Systems, methods, and devices for pressure wave ophthalmic treatment

Abstract

A device, system, and method for treating an eye using external pressure wave generation. A shockwave generator includes a housing including a fluid-filled chamber and an eye-contacting surface or cavity configured to contact a surface of an eye. Coaxially aligned first and second electrodes disposed within the housing are configured to, upon energization, create an electrical arc across a gap between the electrode tips, thereby generating a shockwave in the fluid of the fluid-filled chamber. The shockwave generator is engaged to the surface of the eye prior to focusing the shockwave on a predetermined location on the surface of the eye or a predetermined location under the surface of the eye. A plurality of shockwave generators can be disposed within a fluid-filled chamber of a contact lens, which can include a contact balloon.

Description

[0001] Cross-referencing

[0002] The subject matter of this application relates to the following patent applications: U.S. Provisional Patent Application No. 62 / 884,333, filed August 8, 2019, entitled "Systems, Methods, and Apparatus for Pressure-Wave Ocular Therapy" (Attorney-at-Law No. 56574-703.101); U.S. Provisional Patent Application No. 62 / 979,097, filed February 20, 2020, entitled "Systems, Methods, and Apparatus for Pressure-Wave Ocular Therapy" (Attorney-at-Law No. 56574-703.102); and U.S. Provisional Patent Application No. 63 / 043,988, filed June 25, 2020, entitled "Systems, Methods, and Apparatus for Pressure-Wave Ocular Therapy" (Attorney-at-Law No. 56574-703.103), the entire contents of which are incorporated herein by reference. Background Technology

[0003] Existing methods and devices for treating glaucoma, presbyopia, age-related macular degeneration (AMD), dry eye disease, and other eye conditions may produce less than ideal results.

[0004] For example, many existing methods for treating glaucoma focus on lowering the intraocular pressure (IOP) of the eye and may be more complex and / or invasive than ideal. Current glaucoma interventions include, for example, lateral delivery of medications (such as prostaglandins), stents (such as minimally invasive glaucoma surgery (MIGS) or tubuloplasty), laser-based treatments (such as selective laser trabeculoplasty (SLT) or micropulse laser trabeculoplasty (MLT)), transscleral cyclophotocoagulation (TS-CPC), ultrasound CPC, trabeculoplasty, or trabeculectomy. Complications of such treatments may include low intraocular pressure, hyphema, hemorrhage, high peak IOP rate, decreased visual acuity, and cataract formation. For example, treatments such as trabeculectomy or implantation of glaucoma drainage devices may require invasive surgical intervention and may have adverse safety risks in some cases. Other non-penetrating therapies often become ineffective over time. Treatment with medicated eye drops to lower intraocular pressure may be less than ideal due to poor patient adherence, side effects in certain cases, and variability in dosage and bioavailability among patients. Therefore, there is a need for improved methods and devices for treating glaucoma. Ideally, such methods and devices would be less invasive than some previous treatments and capable of successfully lowering intraocular pressure.

[0005] Existing methods for treating presbyopia focus on improving accommodative amplitude and / or replacing or repairing a patient's near vision function, and may be more complex and / or more invasive than ideal. Current presbyopia interventions include wearable near vision devices (such as glasses or contact lenses), lens or strut implants, pupillary constriction and lens depolymerization drugs, and incision methods. In some cases, complications of such therapies can include invasive complications, drug side effects, etc. Furthermore, these therapies often target only one possible source among many that contribute to reduced accommodation, which may limit the overall efficacy of such therapies as a single treatment modality. Given the above, there is a need for improved methods and devices for treating presbyopia. Ideally, such methods and devices would be less invasive than some previous treatments and capable of successfully increasing accommodative amplitude.

[0006] Existing treatments for AMD focus on delaying the onset of dry AMD and / or closing leaking vascular systems to limit degeneration in wet AMD, and may be less effective than desired and / or unable to reverse degeneration that has already occurred. Current interventions include nutritional interventions, such as high-antioxidant diets for dry AMD, laser photocoagulation for wet AMD, and intraocular anti-vascular endothelial growth factor (VEGF) therapy for wet AMD. Complications of such therapies may include, in some cases, persistent vision loss, a high recurrence rate of leaks in wet AMD cases, macular scarring, ocular infections, increased IOP, retinal detachment, and systemic vascular effects (e.g., hemorrhage, stroke, etc.). Furthermore, once vision is lost, such therapies rarely restore vision. In light of the above, there is a need for improved methods and devices for treating AMD. Ideally, such methods and devices would be less risky than some previous treatments and would be able to successfully delay degeneration and / or restore previously degenerated tissue.

[0007] Existing methods for treating dry eye focus on improving, supplementing, and / or replacing natural tear formation, and may not be as effective as ideal. Current interventions include over-the-counter eye drops (artificial tears), antibiotics, immunosuppressive eye drops, corticosteroid eye drops, ocular inserts, scleral lenses, phototherapy and eyelid massage, lacrimation eye drops, lacrimal duct plugs, and lacrimal duct cauterization. Complications of this therapy include persistent dryness, increased irritation, sweating, corneal abrasion, and other drug side effects. Furthermore, due to lack of patient compliance, side effects in certain situations, and variability in dosage and bioavailability of eye drops between patients, such therapies often require prolonged use, which may not be ideal. Given the above, there is a need for improved methods and devices for treating dry eye. Ideally, such methods and devices would be more effective and provide a longer-lasting improvement in ocular lubrication for patients. Summary of the Invention

[0008] Therefore, it is desirable to provide improved methods and apparatus for treating glaucoma, presbyopia, age-related macular degeneration, dry eye disease, and other ophthalmic conditions. Not all of these aspects or advantages are necessarily achieved through any particular implementation. Therefore, various implementations may be carried out in a manner that achieves or optimizes one or more advantages taught herein, without necessarily achieving other aspects or advantages that may also be taught or implied herein.

[0009] This disclosure generally relates to medical devices and methods, and more specifically to methods and apparatus for treating the eye.

[0010] In a first aspect, an apparatus for treating an eye is provided. The apparatus includes: a housing comprising a fluid-filled chamber and an eye contact surface configured to contact the eye; a first electrode disposed within the housing; and a second electrode disposed within the housing and coaxially aligned with the first electrode, wherein the distal ends of the first electrode and the distal ends of the second electrode are spaced apart by a gap. The first and second electrodes are configured to generate an electric arc across the gap and a shock wave in the fluid within the fluid-filled chamber when energized.

[0011] In some embodiments, the inner surface of the housing may be configured to focus the shock wave onto a predetermined location on or below the surface of the eye.

[0012] In some embodiments, the device may also include a reflector disposed within the housing and configured to focus the shock wave onto a predetermined location on or below the surface of the eye.

[0013] In some embodiments, the device may further include a fluid inlet and a fluid outlet in fluid communication with the fluid-filled chamber.

[0014] In some embodiments, the device may also include one or more wires coupled to the first or second electrode and configured to provide energy thereto.

[0015] In some embodiments, the first electrode and the second electrode may include a first end of the first wire and a second end of the second wire.

[0016] In some implementations, the fluid may include salt water or water.

[0017] In some implementations, the first and second electrodes may be coated with graphene to reduce corrosion during the generation of shock waves.

[0018] In some implementations, the housing may be elliptical.

[0019] In some embodiments, the housing also includes a fluid-filled waveguide disposed between the fluid-filled chamber and the eye contact surface. The fluid-filled waveguide can be configured to fluidly connect the fluid-filled chamber and the eye contact surface.

[0020] In some embodiments, the device may also include acoustic lenses disposed within the housing. The acoustic lenses may be configured to focus shock waves onto one or more predetermined locations on or below the surface of the eye.

[0021] In some embodiments, the device may further include a conductivity sensor at least partially disposed within the fluid-filled chamber. The conductivity sensor may be configured to measure the conductivity of the fluid within the fluid-filled chamber. In some embodiments, the conductivity sensor may include a pair of platinum electrodes.

[0022] In some embodiments, the device may further include a light source that is at least partially disposed within the fluid-filled chamber and configured to emit light toward the surface of the eye. The light source may be configured to emit light having a wavelength sufficient to crosslink tissue.

[0023] On the other hand, a system for treating the eye is provided. This system includes any of the shock wave generating devices and energy sources described herein. The energy source can be operatively coupled to a first and second electrode of an electrode-based device via one or more wires. The energy source may include a laser for fiber-optic-based devices.

[0024] In some implementations, the first electrode may be connected to the positive terminal of the energy source and the second electrode may be connected to the negative terminal of the energy source.

[0025] In some implementations, the energy source may include a high-voltage pulse generator.

[0026] In some embodiments, the system may also include a current sensor coupled to a first electrode or a second electrode, the current sensor being configured to determine the current level flowing to the first electrode or the second electrode.

[0027] In some embodiments, the system may also include a conductivity sensor fluidly coupled to a fluid outlet and configured to measure the conductivity of the fluid as it flows out of the fluid outlet.

[0028] In some embodiments, the system may also include a fluid recirculation system fluidly connected to a fluid outlet and a fluid inlet, and configured to recirculate fluid from the fluid-filled chamber and remove cavitation bubbles from the fluid.

[0029] In some embodiments, the system may further include a reservoir disposed on or below the eye contact surface. In some embodiments, the reservoir may contain oxygen. Alternatively or in combination, the reservoir may contain riboflavin. Alternatively or in combination, the reservoir may contain a therapeutic agent or a drug.

[0030] In another aspect, a device for treating the eye is provided. The device includes: a housing comprising a fluid-filled chamber and an eye contact surface configured to contact the eye; and an optical fiber disposed within the housing. The optical fiber is configured to generate a shock wave in the fluid within the fluid-filled chamber when light energy is emitted from the optical fiber.

[0031] In some embodiments, the inner surface of the housing may be configured to focus the shock wave onto a predetermined location on or below the surface of the eye.

[0032] In some embodiments, the device may also include a reflector disposed within the housing and configured to focus the shock wave onto a predetermined location on or below the surface of the eye.

[0033] In some embodiments, the device may further include a fluid inlet and a fluid outlet in fluid communication with the fluid-filled chamber.

[0034] In some implementations, the fluid may include salt water or water.

[0035] In some implementations, the fluid may include graphene to reduce light emitted from the housing when a shock wave is generated.

[0036] In some implementations, the housing may be elliptical.

[0037] In some embodiments, the housing also includes a fluid-filled waveguide disposed between the fluid-filled chamber and the eye contact surface. The fluid-filled waveguide can be configured to fluidly connect the fluid-filled chamber and the eye contact surface.

[0038] In some embodiments, the device may also include acoustic lenses disposed within the housing. The acoustic lenses may be configured to focus shock waves onto one or more predetermined locations on or below the surface of the eye.

[0039] On the other hand, a system for treating the eye is provided. The system includes a plurality of shock wave generators and contact lenses disposed around the plurality of shock wave generators, the contact lenses including fluid-filled chambers and eye contact surfaces configured to contact the surface of the eye.

[0040] In some embodiments, the contact lens may also include a suction mechanism configured to contact the surface of the eye and maintain contact between the surface of the eye and the eye contact surface.

[0041] In some implementations, each of the plurality of shock wave generators may include an optical fiber.

[0042] In some implementations, each of the plurality of shock wave generators may include a pair of coaxially arranged electrodes and a reflector.

[0043] In some embodiments, the contact lens may include an inflatable housing that includes an eye contact surface.

[0044] In some implementations, the contact lens may include an imaging port configured to receive an imaging device.

[0045] In some implementations, multiple shock wave generators may include multiple electro-hydraulic, piezoelectric, laser, or magnetoelectric shock wave generators.

[0046] In another aspect, a method for treating the eye is provided. The method includes the steps of: attaching an eye contact surface of a shock wave generator to the surface of the eye; generating a shock wave using the shock wave generator; and focusing the shock wave at a predetermined location on or below the surface of the eye.

[0047] In some embodiments, the method may further include inducing microporousization, cavitation, vasodilation, angiogenesis, depolymerization, and upregulation of growth factor production at predetermined locations using focused shock waves.

[0048] In some implementations, the predetermined location may include one or more of the trabecular meshwork, Schrem's canal, limbus, eyelid, meibomian gland, retina, and fovea.

[0049] In some implementations, the method may also include inoculating microbubbles at predetermined locations before generating a shock wave.

[0050] In some implementations, the shock wave generator may include an optical fiber. The step of generating a shock wave may include emitting light energy from the optical fiber into a fluid surrounding the optical fiber.

[0051] In some embodiments, the shock wave generator may include a first electrode and a second electrode. The step of generating a shock wave may include energizing the first electrode and the second electrode to form an electric arc across the gap between their ends.

[0052] In some embodiments, the method may further include: attaching the eye contact surface of the second shock wave generator to the surface of the eye; generating a second shock wave with the second shock wave generator; and focusing the second shock wave onto a second predetermined location on or below the surface of the eye.

[0053] In some implementations, the shock wave generator can be placed in the fluid-filled chamber of the contact lens.

[0054] In some implementations, the shock wave generator can be attached to the test frame.

[0055] In another aspect, a system for treating the eye is provided. The system includes: a shock wave generator configured to generate shock waves; and a fluid-filled waveguide fluidly coupled to the shock wave generator and configured to guide the shock waves to an eye contact surface configured to contact the eye.

[0056] In some implementations, the waveguide may include a stainless steel tube.

[0057] In some implementations, the waveguide may have a length of about 12 mm or more.

[0058] In some implementations, the waveguide may have a diameter ranging from about 1 mm to about 8 mm. For example, the waveguide may have a diameter of about 3 mm or about 8 mm.

[0059] In some embodiments, the system may also include a contact lens coupled to the distal end of the waveguide, the contact lens including a fluid-filled chamber and an eye contact surface.

[0060] In some implementations, at least a portion of the shock wave generator and waveguide can be connected to the test frame.

[0061] These and other embodiments are described in more detail in the following description in connection with the accompanying drawings.

[0062] By incorporating via reference

[0063] All publications, patents and patent applications mentioned in this specification are incorporated herein by reference to the same extent that each individual publication, patent or patent application is specifically and individually indicated to be incorporated by reference. Attached Figure Description

[0064] The novel features of this disclosure are particularly set forth in the appended claims. A better understanding of the features and advantages of this disclosure will be obtained by referring to the following detailed description and accompanying drawings, which illustrate illustrative embodiments utilizing the principles of this disclosure, as shown in the drawings:

[0065] Figure 1 A perspective view of a shock wave generator according to an embodiment is shown;

[0066] Figure 2 A side view of an exemplary shockwave generator near the eye according to an embodiment is shown;

[0067] Figure 3 A top view of a shock wave generator array according to an embodiment is shown;

[0068] Figure 4 A top view of an array of shock wave generators arranged in multiple rows according to an embodiment is shown;

[0069] Figure 5 An embodiment is shown. Figure 4 A side view of the array;

[0070] Figure 6A side sectional view of an exemplary shock wave generator array system, including a cone that is coupled to an eye, is shown according to an embodiment.

[0071] Figure 7 A side sectional view of an exemplary shock wave generator array system including a contact lens that is coupled to an eye, according to an embodiment, is shown.

[0072] Figure 8 A perspective view of a shock wave generator according to an embodiment is shown;

[0073] Figure 9 A side view of multiple shock wave generators coupled to the eye according to an embodiment is shown;

[0074] Figure 10 A side view of multiple shock wave generators attached to the eye according to an embodiment is shown;

[0075] Figure 11 A side sectional view of multiple shock wave generators attached to the eye using a contact balloon, according to an embodiment, is shown.

[0076] Figure 12 A side sectional view of multiple shock wave generators attached to the eye using a contact balloon, according to an embodiment, is shown.

[0077] Figure 13 An exploded side view of an exemplary shock wave generator near the eye, according to an embodiment, is shown;

[0078] Figure 14 An exploded side view of another exemplary shock wave generator near the eye according to an embodiment is shown;

[0079] Figure 15 A side sectional view of multiple shock wave generators attached to the eye using a contact balloon, according to an embodiment, is shown.

[0080] Figure 16 An embodiment of the device is shown attached to the eye. Figure 15 A perspective view of the system;

[0081] Figure 17 The diagram illustrates connections to additional conduits and / or wiring according to an embodiment. Figure 15 A perspective view of the system;

[0082] Figure 18 The diagram illustrates a device with conduits and / or wiring connected to a power source, according to an embodiment. Figure 17 A side view of the system;

[0083] Figure 19A perspective view of a contact balloon including multiple shock wave generators embedded therein, according to an embodiment, is shown;

[0084] Figure 20 A partial perspective view of a plurality of stacked ring conductor shock wave generators according to an embodiment is shown;

[0085] Figure 21 An embodiment is shown. Figure 20 Exploded view of a ring conductor shock wave generator;

[0086] Figure 22 An exemplary treatment mode for glaucoma according to an embodiment is shown;

[0087] Figure 23 An exemplary treatment mode for presbyopia according to an embodiment is shown;

[0088] Figure 24 An exemplary treatment modality for AMD according to an implementation method is shown;

[0089] Figure 25 A top view of an exemplary treatment system for AMD according to an embodiment is shown;

[0090] Figure 26 An embodiment is shown. Figure 25 A side sectional view of the system;

[0091] Figure 27 Another exemplary treatment system for AMD according to an embodiment is shown;

[0092] Figure 28 An exemplary treatment modality for dry eye disease according to an embodiment is shown;

[0093] Figures 29 to 32 An exemplary treatment system for dry eye disease according to an embodiment is shown;

[0094] Figure 33 A top view of an exemplary treatment system for lens softening according to an embodiment is shown;

[0095] Figure 34 A device for use on the eye according to an embodiment is shown. Figure 33 A side sectional view of the system;

[0096] Figure 35 A side sectional view of an exemplary treatment system for presbyopia according to an embodiment is shown;

[0097] Figure 36 A side sectional view of an exemplary treatment system for glaucoma according to an embodiment is shown;

[0098] Figure 37 An embodiment is shown. Figure 36 A top view of the system;

[0099] Figure 38 A side sectional view of an exemplary shock wave generator array according to an embodiment is shown;

[0100] Figure 39 An embodiment is shown. Figure 38 A top view of the array;

[0101] Figure 40 A side sectional view of an exemplary treatment system for AMD according to an embodiment is shown;

[0102] Figure 41 A side sectional view of an exemplary treatment system for dry eye disease according to an embodiment is shown;

[0103] Figure 42 A cross-sectional view of an exemplary laser-based shock wave generator according to an embodiment is shown;

[0104] Figure 43 A side sectional view of a laser-based shock wave generator array in a fluid-filled contact lens balloon according to an embodiment is shown.

[0105] Figure 44 A perspective view of a laser-based shock wave generator array in an annular fluid-filled contact lens according to an embodiment is shown.

[0106] Figure 45 An embodiment is shown. Figure 44 A side sectional view of the system;

[0107] Figure 46 An embodiment is shown. Figure 44 A top view of the system;

[0108] Figure 47 A top view of a laser-based shock wave generator array in an annular fluid-filled contact lens according to an embodiment is shown;

[0109] Figure 48 An embodiment is shown. Figure 47 A side sectional view of the system;

[0110] Figure 49 A side sectional view of an array of shock wave generators arranged in multiple rows and positioned on the eye, according to an embodiment, is shown.

[0111] Figure 50An exemplary row of shock wave generators, according to an embodiment, includes wires disposed within an insulating sheath having multiple holes therein.

[0112] Figure 51 An exemplary row of shock wave generators, according to an embodiment, includes optical fibers disposed within a cladding having a plurality of holes therein.

[0113] Figure 52 An exploded view of an electrode-based shock wave generator according to an embodiment is shown, comprising a conductor disposed within an insulating sheath having a plurality of holes therein.

[0114] Figure 53 An exploded view of a laser-based shock wave generator, according to an embodiment, including an optical fiber disposed within a cladding having a plurality of holes therein;

[0115] Figure 54 A method for treating the eye according to an embodiment is shown;

[0116] Figure 55 A side sectional view of an exemplary laser scanning shock wave generator system including a contact lens that is coupled to an eye, according to an embodiment, is shown.

[0117] Figure 56 A side sectional view of an exemplary multi-fiber laser-based shock wave generator array system including contact lenses, according to an embodiment, is shown.

[0118] Figure 57 A side sectional view of an exemplary shock wave waveguide according to an embodiment is shown;

[0119] Figure 58 A side sectional view of an exemplary shock wave waveguide according to an embodiment is shown;

[0120] Figure 59 A schematic diagram of a wireframe tube shock waveguide according to an embodiment is shown;

[0121] Figure 60 A side sectional view of an exemplary shock wave waveguide according to an embodiment is shown;

[0122] Figure 61 A side sectional view of an exemplary shock wave waveguide according to an embodiment is shown;

[0123] Figure 62 A side sectional view of an exemplary parabolic shock waveguide according to an embodiment is shown;

[0124] Figure 63 A top view of an exemplary contact lens including a shock wave waveguide array according to an embodiment is shown;

[0125] Figure 64 A top view of an exemplary contact lens including an array of shockwave generators for treating meibomian glands, according to an embodiment, is shown.

[0126] Figure 65 A top view of an exemplary contact lens for treating dry eye disease according to an embodiment is shown;

[0127] Figure 66 A side view of an exemplary treatment system including an integrated imaging system according to an embodiment is shown;

[0128] Figure 67 A side view of an exemplary treatment system including an integrated imaging system according to an embodiment is shown;

[0129] Figure 68 A side view of an exemplary treatment system including an integrated imaging system according to an embodiment is shown;

[0130] Figure 69 A schematic diagram of an exemplary system for bubble extraction according to an embodiment is shown;

[0131] Figure 70 A schematic diagram of an exemplary system for bubble extraction according to an embodiment is shown;

[0132] Figure 71 A schematic diagram of an exemplary system for bubble extraction according to an embodiment is shown;

[0133] Figure 72 An electrical schematic diagram of an exemplary treatment system according to an embodiment is shown;

[0134] Figure 73 A side sectional view of an exemplary variable focus treatment system according to an embodiment is shown;

[0135] Figure 74 A side sectional view of an exemplary treatment system for dry eye disease according to an embodiment is shown;

[0136] Figure 75 A side sectional view of an exemplary treatment system for transorbital treatment according to an embodiment is shown;

[0137] Figure 76 A side sectional view of an exemplary treatment system for dry eye disease according to an embodiment is shown;

[0138] Figure 77 A schematic diagram of an exemplary system for measuring electrical conductivity according to an embodiment is shown;

[0139] Figure 78A side view of an exemplary shock wave waveguide including an embedded conductivity sensor according to an embodiment is shown;

[0140] Figure 79 A side view of an exemplary acoustically crosslinked shock waveguide according to an embodiment is shown;

[0141] Figure 80 A side view of an exemplary acoustically crosslinked shock waveguide according to an embodiment is shown;

[0142] Figure 81 A schematic diagram of an exemplary system for passive cavitation detection according to an embodiment is shown;

[0143] Figure 82 An exemplary treatment system including passive cavitation detection according to an embodiment is shown;

[0144] Figure 83 A side view of an exemplary treatment system including a conductivity sensor, acoustic crosslinking, and / or passive cavitation detection according to an embodiment is shown;

[0145] Figure 84 A schematic diagram of an exemplary treatment system including acoustic crosslinking or passive cavitation detection according to an embodiment is shown; and

[0146] Figures 85A to 85F Exemplary treatment modalities for various indications are shown according to embodiments. Detailed Implementation

[0147] In the following detailed description, reference is made to the accompanying drawings, which form part of the description. In the drawings, similar symbols generally identify similar parts unless the context otherwise requires. The illustrative embodiments described in this detailed description, the accompanying drawings, and the claims are not intended to be limiting. Other embodiments and changes may be utilized without departing from the scope or subject matter referred to herein. It will be readily understood that aspects of this disclosure, as generally described herein and illustrated in the accompanying drawings, can be arranged, substituted, combined, separated, and designed in various different configurations, all of which are explicitly contemplated herein. Those skilled in the art will understand that the illustrations in the figures are not necessarily drawn to scale, and many elements may be enlarged or exaggerated for clarity and ease of understanding of the described embodiments.

[0148] Although certain embodiments and examples are disclosed below, the subject matter of the invention extends beyond the specifically disclosed embodiments to other alternative embodiments and / or uses, as well as modifications and equivalents thereof. Therefore, the scope of the appended claims is not limited to any particular embodiment described below. For example, in any method or process disclosed herein, the actions or operations of the method or process can be performed in any suitable order and are not necessarily limited to any particular disclosed order. Various operations may be described sequentially as multiple discrete operations in a manner conducive to understanding certain embodiments; however, the order of description should not be construed as implying that these operations are sequentially related. Furthermore, the structures, systems, and / or devices described herein may be embodied as integrated components or separate components.

[0149] For the purpose of comparing the various implementations, certain aspects and advantages of these implementations have been described. Not all of these aspects or advantages are necessarily achieved by any particular implementation. Thus, for example, various implementations may be carried out in a manner that achieves or optimizes one or more advantages taught herein, without necessarily achieving other aspects or advantages that may also be taught or implied herein.

[0150] This disclosure is described in relation to the deployment of systems, devices, or methods for treating a patient's eye. However, those skilled in the art will understand that this is not intended to be limiting, and that the devices and methods disclosed herein can be used in other anatomical regions and other surgical procedures.

[0151] The embodiments disclosed herein can be combined in one or more of a variety of ways to provide improved methods and apparatus for treating the eye. The ocular tissues, membranes, or pathological changes thereof being treated may include one or more of the trabecular meshwork, sclera, vitreous body, retina, meibomian gland ducts, stigmas (e.g., posterior vitreous stigmas (PVZs)), ciliary body, lens, and affected areas therein.

[0152] The embodiments disclosed herein provide improved methods and apparatus for treating presbyopia, glaucoma, AMD, dry eye disease, other ophthalmic conditions, or combinations thereof. For example, the presbyopia treatment disclosed herein can have a beneficial effect on a patient's intraocular pressure (hereinafter referred to as "IOP"). Alternatively or in combination, for example, the treatment can be directed at glaucoma. The treatments and apparatus disclosed herein can be combined with many known treatment methods and apparatuses. For example, the accommodative restoration described herein can be combined with, for example, many known existing accommodative intraocular lenses (IOLs). Alternatively or in combination, the methods and apparatus disclosed herein can be combined with one or more known glaucoma treatments. Although many embodiments are described with reference to the natural lens of the eye, the embodiments disclosed herein can be used to improve vision using an IOL.

[0153] As used herein, the term "shock wave" refers to an acoustic wave with high energy peaks, pressure jumps / step changes, rapid rise times (e.g., about 10 nanoseconds), high amplitude, and non-periodic / short duration (e.g., about 10 microseconds). Shock waves can also be called pressure waves. Shock waves differ from ultrasound or high-intensity focused ultrasound in that they typically propagate at significantly higher speeds and intensities, and lack the periodicity of ultrasound. Shock waves can be generated by electrohydraulic, piezoelectric, laser, or magnetoelectric devices, as will be understood by one of ordinary skill in the art based on the description herein.

[0154] Extracorporeal shock wave therapy (ESWT) is a non-invasive method for treating musculoskeletal disorders, primarily used to treat exercise-related overuse tendinopathy. ESWT is also used to treat nonunion of long bone fractures, avascular necrosis of the femoral head, chronic diabetic and non-diabetic ulcers, and ischemic heart disease. The shock waves used in ESWT have been shown to have mechanical and cellular effects on the treated tissues. For example, shock wave therapy can produce analgesic effects on the treated tissues. Shock wave therapy has also been shown to stimulate the production of growth factors, including eNOS, nNOS, and VEGF, which promote angiogenesis and cell regeneration. Shock wave therapy can also be used to generate free radicals, which can promote cell destruction when needed.

[0155] Figure 1 A perspective view of a shock wave generator 100 is shown. The shock wave generator 100 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. The housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. The eye contact surface 104 may be configured to engage with the surface of a patient's eye. The first electrode 110 and the second electrode 112 may be coaxially aligned with each other, such that a gap 114 is formed between the distal ends of the electrodes 110.

[0156] Shockwave generator 100 can be configured to generate one or more shockwaves. Shockwave generator 100 can be configured to treat one or more tissues or structures on or beneath the surface of the eye using the shockwaves it generates. The treatment can be non-thermal. The shockwaves can be focused at a predetermined location as described herein or unfocused. The shockwaves can be used for local separation, microporization, dilation, and / or sensing of desired ocular tissues. In some embodiments, the shockwaves can be used to generate biomechanical effects (such as vasodilation, microporization, softening, etc.) and / or biochemical effects (such as neovascularization, etc.) as described herein. In some embodiments, the shockwaves can be used to deliver drugs to ocular tissues.

[0157] For example, applying shockwaves to the eye can be used to (i) increase fluid outflow from the sclera and meibomian gland ducts around the ischemic limbus by upregulating VEGF and TGFβ2 (e.g., angiogenesis) and / or eNOS and nNOS (e.g., vasodilation), (ii) induce stem cell differentiation (e.g., upregulation of Ca2+), (iii) improve visual acuity and accommodative amplitude by dissociating vitreous cavities near the pars plana of the ciliary body, (iv) improve lens compliance by depolymerization, and / or (v) deliver drugs (e.g., glaucoma, anti-VEGF, steroid drugs, etc., via acoustic aperture effect and / or ultrasound delivery). In some embodiments, shockwave therapy can reduce thermal tissue coagulation, perforation, lens or corneal translocation, cataract induction, and / or other adverse distortions that may result from other treatment methods and systems.

[0158] The eye contact surface 104 (also referred to herein as a tissue interface) may be shaped to correspond to the surface of the eye in order to create a seal when placed on the surface of the eye. The eye contact surface 104 may include a flexible material configured to conform its shape to the surface of the eye when placed on it. The eye contact surface 104 may include nylon, polyethylene terephthalate (PET), biaxially oriented polyethylene terephthalate (BoPET), etc.

[0159] The thickness of the eye contact surface 104 can range from about 12 μm to about 100 μm.

[0160] The eye contact surface 104 may have a diameter in the range of about 1 mm to about 8 mm, for example, about 1 mm, about 2 mm, about 3 mm, about 5 mm, about 7 mm or about 8 mm.

[0161] The eye contact surface 104 may comprise a suitable polymer, such as polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), fluorinated ethylene propylene (FEP), or polyoxymethylene (POM, for example, available from DuPont). Polyether block esters, polyurethanes (e.g., polyurethane 85A), polypropylene (PP), polyvinyl chloride (PVC), polyether esters (e.g., available from DSM Engineering Plastics) ), ether or ester copolymers (e.g., butene / poly(alkylene ether) phthalates and / or other polyester elastomers, such as those available from DuPont). ), polyamide (e.g., available from Bayer) Or available from ElfAto Chemical Company ), elastomer polyamide, block polyamide / ether, polyether block amide (PEBA, for example, can be found under trade name) The following are examples of materials: ethylene vinyl acetate copolymer (EVA), silicone resin, polyethylene (PE), Marlex high-density polyethylene, Marlex low-density polyethylene, linear low-density polyethylene (e.g., ), Polyester, polybutylene terephthalate (PBT), polyethylene terephthalate (PET), polypropylene terephthalate, polyethylene naphthalate (PEN), polyetheretherketone (PEEK), polyimide (PI), polyetherimide (PEI), polyphenylene sulfide (PPS), polyphenylene ether (PPO), polyterephthalamide (e.g., Polysulfone, nylon, nylon-2 (e.g., GRK available from EMS American Grilon). Perfluoro(propyl vinyl ether) (PFA), ethylene vinyl alcohol, polyolefins, polystyrene, epoxy resins, polyvinylidene chloride (PVdC), poly(styrene-A-isobutylene-A-styrene) (e.g., SIBS and / or SIBS 50A), polycarbonate, ionomers, biocompatible polymers, other suitable materials or mixtures, combinations, copolymers, polymer / metal composites, etc. In some embodiments, the eye contact surface 104 may include a mixture with a liquid crystal polymer (LCP) (e.g., up to about 6% LCP).

[0162] The fluid-filled chamber 106 may include a fluid disposed therein. The fluid may include a conductive (e.g., conductivity of about 0.6 mS), biocompatible liquid. The fluid may include water or saline solution. The fluid may include a suspension of graphene in saline solution. The fluid may be cooled (e.g., about 10 degrees Celsius). In some embodiments, the shock wave generator 100 may also include a fluid inlet 108 and a fluid outlet 109 in fluid communication with the fluid-filled chamber 106. The fluid may be used to apply the shock wave generated in the gap 114 to the surface of the eye. The fluid may circulate within the fluid-filled chamber 106 via the fluid inlet 108 and the fluid outlet 109. As the pulse delivery of the shock wave proceeds, the fluid circulation may continuously extract metal ions and cavitation bubbles detached from the electrodes 110, 112 generated during shock wave formation.

[0163] In some embodiments, the fluid flowing out of the fluid-filled chamber 106 via the fluid outlet 109 may be sampled periodically or continuously to determine the extent of electrode corrosion. For example, the conductivity of the brine may be sampled (e.g., as a representative of the distance of the gap 114 between the measuring electrodes 110, 112, since the electrodes corrode and metal ions are released into the brine), and the voltage supplied to the electrodes 110, 112 may be adjusted to account for any changes in the induced conductivity.

[0164] The fluid-filled chamber 106 can be configured to act as a reflector to focus the shock wave onto a desired predetermined location. Alternatively or in combination, one or more reflectors can be coupled to the inner surface of the fluid-filled chamber 106 to focus the shock wave. The inner wall of the fluid-filled chamber 106 or the reflector coupled to the inner surface of the fluid-filled chamber 106 can be elliptical. As will be understood by those skilled in the art based on the disclosure herein, other exemplary shapes can be a mixture between spherical and elliptical, elliptical with a stand-off balance, reflectors excluding electrodes for radial wave transmission, coaxial lines with two insulated exposed electrodes, elliptical with flat-end reflectors for asymmetrical shapes, elliptical rings, conical shapes, S-shaped shapes, contact lenses with multiple reflectors and electrodes, tarsal tube engagement shapes, drug reservoirs / stores coupled to a pressure wave generator, suction ring features for stabilizing intraoperative delivery, etc.

[0165] Reflectors can include sapphire, PMMA, graphene-coated polymers, shock-reflective polymers, stainless steel, aluminum, etc. Some examples of suitable metals and metal alloys include stainless steel, such as 304V, 304L, and 316LV stainless steel; mild steel; nickel-titanium alloys, such as linearly elastic and / or hyperelastic nickel-titanium; other nickel alloys, such as nickel-chromium-molybdenum alloys (e.g., UNS: N06625, such as...). 625, UNS: N06022, such as, UNS:N10276, such as, other Alloys, etc.), nickel-copper alloys (e.g., UNS: N04400, such as... 400 400 400, etc.), nickel-cobalt-chromium-molybdenum alloys (e.g., UNS: R30035, such as, (etc.), nickel-molybdenum alloys (e.g., UNS: N10665, such as, ALLOY Other nickel-chromium alloys, other nickel-molybdenum alloys, other nickel-cobalt alloys, other nickel-iron alloys, other nickel-copper alloys, other nickel-tungsten or tungsten alloys, etc.; cobalt-chromium alloys; cobalt-chromium-molybdenum alloys (e.g., UNS: R30003, such as...). (etc.); platinum-rich stainless steel; titanium; combinations thereof; etc.; or any other suitable material.

[0166] In some embodiments, an aluminum dome structure positioned near the shock wave generator can be used to guide the shock wave energy to a second focal point using an elliptical dome or to allow it to enter the tissue in a parallel direction using a parallel dome. The depth of focus of the dome structure can be in the range of approximately 3 mm to approximately 3 cm beyond the first focal point shock wave generator.

[0167] Those skilled in the art will understand that reflectors (e.g., the shape of the fluid-filled chamber 106 and / or other reflectors connected thereto) can be shaped to provide a desired focal point, shock wave pattern, etc.

[0168] The first electrode 110 and the second electrode 112 can be operatively connected to a power source. In some embodiments, the first electrode 110 and the second electrode 112 can be connected to the power source via one or more wires 116. The one or more wires 116 may be insulated. In some embodiments, the first electrode 110 and the second electrode 112 may include the distal ends of one or more wires 116. In some embodiments, the first electrode 110 and the second electrode 112 may include pins connected to the wires 116. In some embodiments, the first electrode 110 and the second electrode 112 may include platinum, tungsten-titanium, aluminum, titanium alloy (Ti-3Al), stainless steel, silver, gold, copper, nickel-chromium alloy, iron, brass, copper-Pt, copper, or combinations thereof.

[0169] In some embodiments, the first electrode 110 and / or the second electrode 112 may be coated with graphene, gold or other materials to reduce corrosion of the electrodes 110, 112 during use.

[0170] The first electrode 110 and the second electrode 112 may have an outer diameter of about 0.5 mm. The first electrode 110 and the second electrode 112 may have an outer diameter in the range of about 0.00785 mm to about 0.8118 mm. In some embodiments, the outer diameter of the first electrode 110 and the second electrode 112 may be within a range defined by any two of the following values: about 0.005 mm, about 0.01 mm, about 0.015 mm, about 0.02 mm, about 0.025 mm, about 0.03 mm, about 0.035 mm, about 0.04 mm, about 0.045 mm, about 0.05 mm, about 0.055 mm, about 0.06 mm, or about 0.07 mm. mm, approximately 0.08 mm, approximately 0.09 mm, approximately 0.1 mm, approximately 0.15 mm, approximately 0.2 mm, approximately 0.25 mm, approximately 0.3 mm, approximately 0.35 mm, approximately 0.4 mm, approximately 0.45 mm, approximately 0.5 mm, approximately 0.55 mm, approximately 0.6 mm, approximately 0.65 mm, approximately 0.7 mm, approximately 0.75 mm, approximately 0.8 mm, approximately 0.85 mm, and approximately 0.9 mm.

[0171] The outer diameters of the first electrode 110 and the second electrode 112 can range from about 20 American wire gauges (AWG) to about 60 AWG. In some embodiments, the outer diameters of the first electrode 110 and the second electrode 112 can be within a range defined by any two of the following values: about 20 AWG, about 25 AWG, about 30 AWG, about 35 AWG, about 40 AWG, about 45 AWG, about 50 AWG, about 55 AWG, and about 60 AWG.

[0172] In some embodiments, the first electrode 110 may be connected (e.g., via wire 116) to the positive terminal of the high-voltage pulse generator, and the second electrode 112 may be connected to the negative terminal of the high-voltage pulse generator to generate a shock wave within the gap 114 between the two electrodes.

[0173] In some implementations, the polarity of the first electrode 110 and the second electrode 112 can be reversible. Polarity reversal during treatment can help extend the lifespan of the first electrode 110 and the second electrode 112, which can lead to increased treatment repeatability across patients and devices.

[0174] The gap 114 between the first electrode 110 and the second electrode 112 can be defined by the distance between the ends of the first electrode 110 and the second electrode 112. In some embodiments, the distance between the electrode ends can be in the range of about 0.05 mm to about 0.5 mm, for example, in the range of about 0.1 mm to about 0.15 mm. For example, the distance can be about 0.05 mm, about 0.06 mm, about 0.07 mm, about 0.08 mm, about 0.09 mm, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm, about 0.14 mm, or about 0.15 mm, about 0.16 mm, about 0.17 mm, about 0.18 mm, about 0.19 mm, about 0.2 mm, about 0.25 mm, about 0.3 mm, about 0.35 mm, about 0.4 mm, about 0.45 mm, or about 0.5 mm.

[0175] The gap 114 between the first electrode 110 and the second electrode 112 may be sufficient to generate a shock wave using voltage pulses ranging from approximately 3 kV to approximately 4 kV. These voltages may be stepped / combined and / or pre-pulsed, and may be in the range of approximately 0-500V, 0-1000V, 0-1500V, 0-2000V, 0-2500V, 0-3000V, 0-3500V, or 0-4000V. The system may be configured to alternate between voltage polarities to extend electrode life.

[0176] The gap 114 between the first electrode 110 and the second electrode 112 may be sufficient to generate a shock wave using a current of about 50 amperes.

[0177] The system may include one or more sensors. For example, sensors may be coupled to one or more electrodes to determine the current flowing to the electrodes. Alternatively or in combination, sensors may be provided to measure the conductivity of saline flowing out of a fluid outlet as described herein. Temperature, acoustic cavitation (i.e., bubble formation) efficiency, and / or fluid pressure sensors may be disposed within the shock wave generation flow chamber (also referred to herein as the fluid-filled chamber) and may be used for intraoperative shock wave amplitude and focus adjustment. One or more sensors may be used to provide uniform, stable delivery of the shock wave during treatment.

[0178] In some implementations, one or more sensors may be configured to perform elastography measurements of various eye tissues (e.g., cornea, lens, and / or retina) based on pressure waves generated by one or more shock wave generators 100.

[0179] In some implementations, the system may include one or more pressure sensors configured as a shock wave generator 100 to provide pressure feedback.

[0180] In some implementations, the housing 102 may be molded or 3D printed, etc.

[0181] In some implementations, the shock wave generator 100 may be positioned at the distal end of the handheld probe.

[0182] Figure 2 A side view of an exemplary shock wave generator 100 adjacent to the eye 200 is shown. The shock wave generator 100 can be used with... Figure 1 The shock wave generator 100 shown is substantially similar. The shock wave generator 100 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. Electrodes 110 and 112 may, for example, include gold-plated leads coupled to one or more insulated wires 116 as described herein. For example, the housing 102 may be elliptical to facilitate focusing the shock wave 204 in a desired direction and onto a desired location on or below the surface of the eye. The housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104 (also referred to herein as a tissue interface). For example, the fluid-filled chamber 106 may be filled with a fluid such as saline 206. The eye contact surface 104 may be configured to engage with the surface of a patient's eye. As described herein, the first electrode 110 and the second electrode 112 may be coaxially aligned with a gap between them.

[0183] Shockwave generator 100 can be configured to focus shockwaves onto a predetermined location on or below the surface of the eye. Shockwave generator 100 can be configured to focus shockwaves onto predetermined locations within eye tissue 200 in a transscleral, translimbal, or transcorneal manner. For example, predetermined locations may include the circumferential (i.e., 360-degree) trabecular meshwork, Schrem's canal, ciliary body (e.g., ciliary processes, muscles, selected portions of the anterior / posterior / equatorial portion of the ciliary body, etc.), pars plana of the ciliary body, ciliary corona, cornea, sclera, lens, retina, fovea, perifoveal region, intermediate vitreous zone (IVZ), posterior vitreous zone (PVZ), vitreous body, eyelids, and / or meibomian glands, one or more of these.

[0184] In some embodiments, the predetermined location may be on the surface of the eye. In some embodiments, the predetermined location may be at a tissue depth ranging from approximately subsurface (e.g., 0.1 mm below the surface) to approximately 30 mm below the surface of the eye.

[0185] In some embodiments, the shock wave can generate intraocular pressure up to about 100 MPa at a predetermined location, for example, in the range of about 0.1 MPa to about 100 MPa. In some embodiments, the shock wave can generate intraocular pressure in the range of about 0.05 MPa to about 5 MPa at a predetermined location.

[0186] In some embodiments, the bonding fluid or gel 202 may be applied to the eye contact surface 104 to facilitate contact between the eye contact surface 104 and the surface of the eye and / or to facilitate the transmission of the shock wave from the shock wave generator to the eye. The bonding fluid or gel 202 may help prevent misdirection of energy due to unwanted reflections caused by an air gap between the shock wave generator 100 and the surface of the eye. In some embodiments, the bonding fluid or gel 202 may include one or more therapeutic substances.

[0187] In some embodiments, the shock wave generator 100 can be configured to operate at approximately 0.1 mJ / mm². 2 Up to approximately 10 mJ / mm 2 The shock wave generator 100 can be configured to deliver energy to the eye within a range defined by any two of the following values: 0.1 mJ / mm². 2 0.2mJ / mm 2 0.3mJ / mm 2 0.4 mJ / mm 2 0.5 mJ / mm², 0.6 mJ / mm² 2 0.7mJ / mm 2 0.8 mJ / mm 2 0.9mJ / mm2 1mJ / mm 2 1.5mJ / mm 2 2mJ / mm 2 2.5 mJ / mm 2 3mJ / mm 2 3.5mJ / mm 2 4mJ / mm 2 4.5 mJ / mm 2 5mJ / mm 2 5.5mJ / mm 2 6mJ / mm 2 6.5mJ / mm 2 7mJ / mm 2 7.5mJ / mm 2 8mJ / mm 2 8.5mJ / mm 2 9mJ / mm 2 9.5 mJ / mm 2 Or 10 mmJ / mm 2 .

[0188] In some embodiments, the shock wave generator 100 may be configured to deliver shock waves with energy rise times ranging from about 10 nanoseconds to about 100 microseconds. In some embodiments, the shock wave generator 100 may be configured to deliver shock waves with energy rise times within a range defined by any two of the following values: 10 nanoseconds, 50 nanoseconds, 100 nanoseconds, 200 nanoseconds, 300 nanoseconds, 400 nanoseconds, 500 nanoseconds, 600 nanoseconds, 700 nanoseconds, 800 nanoseconds, 900 nanoseconds, 1 microsecond, 10 microseconds, 20 microseconds, 30 microseconds, 40 microseconds, 50 microseconds, 60 microseconds, 70 microseconds, 80 microseconds, 90 microseconds, or 100 microseconds.

[0189] In some embodiments, the shock wave generator 100 may have a pulse duration in the range of about 10 nanoseconds to about 10 microseconds. In some embodiments, the shock wave generator 100 may have a pulse duration in the range defined by any two of the following values: 10 nanoseconds, 50 nanoseconds, 100 nanoseconds, 200 nanoseconds, 300 nanoseconds, 400 nanoseconds, 500 nanoseconds, 600 nanoseconds, 700 nanoseconds, 800 nanoseconds, 900 nanoseconds, 1 microsecond, 10 microseconds, 20 microseconds, 30 microseconds, 40 microseconds, 50 microseconds, 60 microseconds, 70 microseconds, 80 microseconds, 90 microseconds, or 100 microseconds.

[0190] In some embodiments, the shock wave generator 100 can deliver the shock wave at a repetition rate in the range of about 1 Hz to about 50 kHz (e.g., in the range of about 1 Hz to about 1 kHz, for example, in the range of about 1 Hz to about 5 Hz). The shock wave may be generated at a frequency of about 10 kHz. In some embodiments, the shock wave generator 100 can deliver the shock wave at a repetition rate within a range defined by any two of the following values: 1 Hz, 5 Hz, 10 Hz, 50 Hz, 100 Hz, 200 Hz, 300 Hz, 400 Hz, 500 Hz, 600 Hz, 700 Hz, 800 Hz, 900 Hz, 1 kHz, 10 kHz, 20 kHz, 30 kHz, 40 kHz, or 50 kHz.

[0191] In some embodiments, the number of shock waves delivered by the shock wave generator 100 can range from about 1 to about 10,000 shock waves. Those skilled in the art will understand that the number of shock waves delivered may depend on the desired tissue transformation outcome of the treatment.

[0192] In some embodiments, the total time for treating the target tissue at the predetermined location can range from about 30 seconds to about 30 minutes, for example, from about 2 minutes to about 5 minutes. In some embodiments, the total time for treating the target tissue at the predetermined location can be within a range defined by any two of the following values: 30 seconds, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 11 minutes, 12 minutes, 13 minutes, 14 minutes, 15 minutes, 16 minutes, 17 minutes, 18 minutes, 19 minutes, 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, 26 minutes, 27 minutes, 28 minutes, 29 minutes, or 30 minutes.

[0193] In some embodiments, the RF frequencies of electrodes 110 and 112 can be in the range of approximately 3-30 Hz and from 300 GHz to 3 THz. Lower power pre-pulses can be used for tissue seeding.

[0194] Shock waves can be focused or unfocused. In some cases, a focused shock wave may be preferred to deliver a larger amount of energy to the target tissue in order to produce a mechanical effect within the tissue. In other cases, an unfocused shock wave may be preferred to deliver a lower level of energy to the target tissue in order to provide a mild biochemical stimulus to the target tissue.

[0195] In some implementations, the shock wave can be focused onto a predetermined location on or below the surface of the eye. The propagation of the focused wave may be non-linear and may become steeper. The shock wave may have a rise time of about 0.01 microseconds, a compression time of about 0.3 microseconds, a positive peak pressure in the range of about 0 to about 100 MPa, and a pressure of about 0 to about 3 mJ / mm². 2 The energy flux density at the predetermined location.

[0196] In some implementations, the shock wave can be delivered to a predetermined location on or below the surface of the eye without focusing. The unfocused wave can be divergent, convergent, or a plane wave. The propagation of the unfocused wave may be linear and may not steepen. The shock wave can have a rise time of about 50 nanoseconds, a compression time of about 200 nanoseconds to about 10 microseconds, a positive peak pressure in the range of about 0 to about 100 MPa, and a pressure of about 0 to about 0.3 mJ / mm². 2 The energy flux density at the predetermined location.

[0197] Figure 3 A top view of an array 300 of shock wave generators 100 is shown. In some embodiments, the array 300 may include eight shock wave generators 100 arranged at equal intervals in a ring of about 10 mm to about 15 mm in diameter surrounding the limbus 302 for limbal-guided glaucoma treatment. As described herein, limbal-guided glaucoma treatment may be focused on the trabecular meshwork and / or Schrem's canal. Focusing shock waves along the trabecular meshwork and / or Schrem's canal to multiple locations may result in tissue expansion and improved fluid outflow, which may reduce IOP in glaucoma patients.

[0198] An array of shock wave generators may include two or more shock wave generators 100. For example, the array may include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 36, 37, 38, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 or more shock wave generators. An array of shock wave generators may include any number of the desired shock wave generators.

[0199] Shock wave generators 100 can be connected in parallel or in series.

[0200] The shock wave generators 100 can be configured to be energized independently or simultaneously. In some embodiments, all shock wave generators 100 can emit simultaneously. In some embodiments, no shock wave generators can emit simultaneously. In some embodiments, at least two shock wave generators 100 can emit simultaneously. In some embodiments, the shock wave generators can be independently controlled.

[0201] In some embodiments, the shock wave generator 100 may be configured to be energized sequentially in the circumferential direction. In at least some cases, it may be preferred to emit one shock wave at a time to avoid the formation of any unexpected structural shockwaves within the eye, which could potentially cause undesirable tissue effects at or outside the intended target location.

[0202] Figure 4 A top view of an array 400 of shock wave generators 100 arranged in multiple rows is shown. Figure 5 A side view of an array 400 arranged on a surface 500 of an eye 200 is shown. The array 400 may include at least two rows of shock wave generators 100. For example, the array 400 may include a first row 402, a second row 404, and a third row 406. The rows may be positioned such that the shock waves generated by each row are aimed at different locations on or below the surface of the eye.

[0203] For example, the first row, 402, can be like this: Figure 3 The arrangement shown surrounds the limbus for treatment and expansion of the trabecular meshwork and / or Schrem's canal. A second row 404 can be arranged radially lateral to the first row 402 and above the ciliary crown to treat the underlying scleral tissue and / or ciliary body. A third row 406 can be arranged radially outward from the second row 404 and positioned above the pars plana of the ciliary body to treat the underlying scleral tissue and / or ciliary body, for example, to increase porosity. For instance, increased porosity in the central matrix near the pars plana and / or ciliary crown can enhance hydrodynamic conduction / transport in the choroidal, ciliary, and / or lymphatic outflow pathways of the eye and reduce intraocular pressure during glaucoma treatment.

[0204] Based on the teachings of this document, those skilled in the art will understand that the number of rows, the spacing between shock wave generators, and the position of the rows can be configured to treat one or more indications as needed. In some embodiments, the rows may be equidistant from each other. In some embodiments, the rows may be spaced apart by different distances. In some embodiments, each shock wave generator within a row may be spaced apart from each other by the same distance (i.e., equidistant). In some embodiments, one or more shock wave generators may be spaced apart from one or more other shock wave generators by unequal distances. In some embodiments, the shock wave generator array may include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more rows as needed. The number of rows may or may not correspond to the number of ophthalmic conditions to be treated in the eye.

[0205] Figure 6 A side sectional view of an exemplary shock wave generator array system 600, including a cone that engages with an eye, is shown. System 600 may include an array of shock wave generators, which may be substantially similar to any shock wave generator array described herein. For example, system 600 may include arrays arranged as... Figures 4 to 5 The array of three spaced-apart annular rows of shock wave generators 100. The shock wave generators 100 can be attached to the surface 500 of the eye 200, for example, the sclera or limbus of the eye. In some embodiments, the shock wave generator 100 may include defined... Figure 1 The fluid-filled chamber shown is housed in a separate housing. Alternatively, one or more shock wave generators 100 may share a fluid-filled chamber or housing. For example, instead of a separate housing, the shock wave generator 100 may be housed within a housing configured to form a water channel 602 for flushing the shock wave generator 100 with fluid. The walls of the water channel 602 may include PET. The system 600 may also include a cone 604 disposed around the wall of the water channel 602, which may include a sight glass and a suction ring.

[0206] Figure 7A side sectional view 200 of an exemplary shock wave generator array system 700, including a contact lens 702 with a surface 500 bonded to an eye 200, is shown. The system may include one or more shock wave generators 100, which may be substantially similar to any shock wave generator array described herein. For example, a shock wave generator 100 may include a pair of electrodes 110, 112 as described herein. The shock wave generator 100 may be disposed below the contact lens 702. A membrane 704 may be disposed across the bottom of the contact lens 702 to form a fluid-filled chamber 106 around the shock wave generator 100. The membrane 704 may include an eye contact surface configured to bond to a surface of the eye, which may be substantially similar to any eye contact surface described herein. As described herein, the fluid-filled chamber 106 may be filled with saline 206. In some embodiments, the shock wave generator 100 may also include a fluid inlet and a fluid outlet in fluid communication with the fluid-filled chamber 106 as described herein.

[0207] In some embodiments, the contact lens 702 may be configured to act as a reflector to focus the shock wave onto a desired predetermined location. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of the fluid-filled chamber 106 to focus the shock wave. The inner wall of the fluid-filled chamber 106 or the reflector coupled to the inner surface of the fluid-filled chamber 106 may be elliptical.

[0208] In some embodiments, system 700 may include an array of shock wave generators 100. For example, system 700 may include eight shock wave generators 100 arranged at 45-degree intervals along a circular pattern above the surface of the eye.

[0209] In some embodiments, the system 700 can be securely attached to the eye using the suction on the inner and outer edges of the annular contact lens 702 (e.g., using a suction ring).

[0210] In some implementations, the membrane may include PET.

[0211] The membrane may include nylon, polyethylene terephthalate (PET), biaxially oriented polyethylene terephthalate (BoPET), etc. The membrane may include suitable polymers such as polytetrafluoroethylene (PTFE), ethylene tetrafluoroethylene (ETFE), fluorinated ethylene propylene (FEP), and polyoxymethylene (POM, for example, available from DuPont). Polyether block esters, polyurethanes (e.g., polyurethane 85A), polypropylene (PP), polyvinyl chloride (PVC), polyether esters (e.g., available from DSM Engineering Plastics) ), ether or ester copolymers (e.g., butene / poly(alkylene ether) phthalates and / or other polyester elastomers, such as those available from DuPont). ), polyamide (e.g., available from Bayer) CRISTA may be obtained from ElfAto Chemical Company. ), elastomer polyamide, block polyamide / ether, polyether block amide (PEBA, for example, can be found under trade name) The following are examples of materials: ethylene vinyl acetate copolymer (EVA), silicone resin, polyethylene (PE), Marlex high-density polyethylene, Marlex low-density polyethylene, linear low-density polyethylene (e.g., ), Polyester, polybutylene terephthalate (PBT), polyethylene terephthalate (PET), polypropylene terephthalate, polyethylene naphthalate (PEN), polyetheretherketone (PEEK), polyimide (PI), polyetherimide (PEI), polyphenylene sulfide (PPS), polyphenylene ether (PPO), polyterephthalamide (e.g., Polysulfone, nylon, nylon-2 (e.g., GRK available from EMS American Grilon). Perfluoro(propyl vinyl ether) (PFA), ethylene vinyl alcohol, polyolefins, polystyrene, epoxy resins, polyvinylidene chloride (PVdC), poly(styrene-A-isobutylene-A-styrene) (e.g., SIBS and / or SIBS 50A), polycarbonate, ionomers, biocompatible polymers, other suitable materials or mixtures, combinations, copolymers, polymer / metal composites, etc. In some embodiments, the film may include a mixture with a liquid crystal polymer (LCP) (e.g., up to about 6% LCP).

[0212] Figure 8A perspective view of a shock wave generator 800 is shown. The shock wave generator 800 may be substantially similar to the shock wave generator 100 described herein, except that the housing 102 may contain a reflector 802 disposed therein, rather than using the inner wall of the housing 102 as a reflector. The shock wave generator 100 may include a pair of electrodes 110, 112 disposed within the housing 102 as described herein. The housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. The eye contact surface 104 may be configured to engage with the surface of a patient's eye. The first electrode 110 and the second electrode 112 may be coaxially aligned with each other, such that a gap 114 is formed between the distal ends of the electrodes 110. As described herein, the fluid-filled chamber 106 may be filled with saline 206. In some embodiments, the shock wave generator 100 may also include a fluid inlet and a fluid outlet in fluid communication with the fluid-filled chamber 106 as described herein. As described herein, the reflector 802 may be configured to help focus the shock wave onto or below a predetermined location on or below the surface 500 of the eye 200.

[0213] Figure 9 A side view of a plurality of shock wave generators 800 attached to a surface 500 of an eye 200 is shown. In some embodiments, the plurality of shock wave generators 800 may be simultaneously disposed on the surface 500 of the eye. For example, the plurality of shock wave generators 800 may comprise a plurality of individual shock wave generators or an array of shock wave generators. In some embodiments, the plurality of shock wave generators 800 may comprise a plurality of shock wave generators disposed at the distal end of a handheld probe.

[0214] Figure 10 A side view of a plurality of shock wave generators 800 bonded to the surface 500 of the eye using a contact lens 1000 is shown. The shock wave generators 800 may be positioned below a contact lens 702. A membrane 704 may be disposed across the bottom of the contact lens 702 to form a fluid-filled chamber 106 around the shock wave generators 800. The membrane 704 may include an eye contact surface configured to bond to the surface of the eye, which may be substantially similar to any eye contact surface described herein. As described herein, the fluid-filled chamber 106 may be filled with saline 206. In some embodiments, the shock wave generators 800 may also include a fluid inlet and a fluid outlet in fluid communication with the fluid-filled chamber 106 as described herein. Alternatively or in combination, one or more of the plurality of shock wave generators 800 may include their own fluid-filled chamber independent of one or more of the other shock wave generators 800. The membrane 704 may be disposed across the bottom of the contact lens 702 to form a separate fluid-filled chamber 106 for the shock wave generator 800, and each shock wave generator 800 may have a dedicated fluid inlet and fluid outlet.

[0215] Figure 11 A side sectional view is shown of a plurality of shock wave generators 100 engaged with a contact balloon (also referred to herein as a fluid pad) 1100 to a surface 500 of an eye 200. The contact balloon 1100 may include an inflatable housing 102 in which the plurality of shock wave generators 100 are embedded. The housing 1102 may define an inner chamber 1106 which may be filled with a fluid such as saline 206 to inflate the housing 1102 before, during, or after placing the contact balloon 1100 on the surface 500 of the eye 200 (e.g., adjacent to the limbus, sclera, eyelids, etc., as described herein). As described herein, each shock wave generator 100 may include a pair of coaxially aligned electrodes 110, 112 and a reflector 802. As described herein, the electrodes 110, 112 may be coupled to a voltage pulse generator. As described herein, reflector 802 can be configured to help focus shock waves onto or below a predetermined location on the surface 500 of eye 200. In some embodiments, shock wave generators 100 can be arranged in multiple annular rows as described herein to target multiple locations of the eye. For example, the first row of shock wave generators can be positioned near the limbus and configured to focus shock waves onto the trabecular meshwork and Schrem's canal. The second row of shock wave generators can be positioned radially outward of the first row and adjacent to the ciliary crown, and the third row of shock wave generators can be positioned radially outward of the second row and adjacent to the plana of the ciliary body. For example, the second and / or third rows of shock wave generators can be configured to focus shock waves onto the sclera, ciliary crown, plana of the ciliary body, ciliary body, IVZ, and / or PVZ.

[0216] In some embodiments, the fluid filling the inner chamber 1106 of the contact balloon 1100 may be a cooled or temperature-controlled liquid.

[0217] The housing 1102 may include a compliant material. Alternatively or in combination, at least a portion of the housing 1102 may include a non-compliant material.

[0218] The housing 1102 may comprise any biocompatible plastic known to those skilled in the art.

[0219] In some embodiments, the bonding fluid or gel may be present on the eye contact surface of the housing to facilitate contact between the eye contact surface and the surface of the eye and / or to facilitate the transmission of shock waves from the shock wave generator to the eye.

[0220] In some embodiments, the therapeutic substance may be disposed between the eye contact surface and the surface of the eye. For example, the therapeutic substance may be disposed in a layer that bonds to the eye contact surface. In some embodiments, the therapeutic substance may comprise microcapsules formed of polymers, starch, and / or glucose. Delivering a shock wave from a shock wave generator within the housing to a predetermined location in the eye can facilitate the delivery of the therapeutic substance to the eye.

[0221] In some embodiments, any shock wave generator described herein can be configured to facilitate the transport of small molecular weight molecules such as methylene blue, riboflavin, or therapeutic small molecules.

[0222] Figure 12 A side sectional view of multiple shock wave generators attached to the eye using a contact balloon 1200 is shown. The contact balloon 1200 can be substantially similar to the contact balloon 1100, except that it can include multiple non-corresponding shock wave generators 100. For example, the contact balloon 1200 may include one or more shock wave generators 100a configured to generate focused shock waves and one or more shock wave generators 100b configured to generate unfocused shock waves. By providing multiple shock wave generators 100 with different focuses, multiple predetermined locations can be treated and / or multiple biological effects can be induced within the same predetermined location using an array of single shock wave generators. The contact balloon 1200 can be attached to the eye using suction rings 1202 on the inner and outer edges of the annular contact balloon 1200.

[0223] Figure 13 An exploded side view of an exemplary shockwave generator 100 adjacent to the eye is shown. The shockwave generator 100 may be embedded within a fluid-filled contact balloon 1300 as described herein. The shockwave generator 100 may include a pair of electrodes 110, 112 with a gap 114 between the ends of the electrodes 110, 112, the gap 114 being configured to generate an electric arc therebetween. As described herein, the contact balloon 1300 may be filled with a fluid such as saline 206, and the generated shockwave may propagate through the fluid 206 (which may act as an acoustic window). As described herein, an acoustic reflector or acoustic lens 1302 may be disposed above the electrodes 110, 112 to focus the shockwave onto or below a predetermined location on or below the surface 500 of the eye 200. For example, the reflector 1302 may be convex. The eye contact surface 1304 of the contact balloon 1300 may be directly or indirectly (e.g., via a gel or saline interface 202 therebetween) attached to the surface 500 of the eye 200. For example, the surface 500 of the eye may include the conjunctiva or cornea of ​​the eye 200.

[0224] Figure 14An exploded side view of another exemplary shock wave generator 100 adjacent to the eye 200 is shown. The shock wave generator 100 can be embedded within a contact balloon 1400 as described herein. The shock wave generator 100 can be substantially similar to... Figure 13 The shock wave generator shown may have a concave shape for the reflector 1402. The eye contact surface 1404 of the contact balloon 1400 may be directly or indirectly (e.g., through the gel or saline interface 202 therebetween) attached to the surface 500 of the eye 200.

[0225] Figure 15 A side sectional view is shown of a plurality of shock wave generators 100 attached to an eye 200 using a contact balloon 1500. Figure 16 It shows the attachment to eye 200 Figure 15 A perspective view of the system. The contact balloon 1500 may include an inflatable housing 1502 in which a plurality of shock wave generators 100 are embedded. The housing 1502 may define an inner chamber 1506 which may be filled with a fluid 206, such as saline, to inflate the housing 1502 before, during, or after placing the contact balloon 1500 on the surface 500 of the eye 200 (e.g., adjacent to the limbus, sclera, eyelids, etc., as described herein). As described herein, each shock wave generator 100 may include a pair of coaxially aligned electrodes and a reflector. As described herein, the reflector may be configured to help focus the shock wave onto a predetermined location on or below the surface of the eye. In some embodiments, the shock wave generators 100 may be arranged in a plurality of annular rows connected by wiring to target multiple locations of the eye. For example, the shock wave generators in the first row may be positioned near the limbus and configured to focus the shock wave onto the trabecular meshwork and Schrem's tube. The second row of shock wave generators can be positioned radially outward from the first row and adjacent to the ciliary crown, and the third row of shock wave generators can be positioned radially outward from the second row and adjacent to the pars plana of the ciliary body. For example, the second and / or third row of shock wave generators can be configured to focus shock waves onto the sclera, ciliary crown, pars plana of the ciliary body, ciliary body, IVZ, and / or PVZ.

[0226] In some embodiments, the fluid 206 filling the inner chamber of the contact balloon 1500 may be a cooled or temperature-controlled liquid.

[0227] The housing 1502 may include a compliant material. Alternatively or in combination, at least a portion of the housing may include a non-compliant material.

[0228] The housing 1502 may comprise any biocompatible plastic known to those skilled in the art. For example, the housing may comprise PMMA or other molded biocompatible materials.

[0229] In some embodiments, the eye contact surface 1504 of the housing can be configured to conform to the surface of the eye in a manner similar to that of a conventional soft contact lens.

[0230] In some embodiments, the bonding fluid or gel may be present on the eye contact surface of the housing to facilitate contact between the eye contact surface and the surface of the eye and / or to facilitate the transmission of shock waves from the shock wave generator to the eye.

[0231] Figure 17 The diagram shows connections to additional conduits and / or wiring 1700. Figure 15 A perspective view of system 1500. In some embodiments, additional conduit and / or wiring 1700 may include a cable comprising an inner conductor and an outer conductive sheath insulated from the inner conductor. A first electrode in a coaxially arranged array of electrodes may be formed at least partially by the center conductor of the cable, while a second electrode in a coaxially arranged array of electrodes may be formed at least partially by the outer conductive sheath of the cable.

[0232] Figure 18 The diagram shows a conduit and / or wiring 1700 connected to a power supply 1802. Figure 17 A side view of system 1800 of system 1500. Piping and / or wiring 1700 may also be connected to a fluid source to inflate the contact balloon and / or circulate fluid for conductivity sampling, as described herein.

[0233] Power supply 1802 may include a high-voltage pulse generator. In some embodiments, power supply 1802 may include a high-voltage capacitor charging power supply. A gated high-voltage electronic driver may be coupled to shock wave generator 100 and is capable of controlling the drive voltage of the electrodes, the dwell time at the start of the current, temperature rise (e.g., at the surface of the electrodes, fluid, or eye), peak pressure, and / or elasticity changes in response to a safety feedback mechanism such as (e.g., sensed by a current sensor as described herein) the maximum current.

[0234] The power supply 1802 can be in the range of approximately 1kV to approximately 10kV.

[0235] Any system described herein may include a processor having a tangible medium (e.g., RAM). Figure 70The processor is shown as 7002. The processor may be configured with one or more instructions to perform any one method and / or any step and sub-step of any of the methods or treatments described herein. The processor may include memory with instructions for performing the method, and the processor may include, for example, a processor system configured to perform the method. In many embodiments, the processor includes array logic such as programmable array logic (“PAL”), for example, configured to perform one or more steps of any of the methods or treatments described herein.

[0236] The processor may include one or more instructions of a therapeutic program contained on a tangible medium such as computer memory or a gate array to perform one or more steps of the therapeutic methods disclosed herein. The processor may also include instructions for treating a patient according to the embodiments described herein.

[0237] The processor can be operationally coupled to an energy source and configured with instructions to deliver energy to a shockwave generator having the therapeutic parameters described herein. For example, the processor can be configured with instructions to deliver multiple shockwaves to a predetermined location on or below the surface of the eye in a desired therapeutic mode and parameters. In embodiments where more than one shockwave generator is coupled to the eye at a time, the processor can be configured with instructions to deliver energy to multiple shockwave generators sequentially or simultaneously based on a predetermined therapeutic mode generated by the processor based on user input (e.g., an image or a desired therapeutic effect).

[0238] Any system described herein may include an imaging system, such as an ultrasound biological microscope (UBM), ultrasound (US) imaging, and / or optical coherence tomography (OCT) device or system. The imaging system may be used to take one or more images of the eye before, during, or after treatment as described herein. A processor or controller may be coupled to the power source and the imaging system and configured with instructions to deliver energy to a shock wave generator and image the tissue during treatment. The system may also include a display coupled to the processor that allows the user to visualize the tissue before, during, or after treatment. The display may show images that allow the user to view the treated tissue and plan the treatment. The images displayed on the display may be provided in real time and may be used before treatment to allow the user to align the tissue and / or monitor the tissue effects of the treatment (e.g., cavitation) to ensure that no unintended effects of the treatment occur (e.g., the structures of the eye changing position relative to each other unnecessarily).

[0239] For example, one or more shock wave generators may include a central aperture configured to allow integration of an OCT or wavefront imaging system or sensor. In some embodiments, multiple shock wave generators may be arranged in a ring around a central imaging system to enable passive cavitation monitoring. Those skilled in the art will understand that many configurations of shock wave generators and imaging devices can be derived based on the description herein.

[0240] Figure 19 A perspective view of a contact balloon 1900 including a plurality of shock wave generators 100 embedded therein is shown. The contact balloon 1900 may be substantially similar to any contact balloon described herein. The plurality of shock wave generators 100 may be substantially similar to any shock wave generator described herein. The shock wave generators 100 may include an array of shock wave generators as described herein. For example, as described herein, the array of shock wave generators may be connected in series or in parallel to a power source via wires 116. As described herein, the array of shock wave generators may be disposed within a fluid-filled chamber 1906 of the contact balloon 1900. As described herein, the fluid-filled chamber 1906 may include a fluid, such as saline solution. As described herein, the contact balloon 1900 may include an inflatable fluid-filled chamber 1906 configured to inflate when fluid is introduced therein. As described herein, the contact balloon 1900 may include a fluid inlet 108 and a fluid outlet 109. As described herein, the contact balloon 1900 can be secured to the eye using a suction device 1202 (e.g., using one or more suction rings).

[0241] Figure 20 A partial perspective view of multiple stacked toroidal conductor shock wave generators 2000 is shown. Figure 21 It shows Figure 20An exploded view of a ring conductor shock wave generator 2000. The stacked ring conductor shock wave generator 2000 may include multiple ring conductors “stacked” around each other, such that adjacent rings are within a predetermined distance of each other. The ring conductors may include insulated conductors 2100 wound around an insulating structure ring 2102. The insulated ring conductor 2102 may include one or more openings 2104 in the insulator, which may be spaced apart by a predetermined distance from another opening in the insulator of the same or adjacent ring conductor to form gaps in which shock waves can be formed in a manner substantially similar to that described herein with respect to the concentric electrode embodiment. Exposed conductor openings 2104 may be used to generate shock waves as described herein. In some embodiments, the insulated conductor 2100 and exposed or non-insulated conductors 2106 may be wound around the insulating structure ring 2102, such that the loop of each insulated conductor alternates between exposed and insulated and back to exposed around the ring 2102. An opening 2104 in the insulated conductor 2100 may be spaced apart by a predetermined distance from the exposed conductor 2106 of the same or adjacent ring conductors to form a gap in which a shock wave can act as described herein. The stacked ring conductor shock wave generator 2000 may be disposed in a fluid (e.g., salt water) environment, such as in a contact lens or balloon contact lens as described herein.

[0242] Figure 22 An exemplary treatment modality for glaucoma is illustrated. One or more shock wave generators (e.g., an array 2200 of shock wave generators 100) may be positioned on the surface 500 of the eye 200 as described herein. The multiple shock wave generators 100 may be substantially similar to any shock wave generator described herein. The shock wave generators may be configured to target one or more tissue locations within the eye 200 to reduce IOP. For example, multiple shock wave generators may be positioned above the limbus 302 of the eye as described herein, and the shock waves may be focused onto the trabecular meshwork and / or Schrem's canal 2202 to cause their dilation and improve fluid outflow from the eye. Alternatively or in combination, multiple shock wave generators may be positioned above the pars plana of the ciliary body as described herein, and the shock waves may be focused onto the sclera 2204 and / or the ciliary body 2210 to create micropores therein and enhance uveal-scleral outflow. Alternatively or in combination, one or more shock wave generators may be placed on the cornea 2206, and the shock waves may be focused onto the retina 2208 to provide it with low-energy acoustic stimulation for vasodilation and angiogenesis, which may enhance neurotrophic delay in retinal ganglion cells (RGCs) and / or retinal pigment epithelial (RPE) cell degeneration. Retinal targeting may also stimulate RPE cells to reset the dynamic equilibrium IOP set point, thereby reducing water generation (and subsequently lowering IOP).

[0243] Figure 23 An exemplary treatment modality for presbyopia is illustrated. One or more shock wave generators (e.g., an array 2300 of shock wave generators 100) may be positioned on the surface 500 of the eye 200 as described herein. The multiple shock wave generators 100 may be substantially similar to any shock wave generator described herein. The shock wave generators may be configured to target one or more tissue locations within the eye 200 to enhance the eye's accommodative amplitude. For example, multiple shock wave generators may be positioned above the sclera 2204 of the eye, and the shock waves may be focused onto the IVZ 2304 and / or PVZ 2306 to disaggregate them and improve their movement. Alternatively or in combination, multiple shock wave generators may be positioned above the ciliary body plana, and the shock waves may be focused onto the sclera 2204 to create micropores therein and enhance the compliance of its ciliary body apex as well as forward and concentric movements. Alternatively or in combination, one or more shock wave generators may be placed on the cornea 2206, and the shock waves may be focused onto the lens 2302 (natural or artificial lens (IOL)) to induce lens disagglomeration and softening and initiate LEC cell apoptosis. Different effects and treatment locations can be targeted by varying the depth of focus (e.g., by adjusting the ellipse of the reflective element), adjusting the amount of energy delivered by each shock wave (e.g., by adjusting the voltage delivered to the electrodes or the laser power), adjusting the repetition rate of treatment, etc.

[0244] Figure 24 An exemplary treatment modality for AMD is illustrated. A shockwave generator 2400, which may be substantially similar to any shockwave generator described herein, may be disposed on the surface of the eye. The shockwave generator 2400 may be configured to focus shockwaves onto the retina 2208. In some embodiments, multiple shockwave generators 2400 may be disposed on the surface 500 of the eye 200 and configured to direct shockwaves to multiple locations on the retina. For example, shockwaves may be directed to the macula, to the perifoveal region, and / or to the central retina (e.g., shockwaves may be directed to a central 6 mm diameter portion of the retina). The shockwaves may be directed to the retina 2208 via the cornea without heating or damaging any tissue therebetween. Shockwave treatment of the central retina may stimulate angiogenesis and vasodilation, while simultaneously targeting nerves and / or endothelial protection to treat retinal ganglion cells (RGCs) and / or retinal vascular plexuses to reduce or reverse the progression of AMD.

[0245] Figure 25 A top view of an exemplary treatment system 2600 for AMD is shown. Figure 26 It shows Figure 25A side sectional view of system 2600. An array of large (e.g., 5 mm outer diameter) shock wave generators 2500 can be positioned in a ring pattern (e.g., a ring approximately 11 mm in diameter) near the limbus 302 of eye 200. By using large shock wave generators 2500, system 2600 may be able to deliver biologically relevant shock wave energy into the eye to a greater depth of focus than might be achievable using smaller shock wave generators. For example, the array may include four shock wave generators 2500. The shock wave generators 2500 can be substantially similar to any shock wave generator described herein. The array of shock wave generators 2500 can be positioned on the surface 500 of eye 200, for example, the sclera 2204. In some cases, it may be advantageous to direct the shock wave through the sclera rather than through the cornea 2206. An array of shockwave generators 2500 can be configured to treat one or more predetermined locations on the retina 2208, such as the perifoveal region (e.g., in a ring-shaped treatment pattern with an intraocular diameter of approximately 6 mm and a depth of approximately 23 mm) to stimulate intraretinal angiogenesis and vasodilation to reduce or reverse the progression of AMD. For example, vascular effects can be stimulated by directing low-energy, wide-band shockwaves to the fovea within a 5.5 mm diameter ring region at the center of the retina for macular exposure. Compared to foveal treatment, perifoveal treatment may result in greater recruitment and stimulation of RPE cells to generate vasodilation and choroidal neovascularization. The shockwaves can be delivered to the retina without damaging the optic nerve.

[0246] Array 2600 may be disposed within contact lens 2602 as described herein. In some embodiments, contact lens 2602 may include imaging port 2604 configured to receive an imaging device (e.g., an OCT transducer) therein. Treatment can be monitored using the imaging device as described herein.

[0247] Figure 27Another exemplary treatment system 2700 for AMD is shown. System 2700 may include a large-diameter shock wave generator 2500 configured to deliver shock waves to the retina 2208. The shock wave generator 2500 may be substantially similar to any shock wave generator described herein. For example, the shock wave generator 2500 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. Housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. The fluid-filled chamber 106 may be configured to act as a reflector to focus the shock wave to a desired predetermined location. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of the fluid-filled chamber 106 to focus the shock wave. The inner wall of the fluid-filled chamber 106 or the reflector coupled to the inner surface of the fluid-filled chamber 106 may be elliptical. The conjugate focus of the ellipse 2702 may be configured such that the shock wave is focused through the lens 2302 of the eye and then refracted onto the retina 2208 of the eye. The shockwave generator 2500 may include an elliptical footprint on the sclera 2204, the footprint being on the order of a 12 mm aperture. Due to the large size of the shockwave generator 2500, the predetermined location on the retina 2208 may be relatively large (e.g., 6 mm in diameter) compared to a smaller shockwave generator that could facilitate faster treatment of the retina 2208. An eye contact surface 104 may be configured to engage with the surface 500 of the patient's eye 200. A bonding fluid or gel (e.g., a water column 2704) may be on or under the eye contact surface 104 to facilitate contact between the eye contact surface 104 and the surface 500 of the eye and / or to facilitate the transmission of shock waves from the shockwave generator 2500 to the eye 200. The first electrode 110 and the second electrode 112 may be coaxially aligned with each other, such that a gap 114 is formed between the distal ends of the electrodes 110, 112. The shockwave generator 2500 may be configured to generate one or more types of shock waves.

[0248] Figure 28 An exemplary treatment modality for dry eye disease is illustrated. In some patients, dry eye may be caused or exacerbated by meibomian gland dysfunction (MGD). Blockage of the meibomian gland 2800 produces an oily substance that prevents the evaporation of the eye's tear film layer (called meibomian fat), which can lead to tear film evaporation and dry eyes. One or more shockwave generators, substantially similar to any of the shockwave generators described herein, can be engaged with the eyelid 2802 adjacent to the meibomian gland, and low-energy shockwaves can be directed to the meibomian gland 2800 to dilate it and promote meibomian fat secretion. Alternatively or in combination, one or more high-energy shockwaves can be directed to the blockage in the meibomian gland to depolymerize or destroy the blockage. In at least some cases, shockwave therapy may be more comfortable and / or more effective than current meibomian gland unblocking therapies, which include thermal pulses, lacrimal duct plugs, and medications.

[0249] Figures 29 to 32 An exemplary treatment system 2900 for dry eye disease is shown. Figure 29 An array 2900 of shock wave generators 100 is shown, which is positioned across multiple meibomian glands 2800 on the inner surface of the eyelids 2802 of the eye (i.e., eyelid placement). Figure 30 An enlarged view of an array 2900 of shockwave generators that can be used to treat meibomian glands 2800 is shown. The array 2900 of shockwave generator 100 can be substantially similar to any shockwave generator described herein. For example, the array 2900 of shockwave generator 100 may include coaxial conductors 110, 112 exposed to fluid as described herein in order to maintain a low profile for patient comfort and ease of use. Figure 31 Multiple radially unfocused shock waves 204 that can be generated by shock wave generator array 2900 to treat meibomian glands 2800 are shown. Figure 32 A cross-sectional view of an eye 200 is shown, wherein an array 2900 of shock wave generators 100 is arranged in a ring around the limbus 302 for treating the meibomian glands 2800 of the eye 100 as described herein. The array 2900 of shock wave generators 100 may be disposed within a fluid-filled chamber 106 having a fluid inlet 108 and a fluid outlet 109 as described herein.

[0250] Figure 33 A plan view of an exemplary treatment system 3300 for softening the lens is shown. Figure 34 It shows the setting on the eye Figure 33 A side sectional view of system 3300. One or more shock wave generators (e.g., a ring array 2200 of shock wave generators 100) may be disposed on the surface 500 of eye 200 as described herein. Multiple shock wave generators 100 may be substantially similar to any shock wave generator described herein. Shock wave generators 100 may be configured to target the lens 2302 (natural or IOL) of eye 200 to soften the lens 2302 (e.g., to improve the eye's accommodative amplitude). For example, multiple shock wave generators 100 may be placed above the sclera 2204 of the eye, and the shock waves may be focused onto the lens 2302 to cause lens decohesion and softening and initiate LEC cell apoptosis.

[0251] Figure 35A side sectional view of an exemplary treatment system 3500 for presbyopia is shown. One or more shock wave generators (e.g., an array 2200 of shock wave generators 100) may be disposed on the surface 500 of the eye 200 as described herein. The plurality of shock wave generators 100 may be substantially similar to any shock wave generator described herein. The shock wave generators 100 may be configured to target one or more tissue locations within the eye 200 to improve the eye's accommodative amplitude. For example, the plurality of shock wave generators 100 may be positioned above the sclera 2204 of the eye, and the shock waves may be focused onto IVZ 2304 and / or PVZ 2306 to deconverge them and improve their motion. For example, the shock wave generators in a first annular row may be configured to focus shock waves onto IVZ 2034, and the shock wave generators in a second annular row disposed radially outward from the first annular row may be configured to focus shock waves onto PVZ 2306. Alternatively or in combination, multiple shock wave generators 3506 may be placed above the ciliary body plana, and the shock waves may be focused onto the sclera 2204 to create micropores therein and enhance the compliance of the ciliary body apex as well as forward and centripetal motion.

[0252] Figure 36 A side sectional view of an exemplary treatment system 3600 for glaucoma is shown. Figure 37 It shows Figure 36 Top view of the system. One or more shock wave generators (e.g., an array 2200 of shock wave generators 100) may be positioned on the surface 500 of the eye 200 as described herein. The multiple shock wave generators 100 may be substantially similar to any shock wave generator described herein. The shock wave generators 100 may be configured to target one or more tissue locations within the eye 200 to reduce IOP. For example, multiple shock wave generators may be positioned above the limbus 302 of the eye as described herein, and the shock waves may be focused onto the trabecular meshwork and / or Schrem's canal 2202 to dilate it and improve fluid outflow from the eye. Shock wave generators positioned above the limbus 302 may be configured as shock wave generators in a first annular row 3602. Alternatively or in combination, multiple shock wave generators 100 may be positioned above the plana of the ciliary body as described herein, and the shock waves may be focused onto the sclera 2204 and / or the ciliary body 2210 to create micropores therein and enhance uveal-scleral outflow. The shock wave generator 100 disposed above the ciliary body plane can be configured as a shock wave generator of a second annular row 3604 disposed radially outward from the first annular row.

[0253] Figure 38 A side sectional view of an exemplary array 3800 of a shock wave generator 100 is shown. Figure 39 It shows Figure 38The system 3800 may include one or more shock wave generators 100, which may be substantially similar to any shock wave generator array described herein. For example, shock wave generator 100 may include a pair of electrodes or optical fibers as described herein. Shock wave generator 100 may be positioned below contact lens 3082. Contact lens 3802 may be substantially similar to any contact lens described herein. Membrane 3804 may be disposed across the bottom of contact lens 3802 to form a fluid-filled chamber 3806 around the shock wave generator. Membrane 2804 may include an eye contact surface configured to adhere to a surface of the eye, which may be substantially similar to any eye contact surface described herein. As described herein, fluid-filled chamber 3806 may be filled with saline and / or graphene. In some embodiments, shock wave generator array 3800 may also include a fluid inlet 108 and a fluid outlet 109 in fluid communication with fluid-filled chamber 3806 as described herein.

[0254] In some embodiments, the contact lens 3802 may be configured to act as a reflector to focus a shock wave onto a desired predetermined location. For example, the inner surface of the contact lens may include one or more elliptical shapes or structures embedded therein. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of the fluid-filled chamber to focus the shock wave. The inner wall of the fluid-filled chamber 3806 or the reflector coupled to the inner surface of the fluid-filled chamber 3806 may be elliptical.

[0255] In some embodiments, the contact lens 3802 may include a thickness of about 2.0 mm, 1.5 mm, 1.0 mm, or 0.5 mm.

[0256] In some embodiments, when the film is disposed on the contact lens 3802, the outer shell of the contact lens 3802 may be located approximately 1.5 mm above the surface of the eye.

[0257] In some implementations, system 3800 may include an array of shock wave generators 100. For example, such as Figure 39 As shown, the system may include eight shock wave generators arranged at 45-degree intervals along a circular pattern above the surface of the eye. For example, a circular pattern with a diameter of 11 mm can space each shock wave generator 4 mm apart from its nearest neighbor.

[0258] In some embodiments, system 3800 may include an array comprising a plurality of shock wave rings as described herein. In some embodiments, when treating glaucoma, a first ring 3808 may have a diameter of approximately 11 mm so that it is positioned above the limbus of the eye when the contact lens is placed on the eye, a second ring 3810 may have a diameter of approximately 14 mm, and a third ring 3812 may have a diameter of approximately 17 mm. In some embodiments, when treating presbyopia, a first ring 3808 with a diameter of approximately 13 mm, a second ring 3810 with a diameter of approximately 16 mm, and a third ring with a diameter of approximately 19 mm can be used to treat the plana of the ciliary body and adjacent structures. In some embodiments, the lens may be aimed using a first ring 3808 with a diameter of approximately 3 mm, a second ring 3810 with a diameter of approximately 6 mm, and a third ring 3812 with a diameter of approximately 9 mm.

[0259] In some embodiments, the system 3800 can be securely attached to the eye using the suction on the inner and outer edges of the annular contact lens 3802 (e.g., using the suction ring 1202).

[0260] Figure 40A side sectional view of an exemplary treatment system for AMD is shown. The system may include a large-diameter shock wave generator 4000 configured to deliver shock waves to the retina 2208. The shock wave generator 4000 may be substantially similar to any shock wave generator described herein. For example, the shock wave generator 4000 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. The housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. The fluid-filled chamber 106 may be configured to act as a reflector to focus the shock wave to a desired predetermined location. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of the fluid-filled chamber 106 to focus the shock wave. For example, one or more reflectors may include an electronically variable acoustic lens 4002 that enables the shock wave to be variably focused on the macula of the retina 2208. The inner wall of the fluid-filled chamber 106 may be elliptical. The conjugate focus of the ellipse can be configured such that the shock wave is focused through the lens 2302 of the eye, and then the lens refracts the shock wave onto the retina 2208 of the eye. The eye contact surface 104 can be configured to adhere to the surface 500 of the patient's eye. A bonding fluid or gel (e.g., a water column) can be on or under the eye contact surface to facilitate contact between the eye contact surface 104 and the surface 500 of the eye and / or to facilitate the transmission of the shock wave from the shock wave generator to the eye. A suction ring 1202 can be disposed on the outer edge of the shock wave generator 4000 to adhere the shock wave generator 4000 to the cornea or sclera of the eye. The first electrode 110 and the second electrode 112 can be coaxially aligned with each other, such that a gap 114 is formed between the distal ends of the electrodes 110, 112. The shock wave generator 4000 can be configured to generate one or more shock waves.

[0261] Figure 41A side sectional view of an exemplary treatment system 4100 for dry eye disease is shown. System 4100 may include a large-diameter shock wave generator 4102 configured to deliver shock waves to a heat-dissipating contact lens 4104 disposed on a cornea 2206 of the eye. The shock wave generator 4102 may be substantially similar to any shock wave generator described herein. For example, the shock wave generator 4102 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. Housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. The fluid-filled chamber 106 may be configured to act as a reflector to focus the shock wave to a desired predetermined location. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of the fluid-filled chamber 106 to focus the shock wave. The inner wall of the fluid-filled chamber 106 or the reflectors coupled to the inner surface of the fluid-filled chamber 106 may be elliptical. An eye contact surface 104 can be configured to engage with a patient's eyelid 2802 (e.g., when the patient's eyes are closed). A heat-dissipating contact lens 4104 can be positioned below the eyelid 2802 on the patient's cornea 2206 to facilitate the transmission of shock waves from the shock wave generator to the eye 200. The heat-dissipating contact lens 4104 can be configured to act as an acoustic reflector and direct shock waves to one or more meibomian glands for the treatment of dry eye as described herein. A suction ring 1202 can be disposed on the outer edge of the shock wave generator 4102 to engage the shock wave generator 4102 with the eyelid 2802. A first electrode 110 and a second electrode 112 can be coaxially aligned with each other, such that a gap 114 is formed between the distal ends of electrodes 110, 112. The shock wave generator 4102 can be configured to generate one or more shock waves.

[0262] Figure 42 A cross-sectional view of an exemplary laser-based shock wave generator 4200 is shown. The shock wave generator 4200 may include an optical fiber cable 4202 disposed within a housing 102. As described herein, the housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. As described herein, the eye contact surface 104 may be configured to engage with a surface 500 of a patient's eye. The optical fiber 4202 may be configured to generate a shock wave in a fluid 206 within the fluid-filled chamber 106 when light energy is emitted from the optical fiber. A laser (e.g., a pulsed laser) may be coupled to the optical fiber 4202 to provide light energy to the optical fiber. As described herein, the shock wave generator system may include one or more sensors.

[0263] Shockwave generator 4200 can be configured to generate one or more shock waves using optical fiber 4202. Shockwave generator 4200 can be configured to use the shock waves it generates to treat one or more tissues or structures on or below the surface 500 of the eye. The treatment can be non-thermal. The shock waves can be focused at a predetermined location as described herein or unfocused. The shock waves can be used for local separation, microporization, dilation, and / or sensing of desired ocular tissues. In some embodiments, the shock waves can be used to generate biomechanical effects (such as vasodilation, microporization, softening, etc.) and / or biochemical effects (such as angiogenesis, etc.) as described herein. In some embodiments, the shock waves can be used to deliver drugs to ocular tissues.

[0264] The fluid-filled chamber 106 may include a fluid 206 disposed therein. The fluid may include a conductive (e.g., conductivity of about 0.6 mS), biocompatible liquid. The fluid may include water or saline solution. The fluid may include a suspension of graphene in saline solution. In some embodiments, the fluid may include a suspension of graphene in saline solution that can sufficiently absorb light to prevent or reduce light emitted by the shock wave generator 4200. The fluid may be cooled (e.g., about 10 degrees Celsius). In some embodiments, the shock wave generator 4200 may also include a fluid inlet and a fluid outlet in fluid communication with the fluid-filled chamber 106. The fluid 206 may be used to bond the shock wave generated in the optical fiber 4202 to the surface 500 of the eye. The fluid may circulate within the fluid-filled chamber 106 via the fluid inlet and fluid outlet. As the pulse delivery of the shock wave proceeds, fluid circulation allows for the continuous extraction of thermal build-up, cavitation bubbles, and ions generated during shock wave formation. In some embodiments, as described herein, the fluid 206 flowing out of the fluid-filled chamber 106 via the fluid outlet may be sampled periodically or continuously.

[0265] The fluid-filled chamber 106 can be configured to act as a reflector to focus a shock wave onto a desired predetermined location. Alternatively or in combination, one or more reflectors substantially similar to any of the reflectors described herein can be attached to the inner surface of the fluid-filled chamber to focus the shock wave. As described herein, the inner wall of the fluid-filled chamber 106 or the reflector attached to the inner surface of the fluid-filled chamber 106 can be elliptical.

[0266] In some embodiments, the optical fiber 4202 may be configured to transmit a collimated beam of light into the fluid in the fluid-filled chamber 106.

[0267] Fiber optic cable 4202 can be connected to an optical energy source, such as a laser. The laser can include a pulsed laser. The laser can be configured to emit light at wavelengths with high water absorption. For example, the laser can be configured to emit light in the mid-infrared wavelength range, such as 1.44 μm, 1.475 μm, 1.55 μm, 1.948 μm, or 6 μm. For example, the laser can include Nd:Yag or Th:Ho lasers, etc.

[0268] In some implementations, the light pulses from the pulsed laser can be from about 1 Hz to about 25 Hz.

[0269] In some implementations, the length of the light energy pulse from the pulsed laser can be on the order of nanoseconds to microseconds.

[0270] In some implementations, the laser can be a free-space scanning laser, or it can be delivered using fiber optic coupling depending on proximity to the target tissue. For example, the scanning laser can be conically attached to the eye. The cone can position the scanning laser at a known working distance above the eye. A saline-filled contact lens balloon can be positioned above the eye within the cone. The outer shell of the contact lens balloon can be transparent to the laser (e.g., infrared transparent when using an infrared laser). The laser can scan above the contact lens balloon, and when the laser reaches the fluid in the contact lens balloon, it can generate a shock wave in a manner substantially similar to that described herein.

[0271] In some implementations, the shock wave generator can be positioned at the distal end of the handheld probe.

[0272] In some implementations, a laser-based shock wave generator 4200 may be positioned near the limbus 302 and configured to focus shock waves onto the trabecular meshwork 4206 and Schrem's canal 2202 and / or open the iridocorneal angle 4204 to treat glaucoma.

[0273] Figure 43A side sectional view of an array 4300 of a laser-based shock wave generator 4200 in a fluid-filled contact lens 4302 is shown. The fluid-filled contact lens balloon 4302 can be substantially similar to any contact lens described herein. For example, the contact balloon 4302 may include an inflatable housing 4304 in which a plurality of elliptical reflectors 4306 are embedded. The housing 4304 may define an inner chamber 4308 which may be filled with a fluid such as saline or graphene-containing saline to inflate the housing 4304 before, during, or after the contact balloon 4302 is placed on a surface of the eye (e.g., adjacent to the limbus, sclera, eyelids, etc., as described herein). One or more optical fibers 4202 may be disposed within the fluid-filled chamber 4308 and configured to thereby generate shock waves as described herein. Elliptical reflectors 4306 embedded along the inner surface of the fluid-filled chamber 4308 can be configured to help focus shock waves onto predetermined locations on or below the surface of the eye, as described herein. In some embodiments, reflectors 4306 can be arranged in multiple annular rows as described herein to target multiple locations of the eye. For example, a first row of reflectors can be positioned near the limbus and configured to focus shock waves onto the trabecular meshwork and Schrem's canal. A second row of reflectors can be positioned radially outward of the first row and adjacent to the ciliary crown, and a third row of reflectors can be positioned radially outward of the second row and adjacent to the ciliary body plana. For example, the second and / or third rows of reflectors can be configured to focus shock waves onto the sclera, ciliary crown, ciliary body plana, ciliary body, IVZ, and / or PVZ. One or more suction rings can be positioned along one or more edges of the contact lens capsule 4302 to secure the contact lens capsule to the surface of the eye, as described herein.

[0274] In some embodiments, the fluid filling the inner chamber 4308 of the contact balloon 4302 may be a cooled or temperature-controlled liquid.

[0275] The housing 4304 may include a compliant material. Alternatively or in combination, at least a portion of the housing 4304 may include a non-compliant material. In some embodiments, the housing may include polymethyl methacrylate (PMMA).

[0276] In some embodiments, a bonding fluid or gel may be present on the eye contact surface 4310 of the housing 4304 to facilitate contact between the eye contact surface 4310 and the surface of the eye and / or to facilitate the transmission of shock waves from the shock wave generator / reflector to the eye.

[0277] In some implementations, the imaging device (e.g., a camera, OCT, or wavefront device) may be positioned within the contact lens (e.g., at the center of the cornea) to facilitate intraoperative accuracy of pressure wave delivery as described herein.

[0278] Figure 44 An array 4400 of laser-based shock wave generators 4200 in an annular fluid-filled contact lens 4402 is shown. Figure 45 It shows Figure 44 Side sectional view of System 4400. Figure 46 It shows Figure 44 The system 4400 is shown in top view. The system 4400 may include one or more shock wave generators 4200, which may be substantially similar to any shock wave generator array described herein. For example, the shock wave generator 4200 may include one or more optical fibers 4202 as described herein. As described herein, the shock wave generator 4200 may be disposed below a contact lens or within a contact lens bulb 4402. A membrane 4404 may be disposed across the bottom of the contact lens 4402 to form a fluid-filled chamber 4406 around the shock wave generator 4200. The membrane 4404 may include an eye contact surface configured to adhere to a surface 500 of the eye, which may be substantially similar to any eye contact surface described herein. As described herein, the fluid-filled chamber 4406 may be filled with saline solution and graphene. In some embodiments, the system 4400 may also include a fluid inlet 108 and a fluid outlet 109 in fluid communication with the fluid-filled chamber 4406 as described herein.

[0279] In some embodiments, the contact lens 4402 may be configured to act as a reflector to focus a shock wave onto a desired predetermined location. For example, the inner surface of the contact lens may include one or more elliptical shapes or structures embedded therein. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of the fluid-filled chamber to focus the shock wave. The inner wall of the fluid-filled chamber or the reflector coupled to the inner surface of the fluid-filled chamber may be elliptical.

[0280] In some embodiments, when the membrane 4404 is placed on the eye, the distal end of the optical fiber 4202 may be located approximately 1.5 mm above the surface of the eye.

[0281] In some embodiments, system 4400 may include an array of shock wave generators 4200. For example, system 4400 may include a plurality of shock wave generators 4200 arranged in a ring pattern. A plurality of optical fibers 4202 may be coupled to contact lens 4402 and disposed within fluid-filled chamber 4406 to generate a plurality of shock waves as described herein.

[0282] In some embodiments, the system 4400 can be securely attached to the eye using the suction on the inner and outer edges of the annular contact lens 4402 (e.g., using the suction ring 1202).

[0283] Figure 47 A top view of an array 4700 of laser-based shock wave generators 4200 in an annular contact lens 4702 is shown. Figure 48 It shows Figure 47 A side sectional view of system 4700. Multiple shock wave generators 4200, which may be substantially similar to any shock wave generator described herein, may be disposed within contact lens 4702. For example, multiple shock wave generators 4200 may include a housing 102 and an eye contact surface 104 defining a fluid-filled chamber 106 therein. Housing 102 may be coupled to or include structures disposed within annular contact lens 4702. For example, housing 102 may include 3D-printed material and may be surrounded by a contact lens material such as PMMA to form an annular contact lens structure 4702 surrounding the shock wave generator 4200. Annular contact lens 4702 may be securely attached to the eye by suction at its inner and outer edges (e.g., using suction ring 1202). Multiple shock wave generators 4200 may include a pair of electrodes or optical fibers configured to generate shock waves within the fluid-filled chamber as described herein. As described herein, the shock waves may be focused onto one or more locations on or below the surface of the eye.

[0284] In some embodiments, the annular contact lens 4702 may include multiple shock wave generators, such as 8 or 16 shock wave generators disposed at a corneal limbal diameter of approximately 11 mm.

[0285] In some implementations, the diameter of each shock wave generator 4200 can be approximately 3 mm.

[0286] In some embodiments, the outer diameter of the annular contact lens 4702 can be approximately 19 mm.

[0287] Figure 49 A side sectional view is shown of an array 4900 of shock wave generators arranged in multiple rows and positioned on the eye. The array of shock wave generators may include wires (e.g., such as...) disposed within an insulating sheath having multiple holes. Figure 50 and Figure 52 (as shown) or an optical fiber disposed within a cladding having multiple holes therein (e.g., as shown) Figure 51 and Figure 53(As shown). One or more shock wave generating wires or optical fibers may be disposed within a fluid-filled contact lens as described herein. The portion of one or more shock wave generating wires or optical fibers disposed near the eye may be annular as described herein. In some embodiments, a fluid-filled contact lens may include three annular shock wave generating wires or optical fibers disposed within its fluid-filled chamber. For example, as described herein, a first wire or optical fiber 4902 may be disposed within the contact lens and above the limbus, a second wire or optical fiber 4904 may be disposed within the contact lens and above the ciliary crown, and a third wire or optical fiber 4906 may be disposed within the contact lens and above the plana of the ciliary body.

[0288] The holes in the shock wave generating wires or optical fibers can be configured to direct the shock wave to one or more locations on or below the surface of the eye, as described herein.

[0289] Contact lenses may include one or more reflective surfaces as described herein (e.g., the inner elliptical wall of a fluid-filled chamber and / or a reflector) to facilitate the focusing of shock waves.

[0290] In some implementations, the hole can be positioned approximately 1 mm above the surface of the eye inside the contact lens.

[0291] Suction can be used to hold the contact lens in place on the eye. For example, a first suction ring can be positioned at the inner edge of the annular contact lens (e.g., about 9 mm), and a second suction ring can be positioned at the outer edge of the annular contact lens (e.g., about 19 mm).

[0292] As described in this article, the fluid can circulate within the fluid-filled chamber.

[0293] Figure 50An exemplary row of 5000 shock wave generators is shown, comprising conductors 5002 disposed within an insulating sheath having a plurality of holes 5004 therein. The conductors may be disposed within an insulating sheath or coating configured to prevent electrical energy from being emitted through them. The conductors may be disposed near the eye, for example, within a low-profile fluid-filled contact lens that is bonded to the surface of the eye as described herein. The fluid-filled contact lens may be configured to focus the shock waves generated by the conductors onto one or more predetermined locations on or below the surface of the eye. The conductors may be disposed in annular loops within the fluid-filled contact lens. In some embodiments, the fluid-filled contact lens may include a plurality of annular conductors disposed therein with a plurality of radial diameters as described herein. One or more holes or apertures may be formed within the insulation at predetermined locations to allow the conductors to function as electrodes and generate shock waves when energized, as described herein. For example, eight side-emitting apertures may be disposed within the cladding to form eight shock wave generators along the length of the conductors. Energy can be transferred from an arc of an electrode exposed by an aperture to the surrounding fluid using a single conductor, which can then generate shock waves as described herein.

[0294] Those skilled in the art will understand that the number of side emission holes disposed within the insulator can be any number required based on the treatment location and mode of interest.

[0295] In some implementations, the wire or cable may have an outer diameter of about 100 μm.

[0296] Figure 51 An exemplary row of shock wave generators 5100 is shown, comprising optical fibers 5102 disposed within a cladding having a plurality of apertures 5104 therein. The optical fibers may be disposed within a cladding configured to prevent light emission through the cladding. The optical fibers may be disposed near the eye, for example, embedded within a fluid-filled annular (e.g., scleral) contact lens as described herein, bonded to the surface of the eye. The fluid-filled contact lens may be configured to focus the shock waves generated by the optical fibers onto one or more predetermined locations on or below the surface of the eye. The optical fibers may be disposed in an annular loop within the fluid-filled contact lens. One or more holes or apertures (i.e., selective removal of the cladding) may be fabricated within the cladding at predetermined locations to allow the optical fibers to emit light through said one or more holes or apertures. For example, nine side-emitting apertures may be disposed within the cladding to form nine shock wave generators along the length of the optical fibers. Because a single optical fiber is used to transmit light energy through the aperture into the surrounding fluid, which then generates shock waves as described herein, the power output of the shock waves generated at each aperture may be the same. Shock waves may be generated simultaneously at each aperture. The mirror can be placed at the far end of the optical fiber.

[0297] Those skilled in the art will understand that the number of side firing holes disposed within the cladding can be any number required based on the treatment location and mode of interest.

[0298] In some implementations, the optical fiber may include a polymicro 50μm core surrounded by a 30μm cladding (for an 80μm outer diameter).

[0299] In some implementations, the optical fiber may include an outer diameter of about 100 μm.

[0300] Figure 52 An exploded view of an array 5200 of a shock wave generator including conductors 5206 disposed within an insulating sheath having a plurality of holes 5204 therein is shown. The conductors 5206 may be disposed within an insulating sheath or coating 5202 configured to prevent electrical energy from being emitted through them. The conductors 5206 may be disposed near the eye, for example, within a fluid-filled contact lens that is bonded to the surface of the eye as described herein. The fluid-filled contact lens may be configured to focus the shock wave generated by the conductors onto one or more predetermined locations on or below the surface of the eye. The conductors 5206 may be disposed in annular loops within the fluid-filled contact lens. In some embodiments, the fluid-filled contact lens may include a plurality of annular conductors disposed therein with a plurality of radial diameters as described herein. One or more holes or apertures 5204 may be formed within the insulator 5202 at predetermined locations to allow the conductors 5206 to function as electrodes and generate shock waves when energized, as described herein. For example, nine side-emitting holes 5204 can be disposed within the cladding 5202 to form nine shock wave generators along the length of the conductor. Energy can be transferred from the arc of the hole-exposed electrode to the surrounding fluid using a single conductor 5206, which can then generate shock waves as described herein. Shock waves can be generated simultaneously at each hole 5204.

[0301] In some embodiments, the holes 5204 may be equidistant along the length of the wire 5206 adjacent to the eye. For example, each of the nine holes 5204 may be spaced 4 mm apart from its nearest neighbor. In some embodiments, the holes 5204 may be unequally spaced along the length of the wire 5206 adjacent to the eye.

[0302] Those skilled in the art will understand that the number of side emission holes 5204 disposed within the insulator 5202 can be any number required based on the treatment location and mode of interest.

[0303] In some embodiments, insulator 5202 may include a polyamide insulator.

[0304] In some implementations, the diameter of the hole 5204 can be approximately 0.5 mm.

[0305] Figure 53 An exploded view of an array 5300 of shock wave generators including optical fibers 5302 disposed within a cladding 5304 having a plurality of holes 5306 is shown. The optical fibers 5302 may be disposed within the cladding 5304, which is configured to prevent light emission through the cladding. The optical fibers 5302 may be disposed near the eye, for example, within a fluid-filled contact lens bonded to the surface of the eye as described herein. The fluid-filled contact lens may be configured to focus the shock waves generated by the optical fibers onto one or more predetermined locations on or below the surface of the eye. The optical fibers 5302 may be disposed in an annular ring within the fluid-filled contact lens. One or more holes or apertures 5306 (i.e., selective removal of the cladding) may be formed within the cladding 5304 at predetermined locations to allow the optical fibers 5302 to emit light through said one or more holes or apertures. For example, nine side-emitting apertures 5306 may be disposed within the cladding 5304 to form nine shock wave generators along the length of the optical fibers 5302. Because a single optical fiber 5302 is used to transmit light energy into the surrounding fluid through aperture 5306, which then generates a shock wave as described herein, the power output of the shock wave generated at each aperture 5306 may be the same. A mirror 5308 may be positioned at the distal end of the optical fiber 5302.

[0306] In some embodiments, the holes 5306 may be equidistantly spaced along the length of the optical fiber 5302 and adjacent to the eye. For example, each of the nine holes 5306 may be spaced 4 mm apart from its nearest neighbor. In some embodiments, the holes 5306 may be unequally spaced along the length of the optical fiber and adjacent to the eye.

[0307] Those skilled in the art will understand that the number of side emission holes 5306 disposed within the cladding can be any number required based on the treatment location and mode of interest.

[0308] In some embodiments, optical fiber 5302 may include a polymicro 50μm core surrounded by a 30μm cladding (for an 80μm outer diameter).

[0309] Figure 54 Method 5400 for treating the eye is shown.

[0310] In step 5401, one or more shock wave generators may be attached to the surface of the eye. The shock wave generators may include any shock wave generator described herein. For example, a single shock wave generator may be attached to the eye as described herein. Alternatively, an array of shock wave generators may be attached to the eye as described herein, such as, for example, using a contact lens or contact balloon.

[0311] In step 5402, one or more shock wave generators may be energized to generate one or more shock waves as described herein. When more than one shock wave generator is energized, the shock wave generators may be energized independently of each other (e.g., sequentially) or together with one or more other shock wave generators (e.g., at least two generators emitting simultaneously). Those skilled in the art will understand that any combination of shock wave generators may be energized individually or independently of each other.

[0312] In step 5403, the shock wave may be focused onto a predetermined location on or below the surface of the eye. Those skilled in the art will understand that the predetermined location can be selected based on the ophthalmic condition to be treated or multiple conditions. For example, when treating glaucoma, the predetermined location may include the trabecular meshwork, Schreim's canal, sclera, and / or retina. In presbyopia, the predetermined location may include the sclera, IVZ, PVZ, and / or lens. In an eye with AMD, the predetermined location may include the macular retina, for example, the fovea or perifovea of ​​the retina. In an eye with dry eye disease, the predetermined location may include the meibomian glands. Those skilled in the art will understand that multiple conditions can be treated in the same eye, and the predetermined location treated in the eye may correspond to the condition to be treated. For example, an eye receiving simultaneous treatment for both glaucoma and presbyopia may have the shock wave focused onto the sclera to create micropores therein, which may improve fluid outflow (and subsequently reduce intraocular pressure during glaucoma treatment) and scleral compliance (which may improve its range of motion during accommodation).

[0313] In step 5404, steps 5401 to 5403 may be repeated as needed to treat the eye condition of concern.

[0314] Although the shock wave generators described herein typically rely on electro-hydraulic shock wave generation, those skilled in the art will understand from the teachings herein that other shock wave generation methods can be utilized, including piezoelectric, laser, and magnetoelectric shock wave generators as described herein. For example, a movable coil or permanent magnet coupled to the eye can also be used as a shock wave generator.

[0315] The shockwave therapy methods described herein can be enhanced by the application of nanoparticles. Compared to the absence of nanoparticles, nanoparticles can mediate the initiation of shock waves at a lower cavitation threshold. Acoustic nanoparticles can be added to the fluid filling chamber of any shock wave generator described herein to lower the threshold for cavitation bubble and shock wave formation. In some embodiments, nanoparticles can be injected (e.g., preoperatively) into the tissue targeted for treatment to enhance extravasation and / or penetration. Alternatively, pre-injection of nanoparticles into the tissue can accelerate and / or prolong inertial cavitation and / or reduce associated side effects.

[0316] Without being constrained by any particular theory, nanoparticle-mediated acoustic cavitation may lead to cytotoxic effects via one or both of the following two main pathways hypothesized in the art: 1. ruptured bubbles directly damage cells through shock waves, shear stress, and the formation of reactive oxygen species, and / or 2. cavitation-induced nanoparticle activation (depending on the nanoparticle formulation and desired effect) can lead to chemical cytotoxicity.

[0317] In some embodiments, nanoparticles may include nanodroplets, nanocones, polymer cups, etc. For example, nanoparticles may include perfluorohexane nanocones, mesoporous silica nanoparticles, solid gas trapping nanoparticles, microbubbles, acoustically vaporizable droplets, polymer cups, etc.

[0318] In any of the embodiments described herein, the housing and / or one or more reflectors coupled to the inner surface of the housing may comprise plastic or metal. In at least some cases, a metal housing or reflector may reflect shock waves more effectively than a plastic housing or reflector because metal has a lower acoustic impedance compared to plastic. This may reduce the input power required to generate the shock wave.

[0319] In some implementations, the array of shock wave generators may include multiple electrodes shaped like wheels and spokes, such that each electrode is electrically connected to each other and can be driven by the same power source and emit simultaneously. The multiple electrodes may be formed from metal foil (e.g., brass, stainless steel, etc.).

[0320] Figure 55A side sectional view 200 of an exemplary laser scanning shockwave generator array system 5500 is shown, including a contact lens 5502 comprising a surface 500 bonded to an eye 200. The contact lens 5502 may be substantially similar to any fluid-filled contact lens described herein. The contact lens may include a membrane or diaphragm 5504 disposed across the bottom of the contact lens 5502 to form a fluid-filled chamber 5506 therebetween. The membrane 5504 may include an eye contact surface configured to bond to the surface of the eye, which may be substantially similar to any eye contact surface described herein. As described herein, the fluid-filled chamber 5506 may be filled with a fluid, such as saline solution. The fluid 206 may include a suspension of graphene in saline solution. In some embodiments, the fluid 206 may include a suspension of graphene in saline solution that sufficiently absorbs light to prevent or reduce light emitted from the scanning laser 5508. In some embodiments, the contact lens 5502 may also include a fluid inlet 108 and a fluid outlet 109 in fluid communication with the fluid-filled chamber 106 as described herein. Fluid 206 can circulate within the fluid-filled chamber 5506 via fluid inlet 108 and fluid outlet 109. The front surface 5510 of the contact lens can include a transparent meniscus window through which light energy can pass. For example, the transparent meniscus window 5510 can be transparent to lasers (e.g., infrared transparent when using an infrared laser). System 5500 may also include a free-space scanning laser 5508. The scanning laser 5508 can be a pulsed laser. In some embodiments, the scanning laser 5508 can be conically engaged with the eye. The cone can position the scanning laser 5508 at a known working distance above the eye. The contact lens 5502 can be disposed above the eye within the cone. The laser 5508 can scan over the contact lens balloon 5502, and when the laser reaches the fluid in the contact lens, it can generate a shock wave in a manner substantially similar to that described herein. Compared to a fixed shock wave generator, the use of the scanning laser 5508 can provide increased spatiotemporal flexibility in the treatment location.

[0321] In some implementations, the system 5500 can be securely attached to the eye using suction on the outer edge of the contact lens (e.g., using a suction ring 1202).

[0322] In some embodiments, membrane 5504 may comprise a PET and / or PTFE separator as described herein. Membrane 5504 may comprise any of the materials described herein.

[0323] Laser 5508 can be configured to emit light at wavelengths with high water absorption. For example, the laser can be configured to emit light in the mid-infrared wavelength range, such as 1.44 μm, 1.475 μm, 1.55 μm, 1.948 μm, 3 μm, or 6 μm. For example, the laser can include Nd:Yag or Th:Ho lasers, etc. In some embodiments, the laser can be configured to emit light in the near-infrared wavelength range. In some embodiments, the laser can be configured to emit light in the long-infrared wavelength range, for example, 10 μm. In some embodiments, the laser can be configured to emit light in the far-infrared wavelength range, for example, at frequencies on the order of several terahertz (THz).

[0324] In some implementations, the light pulses from the pulsed laser can be from about 1 Hz to about 25 Hz.

[0325] In some implementations, the length of the light energy pulse from the pulsed laser can be on the order of nanoseconds to microseconds.

[0326] Figure 56 A side sectional view of an exemplary multi-fiber laser-based shock wave generator array system 5600, including a contact lens 5602, is shown. The contact lens 5602 can be substantially similar to any fluid-filled contact lens described herein. The contact lens 5602 may include a membrane or diaphragm 5604 disposed across the bottom of the contact lens 5602 to form a fluid-filled chamber 5606 therebetween. The membrane 5604 may include an eye contact surface configured to adhere to a surface of the eye, which may be substantially similar to any eye contact surface described herein. As described herein, the fluid-filled chamber 5606 may be filled with a fluid, such as saline solution. The fluid may include a suspension of graphene in the saline solution. In some embodiments, the fluid may include a suspension of graphene in the saline solution that can sufficiently absorb light to prevent or reduce light emitted from a scanning laser. In some embodiments, the contact lens 5602 may also include a fluid inlet and a fluid outlet in fluid communication with the fluid-filled chamber 5606 as described herein. The fluid may circulate within the fluid-filled chamber 5606 via the fluid inlet and fluid outlet. System 5600 may also include one or more fiber optic cables 4202 coupled to the contact lens. The one or more fiber optic cables 4202 may be configured to generate one or more shock waves in the fluid of the fluid-filled chamber 5606 when light energy is emitted from the fiber optic cables. When the laser reaches the fluid in the contact lens capsule 5602, the shock waves may be generated in a manner substantially similar to that described herein.

[0327] A laser (e.g., a pulsed laser) can be coupled to the optical fiber 4202 to provide optical energy to the fiber. In some embodiments, one or more optical fibers 4202 may comprise an optical fiber bundle or a multi-fiber array 5608. Two or more optical fibers 4202 may be bundled in an optical fiber bundle 5608, which may be split into an array of optical fibers 4202 adjacent to the contact lens 5602, and the array of optical fibers 4202 may then be individually coupled to the contact lens 5602 at predetermined locations as described herein.

[0328] In some embodiments, the front surface 5608 of the contact lens 5602 may include a transparent meniscus window through which light energy can pass, as described herein. The optical fiber 4202 may be coupled to the front surface 5608 of the contact lens 5602, such that light energy is transmitted from the optical fiber 4202 through the front surface 5608 of the contact lens 5602 and into the fluid of the contact lens. Alternatively or in combination, the optical fiber 4202 may pass through the front surface 5608 of the contact lens 5602, such that light energy is transmitted directly from the optical fiber 4202 into the fluid of the contact lens.

[0329] In some embodiments, the contact lens 5602 may be configured to act as a reflector (or an array of reflectors) to focus a shock wave onto a desired predetermined location. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of the fluid-filled chamber 5606 to focus the shock wave.

[0330] In some embodiments, the optical fiber 4202 may be configured to transmit a collimated beam of light into the fluid in the fluid-filled chamber.

[0331] Figure 57A side sectional view of an exemplary shock wave generator 5700 including a waveguide 5702 is shown. The shock wave generator 5700 can be substantially similar to any shock wave generator described herein. For example, the shock wave generator 5700 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. The housing may include a fluid-filled chamber 106 and an eye contact surface 104. In some embodiments, the shock wave generator 5700 may also include a fluid inlet 108 and a fluid outlet 109 in fluid communication with the fluid-filled chamber 106 as described herein. Fluid may circulate within the fluid-filled chamber 106 via the fluid inlet 108 and the fluid outlet 109. In some embodiments, the shock wave generating components (e.g., electrodes, laser fibers, etc.) and the fluid-filled chamber 106 may be spaced apart from the eye contact surface 104 by the waveguide 5702. The waveguide 5702 may be disposed between the fluid-filled chamber 106 and the eye contact surface 104. The fluid-filled chamber 106 can be configured to act as a reflector to focus a shock wave via waveguide 5702 to a desired predetermined location. Alternatively or in combination, one or more reflectors can be coupled to the inner surface of the fluid-filled chamber 106 to focus the shock wave. The inner wall of the fluid-filled chamber 106 can be elliptical. Alternatively or in combination, the end of waveguide 5702 including the eye contact surface 104 can be configured to focus the shock wave onto a predetermined location on or below the surface of the eye. The eye contact surface 104 can be configured to engage with the surface of the patient's eye. As described herein, an engaging fluid or gel (e.g., a water column) can be on or below the eye contact surface to facilitate contact between the eye contact surface and the surface of the eye and / or to facilitate the transmission of the shock wave from the shock wave generator to the eye. The first electrode 110 and the second electrode 112 can be coaxially aligned with each other, such that a gap 114 is formed between the distal ends of electrodes 110, 112. The shock wave generator 5700 can be configured to generate one or more shock waves. Waveguide 5702 can be configured to transmit shock waves from the fluid-filled chamber 106 of the shock wave generator to the eye contact surface 104.

[0332] In some embodiments, waveguide 5702 can improve the safety of the shock wave system by increasing the spacing between the fluid electronics of the shock wave generator 5700 and the plane of the eye contact surface 104. Waveguide 5702 can also provide increased fluid volume and length for fluid circulation and bubble removal. In some embodiments, waveguide 5702 can have a length ranging from about 1 cm to about 2 cm. In some embodiments, the length of waveguide 5702 can be about 12 mm or longer. For example, waveguide 5702 can have a length ranging from about 12 mm to about 80 mm.

[0333] In some implementations, waveguides can reduce the need to minimize system components in order to compress them into a space directly adjacent to the eye (e.g., within a contact lens bulb).

[0334] In some embodiments, the shock wave generator 5700, having waveguide 5702, can be mounted on a test frame (such as adjustable goggles) for stress-free packaging into a shock wave delivery accessory. The test frame goggles can be configured to stabilize fluid, electronic, and / or shock wave waveguides and make gentle contact with the eye or eyelid. The test frame can be configured to have an adjustable vertex distance between the frame and the cornea. In some embodiments, the vertex distance can be adjusted to position the shock wave generator approximately 12 mm or more above the eye. One or more shock wave waveguides can extend from the test frame to the surface of the eye.

[0335] In some embodiments, the shock wave waveguide 5702 may include a tubular waveguide. In some embodiments, the shock wave waveguide 5702 may include a solid rod. Those skilled in the art will understand that the waveguide 5702 may include any shape as needed to transmit the shock wave generated by the shock wave generator to the eye.

[0336] In some embodiments, the shock waveguide 5702 may include a material having a reflectivity of about 40% or higher. For example, in some embodiments, the shock waveguide 5702 may include stainless steel, titanium alloy, aluminum alloy, graphene polymer, metallized ceramic, or any combination thereof.

[0337] The shock waveguide 5702 may include a stainless steel tube with an outer diameter ranging from about 1 mm to about 8 mm.

[0338] Figure 58A side sectional view of an exemplary shock wave generator 5800 including a waveguide 5802 is shown. The shock wave generator 5800 may be substantially similar to any shock wave generator described herein. For example, the shock wave generator 5800 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. The housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. The housing 102 may be substantially tubular, wherein the electrodes 110, 112 are disposed near the proximal end of the fluid-filled chamber 106 and the eye contact surface 104 is disposed at the distal end of the fluid-filled chamber 106, and the housing 102 has a central portion providing an extension of the waveguide 5802 between the proximal and distal ends. The proximal end of the fluid-filled chamber 106 may be configured to act as a reflector to focus the shock wave via the waveguide to a desired predetermined location. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of the fluid-filled chamber 106 to focus the shock wave. The inner wall of the fluid-filled chamber 106 may be elliptical. Alternatively or in combination, the distal end of waveguide 5082 may be configured to focus a shock wave onto a predetermined location on or below the surface of the eye. Eye contact surface 104 may be configured to engage with the surface of the patient's eye. As described herein, a bonding fluid or gel (e.g., a water column) may be on or below eye contact surface 104 to facilitate contact between eye contact surface 104 and the surface of the eye and / or to facilitate the transmission of the shock wave from shock generator 5800 to the eye. First electrode 110 and second electrode 112 may be coaxially aligned with each other, such that a gap 114 is formed between the distal ends of electrodes 110, 112. Shock generator 5800 may be configured to generate one or more shock waves. Waveguide 5802 may be configured to transmit the shock wave from the electrodes to eye contact surface 104.

[0339] In some embodiments, the shock wave generator 5800 may further include a fluid inlet 108 and a fluid outlet 109 in fluid communication with the fluid-filled chamber 106 as described herein. Fluid may circulate within the fluid-filled chamber via the fluid inlet and the fluid outlet. The fluid inlet may be configured to deliver fluid to a distal end of the shock wave generator (e.g., the distal end of a waveguide), and the fluid outlet may be configured to remove fluid from a proximal end of the shock wave generator (e.g., near an electrode), such that fluid flows through the housing in a direction opposite to the direction of shock wave propagation.

[0340] Shock waveguides may include stainless steel tubes with an outer diameter ranging from about 1 mm to about 8 mm.

[0341] In some embodiments, the waveguide may have a length ranging from about 1 cm to about 2 cm. In some embodiments, the waveguide may have a length of about 12 mm or longer. For example, the waveguide may have a length ranging from about 12 mm to about 80 mm.

[0342] In some implementations, one or more shock wave generators may be coupled to a fluid-filled contact lens as described herein.

[0343] In some implementations, one or more shock wave generators may be mounted on the test frame, for example, as described herein with adjustable goggles.

[0344] Figure 59 A schematic diagram of the wireframe tube shape of the shock wave waveguide 5800 is shown.

[0345] Figure 60 A side sectional view of an exemplary shock wave generator 6000 including a waveguide 6002 is shown. The shock wave generator 6000 may be substantially similar to any shock wave generator described herein. For example, the shock wave generator 6000 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. The housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. The housing 102 may be substantially tubular, wherein the electrodes 110, 112 are disposed near the proximal end of the fluid-filled chamber 106 and the eye contact surface 104 is disposed at the distal end of the fluid-filled chamber 106, and the housing 102 has an elongated central portion 6002 providing a waveguide between the proximal and distal ends. For example, the eye contact surface 104 may include a PET film as described herein. The proximal end of the fluid-filled chamber 106 may be configured to act as a reflector to focus the shock wave via the waveguide to a desired predetermined location. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of the fluid-filled chamber 106 to focus the shock wave. The inner wall of the fluid-filled chamber 106 may be elliptical. Alternatively or in combination, the distal end of the waveguide 6002 may be configured to focus the shock wave onto a predetermined location on or below the surface of the eye. The eye contact surface 104 may be configured to engage with the surface of the patient's eye. As described herein, a bonding fluid or gel (e.g., a water column) may be on or below the eye contact surface to facilitate contact between the eye contact surface 104 and the surface of the eye and / or to facilitate the transmission of the shock wave from the shock wave generator 6000 to the eye. The first electrode 110 and the second electrode 112 may be coaxially aligned with each other, such that a gap 114 is formed between the distal ends of the electrodes 110, 112. The shock wave generator 6000 may be configured to generate one or more shock waves. The waveguide 6002 may be configured to transmit the shock wave from the electrodes to the eye contact surface.

[0346] In some embodiments, the rod stop 6004 may be disposed at the proximal end of the housing 102. The rod stop 6004 may reflect acoustic energy from the proximal end of the housing 102 back into the tissue.

[0347] In some embodiments, the shock wave generator 6000 may further include a fluid inlet 108 and a fluid outlet 109 in fluid communication with the fluid-filled chamber 106 as described herein. Fluid can circulate within the fluid-filled chamber 106 through the fluid inlet 108 and the fluid outlet 109. The fluid inlet 108 may be configured to deliver fluid to a distal end of the shock wave generator 6000 (e.g., the distal end of waveguide 6002), and the fluid outlet 109 may be configured to remove fluid from a proximal end of the shock wave generator 6000 (e.g., near electrodes 110, 112) such that fluid flows through the housing 102 in a direction opposite to the direction of shock wave propagation.

[0348] The shock wave waveguide 6002 may include a stainless steel tube with an outer diameter in the range of about 1 mm to about 8 mm, for example, about 1 mm, about 2 mm, about 3 mm, about 5 mm, or about 8 mm. The waveguide may have a wall thickness of about 0.5 mm.

[0349] In some embodiments, waveguide 6002 may have a length ranging from about 1 cm to about 2 cm. In some embodiments, the length of waveguide 6002 may be about 12 mm or longer. For example, waveguide 6002 may have a length ranging from about 12 mm to about 80 mm, for example, 20 mm.

[0350] In some implementations, one or more shock wave generators 6000 may be coupled to a fluid-filled contact lens as described herein.

[0351] In some embodiments, one or more shock wave generators 6000 having waveguide 6002 can be mounted on a test frame, for example, as an adjustable goggle as described herein.

[0352] Figure 61A side sectional view of an exemplary shock wave generator 6100 including a waveguide 6102 is shown. The shock wave generator 6100 may be substantially similar to any shock wave generator described herein. For example, the shock wave generator 6100 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. The housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. The housing 102 may be substantially tubular, wherein the electrodes 110, 112 are disposed near the proximal end of the fluid-filled chamber 106 and the eye contact surface 104 is disposed at the distal end of the fluid-filled chamber 106, and the housing 102 has an elongated central portion 6102 providing a waveguide between the proximal and distal ends. For example, the eye contact surface 104 may include a PET film as described herein. The proximal end of the fluid-filled chamber 106 may be configured to act as a reflector to focus the shock wave via the waveguide 6102 to a desired predetermined location 6102. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of the fluid-filled chamber 106 to focus the shock wave. The inner wall of the fluid-filled chamber 106 may be elliptical. Alternatively or in combination, the distal end of the waveguide 6102 may be configured to focus the shock wave onto a predetermined location on or below the surface of the eye. The eye contact surface 104 may be configured to engage with the surface of the patient's eye. As described herein, a bonding fluid or gel (e.g., a water column) may be on or below the eye contact surface to facilitate contact between the eye contact surface 104 and the surface of the eye and / or to facilitate the transmission of the shock wave from the shock wave generator to the eye. The first electrode 110 and the second electrode 112 may be coaxially aligned with each other, such that a gap 114 is formed between the distal ends of the electrodes 110, 112. The shock wave generator 6100 may be configured to generate one or more shock waves. The waveguide 6102 may be configured to transmit the shock wave from the electrodes to the eye contact surface 104.

[0353] In some embodiments, the distal end of waveguide 6102 may include one or more reflectors 6106. One or more reflectors 6106 may be configured to focus shock waves onto a predetermined location on or below the surface of the eye, as described herein.

[0354] In some embodiments, the rod stop 6104 may be located at the proximal end of the housing 102. The rod stop 6104 can reflect acoustic energy from the proximal end of the housing 102 back into the tissue.

[0355] In some embodiments, the first electrode 110 and the second electrode 112 may be heat-shrinkable. Heat shrinkage can protect the electrodes from unwanted moisture contact, which could lead to misleading high-voltage discharges.

[0356] In some embodiments, the shock wave generator 6100 may further include a fluid inlet 108 and a fluid outlet 109 in fluid communication with the fluid-filled chamber 106 as described herein. Fluid can circulate within the fluid-filled chamber 106 through the fluid inlet 108 and the fluid outlet 109. The fluid inlet 108 may be configured to deliver fluid to a distal end of the shock wave generator 6100 (e.g., the distal end of a waveguide), and the fluid outlet 109 may be configured to remove fluid from a proximal end of the shock wave generator 6100 (e.g., near an electrode), such that fluid flows through the housing 102 in a direction opposite to the direction of shock wave propagation.

[0357] The shock waveguide 6102 may include a stainless steel tube with an outer diameter ranging from about 1 mm to about 8 mm, for example, about 2 mm. The waveguide 6102 may have a wall thickness of about 0.5 mm.

[0358] In some embodiments, waveguide 6102 may have a length ranging from about 1 cm to about 2 cm. In some embodiments, the length of waveguide 6102 may be about 12 mm or longer. For example, waveguide 6102 may have a length ranging from about 12 mm to about 80 mm.

[0359] In some embodiments, one or more shock wave generators 6100 having waveguide 6102 can be coupled to a fluid-filled contact lens as described herein.

[0360] In some embodiments, one or more shock wave generators 6100 having waveguide 6102 can be mounted on a test frame, for example, as an adjustable goggle as described herein.

[0361] In some embodiments, an array of shock wave generators 6100 having waveguide 6102 can be positioned near the eye (e.g., coupled to a fluid-filled contact lens) to target one or more treatment sites as described herein. For example, similar to Figure 63 The array can have 8 waveguides in the first row at 12 mm, 10 waveguides in the second row at 16 mm, and a single large waveguide in the center of the eye (0 mm). Those skilled in the art will understand that any number of waveguides can be positioned near the eye in any pattern required to treat the target tissue.

[0362] Figure 62 A side sectional view of an exemplary parabolic shock waveguide 6202 is shown. The shock wave generator 6200 and waveguide 6202 can be substantially similar to... Figure 60 and Figure 61The shock wave waveguide shown may be curved except that the distal end 6204 of waveguide 6202 can be bent. The parabolic shock wave waveguide 6202 may include a parabolic reflector 6206, which is configured to allow for peripheral approach to the eye.

[0363] Figure 63 A top view of an exemplary contact lens 6300 including an array of shock waveguides 6302 is shown. Any shock waveguides described herein can be coupled to the contact lens 6304 as an array of shock wave generators 6302 similar to other arrays described herein. In some embodiments, the array of shock wave generators having waveguides 6302 can be positioned near the eye to target one or more treatment sites as described herein. For example, a central large (8 cm outer diameter) waveguide 6302a can be coupled to the center of the contact lens to treat the lens and / or retina as described herein. A first row of shock waveguides 6302b can be positioned radially outward from the central large waveguide 6302a to treat the trabecular meshwork and / or Schrem's tube as described herein. A second row of shock waveguides 6032c can be positioned approximately 16 mm to treat the pars plana and PVZ as described herein. A suction ring located on the outer edge (approximately 19 mm in diameter) of the contact lens allows the contact lens 6304 to be attached to the surface of the eye or eyelid as described herein.

[0364] Figure 64 A top view of an exemplary contact lens 6400 is shown, including an array of shockwave generators 6402 for treating meibomian glands. The contact lens 6400 may have a radius of curvature of approximately 7.8 mm and approximately 12 mm.

[0365] Figure 65 A top view of an exemplary contact lens 6500 for the treatment of dry eye disease is shown. The contact lens 6500 may include a corneal contact lens that can be configured (e.g., shaped, including suitable materials, etc.) to function as an effective acoustic reflector as described herein.

[0366] Figure 66A side view of an exemplary treatment system 6600 including an integrated imaging system 6002 is shown. System 6600 may include any shock wave generator described herein. For example, system 6600 may include a shock wave generator having a waveguide 6604 coupled to a docking contact lens 6606. The shock wave generator may include a central aperture 6608 configured to allow the imaging system 6602 to be integrated therein. Imaging system 6602 may have a slit-lamp configuration, wherein the central aperture 6608 provides a viewport. The viewport allows a physician to view the eye before, during, or after treatment as described herein. The viewport may be referenced. In some embodiments, imaging system 6602 may include an OCT imaging system. The NIR (e.g., 1064 nm) wavelength laser of the OCT imaging system may be configured to penetrate water and enter tissue to provide interoperable imaging feedback as described herein. In some embodiments, multiple shock wave generators may be arranged in one or more annular rings around the viewport. In some embodiments, shock wave generator electronics and fluid dynamics devices, including saline pumping, degassing, and vacuuming, can be housed on the slit lamp assembly. The slit lamp assembly can be configured for use when the patient is sitting upright.

[0367] Figure 67 A side view of an exemplary treatment system 6700 including an integrated imaging system 6706 is shown. System 6700 may include any shock wave generator described herein. For example, system 6700 may include a shock wave generator having a waveguide 6702 coupled to a test frame 6704 and a mating contact lens. The shock wave generator may include a central aperture 6708 configured to allow the imaging system 6706 to be integrated therein. Imaging system 6706 may include an ultrasound biological microscope (UBM), ultrasound (US) imaging, and / or optical coherence tomography (OCT) apparatus or system. Imaging system 6706 may be used to take one or more images of the eye before, during, or after treatment as described herein. A processor or controller may be coupled to the power source and imaging system and configured with instructions to deliver energy to the shock wave generator and image tissue during treatment. System 6700 may also include a display coupled to the processor that allows the user to visualize tissue before, during, or after treatment. The display may show images that allow the user to view the treated tissue and plan treatment. The images displayed on the monitor can be provided in real time and can be used before treatment to allow users to align tissues and / or monitor the tissue effects of treatment (e.g., cavitation) in order to ensure that no unintended effects of treatment occur (e.g., the structures of the eye changing position relative to each other when not needed).

[0368] In some embodiments, the shock wave generator electronics, waveguide, and fluid interface can be mounted on the test frame 6704 as described herein. Fluid accessories, including saline pumping, degassing, and vacuum, can be accommodated on the IV column as described herein. The test frame configuration can be adapted for use with the patient in a supine / recumbent position.

[0369] Figure 68 A side view of an exemplary treatment system 6800 including an integrated imaging system 6802 is shown. System 6800 may include any shock wave generator described herein. For example, system 6800 may include a shock wave generator having a waveguide 6804 coupled to a surgical microscope 6802. The shock wave generator may include a central aperture configured to allow the imaging system to be integrated therein. Imaging system 6802 may include an ultrasound biological microscope (UBM), ultrasound (US) imaging, and / or optical coherence tomography (OCT) apparatus or system. Imaging system 6802 may be used to take one or more images of the eye before, during, or after treatment as described herein. A processor or controller may be coupled to an energy source and imaging system 6802 and configured with instructions to deliver energy to the shock wave generator and image tissue during treatment. System 6800 may also include a display coupled to the processor that allows the user to visualize tissue before, during, or after treatment. The display may show images that allow the user to view the treated tissue and plan treatment. The images displayed on the monitor can be provided in real time and can be used before treatment to allow users to align tissues and / or monitor the tissue effects of treatment (e.g., cavitation) in order to ensure that no unintended effects of treatment occur (e.g., the structures of the eye changing position relative to each other when not needed).

[0370] In some embodiments, the shock wave generator electronics and fluid dynamics devices may be mounted on the arm of the surgical microscope 6802 or on the IV column described herein. The surgical microscope may be configured for use when the patient is supine / recumbent.

[0371] Figure 69A schematic diagram of an exemplary system 6900 for bubble extraction is shown. Any shock wave generation system described herein can be configured for real-time intraoperative bubble extraction. System 6900 may include one or more shock wave generators 6902, which may be substantially similar to any shock wave generator array described herein. The shock wave generator 6902 may be configured to generate one or more shock waves. One or more shock wave generators 6902 may include a fluid-filled chamber containing a fluid, such as saline, disposed therein. In some embodiments, the shock wave generator 6902 may also include a fluid inlet 108 and a fluid outlet 109 in fluid communication with the fluid-filled chamber. The fluid can be used to bond the fiber-generated shock wave to the surface of the eye. The fluid can circulate within the fluid-filled chamber via the fluid inlet 108 and the fluid outlet 109. As the pulse delivery of the shock wave proceeds, fluid circulation enables the continuous extraction of thermal build-up, cavitation bubbles, and ions generated during shock wave formation. It may be desirable to effectively remove bubbles formed during shock wave generation to prevent trapped bubbles in the fluid from interfering with the formation and / or direction of additional shock waves and related unintended effects. Bubble removal can also improve acoustic energy delivery. In some embodiments, it may be necessary to degas the fluid and recirculate it through a fluid-filled chamber. The recirculation system may include a first pump 6904 that moves fluid from the fluid component of the shock wave generator 6902 to a bubble extraction device 6906 (e.g., MedArray's PermaSelect 2500). Fluid can be drawn from the bubble extraction device 6906 to the vacuum chamber 6908 (e.g., an airtight Schott-Durand glass container) via a vacuum pump 6910 coupled to the vacuum chamber 6908. A brine storage bag 6912 may be in fluid communication with the vacuum chamber 6908 for fluid exchange and equilibration. The degassed fluid can then be drawn from the vacuum chamber 6908 back into the shock wave generator 6902 via the first pump 6904 to complete the recirculation system 6900. The recirculation system 6900 can operate at common peristaltic pump flow rates and vacuum pump ranges. In some embodiments, as described herein, the fluid flowing out of the fluid-filled chamber via fluid outlet 109 can be sampled periodically or continuously.

[0372] In some embodiments, the fluid recirculation system 6900 may be configured to remove fluid from the fluid-filled chamber at a rate ranging from about 0.5 L / min to about 1 L / min. For example, the fluid may be recirculated at a rate ranging from about 750 ml / min to about 1000 ml / min. In some embodiments, the entire volume of the fluid-filled chamber (or fluid-filled contact lens / balloon) may be replaced by the fluid recirculation system 5900 with fresh, degassed fluid after each shock wave is generated.

[0373] In some implementations, the recirculation rate can be approximately 100 mL / min.

[0374] In some implementations, one or more pumps may be peristaltic pumps.

[0375] In some embodiments, the fluid recirculation line 6914 may include a hollow tube. In some embodiments, the fluid recirculation line 6914 may include a silicone tube or a sheath.

[0376] In some embodiments, the fluid recirculation tube 6914 may include an inner surface chemical substance that reduces or prevents cavitation bubbles from being trapped within the tube 6914. For example, the tube 6914 may be coated with a surfactant.

[0377] In some embodiments, the IV column may be positioned proximal to the eye to accommodate one or more of the following: a saline bag reservoir 6912, a programmable pulse generator (2KV / 10KHz), a vacuum pump 6910 for a bubble extraction device, a pump 6904 for extracting saline from the contact lens to drive it into the bubble extraction device, a vacuum container for eye suction, a reservoir bottle for fluid exchange and balancing, and / or a tube 6914 with a valve for control.

[0378] Figure 70 A schematic diagram of an exemplary system 7000 for bubble extraction is shown. The bubble extraction system 7000 can be substantially similar to... Figure 69 The bubble extraction system 7000 is integrated into the test frame goggles 6704. The test frame goggles 6704 can be configured to support shock wave generator electronics, optional waveguides and fluid interfaces as described herein, and can be substantially similar to any goggles described herein.

[0379] Figure 71 A schematic diagram of an exemplary system 7100 for bubble extraction is shown, which is coupled to a contact lens balloon 7102 disposed on a patient's eye 200. The bubble extraction system 7100 can be substantially similar to Figure 70 The system, the bubble extraction system 7100, has a large vacuum chamber mounted on the IV column. The contact lens balloon 7102 can be substantially similar to any contact lens or balloon described herein. Figure 70 Compared to other systems, vacuum tanks can hold large amounts of brine, such as 7 liters. Systems with a capacity of 70 can be configured to hold smaller volumes, such as 500 ml.

[0380] Figure 72An electrical schematic diagram of an exemplary treatment system 7200 is shown. A low-voltage power supply module (LVPS) can be configured to generate one or more voltages, such as +5V, +24V, and +12V. A programmable 0-2kV high-voltage power supply module (HVPS) can be configured to deliver power to a capacitor. For example, an HVPS unit can be configured to deliver approximately 125 watts of power to a capacitor. The capacitor can be rapidly (approximately 1 microsecond) discharged into a saline container via a high-voltage switch (HVSW). The saline container can direct pressure waves to tissue (e.g., through an acoustically transparent, fluid-impermeable membrane). A microcontroller (e.g., an Arduino class) can be configured to control timing and PCT interfaces, as well as monitor safety interlocks.

[0381] Figure 73 A side sectional view of an exemplary variable focus therapy system 7300 is shown. The system 7300 can be substantially similar to... Figure 40The system shown can be used to treat the lens 2302 (or IOL), retina 2208, and / or other target locations within the eye. System 7300 may include a large-diameter shock wave generator 7302 configured to deliver shock waves to the lens and / or retina. The shock wave generator 7302 may be substantially similar to any shock wave generator described herein. For example, the shock wave generator 7302 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. Housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. The fluid-filled chamber 106 may be configured to act as a parabolic reflector to focus planar shock waves to a desired predetermined location. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of the fluid-filled chamber 106 to focus the shock waves. For example, one or more reflectors may include an electronically variable acoustic lens 7304 that allows the shock wave to be variably or adjustablely focused along the z-plane onto the lens 2302 (or IOL) and / or the macula 2208 of the retina. The inner wall of the fluid-filled chamber 106 may be elliptical. The eye contact surface 104 may be configured to adhere to the surface of a patient's eye. A bonding fluid or gel (e.g., a water column) may be on or under the eye contact surface 104 to facilitate contact between the eye contact surface 104 and the surface 500 of the eye and / or to facilitate the transmission of the shock wave from the shock wave generator 7302 to the eye. A suction ring may be disposed on the outer edge of the shock wave generator to adhere the shock wave generator to the cornea or sclera of the eye. The first electrode 110 and the second electrode 112 may be coaxially aligned with each other, such that a gap 114 is formed between the distal ends of the electrodes 110, 112. The shock wave generator 7302 may be configured to generate one or more shock waves. The electronic variable acoustic lens 7304 may include a first shape 7304a configured to focus a shock wave to a first location (e.g., for a softened lens 2302) and a second shape 7304b configured to focus the shock wave to a second location (e.g., for an acoustically stimulated retina 2208). The electronic variable acoustic lens 7304 may be configured to electronically direct the shock wave to any desired treatment location or combination of treatment locations.

[0382] Figure 74 A side sectional view of an exemplary treatment system 7400 for dry eye disease is shown. System 7400 may be substantially similar to... Figure 41The system shown can be used to deliver shockwave therapy to eyelid 2802 while protecting cornea 2206 from the shockwave. System 7400 may include a large-diameter shockwave generator 7402 configured to deliver shockwaves to eyelid 2802 of eye 200. Shockwave generator 7402 may be substantially similar to any shockwave generator described herein. For example, shockwave generator 7402 may include a first electrode 110 and a second electrode 112 disposed within housing 102. Housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. Fluid-filled chamber 106 may be configured to act as a parabolic reflector to focus planar shockwaves to a desired predetermined location. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of fluid-filled chamber 106 to focus the shockwave. The inner wall of fluid-filled chamber 106 or the reflectors coupled to the inner surface of fluid-filled chamber 106 may be elliptical. An eye contact surface 104 may be configured to engage with a patient's eyelid 2802 (e.g., when the patient's eyes are closed). The eye contact surface 104 may include a highly compliant membrane material to facilitate engagement with the eyelid 2802. A corneal protective contact lens 4104 may be disposed on the cornea 2206 below the patient's eyelid 2802 and may act as an acoustic reflector to redirect shock waves passing through the eyelid 2802 away from the cornea 2206. A heat-dissipating contact lens 4104 may be configured to act as an acoustic reflector and direct shock waves to one or more meibomian glands 2800 for treating dry eye as described herein. A suction ring may be disposed on the outer edge of the shock wave generator to engage the shock wave generator with the eyelid. A first electrode 110 and a second electrode 112 may be coaxially aligned with each other, such that a gap 114 is formed between the distal ends of electrodes 110, 112. A shock wave generator 7402 may be configured to generate one or more shock waves.

[0383] Figure 75A side sectional view of an exemplary treatment system 7500 for trans-eyelid treatment is shown. System 7500 may include any of the shock wave generators described herein. In some embodiments, the eye contact surface 104 of the shock wave generator may engage with the patient's eyelid 2802 when the patient's eyes are closed. In some embodiments, system 7500 may include an eyelid contact lens 7502 configured to engage with the patient's eyelid 2802. In some embodiments, the eye contact surface of the shock wave generator may include the eyelid contact lens 7502. In some embodiments, the eye contact surface of the shock wave generator may be configured to contact the eyelid contact lens 7502. In some embodiments, the shock wave generator may be configured to deliver shock waves through the eyelid contact lens 7502 to a predetermined location on or below the surface of the eye (or eyelid). The shock wave may travel through the eyelid 2802 to the predetermined treatment location.

[0384] Figure 76A side sectional view of an exemplary treatment system 7600 for dry eye disease is shown. System 7600 may include any shock wave generator described herein. For example, the system may include a shock wave generator having a waveguide 7602 coupled to a test frame and a docking contact lens. System 7600 may be used to deliver shock wave therapy to eyelid 2802 while protecting cornea 2206 from the shock wave. The shock wave generator may be substantially similar to any shock wave generator described herein. For example, the shock wave generator may include a first electrode and a second electrode disposed within a housing. Housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. Fluid-filled chamber 106 may be configured to act as a parabolic reflector to focus planar shock waves to a desired predetermined location. Alternatively or in combination, one or more reflectors may be coupled to the inner surface of fluid-filled chamber 106 to focus the shock wave. The inner wall of fluid-filled chamber 106 or the reflectors coupled to the inner surface of fluid-filled chamber 106 may be elliptical. The eye contact surface 104 can be configured to adhere to the patient's eyelid 2802 (e.g., when the patient's eyes are closed). The eye contact surface 104 may include a highly compliant membrane material to facilitate adhesion to the eyelid 2802. A corneal protective contact lens 7606 may be disposed on the cornea 2206 below the patient's eyelid 2802 and may act as an acoustic reflector to redirect shock waves passing through the eyelid 2802 away from the cornea. The acoustic reflector lens 7606 may direct shock waves to one or more meibomian glands 2800 to treat dry eye as described herein. The acoustic reflector lens 7606 may be an inflatable 7608 PET and / or PMMA scleral contact lens. The corneal contact surface 7610 of the lens may include PMMA and the eyelid contact surface 7612 of the lens may include PET. Alternatively, the corneal contact surface 7610 of the lens may include PET and the eyelid contact surface 7612 of the lens may include PMMA. The impedance mismatch between the fluid-filled chamber 106 and the air-filled reflective lens 7606 may be large enough (e.g., about 3500 times larger) to cause energy directed to the cornea 2206 to be reflected back to the eyelid 2802. A suction ring may be disposed on the outer edge of the shock wave generator to attach the shock wave generator to the eyelid 2802. The first and second electrodes may be coaxially aligned with each other, such that a gap is formed between the distal ends of the electrodes. The shock wave generator may be configured to generate one or more shock waves.

[0385] In some implementations, the air-filled scleral contact lens 7606 may be sterilizable and / or disposable.

[0386] In some embodiments, the air-filled scleral contact lens 7606 may have a total thickness of about 300 μm. In some embodiments, the PET surface of the lens may have a thickness of about 12 μm. In some embodiments, the PMMA surface of the lens may have a thickness of about 200 μm. In some embodiments, the air chamber 7612 may have a thickness of about 100 μm.

[0387] In some embodiments, the air-filled scleral contact lens 7606 may have a diameter of approximately 19 mm.

[0388] In some embodiments, the air-filled scleral contact lens 7606 has a hyperbolic shape with an arch.

[0389] Figure 77A schematic diagram of an exemplary system 7700 for conductivity measurement is shown. Any system described herein may include a conductivity sensor 7702 configured to measure the conductivity of a fluid flowing or flowing out of a fluid-filled chamber 106. In some embodiments, the conductivity sensor 7702 may be fluidly coupled to a fluid outlet 109 but not located within the fluid-filled chamber 106. In some embodiments, the conductivity sensor 7702 may be embedded within the fluid-filled chamber 106. The conductivity sensor 7702 may periodically or continuously sample the conductivity of the fluid within the fluid-filled chamber 106 to determine the extent of electrode corrosion. For example, the conductivity of brine may be sampled (e.g., as a representative measure of the gap distance between shock wave electrodes, due to electrode corrosion and the release of metal ions into the brine), and the voltage delivered to the shock wave electrodes 110, 112 may be adjusted to account for any changes in the sensed conductivity. In some embodiments, the conductivity sensor 7702 may include a pair of platinum electrodes 7704, 7706 spaced at a fixed distance (e.g., 2 cm). Dual constant current sources 7708, 7710 (e.g., 1 mA) can inject a known current at a known distance (e.g., 1 cm) from a ground electrode (e.g., electrode 112 in some embodiments). The battery constant can be calibrated using a circulating solution with known conductivity (e.g., a fixed concentration of phosphate-buffered saline, potassium chloride, brine, etc.). For example, the conductivity of 0.9% sodium chloride is approximately 16 mS / cm (~K=1 cell calibration) and can be used for the calibration of conductivity sensor 7702. The cell constant is a multiplier constant specific to the conductivity sensor. The measured current is multiplied by the cell constant to determine the conductivity of the solution. The cell constant, referred to as K, is the theoretical electrode consisting of two 1cm square plates spaced 1cm apart. An increase in conductivity can indicate metal immersion in the fluid of fluid-filled chamber 106. A decrease in conductivity can indicate the formation and retention of bubbles within fluid-filled chamber 160. If the conductivity change exceeds an acceptable threshold, treatment can be stopped and the system 7700 can be flushed with fresh fluid to remove metal / bubbles and / or the shock wave generating electrodes 110, 112 can be evaluated.

[0390] In some implementations, the dual current sources 7708 and 7710 can emit pulses synchronously (but 180 degrees out of phase) at approximately 10 kHz. The pulses can have a duty cycle of approximately 20%. For example, the current sources can "turn on" the pulse at 10 kHz for approximately 20 microseconds and "turn off" it for approximately 80 microseconds. 80 microseconds provides sufficient time to detect and / or compare the DC voltage at the conductive electrodes.

[0391] In some embodiments, the platinum conductive electrodes 7704 and 7706 may have a diameter of about 6 mm and a width of about 2 mm. The platinum conductive electrodes 7704 and 7706 may be insulated with stainless steel of about 0.1 mm thickness.

[0392] In some embodiments, the platinum conductive electrodes 7704 and 7706 may have a diameter of approximately 0.5 mm. The platinum conductive electrodes 7704 and 7706 may be insulated with parylene. In some embodiments, the platinum conductive electrodes 7704 and 7706 may have exposed ends that are synchronized (out of phase) with the high-voltage pulses of the shock wave generating electrodes 110 and 112.

[0393] In some embodiments, the conductivity cell may also include a passive cavitation detector or an ultraviolet radiation source as described herein (e.g., as described herein). Figures 84 to 8 (in 5).

[0394] Figure 78 A side sectional view of an exemplary shock wave generator 7800, including a waveguide 7802 and an embedded conductivity sensor 7702, is shown. The shock wave waveguide 7802 may be substantially similar to any shock wave waveguide described herein. The shock wave generator 7800 may be substantially similar to any shock wave generator described herein. For example, the shock wave generator 7802 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. The housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. The housing 102 may be substantially tubular, wherein the electrodes are disposed near the proximal end of the fluid-filled chamber 106 and the eye contact surface 104 is disposed at the distal end of the fluid-filled chamber 106, and the housing 102 has an elongated central portion 7802 providing a waveguide 5802 between the proximal and distal ends. For example, the eye contact surface 104 may include a PET film as described herein. The eye contact surface 104 may be configured to adhere to the surface of a patient's eye. As described herein, a bonding fluid or gel (e.g., a water column) may be present on or beneath the eye contact surface to facilitate contact between the eye contact surface and the surface of the eye and / or to facilitate the transmission of shock waves from the shock wave generator to the eye. In some embodiments, the distal end of the fluid-filled chamber 106 may be referred to as an acoustic emitter. The proximal end of the fluid-filled chamber 106 may include a conductivity cell 7804, which includes a conductivity sensor 7702. The conductivity sensor 7702 may include a pair of platinum electrodes 7704, 7706 spaced at fixed intervals. The pair of platinum electrodes 7704, 7706 may be configured to periodically or continuously sample the conductivity of the fluid in the fluid-filled chamber 106 as described herein.

[0395] Figure 79A side view of an exemplary acoustic crosslinking shockwave generator 7900, including a shockwave waveguide 7902, is shown. Acoustic crosslinking can be used to treat keratoconus or keratoplasty. The shockwave waveguide 7902 can be substantially similar to any shockwave waveguide described herein. The shockwave generator 7900 can be substantially similar to any shockwave generator described herein. For example, the shockwave generator 7900 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. The housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. The housing 102 may be substantially tubular, wherein the electrodes 110, 112 are disposed near the proximal end of the fluid-filled chamber 106 and the eye contact surface 104 is disposed at the distal end of the fluid-filled chamber 106, and the housing 102 has an elongated central portion 7902 providing a waveguide between the proximal and distal ends. For example, the eye contact surface 104 may include a PET film as described herein. The eye contact surface 104 may be configured to engage with the surface 500 of a patient's eye 200. As described herein, a binding fluid or gel (e.g., a water column) may be present on or beneath the eye contact surface 104 to facilitate contact between the eye contact surface 104 and the surface 500 of the eye and / or to facilitate the transmission of the shock wave from the shock wave generator to the eye. In some embodiments, a reservoir 7904 for oxygen and / or one or more therapeutic substances may be disposed on or beneath the eye contact surface 104 for drug delivery to the cornea 2206. The reservoir 7904 may be attached to the eye 200 using a vacuum-sealed retaining ring 1202. The shock wave generated by the shock wave generator can enhance drug delivery to the cornea 2206 (e.g., to the epithelial cells) by fragmenting and / or microporousizing the surface of the corneal tissue of interest to improve drug permeability.

[0396] The PET membrane 104 isolates the high-pressure fluid from the eye and the drug / oxygen reservoir 7904. The PET membrane 104 may be acoustically transparent. The PET membrane 104 may have a thickness ranging from about 2.5 micrometers to about 12.5 micrometers. The PET membrane 104 may be configured to withstand a saline pressure of at least about 100 PSI within the fluid-filled chamber 106. In some embodiments, the PET membrane 104 may be replaced by a focusing / defocusing acoustic lens and / or a planar meniscus lens.

[0397] In some implementations, the therapeutic substance may contain a photosensitizer, such as riboflavin, riboflavin nanoparticles, or rose red.

[0398] Acoustic radiation force (i.e., the force from a shock wave) can drive therapeutic substances into tissues. Alternatively or in combination, electrospraying via Taylor cone and Coulomb fission can be used to disperse therapeutic substances onto tissue surfaces.

[0399] In some embodiments, the reservoir 7904 may include a fluid inlet 7908 and a fluid outlet 7910 for circulating oxygen and / or therapeutic substances from an external source / reservoir to the cornea 2206 below the eye contact surface 104. In some embodiments, the same fluid inlet 7908 and fluid outlet 7910 may be used for each substance. In some embodiments, each substance may have a dedicated fluid inlet and fluid outlet. In some embodiments, an electrochemical cell may be used to generate oxygen for electrolysis and delivery to the eye (e.g., at 15 ml / min of 95% oxygen).

[0400] The proximal end of the fluid-filled chamber 106 may include or be coupled to a light source 7906. For example, the light source 7906 may be an ultraviolet light-emitting diode (LED) (e.g., 365 nm wavelength) or an optical fiber coupled to an external ultraviolet LED or laser. In some embodiments, the light source 7096 may be a green LED (e.g., 525 nm wavelength) or an optical fiber coupled to an external green LED or laser. The ultraviolet light source 7906 may be used to crosslink the cornea 2206 (e.g., for treating keratoconus) during or after oxygen and / or riboflavin (or other ultraviolet-sensitive or photosensitizing therapeutic substances). Oxygen delivery and / or photosensitivity can accelerate crosslinking.

[0401] In some embodiments, the light source 7906 may have approximately 20 mW / cm². 2 The intensity. In some embodiments, the light source 7906 can have approximately 3 mW / cm². 2 The intensity. In some embodiments, the light source 7906 can have approximately 9 mW / cm². 2 The intensity. In some embodiments, the light source 7906 can have approximately 10 mW / cm². 2 The intensity. In some embodiments, the light source 7906 can have approximately 15 mW / cm². 2 The intensity.

[0402] In some implementations, a shockwave generator 7900 can be used to deliver oxygen and / or other therapeutic substances to the eye 200 without simultaneous or subsequent crosslinking.

[0403] In some embodiments, the shock wave generator 7900 may further include a fluid inlet 108 and a fluid outlet 109 in fluid communication with the fluid-filled chamber 106 as described herein. Fluid may circulate within the fluid-filled chamber 106 via the fluid inlet 108 and the fluid outlet 109. The fluid inlet 108 may be configured to deliver fluid to a distal end of the shock wave generator 7900 (e.g., the distal end of waveguide 7902), and the fluid outlet 109 may be configured to remove fluid from a proximal end of the shock wave generator 7900 (e.g., near electrodes 110, 112) such that fluid flows through the housing 102 in a direction opposite to the direction of shock wave propagation.

[0404] The shock wave waveguide 7902 may include a stainless steel tube with an outer diameter ranging from about 1 mm to about 8 mm, for example, about 1 mm, about 2 mm, about 3 mm, about 5 mm, or about 8 mm. The shock wave waveguide 7902 may include a stainless steel tube with an outer diameter of about 7 mm. The waveguide 7902 may have a wall thickness of about 0.5 mm.

[0405] In some embodiments, waveguide 7902 may have a length ranging from about 1 cm to about 2 cm. In some embodiments, the length of waveguide 7902 may be about 12 mm or longer. For example, the waveguide may have a length ranging from about 12 mm to about 80 mm, for example, about 20 mm. The shock wave waveguide 7902 may include a stainless steel tube having a length of about 40 mm.

[0406] In some implementations, one or more acoustic crosslinking shock wave generators 7900 may be coupled to a fluid-filled contact lens as described herein.

[0407] In some embodiments, one or more acoustically crosslinked shock wave generators 7900 having waveguide 7902 can be mounted on a test frame, for example, adjustable goggles as described herein.

[0408] Figure 80 A side view of an exemplary acoustically cross-linked shock wave generator 8000, including a shock wave waveguide 7902, is shown. The acoustically cross-linked shock wave generator 8000 can be substantially similar to... Figure 79The shock wave generator is shown. The acoustic crosslinking shock wave generator 8000 may include a light source 7906 (e.g., a green or ultraviolet LED) as described herein. The light source 7906 may be cyclically turned on and off. In some embodiments, the light source off cycle may correspond to the on cycle of the high-voltage electrodes 110, 112 within the fluid-filled chamber 106 for simultaneous shock wave-mediated drug delivery (e.g., oxygen and riboflavin). The on / off cycle of the light source 7906 (and optionally the shock wave generating electrodes 110, 112) may be approximately every 5 seconds. Oxygen may be generated from the atmosphere by an electrolyzer driven by a low-power current source (e.g., an AA battery) and delivered to the fluid inlet 8002 of the suction ring 1202 at the patient interface. As described herein, riboflavin may be delivered to the same fluid inlet 8002 or a different fluid inlet 8004. Oxygen (and riboflavin, etc.) may be propelled into the cornea 2206 using the shock wave as described herein. The light cycle may be repeatedly turned on / off as needed to achieve the desired corneal crosslinking level.

[0409] For example, tissues can be soaked in 0.1% riboflavin for 30 minutes, and then each eye can be treated with at least approximately 3mW / cm. 2 Ultraviolet irradiation for 30 minutes. In some embodiments, riboflavin delivery can be enhanced by acoustic radiation force shockwave therapy. The acoustic radiation force (i.e., the force from the shockwave) can drive the therapeutic substance into the tissue. Then, 9mW / cm² can be applied for 10 minutes with simultaneous oxygen immersion (e.g., an electrochemical cell flow rate of approximately 16 ml / min). 2 Ultraviolet radiation. Shockwave therapy can be delivered using a system mounted on a pair of experimental goggles.

[0410] In some implementations, riboflavin delivery can be enhanced by using corneal-targeted ultrasound in a 5-minute cycle protecting the epithelium, followed by cellular oxygen production (approximately 90% purity) and delivery at approximately 10 mW / cm². 2 The ultraviolet radiation exposure lasts for approximately 10 minutes. The total treatment time can be approximately 15 minutes per eye.

[0411] Figure 81A schematic diagram of an exemplary system 8100 for passive cavitation detection is shown. Any shock wave generator described herein may include a passive cavitation detector 8104. During pulse emission, the passive cavitation detector 8104 may be configured to detect the shock wave generated by the shock wave generator 8102 (e.g., "main pulse signal delay" 8108) and cavitation formation and collapse 8110 within tissue 200. In some embodiments, the passive cavitation detector 8104 may include a piezoelectric detector, such as a hydropneumatic detector. In some embodiments, the passive cavitation detector 8104 may detect a signal 8106 indicating the formation and collapse 8110 of cavitation bubbles within tissue 200. The signal 8106 may include temporal and spectral information (e.g., rebound hysteresis, intensity, etc.) regarding bubbles that can be extracted surgically. The bubble collapse rate may be related to intraocular pressure (IOP), therefore passive cavitation detection can be used to indirectly measure IOP non-invasively. IOP measurement may be particularly useful in glaucoma treatment and / or improving the safety and efficiency of selective shock wave therapy.

[0412] The dissolution time of steady-state cavitation bubbles in the water of the anterior chamber of the treated eye may be inversely proportional to IOP. A passive cavitation detector 8104 can be used to record tissue bubble characteristics (e.g., reflection amplitude and time of flight) from the anterior chamber. The bubble size induced in the tissue by the spark gap 114 in the fluid-filled impact chamber 106 can be set to two selected average cloud sizes (e.g., adjusted by pulse frequency and voltage), and the tissue steady-state bubble dissolution rate can be extracted after averaging and filtering the passive cavitation detector signal 8106. The procedure can be completely non-invasive and real-time intraoperatively.

[0413] Due to the natural fluid pressure (“IOP”), the eye 200 (i.e., the pressure vessel) exerts a force on the size of the oscillating cavitation bubbles. A passive cavitation detector 8104 and a high-frequency shock wave generator 8102 can interact to extract the maximum “unstimulated” bubble cloud size. Next, a second known stimulus (e.g., 1 / 11 of the primary high-frequency resonance) can be applied via a small ultrasonic generator (e.g., 28 kHz), and the maximum bubble cloud size can be extracted using PCD / PC software. This sequence can be repeated to improve the accuracy of IOP extraction within hundreds of cycles (e.g., 0.1 to 1 second).

[0414] In some implementations, instead of the passive cavitation detector 8104 or in addition to the passive cavitation detector 8104, IOP can be measured using other non-contact methods, such as a blow-through tonometer.

[0415] In some implementations, the passive cavitation detector 8104 can operate at a frequency of about 10 MHz and has a high acoustic impedance.

[0416] In some implementations, it may be beneficial to characterize the shock wave generation and repeatability prior to use to ensure a uniform acoustic energy signal (mean, standard deviation) is emitted for repeated treatments. Any system described herein can have its acoustic emission footprint rapidly examined prior to intraocular use. For example, a sound pressure level (SPL) color map can be sensed onto pressure-sensitive Fujifilm via shock wave exposure. The SPL color map can be image-processed and analyzed for comparison with a reference image utilizing typical treatment settings (e.g., voltage, frequency, etc.) for only a brief period in saline (e.g., 10 ms to 1 second). Pre-cut Fujifilm (grade-sensitive pressure range, packaged in a waterproof plastic sleeve) may be disposable. The highest SPL mapped onto the film can be achieved using a color camera and white light illumination. A duct-like optical fiber can be used to transmit uniform illumination and color maps from and to the camera and film. An accuracy of + / - 15% can be targeted at the start of treatment.

[0417] Figure 82 An exemplary treatment system 8200 including passive cavitation detection is shown. System 8200 may be substantially similar to any system described herein. System 8200 may be configured to treat presbyopia, glaucoma, dry eye disease, AMD, keratoconus, etc., as described herein. System 8200 may include a shock wave generator 8202, which may be substantially similar to any shock wave generator described herein. For example, shock wave generator 8202 may include a first electrode 110 and a second electrode 112 disposed within a housing 102. Housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. Housing 102 may be substantially tubular, wherein electrodes 110, 112 are disposed near the proximal end of fluid-filled chamber 106 and eye contact surface 104 is disposed at the distal end of fluid-filled chamber 106, housing 102 having an elongated central portion 8202 providing a waveguide between the proximal and distal ends. For example, eye contact surface 104 may include a PET film as described herein. The eye contact surface 104 may be configured to engage with the surface 500 of the patient's eye 200. As described herein, an engagement fluid or gel (e.g., a water column) may be present on or beneath the eye contact surface to facilitate contact between the eye contact surface 104 and the surface of the eye 200 and / or to facilitate the transmission of shock waves from the shock wave generator 8200 to the eye 200.

[0418] In some embodiments, the shock wave generator 8200 may further include a fluid inlet 108 and a fluid outlet 109 in fluid communication with the fluid-filled chamber 106 as described herein. Fluid may circulate within the fluid-filled chamber 106 via the fluid inlet 108 and the fluid outlet 109. The fluid may circulate at a rate sufficient to remove bubbles and / or heat formed during shock wave generation (e.g., about 100 ml / min). The fluid inlet 108 may be configured to deliver fluid to a distal end of the shock wave generator 8200 (e.g., the distal end of waveguide 8202), and the fluid outlet 109 may be configured to remove fluid from a proximal end of the shock wave generator 8200 (e.g., near electrodes 110, 112) such that the fluid flows through the housing 102 in a direction opposite to the direction of shock wave propagation.

[0419] The fluid-filled chamber 106 may include a conductivity sensor 7702. The conductivity sensor 7702 may include a pair of low-pressure platinum electrodes 7704, 7706 positioned at a fixed distance (e.g., book-ends for high-pressure shock wave generating electrodes 110, 112). The pair of platinum electrodes 7704, 7706 may be configured to periodically or continuously sample the conductivity of the fluid in the fluid-filled chamber 106 as described herein.

[0420] In some embodiments, a reservoir 7904 for oxygen and / or one or more therapeutic substances may be disposed on or below the eye contact surface 104 for drug delivery to the cornea 2206. The reservoir 7904 may be attached to the eye using a vacuum-sealed retaining ring 1202. Shock waves generated by a shock wave generator can enhance drug delivery to the cornea 2206 (e.g., to epithelial cells) by fracturing and / or microporizing the surface of the corneal tissue of interest to improve drug permeability. In some embodiments, the therapeutic substance may comprise a photosensitizer, such as riboflavin, riboflavin nanoparticles, or rose red.

[0421] In some embodiments, the reservoir 7904 may include a fluid inlet 7908 and optionally a fluid outlet for circulating oxygen and / or therapeutic substances from an external source / reservoir to the cornea beneath the eye contact surface. In some embodiments, the same fluid inlet and fluid outlet may be used for each substance. In some embodiments, each substance may have a dedicated fluid inlet and fluid outlet. In some embodiments, an electrochemical cell 8206 may be used to generate oxygen for electrolysis and delivery to the eye (e.g., at >90% oxygen at 15 ml / min). For example, oxygen may be generated from the atmosphere by an electrolytic cell driven by a low-power current source (e.g., an AA battery) and delivered to the fluid inlet 8002 of the suction ring 1202 at the patient interface. As described herein, riboflavin may be delivered from the reservoir 8204 to the same fluid inlet 8002 or a different fluid inlet 8004. In some embodiments, the reservoir 8204 may be a sterile IV bag or a syringe, etc.

[0422] In some implementations, a shockwave generator 8200 can be used to deliver oxygen and / or other therapeutic substances to the eye without simultaneous or subsequent cross-linking.

[0423] In some embodiments, the proximal end of the fluid-filled chamber 106 may include a passive cavitation detector 8104. The passive cavitation detector may be configured to monitor cavitation and / or IOP during surgery as described herein. The passive cavitation detector can be used to confirm cavitation intensity and initiation within limits, thereby ensuring bubble presence and extraction. The passive cavitation detector can also be used to detect tissue cavitation duration and intensity to estimate IOP.

[0424] In some embodiments, the proximal end of the fluid-filled chamber 106 may include or be coupled to a light source 7906. For example, the light source may be an ultraviolet light-emitting diode (LED) (e.g., 365 nm wavelength) or an optical fiber coupled to an external ultraviolet LED or laser. In some embodiments, the light source may be a green LED (e.g., 525 nm wavelength) or an optical fiber coupled to an external green LED or laser. The ultraviolet light source may be used for corneal cross-linking (e.g., for treating keratoconus) during or after oxygen and / or riboflavin (or other UV-sensitive or photosensitive therapeutic substances) delivery.

[0425] The shock waveguide 8202 may include a stainless steel tube with an outer diameter ranging from about 1 mm to about 8 mm, for example, about 1 mm, about 2 mm, about 3 mm, about 5 mm, or about 8 mm. The shock waveguide may also include a stainless steel tube with an outer diameter of about 7 mm. The waveguide may have a wall thickness of about 0.5 mm.

[0426] In some embodiments, the waveguide may have a length ranging from about 1 cm to about 2 cm. In some embodiments, the waveguide may have a length of about 12 mm or longer. For example, the waveguide may have a length ranging from about 12 mm to about 80 mm, such as about 20 mm. The shock wave waveguide may include a stainless steel tube having a length of about 40 mm.

[0427] In some implementations, one or more acoustically crosslinked shock wave generators may be coupled to a fluid-filled contact lens as described herein.

[0428] In some implementations, one or more acoustically cross-linked shock wave generators with waveguides can be mounted on the test frame, such as adjustable goggles as described herein.

[0429] Figure 83 A side view of an exemplary therapeutic system 8300 including a conductivity sensor, acoustic crosslinking, and / or passive cavitation detection is shown. System 8300 may be substantially similar to... Figure 82 The system shown herein. System 8300 can be configured to treat one or more conditions, and / or target one or more locations on or below the surface of the eye as described herein.

[0430] In some embodiments, the eye contact surface (e.g., PET film) 104 can be securely sealed to the reservoir 7904 to fluidly isolate the shock wave fluid filling chamber 106 from the oxygen / riboflavin reservoir 7904.

[0431] In some embodiments, system 8300 or any system described herein can be used to perform graded treatment of the PVZ as described herein. For example, a frame control can be used to position the aperture of a 3mm focal length shockwave generator above the PVZ on the surface of eye 200. Saline solution can be circulated within fluid-filled chamber 106, and conductivity measurements and passive cavitation detection can be utilized during treatment. Treatment can be patterned in loops along the meridians of the eye in each of the four quadrants of the eye, at approximately four locations (e.g., as described herein). Figure 85B (As shown in the diagram). System 8300 can be positioned at a first location corresponding to the first quadrant, and PVZ can be used to treat for approximately 1 minute with shock waves generated at a voltage of approximately 2 kV and a frequency of approximately 3 kHz. System 8300 can then be repositioned to a second location corresponding to the second quadrant for further treatment, etc. In some embodiments, as described herein, treatment can be performed on eight or more locations along a ring.

[0432] In some embodiments, system 8300 or any system described herein can be used to depolymerize a lens as described herein. For example, the aperture of a planar 8mm shock wave generator can be placed on the cornea of ​​eye 200. Saline solution can be circulated within fluid-filled chamber 106, and conductivity measurements and passive cavitation detection can be performed during treatment. The lens can be treated for approximately 1 minute with shock waves generated at approximately 0.5 kV voltage and approximately 4 kHz frequency.

[0433] In some embodiments, system 8300 or any system described herein can be used to expand and / or clear trabecular meshes and / or Schrem tubes as described herein. For example, a frame control can be used to position the aperture of a planar 3mm shock wave generator on the surface of eye 200 above the limbus. Saline can be circulated within the fluid-filled chamber 106, and conductivity measurements and passive cavitation detection can be utilized during treatment. Treatment can be patterned in loops to four locations along the meridians of the eye in each of the four quadrants of the eye (e.g., as shown in the diagram). Figure 85A (As shown in the diagram). System 8300 can be positioned at a first location corresponding to the first quadrant and can treat the trabecular meshwork and / or Schrem tubes for approximately 30 seconds with a shock wave generated at a voltage of approximately 1 kV and a frequency of approximately 4 kHz. System 8300 can then be repositioned to a second location corresponding to the second quadrant for further treatment, etc. If sufficient cavitation and / or sufficient IOP changes are not detected using the passive cavitation detector 8104, the treatment can be repeated. In some embodiments, as described herein, treatment can be performed at eight or more locations along a ring.

[0434] In some embodiments, system 8300 or any system described herein can be used to dilate and / or clear meibomian glands as described herein. For example, a gas-filled scleral contact lens 7606 can be placed on eye 200 and the eyelid can be closed. An upper and lower shock wave generator can be placed on the eyelid above the meibomian gland. Saline can be circulated within the fluid-filled chamber 106, and conductivity measurements and passive cavitation detection can be used during treatment. The meibomian glands can be treated with shock waves generated at a voltage of approximately 2 kV and a frequency of approximately 4 kHz for approximately 1 minute.

[0435] In some embodiments, system 8300 or any system described herein can be used to crosslink the cornea as described herein. For example, riboflavin can be infused into the cornea at 30-second intervals using shock waves generated at a voltage of about 2 kV and a frequency of about 4 kHz until sufficient riboflavin has penetrated the cornea. Then, an activated ultraviolet laser 7906 (e.g., with an intensity of about 10 mW / cm²) can be used. 2Oxygen is infused for 30 seconds before the 365nm laser. The simultaneous oxygen delivery and laser crosslinking may occur over approximately 10 minutes. Saline can be circulated within the fluid-filled chamber 106, and conductivity measurements and passive cavitation detection can be used during treatment.

[0436] Figure 84 A schematic diagram of an exemplary treatment system 8400 including acoustic crosslinking or passive cavitation detection is shown. System 8400 may be substantially similar to any system described herein. System 8400 may include a shock wave generator, which may be substantially similar to any shock wave generator described herein. For example, the shock wave generator may include a first electrode 110 and a second electrode 112 disposed within a housing 102. Housing 102 may include a fluid-filled chamber 106 and an eye contact surface 104. Housing 102 may be substantially tubular, wherein electrodes 110, 112 are disposed near the proximal end of fluid-filled chamber 106 and eye contact surface 104 is disposed at the distal end of fluid-filled chamber 106, housing 102 having an elongated central portion 8402 providing a waveguide between the proximal and distal ends. For example, eye contact surface 104 may include a PET film as described herein. Eye contact surface 104 may be configured to adhere to the surface of a patient's eye. As described herein, a bonding fluid or gel (e.g., a water column) may be present on or below the eye contact surface 104 to facilitate contact between the eye contact surface and the surface of the eye and / or to facilitate the transmission of shock waves from the shock wave generator to the eye.

[0437] In some embodiments, the shock wave generator may further include a fluid inlet 108 and a fluid outlet 109 in fluid communication with the fluid-filled chamber 106 as described herein. Fluid may circulate within the fluid-filled chamber 106 via the fluid inlet 108 and the fluid outlet 109. The fluid may circulate at a rate sufficient to remove bubbles and / or heat formed during shock wave generation (e.g., about 100 ml / min). The fluid inlet 108 may be configured to deliver fluid to a distal end of the shock wave generator (e.g., the distal end of waveguide 8402), and the fluid outlet 109 may be configured to remove fluid from a proximal end of the shock wave generator (e.g., near electrodes 110, 112) such that the fluid flows through the housing 102 in a direction opposite to the direction of shock wave propagation.

[0438] In some embodiments, the proximal end of the fluid-filled chamber 106 may be configured to act as a reflector to focus a shock wave via a waveguide to a desired predetermined location. Alternatively or in combination, one or more reflectors 802 may be coupled to the inner surface of the fluid-filled chamber 106 to focus the shock wave. The inner wall of the fluid-filled chamber 106 may be elliptical. Alternatively or in combination, the distal end of the waveguide 8402 may be configured to focus the shock wave onto a predetermined location on or below the surface of the eye.

[0439] Alternatively or in combination, the proximal end of the fluid-filled chamber 106 may include a conductivity cell 7702, which includes a conductivity sensor configured to periodically or continuously sample the conductivity of the fluid in the fluid-filled chamber as described herein.

[0440] Alternatively or in combination, the proximal end of the fluid-filled chamber 106 may include a passive cavitation detector 8104 as described herein.

[0441] Alternatively or in combination, the proximal end of the fluid-filled chamber 106 may include a light source 7906 for acoustic crosslinking as described herein.

[0442] In some embodiments, a reservoir 7904 for oxygen and / or one or more therapeutic substances may be disposed on or below the eye contact surface 104 for drug delivery to the cornea as described herein. The reservoir 7904 may be attached to the eye using a vacuum-sealed retaining ring 1202. As described herein, shock waves generated by a shock wave generator can enhance drug delivery to the cornea (e.g., to epithelial cells) by fracturing and / or microporizing the surface of the corneal tissue of interest to improve drug permeability. In some embodiments, the therapeutic substance may comprise a photosensitizer, such as riboflavin, riboflavin nanoparticles, or rose red.

[0443] In some embodiments, the reservoir 7904 may include a fluid inlet 8406 and optionally a fluid outlet 8408 for circulating oxygen and / or therapeutic substances from an external source / reservoir 8404 to the cornea below the eye contact surface. In some embodiments, the same fluid inlet 8406 and fluid outlet 8408 may be used for each substance. In some embodiments, each substance may have a dedicated fluid inlet and fluid outlet. In some embodiments, an electrochemical cell 8206 may be used to generate oxygen for electrolysis and delivery to the eye (e.g., at >90% oxygen at 15 ml / min). For example, oxygen may be generated from the atmosphere by an electrolytic cell driven by a low-power current source (e.g., an AA battery) and delivered to the fluid inlet 8002 of the suction ring 1202 at the patient interface. As described herein, riboflavin may be delivered from the reservoir 8204 to the same fluid inlet 8002 or a different fluid inlet 8004.

[0444] In some implementations, a shock wave generator can be used to deliver oxygen and / or other therapeutic substances to the eye without simultaneous or subsequent cross-linking.

[0445] The shock waveguide 8402 may include a stainless steel tube with an outer diameter ranging from about 1 mm to about 8 mm, for example, about 1 mm, about 2 mm, about 3 mm, about 5 mm, or about 8 mm. The shock waveguide may include a stainless steel tube with an outer diameter of about 3 mm or 7 mm. The waveguide may have a wall thickness of about 0.5 mm.

[0446] In some embodiments, waveguide 8402 may have a length ranging from about 1 cm to about 2 cm. In some embodiments, the length of the waveguide may be about 12 mm or longer. For example, the waveguide may have a length ranging from about 12 mm to about 80 mm, for example, about 20 mm. The shock wave waveguide may include a stainless steel tube having a length of about 15 mm or about 30 mm.

[0447] Figures 85A to 85F Exemplary treatment modes for various target indications are shown. Any shock wave generator or system described herein can be used to treat the indicated indications. For example, one or more shock wave generators, including waveguides, can be mounted on a test frame goggles as described herein in a focus mode for the target indication.

[0448] Figure 85A A treatment modality 8501 for glaucoma is illustrated. Planar waves can be directed at the limbus and / or sclera for micro-ultrasonic perforation. Alternatively or in combination, shock waves can be used for non-thermal ciliary process separation to reduce water generation for glaucoma treatment. In some embodiments, microporous tracks can be created to increase blood, oxygen, nutrient, and / or lymphatic flow and / or increase hydraulic conductivity in tissues.

[0449] Figure 85B Treatment pattern 8502 for presbyopia is shown. Planar waves and / or focused waves can be directed at the limbal sclera and / or posterior vitreous septum for micro-ultrasound perforation and / or fragmentation.

[0450] Figure 85C A therapeutic modality 8503 for corneal drug (e.g., riboflavin) delivery (without epi-fluorescent cross-linking) is illustrated. Low-power plane waves can be directed at the cornea (e.g., epithelial cells) to fragment and micropore its surface, thereby enhancing drug delivery to it.

[0451] Figure 85D Treatment mode 8504 for acoustic crosslinking-accelerated crosslinking is illustrated. Planar waves can be directed to the cornea to enhance riboflavin and / or oxygen delivery as described herein. Ultraviolet light can then be used to irradiate and crosslink the cornea as described herein.

[0452] Figure 85E Treatment mode 8505 for dry eye disease is shown. Planar waves can be directed towards the meibomian tubes / glands of the eyelids, optionally with the aid of contact lenses for corneal protection, vasodilation, and / or detachment.

[0453] Figure 85F Treatment mode 8506 for AMD is shown. Plane waves can be directed at the retina for retinal / lymphatic plexus dilation and / or acoustic stimulation.

[0454] For dry AMD, non-selective low-power treatment may be sufficient to induce acoustic stimulation of the retina, sufficient to induce vasodilation and / or stimulation of senescent retinal cells. For wet AMD exhibiting neovascularization, it may be beneficial to preferentially enhance shockwave therapy at the site of neovascularization in the retina to reduce or eliminate (e.g., break up) the newly formed leaky vascular system while protecting surrounding tissue. In at least some cases, shockwave therapy can be locally enhanced by selectively seeding nanoparticles and / or microbubbles into the tissue. As described herein, low-dose shockwave energy that may have a limited effect on unseeded tissue can selectively fragment microbubble-seeded tissue (e.g., as described herein, ruptured microbubbles may directly damage cells). In some embodiments, microbubbles or microbubble-forming enhancement particles can be injected into the bloodstream and accumulate in retinal tissue adjacent to the neovascular system due to the leaky nature of the retinal neovascular system. Alternatively or in combination, laser energy can be focused onto the retina at the desired treatment site to induce microbubble formation at that site. Multiple wavelength ranges can be used to induce microbubble formation in tissues, including 532 nm, 590 nm, femtosecond lasers, near-infrared, mid-infrared, or 6 μm to 10 μm. The laser can be a picosecond, nanosecond, or microsecond pulsed laser. Once the microbubbles have been seeded, low-energy shockwave therapy can be directed to the retina as described herein and can selectively enhance treatment at the seeded tissue via the microbubbles.

[0455] Any system described herein can be used to perform capsulorhexis or capsiotomy on the lens capsule of the eye. For example, jet microbubbles emitted from a soft contact lens placed on an intraocular lens inserted during lens / cataract treatment may emulsify a 5.5 mm central lens after ultrasound treatment and soften the cataract. Depending on the interaction / patterning of the exposed and circulating microbubbles, this treatment may allow for capsulorhexis or capsiotomy. Microbubbles and / or particles can optionally act as acoustic shielding or cavitation seeding particles. Guided through a thin-capsular IOL inserted during cataract surgery, based on the spatial pattern of the channel and the timing of the flow of either the microbubbles or particles, these microbubbles or particles can deposit energy onto the capsule and / or lens during frontal external shock wave ultrasound treatment.

[0456] As will be understood by those skilled in the art, any shock wave generating apparatus and system described herein may include components that can be combined with or substituted for one another, and therefore any number of combinations may be used. For example, any apparatus and system described having a pair of electrodes for shock wave generation may alternatively utilize piezoelectric, laser, or magnetoelectric shock wave generating mechanisms as described herein. Furthermore, various features of shock wave generating apparatus and systems have been described herein, including corneal protective contact lenses, contact lens balloons, shock wave waveguides, focusing shock wave generators, reflectors, zoom lenses, non-focusing shock wave generators, conductivity sensors, current sensors, pressure sensors, passive cavitation detectors, imaging systems, drug delivery storage devices, crosslinked laser energy sources, fluid recirculation systems for degassing, etc. Those skilled in the art will understand that these features can be combined with or substituted for one another, and therefore any number of combinations may be used.

[0457] This document describes various methods, treatment modalities, and target sites, including a) treatment methods and modalities for presbyopia, glaucoma, dry eye disease, dry AMD, wet AMD, keratoconus, ectasia, etc., and b) target sites on or within the eye, including one or more of the following: trabecular meshwork, Schreim's canal, ciliary body (e.g., ciliary processes, muscles, selected portions of the anterior / posterior / equatorial region of the ciliary body, etc.), pars plana of the ciliary body, ciliary corona, cornea, sclera, lens, retina, fovea, perifoveal region, intermediate vitreous zone (IVZ), posterior vitreous zone (PVZ), vitreous body, eyelids, and / or meibomian glands. One or more people skilled in the art will understand that these treatment methods, modalities, and target sites can be selected based on the indication to be treated or a combination of indications. Devices and systems can be configured to simultaneously or sequentially treat one or more target sites for one or more indications as needed. In some implementations, the system may include multiple shock wave generators located at different positions near the surface of the eye and focused (or unfocused) on different target locations above or below the eye to treat multiple indications without removing the system from the patient's eye. Those skilled in the art will understand that these treatment sites, methods, and modes can be combined or substituted for one another, and therefore any number of combinations can be used.

[0458] Although preferred embodiments of the invention have been shown and described herein, it will be apparent to those skilled in the art that these embodiments are provided by way of example only. Many variations, modifications, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in carrying out the invention. The appended claims are intended to define the scope of the invention, and methods and structures within the scope of these claims and their equivalents are therefore covered.

Claims

1. A device for treating an eye, the device comprising: A housing, the housing including a fluid-filled chamber and an eye contact surface configured to contact the eye; A first electrode, which is disposed within the housing; as well as A second electrode is disposed within the housing and coaxially aligned with the first electrode, wherein the distal ends of the first electrode and the distal ends of the second electrode are spaced apart by a gap. The first and second electrodes are configured to generate an electric arc across the gap and a shock wave in the fluid within the fluid-filled chamber when energized. The device includes a fluid inlet and a fluid outlet that are in fluid communication with the fluid-filled chamber. Its features The device further includes a conductivity sensor at least partially disposed in the fluid-filled chamber and configured to periodically or continuously measure the conductivity of the fluid in the fluid-filled chamber, wherein the conductivity sensor is configured to monitor changes in conductivity caused by metal ions released from the first and second electrodes during corrosion of the first and second electrodes.

2. The apparatus according to claim 1, wherein, The inner surface of the housing is configured to focus the shock wave onto a predetermined location on the surface of the eye or a predetermined location below the surface of the eye.

3. The apparatus of claim 1 or 2, further comprising a reflector disposed within the housing and configured to focus the shock wave onto a predetermined location on the surface of the eye or a predetermined location below the surface of the eye.

4. The apparatus of claim 1 or 2, further comprising one or more wires coupled to the first electrode or the second electrode and configured to provide energy to the first electrode or the second electrode.

5. The apparatus according to claim 1 or 2, wherein, The first electrode and the second electrode include a first end of a first wire and a second end of a second wire.

6. The apparatus according to claim 1 or 2, wherein, The fluid includes salt water or water.

7. The apparatus according to claim 1 or 2, wherein, The first and second electrodes are coated with graphene to reduce corrosion during the use of shock waves.

8. The apparatus according to claim 1 or 2, wherein, The shell is elliptical.

9. The apparatus according to claim 1 or 2, wherein, The housing also includes a fluid-filled waveguide disposed between the fluid-filled chamber and the eye contact surface and configured to be fluidly connected to the fluid-filled chamber and the eye contact surface.

10. The apparatus of claim 1 or 2, further comprising an acoustic lens disposed within the housing and configured to focus the shock wave onto one or more predetermined locations on the surface of the eye or below the surface of the eye.

11. The apparatus according to claim 1, wherein, The conductivity sensor includes a pair of platinum electrodes.

12. The apparatus of claim 1 or 2, wherein the apparatus includes a light source disposed at least partially within the fluid-filled chamber and configured to emit light toward the surface of the eye.

13. A system for treating an eye, the system comprising: The apparatus according to any one of claims 1 to 12; as well as An energy source is operatively connected to the first electrode and the second electrode via one or more wires.

14. The system according to claim 13, wherein, The first electrode is connected to the positive terminal of the energy source and the second electrode is connected to the negative terminal of the energy source.

15. The system according to claim 13 or 14, wherein, The energy source includes a high-voltage pulse generator.

16. The system of claim 13 or 14, further comprising a current sensor coupled to the first electrode or the second electrode, the current sensor being configured to determine the current level flowing to the first electrode or the second electrode.

17. The system of claim 13 or 14, further comprising a conductivity sensor fluidly coupled to the fluid outlet and configured to measure the conductivity of the fluid as the fluid flows out of the fluid outlet.

18. The system of claim 13 or 14, further comprising a fluid recirculation system fluidly connected to the fluid outlet and the fluid inlet and configured to recirculate fluid from the fluid-filled chamber and remove cavitation bubbles from the fluid.

19. The system of claim 13 or 14, further comprising a storage device disposed on or below the eye contact surface.

20. The system according to claim 19, wherein, The storage container contains oxygen.

21. The system according to claim 19, wherein, The storage device contains riboflavin.

22. The system according to claim 19, wherein, The storage device contains a therapeutic agent.

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