an embodiment of the present disclosure.

Typically, OCT systems perform repeated B-scans in synchronization with the laser. The B-scan shows the top surface of the conjunctiva and/or sclera, the boundaries of the ablated holes, and the bottom interface between the sclera and the choroid or ciliary body. Automated image segmentation algorithms may be employed to identify the top and bottom surfaces of the sclera (typically 400-. The distance from the top surface of the sclera to the bottom surface of the aperture is automatically calculated and compared to the local thickness of the sclera. In some embodiments, this occurs in real time. When the aperture depth reaches a predetermined number or fraction of the scleral thickness, ablation stops and the scanning system is indexed to the next target ablation location. In some embodiments, the image may be segmented to identify an inner scleral boundary.

Referring to the steps in the figures, in an example embodiment, the beginning or initialization set of steps occurs first. This starting set of steps begins with locating the hole coordinates in step 412. An AB scan of the target area occurs in step 414. The scan produces an image that is processed in step 416 to segment and identify the scleral boundary. The distance between the conjunctival surface and the scleral border is then calculated in step 418.

After completing this starting set of steps, ablation is started in step 420. A laser beam pulse is emitted in step 422 and then a B-scan is performed in step 424. The B-scan produces an image, which is then segmented in step 426, and the hole depth and ablation rate are calculated from the image. In step 430, the hole depth and ablation rate are compared to a target depth. If the target depth has not been reached, the process loops back to step 422 and repeats. Upon reaching the target depth, step 432 stops the ablation process, and the start process begins again at step 434 with locating to the next hole coordinate. In some embodiments, the OCT system can monitor ablation depth during a single pulse, and as a risk mitigation means can stop ablation, if the procedure is out of range, there can also be other internal procedures that can end the run of ablation; beyond the eye tracking operation limit, beyond the # of the maximum preset pulse, the laser power monitoring is not within the limit. All of this is a risk mitigation measure.

Fig. 6 illustrates an exemplary laser therapy system assembly diagram 600 showing the relationship of the relevant subsystems, in accordance with an embodiment of the present disclosure.

In general, laser treatment system assembly diagram 600 shows a laser 602, laser delivery fiber 120, laser control system 604, monitoring system 608, and beam control system 606.

The laser 602 is typically made up of several subsystems. In an example embodiment, these subsystems include system control electronics 104, Er: YAG laser head 612, laser cooling system 108, HV power supply 110, and system power supply 112. The foot pedal 114 provides some control for the system user. The laser 602 transmits the laser beam to the beam control system 606 via the laser transmission fiber 120.

The beam steering system 606 is generally comprised of beam delivery optics 624, a red spot laser 626, a galvanometer 628, beam delivery optics 630, and active focusing 632.

Laser control system 604 maintains a link with laser 602 via laser synchronization and with beam control system 606 via power control position states. Laser control system 604 is generally comprised of a user interface 614, a power supply 616, a galvanometer controller 618, a galvanometer controller 620, and a microcontroller 622. The laser control system 604 is also operated via a joystick 610.

The monitoring system 6081 s may generally consist of a CCD camera 634 and a vision microscope 636.

In some embodiments, a fiber laser is used, which consists of an undoped cladding and a higher refractive doped core. The laser beam travels through an optical fiber guided within the core and experiences high magnification due to the length of the interaction. Fiber lasers are considered advantageous over other laser systems because they have, among other qualities, simple thermal management properties, high beam quality, high electrical efficiency, high optical efficiency, high peak energy, require, among other things, low maintenance, have superior reliability, no mirrors or beam path alignment, and they are lightweight and generally compact.

In some embodiments of the invention, a spot array may be used so as to ablate multiple holes at a time. In some cases, these spot arrays may be created using microlenses, and are also affected by the properties of the laser. Larger wavelengths may result in a smaller number of spots with increased spot diameters.

Turning to fig. 7, an exemplary laser treatment system 700 is shown in accordance with an embodiment of the present invention. Laser treatment system 700 may generally consist of a control system 702, optics, and a beam controller.

Control system 702 includes monitor 704 and monitor 2706, as well as keyboard 708 and mouse 710, to provide a user with the ability to interact and control with a host computer 724 running a computer program. In many embodiments, the computer programs running on host computer 724 include control programs for controlling the visible deposition laser 712, laser head 714, laser cooling system 716, system power supply 718, laser power supply 720, and beam delivery optics 722.

Also provided in this embodiment are a depth control subsystem 726, a galvanometer 728, a CCD camera 730, a vision microscope 732, a focusing subsystem 734, and beam delivery optics 736.

Fig. 7-1 illustrates another exemplary laser treatment system.

In many embodiments, preoperative measurement of ocular properties and customization of treatment to the needs of individual patients are beneficial. Preoperative measurements of ocular properties may include measuring intraocular pressure (IOP), scleral thickness, scleral stress/strain, anterior vasculature, accommodation response, and ametropia. The measurement of scleral thickness may include the use of Optical Coherence Tomography (OCT). Measurements of scleral stress/strain may include the use of brillouin scattering, OCT elastography, photoacoustics (light plus ultrasound). Measurement of the anterior vasculature may include the use of OCT or doppler OCT. Measurement of refractive error may include the use of products such as the iTrace brand products from Tracey technologies.

The intraoperative biofeedback loop may be important during the procedure in order to keep the physician informed about the progress of the procedure. Such feedback loops may include the use of topography to measure and monitor "distant" regions, such as the anterior ciliary artery.

The biofeedback loop may include a closed loop sensor to correct for non-linearities in the piezoelectric scanning mechanism. In some embodiments, the sensors may provide real-time position feedback within milliseconds and utilize capacitive sensors for real-time position feedback. Real-time position feedback may be transmitted to the controller, and laser operation may be stopped intra-operatively upon identification of a particular biometric based on tissue characteristics.

The sensor/feedback device may also perform biological or chemical "smart sensing" to allow ablation of the target tissue and protect or avoid surrounding tissue. In some cases, such intelligent sensing may be achieved through the use of a biochip incorporated in a housing that is activated by light illumination and senses the position, depth, size, shape or other parameter of the ablation profile. Galvanometer optical components are also contemplated in some embodiments and may be used to measure multiple parameters of laser steering and special functions.

In some embodiments, the described systems, methods, and devices may include image display transmission and GUI interface features, which may include capturing each image frame and sending information to a video display after each shot within a 3-dimensional-7-dimensional microwell before and after the shot of laser light in dynamic real-time and surface views. The GUI may have an integrated 7-way multi-view system for image capture, including: surface, internal well, external well, bottom of microwell, whole eye view, target array region.

In some embodiments, a 7 cube may be the preferred projection of the microprocessor, but other examples exist in the shape of a dimensional sphere, which is integrated into the GUI and microprocessor. The orthogonal projection may include an example as shown in fig. 8.

SVM pattern recognition is integrated into an AI (artificial intelligence) network directed to the microprocessor path. For the non-linear classification problem, the SVM will transform the input space into a higher dimensional space by a non-linear mapping K (X). Thus, the non-linear problem will translate into a linear problem, and then the optimal separation hyperplane will be calculated in the new high dimensional space using Matlab or Mathematica integration programming. Since the optimization function and the classification function only involve the inner products between the samples (xi-xe), the high-dimensional space of the transform is also only the inner products (k (xi) -k (xe)). If kernel function K (xi-K (xe) satisfies the Mercer condition, it corresponds to a transformation space of inner product K (xi, x = (K (xi) -K (x)). common kernel functions include a linear kernel polynomial kernel and a radial bias kernel.

In some cases, the mapping and optimization formulas for machine learning may include:

tools for GUI interfaces and code may include multidimensional scaling, linear discriminant analysis, and linear dimension reduction processing, and local linear embedding and isometric mapping (isomat) also include nonlinear dimension reduction methods.

Continuous mapping that satisfies homotopy (homotopy) lifting properties for any space may be usedp：E→B. Fiber bundles (on a clenching base) constitute an important example. In homotopy theory, any mapping is 'as good as fiberization' -i.e., any mapping can be decomposed into a "mapping path space" as homotopy equivalent, and then fiberized into homotopy fibers.

By definition, the fibers areEA subspace of which isBPoint of (2)bThe inverse of (c). If the foundation spaceBAre paths are connected, the result of the definition is two different points in Bb ₁Andb ₂is homotopically equivalent. Thus, people often say "fiber"F。

Some embodiments may utilize Serre or weak fibrosis. They are able to generate a map of each cylindrical microwell in the array and the entire array across the 3D surface, as well as an interstitial map of the array of wells in the cross-section. An exemplary 3D map 900 is shown in fig. 9.

FIG. 10 illustrates an exemplary design pattern that may be performed as follows. Step 1001: treatment design/planning begins with an organizational hierarchy that is built using 7-sphere mathematical projections over the entire sphere to build a congruential treatment platform (concount point treatment platform) based on 7D shapes and hyperbolic planar tessellation. Step 1002: off-axis mathematical algorithms derived from tissue levels and Fibonacci patterns are displayed as mathematical images. Step 1003: algorithm code is then implemented to develop a customized micropore pattern that reflects the tissue biorheology, including all inputs for stiffness, viscoelastic modulus, topology, topography, biometrics, etc. Step 1004 (not shown): anatomical avoidance software may be executed to erase or eliminate non-targeted fields, arrays, regions. Step 1005 (not shown): the surgeon/user may also manipulate the target area or non-target area via the touch screen interface.

In some embodiments, the described systems, methods, and devices may include the following functionality of a laser user interface system to provide a treatment algorithm. The real-time mathematical images are both merged and displayed in a 3D mathematical file, which may also run in GIF animation format to display a priori information about the validity of the array. The workstation/algorithm works with the VESA system to generate mathematical images for the user/surgeon for the desired configuration of the 3D array on the eye. The topological representation of the image is stereoscopically projected to a display. The array is a pre-specified set of formulas and, in addition, can be modeled in Fibonacci sequencing with a variety of densities, spot sizes, microwell and nanopore geometries and configurations. The benefit of Fibonacci sequencing is to produce the most balanced set of array formulas, which correspond to the body's own natural tissue hierarchy on both the macro and micro scales.

The array may also follow a hyperbolic geometric model or uniform (regular, quasi-regular or semi-regular) hyperbolic tiling, which is the edge-to-edge fill of a hyperbolic plane with regular polygons as faces and vertex transitionable (transitive on its vertices, equiangular, i.e., there is an isometric map that maps any vertex to any other vertex). Examples are shown in fig. 10 and 11. Thus, all vertices are congruent and the tiling has a high degree of rotational and translational symmetry.

The following example represents a heptagonal tile with 3 heptagons around each vertex, which is also regular, since all polygons are of the same size, it may also be given the Schläfli notation.

Uniform tiling can be regular (if also face and edge pass), quasi-regular (if edge pass but not face pass), or semi-regular (if neither edge pass nor face pass). For right triangle: (p q2) There are two regular tiles, which are symbolized by a Schläflip，qAnq，pRepresents it.

An exemplary model is illustrated in fig. 11.

In some embodiments, the described systems, methods, and apparatus may include a mechanism to produce an array of microwells in a controlled non-uniform distribution, or a uniform distribution or a random distribution, and in at least one of a radial pattern, a spiral pattern, a lobed pattern, an asymmetric pattern, or a combination thereof. According to the present disclosure, the lobed spiral pattern may have clockwise and counterclockwise diagonal lines (diagstichy). Fig. 12 illustrates an exemplary schematic representation 1200 of creating an asymmetric controlled distribution of an array algorithm pattern on an eye having a helical leaf-like axis, where each array of microwells appears sequentially. R₀Is the radius of the region corresponding to the center of the meristem, around which micropores are generated. Large vertical arrows indicate vertical pore expansion in the array, while the laterally depicted arrows indicate spatial expansion of the system of new pores. i and j are pairs of consecutive Fibonacci numbers, i.e. such a pair of consecutive Fibonacci numbers is denoted by (i, j). The symbols n, n-i, n-j, n-i-j represent numbers representing the order of appearance of the microwells along the generated helix during expansion of the array. However, they may be better represented by n, n + i, n + j, n + i + j. Within the same family of secondary helices there are consecutive numbers that show a constant difference between them. Thus, for the counter-clockwise family: (n + i) -n = i, which is the Fibonacci number. (n + i + j) - (n + j) = i, which is the same number of Fibonacci. For the clockwise family: (n + j) -n = j, which is the second Fibonacci number. (n + i + j) - (n + i) = j, which is the same number of Fibonacci. Thus, here we have a (i, j) lobed case.

In some embodiments, the microwell array pattern is one of an archimedean spiral, an euler spiral, a fermat spiral, a hyperbolic spiral, a chain spiral, a logarithmic spiral, a Fibonacci spiral, a golden spiral, or a combination thereof.

In some embodiments, the described systems, methods, and apparatus may include creating a 3D micropore model on a sphere. Fig. 13 illustrates an exemplary graphical image 1300 created on a CAD program of an exemplary embodiment of microwells, wherein the pattern has a mechanism to create and expand an array of microwells in the radial and lateral directions using an o-lobed spiral to expand the array face-to-face and edge-to-edge while dominating (mainline) non-uniform distributions with divergence angles consistent with Vogel models and Fibonacci sequences, wherein X microwells are created at multiple densities, sizes and geometries in accordance with the present invention. Although the exemplary embodiment is the anterior or posterior sclera of the eye, it may also be the cornea.

In some embodiments, the described systems, methods, and devices may include utilizing Fibonacci and mathematical parameters to optimize surgical performance, outcome, and safety in laser assisted micropore therapy arrays having patterns of micropores/nanopores, where the patterns are non-uniformly distributed patterns that are transmitted in cross-sectional tissue in registration with existing tissue levels on both a macro-scale and a micro-scale such that there is a congruent rejuvenation effect of the therapy. The therapeutic array or lattice having a plurality of micropores/nanopores/ablations/incisions/targets may be arranged in a non-uniform distribution pattern, wherein the pattern is helical or lobed. The pattern may be described by the Vogel equation. Additionally, included are a variety of other geometries/densities/depths and shapes having a spiral or lobed pattern of flow paths, such as in the form of open channels or pores. The micropores/nanopores may be particularly adapted to correspond to any given contact lens, cover, or other template material or design having a non-uniform distribution pattern. Alternatively, microperforations may be used in combination with conventional perforation-coated or uncoated polymers (such as hydrophilic or hydrophobic types). An array pattern having a non-uniformly distributed pattern of micro-holes and a lens or cover may be used together as a treatment system

As indicated above, fig. 4A- (1-10) and fig. 26-3A illustrate how micro/nanopores may be used to remove surface, subcutaneous, and interstitial tissue and affect surface, interstitial, biomechanical properties (e.g., planarity, surface porosity, tissue geometry, tissue viscoelasticity, and other biomechanical and biorheological properties) of an ablation target surface or tissue of interest. In addition, the present disclosure includes various types of automated processing systems to process the provision of microwells of various compositions and configurations.

The tissue properties affected include porosity, texture, viscoelasticity, surface roughness, and uniformity, among others. Surface characteristics (such as roughness and gloss) are measured to determine quality. Such micro-pores may also affect tissue deformation, flexibility and flexibility, and have a "orange peel" texture. Thus, the properties of the tissue treated with the micropores/nanopores will generally affect and/or improve tissue quality by restoring or rejuvenating the biomechanical flexibility of the tissue at rest and under stress/strain.

As shown below, the microwell pattern may have a plurality of clockwise spirals and a plurality of counterclockwise spirals, wherein the number of clockwise spirals and the number of counterclockwise spirals are Fibonacci numbers or multiples of Fibonacci numbers.

Fig. 14A illustrates an exemplary embodiment of a micropore pattern that can be implemented directly on a target tissue, or alternatively on a contact lens, a mask, or other such template having a micropore pattern with a controlled, non-uniform distribution of micropores in a distribution of a Fibonacci sequence, according to some embodiments of the present disclosure.

Fig. 14B is an exemplary illustration of a lobed spiral pattern with clockwise and counterclockwise skew lines, according to some embodiments of the present disclosure.

Fig. 14C is another exemplary illustration of a lobed spiral pattern having clockwise and counterclockwise skew lines, according to some embodiments of the present disclosure.

FIG. 14D is an exemplary illustration of a Vogel model according to the present disclosure. The Vogel model includes a pattern of florets. In short, each floret is oriented at 137.5 ° towards the next floret. The number of left and right helices is the Fibonacci number. In a typical sunflower, there are 34 in one direction and 55 in the other.

15A-15F are exemplary illustrations of lobed spiral patterns conforming to Vogel models with different divergence angles according to the present disclosure.

FIGS. 16A-16N are exemplary illustrations of exemplary embodiments of microwells derived from icosahedron pattern shapes according to the present disclosure

Fig. 17A-17B, fig. 2K- (18-19) are exemplary illustrations of microwell patterns derived from icosahedron pattern shapes representing fractal spheres and icosahedron/tetrahedron tessellation, according to the present disclosure.

In some embodiments, the exemplary micro-hole patterns shown in fig. 14A-17B above may be pre-drilled into a contact lens or cover. Fig. 18 discloses a contact lens/eye shield cooperating with the micro-hole pattern of fig. 18.

FIGS. 2K1-2K 17; add 3D eye 2 slide illustrates an exemplary embodiment of a microwell pattern having a plurality of microwells of multiple densities and multiple spot sizes according to the present invention

Fig. 2K-20 are exemplary graphic images of exemplary embodiments of micro-holes having a pattern of 41 micro-holes according to the present invention.

Fig. 14A-14D are exemplary illustrations according to exemplary embodiments of the present invention. Sunflower patterns have been described by a Vogel model, which is a type of "Fibonacci helix" or a helix with a fixed Fibonacci angle (which equals 137.508 °) where the divergence angle between successive points is close to the golden angle.

The Vogel model as mentioned is φ =n*a，r=c√nWhere n is the rank number of the floret counting outwards from the center, phi is the angle between the reference direction and the position vector of the nth floret in the polar coordinate system originating at the center of the floret such that the divergence angle α between the position vectors of any two consecutive florets is constant and, with respect to the sunflower pattern, at 137.508 deg., r is the distance from the center of the floret to the center of the nth floret, and c is a constant scaling factor, see fig. 41.

In some embodiments, the microwell pattern may be described by a Vogel model, where n is an ordered number of microwells counted outward from the center of the microwell pattern, φ is an angle between a reference direction and a location vector of an nth microwell in a polar coordinate system derived from the center of the microwell pattern, such that the divergence angle between the location vectors of any two consecutive microwells is a constant angle α, r is the distance from the center of the microwell pattern to the center of the nth microwell, and c is a constant scaling factor.

In some embodiments, all, substantially all, or a portion of the micro-holes of the micro-hole pattern will be described by (i.e., conform to) the Vogel model. In some embodiments, all of the micro-holes of the micro-hole 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 microwells can be described by a Vogel model.

Surface area: the total target tissue surface area affects the amount of total tissue material removed. Generally, as the amount of total tissue surface area increases, the amount of surface material removed also increases. In some embodiments, the total micropore surface area of the target tissue is equal to the total potential surface of the micropore system (i.e., the micropore target area if there are no micropores) minus the total micropore area (i.e., the sum of the areas of all micropores). Thus, depending on the amount of microporous area desired, the amount of total microporous surface area may vary from 1% to about 99.5% of the total potential surface area. See fig. 30.

Depth: referring back to fig. 4A- (5-10), they illustrate that the total target tissue depth affects the amount of total tissue material removed. Generally, as the amount of total tissue depth increases, the amount of interstitial or subcutaneous tissue removed also increases. In some embodiments, the depth of the removed tissue microwells is equal to the total potential subcutaneous and interstitial tissue of the microwell system (i.e., total interstitial and subcutaneous tissue if there are no microwells) minus the total microwell cubic volume (i.e., the sum of the areas of all microwells). Thus, depending on the amount of microporous cubic volume desired, the amount of total microporous cubic volume can vary from 1% to about 95% of the total potential subcutaneous and interstitial cubic volume of microporous tissue.

Density of micropores: the density of the microwell array affects the total amount of microwell area and the total amount of surface, subcutaneous, and interstitial volume removed. It also affects the total number of micropores and the micropore distribution. Various density configurations, pore sizes, and distributions of pores are examples of the invention. The micropores may be provided randomly, uniformly or individually. See FIGS. 2K-1- (A-C) to 2K-17.

Number of micropores: the number of micropores affects the total amount of micropore area and the amount of total surface, subcutaneous and interstitial volume removed. Additionally, the number of micropores affects the density and distribution of micropore coverage on the surface of the micropore system, which in turn directly affects the total volume extraction of the micropore system. In 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 microwells is at least about 45, at least about 96, at least about 151, and at least about 257. For the above and below parameters see also fig. 31-34, 37, 38, 39.

In some embodiments, the number of pores may vary from 36 to 10000 depending on the size of the spot, which may vary from 1nm-600 um. The number of micropores may be within a range including any pair of the previous upper and lower limits. See fig. 41.

In a method of a micro-pore system for delivering laser pulses to target tissue, the divergence angle α is increased or decreased to affect how the micro-pores are placed within the pattern and the shape of the clockwise and counterclockwise spirals the divergence angle is equal to 360 divided by a constant or variable value, thus the divergence angle may be a constant value, or it may vary, in some embodiments the pattern has a divergence angle in polar coordinates that varies from about 100 ° to about 170 °. it has been observed that small variations in the divergence angle may significantly change the array pattern, and may show leaf-like patterns that differ only in the value of the divergence angle, the divergence angle may be 137.3 °. the divergence angle may also be 137.5 °, 137.6 °. in some embodiments the divergence angle is at least about 30 °, at least about 45 °, at least about 90 ° or at least about 120 °. in other embodiments the divergence angle is less than 180 °, such as no greater than about 150 °, the divergence angle may be in a range including any pair of the upper and lower limits of the previous embodiments, the divergence angle is determined by a ratio of between about 137 ° and 140 ° (such as between about 360 ° -140 °. 360 °. a divergence angle determined by dividing a ratio between about 360 ° (see figure) between about 360 ° -138 ° -139 ° and about 138 ° (in some other embodiments, 140 ° -137.6 embodiments, between 137.3 °. 137.

Distance to edge of microwell array: in some embodiments, the overall size of the array pattern may be determined based on the geometry and intended use of the microwell system. The distance from the center of the pattern to the outermost microwell may extend to a distance bordering the edge of the microwell system. Thus, the edges of the outermost microporous system may extend to or intersect the edges of the micropores. Alternatively, the distance from the center of the pattern to the outermost micro-holes may extend to a distance that allows a certain amount of space between the edge of the outermost micro-hole system and the edge of the micro-holes to be free of micro-holes. The minimum distance from the edge of the outermost microwell may be specified as desired. In some embodiments, the minimum distance from the edge of the outermost microwell to the outer edge of the microwell system is a specific distance, identified as a discrete length or as a percentage of the length of the face of the microwell system on which the array pattern appears.

The size of the micropores: in some embodiments, the size of the microwells is determined, at least in part, by the total amount of array area desired for the microwell 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 micropores is constant. In some embodiments, the size of the micro-holes varies with the distance of the micro-holes from the center of the pattern. The pore size can vary from 1nm to 600 um. In some other embodiments, the sizes are 50 μm, 100 μm, 125 μm, 200 μm, 250 μm, 325 μm, 425 μm, and 600 μm.

Shape of the micropores: the shape of the micropores themselves created in connective tissue by electromagnetic radiation has a relative impact on tissue response and wound healing. A square shape heals more slowly than a circular shape. The microwell system is capable of producing a single microwell shape of multiple geometries. In some embodiments, the ideal shape is a square.

The shape is also influential in microwell arrays. The amount of coverage may 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 microwells can be in the form of slits, regular polygons, irregular polygons, ellipsoids, circles, arcs, spirals, channels, or combinations thereof. In some embodiments, the array of microwells has a circular shape. In some embodiments, the shape of the array may be in the form of one or more geometric patterns, preferably an icosahedral or tetrahedral tessellation, in which a plurality of polygons intersect.

Fig. 16A-N show examples of such shaped microwell arrays. The array of microwells is configured such that the pattern resembles a polygon, which may have somewhat precise edges. Tissue removal in these configurations affects biomechanical properties in a mathematically and geometrically balanced manner, resulting in stability to the system.

See also fig. 31-35 for various factors.

Design factors are as follows: design factors influence the overall placement of the microwell array or lattice in 3D tissue, as well as the location relative to the edge of the microwell in relation to the 'environment' within the tissue. The design of the micropores can be adjusted according to the inherent shape of the tissue itself or around the expected physiological anatomy or the impact desired. This may be from dual (infinite) regular euclidean honeycombs, dual polyhedrons, 7 cubes, 7 orthogonal or identical simple lattices, Bravais lattices or non-Bravais lattices;

scale factor: the scale factor affects the overall size and dimensions of the microwell array pattern. The scaling factor may be adjusted such that the edge of the outermost micro-well system is within a desired distance of the outer edge of the micro-well. In addition, the scaling factor may be adjusted such that the inner edge of the innermost micro-pore system is within a desired distance of the inner edge of the micro-pore. Duality can be generalized to n-dimensional spaces and dual polyhedrons; in two dimensions, these are called dual polygons, or dimensions of multiple dimensions of three dimensions or triangles containing vertices, arrays, or both isotropic and anisotropic as well.

Distance between nearest neighboring micropores: in addition to considering the number and size of the micro-holes, the distance between the centers of nearest neighboring micro-holes may be determined. The distance between the centers of any two microwells is a function of other array design considerations. In another embodiment, the shortest distance between the centers of any two microwells is never repeated (i.e., the well-to-well spacing is never the same exact distance). This type of spacing is also an example of controlled asymmetry. In some other embodiments, the shortest distance between the centers of any two microwells is always repeated (i.e., the well-to-well spacing is always the same exact distance). This type of spacing is also an example of controlled symmetry. In some embodiments, the distance between two microwells is randomly arranged (i.e., the well-to-well spacing is random). Thus, the system can provide controlled asymmetry (which is at least partially rotationally asymmetric about the center of the array design or pattern), random asymmetry (which is at least partially rotationally random about the center of the array design or pattern), and controlled symmetry (which is at least partially rotationally random about the center of the array design or pattern) and random symmetry (which is at least partially rotationally random about the center of the array design or pattern).

In some embodiments, the rotational asymmetry extends to at least 51% of the pattern design's micropores. In some embodiments, the rotational asymmetry extends to at least 20 microwells of the array pattern design. In some embodiments, the rotational symmetry extends to at least 51% of the pattern design's micropores. In some embodiments, rotational symmetry extends to at least 20 micropores of the pattern design. In some embodiments, the rotationally random pattern extends to at least 51% of the pattern design's micropores. In some embodiments, the rotational random pattern extends to at least 20 micropores of the pattern design.

In some embodiments, the following equations may be passed: phi =n*α，r=c√nDescribing the aperture pattern in polar coordinates with 51% where n is the order number of the holes counting outward from the center of the hole pattern, #isthe angle between the reference direction and the location vector of the nth hole in the polar coordinate system from the center of the hole pattern such that the divergence angle α between the location vectors of any two consecutive holes is constant, r is the distance from the center of the hole pattern to the center of the nth hole, and c is a constant scaling factor.

Cooperative ocular contact lens/eyeshade

The cooperative ocular contact lens/eyecup (see fig. 27A, 2700, and 40) can be flexible or rigid, soft or rigid. It can be made of any number of various materials, including those conventionally used as contact lenses or eye masks, such as polymers or soft gels of both hydrophilic and hydrophobic or collagen or dissolvable materials or special metals. Exemplary flexible lenses/covers include flexible hydrophilic ("water-loving") plastics.

In some embodiments, the microwell may comprise a plurality of microwell paths arranged in a pattern. The pattern of microporous pathways may include regular polygons, irregular polygons, ellipsoids, arcs, spirals, leaf-like patterns, or combinations thereof. The pattern of micro-pore paths may comprise a radiating arc-shaped path, a radiating spiral path, or a combination thereof. The pattern of micro-pore paths may comprise a combination of an inner radiation spiral path and an outer radiation spiral path. The pattern of gas flow paths may comprise a combination of clockwise and counter-clockwise radiating spiral paths. The microporous pathways may be separate or discontinuous from one another. Alternatively, one or more of the microporous pathways may be fluidically connected. The number of radiating arc-shaped paths ("arcs"), radiating spiral paths, or combinations thereof may vary.

In some embodiments, the microwells may include a pattern that is a controlled non-linear distribution pattern, a controlled linear distribution pattern, or a random pattern. In some embodiments, the ocular contact lens/ocular shield can include a pattern of micropore paths, wherein the pattern of micropore paths is generated according to the x and y coordinates of the controlled non-uniform distribution pattern. The controlled non-uniform distribution pattern used to generate the lens/eyecup aperture paths may be the same or different than the array pattern of the laser aperture algorithm used with the lens/eyecup. In an embodiment, the controlled non-uniform distribution pattern is the same as the array pattern of the laser micro-hole algorithm used with the glasses/eyewear. In some embodiments, the controlled non-uniform distribution pattern is different from the array pattern of the laser micro-hole algorithm used.

In some embodiments, the laser micro-via system may have a leaf-like pattern according to the laser micro-via algorithm embodiments described herein. The glasses/eyecups cooperate with laser microporous systems having a lobed pattern when the laser microporous system comprises a plurality of micropores, a plurality of openings, a plurality of cavities, a plurality of channels, or a combination thereof, the plurality of micropores, the plurality of openings, the plurality of cavities, the plurality of channels, or a combination thereof, configured in a pattern designed to promote improvement of natural biological functions, such as fluid flow, blood flow, muscle movement, and static and dynamic biological functions, through the glasses/eyecups and the tissue having the lobed pattern. The pores, openings, cavities, channels, or combinations thereof may define biological flow paths along, within, or through the support mat, or combinations thereof. In embodiments, the pattern of micropores, openings, cavities, channels, or combinations thereof may be in the form of a regular polygon, an irregular polygon, an ellipsoid, an arc, a spiral, a lobed pattern, or combinations thereof. In another embodiment, the gas flow path may be in the form of a regular polygon, an irregular polygon, an ellipsoid, an arc, a spiral, a lobed pattern, or a combination thereof.

In some embodiments, a suitable spiral or leaf pattern may be generated from the x and y coordinates of any of the leaf array patterns of the microwell system embodiments described above. In an embodiment, the x and y coordinates of the spiral or lobed pattern are transposed and rotated to determine the x 'and y' coordinates of the spiral or lobed support airflow pattern, where θ is equal to π/n in radians, and n is any integer. (x 'and y') may be rendered, such as by using Computer Aided Drafting (CAD) software, to generate a suitable pattern, such as a spiral or leaf pattern.

The pattern may then be used to define a radial precision and spiral path, and an annular path that may intersect the arc and spiral path, or a combination thereof. The annular, arcuate, spiral, or compound channel may be deformed in shape, such as in the form of a groove, cavity, orifice, channel, or other pathway to be formed. Exemplary embodiments of the transposed leaf pattern-based channel pattern are also shown in fig. 10, 13 and 16. Additional exemplary embodiments based on transposed leaf-like patterns are shown in fig. 14A-14D, 15A-15F, and 41.

In some embodiments, the described systems, methods and devices may include methods and devices for treating sclera and adjacent eye structures, as well as partial microperforations and resurfacing, laser eye microperforations for rejuvenation or restoring physiological eye function, and/or for alleviating dysfunction or disease. In various embodiments, the array may employ a plurality of geometries, densities, configurations, distributions, densities, and spot sizes and depths. They may also be planned and executed in advance in various points of time. It may also penetrate the episcleral, scleral parenchyma, or brown layer in any percentage of the desired perforation. Electromagnetic energy applications are also suitable.

Hydrophobic scleral lens wafer customizable, nanometer, mum etc.: in various embodiments, the hydrophobic scleral lens customizable wafer may have variable sizes, typically measured in millimeters, micrometers, or nanometers. Typically, it is a scleral contact lens, which may contain a computer generated customized algorithm for laser treatment of the patient's sclera. First, a retreatable spot may be recorded and the spot may be shaped via a mask or lens (profile). The cover may be made of a variety of materials including one or more hydrophobic polymers or a mixture of polymers that are not penetrable by the laser. In addition to intelligent mapping techniques, this may also provide an increased level of protection for surrounding tissue that will not be treated. The central contact lens may be tinted to protect the cornea from the microscope light and from the laser beam itself. In various embodiments, once the pattern is on the eye, it may be disposable and non-reusable. Alternatively, it may be a pre-packaged sterile container provided.

This may be created by measuring biometrics, morphology, anatomy, topography, keratotomy, scleral thickness, material properties, refraction, light scattering, and other features and qualities that are each imported, uploaded, or otherwise input into a three-dimensional (3D) dynamic FEM module, which is a platform for a "virtual eye". Once all of the optics and information apply the mathematical and physical approach aimed at enhancing accommodation by manipulating the sclera, the system of the present disclosure processes the information of both the cornea and the lens and runs a number of algorithmic tests, and it also gives the desired Zernike profile for the cornea, which will yield the maximum accommodation capacity in the presence of LVC plus accommodation planning. Once completed, the pattern can be generated by ISIS through the virtual eye and there is a visualization of the pattern.

The myeye wafer also marks coordinates at the 12 o 'clock and 6 o' clock meridians for the physician to orient on the eye. The myeye wafer also marks unique and different coordinates at the 10/2/4/7 meridian for the doctor's treatment quadrant orientation. Myeye wafers/contact lenses are produced by respective 3D printers connected to the motherboard of the ISIS. Once completed, the lenses may be sterilized prior to being worn on the patient's eyes.

In some exemplary operations, initially, in some embodiments, a laser, which may be coupled to or contain an eye tracker, is calibrated or activated and the lens is placed in position by the doctor. The wafer acts as both a cap and a guide for the laser.

As shown in fig. 18, the lens design is referred to as "semi scleral contact" (SEQ). The lens has as its starting point the supporting edge of the sclera composed of three curves at the 2.0mm portion of the cornea. The SEQ lens has 10 openings which prevent the lens from getting stuck. Irregular corneal surfaces were corrected using RGP contact lenses, which varied in diameter from 8.0mm to 12.0 mm. The scleral lenses (whether or not there are two) vary in diameter from 22.0mm to 25.0 mm.

To build the lens and final fit, the lens is calculated and produced using formulas. To narrow the entire range, it starts with a sagittal assembly set of 2.70mm, extending to 4.10 mm. The difference in the assembled group is similar to that of the RGP lens with different radii of 0.05mm between the normal steps.

The SEQ assembly group expired with a height difference of 0.1mm sagittal. Despite a DK value of 90 (at request 125) and 10 times SEQ lens opening, the oxygen supply problem persists. Lenses adjusted to be greater than 12.0mm in diameter have much support so that they do not move and therefore no tear exchange can occur.

In some exemplary operations, 1) the lens is placed in position by the doctor since the laser contains an eye tracker. The wafer acts as both a cap and a guide for the laser. 2) The wafer guidance system is unique to the laser; the pattern is placed on the eye and passed through the lens itself, which is perforated during the procedure, resulting in a map of the procedure receiving and all spots recorded by the scanner before and after treatment. 3) ISIS retains this information for the particular patient's eye, 4) in cases where re-treatment is required. All information (topology, etc.) is imported back into the patient's profile for ISIS recalculation and reconfiguration of ' surrounding ' existing blobs for further maximization. 5) ISIS always calculates COP before applying the simulation and calculates predictable COP after applying the simulation, which can inform the patient and surgeon on the amount of possible COP for any particular patient with or without additional LVC. 6) ISIS also demonstrates visual simulation at all distances, both biomechanical functions, optical functions, and by using FEM virtual eyes. 7) ISIS also shows COP, AA, refraction, Zernike profile changes, etc. after operation and continues to capture all database information on the back-end to present more sophisticated and optimized algorithms in the future. 8) ISIS may also dissect various algorithms to enhance understanding of the bi-optic system and to give varying solutions with age based on scleral thickness and other biometric, geometric, optical, etc. The usefulness of this is unlimited, but a particular embodiment is that ISIS can generate an age-related treatment map from the patient's initial examination to the age of the cataract. Thus, the ISIS can predict in advance how many spots and what pattern should be used so that the potential area will be 'determined' on the first wafer by the ISIS to be retreated. This means that at a subsequent visit, when there is a critical loss of COP, ISIS can alert the physician and re-treatment can be started at any time (this will be determined by the physician, patient and ISIS output). 9) ISIS also has audible interaction and if there is a need for intervention, it may also alert the physician during treatment when the intervention is complete and guide the physician as to what examinations should be evaluated for accuracy or for more attention. ISIS may suggest to the physician but the physician controls the selection of the procedure that is to be performed by ISIS, 10) ISIS also has a reference list and may search for papers, knowledge and also recent trends. 11) ISIS looks like SirI for a reference.

Laser features for certain embodiments include Er: a Yag ophthalmic laser medium, may include Er having a wavelength of 2.94 μm: a YAG laser; pulse duration about 250 microseconds; the repetition rate was 3, 10, 15, 20, 25, 30, 40, 50 pps.

Various net absorption profiles of various tissue components may be important. At 2.94 μmThe wavelength laser may be a wavelength closest to a peak absorption of H203.00 μm in the near infrared spectrum. This allows it to efficiently vaporize H20 from the tissue with little thermal effect (ablation mechanism). Laser tissue interaction @2.94 μm: early researchers recognized that 2.94 μm would be a large wavelength for tissue ablation; at 10.6 μm, the water uptake is CO₂10-20 times of the total weight of the composition; at 2.79 μm, the water uptake is Er: 3 times that of YSGG; at 2.94 μm, the ablation threshold of water is about 1J/cm². Ablation occurs immediately and may be a surface effect only. This provides very precise ablation with little collateral tissue damage.

Er: applications of the Yag ophthalmic system may include wide 510K for ablation, incision, and vaporization of soft eye tissue, and therefore extended use is inevitable after the system is employed, including in: ptyerigium surgery; glaucoma surgery; ocular neuron entrapment (posterior sclera); an intraocular capsulotomy; surgery of soft tissue outside the eye; AMD; and others.

Methods and devices for treating scleral and adjacent ocular structures as well as partial microperforation and resurfacing are also contemplated.

As described herein, a system and method for performing partial surface reconstruction of a target region of an eye (e.g., the sclera) using electromagnetic radiation is provided. The electromagnetic radiation is generated by an electromagnetic radiation source. Causing electromagnetic radiation to be applied to a specific portion of a target region of the eye, preferably the sclera. Electromagnetic radiation may be blocked from affecting another portion of the target region of the eye by a mask or scleral lens. Alternatively, the electromagnetic radiation may be applied to a target region of the sclera at a portion other than the specific portion.

Further, described herein is a method for modifying tissue with a quasi-continuous laser beam to change an optical property of an eye, the method comprising controllably setting a volumetric power density of the beam and selecting a desired wavelength for the beam. Tissue modification is achieved by focusing a light beam at a preselected starting point in the tissue and moving the focal point of the light beam in a predetermined manner relative to the starting point, either within a specified volume of the entire tissue or along a specified path in the tissue. Depending on the selected volumetric power density, the tissue on which the focal point is incident may be modified by photoablation or by a change in the viscoelastic properties of the tissue.

Ophthalmic laser system

In various embodiments, an ophthalmic laser system includes a laser beam delivery system and an eye tracker responsive to movement of an eye, the eye tracker operable with the laser beam delivery system for ablating both anterior and/or posterior portions of scleral material of the eye by placing laser beam shots on selected regions of the sclera of the eye. The shots are emitted in a sequence and pattern such that no laser shot is emitted at consecutive locations and no consecutive shots overlap. The pattern is moved in response to the movement of the eye. Since the sclera of the eye is 'off-axis', the scanning mechanism is novel in that it does not operate by fixing the beam on the visual axis of the eye. Referring to fig. 20 and 20 (a-C), more specifically, the 'off-axis' scanning mechanism requires an eye docking system 2000 that utilizes a gonioscopic or guiding system to ablate the opposite quadrants of the sclera outside of the visual axis. The closed loop feedback system is located inside the scanner and also between the eye docking system and the scanner in the form of a magnetic sensor mechanism that both locks the laser head to the eye docking system and triggers both eye tracking and beam delivery by biofeedback positioning of the eye.

In some embodiments, the laser apparatus for rejuvenating a surface includes means for selecting and controlling the shape and size of the area illuminated by each pulse of laser energy without changing the beam fluence. By varying the size of the illuminated area between pulses, certain areas of the surface may erode more than others, and thus the surface may be reshaped. The method and apparatus are particularly useful for removing corneal ulceration and reshaping the cornea to remove refractive error and also for reshaping the optical element. In one embodiment, the beam from the laser enters an optical system housed in an articulated arm and terminating in an eyepiece having a suction cup for attachment to the eye. The optical system comprises a beam forming means for correcting an asymmetric beam cross-section, a first relay optics (telescope), a beam size control system and a second relay optics. The beam size control system has a stop with a shaped window or shaped stop portion and is axially movable along the converging or diverging beam portions. An alternative beam size control system has a stop with a shaped window and located between the coupled zoom systems. Mirrors, adjustable slits and refractive systems may also be used. In some embodiments, the laser may preferably be Er: YAg laser. The apparatus may include: a measuring device for measuring a surface profile; and a feedback control system for controlling the laser operation in accordance with the measured and desired profile.

In some embodiments, the methods, devices, and systems for precise laser intervention for template control described herein improve the accuracy speed range, reliability, versatility, safety, and efficacy of interventions such as laser microsurgery, particularly ophthalmic surgery (including the ability to perform such laser surgery outside the visual axis). Such laser surgery is performed off-axis. Turning back to fig. 19, fig. 19 illustrates an exemplary instrument and system 1900 suitable for use in those specialties where positioning accuracy of the laser treatment is critical as long as precise control of the spatial extent of the laser treatment is desired and/or as long as precise manipulation of a target or a series of targets subject to movement during the procedure will be affected. Thus, system 1900 includes the following key components: 1) a user interface comprised of a video display, microprocessor and controller, gui interface; 2) an imaging system, which may include a surgical video microscope with zoom capability; 3) an automatic 3D target acquisition and tracking system that can follow the movements of the subject's tissues, for example and of the eye, during the operation, allowing the surgeon user to predetermine his shot pattern based on images that are automatically stable over time, 4) a laser with which it can be focused so that only the precise treatment described by the user interface is affected, 5) a diagnostic system that combines mapping and topography, digital data, mathematical data, geometric data, imaging data, by means for measuring precise surfaces and 3D shapes before, during and after the operation, said measurements being performed on-line in a time frame that is not limited to human response times and can be real-time, and 6) a fast and reliable safety means, whereby, if any condition occurs that warrants such interruption of the procedure, for example a safety concern, the laser firing is automatically interrupted.

FIG. 20 (E-I) further illustrates the off-axis features of the laser system, in some embodiments the system may provide 360 degree scanning, the laser transmission may be nominally positioned perpendicular to the surface of the eye for treatment, the axis of rotational symmetry is a fixed point of the eye, the treatment area of the laser is preferably not covered by the eyelid and other features of the patient, the eye fixation axis and the laser beam axis have a fixed angle to expose the aperture in the defined area.

In some embodiments, a system for use in ophthalmic diagnosis and analysis and for supporting ophthalmic surgery may comprise: a 3D-7D mapping means for sensing positions, shapes and features on and in the patient's eye in three dimensions and for generating data and signals representative of such positions, shapes and features; display means for receiving signals from the 3D-7D mapping means for presenting to a user an image representative of the position, shape and characteristics of the eye at a target position; comprising display control means for enabling a user to select a target location and display a cross-section of a portion of the eye both during ablation and after each laser pulse in real time; position analysis means associated with and receiving signals from the three-dimensional mapping means for identifying the occurrence of a change in the position of a feature of the eye; target tracking means associated with the location analysis means for searching for features of the target tissue and finding new locations of said features upon a change in such locations and for generating a signal indicative of the new locations; and tracking and positioning means for receiving said signals from the target tracking means and for performing a change of the new position of said feature in the target of the three-dimensional mapping means to the target tissue, thereby following the feature and stabilizing the image on the display means.

The display means may be a video display and further comprise surgical microscope or digital monitor or smart device means for the patient's eye for acquiring video microscopic images of the target area of eye tissue in real time and for feeding video image information to the video display means to cause such video microscopic images to be displayed, assisting the user in diagnosis and analysis, thereby enabling different cross-sections of the patient's tissue as selected by the user to be displayed in real time.

It is an embodiment that the system in which the positioning means are tracked comprises a turning mirror under automatic control, robotic control, bluetooth control, and that the system comprises an objective lens assembly associated with the mapping means and having a final focusing lens, wherein the turning mirror is positioned within the objective lens assembly and is movable relative to the final focusing lens.

An instrument and system for performing high precision ophthalmic laser surgery at a surgical site, comprising: a laser pulse source for generating an infrared to near-infrared laser beam having a power capable of effecting a desired type of procedure in the eye; a laser firing control member for enabling a surgeon/user to control the target, depth and timing of firing of the laser to achieve a desired procedure; 3D-7D mapping means for the eye of the patient for obtaining data representing the position and shape of features on and within the eye; microprocessor means for receiving data from the three-dimensional mapping means and for converting the data into a format presentable on a screen and useful to a surgeon/user in accurately locating features of the eye and the target and depth of the laser beam within those features; and display means for displaying a microprocessor-generated image representing the topography of the eye and the target and depth of the laser beam before the next pulse of laser light is fired to the surgeon/user in preparation for and during surgery; there is a display control means for enabling the surgeon/user to select a region of the eye for display, including an image of a cross-section of a portion of the eye.

An infrared or near-infrared pulsed, free-running or continuous or Q-switched optical laser power source for generating a laser beam capable of effecting a desired laser in the tissue of a patient, including in the transparent tissue of the patient, optical path means for receiving the laser beam and redirecting the laser beam and, where appropriate, focusing it toward a desired target in the tissue to be operated upon,

a laser housing positioned to intercept and direct the light path member for capturing images of the target along the light path member and for feeding video image information to the video display member and tracking for tracking movement of subject tissue at which the system is aimed before the next pulse of laser light is emitted without damaging the subject tissue and moving the light path accordingly before the next pulse of laser light is emitted so that the information and images produced by the three-dimensional mapping member and by the surgical microscope member and the aim and position of the laser beam follow changes in the position of the tissue. In dynamic real-time and surface views, information is sent to the video display for each image frame taken after each shot within the 3D-7D microwell, before and after the firing of the laser. The GUI includes an integrated multi-view system in 7 directionality for image capture, including: surface, internal well, external well, bottom of microwell, whole eye view, target array region.

In some embodiments, the 7 cube is the preferred projection of the microprocessor: other examples exist in the shape, space of a dimensional sphere, and are integrated into the GUI and microprocessor. The orthogonal projection may include the example shown above in fig. 8.

The instrument may include multi-dimensional scaling, linear discriminant analysis and linear dimension reduction processing, as well as local linear embedding and isometric mapping (ISOMAP). A nonlinear dimension reduction method is also included.

In some embodiments, the instrument may allow for 1D, 2D, 3D, or 4D and up to 7D conversion of topological images or fibrosis. Fibrosis is a generalization of the concept of fiber bundles. Fiber bundles refine the idea of one topological space (called a fiber) that is "parameterized" by another topological space (called a basis). Apart from the fact that the fibers do not require the same space, nor do they require different embryos (homomorphic), the fibrosis is like a fiber bundle; rather, they are only homological equivalents. Continuous mapping when fibrosis is equal to the technical properties of the topological space in 3, 4, 5, 6 and 7 dimensional spherical spacep：E→BSatisfying homotopy lifting properties with respect to any space. Fiber bundles (on a clench base) constitute an important example. In homotopy theory, any mapping is 'as good as fibrosis' -i.e. any mapping can be decomposed as homotopy equivalent into a "mapping path space", followed by the decomposition of fibrosis into homotopy fibres.

The laser workstation may be equipped with three programmable axes (X, Y, Z; may be extended to 5 axes) with an automated rotary table machine, a programmable X, Y, Z-axis and 2 station rotary tables. It may include a Human Machine Interface (HMI) with a secure user access level, diagnostics and data logging for validating processes and user-friendly operations, and a classifier module adapted for unique pulse modulation, wherein: pore diameter: 1-1000 μm; the maximum drilling depth is 0.1 to 2000 mu m; hole tolerance: +/-1-20 mu m

Operational functions may also include networked computer connections, iPad operations, joystick operations, touch screen operations, iPhone operations, remote or bluetooth operations, digital camera integration operations, video integration operations, and others.

System and method for laser assisted ophthalmic drug delivery

Fig. 20J illustrates the aqueous flow within the eye. Aqueous outflow can be regulated by active contraction of the ciliary muscles and trabecular cells. Contraction of the ciliary muscle enlarges the trabecular meshwork and increases outflow and lowers IOP. The contraction of trabecular cells reduces outflow and increases IOP. In some embodiments, the described system will result in an improvement in ciliary muscle dynamics that will improve the hydrodynamics of aqueous humor drainage.

The uveoscleral route is an alternative route for aqueous humor drainage, which may account for 10-30% of all aqueous outflow. For the uveoscleral route, aqueous humor enters the ciliary body and passes between ciliary muscle fibers onto the ciliary body and the suprachoroidal space. Fig. 20 (K-L) illustrates how the described system will increase uveal outflow in some embodiments.

The permeability of the sclera is 10 times that of the cornea and is half that of the conjunctiva. Thus, the permeate can diffuse and enter the posterior segment via the transscleral route. With traditional drug delivery (such as eye drops), about 90% of the drug is lost due to nasolachrymal drainage, tear dilution and tear turnover, resulting in poor ocular bioavailability and less than 5% of the topical drug ever reaches the aqueous humor.

In some embodiments, the described systems, methods and devices of the present disclosure may be used for laser-assisted ocular drug delivery, such as methods and devices for light therapy, e.g., to condition target tissue, e.g., scleral tissue and other intraocular tissues, such as the choroid, the sub-choroidal space, the neuroretina, or others, by ablation, coagulation and/or light therapy. Disclosed is a method for producing an initial permeate surface (a) in a biofilm (1), comprising: a) creating a plurality of individual micro-pores (2) in a biofilm (1)i) Each individual well (2)i) Having a separate infiltration surface (Ai); and b) creating such a plurality and such a shape of individual pores (2)i) So that the initial penetration surface (A) is of a desired value, the initial penetration surface (A) being all the individual micro-pores (2)i) Of the individual penetration surfaces (Ai). A microwell device for performing the method is also disclosed. In this case, the biological surface may be an eye. In the case of the eye: irradiating a region of the sclera so that the therapeutic agent passes through the region produced by the laser radiationOpen area and thus delivered to intraocular target tissue in the anterior or posterior sphere, such as choroid, neural retina, retinal epithelium, uveal tract, vitreous body, or aqueous humor.

In some embodiments, the described systems, methods and devices of the present disclosure may be used for laser-assisted ophthalmic drug delivery, such as methods and devices for smart activated polymeric carriers, which may be light activated, light modified poly (acrylamide), or may be used to fine-manipulate the pore size of nano/microporous materials and demonstrate their application for reversible color modulation of moisture condensation based porous polymeric photonic crystals.

Additionally, in some embodiments, the systems described herein may include one or more of the following: eye docking stations, scleral mask/nozzle guards, nozzles, novel 360 degree articulated arms, novel off-axis scanning, drug delivery systems, depth control, attachments, Fibonacci algorithm, and others. Some options include a hand-held wand, fiber optic handpiece, scanning robotic laser applicator, workstation, remote control via bluetooth or otherwise, hand-held tonometers for pre-and post-operative tonometry, and others.

Fig. 20M illustrates an exemplary hand piece transport system and articulated arm.

For delivery purposes, the eye may be considered to be comprised of two segments. The anterior segment includes the cornea, conjunctiva, sclera, and anterior uvea, while the posterior segment includes the retina, vitreous, and choroid. There are three main routes for delivering drugs to the eye: local, systemic and intraocular injection. Controlled delivery systems, such as ocular inserts, mini-tablets, and disposable lenses, may be applied to the outer surface of the eye for the treatment of diseases affecting the anterior segment of the eye. Prolonged residence time after topical application has the potential to improve the bioavailability of the administered drug, and in addition a range of strategies have been tested to improve penetration including cyclodextrins, liposomes and nanoparticles. Drug delivery strategies for treating diseases of the posterior segment of the eye will be discussed herein. The development of therapeutic agents requiring repeated, long-term administration is a driving force for the development of sustained-release drug delivery systems to result in less frequent dosing and less invasive techniques.

Delivering drugs to the eye is commonly used for two primary purposes. First, for the treatment of extraocular diseases around the eye, such as conjunctivitis, blepharitis, and dry eye, and second, for the treatment of intraocular diseases, such as glaucoma, diabetic retinopathy, uveitis, and age-related macular degeneration (AMD), retinopathy, and biomechanically compressing, restricting, or interfering with the normal physiological function of the subcutaneous vascular, neural, or connective tissues of the ocular tissues. Under normal conditions, a drug administered to the eye as an aqueous solution of eye drops will be rapidly diluted and flushed from the surface of the eye by a continuous stream of tears. Dilution of the drug on the surface of the eye also reduces the flow of the drug from the surface into the eye. Therefore, the eye drops must be administered frequently and at high concentrations in order to reach therapeutic levels. Successful delivery of lipophilic drugs in aqueous eye drop suspensions has led to the development of delivery systems aimed at increasing the residence time of the drug on the surface of the eye. Increased uptake into the eye may be possible by maintaining high levels of drug in the tear fluid over a long period of time. This may also be combined with strategies to improve eye penetration. In addition to using traditional systems such as solutions, suspensions, creams and gels, development has also been made using devices such as inserts and viscoelastic solutions.

In some embodiments, the described systems, methods, and devices of the present disclosure may be used for posterior ocular drug delivery in the posterior sclera, including but not limited to the episcleral periphery and the lamina cribosa. Currently, treatment of disease in the posterior portion of the balloon is hampered by poor efficacy of topical drugs and there is no minimally invasive method of reaching or treating the posterior portion of the balloon.

In some embodiments, fig. 20 (N-O) illustrates treatment zones in the anterior and posterior balls.

In some embodiments, the described systems, methods, and devices of the present disclosure may be used for, but are not limited to, the delivery of pharmaceuticals, nutraceuticals, grape seed extracts, stem cells, plasma-rich proteins, light-activated smart polymer carriers, and matrix metalloproteinases. In some embodiments, fig. 20P illustrates exemplary targets for choroid plexus drug and nutraceutical delivery.

It is difficult to obtain and maintain an effective drug concentration at the site of action. Only about 5% of the applied dose from the eye drops penetrates the cornea to the eye tissue and the dwell time is about 2-5 minutes. Attempts to improve ocular bioavailability include extending the residence time of the drug in the conjunctival sac and improving the penetration of the drug through the cornea (the primary route of entry of the drug into the inner eye). Delivery systems for topical administration include suspensions, gels, erodible and non-erodible inserts and rods.

Increasing the viscosity of the topical formulation may improve retention in the eye, and the combination of viscosity modifiers may prove to be synergistic. Such formulations are particularly useful as artificial tears and ocular lubricants, but may also be used for topical delivery of drugs to the eye. Polyvinyl alcohol (PVA) and cellulose, such as hydroxypropyl methylcellulose, are commonly used as viscosity modifiers because they have a wide range of molecular weights and exhibit compatibility with many topically applied active agents. The particular combination of polymers may be selected to achieve a particular viscosity or gelling characteristic. In situ gelling systems undergo a transition from a liquid phase to a solid phase in response to a trigger (such as a change in pH, temperature in the presence of ions), thereby forming a viscoelastic gel. Poloxamers, block copolymers of poly (oxyethylene) and poly (oxypropylene) form thermoreversible gels at temperatures in the range of 25-35 ℃ and are generally well tolerated. Cellulose Acetate Phthalate (CAP) undergoes a phase change triggered 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 a clear gel in the presence of monovalent or divalent cations. Once it gelled, the first controlled release ophthalmic delivery device was pushed out by Alza in the middle of the 1970 s. It comprises active pilocarpine and alginic acid contained in a reservoir surrounded by two release controlling membranes made of ethylene vinyl acetate copolymer and surrounded by a white retentate. Like liposomes, polymeric microparticle delivery systems, such as microspheres and nanospheres, have been investigated for topical delivery to the eye. Particles in the micron size range are referred to as microspheres, while nanoparticles are sub-micron in diameter. In some embodiments, fig. 20Q illustrates how the described system may be used for transscleral drug delivery and for improved intracellular release and penetration of drugs. They can be manufactured using a variety of techniques including milling and homogenization, spray drying, supercritical fluid techniques, and emulsion solvent evaporation. Incorporation of microparticles into viscous droplets and gels will facilitate easier administration than aqueous suspension formulations. Intraocular drug delivery via scleral blood vessels and aqueous humor. The smart activated polymeric support may be incorporated and may be photoactivated, photo-modified poly (acrylamide), or may be used to finely manipulate the pore size of the nano/microporous material and demonstrate its application for reversible color tuning of porous polymeric photonic crystals based on humidity coagulation. Improving penetration.

As a result, although the topical ocular and subconjunctival sites are thus used for anterior targets, intravitreal administration is desirable for posterior targets. Topical administration of drugs will reduce the likelihood of side effects, particularly for potent molecules with severe side effects, such as immunosuppressants. These may be useful, alone or in combination, for alleviating the diseases associated with dry eye. An effective blood retinal barrier prevents most systemically administered drugs from reaching therapeutic levels in the vitreoretinal space, and the side effects experienced after systemic administration of such effective molecules limit the usefulness of this route. Sustained release can extend the duration of the effective concentration at the site of action, as demonstrated by current delivery systems. Proposed controlled release formulations for intravitreal sustained delivery include liposomal formulations, biodegradable microspheres, biodegradable and non-biodegradable implants. Entrapment of the drug in the nanoparticles prior to incorporation into the contact lens is a strategy that can be used to maintain release. If the nanoparticle size and loading is low, the lens should remain transparent. Particulate polymer delivery may include microspheres or nanospheres, which can be manufactured in a variety of ways, including spray drying, emulsification, and solvent evaporation and precipitation

Microspheres can be used for delivery to the anterior segment, adhesion to the surface of the eye and extended release, but they can also be used as sustained release injectable formulations. Fig. 20R illustrates an exemplary ophthalmic oil comprising a drug-loaded hydrogel embedded on a coiled wire designed for placement in the conjunctival cul-de-sac. Selective targeting of slow-release microspheres loaded with drugs in the eye has also been explored after injection of nanoparticles into the vitreous by modifying the surface of the particles to alter their distribution in the eye. In some embodiments, fig. 20S illustrates a drug delivery carrier. In some embodiments, fig. 20T (1-3) illustrates a 360 scleral wafer.

In some embodiments, a drug delivery system includes a drug and a lens disposed on an eye having a posterior surface comprising: a central portion (cornea) and a scleral portion having an outer edge and an inner edge, and a treatment portion including an outer edge, an inner chamber, and an interlocking carrier reservoir having a plurality of tissue array sizes, shapes, and variations. The corneal portion may be made of silicon carbide to protect the cornea, and or may be metallic. Silicon carbide may be preferred. It is also opaque. The lens may be a scleral lens covering at least 18mm in diameter. The scleral portion of the lens may only contact the sclera. The treated portion of the lens contacts only the sclera and the periphery of the cornea, including the corneoscleral capsule and the limbus.

In some embodiments, the haptic portion of the scleral lens further defines a channel extending radially at least a portion of the distance between the outer edge and the inner edge. The drug may be selected from the group consisting of antibiotics, antivirals, antifungals, antiparasitics, corticosteroids, non-steroidal anti-inflammatory drugs, mydriatic agents, cycloplegics, biologics, agents that alter neovascularization, agents that increase aqueous humor outflow, agents that reduce aqueous humor secretion, antihistamines, secretagogues, mast cell stabilizers, tear supplements, antimetabolites and immunomodulators, VEGF and other posterior drugs such as timoline, and the like.

In some embodiments, the disease treated may include bacterial infections, viral infections, fungal infections, parasitic infections, inflammation, neovascularization, eye surface diseases, glaucoma, allergy, dry eye, dysplasia, tumors, and AMD.

In some embodiments, the treated portion of the lens is made of mesoporous silica. Photoisomerized photoactivated moving parts based on azobenzene derivatives have been used with mesoporous silica. It has been shown that the back-and-forth oscillatory motion acts as a molecular impeller that modulates the release of molecules from the pores of the silica nanoparticles under "remote control" upon optical excitation. Unlike release mediated by many other nanomachines, azobenzene-driven release can occur in aqueous environments. Using photo-activated mesostructured silica (LAMS) nanoparticles, luminescent dyes and ocular drugs are only released inside the target tissue array (e.g. sclera) that is illuminated at a specific wavelength that activates the impeller. The number of released molecules is determined by the light intensity and the irradiation time. The illuminated target tissue array is exposed to a suspension of particles, 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 impeller is excited by light of a specific wavelength. A selected ocular drug that is loaded into and released from an intracellular granule under light excitation, and induces apoptosis. Intracellular release of molecules is sensitively controlled by light intensity, irradiation time and wavelength, and anticancer drug delivery inside the cell is regulated under external control.

The drug delivery system may be used for any drug delivery required for a number of eye surgeries, either for prophylactic or post-operative use, within a pre/peri/post-operative state.

In some embodiments, a transscleral delivery system for treating an eye of a patient includes a device for facilitating transscleral delivery of a drug through a region of the device, and includes an ablator configured to create micropores in the region of the sclera of the eye of the patient, and may include a drug, wherein the drug affects at least one of biological regulation of a target tissue. The drug may be administered transsclerally or intrasclerally to a laser-perforated site having a predetermined osmotic surface over time, wherein the predetermined osmotic surface over time is effective to achieve a predetermined deposition concentration of at least one drug to thereby treat an ocular condition, and further wherein the laser-perforated site includes a plurality of pores having different geometries. The drug may be administered transsclerally or intrasclerally at the first location, and the plurality of drugs may be administered transsclerally or intrasclerally at different locations. Drugs may also be administered into the suprachoroidal space. The drug may be delivered after or during irradiation of the target tissue array.

Turning back to fig. 20-20B, the system of the present disclosure may include an eye docking station 2000. During a medical procedure, the eye docking station 2000 may be positioned over the eye 2010. Fig. 20C illustrates an exemplary top view of the eye docking station 2000. The eye docking station 2000 may provide a four quadrant view. Fig. 20D illustrates an exemplary scleral fixation assembly 2020 that may be attached to the eye docking station 2000.

Turning to fig. 21A-21B, embodiments of nozzle guards 2100 and 2110. In some exemplary operations, FIG. 22 illustrates the nozzle shield 2110 being attached to the nozzle 2200. Fig. 23 illustrates a nozzle 2200 fitted with a disposable insert and filter 2310.

Fig. 24 illustrates a laser-micro-foraminous and exemplary workstation 2400, as well as a handpiece and associated apparatus 2420 for laser surgery of the eye. The workstation 2400 may include the above-described methods, apparatus, and systems for precise laser intervention for template control. As described above, the methods, devices and systems improve the accuracy, speed range, reliability, versatility, safety and efficacy of interventions such as laser microsurgery, particularly ophthalmic surgery, including the ability to perform such laser surgery outside of the visual axis.

The system may include a GUI interface that is a touch screen or remote control. A Graphical User Interface (GUI) is a user interface that allows a user to interact with an electronic device through graphical icons and visual indicators, such as helper symbols, rather than a text-based user interface, typed command tags, or text navigation.

The instrument workstation 2400 may include an articulated arm 2410; a laser housing unit 2500 (fig. 25) comprising a self-contained laser housing unit comprising: a CCD camera; a galvanometer scanner capable of off-axis scanning; an aiming beam; and others.

Fig. 25A-25B illustrate a housing unit 2500 that is rotatable 360 degrees.

The instruments and systems may include a three-dimensional mapping means, at least one communicatively coupled microprocessor, a power source, and a display means including means for presenting an image to the surgeon/user indicating the precise current location of laser aiming and depth in a computer-generated view, typically including a plan view and selected cross-sectional views of the eye representing features of the eye at different depths.

The instruments and systems may also include an optical path with a focusing lens capable of controlling the focusing of the laser beam on the eye tissue, and therefore the depth at which the laser beam is effective is within about 5 microns, with depth control means for the surgeon to vary the focus of the lens to control the depth at which the laser beam is effective.

The instruments and systems may further include system programming means that enable the surgeon/user to pre-program the pattern of lesions in the eye tissue along three axes in three dimensions and activate the laser to automatically follow the path of the pre-selected pre-programmed surgical procedure.

The instrument and system user interface may include equipment for presenting information to the surgeon/user and for enabling control of the surgical procedure by the surgeon/user, including video display means for presenting to the surgeon/user precise information relating to the location in the tissue of the patient at which the system is aimed and the three-7 dimensional topography and contours of features of the subject's tissue, the patterns and meridians of the array, including imaging of cross sections of the tissue, scanning of surfaces and regions, and real-time dynamic control of the firing of the surgical laser beam by the user.

The instruments and systems may contain or include an imaging system connected to a video display member, including a three-to seven-dimensional mapping member for generating, reading and interpreting data to obtain information about the location in seven dimensions of important features of the tissue to be operated upon, and a microprocessor member for interpreting the data and presenting the data to the video display member in a format useful to the surgeon/user, this also including anatomical localizers and eraser techniques with chromophore sensors to sense changes in color, size, water content, shape, spectral properties, optical properties, and with a reverse scan biofeedback function that can outline accurate 3D-7D images of blood vessels, veins, and any other non-target anatomical structures. It can signal the laser to avoid such non-target anatomy. With the eraser function, the user/surgeon can manually mark on the touch screen GUI interface to direct the laser to avoid the erasure area/array/spot/area.

The laser workstation may be equipped with three programmable axes (X, Y, Z; may be extended to 5 axes) with an automatic rotary table machine, a programmable X, Y, Z axis and 2 rotary tables, including a Human Machine Interface (HMI) with secure user access levels, diagnostics and data logging for validation of the process and user friendly operation. Classifier module with adaptive operation function: unique pulse modulation; pore diameter: -1 to 800 μm; the maximum drilling depth is 0.1 to 2000 mu m; hole tolerance: +/-.1 mu m-20 mu m.

Depth control

In virtually all tissues, disease progression is accompanied by changes in mechanical properties. Laser Speckle Rheology (LSR) is a new technique we have developed for measuring mechanical properties of tissue. By illuminating the sample with coherent laser light and calculating the speckle intensity modulation from the reflected laser speckle pattern, the LSR calculates τ, the decay time constant for intensity decorrelation, which is closely related to tissue mechanical properties. The use of LSR technology may be demonstrated by measuring mechanical properties of the tissue. The measurement of LSR of τ was performed on various body membranes (phantom) and tissue samples and compared to the complex shear modulus G measured using a rheometer. In all cases, a strong correlation between τ and G × (r =0.95, p < 0.002) was observed. These results demonstrate the efficacy of LSR as a non-invasive and non-contact technique for mechanical evaluation of biological samples.

It is known that disease progression in major killers such as cancer and atherosclerosis, as well as several other debilitating diseases including neurodegenerative diseases and osteoarthritis, is accompanied by changes in the mechanical properties of the tissue. Most of the available evidence for the importance of biomechanical properties in the assessment of disease is obtained in vitro using traditional mechanical tests, including straining, stretching or manipulating the sample. To address the need for in situ mechanical characterization, a new optical tool may include an LSR.

When a turbid sample, such as tissue, is irradiated by a coherent laser beam, the rays interact with tissue particles and follow paths of different lengths due to multiple scattering. Self-interference of the returning light produces a pattern of dark and light spots (known as laser speckle). Due to the thermal brownian motion of the scattering particles, the optical path may be constantly changing and the speckle pattern fluctuates with a time scale corresponding to the mechanical properties of the medium surrounding the scattering center.

During intraoperative procedures using chromophores and other biofeedback procedures, an open biofeedback loop may be used in various embodiments. In chromophore embodiments, the saturation of color can be measured with sensitivity to micron-scale accuracy to determine correct and incorrect tissue for a surgical procedure. Pulse decisions may be made based on various preset color saturation levels. This is in contrast to prior art systems, which may use only color or other metrics for feedback to the imaging equipment, and not to the actual laser application device that is applying the treatment. Similarly, subcutaneous anatomy avoidance for predictive depth calibration may use tools to determine depth calculations in real-time to determine how close to completing an extraction or other treatment procedure, while also maintaining active monitoring of undesirable and unpredictable anatomy. Thus, hydraulic or other feature monitoring is different from older systems that might monitor the level of surface reflection but are not effective in measuring depth in tissue or other biological matter.

LSR takes advantage of this concept and analyzes the intensity decorrelation of the backscattered rays to produce an estimate of tissue biomechanics. For this purpose, the LSR calculates the intensity decorrelation function of the speckle sequenceg ₂ （t）And its decay time constant τ is extracted as a measure of the biomechanical properties. The objective here is to investigate the LSR measurement and the complex shear modulus of tauGConventional bulk mechanical testing of the relationship between the measurements.

Laser speckle rheological table

The bulk mechanical properties of the tissue and substrate were measured using a desktop LSR apparatus. Such devices include multiple lasers of coherent laser length followed by a linear polarizer and a beam expander. A focal length lens and a plane mirror are used to focus the illumination spot at the target tissue site. The laser speckle pattern is imaged using a high-speed CMOS camera. The image sequence is processed and the correlation between each two frames is calculated to determine an intensity decorrelation functiong ₂ （t）. Temporal and spatial averaging is applied to the pixels of the image sequence to reduce statistical errors. Fitting a single index to the obtainedg ₂ （t）Curve to extract the time constant τ.

The sclera is a viscoelastic tissue and its complex shear modulus can be precisely tuned by remodeling with laser or selective fibrillar and/or microfiber ablation to alter the viscoelastic modulus and reduce biomechanical stiffness. Measuring the mechanical properties by a biofeedback loop during the course of laser surgery enables the evaluation of the LSR's sensitivity to small gradual changes in the mechanical properties and thus obtains the desired effect. Furthermore, a preferred embodiment of the present invention is to simulate the change in viscoelastic modulus by fem (vesa) by predicting the desired pattern of remodeling and/or fibril/microfiber selective ablation by an artificial intelligence algorithm.

Changes in scleral transparency or opacity/transparency may produce scattering features. The final volume fraction is measured to adequately identify strong backscatter signals. The LSR measurement is obtained after a conventional mechanical frequency sweep for a specified duration. Final time point measurements were performed on the treated sclera using both the LSR and AR-G2 instruments.

As used herein, chromophores refers to the water absorption spectrum to quantify the change in tissue chromophore concentration in the near infrared spectrum.

The systems and methods herein can be used to measure the differential path length of photons in a scattering medium using the spectral absorption characteristics of water. Determining this differential path length is a prerequisite for quantifying chromophore concentration changes measured by near infrared spectroscopy (NIRS). Quantification of the tissue chromophore concentration measurement is used to quantify the depth of the ablation rate produced by the water absorption and time resolved measurements of the layers of scleral tissue, as it relates to the ablation rate absorbed, the pulse width and the energy of the laser beam.

In some embodiments, the laser docking station may include a female end of the laser housing unit, which may be implemented using a magnetic sensor between the female and male components, in a closed feedback loop with the laser head. These sensors will detect the spectral reflectance of tissue, which is measured by Er: the properties of the Yag wavelength are determined by Er: YAg absorbs differently.

The number of pulses can be detected by the laser and the CDD camera, which can detect reflected light that is reflected differently by different colors.

Since the sclera is made of 99% water, water can also be used as a chromophore, so the per-hole pulse of the laser treatment in the scleral tissue can be fed back to the laser system and can be exploited by how many pulses per hole and at which tissue level it is, since there is a tissue level in the sclera.

The electrical vibration may provide biofeedback. Quantification of tissue chromophore concentration measurements is performed by comparing differential path estimates resulting from water uptake and time resolved measurements, galvanometer per well pulse, or optics. The sensor is also capable of transmitting and quantifying dynamic changes in the absorption coefficient of water as a function of incident flux at 2.94 μm.

The chromophore concentration, absorption and scattering properties of scleral absorption in the human body and the reduced scattering coefficient of human connective tissue in vivo, such as the sclera of the eye, provide critical information for surgical and clinical purposes regarding non-invasive connective tissue (sclera) diagnosis. To date, few scleral optical properties in vivo have been reported. As previously mentioned, the absorption and scattering properties of the skin in vivo in the wavelength range from 650 to 1000nm are achieved using a "modified double layer geometry" diffusion probe. As disclosed herein, the determination of the spectrum of the scleral optical property is continuous over a range from 500 to 1000 nm. It was found that the concentration of chromophores (such as oxyhemoglobin, deoxyhemoglobin, and melanin) calculated based on the absorption spectra of eighteen subjects at wavelengths above and below 600nm differed due to inherent differences in the interrogation region. The scattering power, which is related to the size of the average scatterer, shows a clear contrast between the scleral photopic, scleral site, and wavelength. The present invention uses the concentrations of oxygenated and deoxygenated hemoglobin evaluated at wavelengths above and below 600nm to distinguish between the target tissue (sclera) and adjacent anatomical structures (arteries/veins). For example, the sclera is not vascularized and will exhibit a deoxyhemoglobin response, while the adjacent vessels will exhibit an osy-hemoglobin response. Diffuse reflectance techniques with visible and near infrared light sources can be used to study the hemodynamic and optical properties of the upper and lower dermis.

Absorption coefficient mu of sclera _a Scattering coefficient mu _s' And chromophore concentration are fundamental properties of tissue that can provide the necessary information for many surgical, therapeutic and diagnostic applications, such as monitoring skin oxygenation, melanin concentration, detecting hydration with fluorescence, laser surgery and photodynamic therapy.

Photon diffusion theory derived from the radiation transport equation is typically used as a forward model to determine the optical properties of an in vivo sample when the source-detector separation is longer than five mean free paths, where the mean free path is defined as 1/(μ [% ]) _a +µ _s' ). This has proven to be an unsuitable model for source-detector separations longer than five mean free paths, because of boundary conditions and multiple scattering in the turbid mediumCannot be satisfied. To limit interrogation to superficial tissue volumes, such as the sclera, source-detector separations shorter than five mean free paths are incorporated. In vivo techniques may employ alternative forward models to determine the optical properties of the sclera. To determine the optical properties of the sclera in vivo, we used visible reflectance spectra with a multi-layer sclera model and guided a predetermined optimization algorithm by using an artificial intelligent FEM integrated OCT, UBM or CCD camera. The multi-layer skin model and many fitting parameters, such as layer thickness, chromophore and scattering properties of each layer and their respective ranges, must be carefully selected in advance to avoid non-uniqueness in solution space.

A system model is employed to extract optical properties from diffuse reflectance spectra collected from the sclera in the body. This technique requires that all chromophores contributing to the measurement signal are known in advance and that the reduced scattering coefficient has a linear relationship with the wavelength in order to separate the absorption and reduced scattering coefficient from the measured reflectance. All constituent chromophores were then identified and the absorption spectra were recovered. Furthermore, the reduced scattering coefficient produces a linear dependence on wavelength, and empirical mathematical models will properly restore tissue optical properties.

Further embodiments herein include the use of a probe design that has been tuned to multiple source-detector pairs such that it can employ a white light source to obtain a continuous spectrum of absorption and reduced scattering coefficient. Advantages of such multi-source detector separation probes include relatively low instrument cost and real-time in vivo self-calibration of instrument response (by using the reflectivity of one source detector pair as a reference and normalizing the reflectivity of the other source detector separation pairs to the reference). The normalized reflectance and source-detector separation are then fitted to a diffusion model by a least squares minimization algorithm to determine the absorption and reduced scatter spectra. The recovered absorption spectrum is fitted linearly to the known chromophore absorption spectrum to extract the chromophore concentration, and the reduced scattering spectrum is fitted to the scattering power law to obtain the scattering power. The probe is used to determine the skin optical properties of the sclera, and also to extract the chromophore concentration and the scattered power of the sclera. It was found that performing a "two region chromophore fit" on the absorbance spectrum would result in a best fit with minimal residual error. By two-region chromophore fitting, we mean that the scleral absorption spectrum is fitted to a set of known chromophore absorption spectra with wavelengths between 500 nm and 600nm, and again between 600nm and 1000nm, respectively. The basic principle for performing a two-region fit is that the sclera has very different optical properties in the visible and NIR wavelength regions, and therefore the sampling volumes at these two regions are very different. Also, a best fit to the reduced scattering coefficient of the skin is obtained when the reduced scattering spectrum is fitted in the regions below and above 600nm, respectively. The scattered power depends not only on the anatomical site but also on the scleral layer. These systems and methods enable simultaneous investigation of superficial tissues in the body at different depths. Significantly different hemoglobin concentrations at the target scleral tissue and non-target adjacent anatomical structures are also disclosed in various embodiments.

The instrument may include a diffusion probe for use with multimode optical fibers for both penetration and detector. The reflectivity can be measured by multiple layers, multiple depths, and the depths can be measured simultaneously. Diffuse reflectance spectroscopy as a tool for measuring absorption coefficients in the sclera, with in vivo imaging combining tissue absorption scattering and hemoglobin concentration, means for lesion prevention depth control and anatomical avoidance guidance for laser surgery, and observation of microporous in vivo biometrics and sustained wound healing changes in tissue.

In laser therapy, the optical properties (absorption and scattering coefficients) are important parameters. The melanin content of the tissue affects the absorption of light in the skin. A diffuse reflection probe is proposed, consisting of a ring of six light transmitting fibers and a central collection fiber system for measuring diffuse reflected light from the sclera. From these measurements, the absorption coefficient was calculated. The system is capable of real-time in vivo techniques to determine absorption coefficients of desired target tissue in the sclera over multiple scleral layers at multiple depths. The three signals that affect the intensity of the diffuse reflected light originate from the properties of the connective tissue. (1) Light scatter changes, rapidly (milliseconds over 10 s) andslowly (i.e. slowly)>-0.5 s) of both，(2) Early (— 0.5-2.5 s) absorption changes from changes in the chromophore redox state, i.e. oxy/deoxy-hemoglobin ratio (referred to as the "initial fall" period), and (3) slower (— 2-10 s) absorption changes due to blood volume increase (associated with the fMRI BOLD signal). Changes in light scattering have been attributed to interstitial volume changes caused by cellular hydration, water content, water movement, and capillary dilation.

Quantitative diffuse optical methods, such as spatially resolved reflectance, Diffuse Optical Spectroscopy (DOS), tomography (DOT), and Diffuse Correlation Spectroscopy (DCS), have extremely high sensitivity to functional and structural changes in connective tissue. Some embodiments may utilize the near infrared spectral region (600-_a) And reduced scattering coefficient (mu)_s′) Providing quantitative determination of several important biological chromophores such as deoxyhemoglobin (HbR), oxyhemoglobin (HbO)₂) Water (H)₂O) and lipids. The concentration of these chromophores represents a direct measure of tissue function, such as blood volume fraction, tissue oxygenation, and hydration. Furthermore, the scattering coefficient contains important structural information about the size and density of scatterers and can be used to assess tissue composition (extracellular matrix proteins, nuclei, mitochondria) and follow the process of tissue remodeling (wound healing, etc.). The system utilizes a limited number of optical wavelengths (e.g., 2-6) and a narrow temporal bandwidth, but forms higher resolution images of the subcutaneous structure by sampling a large number of source-detector "views". To achieve maximum spatial resolution, an ideal DOT design would employ thousands of source-detector pairs and wavelengths. The system further employs a non-contact quantitative optical imaging technique of modulated imaging that is capable of both separating and spatially resolving optical absorption and scattering parameters, thereby allowing wide-field quantitative mapping of tissue optical properties. It uses spatially modulated illumination for imaging tissue components. Periodic illumination patterns of various spatial frequencies are projected over a large area of the sample. According to the illumination pattern, due to the turbidity of the sampleThe diffuse reflection image is modified. Typically, a sine wave illumination pattern is used. Demodulation of these spatially modulated waves characterizes the Modulation Transfer Function (MTF) of the material and embodies the sample optical property information. Color coding is incorporated into the software to allow color assignment and viewing of the overlay on the displayed 3D converted image. Artificial intelligence recognition of anatomical differences in conjunction with color assignment, allowing real-time identification of tissue differences between target tissue and adjacent anatomical structures, and 3D integrated transformed display in conjunction with color assignment of image samples. The anatomical avoidance technique focuses primarily on blood vessels and subcutaneous tissue, using the optical properties of the tissue using reflectance spectroscopy, biofeedback loops, and CCD cameras.

Referring to fig. 26-a, a multi-layered imaging platform 2600 in accordance with some embodiments is illustrated. Platform 2600 may include: HL-halogen lamp; MS-mirroring System DD-digital drive; l2-projection lens; l3-camera lens; LCTF-liquid crystal tunable filter; and CCD VC-CCD Camera. 26-B and 26-C illustrate an exemplary CCD camera with a nozzle. Fig. 26-D illustrates an exemplary camera view using a CCD camera. In certain embodiments, the platform may comprise a solid state laser wavelength Er: yag 2.94 μm, free running system with scanning and long working distance platform, surgery performed in slit lamp seating position, physician control/software dependency, surgery time of minutes for both eyes, etc.

In some embodiments, a method for quantitatively mapping tissue absorption and scattering properties, and thus allowing local sampling of the in vivo concentration of oxygenated and deoxygenated hemoglobin, may be used to selectively identify and differentiate target and non-target tissues for the purposes of surgical planning and laser guidance of laser surgery of the sclera. The consistent dynamic changes in both scattering and absorption are striking showing the importance of optical property separation for quantitative assessment of tissue hemodynamics. These systems and methods integrate a common platform for spatially modulated structured illumination using speckle correlation and fluorescence. The system and method are then used in an intra-body real-time intraoperative setting to provide feedback and guidance to the surgeon. The 3D transformation of the reconstructed images can be viewed simultaneously by a CCD camera in a color-coded distribution to take advantage of the anatomy avoidance software and target treatment that can be intra-operatively modified. The system is further used post-operatively to look at micro-porous tissue subcutaneous biometrics, physiology, wound healing and morphology for further guidance and therapeutic significance.

Use of fluorescence: the sclera had only 25% of the total GAG present in the cornea. Because GAGs attract water, the sclera hydrates less than the cornea (but not 75% less; due to several structures care is taken to maintain lower hydration levels in the cornea). Large variations in fibril size and irregular spacing between scleral components result in light scattering and opacity. The color of the sclera is white when healthy, but may change color over time or due to disease (e.g., hepatitis). Internally, the sclera fuses with choroidal tissue in the suprachoroidal layer. As described herein, the innermost scleral layer is referred to as the brown layer. All of these have specific fluorescence, spectral properties and water content.

Fluorescence and diffuse reflectance spectroscopy are powerful tools for distinguishing one connective tissue from another according to the emission from endogenous fluorophores and the diffuse reflectance of absorbents such as hemoglobin, melanin, water, protein content, etc. However, separate analytical methods are used for the identification of fluorophores and hemoglobin. The estimation of the fluorophore and hemoglobin can be performed simultaneously using a single technique of automated fluorescence spectroscopy. The diagnosis and real-time treatment selection of target and non-target in vivo tissues is an important technical feature herein. The emissions from the prominent fluorophores collagen, flavin adenine dinucleotide, phospholipids and GAGS proteoglycans are analyzed a priori and may also be assigned color labels. The water concentration can also be calculated from the ratio of the fluorescence emissions at 500 and 570 nm. Excitation at 410 nm yields better classification of normal and tumor tissues than at 320nm when using a diagnostic algorithm based on linear discriminant analysis. Fluorescence spectroscopy as a single entity can be used to assess the prominent fluorophores as well as water concentrations in gradient tissues and isolated tissue structures and compositions.

Fluorescence spectroscopy is a tool used to distinguish between target and non-target tissues based on the emission spectral curve from endogenous fluorophores. Fluorescence uses automated fluorescence spectroscopy to estimate the concentration of fluorophores and uses their diagnostic inputs on clinically important in vivo tissues and uses this information via a real-time biofeedback loop as a laser-guided software code platform. Fluorescence emission of scleral tissue was recorded at excitation wavelengths of 320 and 410 nm. Emission characteristics of fluorophores such as collagen, Nicotinamide Adenine Dinucleotide (NADH), Flavin Adenine Dinucleotide (FAD), phospholipids and porphyrins, proteoglycans, GAGs, collagen extracellular matrix and melanocytes of scleral tissues and adjacent anatomical tissues (such as blood vessels, veins, nerves, etc.) are elicited. Accurate tissue classification is then performed using Spectral Intensity Ratios (SIR) and multivariate principal component analysis, linear discriminant analysis (PCA-LDA). The PCA-LDA based diagnostic algorithm provides better classification efficiency than SIR. Furthermore, spectral data based in particular on excitation wavelengths of 100nm to 700nm were found to be more efficient in classification than 320nm excitation using PCA-LDA. The better efficacy of PCA-LDA in tissue classification was further demonstrated by the receiver operator characteristic curve method. The results of this initial data capture represent a system and method for distinguishing various connective tissue components in this preferred embodiment of the scleral connective tissue of the eye from adjacent non-targeted tissue using a real-time fluorescence spectroscopy based tool, which can present significant challenges. The anatomy avoidance system can be reiterated using real-time OCT imaging sensors as well as chromophore sensors (water, color, etc.) or spectroscopy without fluorescence.

There are many biomolecules that can absorb light via an electron transition. Such transitions are relatively energetic and are therefore associated with absorption at ultraviolet, visible and near infrared wavelengths. Molecules typically have a string of double bonds with pi-orbital electrons behaving similarly to electrons in metals, because they collectively act as small antennas that can "receive" electromagnetic waves of passing photons. Photon absorption is possible if the resonance of the pi-track structure matches the wavelength of the photon. The system utilizes these electrical vibrations to impart biofeedback to the laser module to distinguish not only between target and non-target tissue, but also to distinguish actual transitions in tissue from one chromophore to the next, thereby creating an ultra-sensitive hyper-feedback loop. Further, in the field of infrared spectroscopy, various bonds that can resonantly vibrate or distort in response to infrared wavelengths and thereby absorb such photons are studied. Perhaps the most prominent chromophore in biology absorbed via vibrational transition is water. In the infrared, water absorption is the strongest contributor to tissue absorption and is described in the present invention. All other tissues with color chromophores (such as blood vessels, veins, or melanin) are also described as providing biofeedback in their own specific absorption or vibration transitions, and are further defined as tissue properties sensed by these laser modules and other systems and combinations described herein.

In some embodiments, color and chromophore sensing may be used to track blood vessels and other subcutaneous features in the sclera and other eye locations. Similarly, hydration sensing may also be used. In detail, the modified claims include a biofeedback sensor, a scanner including a galvanometer, and a CCD camera providing biofeedback which is used to distinguish between target and non-target tissue in the form of a sensitive biofeedback loop in addition to the transition from one chromophore to the next within the tissue. Such transitions are relatively energetic and are therefore associated with absorption at ultraviolet, visible and near infrared wavelengths. These concepts are not disclosed or taught in the prior art, which facilitates feedback using simple images for the laser modules disclosed therein. Since many biomolecules can absorb light via electronic transitions, sensing and monitoring them can be a useful general imaging capability.

It should be noted that chromophore sensing and monitoring, which is a way to sense and monitor and determine boundaries within tissue, uses color differences based on the intrinsic light absorption of different materials, is an advantageous improvement of the present disclosure. Color sensing and monitoring provides an advantage in that it can identify subtle differences in tissue composition, which can then be used for location-based avoidance and higher accuracy in targeting only those desired tissue locations.

The laser system may be characterized by: flash lamp or solid state laser wavelength Er: yag 2.94 μm, or other wavelengths with high water absorption near the peak, as shown on FIG. 26-2; a fiber optic transmission system having a fiber optic core between 50um and 600um with a hand held probe in contact with the eye; a flash lamp pump; doctor correlation; no eye tracking; operation-time-10 minutes per eye; physician/manual depth control.

An exemplary system functional diagram of a laser system of the present disclosure is illustrated in fig. 3B.

In some embodiments, the features may include: solid state laser wavelength Er: yag 2.94 mu m; free space, short focal length, optical transmission system with hand-held laser head, eye contact; solid-state laser wavelength Er: a Yag 2.94 μm diode, or other wavelength with high water absorption near the peak, as shown on FIG. 26-2; diode pumping; manual positioning; 2D scanning micropore placement; spots 50 to 425 μm, sclera nozzle protection device; with physician/manual depth control; semi-reclining execution; software control/foot pedal; the visualization is monitored. Exemplary system functional diagrams fig. 3A and fig. 27 (a-C).

Engineering advantages may include: lightweight components, more "space" in the handpiece than previous systems, and others. Engineering challenges may include: based on solid-state laser sources in the base station, miniaturization of all components, sufficient power/energy, and others. Clinical advantages may include: easy to use, simple, low technical content, and others. Clinical challenges may include: patient eye movement, still surgeon dependent, extra features on the eye, no eye tracking, depth control, means to keep the eyelids open (fig. 28 (a-C) and 29 (a-B)).

In some embodiments, the features may include: solid state laser wavelength Er: yag 2.94 mu m; free space, short focal length, optical transmission system with manual control, eye contact; solid state laser wavelength Er: a Yag 2.94 μm diode, or other wavelength with high water absorption near the peak, as shown on FIG. 26-2; diode pumping; manual positioning; 2D scanning micropore placement; spots of 50 to 425 μm, a sclera nozzle protection device and a foot pedal; with physician/manual depth control; semi-reclining execution; software control/foot pedal; with visualization camera, articulated arm with handpiece mount and camera, and monitor visualization, as shown in fig. 26A and 24.

Engineering advantages may include: lightweight components, more "space" in the handpiece than previous systems, and others. Engineering challenges may include: based on solid state laser sources in the base station, miniaturization of all components, sufficient power/energy, stability of the articulated arm, CCD camera image zoom and resolution, among others. Clinical advantages may include: easy to use, simple, low technical content, and others. Clinical challenges may include: patient eye movement, still surgeon dependent, extra components on the eye, no eye tracking, depth control.

In some embodiments, the features may include: solid state laser wavelength Er: yag 2.94 mu m; free space, long focal length optical transmission system with automatic control, non-patient contact; solid state laser wavelength Er: yag 2.94 μm, or other wavelengths with high water absorption near the peak, as shown on FIG. 26-2; diode pumping; 6-axis robot positioning; 2D scanning micropore placement; 15 to 20cm working distance with active depth control; a laser power monitor sensor and controller; semi-reclining execution; hands-free/software control/foot pedal; eye tracking; the spots are 50 to 425μm; eye-fixed light sources or LED arrays, ablation debris removal systems, and camera/monitor visualization; surgery time-several minutes for both eyes (as shown in fig. 26.1).

Engineering advantages may include: automation of 6-axis laser positioning, depth control, eye tracking, eye fixation points, multiple treatment modes, ablation material removal, reduced treatment time, surgeon hands-free operation, and others. Clinical advantages may include: ease of use, simplicity, faster, no need for patient eye contact, improved hole repeatability, and others. Clinical challenges may include: automated, high precision beam deflection scanners, patient eye tracking, and depth control.

In some embodiments, the above-described features of the free-space optical transmission system may be combined with the features of the fiber optic transmission system as additional subsystems.

Engineering advantages may include: integrating various subsystems, controllers, displays, and others. Clinical advantages may include: improved camera and visualization, OCT and depth verification, expanded therapeutic capabilities using the advantages of a multi-beam delivery system, and others. Clinical challenges may include: extended controllers and functions in controllers and software.

In some embodiments, the ratio of 2.94 μm Er: the Yag laser may be replaced with other wavelengths having high water absorption, as shown in the wavelength vs water absorption graph (see fig. 26-2), i.e., 2.0 μm, among others.

In some embodiments, the ratio of 2.94 μm Er: the Yag laser may be replaced by other types of Diode Pumped Solid State (DPSS) lasers with single mode emission and higher beam quality that can produce circular, square or rectangular spots.

In some embodiments, the ratio of 2.94 μm Er: the Yag laser may be replaced with other types of Diode Pumped Solid State (DPSS) lasers that combine multiple sources to achieve equivalent fluence.

In some embodiments, the ratio of 2.94 μm Er: the YAG solid-state laser may be replaced with other types of lasers with equivalent flux specifications using shorter pulse lengths. In some embodiments, the features may include: a camera that will provide both high resolution, color images; zoom range so that the surgeon sees the entire eye or bottom of the hole and allows them to monitor the treatment plan and have the opportunity to terminate and turn off the laser if needed; an electronic signal interface that allows the system to obtain image data. When used with internal image processing and analysis, the camera will also provide system control to provide eye position and automatic centering of the patient's eye for treatment, input for eye tracking software, a background image for superimposing the treatment area on the image of the patient's eye. The camera may be placed off the laser axis (see fig. 20F) to enable the field of view to see the treatment area, the entire eye, and to see features of the patient's eye to lock in eye tracking.

Engineering advantages may include: integration of CCD camera image and analysis with eye tracking and laser beam delivery systems and control software. These functions will mitigate the potential risks; keep the doctor in control of the treatment. Clinical advantages may include: improving surgeon visualization and overall control of treatment, risk mitigation of eye movement, and others.

In some embodiments, the features may include: depth control, which can be monitored by OCT and/or other techniques, and will control the remaining scalar thickness below the bottom of the hole without interrupting treatment, while ensuring that the depth of the hole limit is not exceeded. The OCT sensor will be incorporated into the laser beam axis and the optics will match the focal length to the laser beam delivery system, so the OCT system will work as the focus sensor for both OCT and laser systems. OCT will continue to sample the aperture depth and the sampling rate will provide verification between or during laser pulses so that the laser emission can be immediately terminated (for an exemplary OCT system, refer back to fig. 4B).

Engineering advantages may include: integration of the OCT system with the laser beam delivery system and control software. Clinical advantages may include: reduced surgeon dependency, reduced risk of scleral perforation, improved hole depth and repeatability, and others.

In some embodiments, a long working distance system is preferred because 1) it gives more engineering flexibility to fully characterize the process, including improvements: eye tracking, depth control, positioning accuracy, lighting and visualization, plume evacuation, cost advantage; 2) less invasive, non-contact-minimally invasive; 3) automated control/reliable, predictable results; 4) user and patient safety; 5) "no touch" program; and others.

In some embodiments, the features may include: a robot for positioning a laser beam delivery system centerline (in a 6-axis position) for positioning the centerline of the laser over the center of the eyeball at a distance to focus the beam spot on the surface of the sclera; means for rotating the laser beam delivery system 360 ° of rotation around the eye to perform all treatment modes consisting of a single ablation aperture (see the example shown in fig. 20 (E, G, H)).

In some embodiments, features of a robot for positioning a laser beam delivery system may include: long focal length optics, 10-20cm, galvanometer scanner for positioning x and y, angular motion controller for scanning only in the y direction and then step x, autofocus controller for correcting z, focusing to a single patient, means for ablating quadrants in the sub-quadrant portion in combination with reduced motion of the x and y movements and xy scanner beam motion. The robot can control 6 axes similar to a coordinate measuring machine; the laser beam delivery system can be mounted on a rotating mechanism on the axis of symmetry of the patient's eye, with the x, y scanner and focusing mechanism controlling the various axes, and others (see the example shown in fig. 20I).

Other characteristics include stability, speed, small angular accuracy of the x, y scanner(s), quality of the mobile system. Clinical advantages are hands-free operation, limited surgeon training and manual skill, reduced treatment time, no contact with the patient, and others.

In some embodiments, the patient may still move the eye to the desired position. The fixed target can be moved to each of the 4 quadrants, or sub-treatment zones in the quadrants (fig. 2B-2), and the robot or joystick position must track the eye position, including: the nose is raised; the upper temporal aspect; setting the nose; the inferior temporal aspect. Visualization of each quadrant and early working laser ablation/imaging with handheld systems can be provided. The eye fixation position may be integrated with the positioning of the treatment region on the eye based on the particular circumstances of the patient. The ability to move the fixation point of the eye may provide a means for vascular avoidance while moving the treatment region. The movement in the fixed point provides a means for moving the center of the treatment location on the eye. There are also means for breaking up the large treatment pattern into smaller ablation regions, i.e. mosaicing of the entire treatment region, reducing the angle of incidence of the beam at any point to the surface of the eye, and there is no (negate) need to move the laser beam delivery system.

In some embodiments, the fixed point will consist of a single or multiple illumination sources; selectively illuminating based on position relative to the laser beam. The illumination source may be moved with the laser delivery system or have multiple sources in a predetermined location. The illumination source may be an individually addressable LED or an array of LEDs. In conjunction with laser beam positioning, the fixed point position may be fixed or controlled as part of the eye tracking system.

A number of treatment simulations will be discussed. Regional treatment simulation: baseline model with scleral stiffness and tightness of attachment varied in a single intact zone: therapeutic combinations of zones (with and without varying attachment): separately: 0. 1, 2, 3, 4; combining: 1+2+3, 1+2+3+4, 0+1+2+3+ 4; effective rigidity: elastic modulus (E) =1.61 MPa, equivalent to-30 years old; loose attachment between sclera and ciliary body/choroid, where the values in the original accommodation model were used. See fig. 35.

The effects of zone therapy on ciliary body deformation in accommodation may include scleral stiffness, scleral stiffness + attachment.

Referring to the 5 critical zone baseline simulation, different treatment zone shapes can be applied to one scleral quadrant: original model with health regulation of the "aged" sclera: rigid starting sclera: an elastic modulus (E) =2.85 MPa, corresponding to-50 years of age; the close attachment between the sclera and the ciliary body/choroid, all other parameters are changed (ciliary body activation, stiffness of other components, etc.).

The shape therapy simulation may include: baseline model with regional "treatment" scleral stiffness: different zone shapes (without varying attachment) of treatment → treatment stiffness: an elastic modulus (E) =1.61 MPa, corresponding to-30 years of age; the effective stiffness in each zone can be determined by the amount of shape area in each zone and the values in the original tuning model.

The effect of shape therapy on ciliary body deformation in accommodation may include only scleral stiffness.

The treatment stiffness may depend on: pore volume fraction in the treatment area →% scleral volume removed by treatment; pore volume fraction is varied by varying parameters of the ablation pores; and others. Synthetic stiffness estimated as a micro-scale mixture: size within parallel evenly spaced pores/volumes = volume fraction (% of total scleral volume); the remaining volume is the "aged" sclera (E =2.85 MPa); requiring 43.5% removal of volume to change the scleral stiffness in the treatment area from old (50 years) to young (30 years); the protocol (combination of density% and depth) allows a maximum volume fraction of 13.7%, corresponding to a new stiffness of 2.46 MPa; array size = side length (mm) of the square area treated.

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

Exemplary model results are shown in fig. 42.

Treatment surface area = surface area of sclera (mm ^ 2) where treatment was applied, where treatment surface area = array square.

Thickness = thickness of sclera (mm) in the treatment area assumed uniform.

Treatment volume = volume of sclera (mm ^ 2) where treatment was applied, treatment volume = treatment surface area x thickness = array²Thickness of

Density% = percentage (%) of treatment surface area occupied by pores.

Spot size = surface area of one well (mm ^ 2).

# wells = number of wells in the treatment area.

Total pore surface area = total area within the treatment surface area occupied by the pores

Depth = depth of one hole (mm); dependent on pulse per hole (ppp) parameters

Depth% = percentage (%) of thickness extending through the aperture.

As shown in fig. 26-3A, total pore volume = total area within the treatment surface area occupied by the pores

Volume fraction = percentage (%) of the treatment volume occupied by the wells, i.e. the percentage of the scleral volume removed by the laser.

The relationships between treatment parameters include:input parameters for laser treatment; the nature of the sclera; for calculating new stiffness Input device。

The new stiffness of the sclera in the treatment region is calculated.

Volume fraction = percentage (%) of the treatment volume occupied by the wells, i.e. the percentage of the scleral volume removed by the laser.

Stiffness = elastic modulus of the sclera (MPa) before treatment.

Treatment stiffness = treatmentRear endElastic modulus of sclera (MPa); and estimating according to a micro hybrid model.

Input parameters for laser treatment: properties of sclera, input for calculating new stiffness, finite element model for treatment zone Input of typeVolume fraction effect on ciliary body deformation in accommodation: scleral stiffness aloneWhole area of treatment (area fraction) =1）。

Scenario = range of possible combinations of density% and depth,the sclera in all zones changed as a function of pore volume fraction Therapeutic stiffness of response。

Influence of volume fraction on ciliary body deformation in accommodation: scleral stiffness + attachmentFull zone of treatment (zoned) Number =1 × health = original regulation model results。

Scenario = range of possible combinations of density% and depth,the sclera in all zones changed to be in phase with the pore volume fraction Corresponding rigidityVolume fraction effect on ciliary body deformation in accommodation: scleral stiffness + treatment zone shape.

Scenario = range of possible combinations of density% and depth,the sclera in all zones is changed to an aperture with the treatment area Volume fraction and area fraction corresponding therapeutic stiffness。

J/cm2 calculation: j/cm2 x Hz (1/sec) x pore size (cm 2) = W; j/cm2= W/Hz/pore size. Example (c): the PLEASE blob is actually "square", so the area will be calculated based on the square: 7.2J/cm 2=1.1 w/300 Hz/(225 μm 10)^-4）²。

Factors affect the% ablation depth on the living eye during surgery: moisture content on the tissue surface and inside the tissue, tenon's capsule or conjunctival layer, laser emission angle, thermal damage, possibly considering water spray, low temperature spray/freeze eye drops, low temperature hydrogel cartridges in laser disposable systems (perioperative drugs such as antibiotics/steroids).

In some embodiments, the described systems, methods, and devices of the present disclosure may include the following features.

Adjustable micropore density: due to the variable number of micropores created per application area, dose and inflammation control can be achieved. The size of the micropores can be adjusted; dose and flexible patterning of microwells. Adjustable micropore thermal distribution: the system can produce microwells with tunable heat distribution that minimizes the creation of condensation zones. Adjustable depth with depth identification: the system creates micropores in a controlled manner and prevents the ablation anatomy from identifying too deep to avoid the vessel. Fig. 26-4 illustrate anatomy identification. Laser safety level: the device is a class 1c laser device, the system detects eye contact, and the eye pod covers the cornea. Integrated smoke evacuation and filtration: partial ablation can be performed without any additional requirements when installing the smoke evacuation system, since smoke, steam and tissue particles will be sucked out directly by the integrated system. The laser system will have an integrated CCD real-time camera (e.g., endocamera (endocamra)) with a biofeedback loop to the laser guidance system integrated with the GUI display for depth control/limit control. (see FIG. 26-4-1).

In some embodiments, the described systems, methods, and devices of the present disclosure may provide: the laser system biofeedback loop uses melanin content to integrate chromophore identification of color change (computer integration for various pore grading of color change; a priori depth information in regions of 3 thicknesses). A laser system capable of integrating a priori scleral thickness mapping for communication with laser guidance planning and scleral microporation. OCT or UBM or 3D tomography is used. The laser system that issued the code was programmed with controlled pulses for each program. Electronically linked to report to Ace Vision. All data reports (calibration and service data, statistics, etc.). The laser system components are constructed in a modular fashion to facilitate service maintenance and repair management. Including pre-treatment, post-treatment and subsequent pre-treatment self-calibration settings and real-time process calibration. All calibrations are recorded in the database. (plug and play service) laser communication port for online (WIFI service troubleshooting, report generation and communication with company (AVG), WIFI access to diagnostic information (error code/component requirements), and order to assign troubleshooting repair and maintenance or service of an assignment service representative). A spare service suite is created for service maintenance and repair of field repairs. The laser system key card is integrated with controlled pulse programming including time constraints. The aiming beam has a flexible shape to set boundary conditions and also to trigger if the laser nozzle is on axis, level and orientation. The aiming beam coincides with the alignment fixation beam to trigger the system Go No Go to start therapeutic ablation. The laser system requires the inclusion of an eye tracking system and corresponding eye fixation system to make ablation safe to control eye movement. The laser system requires the ability to have "on-axis" transmission through a gonioscopic system, or through slit lamp applications or free space applications, to provide a microhole in the sclera. These would require higher power, good beam quality and integration of fixed targets and/or eye tracking systems. Good beam quality means: the laser system must be focused down to 50 μm and up to 425 μm. The laser system is capable of performing a fast 360 degree procedure by galvanometer scanning and using a robot to change quadrant treatment (4 quadrants per eye, about 10 seconds per quadrant; 1-2 seconds to reposition the laser to the subsequent quadrant) within 40-45 seconds per full eye. The laser system is a workstation integrated with a pedal and a computer monitor; OCT; a CCD camera and/or a microscope system (if desired). A laser system patient positioning table/chair module that is flexible from a supine position; flexible angles; or sitting. An electric chair. (see FIGS. 26-4, which illustrate anatomical structure recognition.)

In some exemplary operations, the described systems, methods, and devices of the present disclosure may include the following medical procedures: 1) the user manual may give information about the correct operation (handle) of the system. 2) An eye applicator is placed over the treatment area and an applicator unit is placed over the eye applicator. 3) The user may set the treatment parameters. 4) The user starts the treatment process. 5) The user may be notified about the continued status of the treatment. 6) The user may be informed about the calibration of the energy on the eye before and after treatment. 7) To prevent undesirable odors, ablation smoke may be prevented from spreading. 8) The user may be informed about the visualization of the eye during, between quadrants and after treatment.

Typically, the system will have low maintenance. If necessary, system service can be performed as quickly as possible, resulting in minimal downtime. Furthermore, the cost of service may be lower than with conventional laser systems. The applicator unit, the eye applicator and the disposable insert can be handled easily and hygienically, in particular when attached and detached. The software may allow data exchange between the device and the PC.

Micropore-exemplary parameters

。

The service requirements may include: annually or a maximum after 1000 processes, whatever happens first. Annual or maximum after 2000 processes, whatever happens first. Annually or at a maximum after 3000 processes, whatever happens first. Or otherwise. Total product lifetime: all components can be rated to withstand a product life of at least 5 years. Cleaning: the entire system was wiped and cleaned with a damp cloth that was not saturated with standard hand sanitizer. The system operation is performed by a pre-approved electronic key fob. Patient position: the patient may be in a horizontal position. Visualization is required during surgery: illumination assistance of the eye provides visualization-either an external light source or integrated into the laser adapter fixture, the GUI of the CCD camera and computer monitor is a required module. The patient may be in a horizontal, inclined or sitting position. The patient's eyes are protected during the procedure. The operation is as follows: when the applicator and insert are attached, the system may only allow activation of the laser with proper tissue contact and with authenticated user access. Hole depth monitor: maximum depth monitored by the end switch (optical or peer monitoring). Depth monitor/depth control is incorporated. Management of intraoperative eye movement: for fully contactless eye surgery, there are eye tracking techniques with corresponding eye fixation targets. Vasculature avoidance: the ocular vasculature is scanned/defined to avoid micropores in this region. See fig. 4A (1-10) which illustrates how microwells/nanopores can be used to remove surface, subcutaneous and interstitial tissue and affect surface, interstitial, biomechanical properties (e.g., planarity, surface porosity, tissue geometry, tissue viscoelasticity and other biomechanical and biorheological properties) of an ablation target surface or tissue.

The performance requirements may include: variable pore size, pore array size and pore location. Preparation time: 5 minutes from the power-on of the device until the start of the microperforation process (assuming average user reaction time). The robots are merged according to quadrants to meet the treatment time requirements. Treatment time for one surgery was <60s, 45 s. The treatment time requirement is achieved by quadrant merging robots. Diameter of the micropores: is adjustable between 50 mu m and 600 mu m. Tissue ablation rate: is adjustable between 1 and 15 percent. Micropore array size: the area is adjustable between 1mm x 1mm and 14 x 14mm, and the square holes are used for customizing the shape array. Multiple ablation mode capabilities. Short press to activate and deactivate the laser: the actual microperforation process may be initiated by pressing the foot switch for only a short period of time, rather than pressing it during the entire microperforation. Stopping the laser may be done the same. Depth of the ablation hole: 5% to 95% of the scleral thickness. Biocompatibility: all tissue contacting components are made of materials that meet the requirements of the medical device.

In some embodiments, the system may include: laser wavelength: 2900nm +/-200 nm; water absorption maximum around mid IR. Maximum laser fluency: being more than or equal to 15.0J/cm in organization, being more than or equal to 25.0J/cm in organization; to extend the therapeutic potential of 2900nm +/-200 nm; water absorption maximum around mid IR. Laser setting and combining: the laser repetition rate and pulse duration may be adjustable by using a predefined combination in the range of 100-. The range can be regarded as the minimum range, is more than or equal to 15.0J/cm in organization, and is more than or equal to 25.0J/cm in organization，To expand the treatment possibilities. Number of active treatment pulses per well: the "active" setting may also be selectable to create pores deep into the dermis, e.g., with>1mm deep. Since depth is primarily flux controlled, a high number of pulses per well will automatically result in a larger depth value. Thus, the per-hole pulse (PPP) value is adjustable between 1-15 PPP. The laser repetition rate and pulse duration may be adjustable by using a predefined combination in the range of 100-500 Hz and 50-225 μ s. The range may be considered a minimum range. Vibration and vibration: the device may be capable of withstanding a single use or multiple uses as providedUsing truck transport (in the case of service or repair) inside the package. The "active" setting may also be selectable to create pores deep into the dermis, e.g., with>1mm deep. Since depth is primarily flux controlled, a high number of pulses per well will automatically result in a larger depth value. Thus, the per-hole pulse (PPP) value may be adjustable between 1-15 PPP. Preventing odor diffusion: a system can be implemented that reduces the spread of bad smells to a minimum. GUI: the user interface may be supported by a reasonable display size. Audible noise: the maximum noise generated by the system (100% for cooling and evacuation systems) must not exceed 70 dBA or 50 Dba. Damping properties of the cell: the unit can withstand a drop of a certain height without any significant damage leading to system failure. System connectivity to one or more of USB, LAN, WLAN, bluetooth, Zigbee.

The physical requirements may include: the laser system may be incorporated into a "cart" type workstation unit with lockable wheels and counterweight/articulated arms, such as to prevent the cart from tipping over during use or transport (see fig. 24 and 26-5). There is no tilt requirement. Weight: weight (cart + balance weight/articulated arm): <100 kg. Auxiliary equipment: video surveillance systems, such as for use with standard eyepieces, and the like. Shipping and use temperature and relative humidity specifications: humidity: < 70% RH, no coagulation; working temperature: 18 to 35 ℃; humidity: < 70% RH, no coagulation; storage and transportation temperature: -10 to 60 ℃.

Design and availability: the availability of the design may meet the general needs of the target user population, including primary users, doctors, and medical personnel. And (3) balancing the weight: the weight balance of the unit can reach market acceptance. Shape of the applicator unit: the shape of the cells may be optimized. Radius of action: the connection between the desktop unit and the handheld unit may allow an action radius of at least 1.2 m. Good vision to see proper positioning of the eye: the user may be able to verify proper positioning of the laser on the eye tissue. Convenient handling of the applicator and insert: the applicator and insert may be easily attachable and detachable.

The fields of application permitted on the human body: generally, the device may be applied to the eye. Biocompatibility: all tissue contacting components are made of materials that meet the requirements of the medical device.

The accessory may include: applicator insert (disposable part): a disposable component for collecting ablated tissue, the component establishing a hygienic interface between the device and the tissue. Ocular pod (optional): the applicator may be reusable, easy to clean, biocompatible, and sterilizable. A foot switch: the foot switch operates for standard laser transmission.

Some embodiments in the present application include the use of pulsed 2.94 μm Er: YAG laser and hand-held probe to ablate a hole in the sclera, modifying the configuration of the system of plasticity of a region of the sclera.

In some embodiments, the system comprises a portion of a PLEASE ™ platform and an additional volt 3mikron ™ class IV Er: YAG fractional laser system. The main components are: igaxy modules, spherical application (e.g. dish) modules include: 3 mikron's DPM-2 (Er: YAG), scanning unit and eye tracking, robotic platform for positioning, touch screen control display, camera system, microscope, suction system, depth detection system, illumination and laminar flow, aiming beam. The mobile cart module may include: a power supply, a touch screen control display for non-surgical personnel, a control and cooling unit, a DriCon ™ platform, a wireless foot pedal, and others.

In some embodiments, some or all of the system may be easily positioned over the patient's face. The igaxy module (see also fig. 26-1) allows the establishment of a local sterile environment with internal laminar flow. The igaxy module covers all relevant parts of the treatment process, such as the electromechanical motion system, which moves the laser to a selected treatment area on the sclera with high precision.

The system may include the ability to ensure control and warning/control functions that can reliably detect the depth of tissue ablation and ultimately the interface between the sclera and choroid, and effectively prevent ablation beyond the ablation depth of the sclera, the ability for the system to have ergonomic and clinical utility and be acceptable for use by a physician, the ability to have high reliability and control to ensure patient safety and reproducibility of the procedure, the ability to scan at greater working distances to produce rapid procedures.

In some embodiments, the system includes a display included in the igaxy module to view tissue regions (physician display), controls, and safety (see also below), including laser supply, electronic and motion control platforms, and a safe, direct interface to the iBase station. The system may also include a motion platform: a translation stage to position the laser and optics and scanner in a specific area: 3mikron module and beam forming optics, depth control system to avoid too deep ablation, eye tracking module, safe aspiration and laminar flow for the operator. Beam deflection is synchronized with eye tracking for microwell array generation. Other components and functions include: camera units for vision, IBase smart mobile base stations, operator displays for control and safety, distribution of power to different modules, water cooling of laser systems, optional foot pedals, communication interfaces with the outside world, commissioning, updating and other functions, and main power for a wide range of power supplies for international operation.

As described above, in some embodiments, the described systems, methods, and devices of the present disclosure may include creating a finite element model of the accommodation mechanism including seven major zonule pathways and three ciliary muscle portions, calibrating and validating the model by comparison with previously published experimental measurements of ciliary muscle and lens movement during accommodation, and using the model to study the effects of zonule anatomy and ciliary muscle architecture on health accommodation function. The model may include the lens geometry and lens-outer structure, as well as simulations of accommodation driven by novel zonule stretching and muscle contraction.

In some embodiments, the described systems, methods, and devices of the present disclosure may include a method for altering a biomechanical property of a biological tissue using a complex formed from a matrix of perforations on the tissue, where the configuration is based on a mathematical algorithm. The change in the biomechanical properties of the biological tissue are related to the elasticity, cushioning, elasticity, mechanical damping, flexibility, stiffness, hardness, configuration, alignment, deformation, mobility, and/or volume of the tissue. The matrix of perforations forms a non-monotonic force deformation relationship on the tissue that has a range of isotropic elastic constants across the medium. Each matrix formation creates a linear algebraic relationship between row length and column length, where each puncture of the tissue has a continuous linear vector space with a derivative up to n. Where N is an infinite number. The composite creates a total surface area, wherein each perforation has a proportional relationship to the total surface area of the tissue. The composite may also be arranged to achieve a balance of forces, stresses and strains and reduce shear effects between matrix formation and perforation. Each perforation may be an ablation volume of tissue defining a lattice of dots on the tissue, wherein a preferred shape of the ablation volume is cylindrical. The matrix formation consists of mosaics with or without repeating patterns, where the mosaics are euclidean, non euclidean, regular, semi regular, hyperbolic, parabolic, spherical or elliptical and any variation thereof. Each perforation may have a linear relationship with the other perforations in each matrix formation and the composite of the matrix, respectively. Mosaicing is directly or indirectly related to the stress and shear strain atomic relationship between tissues by computing a mathematical array of position vectors between the perforations. The atomic relationship is a predictable relationship of the volume removed by each perforation to changes in biomechanical properties, which are considered elements of a mathematical algorithm. The predictable relationship of the volumes removed may be mutually exclusive. The tessellation may be a square, which may be subdivided into tessellations of the derivatives of equiangular polygons to n. In some embodiments, the mathematical algorithm uses the factor Φ or Phi to find the most efficient placement of the matrix to change the biomechanical properties of the tissue. The factor Φ or Phi can be 1.618 (4 significant digits) which represents any fraction across the vector of a set of lattices having the shortest length relative to the length of all other vectors. In some embodiments, the mathematical algorithm of claim 1 comprises a non-linear hyperbolic relationship between planes of biological tissue and at any boundary or partition of adjacent tissue, planes and spaces within and outside the matrix.

In some embodiments, the described systems, methods, and devices of the present disclosure may include a protective lens 2700 as shown in fig. 27A-C.

In some embodiments, the described systems, methods, and apparatus of the present disclosure may include a sight glass 2810/2820/2830 as shown in various embodiments in fig. 28A-C. 29A-B illustrate an exemplary procedure using a scope 2830.

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

It is noted that aspects of the disclosure may be described herein as a process which is depicted as a flowchart, a flow diagram, a structure diagram, or a block diagram. Although a flowchart may describe the operations as a sequential process, many of the operations can be performed in parallel or concurrently. In addition, the order of the operations may be rearranged. When the operation of the process is completed, it terminates. A process may correspond to a method, a function, a procedure, a subroutine, a subprogram, etc. When a process corresponds to a function, its termination corresponds to a return of the function to the calling function or the main function.

The above described implementations are believed to be novel over the prior art and are believed to be critical to the operation of at least one aspect of the present disclosure and the achievement of the above described objectives. The words used in this specification to describe the present embodiments are to be understood not only in the sense of their commonly defined meanings, but also by special definition in this specification: structure, material, or acts beyond the scope of the commonly defined meanings. Thus, if an element can be understood in the context of this specification as including more than one meaning, then its use must be understood as being generic to all possible meanings supported by the specification and by the word or words describing the element.

The definitions of the words or figure elements above are meant to include not only the combination of elements which are literally set forth, but all equivalent structure, material or acts for performing substantially the same function in substantially the same way to obtain substantially the same result. In this sense, therefore, it is contemplated that an equivalent substitution of two or more elements may be made for any one of the elements described and various embodiments thereof or that a single element may be substituted for two or more elements in a claim.

As will be recognized by those of ordinary skill in the art, changes that are now known or later devised from the claimed subject matter are expressly contemplated as being equivalents within the intended scope and its various embodiments. Accordingly, obvious substitutions now or later known to one with ordinary skill in the art are defined to be within the scope of the defined elements. The disclosure is therefore intended to 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 idea.

In the foregoing description and in the drawings, like elements are identified with like reference numerals. The use of "e.g.," such as, "etc" and "or" indicates a non-exclusive alternative without limitation unless otherwise specified. The use of "including" or "comprising" means "including but not limited to" or "including but not limited to" unless otherwise specified.

As used above, the term "and/or" placed between a first entity and a second entity refers to one of: (1) a first entity, (2) a second entity, and (3) the first entity and the second entity. Multiple entities listed with "and/or" should be interpreted in the same way, i.e., "one or more" of the entities so connected. In addition to the entities specifically identified by the "and/or" clause, other entities may optionally be present, whether related or unrelated to those specifically identified. Thus, as a non-limiting example, in one embodiment, when used in conjunction with an open language such as "including," references to "a and/or B" may refer to a only (optionally including entities other than B); in another embodiment, only B (optionally including entities other than a); in yet another embodiment, refer to both a and B (optionally including other entities). These entities may refer to elements, roles, structures, procedures, operations, values, and the like.

It should be noted that where a discrete value or range of values is set forth herein (e.g., 5, 6, 10, 100, etc.), it is noted that unless otherwise stated, that value or range of values can be more broadly claimed than a discrete number or range of numbers. Any discrete values mentioned herein are provided merely as examples.

Terms as used above may have the following definitions.

Collagen consists of 3 individual strands of α and/or β chains to form a triple helix collagen fibrils are 25-230 nm in diameter and are arranged into bundles of fibrils that are highly disordered and variable in size within the scleral stroma, and that are very ordered and uniform in size within the corneal stroma type 1 is the most common collagen found in the cornea and sclera.

The spiral wound in the collage molecule has a non-helical portion at the end of the strand. Single molecules from natural linkages produce long collections of parallel molecules, i.e. collagen fibrils. The structure of collagen fibrils is produced by intermolecular cross-linking.

Collagen in the cornea and sclera is associated with polysaccharide molecules called glycosaminoglycans (GAGs). Proteoglycans are the core proteins to which many GAGs are attached and they form a matrix around collagen fibrils. The major GAGs in the cornea and sclera are dermatan sulfate and keratan sulfate. Collagen fibrils in the cornea and sclera are then surrounded by and embedded in proteoglycans.

GAGs are fairly large molecules. They also have a very negative charge and therefore attract positively charged molecules such as sodium. Sodium comes with water, so tissues with large amounts of GAG will absorb considerable water if left to their own facility. H₂The combination of O produces a gel around the collagen fibrils, thereby creating a matrix. The corneal stroma has a higher affinity for water, while the cornea has a very narrow limit because it must remain transparent. In the cornea, the spacing of collagen is critical for its transparency. The water content needs to be maintained at a stable level to maintain regular intervals of collagen.

Typically, the sclera acts to maintain the shape of the eye and resist deformation forces both Internal (IOP) and external. The sclera also provides attachment points for the extraocular muscles and optic nerve. The opacity of the sclera is caused by many factors including the number of GAGs (glycosaminoglycans-complex carbohydrates covalently bound to collagen) (fig. 8.3, page 327), the amount of water present, and the size and distribution of collagen fibrils.

The sclera had only 25% of the total GAG present in the cornea. Because GAGs attract water, the sclera hydrates less than the cornea (but not 75% less; due to several structures care is maintained at lower hydration levels in the cornea). Large variations in fibril size and irregular spacing between scleral components result in light scattering and opacity. The color of the sclera is white when healthy, but may change color over time or due to disease (e.g., hepatitis). Internally, the sclera fuses with choroidal tissue in the suprachoroidal layer. The innermost scleral layer is called the brown layer.

The sclera comprises a number of pores in which structures pass through or interrupt the expansion of the sclera. At the posterior pole of the eye, the optic nerve passes through the posterior scleral layer. This region is bridged by a network of scleral tissue called the lamina cribosa. The lamina cribosa is the weakest part of the sclera. Elevated IOP may lead to bulging and subsequent tissue damage at the optic nerve. The scleral blood supply is very limited and the tissue is mostly avascular. It does not contain capillary beds, only a few small branches from the outer layer of the sclera and choroid and branches from the long posterior ciliary arteries. The sclera thickness varied from 1.0 mm at the posterior pole to 0.3 mm after rectus muscle insertion. The sclera covered 5/6 (about 85%) of the entire eye.

The sclera consists of 3 layers: (1) the outer layer of the sclera, which consists of loose vascular connective tissue. The branches of the anterior ciliary artery form a network of capillary vessels prior to insertion of the rectus muscle. Surrounding the surrounding cornea and physically linked to the tenon's capsule by the strands of connective tissue (see orbital research guidelines). The sclera becomes thinner towards the back of the eye. (2) The scleral stroma is a thick dense layer of connective tissue that is continuous with the corneal stroma at the limbus. (3) The brown layer refers to the few pigmented cells that remain attached to the sclera after removal of the choroid.

The tear layer consists of three layers, which together are 7 μm thick. The outer or foremost layer (1) is the lipid layer and the middle layer (2) is the aqueous layer of the atrium derived from the lacrimal gland. The mucus layer (3) is in contact with squamous cells (posterior layer).

The cornea functions as the principal refractive element of the eye. The most important feature is transparency. The cornea typically comprises about 1/6 of the outer layer of the eye. A curvature radius of 8 mm; in general, the cornea is 0.52-0.53 mm thick at the center and 0.71 mm thick at the periphery. The posterior (inner) side of the cornea has a smaller radius of curvature than the anterior side.

The cornea is the primary refractive component of the eye, contributing more than 40 diopters. It is avascular and transparent, with excellent light transmission. The anterior part of the cornea is covered with a tear film (see above). The optical zone is a circular area of the cornea, located 4mm around the corneal vertex. Central radius of curvature and refractive power: air/tear interface + 43.6D; tear/cornea + 5.3D; cornea/aqueous humor-5.8D; total central power = 43.1D.

The cornea consists of five layers. They are, from front to back: 1) epithelium; 2) bowman; 3) the interstitium; 4) decemet; 5) endothelium, endothelium.

The epithelial layer is the first corneal layer and is the most complex. The epithelial cell layer is comprised of-6-8 rows of cells. The epithelial layer is about 50 μm thick. The whole cornea is approximately 500 and 700 microns (mum) thick (0.5 to 0.7 mm). The superficial layer (anterior) consists of non-pigmented squamous cells with a flat appearance. The surface of these cells consists of numerous microvilli, which serve to increase surface area and stabilize the tear film 'layer'. Squamous cells are connected by tight junctions, i.e., zonula Occludens. This creates an effective barrier to the exclusion of foreign objects that may cause damage. As surface cells age, their attachment is lost and the cells are shed in the tear film. New cells migrate outward from the more interior rows of epithelial cells (bowman) to the tear film layer.

The corneal epithelium is subdivided into 3 sections: 1) a layer of squamous cells at the surface of the cornea, 2) winged cells having a winged appearance, and 3) columnar basal cells. All 3 cell types were originally derived from columnar basal cells. Thus, the cells are constantly renewed along the substrate surface and eventually (within about 10 days) will renew the entire new cell layer. The basal cells communicate through the gap connection. The middle layer of the winged cells is 2-3 layers thick. These cells are polyhedral and have a convex anterior surface and a concave posterior surface. The rearmost cell layer consists of a single row of columnar basal cells. Cells transform from columnar to cubic to squamous. Programmed cell death is called apoptosis. This process occurs throughout the body, including the corneal epithelial cells. Cells are linked to adjacent cells by desmosomes and to basement membrane by hemidesmosomes. The basement membrane (Bowman) is formed by secretions from basal epithelial cells. New epithelial cells form around the cornea, and then they migrate toward the center of the cornea. The epithelial layer of the cornea has 325000 nerve endings. These nerve endings are from about 2000 nerves from the medial and lateral long ciliary nerves.

The Bowman's layer (formerly Bowman's membrane) is the second corneal layer. This layer of the cornea is about 10 μm thick. It is a dense sheet of acellular fibers of randomly arranged interwoven collagen fibers. The fibrils are 20-25 μm in diameter. Bowman's layer is the transition layer between the basal epithelium and the stroma. This layer is produced by the epithelium; it does regenerate, but is very slow. Corneal nerves cross the layer that loses their Schwann cell coverage and penetrate into the overlying epithelium as unmyelinated fibers. Bowman's layer terminates at the pericornea.

The corneal stromal layer is the third layer, also known as the lamina propria. It is 500 to 700 microns thick, accounting for about 90% of the total corneal thickness. It consists of collagen fibrils and fibroblasts. Fibroblasts in the corneal stroma are commonly referred to as keratocytes [ formerly known as keratosomes ] and are specialized fibroblasts that produce collagen fibrils during development and maintain connective tissue in the mature eye. The collagen fibrils of the cornea are 25-35nm in diameter and are grouped into flattened bundles called lamellae. 200-300 lamellae were distributed throughout the corneal stroma. All lamellae extend parallel to the surface of the cornea. These stacked fibers account for 90% of the thickness and volume of the cornea. Adjacent lamellae are at an angle to each other; each lamella extends across the entire cornea; each fibril extends from limbus to limbus. In the first 1/3 of the matrix, the slices were 5-30 μm wide and 0.2-1.2 μm thick. Post 2/3 for the matrix was more regular and larger (100-. At the innermost layer, the next adjacent corneal layer, the Descemet membrane, collagen fibrils are interwoven to form a dense but thin collagen sheet that contributes to maintaining the attachment between the stroma and the Descemet membrane. The corneal cells in the stroma produce fibrils that make up the lamellae. Between the fibrils is a matrix comprising proteoglycans (proteins with carbohydrate glycosaminoglycans (GAGs)). GAGs are hydrophilic negatively charged, located around a specific site around each collagen fibril. The hydrophilic nature of GAGs serves to keep the matrix fully hydrated, which helps to maintain the spatial arrangement of fibrils. Corneal hydration and the regular arrangement of fibrils contribute to the transparency of the cornea. Thus, proper hydration is critical to maintaining transparency. Proper hydration is maintained by the action of the epithelium and endothelium to maintain equilibrium (primarily by pumping water out of the cornea).

The fourth corner film layer is a Descemet film layer. Its function is to act as a tough, resistant barrier to the perforation of the structure and cornea. Secreted by the endothelium. It has 5 kinds of collagen, mainly VIII type. It is considered to be the basement membrane of the endothelium. This layer is constructively added with new material, so it becomes thicker with age; it is about 10 microns thick. It has an anterior portion that presents a banded appearance, like the lattice of collagen fibrils. The posterior part of the Descemet membrane is banded and secreted throughout life by endothelial cells.

Some terms may have different definitions, in part or in whole, than those in this document. For example, shrinkage has been defined to mean: narrowing or pulling together < constrict pupil of eye >; is subjected (as part of the body) to compression < contracting nerve >; becoming stenotic; becoming tighter and narrower, or something becoming tighter and narrower, such as a drug causing a vessel to constrict.

Contractures have been variously defined to mean: permanent shortening that produces deformation or distortion (e.g., muscle, tendon, or scar tissue); shortening; become reduced in size; in the case of muscles, shorten or sustain an increase in tension; obtained by infection or infestation; a clear bilateral commitment by psychotherapists and patients to guidelines for established actions to achieve psychotherapeutic goals; straightening the limb to reduce or eliminate the angle formed by the bend; the distal segment of the limb is placed in such a position that its axis is continuous with the axis of the proximal segment.

Extension has been defined to mean: an additional part, i.e. a part that has been or can be added, or a part that can be pulled out to enlarge or lengthen something.

Dilation has been defined in each case to mean: the behavior or course of dilation; the mass or state of expansion; the process of increasing in size, number or importance, or in this way making something more up, becomes exaggerated: added course, or something added in size, degree, range, or quantity.

Perforations have been defined in various forms to mean: punching one or more holes in something; the spine has one or more apertures.

In diagnostic or therapeutic radiology, plates made of one or more metals, such as aluminum or copper, placed in an x-or gamma-ray beam allow a greater proportion of higher energy radiation to pass through and attenuate lower energy and less desirable radiation, thereby increasing the average energy or the hardening beam. Apparatus for isolating segments of a spectrum in a spectrophotometric analysis. Mathematical algorithms applied to image data are used for the purpose of improving image quality, usually by suppressing or enhancing high spatial frequencies. Passive electronic circuits or devices that selectively allow certain electrical signals to pass through. A device for placement in the inferior vena cava to prevent clotting in the lower extremities from causing pulmonary embolism. There are many variations.

Piercing is defined as forming one or more holes in something; perforation for tearing: perforating the paper with a row of small holes to make it easier to tear it open; penetrate something: penetrate or pass through something; organisms with small pores: small holes are decorated; organisms with transparent spots: dotted with transparent spots.

Perforating: drilling, boring, drilling, driving, boring, honeycombing, piercing, penetrating, piercing, digging, probing, punching, piercing, slitting, piercing, digging, chiseling, digging, penetrating, perforating, piercing, digging, piercing, perforating, reaming, perforating, engraving, tunneling, perforating

Crenels have been defined as: retracting; grooving; as with serrated leaves; square notches with repetition like those in battlements; "modeling of sawtooth"

Compression: decrease in size, decrease in volume or mass of something by applying pressure, or a condition that has been treated in this manner.

And (3) reducing pressure: and (3) pressure reduction: a reduction in ambient or intrinsic pressure, in particular a reduction in the controlled pressure experienced by divers to prevent decompression sickness; reducing pressure in the organ: surgery to reduce pressure in an organ or part of the body, for example caused by fluid on the brain, or to reduce pressure of tissue on nerves; calculating data expansion: expanding the compressed computer data to full size.

Flexible: easy to be led or directed; 'a fictitious crowd good for publicity' which can easily adapt to different situations; "person with strong adaptability"; "Flexible personality"; "elastic terms under contract" [ elastic, flexible, pliable ]; "Flexible line"; "a flexible sapling" [ flexible, flexible ]; [ ductility, forgeability, flexibility, stretchability, elongatability ]

Flexible: capable of being bent or flexed or twisted without breaking; can be shaped or bent or pulled out; "ductile copper"; "wrought metals such as gold"; "they soak the leather to make it pliable"; "flexible molten glass"; "made of a high tensile steel alloy".

Diaphragm: a muscle membrane partition separating the abdominal cavity and the thoracic cavity and functioning in respiration; also known as diaphragm (midriff); a thin disc, in particular in a microphone or a telephone receiver, which vibrates in response to sound waves to generate electrical signals, or in response to electrical signals to generate sound waves; the muscle membrane separator separates the abdominal cavity and the thoracic cavity and functions in breathing.

A hole as used herein refers to a tiny opening in a tissue as in the skin of a human or animal, e.g. serving as an outlet for perspiration.

The nuclear pore in the membrane of the nuclear envelope opens, which allows exchange of material between the nucleus and the cytoplasm.

Nucleic acids can be defined as polymers consisting of nucleotides; such as DNA and RNA.

Claims (30)

1. A system for providing microporous medical treatment to improve biomechanics, the system comprising:

a laser for producing a beam of laser radiation on a treatment axis that is not aligned with the patient's visual axis, operable for use in a subcutaneous ablation medical treatment to produce an array pattern of biomechanically improved microwells;

a housing;

a controller within the housing in communication with the laser and operable to control dosimetry of the beam of laser radiation as applied to target tissue;

a lens operable to focus a beam of laser radiation onto target tissue;

an automated off-axis subcutaneous anatomy tracking, measurement, and avoidance system; and is

Wherein the array pattern of micropores is at least one of a radial pattern, a spiral pattern, a leaf pattern, or an asymmetric pattern.

2. The system of claim 1, wherein the array pattern of microwells is a spiral pattern of an archimedean spiral, an euler spiral, a fermat spiral, a hyperbolic spiral, a chain spiral, a logarithmic spiral, a Fibonacci spiral, a golden spiral, or a combination thereof.

3. The system of claim 1, wherein the pattern of the array of microwells has a controlled asymmetry.

4. The system of claim 3, wherein the controlled asymmetry is at least a partial rotational asymmetry about a center of the array pattern.

5. The system of claim 1, wherein the pattern of the array of microwells has controlled symmetry.

6. The system of claim 5, wherein the controlled symmetry is at least partial rotational symmetry about a center of the array pattern.

7. The system of claim 1, wherein the array pattern has a plurality of clockwise spirals and a plurality of counterclockwise spirals.

8. The system of claim 7, wherein the number of clockwise spirals and the number of counterclockwise spirals are the Fibonacci number or a multiple of the Fibonacci number.

9. The system of claim 7, wherein the number of clockwise spirals and the number of counterclockwise spirals are in a ratio that converges on the golden ratio.

10. The system of claim 4, wherein the at least partial rotational asymmetry extends to at least 51% of microwells of the array pattern.

11. The system of claim 4, wherein the at least partial rotational asymmetry extends to at least 20 microwells of the array pattern.

12. The system of claim 6, wherein the at least partial rotational symmetry extends to at least 51% of the pattern's micropores.

13. The system of claim 6, wherein the at least partial rotational symmetry extends to at least 20 microwells of the array pattern.

14. The system of claim 1, wherein the pattern of the array of microwells has random asymmetry.

15. The system of claim 1, wherein the pattern of the array of microwells has random symmetry.

16. A method of providing microporous medical treatment to improve biomechanics, comprising:

in a subcutaneous ablation medical treatment, a treatment beam is generated by a laser on a treatment axis that is not aligned with the patient's visual axis to produce an array of biomechanically improved microwells;

controlling dosimetry of the treatment beam while applied to the target tissue by a controller in electrical communication with the laser;

focusing the therapeutic light beam through a lens onto the target tissue;

monitoring the eye position for applying the treatment beam by an automated off-axis subcutaneous anatomy tracking, measurement, and avoidance system; and is

Wherein the array pattern of micropores is at least one of a radial pattern, a spiral pattern, a leaf pattern, or an asymmetric pattern.

17. The method of claim 16, wherein the pattern of the array of microwells is a spiral pattern of an archimedean spiral, an euler spiral, a fermat spiral, a hyperbolic spiral, a chain spiral, a logarithmic spiral, a Fibonacci spiral, a golden spiral, or a combination thereof.

18. The method of claim 16, wherein the pattern of the array of microwells has a controlled asymmetry.

19. The method of claim 18, wherein the controlled asymmetry is at least a partial rotational asymmetry about a center of the array pattern.

20. The method of claim 16, wherein the pattern of the array of microwells has controlled symmetry.

21. The method of claim 20, wherein the controlled symmetry is at least partial rotational symmetry about a center of the array pattern.

22. The method of claim 16, wherein the array pattern has a plurality of clockwise spirals and a plurality of counterclockwise spirals.

23. The method of claim 22, wherein the number of clockwise spirals and the number of counterclockwise spirals are the Fibonacci number or a multiple of the Fibonacci number.

24. The method of claim 22, wherein the number of clockwise spirals and the number of counterclockwise spirals are in a ratio that converges on the golden ratio.

25. The method of claim 19, wherein the at least partial rotational asymmetry extends to at least 51% of microwells of the array pattern.

26. The method of claim 19, wherein the at least partial rotational asymmetry extends to at least 20 microwells of the array pattern.

27. The method of claim 21, wherein the at least partial rotational symmetry extends to at least 51% of the pattern's micropores.

28. The method of claim 21, wherein the at least partial rotational symmetry extends to at least 20 microwells of the array pattern.

29. The method of claim 16, wherein the pattern of the array of microwells has random asymmetry.

30. The method of claim 16, wherein the pattern of the array of microwells has random symmetry.