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WO2025006635A9 - Thérapie laser pour traitement et prévention de maladies oculaires à l'aide de faisceaux annulaires - Google Patents

Thérapie laser pour traitement et prévention de maladies oculaires à l'aide de faisceaux annulaires Download PDF

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Publication number
WO2025006635A9
WO2025006635A9 PCT/US2024/035662 US2024035662W WO2025006635A9 WO 2025006635 A9 WO2025006635 A9 WO 2025006635A9 US 2024035662 W US2024035662 W US 2024035662W WO 2025006635 A9 WO2025006635 A9 WO 2025006635A9
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Prior art keywords
eye
laser
annulus
treatment
examples
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WO2025006635A1 (fr
Inventor
Giorgio Dorin
Michael K. BALLARD
David Squires
Brian Catanzaro
William Eddington
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Aleyegn Technologies LLC
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Aleyegn Technologies LLC
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/008—Methods or devices for eye surgery using laser
    • A61F9/00821—Methods or devices for eye surgery using laser for coagulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/008—Methods or devices for eye surgery using laser
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/008—Methods or devices for eye surgery using laser
    • A61F2009/00861—Methods or devices for eye surgery using laser adapted for treatment at a particular location
    • A61F2009/00863—Retina
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/008—Methods or devices for eye surgery using laser
    • A61F2009/00861—Methods or devices for eye surgery using laser adapted for treatment at a particular location
    • A61F2009/00868—Ciliary muscles or trabecular meshwork
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/008—Methods or devices for eye surgery using laser
    • A61F2009/00861—Methods or devices for eye surgery using laser adapted for treatment at a particular location
    • A61F2009/00872—Cornea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/008—Methods or devices for eye surgery using laser
    • A61F2009/00885—Methods or devices for eye surgery using laser for treating a particular disease
    • A61F2009/00891—Glaucoma
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/008—Methods or devices for eye surgery using laser
    • A61F2009/00897—Scanning mechanisms or algorithms

Definitions

  • FIELD Trans-scleral ab externo IOP lowering and trans-pupillary neuroprotection laser treatments are disclosed for the clinical management of patients with ocular hypertension and/or glaucoma and for the treatment and/or prevention of related diseases.
  • BACKGROUND Glaucoma is an optic neuropathy characterized by increased intraocular pressure (IOP) that damages the retina ganglion cells and the nerve fibers in the optic disc.
  • IOP intraocular pressure
  • Aqueous humor is produced from the ciliary processes, moves through the pupil then into the anterior chamber and through the trabecular meshwork, Schlemm’s canal, and uveoscleral outflow pathways.
  • Increased IOP results from an imbalance between the production of aqueous humor and resistance to its outflow through the normal outflow tracts.
  • Glaucoma can lead to chronic, progressive deterioration of the optic nerve that results in cupping and atrophy of the optic disc.
  • the nerve damage causes a progressive loss of the peripheral visual field followed by a loss of central vision and irreversible blindness if not timely treated.
  • the goal of current glaucoma treatments is to stop or slow disease progression by reducing IOP, which has been the only known modifiable risk factor.
  • the most common treatment for glaucoma is the life-long use of IOP-lowering medication, such as eye drops containing prostaglandin analogs, beta-adrenergic receptor antagonists, alpha2-adrenergic agonists, and miotic agents. Although these medications have improved the treatment of glaucoma, they have local and systemic side-effects.
  • Argon laser trabeculoplasty uses a gonioscopic lens applied to the eye to deflect a laser beam through the cornea and into the angle of the anterior chamber of the eye to directly irradiate the trabecular meshwork.
  • ALT was the first type of LT introduced in the 1970s and it has subsequently been practiced using a variety of lasers, wavelengths, and treatment techniques. Some of these techniques are Diode Laser Trabeculoplasty (DLT), Selective Laser Trabeculoplasty (SLT), Micropulse Laser Trabeculoplasty (MLT), and Titanium-Sapphire Laser Trabeculoplasty (TLT).
  • DLT Diode Laser Trabeculoplasty
  • SLT Selective Laser Trabeculoplasty
  • MLT Micropulse Laser Trabeculoplasty
  • TLT Titanium-Sapphire Laser Trabeculoplasty
  • LT is normally an ab interno procedure that is performed trans-corneally using a slit-lamp delivery system and a corneal contact goniolens to visualize and precisely direct the laser beam into the anterior angle of the eye, below the Schwalbe Line (SL), to the pigmented trabecular meshwork where the laser energy is absorbed and converted into heat.
  • Laser wavelengths in the 488-810 nm range have been used for these procedures to specifically interact with the darkly pigmented cells in the TM.
  • Trans-corneal LT procedures are challenging and contact between the gonioscopy lens and the eye can induce iatrogenic corneal lesions such as punctate keratopathies and infections.
  • LT has also been performed ab externo using a trans-scleral approach with a 532 nm SLT frequency-doubled Q-switched 3-ns Nd:YAG laser beam (Geffen et al., J. Glaucoma 26:201-207, 2017) or a 810 nm MDLT micropulsed laser beam (see Aquino MC and Chew PK, External Micropulse Diode Laser Trabeculoplasty (EMDLT) for Primary Open Angle Glaucoma: a pilot study. P4-097 European Glaucoma Society 2018 Annual Congress, Firenze, Italy; and U.S. Patent No.8,945,103).
  • EMDLT External Micropulse Diode Laser Trabeculoplasty
  • the SLT or the EMDLT laser beam is applied ab-externo over the perilimbal area through the corneoscleral junction to affect the conventional outflow pathway structures (collector channels, Schlemm’s canal, juxtacanalicular, corneoscleral and uveal TM).
  • Trans-scleral procedures have generally not used infrared wavelengths that are known to be absorbed by water in the superficial scleral cells because superficial absorption would prevent the laser energy from reaching the targeted deeper structures, such as the trabecular meshwork.
  • a scleral indentation probe has generally been considered necessary to maximize laser energy penetration deep into the sclera.
  • Scleral indentation moves the laser energy source closer to the deep scleral targets and expresses water from underlying scleral cells to reduce both absorption and scattering of the light energy by water molecules in the superficial sclera.
  • Manual movement of the laser probe against the eye limits the laser movement speed because fast movements abrade or otherwise traumatize the eye being treated.
  • the speed and the positioning of the laser probe cannot be precisely controlled by the surgeon in a consistent manner resulting in practically unrepeatable and grossly variable laser energy deposition in each treatment.
  • Optical coherence tomography angiography has facilitated the detection of areas of retinal capillary hypo-perfusion in patients with chronic progressive neurotrophic neurodegenerative retinopathies including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), and in patients with POAG.
  • AMD age-related macular degeneration
  • DR diabetic retinopathy
  • RP retinitis pigmentosa
  • Glaucoma has been associated with reduced blood perfusion in the retina, and the presence of capillary hypo-perfusion correlates to later measures of nerve fiber thinning and visual field defect progression.
  • IOP lowering treatments alone may not be sufficient to prevent visual loss progression has led to increased interest in neuroprotective treatments to improve the neurotrophic balance, thus the health and function of the optic nerve and retina.
  • US 9,962,291 discloses the use of subthreshold photocoagulation of the retina, in the pattern of a grid or rotated line.
  • a need remains for improved systems and methods for treating glaucoma by reducing/controlling IOP and by administering an effective neuroprotective therapy to slow, stop, and possibly reverse the neurodegenerative progression.
  • an apparatus includes an optical system configured to produce a first annulus and second annulus at a target with respective first and second 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 diameters, wherein the first annulus has a first wavelength and the second annulus has a second wavelength longer than the first wavelength, wherein the optical system includes an axicon system including a first axicon element and a second axicon element, the axicon system configured to define a relationship between the first and second diameters.
  • Some examples further include a first beam source configured to emit light at the first wavelength, a second beam source configured to emit light at the second wavelength, an optical fiber coupled to the first and second beam sources to receive and direct the light at the first and second wavelengths and to emit the light from a fiber end at the first and/or second wavelength, wherein the fiber end is coupled to the optical system to produce the respective first annulus and/or second annulus at the target with a non-varying relative relationship based on the common emission of the light at the first and second wavelengths from the fiber end, and a controller coupled to control emission of the first beam source and second beam source.
  • the optical system comprises achromatic imaging optics situated to receive the light at the first and second wavelengths from the fiber end and to direct the light at the first and second wavelengths to the axicon system.
  • the first and second axicon elements are configured to define the relationship between the first and second diameters as co- radial.
  • Some examples further include a housing that supports the axicon system and that includes a shelf configured to space apart the first axicon element and second axicon element by a predetermined amount.
  • Some examples further include a movement stage coupled to the axicon system and configured to translate the axicon system along an optical axis of the optical system to vary the first and second diameters by the same amount.
  • Some examples further include a speckle reducer coupled to the path of the light at the second wavelength and configured to reduce irradiance spikes in the second annulus.
  • the target is an eye
  • the first wavelength is a visible wavelength
  • the second wavelength is a water-absorptive infrared wavelength
  • the first annulus is configured to allow alignment of the second annulus in a perilimbal region of the sclera radially outward from the corneolimbal junction.
  • the controller is configured to scan a diameter the first annulus and/or second annulus during a treatment of the target.
  • the controller comprises a processor, and memory including stored computer-readable instructions that, responsive to execution by the processor, cause the apparatus to form the second annulus on the external surface of the eye with an irradiance and for a duration that produces a broad geographic nonlethal hyperthermia to underlying sub- scleral biological structures providing primary and non-conventional outflow pathways without causing photocoagulation of the tissue of the eye.
  • Some examples further include a trans-pupillary beam source configured to produce a trans-pupillary beam for directing through the pupil of an eye, 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 wherein the controller is configured to control emission of the trans-pupillary beam source to emit the trans-pupillary beam to a plurality of trans-pupillary treatment locations and to induce sublethal thermal elevations eliciting therapeutic biomodulation at the target eye tissue within a predetermined therapeutic temperature range, the plurality of trans-pupillary treatment locations including a predetermined curvilinear treatment pattern on target eye tissue of the eye comprising multiple concentric annuli on the macula around but not on the foveal avascular zone.
  • the optical system is configured to direct the trans-pupillary beam to the plurality of trans-pupillary treatment locations.
  • a separate optical system is configured to direct the trans-pupillary beam to the plurality of trans-pupillary treatment locations.
  • methods include producing the first annulus and/or second annulus.
  • methods include arranging lens elements to form the optical system.
  • an ab externo automated laser treatment apparatus for treating an eye in a subject, includes a non-contact laser source configured to produce a continuous- wave laser beam having at least one wavelength to treat the eye by directing the laser beam from a location spaced from the eye, wherein the at least one wavelength is a near-infrared wavelength in the range of about 1.0-2.2 ⁇ m, an optical system configured to receive and direct the laser beam to form an annulus at an external perilimbal surface region of the eye, wherein the annulus has an inner diameter and outer diameter situated between 0-4 mm posterior to a corneolimbal junction, a processor, and memory including stored computer-readable instructions that, responsive to execution by the processor, cause the laser treatment apparatus to form the annulus on the external surface of the eye with an irradiance and for a duration that produces a broad geographic nonlethal hyperthermia to underlying sub-scleral biological structures providing primary and non- conventional outflow pathways without causing photocoagulation of the tissue of the eye.
  • the optical system includes an axicon system situated to convert a cross-sectional shape of the laser beam into the annulus.
  • the axicon system includes first and second axicon elements that form an achromatic axicon doublet.
  • the optical system includes an achromatic lens situated to focus the annulus at the external surface of the eye.
  • the axicon system is situated between the achromatic lens and the eye and further comprising one or more movement stages coupled to the axicon system and configured to translate the axicon system to adjust a diameter of the annulus.
  • the movement stage is configured to scan the diameter of the annulus over time during a treatment.
  • the apparatus is configured to direct the continuous-wave beam and/or annulus at a duty-cycle based on power and/or scanning to reduce a likelihood of tissue damage to the surface or surface regions of 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 the eye.
  • the annulus is a first annulus and further comprising a visible light source coupled to the optical system, wherein the axicon system is configured to produce a second annulus with the light from the visible light source, wherein the first annulus and second annulus are co-radial.
  • Some examples further include a temperature sensor coupled to detect a surface temperature of the eye being treated.
  • the temperature sensor is coupled to detect the surface temperature of the eye at the location of the annulus on the surface of the eye.
  • the temperature sensor comprises an imaging camera, thermographic camera, and/or thermal sensor.
  • the stored computer-readable instructions include instructions that, responsive to execution by the processor, cause the apparatus to adjust one or more laser parameters during the treatment in response to the detected surface temperature.
  • the instructions are configured to: compare the measured surface temperature to a predetermined thermal model relating scleral surface temperature change produced by laser beam to tissue damage of the conjunctiva or sclera, and reduce the surface temperature in response to the comparison by reducing laser power or powering down the laser.
  • the instructions are configured to: compare the measured surface temperature to a predetermined thermal model relating eye surface temperature change produced by the laser beam to a temperature change of the underlying sub-scleral biological structures, and maintain a temperature of the sub- scleral biological structures within a temperature range that provides the nonlethal hyperthermia without photocoagulation by dynamically adjusting the one or more laser parameters during the treatment duration.
  • the one or more laser parameters include one or more of: irradiance, duration, laser power, laser duty cycle, irradiance profile, annulus mean diameter, annulus thickness, annulus inner diameter, annulus outer diameter.
  • the temperature sensor is configured to detect the surface temperature during one or more duty-cycle off-periods of the continuous-wave beam during treatment.
  • the irradiance is at least 0.1 W/cm 2 and at most 2.0 W/cm 2 .
  • the wavelength or the second wavelength is between 1.4 ⁇ m and 1.6 ⁇ m.
  • the wavelength or the second wavelength is 1.475 ⁇ m or 1.550 ⁇ m.
  • the duration is at least 30 seconds.
  • FIG.1 schematically illustrates traditional prior art trans-corneal laser trabeculoplasty performed using a slit-lamp laser delivery system and a corneal contact gonioscopy lens to visualize and direct the laser beam ab-interno at the pigmented trabecular meshwork (TM) below the Schwalbe Line (SL) in the angle of the eye’s anterior chamber.
  • TM pigmented trabecular meshwork
  • SL Schwalbe Line
  • FIGS 2A and 2B schematically illustrate an example of a trans-scleral laser trabeculoplasty method which directs laser energy at the surface of the eye without contacting that surface.
  • a laser beam is directed ab-externo to the perilimbal area through the corneoscleral junction over the outflow pathway structures.
  • FIG.3 schematically illustrates the anatomy of the corneoscleral junction bounded anteriorly by the corneolimbal junction and posteriorly by the sclerolimbal junction.
  • FIGS.4A and 4B are schematic drawings that show one or more locations of generally annular treatment patterns with various radii R 1 , R 2 and R 3 at which the trans-scleral laser can be directed at the eye.
  • OA is the optical axis of the eye.
  • FIG.4C is a front view of the eye, schematically illustrating a treatment pattern of laser irradiation is directed to the region of the corneoscleral junction to lower IOP.
  • the arcuate pattern is interrupted nasally and temporally; the illustrated superior and inferior arcs are continuous in that they have no internal interruption of either arc.
  • FIG.4D is a view similar to FIG.4C but illustrating a treatment pattern of laser irradiation continuously directed to the perilimbal region without the nasal and temporal interruptions.
  • FIG.4E is a front view of the eye similar to FIG.4C but showing multiple annular patterns with laser energy directed to the region of the corneoscleral junction at locations R 1 , R 2 and R 3 to lower IOP.
  • FIG.4F illustrates the method of applying the trans-scleral laser energy to the eye without contacting the surface of the eye.
  • FIGS.4G, 4H, 4I and 4J illustrate examples of a cycle of the cyclic treatment.
  • FIG.4K schematically illustrates angular locations around the right and left eyes.
  • FIG.4L schematically illustrates an angle between the optical axis of the eye and the incident laser beam at the surface of the eye.
  • FIG.4M schematically illustrates the continuous movement of the laser beam as it moves along an annular treatment pattern and through a contact lens to induce a heat wave in the sclera.
  • FIGS.4N, O and P schematically illustrate three-dimensional heat propagation, 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 accumulation and relaxation in the scleral wall as a non-contact laser directed at the scleral surface moves rapidly across the sclera.
  • FIGS.4Q, R, S, T, U, V, W and X are a two-dimensional illustration of the advance and retreat of the thermal wave through the scleral wall.
  • FIGS 4Y and 4Z are graphs illustrating the effect of laser speed and duty cycle on peak tissue temperature.
  • FIG.5A is a perspective view of a patient interface for stabilizing and cooling the eye during the trans-scleral procedure.
  • FIG.5B is a cross-sectional view of the patient interface illustrating a graphene contact lens held by a contact lens holder that cools the lens and permits suction contact between the lens holder and the eye. Laser triangulation for Z-focus camera viewing is also illustrated.
  • FIG.5C is a bottom perspective view of the patient interface, showing the graphene contact lens surrounded by a silicone sealing member.
  • FIG.6A is a perspective view of the speculum
  • FIG.6B is a perspective view of an embodiment of the contact lens holder retained within the speculum
  • FIG.6C is an isolated cross-sectional view of the contact lens holder with an internal cooling channel to circulate cooling fluid and cool the contact lens.
  • FIG.6D is an exploded view of the interface cone, contact lens holder and speculum.
  • FIG.6E is an enlarged side-sectional view of the lens holder showing the contact lens vaulting over the suction chamber.
  • FIG.7A illustrates the speculum as it would be placed in a subject’s eye to expose the sclera for the trans-scleral procedure.
  • FIG.7B schematically illustrates the assembled patient interface in the eye.
  • FIG.8A is a cross-sectional view illustrating the patient interface docked to the eye of a recumbent subject with laser energy directed at the eye.
  • FIG.8B is a schematic view of a 3-D scanner to image the front of an eye for treatment and/or positioning the patient interface.
  • FIG.9A is a side view of a control box for the patient interface, and a source of cooling liquid.
  • the patient interface includes a laser cone that projects from the bottom face of the control box and is connected to a lens holder and speculum. Tubing connects the source of cooling liquid with the interface to cool the lens.
  • FIG.9B is a perspective view of the control box of FIG.9A, illustrating tubing clamps that reduce tip/tilt stress on the contact lens holder, and more clearly illustrating inlet and outlet tubing for the cooling liquid, and suction control tubing that communicates with the suction chamber.
  • FIG.9C is a perspective view of a control arm for positioning and docking the patient interface with the eye of the subject. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024
  • FIGS.10A and 10B are schematic diagrams of an automated computer-controlled system for the treatment method.
  • FIG.11 shows an image of an eye taken by a camera after docking the patient interface and system to the eye, in accordance with embodiments, with an image of the limbus illustrated on the eye.
  • FIG.12A shows an imaging scheme which may be used to estimate the shape of the limbus and the corneoscleral or corneolimbal junction.
  • FIG.12B is a flowchart of an example method of imaging and determination of treatment locations.
  • FIGS.13A-13D show an exemplary process for generating a treatment pattern based on one or more locations of the limbus and corneoscleral junction.
  • FIG.14 is a flowchart of a method for determining a target treatment location, in accordance with embodiments.
  • FIG.15 is a perspective, and partially cross-sectional, schematic view of a human eye.
  • FIG.16 is a photographic image of the fundus including the central retina showing the macula, the fovea avascular zone (FAZ), and the foveola at the center of the image.
  • FIG.17A is a retinal image similar to the image in FIG.16 but showing target regions for pan-macular non-damaging laser photostimulation as viewed through the pupil. A cross-section of the macula is shown at the bottom of FIG.4A and illustrates the varying thickness of the macula from its central to peripheral zones.
  • FIG.17B is a schematic of a retina similar to FIG.17A but including an example of a circular laser beam scan pattern.
  • FIGS.18A-18G is a series of retinal images similar to FIG.17B, illustrating patterns of irradiation of the retina during later panmacular laser photostimulation treatment.
  • FIG.19 is schematic showing the relative locations of laser spots with respect to the central fovea avascular zone (FAZ) applied to perform a central retinal photostimulation treatment.
  • FIG.20 is a graph illustrating an example of retinal heating gradients during treatment.
  • FIG.21 is a schematic of an example optical imaging and scanning system.
  • FIG.22 is an end view schematic of an example treatment scan pattern that treats both the sclera and retina.
  • FIG.23 is a flowchart of an example method of treatment.
  • FIGS.24A-24C illustrate retinal areas and example laser treatment patterns.
  • FIG.25 is a schematic of an example laser treatment apparatus.
  • FIG.26 is a schematic of an example laser treatment system that produces annular shaped beams.
  • FIG.27 is a schematic of an example laser eye treatment system that produces annular shaped beams with an axicon optical system.
  • FIG.28 is an end view of a bundled arrangement of optical fibers to selectively produce an annulus.
  • FIG.29 is an end view of an annulus produced with the bundled arrangement of FIG.28.
  • FIG.30 is a graph of an example treatments performed using an annular beam according to various disclosed apparatus capable of producing annuli.
  • FIG.31 is a graph of example treatment durations in relation to various example beam parameters.
  • FIG.32 is a graph of example treatment characteristics for continuous-wave annular beams.
  • FIG.33 is an end view schematic illustration of an example beam annulus at an eye.
  • FIGS.34A-34E are side cross-sectional irradiance profiles for example beam annuli.
  • FIG.35 is a flowchart of an example laser treatment methods that include surface temperature detection.
  • FIG.36 is a schematic of an example laser treatment system that can monitor and control an inferred temperature.
  • FIG.37 is a schematic of an example laser treatment system for laser-treating an eye and aiming the laser treatment with an aiming annulus.
  • FIG.38 is a schematic of an axicon-based optical system that can be used to produce a treatment annulus and an aiming annulus.
  • FIG.39 is an end view of an annulus that can be produced various disclosed apparatus and that includes visible and infrared annulus portions.
  • FIG.40 is an end view modeled image of an aiming annulus having a smaller diameter than a treatment annulus.
  • FIG.41A is a side view schematic of an example axicon-based optical system.
  • FIG.41B is a side view ray-trace of the example axicon-based optical system of FIG.41A.
  • FIGS.42A-42B are graphs of refractive index with respect to wavelength for fused silica and zinc sulfide, respectively.
  • FIGS.43A-43B are side and end view cross-sectional irradiance profiles for annuli produced with the optical system shown in FIG.41A with the axicon at a 5 mm position.
  • FIGS.44A-44B are side and end view cross-sectional irradiance profiles for annuli produced with the optical system shown in FIG.41A with the axicon at a 30 mm position.
  • FIGS.45A-45B are side and end view cross-sectional irradiance profiles for annuli produced with the optical system shown in FIG.41A with the axicon at a 55 mm position.
  • FIG.46 is a flowchart of example methods of producing a first annulus and/or second annulus at a target.
  • FIG.47 is a schematic of an example laser treatment system.
  • FIG.48 is a ray diagram of an example lens system.
  • FIGS.49A-49B ray diagrams of an example lens system with an axicon assembly at near and far positions, respectively.
  • FIG.50 is a schematic of an example laser treatment system with ray diagrams associated with power detection and target imaging optics.
  • FIG.51 is a side cross-sectional schematic of an example axicon doublet.
  • FIG.52 is a flowchart of an alignment method.
  • a “Posterior” refers to the back of the eye, toward the posterior pole.
  • a “limbus-contoured” treatment pattern refers to treating locations on the surface of the eye that mimic the outline of the limbus of that eye. The treatment pattern may be at the limbus itself, or spaced posterior to the corneolimbal junction, but retaining the limbal outline of the specific patient being treated.
  • a “non-contact laser source” refers to a laser source (e.g., including one or more diodes at the same or different wavelengths, beam splitting optics, beam shaping optics, optical scanner components, etc.) that produces a laser beam that is directed to the intended target and that does not have parts in contact with the target surface irradiated by the laser source.
  • the laser beam is not emitted from a probe in contact with the irradiated surface.
  • the “optical axis” of the eye is the straight line passing through the geometrical center of the cornea and the nodal (central) point of the eye.
  • “Therapeutic biostimulation” refers to stimulation of biological mechanisms that achieve a therapeutic effect (such as lowering IOP or improving the trophism in the retina).
  • “Thermal preconditioning” refers to preliminary mild step-rise heating of tissue to protect it from thermal damage and make it more damage-resistant at even more elevated temperatures.
  • Treatment patterns may have various shapes.
  • a circumferential pattern surrounds a curved structure, such as the limbus, for example in a curved or polygonal shape.
  • An “annular” pattern surrounds a reference structure (such as the limbus or foveal avascular zone) and is generally ring/oval-like.
  • An ab externo trans-scleral automated photothermal laser delivery system lower intraocular pressure by irradiating an eye in a subject from a non-contact laser energy source that is configured to direct laser energy from a location spaced from the eye.
  • the laser energy has a near-infrared wavelength of 0.8-2.2 ⁇ m or 1-2.2 ⁇ m, such as 1.0 to 1.7 ⁇ m, for example a wavelength of about 0.80-0.85 ⁇ m or a wavelength of about 1.4-1.6 ⁇ m. In some disclosed embodiments the wavelength is 1.47 ⁇ m.
  • a processor may be configured with instructions to direct the laser energy to a plurality of treatment locations irradiated in a predetermined treatment pattern on an external surface of the eye.
  • the treatment locations are for example 0-5 mm (such as 1-5 mm) anterior or 0-4 mm (such as 1-4 mm) posterior to the corneolimbal junction, and the laser energy is repetitively directed to the same irradiated treatment locations of the eye.
  • the treatment locations are irradiated at time intervals that induce protective thermal preconditioning and therapeutic bio-stimulation of one or more structures of the eye, i.e. the trabecular meshwork and/or ciliary body to lower IOP.
  • An energy delivery system coupled to the energy source and the processor is configured to repetitively deliver the energy specifically to the plurality of predetermined irradiated treatment locations on the predetermined treatment pattern at the intervals that induce protective thermal preconditioning, propagation of a heat wave to targeted structure deeper in the eye, and hyperthermia and bio-stimulation of the targeted structures.
  • a processor is configured with instructions to repetitively deliver the energy specifically to the plurality of irradiated treatment locations at intervals that target an increase in the temperature of the outer 200-550 ⁇ m scleral layers to a temperature of about 43- 57°C.
  • the irradiance of the laser energy and a scanning speed with which the laser energy moves around the treatment pattern increases the temperature of the outer 200-550 ⁇ m scleral layers to a temperature of about 43-57°C, or less than 45°C or about 43-45°C.
  • the increase in temperature of the tissue is, for example, no more than 8 or 10°C above the baseline temperature of the tissue.
  • the peak temperature of the tissue is below a coagulation temperature of the irradiated tissue.
  • the processor may be configured with instructions to receive an input corresponding to a location of the corneolimbal junction or limbus of the subject and determine the plurality of treatment locations in response to the input.
  • the treatment locations are offset radially outward from the input location corresponding to corneolimbal junction or limbus to contour the 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 treatment pattern to the anatomy of the eye of the subject and achieve customized delivery of the heat wave to the targeted deeper structures.
  • the treatment locations are within a 360° pattern posterior to the corneolimbal junction.
  • the treatment locations can be coextensive with the 360° treatment pattern, or only along portions of the treatment pattern (for example in multiple arcs or spots on the treatment pattern).
  • the processor directs the laser energy to a set of pre-identified treatment locations on the surface of the eye during a first treatment cycle, and during one or more subsequent treatment cycles (repeat cycles) directs the laser energy to the same or a subset of the same pre-identified treatment locations.
  • Precise cyclic thermal elevation of scleral tissue underlying the pre-identified treatment locations at intervals of time induces thermal elevation/relaxation cycles of the irradiated tissue to occur between treatment cycles and propagation of the heat wave to target structures deeper in the eye.
  • the processor sets the speed of each treatment cycle to achieve the thermal relaxation by spacing irradiation of the treatment locations at intervals that produce a targeted time-temperature history.
  • the interval between irradiation of the same treatment location produces a duty factor, (the ratio between the active exposure ON time/[active exposure + relaxation OFF time]), in the 2-50% range.
  • the interval between irradiation of the same treatment location is about 10-300 ms, for example 100-200 ms.
  • the time interval between irradiations of a specific treatment location may vary depending on other parameters.
  • the predetermined treatment pattern extends through all or a portion of a 360° limbus-guided circumferential pattern or annulus which is located about 1- 1.5 mm posterior to the corneolimbal junction.
  • the energy pattern can be delivered in many configurations, for example a portion of an annulus, a polygon, or intermittent treatment along a generally circumferential pattern.
  • the treatment pattern extends through a 120° arc.
  • Other predetermined treatment patterns may extend through a generally annular shape about 2 mm to 3 mm and/or 3 mm to 4 mm posterior to the corneolimbal junction. Since the limbus and corneolimbal junction may be other than circular, a pattern spaced a fixed distance from the corneolimbal junction through 360° will mimic the shape of the limbus and corneolimbal junction.
  • Limbus-guided patterns may for example be ovoid, elliptical, generally arcuate with non-arcuate segments, or irregularly-shaped but otherwise surrounding the limbus.
  • a treatment pattern provides a template on which treatment locations may be located, and the treatment locations on the treatment pattern may be either contiguous (in a 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 continuous pattern) or not contiguous (spaced treatment locations such as spots or arcs positioned at intervals around the treatment pattern).
  • the predetermined treatment pattern may be one or more treatment patterns that specifically and/or differently target the aqueous production and outflow pathways such as the ciliary body and the trabecular meshwork.
  • the annuli are spaced about 1.5 mm, 2.5 mm and 3.5 mm posterior to the corneolimbal junction to target the outflow pathways at 1.5 mm, the pars plicata at 2.5 mm and the pars plana at 3.5 mm.
  • the 360° pattern may be interrupted to avoid anatomic structures within the eye that could be harmed by irradiation.
  • the pattern is interrupted nasally and temporally, such as by 10-30° nasally and/or 10-30° temporally.
  • a heat sink such as a curved contact lens, is placed in contact with the eye over the treatment locations to conduct heat externally away from the treated surface of the eye.
  • the lens may be a cooled lens that substantially conforms to the surface of the eye, and which is either pre- cooled or cooled in situ while applanated on the surface of the eye.
  • the protective thermal preconditioning and therapeutic bio-stimulation may be controlled by one or more of the laser’s power, irradiance, scanning speed, cycle repetition rate, number of cycle repetitions, spot size and duty cycle.
  • the processor is configured to direct the laser energy to the treatment location in a spot having a diameter of 500-1000 ⁇ m, for example about 600 ⁇ m.
  • the system may also include an optical imaging system for detecting the limbus and/or corneolimbal junction of the subject.
  • the processor may be configured to identify the predetermined treatment locations as determined by the shape and size of the limbus and/or corneolimbal junction of the eye of the subject.
  • the 360° locations identified by the processor may be circular, oval, elliptical, egg-like, non-circular, non-elliptical, asymmetrical or other shapes determined by the anatomy of an individual limbus.
  • the contoured annulus patterned by the shape of the limbus or corneolimbal junction is in effect a larger (such as greater diameter) version of the limbus or corneolimbal junction of the specific subject being treated.
  • Disclosed embodiments of the present method trans-sclerally deliver laser energy, for example near infrared laser energy (such as from a 1.475 ⁇ m IR laser), with low scattering.
  • the laser may be a continuous wave (CW) infrared laser.
  • the laser energy interacts with water- containing cells in the superficial sclera (for example to a depth of 200-500 ⁇ m beneath the surface of the sclera) instead of interacting primarily with pigmented cells in deeper ocular structures such as the trabecular meshwork.
  • water in the cells absorb the laser energy in the superficial sclera, a thermal elevation is created and cell transduction cascades in the deeper ocular structures are affected.
  • the laser energy may be repetitively and specifically applied to the same treatment 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 locations at intervals spaced in time by the period of a treatment cycle to generate a heat wave at each treatment location that propagates three-dimensionally or 360° spherically into deeper scleral layers and to the structures of the aqueous outflow tract and/or the ciliary body.
  • the energy delivery achieves a photo-stimulation therapeutic threshold through a gentle photothermal rise that avoids complications, such as those associated with ALT burns or with SLT’s cavitation interaction.
  • This method avoids the necessity of gonioscopic targeting of the laser to the trabecular meshwork in the iridocorneal angle (FIG.1) and avoids the iatrogenic drawbacks of moving a contact probe over the surface of the eye.
  • the procedure may also be performed under topical anesthesia and without peri-retrobulbar block.
  • the laser continuously irradiates a 360° treatment pattern, or portions of the pattern, in a clockwise direction beginning at 0° and moving in one direction through 360° before beginning and repeating the cycle again. Such a cycle could alternatively proceed in a counter clockwise direction or ping pong around to non-adjacent locations on the treatment pattern to complete the cycle.
  • a laser spot of a specified diameter may sequentially irradiate the target pattern om a ping pong manner at 0°, 180°, 10°, 190°, 20°, 200°, 30°, 210°, 40°, 220°, etc. through an entire 360° pattern to form either a continuous or discontinuous pattern.
  • each cycle irradiates selected treatment locations, and all the treatment locations may be irradiated before proceeding to the next cycle.
  • the plurality of treatment locations on the pattern may correspond to an angle within a range from about 30° to about 360° around a sclera of the eye, for example within a range from about 90° to about 360°, within a range from about 90° to about 150, 160, 170 or 180°, or within a range from about 180° to about 360°.
  • a plurality of treatment locations may correspond to an angle of about 30°, about 45°, about 60°, about 75°, about 90°, about 150°, about 180°, about 270°, or about 360°.
  • the treatment pattern may be a continuous treatment pattern such as an annulus that forms an uninterrupted curve, or a discontinuous treatment pattern having spaces between “dashes” or “spots” of treatment along the treatment pattern.
  • the treatment pattern may be a plurality of treatment patterns, and the plurality of patterns may be overlapping or non-overlapping.
  • the plurality of annuli may overlap to generate a treatment annulus with a width greater than the spot size of the laser energy beam.
  • Non-overlapping annuli will have a pre-determined radial distance between each of the plurality of treatment patterns.
  • each non- overlapping treatment pattern may be a different fixed distance from the corneolimbal junction so that each of the patterns is a limbus contour-guided pattern of different circumference.
  • the scanning speed of circumferential movement of the laser around the treatment pattern to treat all the treatment locations determines the interval between irradiation of each treatment location on the annulus. Movement of the laser during the interval between repetitive irradiations of a specific treatment location fractionates delivery of energy to each treatment location to permit thermal relaxation between irradiation of each treatment location.
  • the total energy delivered to each treatment location may be determined in part by the number of cycles, with total energy being a product of the number of cycles times the energy applied per cycle.
  • FIG.2A schematically illustrates a method of lowering IOP.
  • Laser energy is emitted from a non-eye contacting laser energy source 18 spaced from the surface of the eye and directed toward the corneoscleral junction 20, which is the transition zone between the cornea and the sclera.
  • FIG.2B is an enlarged view of the box in FIG.2A to better illustrate the corneoscleral junction at which the laser energy is directed to propagate heat waves to the underlying trabecular meshwork and other structures of the aqueous outflow tract.
  • FIG.3 is a further enlarged view of the corneoscleral junction 20 where the cornea 22 meets the sclera 24.
  • the limbus 26 which forms the corneoscleral junction is bounded internally (within the eye) by Schwalbe's line (SL) 28 and the scleral spur (SS) 30.
  • Limbus 26 is bounded externally (at the surface of the eye) by the corneolimbal junction (CLJ) 32 and sclerolimbal junction (SLJ) 34.
  • CLJ corneolimbal junction
  • SLJ sclerolimbal junction
  • the CLJ 32 is also known as the apparent or anterior limbus
  • the SLJ 34 is also known as the surgical or posterior limbus.
  • the conjunctiva and capsule of Tenon fuse before inserting approximately 0.5 mm posterior to the CLJ.
  • the underlying ciliary body 36 that produces the aqueous humor is divided into the pars plicata 38 and pars plana 40.
  • the trabecular meshwork (TM) 42 is located around the base of cornea 22, near ciliary body 36, and is part of the apparatus for draining aqueous humor from the eye.
  • Schlemm’s Canal 44 is a circular lymphatic-like vessel around the base of the cornea 22 adjacent trabecular meshwork 42 that is also part of the aqueous outflow tract.
  • the distance from the corneolimbal junction 32 to the sclerolimbal junction 34 is about 2 mm in a typical eye.
  • Irradiating the limbus and/or perilimbal region propagates the heat waves that travel through the sclera to photostimulate most of the structures of the primary aqueous humor outflow pathway, such as the collector channels and/or their ostia, Schlemm’s Canal, the juxtacanalicular TM, Corneoscleral TM and Uveal TM. All these structures lie in the space underneath the limbus.
  • the collector channels and/or their ostia, Schlemm’s Canal the juxtacanalicular TM, Corneoscleral TM and Uveal TM. All these structures lie in the space underneath the limbus.
  • 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 some instances only a single treatment pattern at a distance R 1 posterior to the corneolimbal junction is used.
  • two treatment patterns at R1, R2 posterior to the corneolimbal junction are used to achieve greater spread of the thermal wave to more of the structures of the aqueous humor outflow pathway and/or the aqueous humor production structures (in the ciliary body).
  • three treatment patterns R 1 , R 2 , R 3 posterior to the corneolimbal junction are treated to achieve extensive spread of the thermal wave to the targeted structures of aqueous humor production and outflow.
  • more than three treatment patterns can be used, for example four, five or six treatment patterns each at a fixed distance from the corneoscleral junction.
  • the distances R1, R2, R3 from the corneolimbal junction can be a custom pattern that mimics the often-irregular contour of the corneolimbal junction such that each of R1, R2, R3 are a constant distance from the corneolimbal junction but different distances from the optical axis throughout the 360° of the pattern.
  • the distances R1, R2, R3 are fixed distances from the optical axis throughout the 360° of the pattern such that the treatment pattern has a substantially constant radius.
  • R 1 may have a fixed radius of 7.5 mm from the optical axis to space it on average 1.5 mm from the corneolimbal junction.
  • R2 may have a fixed radius of 8.5 mm from the optical axis to space it on average a distance of 2.5 mm from the corneolimbal junction
  • R 3 may have a fixed radius of 9.5 mm from the optical axis to space it on average a distance of 3.5 mm from the corneolimbal junction.
  • FIGS.3, 4A and 4B show examples of locations where the perilimbal region may be irradiated at distances R1, R2,and/or R3 posterior to the corneolimbal junction 32.
  • R1, R2, and R3 may respectively be about 0, 1.5 and 2.5 mm posterior to the corneolimbal junction 32, or about 1.5 mm, 2.5 mm and 3.5 mm posterior to corneolimbal junction 32.
  • R1 may be 0-2 mm posterior to the corneolimbal junction
  • R 2 may be 2-3 mm posterior to corneolimbal junction 32
  • R3 may be 3-4 mm posterior to corneolimbal junction 32.
  • R2 2.25, 2.5, 2.75, 3.0, or 3.25, or more posterior to the corneolimbal junction
  • R 3 3.5, 3.75, 4.0, 4.25, 4.5, 4.75 mm or more posterior to the corneolimbal junction.
  • R1 is between about 1-2 mm from the corneolimbal junction
  • R 2 is between about 2-3 mm posterior to the corneolimbal junction
  • R 3 is between about 3-4 mm posterior to the corneolimbal junction
  • R1, R2, and R3 are different distances.
  • the anatomy of the eye may be imaged, for example using an operating microscope, to identify the shape of the limbus to overlay a treatment pattern that may then be applied to the eye by automated irradiation of treatment locations at the designated treatment locations.
  • an image analysis software program will recognize the limbus and its anterior margin (the corneolimbal junction).
  • An automated system may be programmed to identify the treatment pattern based on the “custom-limbus” pattern that is posteriorly offset from the corneolimbal junction by a selected constant distance from the corneolimbal junction so that the treatment annulus mimics the actual shape of the limbus of the patient.
  • the shape of the limbus often varies between patients hence customizing the contour of the treatment pattern to the contour of the patient’s limbus improves treatment outcomes and/or avoids side-effects that may be caused by unintentional irradiation of eye structures in patients with unusual eye anatomies.
  • Imaging and automated movement of the laser beam along the treatment pattern for example in a pre-programmed treatment pattern, achieves precise irradiation of sequential treatment locations on the custom limbus pattern.
  • the automated process permits controlled timing of the interval required for the laser to move through the sequential treatment locations to set pre-selected periods of delay before subsequent irradiation of the sequential treatment locations during a subsequent treatment cycle of the cyclic treatment. Since the laser energy is not applied from a contact probe, the laser beam may moved over the sclera or other portions of the eye at a much faster speed than could generally be achieved with a contact and indented probe.
  • Optical coherence tomography (OCT) or high intensity focused ultrasound (HIFU) are examples of imaging modalities used to identify one or more of the targeted structures. For example, the 360° locations of the inner and outer margins of the limbus may be imaged by OCT, as disclosed in U.S. Patent No.9,618,322.
  • treatment locations may be selected on annuli that are offset by the desired distances R1, R2, and/or R3 from that anterior margin.
  • An automated system can then precisely irradiate the treatment annulus or annuli at repeatable locations.
  • the locations R1, R2, and R3 irradiate the sclera overlying different structures of IOP homeostasis, such as the aqueous outflow and production structures.
  • R 1 is positioned to irradiate the primary aqueous outflow pathways
  • R2 is positioned to irradiate the pars plicata ciliary body that produces aqueous humor
  • R 3 is positioned to irradiate the pars plana and the unconventional uveoscleral outflow pathway. Tailoring the locations of the treatment patterns to the specific anatomy of the eye of the subject improve treatment outcomes while 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 reducing the likelihood of complications. The operator may assess the reason(s) for the loss of IOP homeostasis in a particular patient and direct the laser energy to the targeted location(s) that will restore IOP homeostasis.
  • the laser energy and hyperthermic stimulation may be directed at least or exclusively to the ciliary body (such as the pars plicata at R 2 , and/or the pars plana at R 3 ). If the increased IOP is considered to be due to resistance in the conventional or in the uveoscleral outflow pathways, the laser energy and hypothermic stimulation may be directed at least or exclusively to R1. If increased IOP is likely due to both over-production of aqueous and impaired outflow, then both production and outflow pathways may be targeted, for example at R 1 , R 2 , and R 3 .
  • an annular treatment pattern is applied at a distance of about 1.5 mm posterior to the corneolimbal junction, with the treatment locations interrupted to form multiple arcs, such as a superior arc 50 and an inferior arc 52.
  • Each of these illustrated arcs is uninterrupted in that the treatment locations are contiguous and not spaced, but the arcs are separated by temporal and nasal interruptions to avoid irradiation of structures in the region.
  • the contiguous locations are treated by moving a continuous wave laser beam along the arc with the laser on. Interruptions may be formed by turning the laser off and on in pulses to form the non- contiguous treatment locations.
  • the laser beam is circumferentially moved over the superior and/or inferior arcs 50, 52 with steady and repeatable speed by a computer-driven electro-optical scanner that assures consistent and always repeatable treatments with reliable amounts of laser energy deposition.
  • the laser energy is delivered in an arcuate pattern to produce two 150° arcs.
  • the illustrated arcs are continuous except for being interrupted from about 8:30-9:30 o’clock (255° to 285°) and the 2:30-3:30 o’clock (75° to 105°) positions to avoid the long ciliary nerves, minimize pain, and avoid the risk of anterior segment ischemia.
  • annular treatment pattern 54 is applied at a distance of about 3.5 mm posterior to the corneolimbal junction, but in a non-discontinuous pattern which is not divided into superior and inferior arcs.
  • multiple annular treatment patterns are applied at R1, R2, and R 3 in a superior and inferior arc.
  • FIG.4F illustrates a treatment pattern that includes a superior primary arc 56 and inferior primary arc 58, but each of the superior and inferior arcs is itself a series of subsidiary discontinuous arcs that is each irradiated by a laser beam of that path or shape that pulses (on/off) as it moves through arcs 56, 58.
  • the laser beam in this instance does not continuously irradiate the eye along the entire path of superior primary arc 56 or inferior primary arc 58.
  • the sequence of irradiating treatment locations need not always be in a circular direction progressively around the eye.
  • one of the subsidiary arcs in primary arc 56 could be 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 irradiated, followed by irradiation of a subsidiary arc in inferior arc 58, and the irradiation pattern could ping-pong back and forth between the arcs 56, 58.
  • the sequence in which the subsidiary arcs is irradiated would generally be the same in each treatment cycle to set a preselected period during which the desired thermal relaxation can occur at each treatment location before the next irradiation cycle begins.
  • the speed of movement of the laser beam along the arc and/or the use of a pulsed laser can both affect the duty cycle, and selection of a uniform period for each cycle establishes a fixed interval between irradiation of each treatment location.
  • the period of each cycle is the time between beginning a first cycle and starting the next cycle.
  • a uniform period for each cycle may be achieved by moving the laser beam at a constant velocity through the multiple cycles.
  • the laser beam is moved at a sufficient velocity, such as 1-100 mm/s or 1-50 mm/s to achieve the desired thermal preconditioning and relaxation.
  • the velocity is at least 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mm/s.
  • the velocity is no more than 200 mm/s.
  • a period of thermal relaxation at each treatment location is also set by the period of each cycle. For example, in FIG.4G a single cycle is illustrated that begins with irradiation of the eye at the 90° location and continues in a clockwise direction around the eye through the 180°, 270° and 360° locations before returning to the 90° location. The next cycle then repeats that process.
  • This pattern can be repeated, for example, by moving the laser beam of a continuous wave (CW) laser over the surface of the eye at a velocity, such as a preselected constant velocity, in the treatment pattern to set the period of thermal relaxation for each of the treatment locations.
  • the treatment location at 90° will be the first location irradiated in the first cycle, and the first location irradiated in the second cycle and subsequent cycles.
  • the interval between irradiations of the 90° treatment location in this example is equal to the period of the cycle.
  • a cycle begins with the laser irradiating the surface of the eye at 285° and moving along the treatment annulus to the 75° location.
  • the laser is then turned off as the laser moves over the 75° to 105° locations, but the laser is then turned on again from the 105° to 255° locations.
  • the formation of the superior and inferior arcs occurs in one cycle.
  • only one of a superior or inferior arc would be irradiated, and in such an instance the laser may start, for example, at 285° and move to 75° for the completion of one cycle.
  • the next cycle would then begin at 285° and move to 75° for the completion of subsequent cycles, either by continuing the clockwise movement of the laser beam around the eye or by redirecting the laser beam directly from the 75° location to the 285° location.
  • Each movement of the laser through the 360° annular pattern (or treatment of all the locations in the 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 pattern being used) will be one cycle of treatment that can be repeated a desired number of times.
  • the period for thermal relaxation (the period of the cycle) is generally fixed throughout the multiple cycles of irradiation by moving the laser beam at a constant velocity throughout the cycles, however variable intervals may also be used as desired to achieve the therapeutic effect.
  • FIG 4I illustrates yet another example of a treatment pattern that includes multiple arcs of intermediate length around the treatment annulus that are applied in a clockwise fashion.
  • FIG.4J illustrates yet another treatment pattern in which the treatment annulus is made of multiple laser spots or arcs that are applied in a sequential fashion.
  • a first cycle may constitute the completion of the sequence of arcs in FIG.4I or the sequence of laser spots shown in FIG.4J, and subsequent cycles would constitute subsequent scleral irradiation in the same locations and in the same sequence in which they were applied in the first cycle.
  • the described treatment patterns are applied in a clockwise direction, but they may of course also be applied counterclockwise or in other patterns that do not move uniformly in one direction or the other around the eye.
  • FIG.4K which divides the right and left eyes into thirty-six equally spaced 10° segments. Treatment locations may for example be identified at each of the 10° locations or a subset of those locations.
  • FIG.4L schematically illustrates an eye 70 having a cornea 72 and an optical axis OA that passes near the center of the cornea and is normal (perpendicular) to the surface of the cornea.
  • a laser energy source (such as a CW diode laser) 74 is spaced outwardly from eye 70 and directs a laser beam 76 toward the surface of the eye at an angle ⁇ to OA to irradiate the surface of the eye and create a thermal wave that penetrates to the aqueous outflow structures and/or the ciliary body.
  • the laser beam does not continue into the center of the globe, but to illustrate the angle between the laser beam and OA the path of the laser is traced in a dashed line to the center of the eye.
  • the angle ⁇ is 30-50°, for example 35-40°, but the angle at which beam 76 impinges the eye may vary because the therapeutic effect of the disclosed method is achieved by the generation of a heat wave that can nonspecifically propagate through the sclera to heat the aqueous outflow structures and/or the ciliary body.
  • the laser beam therefore need not be aimed directly at a structure to take advantage of the propagated thermal wave.
  • FIG.4M illustrates a laser beam 76 directed at sclera 78 through a heat sink contact lens 80 on the surface of sclera 78.
  • Beam 76 has a width 82 (e.g.600 nm) and beam 76 moves with a 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 selected velocity in a direction of movement 84 to create a heat wave 86 that spreads three- dimensionally in the x-y-z direction through the superficial sclera toward the underlying targets for modulating IOP homeostasis.
  • the heat wave is three-dimensionally propagated to the underlying tissue along the path of the laser.
  • the laser is moved along a pattern shown in any one of FIGS.4C through 4J.
  • the angle of impact with the sclera may be chosen to minimize reflection and scattering of the laser energy and promote effective tissue penetration.
  • the laser impinges sclera at an angle of 90 ⁇ 45° with respect to the eye globe tangent at the point of impingement.
  • a contact lens 80 or the sclera 78 itself can contribute or produce a general direction of propagation of the beam 76 into the sclera 78.
  • Contact lens 80 (FIG.4M) acts as a heat sink that conducts heat away from the surface of the eye.
  • the lens has suitable optical properties to allow visualization of the eye through the lens and also to provide or assist with providing the selected angle of incidence on the sclera.
  • light is directed with a laser scanner (such as a 2-mirror galvanometer scanner) through an objective lens (such as an F ⁇ lens) and parallel to an optical axis of the objective lens to the eye, typically with the OA of the eye collinearly aligned with the optical axis of the objective lens.
  • the sclera and eye have a refractive index (e.g., 1.3-1.5) greater than the refractive index of the air (about 1.0) and the radial position of impingement at the sclera is associated with a tangent that is not perpendicular to the OA of the eye, the incident laser beam, even without the presence of the contact lens 80 is refracted at an angle towards the OA of the eye rather than parallel to it.
  • the contact lens 80 can also assist with this refraction with a preconfigured refractive index or curvature that produces a desired angle of incidence to the sclera for a beam received at the contact lens 80 that is propagating parallel to the OA of the eye.
  • the lens has optical smoothness with maximized transmission of the laser beam, and low amounts of light scatter to permit visualization of the eye, e.g., through a CCD or CMOS camera or through an operating microscope.
  • the lens may be multi-layered and contain for example a layer of graphene to enhance the heat conducting properties of the lens.
  • the lens is also cooled, for example by one or both of pre-cooling or in situ cooling on the eye.
  • a patient interface for performing in situ cooling is described in FIGS.5A-5C.
  • Three-Dimensional Propagation of Thermal Wave over Time 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 Propagation of the thermal wave through a section of the scleral wall over time is further illustrated in FIGS.4N-P.
  • FIG.4N illustrate sequential events caused by laser irradiation on an annulus described by the sliding of a series of interrupted spots from a laser beam moving at a velocity of 50 mm/s across the scleral surface.
  • the laser energy is applied in FIG.4N generally perpendicular to the scleral surface, and as each laser spot is irradiated heat is propagated in a thermal wave below the scleral surface toward deeper structures.
  • FIG.4O shows that the thermal wave propagates deeper into the sclera until it reaches targeted sub-scleral structures such as the trabecular meshwork and ciliary body (inset).
  • the wave recedes again toward the scleral surface as thermal relaxation occurs.
  • FIGS.4Q-4X similarly illustrate propagation and retraction of a thermal wave toward and away from the trabecular meshwork (TM level).
  • TM level trabecular meshwork
  • FIGS.4Q the thermal wave is propagated at the scleral surface by laser irradiation.
  • S, T and U the wave progressively advances over the next 1.64 seconds to penetrate and pass into the TM.
  • FIGS.4V, W and X show a period of thermal relaxation during which the thermal wave moves away from the TM level and back toward the scleral surface.
  • FIG.4Y illustrates that peak temperature increase of irradiated tissues can be controlled by altering the speed of laser movement with respect to the sclera. Peak tissue temperatures increase as the speed of laser movement decreases because more energy is delivered to each irradiated lactation, at a constant laser power and duty cycle, per unit time.
  • the graph shows peak temperature changes in irradiated scleral tissue at a laser power of 0.8W, and a duty cycle of 3.44%, when the laser is moved at 5, 10, 25 and 50 mm/sec through a 200° arc.
  • FIG.4Z illustrates that duty cycle can also be used to control peak tissue temperature in combination with laser speed.
  • peak temperatures were compared at a laser power of 0.8W moving through an arc of 4° with a duty cycle of 11.5% or 172% at a laser speed of 5, 10, 25 and 50 mm/sec. Peak temperature was substantially similar for both duty cycles at 10, 25 and 50 mm/s, but at slow laser speeds of 5 mm/s the peak temperature increased from about 33°C to 37°C.
  • Beam Size The diameter of the laser beam at the surface of the eye is sufficiently large to direct the thermal wave to the targeted aqueous production and/or aqueous outflow structure(s). Beam placement refers to the location of the center of the beam with respect to a reference point.
  • the diameter of the beam may be 500-1000 ⁇ m, such as 600 ⁇ m.
  • a 600 ⁇ m diameter laser beam may be centered on an annular treatment pattern 1.5 mm posterior to the corneolimbal junction to therapeutically stimulate most of the primary aqueous outflow pathway structures with the generated heat and spreading thermal wave.
  • the 600 ⁇ m diameter laser beam may also be projected in an annular pattern with the beam centered 3.5 mm posterior to the corneolimbal junction to target the pars plana unconventional uveoscleral outflow pathway.
  • the 600 ⁇ m diameter laser beam may also be projected in an annular pattern with the beam centered 2.5 mm posterior to the corneolimbal junction to target the pars plicata.
  • the trans-scleral laser cyclic irradiation with a beam of this size causes the localized photothermal elevations that produce biomechanical responses with minute morphologic changes in the microarchitecture of the perilimbal, pars plicata and pars plana regions, with the motion and reorganization of the aqueous humor outflow pathways that enhance both conventional (trabecular meshwork) and non-conventional (uveoscleral) outflows that result in early IOP reduction.
  • the concomitant photo-stimulating hyperthermia (for example to a temperature of 43 – 45°C) without photocoagulation of the sclera leads to heat spread and decay in surrounding tissues to re- equilibrate and return the treatment location toward or to baseline body temperature.
  • the repetitive irradiation and thermal decay triggers bio-chemical responses with a biological cascade of cytokine expression and subsequent endogenous molecular transcriptional activities that contribute to long-lasting IOP lowering effect.
  • the 1.475 ⁇ m IR laser wavelength imparts a safe and effective time- temperature-history profile that lowers IOP through one or more of increased trabecular meshwork outflow (trabeculoplasty-effect); increased uveoscleral outflow effect and decreased aqueous humor production (ciliary processes treatment-effect).
  • Different time-temperature-history profiles can produce photocoagulation, photostimulation and hyperthermia without undesirable tissue coagulation by thermally-preconditioning the scleral tissue to induce thermotolerance.
  • the thermotolerance is a temporary state of resistance to heat-induced cellular death, and the thermotolerance is achieved by the repetitive irradiation of treatment locations at spaced intervals and gradually increasing temperatures.
  • Thermotolerance permits a treatment location to be irradiated repeatedly while minimizing tissue damage to the treatment location.
  • 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 Irradiance, Scanning Speed, Exposure Time, Cycle Repetition Rate The combined therapeutic effect and protective thermal-preconditioning are controlled by a variety of factors that control the temperature generation-re-equilibration photothermal process.
  • the laser beam may be projected through a limbal- guided scanning computer-controlled electro-optical delivery system to irradiate the sclera in the different arc patterns at the different distances posterior to the limbus at programmed scanning speeds (exposure time) and other selected variables to create unique time-temperature histories with photothermal elevations that concomitantly produce IOP lowering biomechanical and biochemical responses.
  • the laser irradiance (power over unit of area in W/cm 2 ) and the scanning circular speed (mm/s) may be selected to create a temperature rise within 8 - 20°C above the 37°C body temperature in the sclera when irradiated by the scanning laser beam, for example a 0.6 mm diameter laser beam.
  • the temperature of the first 200 ⁇ m deep scleral layers can be elevated to about ⁇ 45° - 57°C (37° + 8° or 20°) by controlling laser irradiance (W/cm 2 ) and exposure duration (which is determined by the scanning speed in mm/s and by the number of repetition).
  • the laser power for the first treatment cycle may be set to start at a fraction (such as less than 50%, 40%, 30% or 20%) of the threshold power that would cause an immediate coagulation reaction.
  • the laser power is automatically step raised at each successive cycle (for example to 25% at the 2 nd cycle, to 30% at the 3 rd cycle and to 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% at each successive cycle) to reach the 100% at the 17 th cycle without causing any visible coagulation effect due to the thermo-conditioning process that increases the thermotolerance or resistance to heat cellular death.
  • the targeted peak temperature may be rapidly reached and then decreased to maintain the dwelling period at the peak temperature elevation.
  • the exposure and the heat production are terminated, but the generated heat spreads and decays toward adjacent surrounding cooler tissues in a thermal relaxation process to eventually re-equilibrate with the body baseline temperature (37°C).
  • the exposure duration of each portion of the scleral annulus is about 2- 120 ms, for example 2-20, 10-20, 10-15, 12, 24, 60 or 120 ms.
  • the duration of the irradiation at each point in the middle of the annulus width may depend on the beam circular scan speed: at 1.0 mm/s the irradiation time at each cycle is 0.6 s or 600 ms; at 5.0 mm/s the irradiation time at each cycle is 0.12 s or 120 ms; at 10.0 mm/s, 60 ms; at 15.0 mm/s, 40 ms; at 20.0 mm/s, 30 ms; at 25.0 mm/s, 24 ms; at 30.0 mm/s, 20 ms; at 50.0 mm/s, 12 ms; at 100.0 mm/s, 6 ms; at 300.0 mm/s, 2 ms.
  • heat may also be continuously subtracted from the conjunctival/scleral superficial layers by the heat sink, such as a chilled contact lens that cools, protects, and spares those superficial layers from cumulative thermal damage.
  • the heat sink allows the duration of the temperature elevation to be prolonged for the time needed to permit its decaying heat-wave to reach the deep targets at the selected photo-thermal-stimulation temperature and sustain the propagation of heat waves for the duration required for an effective hyperthermia therapy, for example 25 seconds or more.
  • the system described herein can therefore induce the therapeutic photothermal effects without the use of contact probes having protruding fiberoptic tips that are dragged along the eye to potentially cause discomfort and scratch the sclera.
  • the non-contact laser source may also be moved at a more rapid velocity through the treatment pattern than could generally be achieved with a contact probe moving against the eye.
  • the automated or computer-implemented features of the system also help achieve more consistent treatment that avoids subjective variations in precisely positioning and controlling the speed of laser energy delivery.
  • the trans-scleral cyclic laser therapy does not require retrobulbar block. It is also more efficient because it non-specifically 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 converts electromagnetic energy into heat in cellular water, and not only in pigmented cells.
  • the cyclic laser therapy also produces beneficial photothermal stimulation/hyperthermia by modulating the time-temperature-history of the tissue, for example through computer-controlled laser power, the beam moving speed (laser “ON” exposure time) and the cycle repetition time (Period T and duty factor) and the number of repeated cycles (duration of the sustained hyperthermia).
  • the system includes a patient interface for docking the non-contact laser energy source spaced away from the eye.
  • the patient interface may include a spacer that maintains the eye in a substantially fixed location and/or focal distance for imaging and treatment.
  • the spacer may, for example, be in soft contact with the surface of the eye and maintain the laser energy source spaced from (not contacting) the surface of the eye.
  • the patient interface may further include a speculum for placement between the eyelids of the subject to keep the eye open and better expose the eye (particularly the sclera) to the laser energy.
  • the patient interface includes a lens holder that stably positions a contact lens over the surface of the eye to serve as a heat sink and conduct heat outwardly away from the eye.
  • the lens may be a scleral contact lens that contacts the sclera at the treatment locations.
  • the contact lens holder may also include a fixation ring having a resilient sealing face to seat against the eye, and the system may be configured to maintain adjustable negative pressure within the fixation ring between the eye and contact lens to secure the patient interface to the surface of the eye and substantially immobilize the eye of the subject during the procedure.
  • a positioning arm positions the patient interface at a treatment orientation to the surface of the eye of the subject in a selected treatment orientation.
  • the positioning arm may be driven by an X-Y-Z controller that precisely aligns and registers the spacer and ring in contact with the eye to precisely apply the laser energy to the eye.
  • the spacer and/or fixation ring may be cooled to protect the superficial layers of the sclera from thermal damage during laser irradiation of the eye.
  • internal flow channels are present in the spacer and/or lens holder, and the system is configured to introduce a cooled fluid (such as water or saline solution) through the fluid flow channels to cool the spacer and/or fixation ring and/or contact lens.
  • the spacer can dock to the lens holder for holding a laser output the spaced distance from the contact lens heat sink.
  • the resilient sealing ring on the lens holder which extends around the contact lens to create a sealing chamber between the contact lens and the eye, retains the lens 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 holder against the eye to substantially immobilize the eye when a suction is applied to the sealing chamber or at least neutralize differential movement of the eye with respect to the laser.
  • the sealing chamber under the lens communicates with a suction port through which negative pressure is selectively and/or adjustably applied to the sealing chamber to optionally secure the lens holder to the eye to control eye movement during the procedure.
  • a laser triangulation system provides Z- focus camera viewing of the contact lens, and the X-Y-Z positioner positions the patient interface with the sealing ring of the lens holder against the eye of the subject, with the spacer docked to the lens holder.
  • the patient interface assembly includes a spacer cone, such as a frustoconical spacer that tapers from an enlarged first face to a smaller second face.
  • a laser emission source (such as an objective lens) is carried by the cone and spaced away from the smaller second face.
  • the lens holder is a collar that tapers from a larger first face of similar shape and size to the second face of the spacer with which it docks, to a smaller second face of the lens holder collar that is circumscribed by a resilient patient fixation ring to form the seal against the eye to be treated.
  • the lens holder collar includes an internal cooling fluid passageway, an inlet port and an outlet port for circulating cooling fluid through the collar.
  • the heat sink contact lens is retained in the fixation ring and forms the suction chamber between the contact lens and the eye when the collar is docked against the eye of the subject and air in the suction chamber is withdrawn from the chamber.
  • the suction applied by the suction chamber may be varied depending on clinical circumstances.
  • the vacuum can be very low or not used at all.
  • the blades of the speculum are inserted into the eye to separate the eyelids to expose the sclera.
  • the lens holder is retained between the blades of the speculum and air is optionally suctioned from the sealing chamber.
  • the X-Y-Z positioner is adjusted to dock the spacer to the lens holder, and cooling liquid is introduced through the internal cooling channels of the lens holder via the fluid inlet and outlet ports.
  • the contact lens and eye may be viewed with optical viewing software and a laser treatment of the eye performed through the patient interface, with the laser held in a spaced relationship to the sclera.
  • the spacer permits therapeutic laser energy to be applied to the eye from a laser energy source spaced from the surface of the eye.
  • a patient interface 100 docks the laser treatment device to an eye to be treated.
  • Interface 100 includes a spacer 102 and lens holder 104.
  • the lens holder 104 is configured to retain a heat sink, such as an ophthalmic contact lens 106 against the surface of an eye to be 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 irradiated.
  • the lens has a radius of curvature of about 11.5 mm and a diameter of about 15-20 mm.
  • the lens may be a scleral lens that has an apical clearance of the cornea (for example a 1 mm apical clearance), and the peripheral edge of the lens seats against the sclera.
  • the lens vaults over the eye to form a suction chamber.
  • a resilient sealing ring 120 circumscribes the peripheral edge of contact lens 106 to establish a seal between contact lens 106 and the surface of an eye to which contact lens 106 is applied.
  • the radius of curvature of lens 106 may be greater than the radius of curvature of the cornea over which it is placed so the lens 106 vaults over the eye to form a suction chamber 123 within sealing ring 120 between contact lens 106 and the surface of the eye to which contact lens 106 is applied.
  • a small central hole 122 in contact lens 106 permits air and tear fluid to move through lens 106.
  • a suction passageway 124 extends through a wall of lens holder 104 and communicates with an external suction port 126.
  • Hole 122 in lens 106 permits air to pass into sealing chamber while still maintaining the negative pressure in the sealing chamber.
  • a video camera displays docking contact proximity by triangulating on hole 122 with two low power laser spots as they converge displaying approaching proximity sensing of cone contact lens to patient eye.
  • the triangulation laser spots generated by laser emitters 128 are coincident at the contact lens center in the treatment eye focus-plane.
  • the inner face of contact lens 106 that is placed against the eye may be a graphene face to enhance the heat sink properties of the lens, as disclosed in greater detail in US 2018/0177632.
  • Spacer 102 is secured to a control box 118 containing a laser source that is controllable to target laser beam 82 (FIG.4M) through the chamber within spacer 102 and toward contact lens 106.
  • Laser beam 84 may be controlled, for example, to move it through an arcuate path 84 (FIG.4M and FIG.8A) that directs laser energy toward the eye to irradiate the eye in the annular treatment pattern.
  • Laser beam 84 passes through contact lens 106 to induce a targeted hyperthermia with the selected time-temperature history response in the sclera and/or in the retina of the treated eye that propagates the thermal wave to adjacent tissues in the eye. Angles of incidence can depend on the selected treatment locations.
  • impingement of a treatment beam at the sclera can be normal to the tangent of the sclera (or otherwise at an angle that is not parallel to the optical axis of the eye) and impingement of a treatment beam that passes trans-pupillary through the pupil will generally propagate parallel 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 to the optical axis (or close to parallel) to treat pan-macular annuli concentric to the foveal avascular zone or other fundus features.
  • a common lens can be used for beam delivery or alternative lenses may be used in some examples, in providing a larger angle of incidence at scleral treatment locations.
  • a mirror surface similar to a gonioscopy lens delivery configuration may be used to provide ab externo delivery to the sclera, such as by having a conical reflective inner surface of the patient interface 100 (such as with the conical spacer 154 discussed below).
  • Interface 100 may also include an eye speculum 132 (FIGS.6A and 6B) that includes a pair of opposing plastic arms 134, 136 that are joined at a flexible pivot point 142 that biases arms 134, 136 to the open positions shown in FIGS.6A and 6B.
  • the unjoined open ends of arms 134, 136 each carry curved a speculum blade 138, 140 that are configured to fit within the palpebral fissure of the eye.
  • Speculum 132 is sufficiently flexible about pivot point 142 that the speculum arms 134, 136 may be moved toward one another to narrow the distance between blades 138, 140 and facilitate insertion of the speculum into an eye to better expose the sclera that is to be irradiated.
  • the outward bias of arms 134, 136 will return the arms to the open position shown in FIGS.6A and 6B to maintain exposure of the targeted eye tissue to be treated.
  • Different size speculums may be used to open the eyelids to a preselected distance, for example 20 mm, 22 mm or 24 mm at the point of greatest separation between the eyelids.
  • Speculum 132 is also configured to conform to and secure collar 104 between blades 138, 140.
  • collar 104 includes a substantially cylindrical top portion 144 and a substantially cylindrical lower portion 146 joined by an angled shoulder 148 that narrows the inner diameter of collar 104 from the top portion to the bottom portion.
  • Internal fluid passageway 108 extends circumferentially around top portion 144.
  • Resilient sealing ring 120 seats in a circumferential recess on the inner face of lower portion 146 to hold heat sink contact lens 106 centered in the lower open face of collar 104, with central hole 122 of the contact lens substantially at the center of the face.
  • FIG.6D is an exploded view of interface 100 that shows how spacer 102, collar 104 and speculum 132 are assembled.
  • Collar 104 is placed between blades 138, 140 of speculum 132 and the inner faces of the speculum blades conform to the external cylindrical surface of lower portion 146 of the collar to engage and retain the collar between the blades. Spacer 102 may then be docked against collar 104.
  • An example of spacer 102 in FIG.6D has a shape that tapers from an open top face circumscribed by circular lip 150 to a narrower bottom face circumscribed by a circular lip 152 that mates with top portion 144 of collar 104.
  • Spacer 102 includes an upper generally cylindrical collar 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 152 joined to a frustoconical middle section 154 that tapers to a docking section 156 from which depend snap-fit members 158 to engage the inner face of portion 144 of collar 104 and retain spacer 102 in selective engagement with collar 104.
  • Snap-fit members 158 are coupled to complementary members inside collar 104 for releasably interconnecting spacer 102 and collar 104 with a compression fitting for conveniently connecting and disconnecting the spacer and collar.
  • FIG.6E is an enlarged view of collar 104 with the peripheral edge of contact lens 106 seated in an internal lip of collar 104 with central hole 122 centered in collar 104.
  • Suction chamber 123 is formed below contact lens 106, and chamber 123 communicates with suction line 124 through an opening in collar 104 below the peripheral edge of contact lens 106.
  • External suction port 126 draws a suction through line 124 to establish suction between contact lens 106 and the surface of the eye to retain collar 104 and patient interface 100 relatively immobile against the eye.
  • FIG.7A illustrates speculum 132 positioned in the palpebral fissure 158 of a subject to expose sclera 24 for treatment.
  • FIG.7B shows assembled interface 100 with spacer 102 docked against collar 104, and collar 104 itself retained between blades 138, 140 of speculum 132 with contact lens 106 placed against the surface of the eye (for example the cornea and/or sclera).
  • Interface 100 substantially immobilizes the eye of the subject being treated to inhibit differential motion of an eye with respect to a laser beam directed toward the eye from a laser energy source 74 spaced outwardly from the surface of the eye. Control of eye movements is particularly effectively achieved by suctioning air from the suction chamber within sealing ring 120 below contact lens 106.
  • Suction may be guided by clinical circumstances.
  • the procedure may be performed without suction or with suction.
  • the negative pressure in the suction chamber is controlled for example to under 35 mm Hg.
  • gentle levels of suction are preferred that do not increase IOP by more than 5 mm Hg.
  • Central hole 122 of contact lens 106 permits an inflow of air into the suction chamber to help regulate the pressure in the suction chamber in combination with the outflow of air from the chamber induced by the applied suction.
  • the patient interface 100 improves detection of the limbus and/or corneolimbal junction with an optical imaging system.
  • Differential movement of the eye with respect to the laser beam may be minimized by also using patient interface 100 (FIG.8A) to control relative movement of the eye to avoid interfering with targeted delivery of the laser energy.
  • the resilient sealing face of sealing ring 120 is seated against the eye and suction is drawn between lens 106 and eye 70 to 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 minimize the differential eye movement.
  • Patient interface 100 may also maintain the non-contact laser energy source or optic 74 at a predetermined distance from and not contacting the surface of eye 70.
  • the laser energy may be trans-sclerally delivered by the patient interface under spatial and temporal processor control while cooling the surface.
  • a method is performed with a computer-driven electro-optical scanning beam delivery system 200 (FIG.8B) designed for limbus- guided non-contact trans-scleral cyclo-deposition of infrared (I.R.) electromagnetic energy (for example 1.475 ⁇ m laser energy) in arcuate or circumferential arc patterns at selectable scleral meridian positions posterior to the anterior (apparent) limbus over i) perilimbal outflow structures (collector channels, Schlemm’s canal, trabecular meshwork); ii) pars plicata ciliary body; and iii) the pars plana uveoscleral region.
  • I.R. infrared
  • electromagnetic energy for example 1.475 ⁇ m laser energy
  • the scanning speed is adjustable, for example within the range of 0.1 – 50 mm/s.
  • the amount of infrared laser energy delivered may be titrated with the laser irradiance (W/cm 2 ) and the exposure duration (by controlling the cyclic scanning rotational speed in mm/s) to produce localized photo-thermal elevations, which are non-coagulative, but that may induce biomechanical responses with minute morphologic changes to the microarchitecture of the perilimbal, pars plicata and pars plana regions, that result in reorganization of the aqueous humor (AH) outflow pathways that enhance both conventional (trabecular meshwork) and non- conventional (uveoscleral) outflows.
  • AH aqueous humor
  • FIG.8B shows a representative optical system 200 that is configured to direct a laser beam to a targeted surface of eye 70 and rapidly move beam (as in FIG.4M or 8A) in rotational or other cycles around the optical axis OA of eye.
  • the optical system may be a digital Galvano scanner system, such as one from Canon in which an LED optical encoder (digital position sensor) and high-speed digital servo controller scans a laser beam across the eye with high precision and accuracy.
  • the movement of the scanned beam may, for example, be in a clockwise or counterclockwise movement inside interface 100.
  • Optical system 200 of FIG.8B produces an optical beam 202 from an optical beam source 206.
  • Optical beam source 206 includes one or more laser sources, such as one or more semiconductor diode lasers, fiber lasers, solid state lasers, frequency changing nonlinear optical materials (e.g., frequency doubling), etc.
  • optical beam 202 has a predetermined wavelength (corresponding to one or more specific wavelengths and/or wavelength ranges) that is selected to be in the infrared region of the optical spectrum of about wavelength of 800-2200 nm or 1000-2200 nm, such as 1000 to 1700 nm or 875 nm to about 2100 nm, for example 1000 to 2100 nm.
  • the predetermined wavelength of optical beam 202 is selected to produce the trans-scleral therapeutic hyperthermia already described.
  • the predetermined wavelength may be selected to be sufficiently long that the optical beam 202 is absorbed by water in the scleral cells of eye 104, to a greater extent than would occur with shorter wavelengths such as 808 nm, 650 nm, 532 nm, 355 nm.
  • optical beam 202 has a wavelength at 1475 nm and is generated in optical beam source 206 with a 1475 nm diode laser. The increased absorption at the longer predetermined wavelengths can allow the optical beam 202 to be directed to the eye target 70 through an offset 208 (e.g., free space) between a focusing lens 220 of the optical system 200 and target eye 70.
  • optical beam 202 is emitted from optical beam source 206 as a collimated beam propagating along an optical axis 210.
  • a lens group 212 is configured to adjust beam characteristics, such as beam area, divergence, convergence, etc.
  • a beam width shown generally in relation to side rays 213a, 213b can be adjusted with lens group 212.
  • Optical beam 202 is received by an optical scanner 214 that is configured to vary the direction of optical beam 202 and can, for example, move the beam in a rotary movement within interface 100.
  • optical scanner 214 deflecting optical beam 202 along three optical beam paths 216a, 216b, 216c.
  • Reflective element 218 is situated to redirect beam paths 216a-216c of optical beam 202.
  • a beam splitting element 219 is situated to receive optical beam 202 and pass optical beam 202 to a focusing lens 220, which can include one or more lens elements.
  • a camera 222 is also coupled to the optical system 200 by the beam splitting element 219.
  • a surface 224 of the beam splitting element 219 can include a wavelength-selective coating that is configured to receive illumination from the eye target 70 through the focusing lens 220 and to direct the illumination to a reflective element 226 that directs the illumination to the camera 220 to image eye target 70.
  • Optical scanner 214 can be of various types that are suitable to scan an optical beam relative to eye target 70, including XY galvo scanners, 3D scanners, electro-optic scanners, or acousto-optic scanners.
  • a controller 228 can be coupled to the optical beam source 206, optical scanner 214, and/or camera 222 to coordinate and control emission of optical beam 202 from optical beam source 206, scanning of the optical beam 202 with the optical scanner214, and alignment of the optical scanner 214 relative to the eye target 70 or other process monitoring of the eye target 104.
  • Controller 228 typically includes a processor and memory that can store scan files, laser parameters, and software for aligning and/or laser processing eye targets.
  • the controller 228 can be of various types, including one or more computing devices, computing units, PLCs, PALs, ASICs, etc.
  • the memory can include volatile memory, such as registers, cache, and RAM, as well as non-volatile memory, or a combination.
  • the memory is accessible by the processor (or processors) of the controller and can store the software in the form of computer-executable instructions that can be executed by the processor.
  • the controller 228 can be distributed between different components (such as between the optical beam source 206 and the optical scanner 214), and in some examples communication is not required between all components.
  • optical beam 202 is a continuous-wave beam that is focused or defocused to a selected spot size at a predetermined position that is radially spaced outward from a corneolimbal or corneoscleral junction of eye 70.
  • optical beam 202 is directed along the optical beam paths 216a, 216c to positions at eye target 70 that are radially spaced outward from the corneolimbal or corneoscleral junction, and the optical beam path 216b at eye target 70 can also understood to be radially spaced outward from the corneolimbal junction if the position is sufficiently below or above the plane of the figure.
  • the controller 228 controls the optical scanner 214 to scan the optical beam 202 in a cyclical annular pattern radially spaced outward from the corneal-scleral junction.
  • the scanning of the optical beam 202 produces a selected duty cycle of heating at sequential azimuthal positions of the annular pattern at the eye target 70 so that thermal relaxation can occur between scan cycles.
  • Unexpected lens slippage and/or eye movement may be detected by the camera software.
  • the camera display at Z-focus provides added assurance of alignment.
  • interface 100 may be suspended from and positioned by control box 118 that includes a handle 172 on a side face of the box for manually moving or positioning the 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 unit, a tubing clamp 174 for suspending tubing without inducing torque on interface 100, and a peristaltic pump 176 (such as a Welco Ultra pump) for controlled movement of cooling liquid from a source 178 of cooled liquid, such as sterile saline or water, for example phosphate buffered saline (PBS).
  • a source 178 of cooled liquid such as sterile saline or water, for example phosphate buffered saline (PBS).
  • the illustrated pump 176 may move the cooling fluid at up to 100 ml/min, but generally the peristalic flow rates are controlled to about 50 ml/min to cool the contact lens 106 in holder 104 as the cooled liquid moves from source 178 through tubing 180 and pump 176.
  • Contact lens fogging can be minimized with the coolant liquid temperature set to about -10 °C.
  • the lens heat capacity requirement is determined by thermal profiling of the material of the lens, such as a PMMA or BK7 lens.
  • pump 176 moves cooled liquid from control box 118 to interface 100 through an inlet line 182 that communicates with inlet port 110 to move the cooled liquid through channels 108 in lens holder 104 to cool lens 106 in situ.
  • Control box 118 may include a laser support structure (not shown), such as that disclosed in US 2018/0177632.
  • the laser support structure may include one or more channels accommodating one or more optical fibers or light source cables.
  • An optics tray may support one or more optical components that direct one or more lasers to a surface of eye 70, as described for example with respect to FIG.8B.
  • One or more optical components may also be contained within interface 100 to illuminate the eye.
  • Control box 118 may be suspended from a positioning arm, such as an X-Y-Z positioning arm 186 (FIG.9C) that may be computer-controlled for precise placement of the control box 118 and interface 100.
  • Arm 186 is secured to box 118 by a flange 188 that has positioning knobs 190 that can be loosened to move flange 188 in a horizontal plane.
  • Patterned Energy Delivery System and Processor For any of the desired treatment patterns, a processor may be coupled to the laser energy source and the scanner and configured with instructions to heat tissue at the plurality of treatment locations, providing an automated or computer-implemented treatment method that more precisely delivers energy to the preselected treatment locations.
  • FIG.10A illustrates a system 600 for patterned delivery to an eye 602, in accordance with embodiments.
  • the system 600 includes a processor 604 having a tangible medium 606 (e.g., a RAM).
  • the processor 604 is operatively coupled to a first light source 608, an optional second light source 610, and an optional third light source 612.
  • the first light source 608 emits a first beam of light 614 that is scanned by X-Y scanner 616 through an optional mask 618 and optional heat sink 620 onto the eye 602.
  • the mirror 622 directs light energy from the eye 602 to a viewing camera 627 coupled to a display 628.
  • An independent non-treatment light source for the optional viewing camera can be provided, for example.
  • the mirror 622 may direct a portion of the light beam returning from eye 602 to the camera 627, for example.
  • the second light source 610 emits a second beam of light 630 that is combined by a first beam combiner 632 with the first beam of light 614 prior to passing through X-Y scanner 616.
  • the third light source 612 emits a third beam of light 634 that is combined by a second beam combiner 636 with the second beam of light 630 prior to passing through the first beam combiner 632.
  • the processor may be configured with one or more instructions to perform any of the methods and/or any one of the steps and sub-steps of the methods or treatments described herein.
  • the processor may comprise memory having instructions to perform the method, and the processor may comprise a processor system configured to perform the method for example.
  • the processor comprises array logic such as programmable array logic (“PAL”) configured to perform one or more steps of any of the methods or treatments described herein, for example.
  • PAL programmable array logic
  • the processor may comprise one or more instructions of a treatment program embodied on a tangible medium such as a computer memory or a gate array to execute one or more steps of a treatment method as disclosed herein.
  • the processor may comprise instructions to treat a patient in accordance with embodiments described herein.
  • the processor may be configured with instructions to determine one or more locations of the limbus, and/or one or more locations of the corneolimbal junction. In response to the determined location of limbus, for example, one or more locations of the corneolimbal junction may be determined.
  • the processor may be configured with instructions to determine a treatment pattern based on the one or more locations of the limbus and/or the one or more locations of the corneolimbal junction.
  • the treatment pattern may for example comprise a treatment pattern that is spaced one or more of 1.5 mm, 2.5 mm and 3.5 mm from the corneolimbal junction.
  • the processor 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 may be configured to deliver non-coagulative energy to the treatment locations on the treatment pattern to induce the thermal effects described herein.
  • the optical delivery system may comprise one or more of the first light source, second light source, third light source, X-Y scanner, optional mask, or a heat sink. The energy is directed by the automated optical energy delivery system to achieve repeatable heating of the same locations during repetitive cycles of heating.
  • the beams of light 614, 630, and 634 can be scanned onto the eye 602 at a specified X and Y position by the X-Y scanner 616 to treat the eye 602.
  • An optional mask 618 can be used to mask the light applied to the eye 602, for example, to protect masked portions of the eye 602 while treating other portions as described herein.
  • An optional heat sink 620 can be placed on the eye 602 during treatment to avoid heating specified portions of the eye 602, as described herein.
  • the system 600 can be used to apply light energy to the eye 602 in accordance with any suitable treatment procedure, such as the embodiments described herein.
  • the first light beam 614 has a first wavelength
  • the second light beam 630 has a second wavelength
  • the third light beam 634 has a third wavelength.
  • Each wavelength can be the same or a different wavelength of light.
  • the processor can be coupled to each of the light sources to selectively irradiate the eye with light having wavelengths within a desired range of wavelengths.
  • the software may comprise instructions of a treatment table so as to scan the laser beam to desired treatment locations as described herein, for example.
  • the laser system 600 may comprise an OCT system 625, such as a commercially available OCT system.
  • the OCT system may for example be a CASIA2 or CASIA SS-100 OCT scanner (TOMEY).
  • the OCT system may for example be a commercially available OCT system such as one sold by Tomey, Heidelberg, Visante, or Optovue.
  • the OCT system can be coupled to the viewing optics and laser delivery system with a beam splitter 626.
  • the viewing optics may for example comprise an operating microscope (such as one sold by Zeiss, Haag Streit, Leica, or Moller Weidel), a slit lamp, or other custom optics.
  • the OCT system can be used to measure the eye in situ during treatment.
  • the OCT system can be used to generate OCT images as described herein in order to generate tomography of the eye to determine the location of target tissues, movement of target tissues, and stretching of target tissues as described herein.
  • the OCT system 625 can be coupled to processor 604 and used to control the laser system with a feedback loop, for example.
  • Ophthalmoscopes or other suitable eye imaging devices can be used to generate images of the exterior and/or interior of the eye, and can include imaging detectors such as CCD or CMOS detectors. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024
  • the processor can be configured with instructions to scan the laser beam on the eye in accordance with the treatment patterns and parameters as described herein.
  • FIG.10B shows another embodiment of a treatment system which may be used for any of the treatment methods described herein.
  • the system may comprise a laser scanner (such as that shown in FIG.8B) which directs and scans laser energy from a continuous wave or pulsed laser to one or more locations on or inside the eye.
  • the scanner may be coupled to a patient interface or patient coupling structure as described herein.
  • the scanner may further be coupled to an imaging system, for example a camera, OCT, UBM, ophthalmoscope, etc., as described herein.
  • the imaging system may be used to capture one or more images of the eye before, during, or after treatment as described herein.
  • a processor or controller may be coupled to the energy source (such as the laser) and the imaging system and be configured with instructions to scan the energy beam to a plurality of locations or in one or more patterns and image the tissue during treatment.
  • the system may also comprise a display coupled to the processor that allows the user to visualize the tissue prior to, before, or after treatment.
  • the display may show images that allow the user to see the tissue treated and plan the treatment. Images shown on the display may be provided in real-time and can be used prior to treatment to allow the user to align the tissue and/or select a treatment zone or pattern to target. Identified target treatment zones may be input by the user to program the treatment depth, location, and pattern in response to the images shown on the display.
  • the imaging system can be used to visualize movement of ocular structures during treatment in order to detect beneficial treatment effects.
  • the glaucoma treatment systems described herein may simultaneously provide imaging guidance, quantitative characterization of the tissue (for example measuring mechanical properties such as elasticity or the presence of tissue coagulation), and/or perform therapeutic tasks.
  • the treatment system described herein may comprise two or more lasers.
  • the processor may be configured with instructions to treat the eye with a first wavelength of light at a first location (or plurality of locations) and a second wavelength of light at a second location (or plurality of locations).
  • the treatment system described herein may comprise one or more lasers within a range of about 1.0 ⁇ m to about 2.2 ⁇ m, about 1.4 ⁇ m to about 1.5 ⁇ m, for example about 1.47 ⁇ m.
  • FIG.11 shows an image of an ex vivo porcine eye taken with a camera after docking the patient interface and system to the eye.
  • the limbus was clearly visible for use to pattern glaucoma treatment relative to the location of the limbus or corneolimbal junction.
  • Patterning may be 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 selected manually by the user (e.g. medical professional) or the patterns may be determined automatically (or semi-automatically) by the system based on an estimated location of the limbus, or other fiducial of interest.
  • the location of the limbus may be estimated manually by the user or determined automatically through imaging and feature detection.
  • the location of the limbus may for example be “tracked” automatically by the system using a camera and/or other imaging system such as OCT as described herein.
  • the location of the limbus may comprise a complete, annular outline of the limbus or may comprise multiple locations along the limbus which may be used as reference points for determining the shape of the limbus and/or where treatment should occur (i.e. an incomplete outline of the limbus).
  • Identification of one or more locations of the limbus as described herein may be used to estimate one or more treatment locations.
  • the anterior border of the limbus may be used as a surrogate for the corneolimbal junction 32. Alternatively, or in combination, one or more locations of the corneolimbal junction 32 may be estimated from one or more OCT slices.
  • a single OCT image taken through the center of the eye may be used to identify two locations of the corneolimbal junction (one on either side of the eye) and the treatment locations/pattern may be determined in response to the two corneolimbal junction locations identified.
  • multiple OCT images may be taken at different angles relative to the center of the eye and a plurality of the corneolimbal junction locations may be identified and used to estimate the shape of the corneolimbal junction.
  • FIG.12A shows one such imaging scheme which may be used to estimate the shape of the corneolimbal junction.
  • Multiple OCT images may be taken across the center of the eye at varying angles and the one or more location of the corneolimbal junction may be estimated from each image.
  • the locations may then be used to estimate the shape of the corneolimbal junction using partial 3-D reconstruction.
  • the location and/or shape of the corneolimbal junction may be estimated in response to a plurality of limbus locations of the eye.
  • an image e.g. an anterior image of the eye
  • the locations of the limbus, or plurality of limbus locations may be determined, based on the image of the eye. For example, by detecting changes in intensity in the anterior image (e.g. across the image, over a series of images, etc), the location of a plurality of limbus locations may be determined.
  • one or more processors may be utilized to analyze the image to determine the limbus locations. Based on the plurality of limbus locations, a plurality of the corneolimbal junction locations may be estimated substantially as described throughout.
  • Suitable techniques for automated image analysis include automated digital image processing techniques, including 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 machine learning, object identification algorithms, pattern recognition algorithms, video tracking algorithms, convolutional neural networks, etc.
  • FIG.12B shows an example of an automated process 1200 for determining treatment locations.
  • an image of the eye is obtained with a suitable imaging device, and at 1204, image features in the image are analyzed with digital image processing techniques, such as through any of the digital image processing techniques described herein.
  • suitable treatment locations are determined relative to the features in the image. For example, where anatomical features are found, such as a corneolimbal junction in trans-scleral treatment examples or fundus features like the macula or optic disk in trans-pupillary examples, suitable treatment locations can be determined relative to and based on the found features.
  • the treatment locations can be converted to suitable laser scanner commands for an aligned and calibrated laser scanner and a scanner command table that maps scanner command values to one or more scanning planes, surfaces, or volumes.
  • FIGS.13A-13D show an example of a process for generating a treatment pattern based on one or more locations of the limbus.
  • FIG.13A shows an anterior image of an eye taken with a front camera of a CASIA2 OCT system.
  • the anterior image of the eye may be transferred to the processor for detection of the limbus edge.
  • FIG.13B shows the image after processing to determine the boundaries (edges) of the limbus.
  • the portion of the eye within the limbus has been colored white while the portion of the eye outside the limbus has been colored black.
  • This black and white image may then be used to generate X-Y coordinates of the edge of the limbus.
  • the processor may then use the X-Y coordinates to generate an outline of the limbus which may be overlaid onto a real-time image of the eye shown on the display as shown in FIGS.13C.
  • the X-Y coordinates may be registered with the real-time image of the eye such that the limbus shown on the display and the X-Y coordinate generated limbus outline are co-aligned.
  • Treatment patterns can also be automatically generated based on the outline. Where arcs are formed, treatment patterns can be generated using the orientation of the patient so as to align the arcs relative to superior/inferior directions or selected azimuths.
  • posterior trans-pupillary images can be taken using the CASIA2 OCT system or another camera, and anatomical feature boundaries determined so that laser scanning coordinates may be generated relative to the anatomical feature boundaries.
  • the image may also display fiducials with reference to the center of the eye to aid in centration of treatment, for example circles displayed radially outward every 5 mm from the center of the eye.
  • the processor may further use the X-Y coordinates and/or the generated outline of the limbus to determine a treatment pattern, for example a series of limbus-guided treatment locations. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 It will be understood by one of ordinary skill in the art that during use the limbus outline and/or treatment patterns may be registered to one another (i.e.
  • FIG.14 shows a method for determining a target treatment location.
  • the method may use one or more of the systems described herein.
  • an anterior image of the eye may be obtained by a camera or video recorder.
  • a posterior image may be taken.
  • the image of the eye may be displayed to a user as described herein, though in some examples image display for a user or user-intervention based on the obtained image is not needed.
  • one or more images of the eye may optionally be obtained.
  • a plurality of locations of the corneolimbal junction may be determined from the anterior image of the eye, the one or more OCT images of the eye, or any combination thereof.
  • a plurality of locations of macular features such as a foveal avascular zone, optic nerve, etc., are determined from a posterior image, OCT image, or combination.
  • the plurality of locations of the corneolimbal junction or macula may be estimated manually by the user or automatically by the processor.
  • the plurality of the corneolimbal junction locations may optionally be registered with a corresponding plurality of anterior or posterior image locations.
  • a plurality of treatment locations for the eye may be determined in response to the plurality of locations of the corneolimbal junction or macular features.
  • the plurality of treatment locations may be determined manually by the user or automatically by the processor.
  • the treatment locations may be overlaid onto the anterior image shown on the display, though such display may be omitted in automated or streamlined processing.
  • the treatment locations may optionally be adjusted or approved by the user.
  • treatment energy may be directed to the treatment locations displayed on the image by a laser source and scanner as described herein.
  • the laser source includes a plurality of lasers operating at different wavelengths or suitable for operating in selected modes (such as pulsed, continuous-wave, or with selected pulsed characteristics, such as repetition rate, pulse duration, power, pulse energy, etc.).
  • the treatment may be viewed and/or automatically monitored in real-time at the treatment locations to adjust or halt treatment if movement of the eye occurs.
  • a processor may be provided that is configured with instructions for performing the series of steps illustrated in FIG.14.
  • the processor may provide instructions to obtain an anterior and/or posterior image of the eye.
  • the image of the eye may be obtained 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 with a camera with aid of the processor.
  • the processor may be configured with instructions for receiving an image of the eye.
  • the processor may provide instructions to display one or more of the images of the eye.
  • the processor may provide instructions to obtain OCT image(s) of the eye.
  • the processor may provide instructions to determine a plurality of locations of the corneolimbal junction of the eye.
  • the processor may estimate in some instances the plurality of the corneolimbal junction canal locations in response to the anterior image of the eye and/or the plurality of retinal locations in response to the posterior image of the eye.
  • the processor may estimate the plurality of Schlemm’s canal locations, retinal locations, or other ocular locations, in response to the plurality of OCT images of the eye.
  • the processor may be configured with instructions to generate a plurality of treatment locations.
  • the processor may be configured with instructions to generate the plurality of treatment locations for the eye in response to the plurality of the corneolimbal junction locations.
  • the processor may provide instructions to overlay treatment locations on the anterior and/or posterior images of the eye.
  • the processor may be configured with instructions to overlay the plurality of treatment locations and the plurality of the corneolimbal junction locations on the anterior image of the eye.
  • the processor may be further configured to register the plurality of locations of the corneolimbal junction with a corresponding plurality of anterior image locations.
  • the processor may be further configured with instructions to overlay the plurality of treatment locations and the plurality of retinal locations on the posterior image of the eye, and the processor may be further configured to register the plurality of locations of the retina with a corresponding plurality of posterior image locations.
  • the processor may provide instructions to direct treatment energy to treatment locations on the display.
  • the processor may be configured with instructions to alternate treatment at a first plurality of treatment locations with treatment at a second plurality of treatment locations.
  • the processor may be configured with instructions to generate a treatment table that includes a plurality of coordinate reference locations corresponding to the plurality of treatment locations overlaid on the anterior and/or posterior images.
  • the energy source directed to the eye may comprise a pulsed laser source wherein each of the plurality of coordinate references corresponds to a pulse from a laser source.
  • the processor may provide instructions to display treatment in real-time at the treatment locations. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024
  • FIG.15 schematically shows an example of a human eye including the cornea, lens, iris, and pupil structures near the anterior surface of the eye, and the retina, macula, and optic nerve towards the posterior pole of the eye.
  • FIG.16 shows the central retina of FIG.15 within the vascular arcades, including the darker macula portion near the center.
  • the sclera of the eye (adjacent to the cornea) is targeted for irradiation with a 1475 nm trans- scleral laser beam with a selected set of trans-scleral laser and scan parameters for IOP lowering treatment, and/or the retina of the eye, for example macula, is targeted for irradiation with an 810 nm separate set of trans-pupil laser and scan parameters for panmacular neuroprotective therapy, thereby inducing sublethal and therapeutically advantageous biomodulation or biostimulation of eye tissue in one or both places, e.g., during a complete treatment window or instance.
  • Therapeutic benefits can include reduced intraocular pressure (IOP), neuroprotection, and comprehensive management of glaucoma such as open-angle glaucoma.
  • Biomechanisms the central retina of the eye can receive sublethal laser photostimulation, for the treatment chronic progressive neurogenerative vascular retinopathies and of other disorders, such as POAG, that share similar common characteristics.
  • Sublethal non-damaging laser photostimulation of the central retina targets the retinal pigment epithelium (RPE) cells with subthreshold laser energy so as to trigger a stress response.
  • RPE retinal pigment epithelium
  • the stress response can be configured to activate a cascade of molecular cellular biochemical activities that can rebalance pathological retinovascular neuro-trophic deficiencies preventing and possibly reversing progressive apoptotic processes (i.e. the loss of retinal ganglion cells in POAG).
  • laser parameters are selected such that energy is delivered in patterns configured to produce biological effects in a photo-thermal-stimulation therapeutic window that is above an activation threshold but 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 below a lethal threshold (e.g., between 44 °C and 50 °C).
  • various parameters are selected to recruit and activate in a pathoselective manner a large amount, and preferably the highest possible number of, RPE cells for the biological photo-stimulation process.
  • Such photo-thermal-stimulation can be configured so as not to harm or have an effect on normal healthy RPE cells but activates endogenous reparative and/or regenerative processes that selective affect and improve only dysfunctional RPE cells according to their specific dysfunction.
  • a primary response to RPE sublethal photostimulation is understood to be the activation of heat shock proteins (HSPs) and of cytokine expression, which triggers a cascade of events leading to RPE cellular repair, replacement and regeneration.
  • HSPs heat shock proteins
  • cytokine expression which triggers a cascade of events leading to RPE cellular repair, replacement and regeneration.
  • Such effects can result in improved transport function, normalized retinal autoregulation, reduced biomarkers of chronic inflammation, reparative acute inflammation, and immunomodulation.
  • Such effects can provide neuroprotection, neuro-trophic enhancement, with restoration and/or regeneration of sick dysfunctional cells, reducing, delaying, or preventing vision loss, for example restoring visual functions in various chronic progressive degenerative retinal disorders and in POAG (which can share similarities).
  • the effects of subthreshold laser central retina sublethal photostimulation with no discernable retinal damage can be entirely “homeo-trophic,” normalizing retinal function, reducing disease progression and the risk of visual loss.
  • retinal cytokine expression can be neuroprotective in POAG in the same way that it is retinal protective in diverse chronic progressive retinopathies that are pathogenically disparate, that exhibit very different drug response profiles (such as diabetic macular edema (DME) and central serous retinopathy (CSR)) and that respond in ways specific to, and characteristic of, the particular disease process.
  • Sublethal RPE laser photostimulation can be a non-specific trigger of disease specific RPE HSP activation and cellular repair.
  • sublethal RPE laser photostimulation can only normalize the function of dysfunctional cells, it is also pathoselective, affecting abnormal cells while having negligible effect on the healthy ones, as has been clinically observed in the significantly greater improvements in eyes with the worst pre-treatment conditions.
  • Disease specific response can be further demonstrated by the characteristically different Pattern ElectroRetinoGraphy (PERG) responses in dry AMD compared to the PERG responses in inherited retinopathies after subthreshold laser central retina sublethal photostimulation treatment.
  • PERG Pattern ElectroRetinoGraphy
  • the therapeutic response while always homeotrophic, is different, and reflects the nature of 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 the underlying retinal abnormality (the disease specific repair response).
  • POAG may represent, at least in part, a primary optic neuropathy or a manifestation of central nervous system disease.
  • Electrophysiologic tests such as PERG and visually evoked potential (VEP) testing can objectively measure and monitor electrophysiologic indices of functionality of the ganglion cells and of the optic nerve.
  • retinogenic loss of neurotrophism is a separate and unique retinal disease entity that may underlie some, or all, cases of OAG, though further study is required.
  • Subthreshold panmacular micropulse laser photo-stimulation treatment has been disclosed by Luttrull et al., Chapter 20 - Glaucoma research and Clinical Advances: 2018 to 2020: Samples JR and Klepper PA, Eds.
  • Subthreshold panmacular micropulse laser can restore RPE cells transport and gene expression functions, improving retinal trophic deficiency and resulting in increased ganglion cells electrophysiologic functionality on pattern electroretinography (PERG) and in improved visual functions on automated perimetry. These improvements indicate that the sublethal laser photostimulation can rescue dysfunctional but still viable retinal elements, possibly through the upregulation of endogenous neuro-enhancing and neuro-protective neuro-trophic factors, promoting the long-term survival and enhancing the functionality of ganglion cells and other neurons.
  • POAG shares most of the common characteristics found in any and all chronic progressive degenerative retinopathies (AMD, DR, CSC, RP, etc.) and POAG could similarly benefit from the same sublethal laser photostimulation of the RPE.
  • HSPs heat shock proteins
  • PEDF pigment epithelium derived factor
  • intracellular repair, replacement, regeneration, improved RPE cell function upregulation of pigment epithelium derived factor (PEDF), intracellular repair, replacement, regeneration, improved RPE cell function, normalized retina homeotrophy autoregulation, suppression of apoptosis, reduction of chronic inflammation biomarkers, and restoring reparative immunomodulation responses, including the mobilization to the retina of bone marrow-derived hematopoietic stem cells able to differentiate in epithelial and/or endothelial cells.
  • HSPs heat shock proteins
  • TTT laser trans-pupillary thermo therapy
  • HSPs endogenous neuroprotective heath shock proteins
  • Heat shock proteins are a group of proteins that are upregulated by hyperthermia or other types of physiological and environmental stress. HSPs can enhance cell survival under conditions of further severe stress. Some of HSPs are constitutively expressed, whereas other HSPs are inducible in response to various kinds of stress.
  • HSP70 family which consists of Hsc70 or constitutive form, and HSP72 or inducible form, can have a protective effect against ischemia, seizures, and axotomy.
  • retinal ganglion cells RRCs
  • RRCs retinal ganglion cells
  • TTT is a treatment modality in which hyperthermia is created with infrared irradiation energy directly delivered to the posterior segment of the eye by, e.g., an 810 nm diode laser. TTT can be performed with a broad beam and long exposure times.
  • TTT increases temperature in treated tissue up to 10 °C above baseline levels.
  • various intraocular tumors i.e., choroidal melanoma, hemangioma, and retinoblastoma
  • TTT increases the temperature in the treated tissue, and therefore TTT may stimulate the expression of HSPs.
  • TTT performed on the optic nerve head which is a primary site of 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 glaucomatous optic nerve damage, induced expression of HSP72 effectively in the treated tissue.
  • Optimal parameters of TTT for maximal HSP72 expression in the optic nerve head with no damage to the ocular tissues were determined by Kim et al. (Kim JM, Park KH, Kim YJ, Park HJ, Kim DM. Thermal injury induces heat shock protein in the optic nerve head in vivo. Invest Ophthalmol Vis Sci 2006;47:4880-4894) to be 100 mW for 60 s.
  • TTT was applied to an optic nerve crush injury model of the rat to investigate neuroprotective effect and it was found that the use of TTT increased the survival of RGCs in retinal areas close to the optic nerve head in the optic nerve crush injury model of the rat.
  • many patients may require or benefit from the IOP lowering treatment complemented with neuroprotective therapy.
  • trans-pupillary sub-lethal photothermal stimulation therapy methods are performed optionally in association with systems configured for trans-scleral laser treatments for the reduction of IOP.
  • system examples are operable to perform neuroprotective trans-pupillary sub-lethal photothermal stimulation therapy of the central retina, which can elicit biochemical responses that can result in neuroprotection, neuroenhancement and possibly regeneration of retinal ganglion cells (RGCs), including by way of example “starving, sick, but not yet dead” RGCs, for the goal of delaying, preventing, or even restoring the loss of visual functions in eyes with POAG and other retinovascular trophic neuropathies.
  • RGCs retinal ganglion cells
  • retinal sub-lethal photo- stimulation is achieved using annular (e.g., circular) treatments that produce an advantageous temperature distribution profile having a flat top histogram characteristic over the panmacular area (including the central fovea, if needed) that does not exceed 45-47 Celsius, and thereby avoids a central cumulative thermal peak rise with a gaussian like thermal peak profile.
  • annular e.g., circular
  • a diode laser operating at a selected wavelength, e.g., 810 nm, in a repetitive micropulse emission mode is directed in circular patterns irradiating an annulus, avoiding irradiation of a 1.0 – 2.0 mm central hole centered over the fovea, and expanding an external edge a predetermined distance, such as up to about 3 disk diameters (4.5-5.0 mm).
  • a predetermined distance such as up to about 3 disk diameters (4.5-5.0 mm).
  • Example interface apparatus 100 shown in FIG.8A can be used to couple a non-contact laser system 74 (with a scan optic portion of the laser system being shown for simplicity) to an eye 70 that receives biostimulation treatment in accordance with method examples herein.
  • a laser beam 71 is directed by the non-contact laser system (e.g., with a laser scanner) through a pupil of the eye 70 to the macular region of the retina of the eye 70.
  • Example optical scanning system 200, shown in FIG.8B can be configured to direct beams trans-sclerally and trans-pupillary.
  • An optical beam source 206 emits an optical beam 202 that is directed through optics and with a laser scanner 214 (e.g., a two-axis or three-axis galvo-scanner) and focusing optics 220 to an eye 70.
  • the optical beam 202 can have a wavelength of about 1475 nm based on emission from a 1475 nm diode laser of the optical beam source 206
  • the optical beam 202 can have a wavelength of about 810 nm based on emission from an 810 nm diode laser of the optical beam source 206. It will be appreciated that other wavelengths can also be used.
  • wavelengths can be selected based on the location and absorptivity (such as the absorbing chromophores) of targeted eye tissue.
  • the optical scanning system 200 is configured to direct the optical beam 202 at least one of trans-sclerally (e.g., 1475 nm) or trans- pupillary (e.g., 810 nm), as well as both.
  • FIG.17A a macula of a retina is divided in a plurality of circular (or oval) regions concentric about an umbo, including a foveola, foveal avascular zone (FAZ), fovea, parafovea, and perifovea, in the order of increasing diameter and radial distance from the center of the umbo. Typical dimensions of the illustrated regions are shown.
  • FIG.17B shows a plurality of concentric paths for a laser beam directed to the macula to biostimulative treatment.
  • spot size and scan pattern radii can be based on average or typical dimensions of the macula, and in further examples, radii and/or spot size can be adjusted or selected after imaging and examining a patient macula (e.g., through an anatomical estimation of dimensional differences, such as color, relative to a typical macula, by an expert or with machine learning image identification software tools).
  • FIGS.18A-18G depict an example trans-pupillary treatment method at different times during the treatment process.
  • a spot 502 of a pulsed laser beam is directed through a pupil of a human eye and impinges at an outer location of a macula 504 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 (e.g., in or proximate the perifovea) of the eye.
  • the macula 504 is shown on-axis through the pupil, with a cross-sectional depiction projected below the on-axis view.
  • FIG.18B shows a time 500b immediately after initial time 500a as the spot 502 is scanned in a clockwise direction along an unprocessed first annulus 506a of a curvilinear scan path 508 about the macula 504.
  • Unprocessed second, third, fourth, and fifth annuli 506b-506e are also shown to adjoin each other at their neighboring beam boundaries to form a contiguous area for treatment that excludes the FAZ, foveolar, and umbo.
  • the beam boundaries are defined as a radial location of the spot 502 where an intensity of the pulse of the pulsed laser beam drops to a predetermined value, such as full-width half-max (FWHM), 1/e, 1/e 2 , zero, etc.
  • FWHM full-width half-max
  • Beam intensity is preferably uniform across the spot, so as to avoid uneven heating or temperature spikes towards a spot center. Uniform intensity can be achieved through various ways, such as homogenizing light pipes, lens arrays, diffusers, etc. Spot size can be fixed in some examples, or adjusted with, e.g., a beam expander or other optics.
  • FIG.18C depicts a time 500c after the spot 502 has completed treatment of the unprocessed first annulus 506a to form a processed first annulus 510a.
  • the spot 502 proceeds on the curvilinear scan path 508, now scanning clockwise along the unprocessed second annulus 506b.
  • FIG.18D shows a time 500d during laser treatment after the pulses of the pulsed laser beam have been scanned to complete a processed second annulus 510b.
  • the spot 502 is then directed to begin scanning along the curvilinear scan path 508 around the unprocessed third annulus 506c.
  • the treatment process has formed a processed third annulus 510c, and the laser spot 502 is directed along the curvilinear scan path 508 to begin treating the unprocessed fourth annulus 506d with the pulses of the pulsed laser beam.
  • FIG.18F shows a time 500f during laser treatment after which processed annuli 506a-506d have been completed, and the scanning of the unprocessed annulus 506e is to begin.
  • FIG.18G shows a time 500g after the spot 502 has been directed consecutively directed through each of the unprocessed annuli 506a-506e to form the processed annuli 510a-510e.
  • more or fewer than five annuli can be used, typically accompanying a different or variation in beam spot diameter.
  • FIG.19 shows a dimensioned representation 1900 of the positions of beam spots 1902a- 1902e at different distances from a central umbo position 1904, and the positions of beam spots 1906a-1906e arranged at opposite positions that corresponds to distances that are diameter lengths of respective concentrically arranged treatment annuli, such as the annuli 506a-506e shown in FIGS.18A-18F.
  • the FAZ is approximately 0.5 mm wide, and thus radially interior positions of the beam boundaries of the beam spots 1902e, 1906e define a distance 1908, and corresponding circular area during annular treatment, in which laser beam treatment does 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 not occur through direct irradiation.
  • cumulative radial lengths 1912a, 1912b can be defined, such as 2.5 mm for a common spot size of 0.5 mm.
  • an overall length 1914 can be defined for an outer treatment diameter, and an outer annulus diameter 1916 (aligned with a beam spot center) can be smaller by one radially extending spot size.
  • the profile 2002 is produced with an annular pattern of a pulsed laser beam scanned about five annuli, with a first ring having a beam center radius of 2.5 mm, a second ring having a 2.0 mm radius, a third ring having a 1.5 mm radius, a fourth ring having a 1.0 mm radius, and a fifth ring having a 0.5 mm radius.
  • a circular beam spot having a diameter of 0.5 mm at the macula defines an irradiative beam boundary that avoids direct irradiation of the FAZ, foveolar, and umbo of the macula.
  • the spot size in the radial direction of the annuli and the annuli radii define a contiguous laser treatment area.
  • laser beam and scan parameters further include a constant scan speed of 1.66 mm/s during the scanning of one or more of the annuli thereby providing a 300 ms exposure time at each RPE cell irradiated by the beam spot diameter in the scanning annulus. It will be appreciated that other speeds can be selected so as to produce a range of exposure times in additional examples, such as 10 ms, 50 ms, 100 ms, 200 ms, 500 ms, etc.
  • a series of processing pulses are generated and directed to the macula according to the annular pattern of five annuli at the constant scan speed.
  • the processing pulses for the pulsed laser beam can have a pulse period of 2 ms (0.5 kHz pulse repetition rate) with a 5% duty cycle, corresponding to a processing pulse duration (FWHM, or other suitable metric) of 100 ⁇ s.
  • FWHM processing pulse duration
  • a pulse to pulse area overlap at the macula of greater than 99% is achieved, with an irradiation area density at the macula greater than 99%.
  • the peak power of the micropulse is set to 100 mW (e.g., with a duty cycle of 5% -- 0.1 ms “ON” and 2 ms period), this can correspond to an average power of 5 mW for a continuous wave (CW) equivalent setting.
  • the power density (irradiance) for the laser micropulse at the macula is approximately 50 W/cm 2 (without considering absorption/scattering losses in the ocular media).
  • the peak power of the micropulse is set to 1000 mW with the same 5% duty cycle, producing an average power of 50 mW for a continuous wave equivalent setting, and resulting in a power density at the macula of 510 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 W/cm 2 .
  • laser and scan treatment parameters can be varied by selected amounts that achieve similar treatment effects, such as by varying values by 1%, 2%, 5%, 10%, 50%, 100%, etc.
  • a total area of about 23.5 mm 2 is treated with the processing pulses, resulting in the delivery of 141 mJ of total energy at a fluence of 600 mJ/cm 2 , using a 100 mW micropulse peak power.
  • This delivery can be similar to a fluence of about 760 mJ/cm 2 directly delivered to an RPE cell with 150 micropulses of 1 mJ each, over a duration of 300 ms.
  • each 0.5 mm diameter area receives a total energy of 15-30 mJ.
  • repetitive pulse application at low duty cycle can reduce the significance of a total process fluence upon therapeutic effectiveness as time-based characteristics take on increased significance.
  • Scan breaks or pauses can occur between annuli or during processing of an annulus, and can be selected to be repetitive or periodic, e.g., based on characteristics of the laser source generating the pulsed laser beam, such as a duty cycle defined for CW pulses, where the processing pulses are generated by modulating or chopping the CW pulses.
  • a temperature in the FAV, foveolar, and umbo can increase to be within a therapeutically advantageous range, e.g., between TLOWER and TUPPER, without exceeding the range (e.g., by avoiding a temperature profile as depicted with the “excessive treatment” line).
  • FIG.21 shows an example of an apparatus 2100 that can be used for treating the retina 2102 and/or sclera 2104 of an eye 2106 of a treatment subject (typically human), as well as other target tissue of the eye 2106.
  • the apparatus 2100 includes a patient interface device 2108 that couples the apparatus 2100 to the eye 2106.
  • the apparatus 2100 includes a light source that includes a plurality of laser sources, such as a trans-pupillary laser source 2110 that can generate laser pulses at predetermined durations, repetition frequencies, powers, duty cycles, etc., at a wavelength of 810 nm, and a trans-scleral laser source 2112 that can generate a continuous-wave laser beam at 1475 nm.
  • a trans-pupillary laser source 2110 that can generate laser pulses at predetermined durations, repetition frequencies, powers, duty cycles, etc., at a wavelength of 810 nm
  • a trans-scleral laser source 2112 that can generate a continuous-wave laser beam at 1475 nm.
  • other additional laser sources can be used, and other laser source characteristics, including continuous-wave or pulsed, wavelength, power, etc., can be selected 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 based on the eye tissue targeted and the type of laser treatment process used for the targeted eye tissue.
  • the plurality of laser sources can be directed to propagate along a common optical path 2113 with a beam splitter 2114.
  • An optical beam scanner 2116 such as a two-axis or three-axis galvanometer scanner, is coupled to the common optical path 2113 to receive the laser beam from the plurality of laser sources and directs the beam towards a predetermined location of the eye 2106 according to a predetermined scan pattern, depending upon on the treatment process selected.
  • a detector 2118 such as a camera, photodiode, CCD, CMOS, imaging system (such as an OCT system), etc., is optically coupled to the eye 2106, e.g., through a beam splitter 2120.
  • the optical coupling for the detector 2118 is between the optical beam scanner 2116 and the patient interface device 2108, though other positions are possible, including between the beam splitter 2114 and the optical beam scanner 2116.
  • the detector 2118 can be used, for example, to monitor a position of the eye tissue that will be processed or that is being processed, so that the optical beam scanner 2116 can direct the laser beam or beams from the plurality of laser sources to the targeted locations of the eye 2106.
  • the working distance of the laser beam or beams is substantially larger than a propagation distance difference between the scleral tissue and the retinal tissue, such that a commanded focal plane does not change during processing different portions of the eye 2106.
  • the commanded focus can vary, e.g., between a location at the sclera and at the retina, or at different locations of the sclera or retina.
  • the plurality of laser sources such as the laser sources 2110, 2112, the optical beam scanner 2116, and the detector 2118 can be coupled to a computing unit 2122.
  • the computing unit 2122 includes a processor 2124 and a memory 2126 having stored instructions executable by the processor 2124 for controlling laser treatment, such as laser beam characteristics, laser wavelength selection, pulse repetition rate, duty cycle, beam initiation, scan pattern commands, and eye registration and/or scan calibration, by way of example.
  • the memory 2126 can be configured with one or more pattern command files defining scan positions and paths for directing the laser beam with the optical beam scanner 2116 in relation to the patient interface 2108 with the eye 2106 in a predetermined position.
  • the computing unit 2122 can also receive signals from the detector 2118 and use the received signals to generate an image of the eye 2106 before, during, and/or after treatment.
  • the detector 2118 can provide location information for the eye 2106 so that pattern command files can be updated so that scanning can be performed in relation to the detected location information. Suitable location information can include anatomical reference features, color variations, reflectivity variations, etc.
  • the detector 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 2118 can be configured to detect a temperature of the target eye tissue, e.g., with a pyrometer, and the detected temperature can be used to adjust laser beam characteristics, such as pulse duration, peak power, repetition rate, etc., including in situ during treatment.
  • the memory 2126 is configured with instructions for the processor 2124 to control and direct delivery to macular annuli a total laser energy in the range of 1 J to 3 J in an annular processing area surrounding the foveal avascular zone of 20 mm 2 to 30 mm 2 (e.g., 23.5 mm 2 ) at a peak pulse power in the range of 1 W to 2 W, and to deliver to annuli on the sclera in the form of N continuous-wave cycles at a constant scan speed in the range of 5 mm/s to 200 mm/s at a scleral radius and along a circumferential arc length that corresponds to a cycle duty factor for the annuli in the range of 0.5% to 50% and that does not produce photocoagulative effects with temperature rise in the range of 8 °C to 20 °C and exposure times proportionally reduced.
  • Suitable values can be determined from clinical practice on specific patient cohorts. For example, treatment parameters providing subthreshold non-damaging pan-macular laser photo-thermal-stimulation for diverse patients may vary with different ethnicity, pigmentation, morphology, ocular characteristics and glaucoma conditions. In particular, the non-uniformity or great variability of the distribution of melanin (the main absorbing chromophore) in the human retinal pigment epithelium RPE, tends to alter the photo-thermal effects more than laser pulse fluence parameters. Energy values can be determined from or vary based on selected wavelength, including pigmentation variation among patients, and can affect and determine suitable thermal elevations.
  • Such delivery to macular annuli can correspond to delivery of repetitive pulse trains of 150 micropulses over each consecutive 300 ms period, a laser spot diameter of 500 ⁇ m, a laser spot area of 0.00196 cm 2 , an irradiance range of 510 to 1020 W/cm 2 , a single micropulse duration of 0.1 ms in an energy range of 0.1 to 0.2 mJ producing a 150 pulse exposure energy range of 15 to 30 mJ and a single micropulse fluence of 51 to 102 mJ/cm 2 .
  • laser parameters using other retinal laser devices performed successful and effective non-damaging pan-macular photostimulation retinal treatments, and example devices herein can be controlled to deliver laser exposures similar to such clinically validated procedures.
  • the laser parameters included an 810 nm diode laser operated in a micropulse emission mode at 5% duty cycle of a 2.0 ms period (0.1ms ON + 1.9 ms OFF) and 500 pps repetition rate, an exposure duration of 300 ms (delivering a train of 150 micropulses), a laser spot diameter of 500 ⁇ m, a laser spot area of 0.00196 cm 2 , a laser power of 1.7 W, an irradiance of 867 W/cm 2 , a single micropulse (0.1s) energy of 0.17 mJ, a 150-pulse exposure total energy of 25.5 mJ, and a single micropulse fluence 86.7 mJ/cm 2 .
  • RPE cells at the edges of a selected annulus can be exposed to laser energy for a shorter duration relative to portions more central to the selected annulus (due to the circular shape of the spot) and will receive less energy (e.g., fewer than 150 pulses).
  • this reduction can be compensated by the proximity the photo-thermal-stimulation effects from an adjacent treatment annulus.
  • a radial overlap of adjacent annuli can be provided to reduce a fluence variation in the radial direction.
  • the one or more pattern command files can include a first set of pattern commands for a trans-scleral treatment, a second set of pattern commands for a trans-pupillary treatment proximate a macula, and a third set of pattern commands for a trans-pupillary treatment proximate an optic disk.
  • some treatments can be applied prophylactically, such as before an onset of glaucoma or without an indication of glaucoma, to reduce the probability of glaucoma occurring or retard glaucoma development.
  • a view of an eye shown in FIG.22 shows an example of trans-scleral treatment annular scan paths and trans-pupillary treatment annular scan paths overlaid on the eye.
  • the trans-scleral pattern commands can be configured to control beam characteristics and to direct the beam to a plurality of treatment locations 0-4 mm posterior to the corneolimbal junction on an external surface of the sclera 2104.
  • At least one (and typically all) of the treatment locations can include a curvilinear or arcuate scan path segment of a predetermined length (e.g., a full circle or an arcuate portion thereof), and the laser beam, operating a continuous-wave mode (though a continuous series of pulses can be used in some examples), is repetitively directed to scan along the same scan path segment at a predetermined scan speed.
  • the length and scan speed can define a duty factor for the repetitions that is sufficient to induce protective thermal preconditioning and therapeutic bio-stimulation of one or more of the trabecular meshwork and/or ciliary body of the eye.
  • the 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 plurality of trans-scleral treatment locations are defined by three concentric circular scan paths at different diameters in the range of 0-4 mm posterior to the corneolimbal junction on an external surface of the eye (e.g., 1 mm, 2 mm, and 3 mm, 1.5 mm, 2.5 mm, and 3.5 mm, etc.), with each circular scan path including a single scan path arc segment forming a complete circle or less than a complete circle or including multiple arcuate segments including contiguous, spaced apart, and/or overlapping segments.
  • each of circular scan paths includes a superior 150° arc from 9:30 to 2:30 o’clock and an inferior 150° arc from 3:30 to 8:30 o’clock while avoiding the nasal and temporal 30° arcs.
  • the second set of trans-pupillary treatment commands can be configured to control beam characteristics and to direct the beam to a plurality of treatment locations at the macular region of the retina 2102 exclusive of the FAZ, foveola, and umbo.
  • the plurality of treatment locations includes five annular scan paths concentric about the FAZ, scanned in a sequence from the outer-most larger diameter annulus to the inner-most smallest diameter annulus.
  • An inner most annulus has an inner beam boundary that adjoins or is adjacent to the FAZ so as to avoid direct irradiation of the FAZ, and, beginning with the inner most annulus, each outer beam boundary adjoining or adjacent to (or overlapping in some examples) the next larger diameter annulus so as to form a contiguous treatment area.
  • the outer most annulus of the five annuli can have an outer beam boundary at a radius of 2.75 mm for a typical human eye macula. In other examples, fewer or more than the five annuli can be scanned, and different beam spot dimensions in the radial direction can be used.
  • the beam spot is circular resulting in a common value for the beam spot dimension along the direction of scanning and the beam spot dimension in the radial direction from the umbo, and in further examples oval, square, rectangular, or other non-circular beam spot shapes can be used.
  • the treatment annuli can be scanned in a sequence from largest diameter to smallest, and the sequence can be associated with a suitable temperature increase in the FAZ, foveola, and umbo to within a therapeutic temperature range, such as between 37-47 °C.
  • the thickness of different annuli can be different.
  • the beam characteristics for the laser beam targeting the macular region can include pulsed operation with selectable pulse characteristics.
  • the pulse repetition rate and curvilinear scan speed can be selected such that each individual retinal pigment epithelium (RPE) cell within the laser treatment area receives approximately 150 pulses.
  • RPE retinal pigment epithelium
  • a scan speed of 1.666 mm/s 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 and a pulse repetition rate 0.5 kHz (2 ms pulse period) can be used, thereby irradiating approximately 150 pulses over 300 ms.
  • a time-temperature history of 150 consecutive small non-lethal temperature spikes can be created for each RPE cell, each spike producing a very high rate of temperature change that elicits a biological stress response but that does not kill the RPE cell.
  • each spike can infer to the cell a thermal shock at a rate of approximately 70,000 °C/second.
  • the third set of trans-pupillary treatment commands can be configured to control beam characteristics and to direct the beam to a plurality of treatment locations proximate the optic disk region of the retina 2102 but exclusive of the optic disk and underlying optic nerve (e.g., by having irradiated laser light avoid substantial impingement on the area bounded by the dura mater of the optic nerve).
  • the plurality of treatment locations can include a similar scan pattern as the second set of trans-pupillary treatment commands, but instead navigating around the optic disk.
  • the plurality of treatment locations can include five annular scan paths concentric about the optic disk, scanned in a sequence from the outer-most larger diameter annulus to the inner-most smallest diameter annulus.
  • An inner most annulus has an inner beam boundary that adjoins or is adjacent to the optic disk so as to avoid direct irradiation of the optic nerve, and, beginning with the inner most annulus, each outer beam boundary adjoining or adjacent to (or overlapping in some examples) the next larger diameter annulus so as to form a contiguous treatment area.
  • the outer most annulus of the five annuli can have an outer beam boundary at a radius of 3.46 mm for a typical human eye optic disk.
  • the five annuli can be oval-shaped, e.g., with an outer beam boundary along a minor diameter ( ⁇ 1.76 mm) direction at a radius of 3.38 mm for a typical human eye optic disk.
  • fewer or more than the five annuli can be scanned, and different beam spot dimensions in the radial direction can be used.
  • the beam spot is circular resulting in a common value for the beam spot dimension along the direction of scanning and the beam spot dimension in the radial direction from the optic disk center, and in further examples oval, square, rectangular, or other non-circular beam spot shapes can be used.
  • the treatment annuli can be scanned in a sequence from largest diameter to smallest, and the sequence can be associated with a suitable temperature increase in the areas having retinal cells surrounding the optic disk to within a therapeutic temperature range, such as between 37-47 °C.
  • the thickness of different annuli can be different. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 Because of the proximity between the macula and the optic disk at the fundus of the typical human eye, examples of annuli formed with the second and third sets of trans-pupillary treatment commands can be made to overlap at the fundus, resulting in double-stimulation treatment of selected areas.
  • Examples herein can also include avoidance of double-treatment, by changing scan patterns associated with the second and/or third sets of trans-pupillary treatment commands so that beam spots delivered along one beam scan paths (such as a path encircling the macula) do not substantially overlap beam spots delivered along an adjacent beam scan path (such as another path encircling the optic disk). Additional treatment pattern options are shown in FIGS.24A-24C.
  • trans-pupillary treatment commands produce example laser scan paths proximate the optic disk that generally follow the oval contour of the optic disk.
  • FIG.24B shows a trans-pupillary treatment area that surrounds and avoids the optic disk and the foveal avascular zone.
  • a scan path or paths defining the trans-pupillary treatment area can include contoured circles and ovals (similar to that shown in FIG.24A), but other scan paths can be chosen as well to “paint” the selected treatment area proximate the optic disk and macula.
  • the scan path of the laser beam treats the area without overlapping scan path segments in one pass, though in additional examples paths can be retraced.
  • treatment parameters are selected to produce subthreshold sublethal laser photostimulation of the retina that triggers a stress response by targeting retinal pigment epithelium (RPE) cells through continuous scanning of a laser beam according to predetermined scan patterns and with selected CW or pulsed laser parameters and laser scan parameters.
  • FIG.24C shows another example treatment pattern in which an area of the retina is targeted for subthreshold sublethal laser photostimulation but an area corresponding to the position of a papillomacular nerve bundle is avoided.
  • a macular area including a perifovea and other macular areas outside an FAZ, is avoided, but in some examples, a macular area exclusive of the papillomacular nerve bundle or including the papillomacular nerve bundle can be treated.
  • the second and third sets can also be combined to form a single set of treatment commands.
  • the macula and optic disk can be located and their positions determined, and the second and third sets of treatment locations and corresponding treatment commands can be defined in relation to the determined positions.
  • detected features can be processed through one or more image identification or pattern recognition algorithms (such as deep learning, convolutional neural networks, circle Hough Transform, etc.) to determine centroid positions, boundaries, orientations, relative positions, distances, etc., for a patient’s macula and optic disk (or cornea/sclera features in trans-scleral treatments) and the treatment commands can be updated so that the laser beam is scanned to a correct position of the patient’s eye.
  • image identification or pattern recognition algorithms such as deep learning, convolutional neural networks, circle Hough Transform, etc.
  • Treatment or treatments can be performed using calibrated systems.
  • laser power of the systems can be calibrated at 2302 using a detector to compare commanded peak and/or average powers to actual powers.
  • the commanded locations for the laser beam delivery using the optical beam scanner and patient interface device can be compared to actual locations of beam delivery in one or more predetermined working planes or surfaces (e.g., that align with expected scleral or retinal surfaces) using spatial calibration devices, such as laser test surfaces and/or coordinate measuring machines or probes.
  • one or more sets of treatment pattern commands for a specific patient and corresponding to a pre-planned nomogram or a custom generated nomogram can be produced using software.
  • the patient is readied in a supine position for treatment, and anesthetic can be applied if appropriate, including by pre-instilling Thealose Duo drops (Thealose 3% API – Thea Pharma) for 10 minutes or longer, 2 drops per minute on the selected eye to receive treatment prior to anesthetic instillation.
  • Topical proparacaine drops can be instilled when the treatment is ready to begin.
  • a speculum can be placed in the eye and a patient interface device can be centered on the cornea. Suction can be applied, and a cone of the speculum docked to the PID.
  • FIG.25 shows an example laser treatment apparatus 2500 that can be used to deliver laser treatments in accordance with the various examples described herein.
  • the apparatus 2500 includes a laser head 2502 slidably coupled to rails 2504a, 2504b so that the laser head 2502 can be fixed in a predetermined orientation in relation to a head rest 2506 and can slide towards the head rest 2506.
  • the rails 2504a, 2504b are arranged in a fixed relation to the head rest 2506, though each can be adjustable, including relative to each other.
  • the rails 2504a, 2504b can be attached to a body support 2508, such as a recliner (e.g., a dental chair) having back and/or foot rests that can 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 be reclined backwards and fine adjusted through electrical controls.
  • the patient can also be positioned supine on a gurney. In additional examples, the patient can be upright with the view in FIG.25 looking downwards onto the patient’s head.
  • the head rest 2506 can be firmly attached to, and adjustable relative, to the body support 2508, through one or more pivoted support members 2510a-2510d.
  • the head rest 2506 can be configured as a horse-shoe shaped head rest that includes opposing adjustable pads 2512a, 2512b coupled to support members 2410a, 2510b. In representative examples, the head rest 2506 can be adjusted to accommodate different head sizes.
  • the laser head 2502 can be coupled to an end of an articulating support arm and stand 2514 that includes pivoted support members 2516a-2516c configured to allow movement and rotation of the laser head 2502, allowing the laser head 2502 to be brought in proximity to the body support 2508 and head rest 2506.
  • the laser head 2502 can be removably coupled to the rails 2504a, 2504b so that the laser head 2502 can be secured and slidably translated along the rails 2504a, 2504b. Once mechanically mounted or ‘clicked-in’ to the rails 2504a, 2504b, the laser head 2502 can also be adjusted in various directions with internal movement stages for fine adjustments and to center optical components of the laser head 2502 in relation to a patient’s eyes.
  • the attaching of the laser head 2502 to the rails 2504a, 2504b, a physician can be allowed to sit adjacent to the patient’s head and control coupling of the laser head 2502 to the patient’s eye or eyes through a patient interface device (PID) 2518 (such as the patient interface device 100 shown in FIGS.5A-5C, by way of example).
  • the PID 2518 can be affixed to the laser head 2502 and brought into contact with the patient’s face and eye.
  • the PID 2518 can include a liquid cooled suction ring configured to provide a coolant solution (such as PBS saline solution) to the cornea of the patient.
  • the PID 2518 and laser head 2502 can be aligned with the patient’s eyes with the patient’s head resting in the head rest 2506.
  • a foot pedal can be used by the physician for manual laser application, imaging controls, or mechanical adjustment.
  • the laser head 2502 typically includes a plurality of laser sources, such as two laser sources, three laser sources, four laser sources, or more, and a laser scanner, such as a 2-mirror galvo-scanner or two double-wedged prisms.
  • the laser head 2502 includes a laser source configured to generate a laser beam at about 1470 nm, which can be used in trans-scleral treatments described herein, such as for lowering intraocular pressure or providing preventive treatments.
  • the laser head 2502 further includes a laser source configured to generate a laser beam at about 810 nm, which can be used in trans-pupillary treatments described herein, such as for retinal neuroprotection applications.
  • the laser source at 810 nm (or another laser source) can generate a laser beam configured for standard glaucoma treatment 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 modalities such as diode laser trabeculoplasty (DLT), micro pulse diode laser trabeculoplasty (MDLT) and Laser cyclophotocoagulation (LCP).
  • DLT diode laser trabeculoplasty
  • MDLT micro pulse diode laser trabeculoplasty
  • LCP Laser cyclophotocoagulation
  • the laser head 2502 further includes a laser source configured to generate a laser beam at about 635 nm, which can be used for aiming and centering the other laser beams generated and scanned with the laser head 2502.
  • the laser scanner of the laser head 2502 can be used to guide the one or more laser beams through the PID 2518 and/or contact lens coupled to the patient’s eye.
  • a fixed objective lens such as an F ⁇ lens or other scan optic
  • a rotatable lens fixture can be provided so that alternative objectives (or no objective) can be coupled between the laser scanner and the PID 2518.
  • each of the laser beams emitted from the laser sources can have a fixed spot size, though some examples can include a variable spot size, e.g., with an in-line beam expander or zoom lens.
  • the laser beams typically have a uniform “top-hat” intensity profile, provided by suitable homogenizing optics, such as homogenizing waveguides and/or lens arrays.
  • the laser head 2502 can also include one or more imaging devices, such as a camera can be coupled through the PID 2518, e.g., through the laser scanner and/or objective lens, to image the eye of the patient.
  • More complex imaging devices such as an OCT apparatus 2520 can be stationed separated and coupled to the laser head 2502, e.g., along the support members 2516a- 2516c, where there is insufficient form factor for housing in the laser head 2502.
  • a display 2522 can be coupled to the stand 2514 to show images of the eye and/or provide a graphical user interface for control of the laser treatment.
  • the display 2522 and laser head 2502 can be coupled to a laser controller 2524 (such as a PC or other computing device), which can include a processor and memory storing instructions to control laser treatment.
  • the laser sources are situated in the laser head 2502 at the end of the support member 2516c, though in other examples, the laser sources can be coupled to the articulating support arm and stand 2514 at other positions and coupled along the support members 2516a-2516c through suitable waveguides, such as optical fibers.
  • the physician can align the optics and laser beams emitted by the laser head 2502 through the PID 2518 with the patient’s eyes by using an aiming beam, camera, and/ imaging device.
  • the laser controller 2524 can include an input interface configured with user controls to activate one or more treatment routines. For example, existing treatment patterns can be pre-loaded in the laser controller 2524 or additional routines, such as patient-specific ones, can be loaded from an external device.
  • a “trabeculoplasty-like” response can be defined as a stress response of the trabecular meshwork I to a nonlethal thermal injury, which is the nonspecific stimulus created by each diverse treatment technique.
  • the response triggers a cascade of disease-specific, biochemical activities in all aqueous dynamic regulating cells, that result in IOP reduction and restored IOP homeostasis.
  • the current view on the mechanism of action of all trabeculoplasty-like responses is (hypothesis): any unnaturally steep thermal rise in the aqueous humor (AH) regulating structures (trabecular meshwork, SC, collector channels, ciliary body, uveoscleral route) prompts a common stress response in which integrin activation leads to the production of inflammatory cytokines interlukin-1 beta (IL-1 ⁇ ) and tumor necrosis factor alfa (TNF- ⁇ ).
  • IL-1 ⁇ interlukin-1 beta
  • TNF- ⁇ tumor necrosis factor alfa
  • MMP stromelysin matrix metalloproteinases
  • TIMP tissue inhibitors of metalloproteinases
  • ECM extracellular matrix
  • HSP heat shock proteins
  • GAG glycosaminoglycan
  • the temperature of the triggering stimulus is the determinative factor for safe and effective trabeculoplasty-like responses. That is, it is not the type of energy (cw or ⁇ P laser, ultrasound), or the type of laser, or the laser parameters ( ⁇ , P, E, irradiance, fluence) that are determinative. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 Rather, those modes only modulate the determinative factor of the temperature rise ( ⁇ T). If ⁇ T is too low, i.e., below the threshold of biochemical activation, there is no treatment (e.g., MLT with insufficient power).
  • ⁇ T is too high, there is treatment, but also iatrogenic destruction (e.g., bubbles in SLT’s thermolysis, burns in ALT’s coagulation, etc.). Tissue damage is not a prerequisite for obtaining an IOP reduction, and therefore it should be preferably minimized or avoided entirely.
  • the ability of controlling the ⁇ T rise allows the direct creation of a 43-45 °C hyperthermia rather than indirectly deriving it from a higher ⁇ T, thereby sparing the trabecular meshwork from unnecessary iatrogenic damage.
  • Hyperthermia is defined as the condition of having a body temperature above normal.
  • Nondamaging therapeutically effective hyperthermia is performed by rising the normal baseline temperature of viable human cells from 36 0C to 43-45 0C. This thermal elevation maintained for at least 30 seconds can constitute the nonlethal mild stimulus sufficient to activate the trabeculoplasty-like stress response in the targeted viable cells.
  • nondamaging and repeatable hyperthermia therapy are treatments that can be applied that do not leave discernable endpoints (alias iatrogenic changes like ALT’s trabecular photocoagulation burns, SLT’s trabecular selective photothermolysis bubbles, etc.). Hyperthermia absence of visible laser impacts clashes against long established and deeply rooted theories on the therapeutic values of some laser tissue destruction.
  • hyperthermia stimulates a trabeculoplasty-like response, which might be obtained in all other non-incisional hypotensive laser techniques, but with an important difference: a 440C hyperthermia is directly created sublethal and does not cause iatrogenic damage.
  • ring beam annular transpupillary neuroprotective treatments can be performed by systems employing transscleral treatments (“dual laser” systems), either with a set of at least some common optical components or with an alternative set of optical components, or with systems that do not provide transscleral capabilities.
  • a transpupillary laser beam such as one operating in the near IR, e.g., 810nm, is used to perform nondamaging subvisible laser pan-macular photostimulation therapy aimed to the central retinal pigment epithelial (RPE) cells.
  • RPE retinal pigment epithelial
  • Glaucoma Optic Neuropathy is a vascular disorder, a “Glaucoma Vasculopathy”, whose pathogenesis is not an acute infarction, but a chronic hypoxia secondary to chronic ischemia.
  • Glaucoma Vasculopathy presents many similarities with other chronic, progressive, neurodegenerative retinovascular disorders of diverse etiopathogenesis that benefit from nondamaging pan-macular photostimulation with the micropulse laser.
  • the RPE is neurotrophic to the retina.
  • a treatment that can restore normal RPE’s neurotrophism, slowing, stopping, or reversing the loss of vision, is Neuroprotective.
  • Panmacular photostimulation restores RPE’s trophism relinquishing the chronic hypoxia that could be initiated by dysfunctional RPE transport, a likely origin of the progressive apoptotic neurodegeneration in Glaucoma Vasculopathy and other retinovascular diseases. This mechanism can explain the improvements in macular perfusion and visual function reported after panmacular photostimulation.
  • Micropulse laser subthreshold photostimulation triggers a biochemical response that mediates the expression of heat shock proteins (HSP), glial fibrillary acidic proteins (GFAP), upregulation of Müller cells, neurotrophic factors and the mobilization of bone marrow derived hematopoietic stem cells, that rescue and regenerate dysfunctional RPE cells, restoring their trophism.
  • HSP heat shock proteins
  • GFAP glial fibrillary acidic proteins
  • This biochemical response cascade following the expression of heat-shock proteins is also activated by the nonlethal hyperthermia thermal stress of subthreshold continuous wave (CW) laser pan-macular transpupillary thermotherapy (TTT), in accordance with disclosed examples, which has been shown effective at repairing RPE dysfunctional cells, restoring their viability and returning them to a more normal functional state.
  • CW laser pan-macular transpupillary thermotherapy TTT
  • micropulse or CW subthreshold laser panmacular photostimulation treatments can be prophylactically performed to prevent the onset of apoptosis of the retinal ganglion cells (RGC) in preperimetric glaucoma, therapeutically administered to slow/stop the progressive loss of RGC sensitivity and of visual field in patients with glaucomatous optic neuropathy (GON), and always PRN repeatable.
  • RGC retinal ganglion cells
  • Neuroprotection, neuro- enhancing, or neuro-regeneration could represent a giant step to slow, stop or reverse neurodegeneration, a true paradigm shifts in glaucoma management.
  • FIG.26 is an example laser treatment system 2600 configured to produce a sublethal rise in temperature in a set of sub-scleral biological structures of an eye 2602 in accordance with the trabeculoplasty-like response described above.
  • the system 2600 is operable to produce a laser beam 2601 with an annular shape 2603 (only a schematized vertical cross-section being shown; also referred to as an annular beam 2603) that can be used to minimize, avoid, or reduce tissue damage relative to other techniques that may produce IOP reductions.
  • the sub-scleral biological structures which can include (ordered posteriorly) trabecular meshwork, Schlemm’s canal, collector channels, ciliary body, pars plana, and uveoscleral outflow pathways, etc., are situated a few hundred microns beneath a perilimbal region 2604 (shown between dashed lines) of a conjunctiva and underlying sclera 2606.
  • Described approaches are generally configured to provide a broad geographical treatment to an array sub-scleral biological structures through a thermal spreading of delivered energy. In heating a wider area through sustained delivery of energy to achieve an elevated hyperthermic temperature in these structures, the broad geographic treatment can address the full primary and nonconventional outflow paths.
  • SLT typically involves delivering high irradiance spots in the trabecular meshwork alone. Similar with ab externo SLT treatment, treatment is aimed at the limbus typically with high energy visible wavelengths.
  • the targeted structure was the trabecular meshwork based on the understanding that its location was where the resistance to outflow builds up. It was thought that by creating holes, artificial paths would be created for outflow.
  • holes to create holes in the trabecular meshwork, it was targeted and heated precisely and locally to produce the holes.
  • their draining efficacy would reduce over time as natural healing processes would form scar tissue.
  • the process of producing trabecular holes would provide some IOP lowering benefits though the lasting benefits did perdure 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 long after the inevitable holes healing from the tissue destruction. Rather, the photothermal stimulation of the cells was responsible for activating the biological cascade resulting in the lasting pressure reduction.
  • the treatment examples described herein can be generally configured to transsclerally target a broad perilimbal geographic area overlying the whole aqueous humor outflow regulating structures, from the conventional outflow pathways through the uveoscleral outflow pathways.
  • glaucoma multifactorial disease open angle glaucoma, angle closure glaucoma, normotension glaucoma, pigmentary glaucoma, etc.
  • a nondamaging hyperthermia can stimulate similar beneficial biological responses in all dysfunctional cells, without involving or harming the healthy ones. That is, it has been found that other parts of the anatomic outflow autoregulating system can also benefit from hyperthermic activation of biological cascades responses that can provide some restoration of lost homeostasis.
  • the benefits that can be obtained with the approaches and systems described herein can produce lasting benefits for a variety of glaucoma types.
  • a hyperthermic response is obtained for a range of sub-scleral biological structures by irradiating the perilimbal sclera with a large, doughnut- shaped laser beam (e.g., annulus 2607) to the perilimbal surface of the eye.
  • a large, doughnut- shaped laser beam e.g., annulus 2607
  • the resulting therapeutic responses can be provided to all the dysfunctional cells in the conventional outflow pathway and the uveoscleral outflow pathway.
  • the field of laser irradiation of the annular beam 2603 can extend across the surface of the conjunctiva to form the 3600 beam annulus 2607 in at least part of the perilimbal region 2604.
  • the annulus 2607 can be coextensive with the perilimbal region 2604.
  • the perilimbal region 2604 can be defined as a radial range adjacently posterior to a corneolimbal junction 2608, though such ranges can vary and depend on the anatomical characteristics of the patient’s eye. For example, ranges can include between 0 and 4 mm posteriorly to the corneolimbal junction 2608, 1 to 4 mm, 1 to 3 mm, 2 to 4 mm, 1.5 to 4 mm, etc.
  • the perilimbal region being posterior to the corneolimbal junction can be defined as a radial distance projected in a flat plane (e.g., perpendicular to the optical axis of the eye) which can therefore correspond to a measurement direction of the width of the annulus 2607.
  • the perilimbal region being posterior to the corneolimbal junction can be defined as a distance tangent to an angled surface of the eye or a distance in a posterior direction (parallel to the eye’s optical axis).
  • a cornea 2610 is intentionally avoided by the beam annulus 2607, e.g., by being protected from accidental exposure by a corneal shield and/or 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 positioning of the beam annulus 2607 on the perilimbal region 2604 such that limited or no irradiation is directed radially inward from the inner annular boundary of the perilimbal region 2604.
  • the system 2600 includes a continuous-wave laser source 2612 situated to produce a source laser beam 2614.
  • Annulus optics 2616 are situated to receive the source laser beam 2614 and to adjust the laser beam 2614 so that the beam 2601 forms the annular shape 2603 and produces the beam annulus 2607 at the perilimbal region 2604.
  • the annulus optics 2616 typically includes one or more lenses and/or mirrors or other optical components that are situated to produce the beam annulus 2607.
  • the beam annulus 2607 extends a complete circular extent of the perilimbal region 2604.
  • the beam annulus 2607 extends to form one or more arc segments each extending through at least a portion of the circular extent of the perilimbal region 2604, e.g., at least 50%, 60%, 70%, 80%, 90%, or 95% of the circular extent of the perilimbal region 2604.
  • the annulus optics 2616 include at least an axicon situated to form the annular shape 2603.
  • multiple axicons can be used.
  • one or more axicons can be combined with one or more beam expanders and/or focusing lenses to form the annular shape 2603.
  • relative distances between one or more optical components can be adjustable to vary characteristics of the beam annulus 2607 relative to the perilimbal region 2604, such as width of the beam annulus 2607 (i.e., a thickness of the annulus) or a mean diameter of the beam annulus 2607.
  • adjustment of the beam annulus 2607 can be performed cyclically with respect to time, e.g., to produce a dithering effect in which the beam annulus 2607 is scanned or altered periodically. In further examples, adjustment can be performed in response to an over-temperature detection of the eye 2602 or to control one or more treatment parameters (such as laser beam power, applied irradiance, and/or treatment duration) based on the detected temperature and one or more temperature setpoints.
  • the annulus optics 2616 can be integrated or partly integrated with the laser source 2612 to include an optical fiber bundle arranged in an annulus.
  • the optical fiber bundle can include a plurality of optical fibers with each fiber coupled to a respective source portion of the laser source 2612, e.g., separate laser diode sources.
  • the separate optical fibers emit respective beams that can directed to the perilimbal region 2604 to form the annular shape 2603, e.g., directly or through one or more optics that focus or adjust the characteristics of the respective beams to form the annular shape 2603.
  • the annular arrangement of the fiber 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 bundle is more than one diameter thick and the respective beam sources are separately addressable to adjust a position or size of the annular shape 2603.
  • adjustments can be used to track eye movement, to accommodate eyes of different sizes by providing fine adjustments to the laser beam 2601 relative to the perilimbal region, or to dynamically adjust the annular shape 2603 or beam annulus 2607 as needed, such as according to a specific nomogram.
  • the laser source 2612 is configured to produce the laser beam 2601 with a selected continuous-wave power profile selected to produce the temperature rise in the sub-scleral biological structures and thereby producing therapeutic effects discussed herein.
  • the continuous-wave power profile can include a step increase to a selected power level, though other power profiles are possible in other examples, such as a ramp, multiple steps, periodic, oscillating between non-zero power levels, sinusoidal, arbitrary functions, or a combination.
  • the annulus optics 2616 are configured to provide the annular beam 2603 with a selected continuous- wave irradiance (or irradiances) (W/cm 2 ) at the beam annulus 2607.
  • the continuous-wave power and irradiance are provided for the beam annulus 2607 for a duration sufficient to produce a selected rise in temperature of the sub-scleral biological structures.
  • the wavelength of the laser beam 2601 is typically provided to be within an infrared water- absorptive range, such as 1.4-1.6 ⁇ m, preferably about 1.475 ⁇ m.
  • the deeper infrared region of the electromagnetic spectrum specifically allows for increased interaction with water in the sub-scleral structures, thereby allowing localized absorption and heating which can increase temperature without causing photocoagulation.
  • an applied continuous-wave irradiance can be constant for all or a significant fraction of a treatment during which the beam annulus 2607 is applied to the surface of the eye 2602, but irradiances can be variable over time and/or area in some examples as well. Stated continuous-wave irradiances can correspond to an average irradiance applied across an area of the beam annulus 2607 at a selected point in time during treatment. In some examples, a peak irradiance can be higher than an average irradiance, e.g., due to non-uniform or non-flat-top beam characteristics.
  • the beam annulus 2607 can have Gaussian, super-Gaussian, skewed, depressed, or other irradiance profile, typically in a radial or thickness direction of the beam annulus 2607.
  • Beam edges of various examples described herein, such as inner and outer annular diameters, can be defined in various ways.
  • a beam edge can correspond to a position beam irradiance decreases to zero, 1/e of a maximum irradiance value, 1/e 2 , a full-width half- maximum, a percentage of an average, or another suitable metric.
  • suitable applied irradiances can be in the range of 0.01 to 0.1 W/cm 2 , 0.1 to 0.5 W/cm 2 , 0.5 to 1.0 W/cm 2 , 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 1.0 to 1.5 W/cm 2 , 1.5 to 2.0 W/cm 2 , or 2.0 to 5.0 W/cm 2 .
  • an average irradiance higher than about 1.5 W/cm2 is specifically avoided.
  • a constant irradiance of about 1.1 W/cm 2 is applied across an annular area of about 0.98 cm 2 for a duration of about 30 s.
  • the beam annulus 2607 can be applied by directing the continuous-wave laser beam 2601 continuously, i.e., without being pulsed, for a sufficient duration to elevate the temperature of the sub-scleral biological structures into a therapeutic treatment temperature window for a sufficient duration providing a therapeutic effect.
  • the continuously applied beam is scanned radially, e.g., by varying an effective diameter, edge position or positions, and/or irradiance profile of the annular beam 2603. Radial scanning can be bi- directional, e.g., oscillating between radially inward and radially outward annular positions.
  • radial scanning can be uni-directional, e.g., repetitively translating from a radially outward position to a radially inward position only, or from a radially inward position to a radially outward position only.
  • more complex scan patterns can be provided, such as a single annular beam that splits into two annular sub-beams with one scanning radially outward and one scanning radially inward, or two beams initiating at radially inward and outward positions respectively that scan to form a single beam at the middle.
  • the beam annulus 2607 can be applied by the directing the continuous- wave laser beam 2601 with periodic or cyclic power profile, providing one or more durations of no irradiation between durations of irradiation.
  • the off-time or off-times can correspond to a duty- cycle of applied laser energy to the surface of the eye 2602 so as to provide a pause or break that allows surface temperature to cool before applying successive window of continuous-wave irradiation.
  • the heating of the sub-scleral structures continues to occur as successive waves of heat conductively diffuse and cause the temperature of the targeted sub-scleral biological structures to remain elevated to a hyperthermic level for the continuous therapeutic duration.
  • the temperature of the sub-scleral biological structures is increased to a range between about 43-45 °C using the laser beam 2601 in order to produce hyperthermic therapeutic effects.
  • a gradient of about 7-9 °C can be provided and maintained for a sufficient duration to achieve the 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 therapeutic heating.
  • the sufficiency of the duration providing a therapeutic effect can correspond to a duration of about 30 s.
  • Other durations may be suitable depending on the particular characteristics of the eye or subject, such as between about 20-40 s, 25-35 s, 28-32 s, 15-30 s, 30-60 s, greater than 60 s, etc.
  • a system controller 2618 or other computing device typically includes one or more processors and memory configured with instructions to control the various components of the system 2600 to deliver the laser treatment.
  • the system 2600 can include an imaging/detection optics 2620 optically coupled to view the eye 2602.
  • the imaging/detection optics 2620 can include an imaging camera, thermographic camera, and/or thermal sensor.
  • the imaging/detection optics 2620 can be used by the system 2600 to manually or automatically align the beam annulus 2607 with the eye 2602 to be treated or during treatment.
  • a beam splitter 2622 is situated to optically couple the imaging/detection optics 2620 to the eye 2602. The beam splitter 2622 or other beam pickoff can also be part of the annulus optics 2616.
  • detection through the annulus optics 2616 can allow the area of the eye that is viewable by a sensor or imaging device of the imaging/detection optics 2620 to correspond to the area of the beam annulus 2607 or perilimbal region 2504.
  • a beam block 2623 can be situated at one or more positions between the laser source 2612 and the eye 2602 to block selected irradiation from being directed towards the eye 2602, such as a zero-order diffraction light.
  • the controller 2618 can be further coupled to the laser source 2612 and annulus optics 2616 to adjust various parameters of the laser treatment.
  • the controller 2618 can be configured to turn on and off the laser source 2612 to produce the source laser beam 2614 for a controllable duration and power level according to a selected power profile.
  • the controller 2616 can be configured to control lens or mirror components of the annulus optics 2616, e.g., to adjust a position of the annular shape 2603 relative to the perilimbal region 2604, a thickness of the annular shape 2603, a mean diameter of the annular shape 2603, etc.
  • adjustments of the annular beam 2603 can be provided preceding a treatment duration, e.g., to provide a correct positioning of the annular beam 2603 relative to the surface of the eye 2602, such as relative to the corneolimbal junction 2608, an optical axis of the eye 2602, targeted treatment boundaries for the annular beam 2603 (such as various distances from the corneolimbal junction), etc.
  • adjustments of the annular beam 2603 can be provided additionally or instead during an active treatment.
  • Beam adjustments during an active treatment can include dithering the beam annulus 2607, such as by varying a mean diameter of the 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 beam annulus 2607 to scan within the perilimbal region 2604. Such scanning can also provide a cyclic pause in laser beam exposure to portions of the treatment area in the perilimbal region 2604 to allow surface temperatures to cool and thereby reduce the likelihood of damage to the conjunctiva or underlying sclera given the extended duration of the treatment.
  • adjustments to the annular beam 2603 can be provided during a treatment in response to a surface temperature detection obtained with the imaging/detection o- optics 2620.
  • the treatment controller 2618 can be configured to monitor the detected surface temperature of the perilimbal region 2604 at or near where the beam annulus 2607 is delivered. The controller 2618 can then dynamically compare the measured surface temperature to a look-up table relating surface temperature to temperature of targeted sub-scleral biological structures and then adjust characteristics of the beam annulus 2607, such as laser power, annulus position, annulus size, etc., in order to maintain the temperature of the sub-scleral biological structures within an elevated therapeutic range for a sufficient therapeutic duration.
  • the correlated model prediction can depend on various treatment parameters, such as delivered power, aggregated fluence, temporal position of the current treatment run, etc. Models can be created through experiments of eyes or structures thermally similar to eyes.
  • a perilimbal doughnut-shaped IR 1.475 ⁇ m laser beam is projected to produce a “low irradiance/long exposure” irradiation.
  • the irradiance (W/cm 2 ) can be temperature-controlled to balance the heat generated at the sclera with the heat dissipated toward sub-scleral targets, such as three cooler targets of the conventional outflow pathway (TM, SC, CC), the ciliary body, and the pars plana uveoscleral outflow pathway. These targets generally underlie three successively larger radii outward from the limbus.
  • a 43-45 0C nonlethal hyperthermia is created and maintained for ⁇ 30 s, with no damage to the laser absorbing conjunctiva and superficial sclera.
  • Consistent thermal conversion can be provided by a relatively uniform distribution of cellular water, the main absorbing chromophore of this IR laser wavelength. Such a consistency is unattainable with visible laser wavelengths absorbed by unevenly distributed melanin and hemoglobin chromophores.
  • disclosed examples can provide consistent laser energy/heat photothermal conversion in cellular water.
  • Laser Trabeculoplasty is an effective hypotensive glaucoma treatment, which has been recently reevaluated to primary intervention by the outcomes of the benchmark LIGHT trial that has validated the values of SLT as a first line treatment. Furthermore, the NIH/NEI founded COAST trial currently in progress may provide conclusive evidence that will prompt the paradigm shift from LT treatment to LT periodic ongoing therapy. There are common pathways affecting the IOP lowering, that are activated by different nonspecific stimuli, and what was once believed to be the response to a photocoagulation or to a photo-ablation, or to a photo-thermolysis of the TM, can now be understood as the response to a photothermal-stimulation that does not require prerequisite tissue destruction.
  • a non-gonioscopic, ab-externo, photothermal stimulation is used to trigger a trabeculoplasty-like stress response provide an advantageous and therefore desirable option for the early and the long-term management of patients with chronic progressive neurodegenerative glaucoma.
  • the hyperthermia at the humor aqueous regulating structures (trabecular meshwork, Schlemm’s canal, connector channels, ciliary processes, and uveoscleral outflow) provides an IOP lowering therapeutic effect triggered by a trabeculoplasty-like response, which is similar in all non- incisional and non-pharmaceutical hypotensive treatments.
  • a 43-45 0C hyperthermia stimulus can be directly created sublethal, while.
  • FIG.27 is an example laser eye treatment system 2700 that includes an axicon 2702 configured to produce an annular beam 2704.
  • the axicon 2702 is diffractive axicon, through refractive types may be used as well.
  • the system 2700 includes a laser source 2706 situated to produce a source beam 2708.
  • the source beam 2708 is collimated, e.g., with one or more collimating optics 2710, to produce a collimated beam 2712.
  • the laser source 2706 includes collimating optics and produces the collimated beam 2712 as its output.
  • the system 2700 can include a beam expander 2714 that include one or more optical elements situated to adjust a collimated beam width of the beam 2712 to produce a collimated beam 2716 having a larger or smaller width or diameter.
  • a focus lens 2718 can be situated to receive the collimated 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 beam 2716 and to produce a focusing beam 2720.
  • the axicon 2702 can then receive the focusing beam 2720 and produce the annular beam 2704.
  • the annular beam 2704 can be brought to a focus at a focus plane 2722, which preferably corresponds to a surface of an eye being treated.
  • the system 2700 can include a controller 2724 that can be coupled to the laser source 2706 to control when the annular beam 2704 is produced along with duration and/or power level or irradiance.
  • the controller 2724 can be coupled to the beam expander 2714 to adjust a width of the collimated beam 2716 and thereby control a thickness of the annular beam 2704 at the focus plane 2722.
  • the controller 2724 can be coupled to one or more movement stages, such as stages 2726, 2728, to control a relative movement between different optical components of the system 2700 and the plane 2722.
  • the axicon 2702 can be translated along an optical axis of the beam 2704, e.g., to or away from the focus lens 2718, to thereby increase or decrease a mean diameter of the annular beam 2704 at the focus plane 2722.
  • system 2700 can include other components, such as one or more components similar to those shown in any of the examples previously described hereinabove, including but not limited to other laser sources at other wavelengths (e.g., for trans-pupillary treatments), patient interface devices, imaging devices, standoffs, etc., though such components are not shown for clarity of illustration.
  • examples of the system 2700 are not limited to the displayed arrangement.
  • various components can be omitted, added, or arranged in various positions or orders relative to each other and can include additional or fewer lens or lens assemblies.
  • an additional axicon may be situated to generate a collimated or focused annular beam.
  • FIG.28 is bundled arrangement 2800 of optical fibers 2802 that can be used as an optical source for generating an annular beam that can be directed to an eye of a patient.
  • the optical fibers 2802 can be closely packed in various forms, such as hexagonally as shown, circular, or another shape.
  • separate laser sources may be coupled to each optical fiber 2802 and selectively powered so that an annular shape formed by illuminating a circular set of the optical fibers 2802 can be adjusted with respect to centroidal position, diameter, and/or annular width.
  • as few as one row of the optical fibers 2802 is arranged to form a circle.
  • the output beams from fibers 2802 can be directed directly to an eye or to various intermediate optics, such as one or more focusing lenses, beam expanders, etc., before forming an annular beam cross- section at the eye for treating sub-scleral biological structures.
  • Overlaid in FIG.28 is an example inner, middle, and outer diameters 2804a,2804b, 2804c of a perilimbal treatment zone of an eye, though the size and shape may be adjusted and need not correspond to the cross-sectional dimensions of the bundled arrangement 2800.
  • FIG.29 is an annular waveguide 2900 configured to 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 emit an annular beam from a waveguide output.
  • the annular beam can be used as a source beam that can be imaged and/or reshaped to form a fixed or variable treatment annulus at an eye.
  • an annular aperture can be used to produce a source beam.
  • FIG.30 is a graph 3000 of an example treatment performed with a continuously applied annular beam.
  • a beam is generated with a selected irradiance profile 3002, e.g., a constant irradiance produced at a constant laser power.
  • a temperature 3003 of certain sub-scleral biological structures increases over time to a therapeutic range 3004 that produces a trabeculoplasty- like response.
  • the range 3004 is between 43-45 °C. Entrance into this therapeutic range 3004 can occur at an initial time t1 and can be sustained for a duration that terminates at a time t2. So as to define a therapeutic hyperthermic treatment window t 2 -t 1 .
  • the duration t 2 -t 1 can correspond to a therapeutic hyperthermic treatment window during which the sub-scleral structures are elevated within the range 3004.
  • Representative treatment windows have an extended duration compared to other approaches, with many suitable durations being greater than or equal to about 30 s, though durations may vary depending on the patient’s characteristics and conditions.
  • the irradiance can be reduced before the time t 2 , such as at a time t off , by reducing or ceasing laser power.
  • non-constant irradiances may be used in some examples.
  • an irradiance profile 3006 can include a higher initial irradiance before decreasing to a constant irradiance for a subsequent duration.
  • other irradiances may be used in continuously directing an annular beam to an eye to produce a trabeculoplasty-like response.
  • the annular beam can be continuously applied to a specific annular area, such as perilimbal region adjacent to a corneolimbal junction.
  • the annular beam can be scanned through the targeted perilimbal region, e.g., by smoothly or abruptly changing the diameter and/or width of the annular beam.
  • the irradiance for a particular area in the targeted perilimbal region can also vary based on the movement and positioning of the annular beam relative.
  • FIG.31 is a graph 3100 showing an example showing an interplay between power 3102, irradiance 3104, and annular beam area 3106.
  • a laser beam can be produced with a constant power.
  • a higher initial irradiance can be produced until a time tchange, e.g., by varying the annular area 3106 through a smaller initial annular width.
  • Smaller initial irradiances, larger initial areas, larger or smaller initial beam powers, etc., 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 may be used and adjusted to deliver energy for a sufficient duration to produce at a trabeculoplasty- like response.
  • FIG.32 is a graph 3200 of another example treatment performed with an annular beam having a continuous-wave power.
  • a power profile 3202 includes a series of alternating on- durations and off-durations for applying the continuous-wave annular beam to the conjunctiva in a targeted perilimbal region adjacent to a corneolimbal junction. As shown, the power profile 3202 has a duty cycle of about 66%, with on-durations lasting for 100s of milliseconds to seconds. Other duty cycles are possible, such as 5%, 10%, 25%, 50%, 80%, 95%, etc.
  • the annular beam is applied to raise a temperature 3203 of targeted sub-scleral biological structures into a therapeutic hyperthermic temperature range 3204 for a selected target duration t2-t1 associated with beneficial therapeutic effects (such as at least 20 s, 25 s, 30 s, etc.).
  • power profiles can include a duty cycle that varies throughout the treatment, e.g., by increasing and/or decreasing with time.
  • Other treatment parameters can also be varied or included.
  • irradiance characteristics of the annular beam can be varied with respect to time, such as by adjusting the laser beam power and/or irradiance profile.
  • the annular beam can be scanned such that a position (e.g., a mean diameter) and/or area (e.g., an annular thickness) of the annular beam changes with respect to time.
  • treatment parameters can be adjusted dynamically in response to a detected parameter during treatment, such as surface temperature.
  • detections can occur continuously or at discrete times during treatment. Detections can be coordinated with annular beam timing in some examples.
  • a thermal imaging device such as a camera, CCD, pyrometer, or other device can be coupled to monitor a temperature of a selected surface during treatment. In some instances, the monitoring can be coordinated with and/or use information obtained from the time periods during which the laser beam is off or not being applied to the selected surface.
  • the thermal imaging device can be gated to detect the surface based on the off periods.
  • a temperature decay profile detected during the off period can be used to assist with determining a temperature of the sub-scleral biological structures and whether the sub-scleral temperature is within the therapeutic hyperthermic temperature range 3204.
  • FIG.33 is a beam annulus 3300 that is directed to a target perilimbal region 3302 of an eye 3304 for treatment.
  • a cornea 3306 of the eye 3304 is approximately circular and an optical axis 3308 of the eye 3304 approximately centered in the cornea 3306.
  • Other ocular features such as the 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 iris and pupil are omitted for clarity.
  • a conjunctiva 3310 is situated radially outward from the cornea 3306 and generally separated by a corneolimbal junction 3312.
  • the region 3302 corresponds to a surface of the conjunctiva 3310 to which the beam annulus 3300 is directed to locally heat to a hyperthermic level a broad geographic set of underlying sub-scleral biological structures in order to produce a therapeutic response.
  • the perilimbal region 3302 can be defined as being adjacent to the corneolimbal junction 3312 and extending radially outward from the corneolimbal junction 3312.
  • An inner diameter of the perilimbal region 3302 can be at the corneolimbal junction 3312, but in more representative examples the inner diameter begins about 1 mm posteriorly to the corneolimbal junction 3312.
  • the outer diameter of the perilimbal region 3302 can be about 4 mm posterior to the corneolimbal junction 3312, though other outer diameters can be used in some examples.
  • the beam annulus 3300 includes inner and outer annular edges 3314a, 3314b within which most or all of the energy of the beam annulus 3300 lies and a central axis 3316 bisecting the edges 3314a, 3314b.
  • the beam annulus 3300 can be configured to extend across the entirety of the perilimbal region 3302.
  • the beam annulus 3300 can be scanned radially inward and/or outward, e.g., as shown by scan arrow 3318 and an inner repositioned beam annulus 3320.
  • FIG.34A-34E show different irradiance profiles 3400A-3400E and scanning techniques that can be used or combined in various examples.
  • the profiles 3400A-3400E are generally shown cross-sectionally with the thickness direction of the beam annulus shown horizontally.
  • the profile 3400A has a flat-top irradiance distribution and the profile 3400A is scanned radially to a second position (shown dashed).
  • the profile 3400B has a more Gaussian distribution and it is also scanned radially to a second position (shown dashed).
  • the profile 3400C has a skewed distribution towards an inner portion of an associated targeted perilimbal region.
  • the profile 3400C is scanned radially to a second position (shown dashed).
  • the skew of the profile 3400C is adjusted so that The skew continues to be directed towards the inner portion of the targeted perilimbal region.
  • the skew can remain the same through scanning, or the skew can be skewed towards an outer portion of the perilimbal region and adjusted during the scanning so that the skew becomes directed towards an opposite outer portion of the targeted perilimbal region.
  • the profile 3400D has a depressed inner region. In some examples, the profile 3400D can also be scanned.
  • the profile 3400E has a skew towards an outer region of a targeted perilimbal region, and during treatment the profile 3400E is adjusted to a second position (shown dashed) in which the skew is skewed towards an opposite outer region of the targeted perilimbal region, e.g., without scanning.
  • 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 various methods can be employed with described apparatus, including methods of treating or preventing eye conditions.
  • methods can include directing a continuous-wave beam annulus to a surface of an eye about 0 to 4 mm posteriorly from a corneolimbal junction.
  • the beam annulus can have a water absorptive wavelength of about 1.475 ⁇ m and can be directed in a controlled manner to the surface elevate a temperature of various sub- scleral biological structures into a therapeutic range of about 43 to 45 °C. Through this surface beam direction, the sub-surface therapeutic temperature can be sustained for a therapeutic duration of about at least 30 s.
  • the apparatus can be aligned in relation to the surface of the eye, the continuous-wave beam can be formed with fixed power and irradiance characteristics, and the beam can be directed for a fixed duration.
  • characteristics of the alignment, beam formation, and beam direction can be adjusted before and/or during the treatment.
  • FIG.35 is a flowchart of further example methods 3500 that can be used to adjust treatment based on a detected surface temperature.
  • a continuous-wave laser beam is directed to a scleral surface while avoiding the cornea.
  • the laser energy is absorbed by surface and sub-surface tissue, causing a controlled increase in temperature of sub-scleral biological structures into a therapeutic hyperthermic temperature window and causing the delivery of energy to occur for an extended duration to maintain the elevated temperature for a therapeutically significant duration.
  • the laser is directed to the scleral surface in the form of an annulus.
  • a surface temperature at or near the scleral surface where the laser beam is applied can be detected at 3504.
  • the surface detected can correspond to the annular area of the beam annulus or an annular area of the surface to be treated. Detection or imaging can occur before and during beam delivery. In some examples, detection can occur during time periods in treatment when the laser beam is not being received by the eye, such as breaks or pauses in the beam delivery. In various examples, methods 3500 can use the surface temperature detection to control laser beam delivery and the associated rise in temperature of the sub-scleral biological structures. For example, at 3506, the surface temperature can be compared with a predetermined thermal model of the eye relating the change in scleral surface temperature caused by the delivery of the laser beam energy to a prediction of tissue damage to the conjunctiva or other biological structures.
  • the predetermined thermal model can relate the detected surface temperature to the laser parameters used to generate the temperature increase. Based on this comparison, at 3508, the laser parameters can be adjusted to reduce the surface temperature, e.g., by reducing laser power or 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 turning off the laser.
  • the predetermined thermal model can define a single maximum temperature that should not be exceeded.
  • the predetermined thermal model can define different maximum temperatures based on laser parameters used, treatment duration or temporal position within the treatment session, and/or characteristics of the patient or eye being treated.
  • the comparison and temperature reduction can also operate as a safety interlock mechanism to protect the eye and to ensure compliance of the laser system with health requirements.
  • detected surface temperature can be used as measurement variable to control around, with the measured surface temperature being correlated to a temperature of sub-scleral biological structures being targeted for treatment.
  • the measured surface temperature can be compared with a surface temperature of a predetermined thermal model relating scleral surface temperature increase caused by the laser beam and a temperature increase of targeted underlying sub-scleral biological structures. Based on the comparison, at 3512, one or more laser parameters can then be dynamically adjusted during the treatment to thereby maintain the elevated temperature of the sub-scleral biological structures within the therapeutic hyperthermic temperature window.
  • FIG.36 is an example laser treatment system 3600 that can be used to monitor and control an inferred temperature of sub-scleral biological structures targeted for a therapeutic hyperthermic treatment by using scleral surface temperature measurements.
  • the system 3600 includes a laser and optics subsystem 3602 that is configured to direct a laser beam to an eye’s perilimbal surface region 3604.
  • a temperature sensor/imager 3606 is coupled to detect a surface temperature of the perilimbal surface region 3604, e.g., through the optics of the laser and optics subsystem 3602. The surface temperature is detected and converted to temperature measurements 3608.
  • a thermal model look-up table 3612 or other control arrangement can be used to relate the measured surface temperature measurements 3608 to the temperature of the underlying sub-scleral biological structures so that session laser parameters 3614 can be dynamically updated in response to the surface temperature measurements 3608.
  • the model estimates and associated adjustments can be determined using the temperature measurements 3608, the current and past laser parameters 3614 used in the session, and the duration of delivery (e.g., tracked with a session timer 3616).
  • the system 3600 can be operable to maintain the temperature of the targeted sub-scleral biological structures within an elevated therapeutic range for an extended duration.
  • FIG.37 is an example of a laser treatment system 3700 that can be used to laser-treat an eye 3702 to produce a sublethal rise in temperature in a set of sub-scleral biological structures of the eye 3702 in accordance with the trabeculoplasty-like response described hereinabove.
  • the system 3700 can include many components similar to system 2600, e.g., a laser source 3712 (such as a CW laser source), annulus optics 3716, a treatment controller 3718, imaging/detection optics 3720, and/or a beam splitter 3722 to couple the imaging/detection optics 3720 and annulus optics 3716 to the eye 3702.
  • a laser source 3712 such as a CW laser source
  • annulus optics 3716 to couple the imaging/detection optics 3720 and annulus optics 3716 to the eye 3702.
  • the laser treatment system 3700 can be configured to produce a sublethal rise in temperature in a set of sub-scleral biological structures of an eye 3702 in accordance with the trabeculoplasty-like response described above.
  • the system 3700 is operable to produce a laser beam 3701 with an annular shape 3703 (only a schematized vertical cross-section being shown; also referred to as an annular beam 3703) that can be used to minimize, avoid, or reduce tissue damage relative to other techniques that may produce IOP reductions.
  • the sub-scleral biological structures which can include (ordered posteriorly) trabecular meshwork, Schlemm’s canal, collector channels, ciliary body, pars plana, and uveoscleral outflow pathways, etc., are situated a few hundred microns beneath a perilimbal region 3704 (shown between dashed lines) of a conjunctiva and underlying sclera 3706.
  • the field of laser irradiation of the annular beam 3703 can extend across the surface of the conjunctiva to form a 3600 beam annulus 3707 in at least part of the perilimbal region 3704.
  • the perilimbal region 2604 can be defined as a radial range adjacently posterior to a corneolimbal junction 3708, though such ranges can vary and depend on the anatomical characteristics of the patient’s eye.
  • the application of the beam annulus 3707 can be used to produce the hyperthermic response for the range of sub-scleral biological structures.
  • the system 3700 can also include an aiming source 3719 situated to produce light with a visible wavelength (e.g., in the range from about 380 nm to about 700 nm) that can be coupled with the therapeutic light with a beam splitter 3721 or other beam coupler.
  • the visible light and therapeutic light can form a common beam 3714 that can be received by the annulus optics 3716.
  • the CW laser source 3712 and the aiming source 3719 can be coupled into a common optical fiber that is arranged to emit light towards the annulus optics 3716.
  • the annulus optics 3716 can thereby direct and form the annulus beam 3703 with both visible and therapeutic wavelengths.
  • a visible portion of the beam annulus 3707 has a smaller inner diameter at the eye than an inner diameter of a therapeutic portion of the beam annulus 3707.
  • the visible portion of the annulus beam 3703 can form an aiming beam portion of the beam annulus 3707 that can be aligned in relation to the perilimbal region 3704 and/or 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 corneolimbal junction 3708. This can ensure that the therapeutic light of the therapeutic portion of the beam annulus 3707 is aligned with a target area for treatment and does not impinge on the cornea or a non-target region.
  • the visible portion of the beam annulus 3707 can be viewed with the imaging/detection optics 3720, or by directly viewing the eye 3702 from a side.
  • an inner diameter of the therapeutic portion of the beam annulus 3707 can coincide or approximately coincide with an outer diameter of the aiming portion of the beam annulus 3707.
  • the therapeutic and aiming portions of the beam annulus 3707 can be spaced apart or can overlap.
  • the different optical sources 3712, 3719 can be independently controlled so that the visible light can be turned on for alignment purposes before therapeutic light is turned on.
  • infrared light of the annulus 3707 for glaucoma treatments described herein it can be beneficial to have knowledge of location of that infrared light at the eye so as to prevent accidental damage to the eye.
  • Infrared light is invisible to the human eye and common RGB cameras.
  • infrared cameras are generally expensive, can require cooling, and often provide low resolution images.
  • an infrared beam is only rendered visible with an infrared camera while the infrared beam is in an on-state, which can be dangerous if its aimed location is unknown before turning it on.
  • a visible guide beam (also referred to as an aiming beam) is provided that can indicate the location of the infrared beam, e.g., before turning on the infrared beam to provide therapeutic treatment with the infrared light.
  • the visible guide beam can create an “exclusion zone” with the substantial certainty that the infrared light is or will not be in that region. For eye treatment, this exclusion zone can correspond to the iris, pupil, and/or cornea of the eye.
  • the infrared beam and the aiming beam can be provided with this substantial certainty by being created such that the infrared beam and the aiming beam form annuli in the same relationship to each other.
  • the infrared light and the visible light that form the respective annuli at the eye have a common emission origin upstream from the eye, and subsequently follow a common optical path through a set of annulus optics that form the annuli at the eye.
  • separate optical paths can become misaligned or can degrade separately over time, thereby removing the exclusion zone certainty.
  • the infrared beam and visible beam can be provided with a common emission origin with the use of an optical fiber as an input for an optical system forming the annuli at the eye.
  • a visible beam source and a separate infrared beam source can each generate light that is coupled into a common delivery 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 (optical) fiber, and an output of the delivery fiber can be situated to emit an input beam for the optical system.
  • the visible light annulus formed at the eye can be coincident with the infrared light annulus formed at the eye.
  • the optical system can use one or more refractive axicons to form an annulus at the treatment surface.
  • the axicon will typically cause the visible light portion of the annulus to lie farther out (e.g., have a larger diameter) than the infrared light portion of the annulus.
  • the optical system can be configured so that infrared light portion of the annulus is farther out (e.g., has a larger diameter) than the visible light portion of the annulus. This can allow a physician to have certainty that the infrared light does not enter the pupil of the eye because the pupil is situated in the exclusion zone arranged in relation to the visible light portion of the annulus.
  • Refractive axicons are lenses that include a conical surface and an opposing surface that is often flat though other surface profiles may be used. The axicon receives an incoming beam of light and converts it to a diverging cone of light.
  • a positive axicon causes a collimated input beam to converge and then quickly to diverge
  • a negative axicon causes a collimated input beam to diverge.
  • the axicon will typically create the undesirable output in which the visible light annulus is outside the infrared annulus. This is because the index of refraction for many practical optical materials decreases with increasing wavelength and the axicon will refract light according to Snell’s law (which defines the refraction angle based on the refractive index of the axicon material).
  • the refraction angle of the axicon generally increases for decreasing wavelength thereby placing the refracted visible light outside the infrared light portion of the annulus.
  • the effect is similar for both positive and negative axicons, such that for a commonly collimated input beam, a visible light annulus is always positioned outside of the infrared light, or at best, nearly coincident with the infrared light.
  • the visible light portion of the annulus formed at the eye can be made to have an inner diameter that is smaller than an inner diameter of the infrared light portion of the annulus.
  • a guide beam of visible light can be created that has a fixed correspondence to a co-axial beam of infrared light.
  • the guide beam can be created in such a way that the visible light can be turned on independent of the infrared light, so that an operator can have knowledge that the infrared light will be in the intended treatment zone before the infrared light is turned on.
  • an exclusion zone can be defined with the visible light, e.g., if the pupil of the eye is contained inside the ring of visible light, then the infrared light is necessarily outside this ring and therefore not a threat to the eye.
  • the diameters of the annulus can be changed to accommodate different eye diameters and therefore different diameters of the corneolimbal junction 3708.
  • the diameter can be scanned (or dithered) during the treatment to smooth over delivery of the infrared energy in the perilimbal region 3704.
  • Chromatic aberration is the effect responsible for the fact that the visible and infrared light are refracted through two different angles. As discussed above, refractive index of a material typically varies with respect to wavelength.
  • chromatic aberration can be intentionally introduced into the visible and infrared source light preceding the input to the axicon.
  • chromatic aberration of the opposite sign can be introduced in the pre-axicon optics to induce an effect opposite to and larger than the aberration effect introduced by the axicon.
  • the visible light portion of the source beam is not collimated as it impinges the axicon where the infrared light portion of the source beam is collimated as it impinges the axicon
  • the visible light portion can be directed to a different diameter position at the eye relative to the infrared light.
  • the visible light converging or diverging to the axicon so as to achieve the positioning of the visible light portion of the annulus with a smaller inner diameter than the infrared light portion of the annulus, depends on whether the axicon is positive or negative.
  • axicon optical systems can include lens elements that introduce a degree of chromatic aberration that is sufficiently large to counteract or reverse the normal effect of an axicon so that a visible light portion of a generated annulus has a smaller inner diameter than an infrared light portion of the annulus.
  • the chromatic aberration can be introduced preceding one or more of the axicons of the optical system, so that there is a difference with respect to collimation, convergence, and/or divergence between the infrared portion of the source beam and the visible portion of the source beam propagating along a common optical axis.
  • the chromatic aberration can be introduced preceding one or more of the axicons of the optical system, so that there is a difference with respect to beam width (e.g., convergent or 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 divergent, but more typically collimated) between the infrared portion of the source beam and the visible portion of the source beam propagating along a common optical axis at the input of the axicon element.
  • the portion of the optical system preceding the axicon can operate as a wavelength-sensitive beam expander causing a visible beam portion of an input beam to have a smaller diameter at the input of the axicon than an infrared process portion of the input beam.
  • chromatic aberration is something that is commonly sought to be minimized.
  • a camera lens for example, it is generally desirable that each red, green, and blue image to coincide, and so a camera lens with this degree of chromatic aberration described would be useless in such camera systems.
  • axicons can be made from fused silica while one or more other lens elements are made from other materials, such as zinc sulfide.
  • fused silica and zinc sulfide transmit both infrared and visible light
  • the difference in refractive index between infrared wavelengths and visible wavelengths is significantly greater with zinc sulfide, allowing it to be an effective lens material in building up a large degree of chromatic aberration to overcome the natural chromatic aberration of the axicon.
  • fused silica in the axicon which has a relatively small difference in refractive index between infrared and visible, allows there to be a smaller aberration contribution by the axicon to overcome.
  • non-axicon optical systems can be configured with similar properties as axicon-based optical systems described herein in which the visible light can be inside the IR light rather than the visible and IR light being coincident or with the visible outside the IR.
  • Each non- axicon optical system (masking, DMD, fiber array, etc.) can use a relay lens that is situated to project an annular image onto the eye.
  • the relay lens can be configured to introduce a large chromatic aberration as described herein so that the visible ring can be formed inside the IR ring.
  • a relay lens (which include one or more lens elements) receiving the annuli can introduce a large amount of lateral chromatic aberration as it projects the annuli to the eye.
  • the visible ring can be formed inside infrared annulus to create an exclusion zone.
  • the relay lens can be configured to have two separate magnifications for visible and infrared wavelengths.
  • FIG.38 is an example axicon-based optical system 3800 for therapeutic processing of an eye 3802, e.g., according to any of the therapeutic techniques described herein.
  • the system 3800 includes an infrared stimulation source 3804 and visible aiming source 3806, each generating light 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 that can be coupled into an optical fiber 3808.
  • the stimulation source 3804 can generate stimulation light configured to provide a therapeutic effect according to techniques described herein, e.g., infrared light having a wavelength longer than 1 ⁇ m and water-absorptive (e.g., in the range of 1.4-1.6 ⁇ m, with 1.475 ⁇ m or 1.55 ⁇ m being suitable in many examples).
  • the visible aiming source 3806 generates visible light that is in the visible spectrum, e.g., in the range of about 380 nm to about 700 nm.
  • the visible light can have a red wavelength, such as in the range 630 nm to 670 nm.
  • the stimulation light and visible light can be coupled into the optical fiber 3808 in various ways, e.g., through fiber or free-space.
  • separate fibers coupled to the stimulation and aiming sources 3804, 3806 can propagating the respective lights and be situated as inputs to a fused fiber coupler.
  • the fused fiber coupler can have an output fiber portion that propagates both lights and that can correspond to or be coupled to an input end of the optical fiber 3808.
  • the stimulation light and visible light can be directed to a wavelength multiplexer, e.g., a prism having a surface that is either reflective or transmissive at the wavelength (or wavelengths) of the stimulation light or the visible light, so that both lights can be combined to propagate along a common optical path to couple into an input end of the optical fiber 3808.
  • the stimulation and visible lights can be coupled into a common core of the optical fiber 3808 so that the lights can mix and be emitted from the core at an output end of the optical fiber 3808 in a mixed state.
  • the emitted light from the output end of the optical fiber 3808 can be received by an axicon optical system 3810 that can be situated to receive the light and produce an annulus at the surface of the eye 3802.
  • Suitable core diameters at the output end of the optical fiber 3808 can include 25 ⁇ m, 50 ⁇ m, 100 ⁇ m, 125 ⁇ m, 200 ⁇ m, etc.
  • the core diameter at the output can determine a radial intensity distribution in a downstream annulus produced with the axicon optical system 3810. For example, a smaller optical fiber core diameter can produce a smaller thickness and steeper drop-off in the intensity distribution of the annulus.
  • the co- propagation of the stimulation and visible lights in the optical core and the common emission of the stimulation and visible lights from the optical core can be used to produce a well-defined and robust optical source for a subsequent axicon optical system 3810 that produces an annulus at the surface of the eye.
  • FIG.39 shows a schematic depiction of a beam annulus 3900 produced at a processing plane (e.g., corresponding to the plane of FIG.39) with various optical systems described herein, such as axicon-based optical systems including but not limited to axicon-based optical system 3800.
  • the processing plane can be made to intersect a circular region of the eye that begins at or near and extends radially outward from a corneolimbal junction of the eye, so that the beam annulus 3900 is projected onto the curved surface of the eye on the conjunctiva.
  • the beam annulus 3900 includes a visible annulus portion 3902, indicated with inner and outer beam boundaries 3904a, 3904b (dashed lines) and center diameter 3906 (centerline), and an infrared annulus portion 3908, indicated with inner and outer beam boundaries 3910a, 3910b (solid lines) and center diameter 3912 (centerline).
  • the annulus portions 3902, 3908 can be concentric.
  • the annulus portions 3902, 3908 can maintain a constant or approximately constant relative radial relationship to each other over a range of adjustments to a diameter 3914 (small dashed line) of the beam annulus 3900.
  • a diameter 3914 small dashed line
  • controlled movement of an axicon or other optical element of an axicon-based optical system can cause a change in the diameter 3914 of the beam annulus 3900.
  • Change of the diameter 3914 can also cause the diameters 3906, 3912 of the visible and infrared annulus portions 3902, 3908 to change by the same or approximately the same amount over a suitable range.
  • this change, or variation can be used to adapt the beam annulus 3900 to a size of an eye that is being treated and/or the change can be varied over time during the treatment of an eye, e.g., to scan annular energy radially across a target surface of the conjunctiva associated with underlying structures to be treated.
  • Examples of constant or approximately constant relative radial relationship for various described examples can include less than or equal to +/- 1%, 2%, 5%, or 10% over a portion of a range of translation, e.g., 5%, 10%, 20%, or 50% of a range of translation.
  • the constant or approximately constant relative radial relationship can be maintained at least in part due to emission of visible and infrared source light portions, associated with the respective annulus portions 3902, 3908 of the beam annulus 3900, from a common optical fiber tip.
  • the constant or approximately constant relative radial relationship such that the inner boundary 3904a of the visible annulus portion 3902 is radially inward from the inner boundary 3910a of the infrared annulus portion can be maintained due to chromatic aberration intentionally introduced by an axicon-based or other optical system that produces the beam annulus 3900.
  • both common emission and intentional 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 chromatic aberration in an axicon-based optical system are used to produce the beam annulus 3900 with the inner boundary 3904a of the visible annulus portion 3902 radially inward from the inner boundary 3910a of the infrared annulus portion.
  • the inner boundary 3904a of the visible annulus portion 3902 is radially inward from the inner boundary 3910a of the infrared annulus portion 3908 such that there is a significant overlap (e.g., greater than 50%) of the annulus portions 3902, 3908.
  • the amount of overlap can be different and can be determined based on pre-configured parameters of the optical system used to produce the beam annulus 3900, such as optical surface parameters, compositions, fiber sizes, wavelength dependent aberration, etc.
  • the known relative radial relationship can be used to allow an operator or automated alignment mechanism to precisely align the infrared annulus portion 3908 relative to one or more features of the eye without seeing or the treatment system detecting positional features of the infrared annulus portion 3908.
  • the outer boundary 3904b of the visible annulus portion 3902 can be the same as or near the inner boundary 3910a of the infrared annulus portion 3908 (e.g., with some small amount of overlap or by being spaced apart with effectively zero overlap) and the radial thicknesses of the annulus portions 3902, 3908 can be approximately the same. This can allow for precise positioning of the infrared annulus portion 3908 such that the infrared annulus portion 3908 lies in a perilimbal treatment region of the eye posterior to the corneolimbal junction.
  • a 2 mm thickness of the adjacent infrared annulus portion 3908 can then lie within the perilimbal region.
  • the inner boundary 3910a can be positioned at 2 mm radially outward from the corneolimbal junction and the outer boundary 3910b can be positioned at 4 mm radially outward from the corneolimbal junction.
  • various annular thicknesses and overlaps may be used in different examples.
  • FIG.40 is an optical modeling image 4000 of an example visible annulus 4002 that lies within a therapeutic process annulus 4004. As shown, an outer boundary of the visible annulus 4002 adjoins an inner boundary of the therapeutic process annulus 4004.
  • the annuli 4002, 4004 are formed with an axicon-based optical system.
  • FIG.41A-41B is an optical system 4100 that can be used to produce therapeutic and aiming annuli for treatment of an eye or other surfaces of interest (including other anatomical regions such as skin), e.g., according to any of the methods described herein.
  • the optical system 4100 can include, in order from an object side to an image side along an optical axis 4101, an object source 4102, a window element 4104, a first lens element 4106, a second lens element 4108, a third lens element 4110, a fourth lens element 4112, and an image plane 4114 (shown in the ray trace in FIG. 41B).
  • the object source 4102 can correspond to a tip of an optical fiber and an aperture stop of the system 4100 can be defined at the emission plane of the fiber tip.
  • the window element 4104 can include object and image surfaces 4116, 4118 and can be situated a short distance from the object source 4102 can be made of fused silica or another material. In some examples, at least portion of one or both surfaces 4116, 4118 can be coated with a wavelength sensitive coating to provide filtering of undesired wavelengths and/or anti-reflective characteristics.
  • the window element 4104 can include an obscuration region on one or both surfaces 4116, 4118 that can serve to block and/or scatter unwanted light.
  • a circular opaque region 4120 is situated on the surface 4116 and centered about the optical axis 4101.
  • the obscuration region can be situated to block and/or scatter primarily paraxially directed light. Blocking of such light can reduce additional undesirable subsequent scattering by the fourth lens element 4112, which is typically an axicon lens element.
  • the obscuration region can be arranged on a separate element adjacent to the window element 4104.
  • the first lens element 4106 has object and image side surfaces 4122, 4124.
  • the object and image side surfaces 4122, 4124 can be convex near the optical axis 4101.
  • one or both of the surfaces 4122, 4124 can be aspheric.
  • the object side surface 4122 is aspheric and the image side surface 4124 is not.
  • the first lens element 4106 can be made of a suitable material having a dispersion sufficient to provide a refractive index that varies significantly between a visible aiming wavelength and an infrared process wavelength. In some examples, the first lens element 4106 can be made of zinc sulfide.
  • the second lens element 4108 has object and image side surfaces 4126, 4128.
  • the object side surface 4126 can be convex near the optical axis 4101 and the image side surface 4128 can be concave near the optical axis 4101. In various examples, one or both of the surfaces 4126, 4128 can be aspheric.
  • the object side surface 4126 is not aspheric and the image side surface 4128 is aspheric.
  • the second lens element 4108 can be made of a suitable material having a dispersion sufficient to provide a refractive index that varies 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 significantly between a visible aiming wavelength and an infrared process wavelength.
  • the second lens element 4108 can be made of zinc sulfide or a material that is similar or identical to a material composition of the first lens element 4106.
  • the third lens element 4110 has object and image side surfaces 4130, 4132.
  • the object side surface 4130 can be concave and the image side surface 4132 can be convex near the optical axis 4101.
  • one or both of the surfaces 4130, 4132 can be aspheric.
  • the object side surface 4130 is not aspheric and the image side surface 4132 is aspheric.
  • the third lens element 4110 can be made of a suitable material having a dispersion sufficient to provide a refractive index that varies significantly between a visible aiming wavelength and an infrared process wavelength.
  • the third lens element 4108 can be made of zinc sulfide or a material that is similar or identical to a material composition of the first lens element 4106 and/or second lens element 4108.
  • the fourth lens element 4112 has object and image side surfaces 4134, 4136.
  • the fourth lens element 4112 can be an axicon.
  • the fourth lens element 4112 is a positive axicon with the object side surface 4134 being flat and the image side surface 4136 having a convexly conical surface.
  • One or both of the surfaces 4134, 4136 can be aspheric.
  • the conical surface of the axicon can have various angles, such as between about 2 degrees and 30 degrees, though other angles are possible.
  • the fourth lens element 4112 is made of a material having a smaller dispersion relative to one or more of the first, second, and/or third lens elements 4106, 4108, 4110, such that the material of the fourth lens element 4112 has a refractive index that varies less between a visible aiming wavelength and an infrared process wavelength.
  • the fourth lens element 4112 is made of fused silica.
  • the fourth lens element 4112 is made of a material that can be shaped through diamond turning.
  • the fourth lens element 4112 can include an obscuration region on one or both surfaces 4134, 4136 that can serve to block and/or scatter unwanted light.
  • a circular opaque region 4137 is situated on the surface 4136 and centered about the optical axis 4101.
  • the obscuration region can be situated to block and/or scatter primarily paraxially directed light. Blocking of such light can reduce light that could be scattered by the rounded surface at the conical apex of the surface 4136 that could have undesirable penetration into a sensitive downstream axial region, such as through the cornea.
  • the obscuration region can correspond to a separate element arranged adjacent to the fourth lens element 4112.
  • the first equation is for a standard surface and the second equations includes the addition of several polynomial terms for an odd asphere (which includes both odd and even powers of r).
  • the odd order aspheres include both a conic constant and polynomial coefficients ( ⁇ values).
  • thicknesses can be air or a glass (which generally can refer to any suitable material that can refract light) and units are in millimeters.
  • a standard surface type can refer to a spherical or flat surface (e.g., with flat surface having an infinite radius).
  • Thickness refers to a mechanical center thickness which often is referred to as a vertex-to-vertex distance.
  • Material can refer to the name of the material used to compute refraction of light.
  • Clear semi-dia refers to half the diameter of the portion of the lens element that light travels through.
  • Mech semi- dia refers to half the physical diameter of the lens element.
  • Conic refers to the conic constant as found in the standard surface and odd asphere definitions provided in the subsequent tables. Detailed refractive index information for fused silica and zinc sulfide is shown in the graphs in FIGS.42A-42B. Table 1: Surface data for an example of optical system 4100
  • the optical system 4100 can be used to produce an annulus at the image plane 4114 and the annulus can include therapeutic and aiming component annuli, e.g., an infrared annulus and an adjacent visible annulus (spaced apart or overlapping).
  • therapeutic and aiming component annuli e.g., an infrared annulus and an adjacent visible annulus (spaced apart or overlapping).
  • the detailed data and characteristics described above for the particular example of the system 4100 can produce the therapeutic and aiming annuli with a fixed spacing relative to each other at the image plane 4114, preferably with the aiming annulus portion having a smaller diameter than the therapeutic annulus portion.
  • the optical system 4100 can be configured to provide this diameter difference with respect to wavelength based at least in part on the difference in materials between the lens elements 4106, 4108, 4110 having a more dispersive refractive index relation with respect to wavelength and the fourth lens element 4112 having a less dispersive refractive index relation with respect to wavelength.
  • the lens elements 4106, 4108, 4110 can be configured to provide different collimated or near collimated beam widths at the input surface 4134 of the fourth lens element 4112 such that the annuli have different diameters at the image plane 4114.
  • the beam width of a visible wavelength portion of the light received by the surface 4134 can be smaller than the beam width of an infrared wavelength portion of the light received by the surface 4134.
  • the fourth lens element 4112 can be coupled to a movement stage 4138 to translate along the direction of the optical axis 4101 to vary a distance between the fourth lens element 4112 and at least the third lens element 4110.
  • the first, second, and third lens elements 4106, 4108, 4110 can remain fixed relative to each other and the fourth lens element 4112 can translate relative to these elements.
  • the fourth lens element 4112 can be translated to adjust a diameter of the annulus produced at the image plane 4114 and thereby the diameters of any component annuli (such as visible and infrared) of the annulus that is produced.
  • Such adjustment can be performed to adjust annular diameters to correspond to a particular diameter of the target (such as a natural variation in eye diameters or other target variations) and/or to scan the annular diameter during a treatment (smaller to larger, larger to smaller, between smaller and larger, etc.).
  • Various translational ranges can be provided in different examples, e.g., 5 mm, 10 mm, 20 mm, 50 mm, etc.
  • an irradiance profile of individual component annuli across a radial thickness of the component annulus can be relatively uniform across the radial thickness, e.g., similar to those shown in FIGS.34A or 34B.
  • FIGS.43A-43B show the side cross-sectional and on-axis irradiance profiles at an imaging plane, e.g., image plane 4114 (which can correspond to a target position of an eye), for an annulus produced by an axicon-based optical system such as the detailed example of the optical system 4100.
  • an irradiance of a visible portion of the beam annulus inner peaks 4302a, 4302b drops to approximately zero at about 7 mm from an optical axis center and an infrared portion of the beam annulus (outer peaks 4304a, 4304b) has an inner radius where the irradiance is zero at about 8 mm from the optical axis center.
  • FIGS.44A-44B show similar side cross-sectional and on-axis irradiance profiles at an imaging plane except with the axicon positioned at a 30 mm position relative to the third lens element 4110.
  • An irradiance of a visible portion of the beam annulus (inner peaks 4402a, 4402b) drops to approximately zero at about 6 mm from an optical axis center and an infrared portion of the beam annulus (outer peaks 4404a, 4404b) has an inner radius where the irradiance is zero at about 7 mm from the optical axis center.
  • FIGS.45A-45B show another set of similar side cross-sectional and on-axis irradiance profiles at an imaging plane except with the axicon positioned at a 55 mm position relative to the third lens element 4110.
  • An irradiance of a visible portion of the beam annulus drops to approximately zero at about 5 mm from an optical axis center and an infrared portion of the beam annulus (outer peaks 4404a, 4404b) has an inner radius where the irradiance is zero at about 6 mm from the optical axis center.
  • the inner diameter of the infrared annulus deceases to about 6 mm as the distance between the axicon and the image plane decreases.
  • the relative radial spacing and irradiance characteristics of the component visible and infrared annuli remain approximately the same even after the diameter of the annulus decreases.
  • FIG.46 is an example set of methods 4600 that can be used with the various disclosed example apparatus and techniques described herein (including but not limited to optical systems 2600, 3700, 3800, 4100).
  • a first annulus is formed at a target by directing light with a first wavelength from an emission source through an optical system configured to produce an annulus.
  • a second annulus can be formed at the target by directing light with a second wavelength longer than the first wavelength though the optical system from the emission source, wherein the second annulus is concentric with the first annulus and has a larger diameter. This can be useful in various applications where it may be important that the second annulus is radially spaced outward from the first annulus and the second annulus has a longer wavelength, such as an infrared wavelength.
  • Some example applications can include those where an eye’s sclera is therapeutically treated with infrared light and the first annulus can have a visible wavelength to assist with aiming and safety margin to avoid light intrusion through the cornea.
  • diameters of first and second annuli that can be produced at the target can be changed, and the diameter changes can occur by the same or similar amounts, by translating an axicon of the optical system relative to other lens elements of the optical system. Such variation can allow adjustments to the diameter of the second annulus with confidence even while light of the second annulus is not being applied or is not seen or detected.
  • the light of the first and second annuli can be emitted at the same time or one annulus can be produced while the other is not produced.
  • FIG.47 is another example laser treatment system 4700 that can be used, for example, to produce a sublethal rise in temperature in a set of sub-scleral biological structures of an eye 4702 in accordance with the trabeculoplasty-like response described hereinabove.
  • the system 4700 is operable to produce a beam 4701 with an annular shape 4703 (only a schematized vertical cross- section being shown; also referred to as an annular beam 4703) to form an annulus 4707 at the eye 4702.
  • an annular shape 4703 can be used to minimize, avoid, or reduce tissue damage relative to other techniques that may produce IOP reductions.
  • the sub-scleral biological structures which can include (ordered posteriorly) trabecular meshwork, Schlemm’s canal, collector channels, ciliary body, pars plana, and uveoscleral outflow pathways, etc., are situated a few hundred microns beneath a perilimbal region 4704 (shown between dashed lines) of a conjunctiva and underlying sclera 4706.
  • the perilimbal region can be generally posterior to a corneolimbal junction 4708. Examples can provide treatment to the eye 4702, e.g., similar to system 2600 and/or other systems described herein.
  • the system 4700 includes at least a therapeutic laser source 4712 situated to produce a source laser beam 4714.
  • the laser source 4712 is typically a continuous-wave laser source.
  • the system 4700 can further include an aiming source 4713 situated to produce a visible beam 4715.
  • the aiming source 4713 can be one or more LEDs or laser sources.
  • Achromatic imaging optics 4716 e.g., in the form of a plurality of lens elements (such as two, three, or more), are situated to receive the source laser beam 4714 and visible beam 4715 (simultaneously and/or separately).
  • the beams 4714, 4715 are coupled into a common optical fiber 4717 and the achromatic imaging optics 4716 can be situated to receive the source laser beam 4714 and visible beam as a rapidly diverging beam 4718 emitted from an end of the optical fiber 4717.
  • the fiber 4717 is a multimode fiber.
  • the numerical aperture of the fiber was 0.22 though it will be appreciated that other larger or smaller NAs may be used in various examples.
  • the achromatic imaging optics 4716 can be used to magnify the laser beam 4714.
  • Three or more lens elements can be suitable based on the large divergence.
  • two or more of the optical elements of the achromatic imaging optics are glued or cemented together.
  • at least two different materials are used for two or more of the lens elements (e.g., silicon dioxide with various dopants).
  • 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 By way of example, if other optics are not situated after the achromatic imaging optics 4716, the achromatic imaging optic 4716 can be positioned to form an enlarged image of the fiber tip at an image plane (e.g., at the eye 4702).
  • the irradiance profile of the image can be a relatively uniform or top-hat profile.
  • the optics 4716 are achromatic, the enlarged image can be formed such that two different selected wavelengths (e.g., a visible wavelength associated with the visible source 4713 and a therapeutic infrared wavelength associated with the laser source 4712) overlap with a minimal deviation associated with chromatic aberration.
  • This can be convenient in various ways to streamline alignment operations between the laser source 4712, achromatic imaging optics 4716, and other components of the system 4700.
  • the achromatic imaging optics 4716 can be arranged closer together as a unitary element that can be premanufactured as a stand-alone lens assembly.
  • the visible wavelength can be used to align the laser source 4712 with the achromatic imaging optics 4716 without requiring an expensive infrared camera, and similar alignment procedures can follow with the remaining optics including in the absence of an infrared camera.
  • the irradiance profile of the annulus 4707 that can be produced can also have a relative crisp and uniform irradiance profile in the radial (and circumferential) direction, improved energy delivery can be provided during therapeutic treatment along with more well-defined information indicating the position of the annulus 4707.
  • the irradiance profiles of co-radial therapeutic and visible light portions can substantially overlap, e.g., with outer or inner radii of respective portions different by less than about 5%, 2%, 1%, etc., of an annular thickness.
  • the system 4700 can include annulus optics 4720 that can be situated downstream from the achromatic imaging optics 4716 to receive the beam 4718 and to cause the beam to form an annular shape at a downstream position from the annulus optics 4716, e.g., proximate the eye 4702.
  • the annulus optics 4720 can include one or more axicon elements.
  • the annulus optics 4720 can be achromatic or have a selected amount of chromatic aberration between at least two wavelengths, such as visible and therapeutic.
  • the annulus optics 4720 include two axicon elements made of different materials to form an axicon doublet. After propagation through the annulus optics 4720, the beam 4701 can form the annular shape 4703 and produce the beam annulus 4707 at the perilimbal region 4704.
  • the portion of the annulus 4707 that is therapeutic can be concentric with but radially spaced in relation to the portion of the annulus 4707 that is visible by various amounts based on the selected amount of chromatic aberration, including co-radial, the visible radius smaller than the 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 therapeutic radius, or the therapeutic radius smaller than the visible radius.
  • radius generally refers to half a diameter and the terms may be used interchangeably.
  • the radial spacing can be adjusted by varying the slope of one or more of the conical axicon surfaces.
  • the portions are co-radial thereby making the two or more axicon elements achromatic and providing a high degree of confidence regarding the positioning of the therapeutic portion relative to the eye even while only using the visible portion for alignment.
  • the visible radius can be smaller than the therapeutic radius to allow some safety margin in relation to the cornea or to provide a way to position the therapeutic ring using alignment of the visible portion with the corneolimbal junction (or other identifying features of the eye).
  • a movement stage 4722 such as a linear translation stage can be coupled to the annulus optics 4720 to move the annulus optics 4720 (typically as a unit) relative to the achromatic imaging optics 4716.
  • This movement can increase a radius of the annulus 4707 while maintaining the spacing relationship between the therapeutic and visible portions.
  • Such movement can be used in various ways in connection with treatment, such as to adjust to differently sized eyes and/or to scan radially or dither during treatment to smooth delivery of energy to the perilimbal region 4704.
  • One or more additional movement stages can also be coupled to different components of the system for adjustments and/or alignment purposes.
  • one or more stages can be coupled to the fiber 4717 and/or the achromatic imaging optics 4716 to adjust a distance between them and operate as a focus adjustment. In some examples, this can adjustment be performed only during manufacture or refurbishment and in further examples this can form part of the system 4700.
  • the availability of this adjustment can allow for more slack in the tolerancing of the lens surfaces of the achromatic imaging optics 4716 because the distance can be adjusted to compensate for some surface errors.
  • the system 4700 can include additional components along the path from the laser source 4712 to the eye 4702.
  • a beam splitter 4724 can be situated between the achromatic imaging optics 4716 and annulus optics 4720 to direct a portion of the light that travels through the achromatic imaging optics 4716 to imaging/detection optics 4726 for power detection.
  • a beam splitter 4728 can be situated after the annulus optics 4720 to collect light that travels backwards from the eye 4702 towards the annulus optics 4720 and direct the light towards the imaging/detection optics 4720 for imaging of the eye 4702, alignment, or other purposes.
  • a vibrator 4730 e.g., DC motor, piezoelectric transducer, etc.
  • the movement can reduce a speckle associated with the laser source 4712 by rapidly varying optical path length to 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 smooth out irradiance spikes.
  • a diffuser or other speckle reducer may be situated along the optical path, e.g., immediately after the achromatic imaging optics 4716 or at another location, to produce a similar smoothing and reduction of irradiance spikes.
  • a system controller 4732 or other computing device can be coupled to the various components of the system 4700 to control operation, e.g., similar to other examples described herein.
  • Example vibrational frequencies can be in the range 10 Hz to 1 kHz, though other frequencies or frequency ranges (including larger ones) may be used in some examples.
  • FIG.48 is a lens system 4800 that can be used to produce a beam annulus 4800, e.g., for system 4700 or other systems described herein.
  • the lens system 4800 includes a source position, which typically corresponds to a fiber tip aligned to direct therapeutic and/or visible light in the form of a beam 4802 along an optical axis 4801.
  • the beam 4802 is directed along the optical axis (which can be bent or jogged as needed) to form an annulus 4803 at a downstream location near an eye, typically corresponding to an image plane 4805.
  • the lens system further includes an achromat 4804 that includes first, second, and third lens elements 4806a, 4806b, 4806c.
  • the beam 4802 is slightly converging after the achromat 4804 and is subsequently received by an axicon doublet 4808 that includes first and second axicon lens elements 4810a, 4810b.
  • the axicon doublet 4808 can be an achromatic axicon doublet.
  • three of the four surfaces of the axicon doublet 4808 are non-planar, e.g., the second, third, and fourth surfaces.
  • Detailed optical data for an example of the optical system 4800 is summarized in Table 4, with units in millimeters. While no aspheres are used which can streamline manufacturing, some examples can use aspheric surfaces.
  • Table 4 Surface data for an example of optical system 4800 Surface Type Radius1 Radius2 Thickness Position Material Special Fib r Ti eff 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 Instrument 10 Window 3 190 11 Image Plane 241.19707 assembly 4902 that is situated in a near position in FIG.49A and in a far position in FIG.49B.
  • the system 4900 is similar to the system 4800 but with additional components or similar to the system 4700 but with fewer components.
  • FIG.50 shows another example treatment system 5000 that includes an optical system 5002 that can treat an eye 5004.
  • the system 5000 can be similar to other systems described herein.
  • the system 5000 can include a beam splitter 5006 that be arranged in a path of a treatment beam 5008.
  • the beam splitter 5006 can be operable to direct a portion of the treatment beam (or aiming beam) 5008 to an optical detector 5010.
  • the optical detector 5010 can detect the power of the treatment and/or visible light that is being directed towards the eye 5004.
  • the optical system 5002 can include another beam splitter 5012 that can be used to direct light from the eye 5004 to a camera system 5014.
  • the camera system 5014 can image the eye 5004, e.g., to assist with positioning the treatment beam on the eye 5004.
  • FIG.51 is an axicon doublet 5100 that can be configured to be achromatic or have selectable achromaticity.
  • the axicon doublet 5100 can include a first axicon element 5102 having first and second surfaces 5104a, 5104b and a second axicon element 5106 having first and second surfaces 5108a, 5108b.
  • surfaces of the axicon elements 5102, 5106 can include concave and/or convex surfaces.
  • the second surface 5104b and first surface 5108a can be convex and concave, respectively. Selected examples can be configured so that the surfaces 5104b, 5108a complement each other so that they can contact each other. With the same or a similar relationship, this can allow alignment and assembly of the two elements 5102, 5106 to be streamlined.
  • the conical shape of the axicon elements 5102, 5106 can ensure that an abutment between the surfaces 5104b, 5108a is aligned with a common optical axis 5109, in contrast to spherical lenses which can misalign based on their ball-and-socket characteristics.
  • abutting surfaces can be glued or cemented together.
  • a shelf or other protrusion 5110 can extend, such as from a housing or support 5112, to 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 space apart the first and second axicon elements 5102, 5106 by a predetermined amount.
  • the support 5112 can be washer or other spacer.
  • FIG.52 is a method 5200 of constructing and aligning a therapeutic treatment system, such as the system 4700, etc.
  • a fiber can be coupled to therapeutic and visible light sources to emit a beam of therapeutic and/or visible light towards the eye.
  • the fiber end can be aligned with achromatic imaging optics by analyzing a visible spot produced at a treatment plane. For example, various distortions of the spot can indicate the distance is incorrect (e.g., out-of-focus) and/or that the emission axis of the fiber is not aligned with the achromatic imaging optics.
  • a housing that supports the various components of the therapeutic treatment system can include surfaces to which the components can be registered (e.g., bores, protrusions, threads, etc.).
  • the achromatic imaging optics can come in the form of a pre-packaged lens system, allowing adjustment of the pre-packaged lens system as a unit to streamline installation and alignment.
  • annulus optics can be formed by positioning a first axicon element in relation to second axicon element to form an annulus optics assembly and then the assembly can be coupled to a linear translation stage.
  • the alignment of the two axicon elements can be relatively straightforward based on the conical shape of adjacent surfaces.
  • a cone-in-cone feature of adjacent axicon elements can provide some degree of self-alignment.
  • the annulus optics can also come in the form of a pre-packaged axicon lens system and can be inserted and adjusted as a unit to streamline installation and alignment.
  • the translation stage supporting the annulus optics can be adjusted to a near position (e.g., proximate the achromatic imaging optics) and then the translation stage can be adjusted with the annulus optics at the near position.
  • alignment can proceed by analyzing the visible annulus produced at the treatment plane (i.e., without necessarily using the therapeutic light) and adjusting pitch/yaw of the translation stage at the near position.
  • the translation stage supporting the annulus optics can be adjusted to a far position (e.g., closer to the eye) and then the translation stage can be adjusted with the annulus optics at the far position in a similar fashion.
  • An ab externo automated laser treatment system for treating an eye in a subject, comprising: a non-contact laser source configured to generate a laser beam having at least one wavelength to treat the eye by directing the laser beam from a location spaced from the eye, wherein the at least one wavelength is a near-infrared wavelength in the range of about 0.5-2.2 ⁇ m; a laser scanner optically coupled to the non-contact laser source to receive the laser beam from the non-contact laser source and to scan the laser beam relative to the eye; and a processor, and memory including stored computer-readable instructions that, responsive to execution by the processor, cause the laser treatment system to direct the laser beam to a plurality of trans-scleral treatment locations to be irradiated in a predetermined treatment pattern on an external surface of the eye, wherein the trans-scleral treatment locations are 0-4 mm posterior to the corneolimbal junction, and wherein the laser beam is repetitively directed to the same irradi
  • the memory includes stored computer-readable instructions that cause the laser treatment system to direct the laser beam to a plurality of trans- pupillary treatment locations and to induce sublethal thermal elevations eliciting therapeutic 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 biomodulation at the target eye tissue within a predetermined therapeutic temperature range, the plurality of trans-pupillary treatment locations including a predetermined curvilinear treatment pattern on target eye tissue of the eye comprising multiple concentric annuli on the macula around but not on the foveal avascular zone. 3.
  • the memory includes stored computer- readable instructions that cause the laser treatment system to direct the laser beam to a plurality of trans-pupillary treatment locations and to induce sublethal thermal elevations eliciting therapeutic biomodulation at the target eye tissue within a predetermined therapeutic temperature range, the plurality of trans-pupillary treatment locations including an area (i) surrounding the macula, but not on the foveal avascular zone, and (ii) surrounding the optic disk, but not on the optic disk or adjacent peripapillary crescent. 4.
  • the memory includes stored computer-readable instructions that cause the laser treatment system to direct the laser beam to a plurality of trans-pupillary treatment locations and to induce sublethal thermal elevations eliciting therapeutic biomodulation at the target eye tissue within a predetermined therapeutic temperature range, the plurality of trans-pupillary treatment locations including an area surrounding the optic disk, but not on the optic disk or adjacent peripapillary crescent.
  • the memory includes stored computer-readable instructions that cause the laser treatment system to direct the laser beam to a plurality of trans-pupillary treatment locations and to induce sublethal thermal elevations eliciting therapeutic biomodulation at the target eye tissue within a predetermined therapeutic temperature range, the plurality of trans-pupillary treatment locations including an area adjacent to the foveal avascular zone, but not on the area of the papillomacular bundle. 6.
  • the processor is configured with instructions to repetitively deliver the laser beam to the plurality of irradiated trans-scleral treatment locations at intervals that target an increase in the temperature of the outer 200-500 ⁇ m scleral layers to a temperature of about 45-57 °C.
  • the laser parameters are configured to provide irradiance of the laser beam and a scanning speed with which the laser beam moves around the predetermined treatment pattern increases the temperature of the outer 200 ⁇ m scleral layers to the temperature of about 43-57 °C, optionally about 43-45 °C. 10.
  • the processor is configured with instructions to receive an input corresponding to a location of the corneolimbal junction or limbus of the subject and wherein the processor is configured to determine the plurality of trans-scleral treatment locations in response to the input and wherein the plurality of trans-scleral treatment locations is offset radially outward from the input location corresponding to corneolimbal junction or limbus to contour the treatment pattern to the anatomy of the eye of the subject.
  • trans-scleral treatment locations are in a 360° annular pattern posterior to the corneolimbal junction
  • the processor is configured to direct the laser beam to a set of pre-identified trans-scleral treatment locations on the surface of the eye during a first treatment cycle, and during a subsequent treatment cycle direct the laser beam to the same pre-identified trans-scleral treatment locations, to achieve precise cyclic thermal elevation of scleral tissue underlying the pre-identified trans-scleral treatment locations at intervals of time with thermal relaxation of the irradiated tissue between treatment cycles.
  • the processor is configured to set the speed of each treatment cycle to achieve the thermal relaxation by spacing irradiation of the trans-scleral treatment locations at sufficient intervals that an exposure time and relaxation time produce a targeted time-temperature history.
  • the interval between irradiation of the same trans-scleral treatment location produces a duty factor, corresponding to the ratio between the active exposure ON time / (active exposure + relaxation OFF time), in the 2 – 50 % range.
  • the interval between irradiation of the same trans-scleral treatment location is about 10-300 ms, optionally about 100-200 ms. 15.
  • the predetermined treatment pattern is located about 1.5 mm posterior to the corneolimbal junction. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 16.
  • the predetermined treatment pattern comprises multiple annular treatment patterns, and wherein the multiple annular treatment patterns are spaced about 1.5 mm, 2.5 mm and 3.5 mm posterior to the corneolimbal junction, wherein the annular treatment patterns comprise one or more of circular, oval, elliptical, egg-like, non-circular, non-elliptical, or asymmetrical patterns, or patterns that correspond to the shape of Schlemm’s canal or the limbus. 17.
  • the laser beam has a near- infrared wavelength of 0.8-2.2 ⁇ m, optionally including a wavelength of 1-2.2 ⁇ m, 1.0-1.7 ⁇ m, 0.80-0.85 ⁇ m, 1.4-1.6 ⁇ m, and/or 1.47 ⁇ m.
  • the laser beam has a near-infrared wavelength of about 1.4-1.5 ⁇ m, optionally at 1.47 ⁇ m.
  • the protective thermal preconditioning and therapeutic bio-stimulation are controlled by one or more of the laser’s power, irradiance, scanning speed, cycle repetition rate, number of cycle repetitions, spot size and duty cycle. 25.
  • any one of paragraphs 1-24 wherein the processor is configured to direct the laser beam to the trans-scleral treatment location in a spot having a diameter of 500-1000 ⁇ m, optionally about 600 ⁇ m. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 26.
  • the system of any one of paragraphs 1-25 further comprising an optical imaging system for detecting the limbus and/or corneolimbal junction of the subject.
  • the processor is configured to identify the predetermined trans-scleral treatment locations at locations determined by the shape of the limbus and/or corneolimbal junction of the eye of the subject. 28.
  • any one of paragraphs 1-27 further comprising a patient interface for docking the non-contact laser source spaced away from the eye, the patient interface comprising a spacer that maintains the eye in a substantially fixed location for imaging and treatment, and the spacer maintains the non-contact laser source spaced from and not contacting the surface of the eye. 29.
  • the patient interface further comprises a speculum for placement between the eyelids of the subject to expose the eye to the laser beam.
  • the patient interface further comprises a fixation ring for a contact lens
  • the fixation ring comprises a resilient sealing face
  • the system is configured to maintain negative pressure between the contact lens and the fixation ring to secure the patient interface to the surface of the eye and substantially immobilize the eye of the subject.
  • the negative pressure is adjustable.
  • the system is configured to cool the spacer and/or fixation ring and/or contact lens.
  • each annulus on the macula of the curvilinear treatment pattern comprises a plurality of evenly-spaced and overlapping laser pulse spots sequentially delivered along a complete circle to produce an irradiated annular treatment zone within each annulus, wherein the laser pulse spots are delivered at a common scan speed for all macular annuli.
  • each concentric annulus has a width of between 400 ⁇ m and 600 ⁇ m.
  • the laser source is configured to produce the laser beam with pulses at a pulse repetition period in the range of 1-3 ms, pulse repetition rate of 1000 to 333 pulses per second and a pulse duration in the range of 20-500 ⁇ s. 39.
  • the laser source is configured to produce the laser beam with pulses at a pulse repetition period in the range of 1.5-2.5 ms, pulse repetition rate of 666 to 400 pulses per second, and a pulse duration in the range of 50-150 ⁇ s.
  • the laser source is configured to produce the laser beam with pulses at a pulse repetition period in the range of 1.8-2.2 ms, pulse repetition rate of 556 to 455 pulses per second, and a pulse duration in the range of 80-120 ⁇ s. 41.
  • annuli comprise three to five contiguous concentric annuli on the macula, each annulus having a substantially equal width
  • the plurality of trans-scleral treatment locations comprises three concentric annuli on the sclera around the limbus at radii R1, R2 and R3 that correspond respectively to locations overlying the primary aqueous outflow pathway, the pars plicata ciliary body, and the pars plana.
  • annuli comprise five contiguous annuli on the sclera, each annulus having a width of approximately 500 microns, and wherein the plurality of trans-scleral treatment locations comprises three concentric annuli on the sclera at distances of approximately 1.5, 2.5 and 3.5 mm from the corneoscleral junction.
  • the sublethal thermal elevations correspond to a raise in the temperature of the target tissue in the annuli on the macula to a temperature of no more than 47oC, and the laser beam raises the temperature of the target tissue in the trans-scleral treatment locations to no more than 57oC. 44.
  • the laser source comprises a first diode laser source operable to produce a pulsed laser beam at 810 nm for directing to the trans- pupillary treatment locations, a second diode laser source operable to produce a continuous-wave laser beam at 1475 nm for directing to the trans-scleral treatment locations, and at least one beam splitter situated to receive and direct the beam at 810 nm and the beam at 1475 nm along a common optical path for receiving by the laser scanner. 45.
  • An ab externo automated method for treating an eye in a subject comprising: directing laser energy having a near-infrared wavelength of about 0.5-2.2 ⁇ m from a location spaced from the eye to a plurality of trans-scleral treatment locations to be irradiated in a predetermined treatment pattern on an external surface of the eye, wherein the trans-scleral treatment locations are 0-4 mm posterior to the corneolimbal junction, and wherein the laser energy is repetitively directed to the same irradiated trans-scleral treatment locations on the surface of the eye, and the trans-scleral treatment locations are irradiated at intervals sufficient to induce protective thermal preconditioning and therapeutic bio-stimulation of one or more of the trabecular meshwork and/or ciliary body without photocoagulation of the tissue of the eye.
  • the method of paragraph 46 or 47 further comprising directing laser energy having a near-infrared wavelength of about 0.5-2.2 ⁇ m from the location spaced from the eye to a plurality of trans-pupillary treatment locations to induce sublethal thermal elevations eliciting therapeutic biomodulation at the target eye tissue within a predetermined therapeutic temperature range, the plurality of trans-pupillary treatment locations including an area (i) surrounding the macula, but not on the foveal avascular zone, and (ii) surrounding the optic disk, but not on the optic disk or adjacent peripapillary crescent. 49.
  • any one of paragraphs 46-48 further comprising directing laser energy having a near-infrared wavelength of about 0.5-2.2 ⁇ m from the location spaced from the eye to a plurality of trans-pupillary treatment locations to induce sublethal thermal elevations eliciting therapeutic biomodulation at the target eye tissue within a predetermined therapeutic temperature range, the plurality of trans-pupillary treatment locations including an area surrounding the optic disk, but not on the optic disk or adjacent peripapillary crescent.
  • any one of paragraphs 46-49 further comprising directing laser energy having a near-infrared wavelength of about 0.5-2.2 ⁇ m from the location spaced from the eye to a plurality of trans-pupillary treatment locations to induce sublethal thermal elevations eliciting therapeutic biomodulation at the target eye tissue within a predetermined therapeutic temperature range, the plurality of trans-pupillary treatment locations including an area adjacent to the foveal avascular zone, but not on the area of the papillomacular bundle. 51.
  • repetitively delivering the energy to the plurality of irradiated trans-scleral treatment locations comprises delivering the energy at intervals that target an increase in the temperature of the outer 200-500 ⁇ m scleral layers to a temperature of about 45-57 °C. 54.
  • the directing the laser energy includes at a selected irradiance and scanning speed that increases the temperature of the outer 200 ⁇ m scleral layers to the temperature of about 43-57 °C, optionally about 43-45 °C. 55.
  • trans-scleral treatment locations are in a 360° annular pattern posterior to the corneolimbal junction
  • the laser energy is directed to a set of pre-identified trans-scleral treatment locations on the surface of the eye during a first treatment cycle, and during a subsequent treatment cycle the laser energy is directed to the same pre-identified trans-scleral treatment locations, to achieve precise cyclic thermal elevation of scleral tissue underlying the pre-identified trans-scleral treatment locations at intervals of time with thermal relaxation of the irradiated tissue between treatment cycles.
  • each treatment cycle is performed during a duration that achieves the thermal relaxation by spacing irradiation of the trans- scleral treatment locations at sufficient intervals that an exposure time and relaxation time produce a targeted time-temperature history.
  • 58. The method of any one of paragraphs 46-57, wherein the same trans-scleral treatment location is irradiated at intervals that produce a duty factor, corresponding to the ratio between the active exposure ON time / (active exposure + relaxation OFF time), in the 2 – 50 % range.
  • 59. The method of paragraph 58, wherein the same trans-scleral treatment location is irradiated at intervals of about 10-300 ms, optionally about 100-200 ms. 60.
  • the predetermined treatment pattern to which the laser energy is directed is located about 1.5 mm posterior to the corneolimbal junction.
  • the predetermined treatment pattern to which the laser energy is directed comprises multiple annular treatment patterns, and wherein the multiple annular treatment patterns are spaced about 1.5 mm, 2.5 mm and 3.5 mm posterior to the corneolimbal junction, and wherein the multiple annular treatment patterns comprise one or more of circular, oval, elliptical, egg-like, non-circular, non-elliptical, or asymmetrical patterns, or patterns that correspond to the shape of the corneolimbal junction or the limbus.
  • any one of paragraphs 46-61 wherein the laser energy is directed to a 360° predetermined treatment pattern that is interrupted nasally by 10-30° and temporally by 10- 30°.
  • 63 The method of any one of paragraphs 46-62, wherein the laser energy is directed to trans-scleral treatment locations on multiple annular treatment patterns that target the (a) perilimbal outflow structure; (b) pars plicata; and (c) pars plana.
  • 64 The method of any one of paragraphs 46-63, further comprising placing a heat sink in contact with the eye over the trans-scleral treatment locations to conduct heat away from the surface of the eye. 65.
  • placing the heat sink in contact with the eye comprises placing a curved contact lens on the surface of the eye. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 66.
  • placing the contact lens on the eye comprises placing a cooled contact lens that substantially conforms to the surface of the eye. 67.
  • any one of paragraphs 46-69 wherein the protective thermal preconditioning and therapeutic bio-stimulation are controlled by one or more of the laser’s power, irradiance, scanning speed, cycle repetition rate, number of cycle repetitions, spot size and duty cycle.
  • the laser energy is directed to the treatment location in a spot having a diameter of 500-1000 ⁇ m, optionally about 600 ⁇ m.
  • the method of any one of paragraphs 46-71 further comprising detecting the limbus and/or corneolimbal junction of the subject with an optical imaging system. 73.
  • the patient interface further comprises a speculum for placement between the eyelids of the subject to expose the eye to the laser energy, and the speculum is placed between the eyelids to expose the sclera of the subject.
  • the patient interface further comprises a fixation ring for a contact lens, and the fixation ring comprises a resilient sealing face, and the fixation ring is placed against the eye of the subject and suction is applied to between the contact lens and eye to create negative pressure and secure the fixation ring to the eye and substantially immobilize the eye of the subject.
  • the laser energy directed to the trans-pupillary treatment locations comprises a pulsed laser beam at 810 nm
  • the laser energy directed to the trans-scleral treatment locations comprises a continuous-wave laser beam at 1475 nm
  • the laser energies are directed along a common optical path from at least one beam splitter.
  • a patient interface assembly for docking a laser treatment device to an eye to be treated with the laser treatment device, the patient interface system comprising: a lens holder configured to retain a contact lens heat sink against the eye, wherein the lens holder includes internal cooling channels that communicate with fluid flow inlet and outlet ports; and a spacer dockable to the lens holder for holding a laser output a spaced distance from the contact lens heat sink.
  • the patient interface of paragraph 93 further comprising a resilient sealing ring on the lens holder that extends around the contact lens to create a sealing chamber between the contact lens and the eye to retain the lens holder against an eye when a suction is applied to the sealing chamber, and the sealing chamber communicates with a suction port.
  • the patient interface of paragraph 94 wherein the contact lens comprises a contact lens with a central opening to permit air to pass into the sealing chamber while still maintaining the negative pressure in the sealing chamber.
  • 97. The patient interface of any one of paragraphs 93-96, further comprising a laser triangulation system for Z-focus camera viewing of the contact lens. 98.
  • a patient interface for docking a laser treatment device to an eye to be treated with the laser treatment device comprising: a spacer, such as a frustoconical spacer, that tapers from an enlarged first face to a smaller second face, and a laser emission source carried by the cone and spaced away from the smaller second face; a lens holder collar that tapers from a larger first face for mating with the second face of the spacer to a smaller second face that is circumscribed by a resilient patient fixation ring to form a seal against the eye to be treated, wherein the collar comprises an internal cooling fluid passageway, an inlet port and an outlet port for circulating cooling fluid through the collar; a heat sink contact lens held in the collar above the fixation ring to form a suction chamber
  • a method of docking the laser treatment device of paragraph 99 to an eye to be treated with the laser treatment device comprising inserting the blades of the speculum into the eye to separate the eyelids and expose the sclera, retaining the lens holder between the blades of the speculum and optionally suctioning air from the sealing chamber, activating the X-Y- Z positioner to dock the spacer to the lens holder, and introducing cooling liquid through the internal cooling channels of the lens holder by introducing cooling liquid through the fluid inlet port and out of the fluid outlet port.
  • the method of paragraph 100 further comprising viewing the contact lens and eye with optical viewing software.
  • the method of paragraph 100 further comprising viewing the retina of the eye with optical viewing software.
  • An apparatus comprising: an optical system configured to produce a first annulus and second annulus at a target with respective first and second diameters, wherein the first annulus has a first wavelength and the second annulus has a second wavelength longer than the first wavelength, wherein the diameter of the first annulus is smaller than the diameter of the second annulus.
  • the apparatus of claim 104 further comprising: a first beam source configured to emit light at the first wavelength; a second beam source configured to emit light at the second wavelength; an optical fiber coupled to the first and second beam sources to receive and direct the light at the first and second wavelengths and to emit the light from a fiber end at the first and/or second wavelength, wherein the fiber end is coupled to the optical system to produce the respective first annulus and/or second annulus at the target; and a controller coupled to control emission of the first beam source and second beam source.
  • the optical system comprises a first set of one or more lens elements and at least one axicon lens element, wherein the first set of one or more lens elements is configured to provide collimated light at the first wavelength at an input of the axicon lens element with a first beam width and to provide collimated light at the second wavelength at the input of the at least one axicon lens element with a second beam width greater than the first beam width.
  • the first set of one or more lens elements comprises three lens elements configured to provide the collimated lights.
  • a material composition of the first set of one or more lens elements comprises a first material and the material composition of the at least one axicon lens element comprises a second material different from the first material, wherein the difference corresponds to a larger refractive index between the first and second wavelengths for the first material relative to the second material.
  • a movement stage coupled to the at least one axicon lens element and configured to translate the at least one axicon lens element along an optical axis of the optical system to vary the first and second diameters by the same or approximately the same amount.
  • any of claims 106-109 wherein the controller is coupled to the movement stage to translate the at least one axicon lens element along the optical axis of the optical system.
  • the target is an eye
  • the first wavelength is a visible wavelength
  • the second wavelength is a water-absorptive infrared wavelength
  • the first annulus is configured to become aligned relative to a corneolimbal junction so that the second annulus becomes directed to a perilimbal region of the sclera radially outward from the corneolimbal junction.
  • controller configured to scan a diameter the first annulus and/or second annulus during a treatment of the target.
  • controller comprises a processor, and memory including stored computer-readable instructions that, responsive to execution by the processor, cause the apparatus to form the second annulus on the external surface of the eye with an irradiance and for a duration sufficient to produce a broad geographic nonlethal hyperthermia to underlying sub-scleral biological structures providing primary and non- conventional outflow pathways without causing photocoagulation of the tissue of the eye.
  • controller comprises a processor, and memory including stored computer-readable instructions that, responsive to execution by the processor, cause the apparatus to form the second annulus on the external surface of the eye with an irradiance and for a duration sufficient to produce a broad geographic nonlethal hyperthermia to underlying sub-scleral biological structures providing primary and non- conventional outflow pathways without causing photocoagulation of the tissue of the eye.
  • any of claims 105-113 further comprising a trans-pupillary beam source configured to produce a trans-pupillary beam for directing through the pupil of an eye
  • the controller is configured to control emission of the trans-pupillary beam source to emit the trans-pupillary beam to a plurality of trans-pupillary treatment locations and to induce sublethal thermal elevations eliciting therapeutic biomodulation at the target eye tissue within a predetermined therapeutic temperature range, the plurality of trans-pupillary treatment locations including a predetermined curvilinear treatment pattern on target eye tissue of the eye comprising multiple concentric annuli on the macula around but not on the foveal avascular zone.
  • a trans-pupillary beam source configured to produce a trans-pupillary beam for directing through the pupil of an eye
  • the controller is configured to control emission of the trans-pupillary beam source to emit the trans-pupillary beam to a plurality of trans-pupillary treatment locations and to induce sublethal thermal elevations eliciting therapeutic biomodulation at the
  • the apparatus of claim 114 wherein the optical system is configured to direct the trans-pupillary beam to the plurality of trans-pupillary treatment locations.
  • 116. The apparatus of claim 114, wherein a separate optical system is configured to direct the trans-pupillary beam to the plurality of trans-pupillary treatment locations.
  • 117. A method, comprising producing the first annulus and/or second annulus with any of the apparatus of claims 104-116.
  • 118. comprising, arranging lens elements to form the optical system of any of claims 104-117. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 119.
  • An ab externo automated laser treatment apparatus for treating an eye in a subject, comprising: a non-contact laser source configured to produce a continuous-wave laser beam having at least one wavelength to treat the eye by directing the laser beam from a location spaced from the eye, wherein the at least one wavelength is a near-infrared wavelength in the range of about 1.0-2.2 ⁇ m; an optical system configured to receive and direct the laser beam to form an annulus at an external perilimbal surface region of the eye, wherein the annulus has an inner diameter and outer diameter situated between 0-4 mm posterior to a corneolimbal junction; a processor, and memory including stored computer-readable instructions that, responsive to execution by the processor, cause the laser treatment apparatus to form the annulus on the external surface of the eye with an irradiance and for a duration sufficient to produce a broad geographic nonlethal hyperthermia to underlying sub-scleral biological structures providing primary and non- conventional outflow pathways without causing photocoagulation of the tissue of the eye.
  • the optical system includes at least one axicon situated to convert a cross-sectional shape of the laser beam into the annulus.
  • the at least one axicon includes a diffractive axicon.
  • the optical system includes a focus lens situated to focus the annulus at the external surface of the eye.
  • the axicon is situated between the focus lens and the eye and a relative distance between the axicon and the focus lens is adjustable to adjust a mean diameter of the annulus at the external surface of the eye.
  • any of claims 119-123 wherein the optical system includes a beam expander situated to adjust a thickness of the annulus.
  • the apparatus of any of claims 119-124 further comprising one or more movement stages coupled to one or more lenses or mirrors of the optical system and configured to translate and/or rotate the one or more lenses or mirrors to adjust a positioning of the annulus relative to an optical axis of the eye.
  • the optical system is configured to scan one or more characteristics of the annulus over time. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 127.
  • the apparatus of claim 126 wherein the one or more characteristics includes an irradiance profile across a thickness direction of the annulus, a mean diameter of the annulus, and/or a position of the inner and/or outer diameters.
  • the apparatus is configured to direct the continuous-wave beam and/or second annulus at a duty-cycle based on power and/or scanning to reduce a likelihood of tissue damage to the surface or surface regions of the eye.
  • the apparatus of claim 129 wherein the temperature sensor is coupled to detect the surface temperature of the eye at the location of the annulus on the surface of the eye.
  • the temperature sensor comprises an imaging camera, thermographic camera, and/or thermal sensor.
  • the stored computer- readable instructions include instructions that, responsive to execution by the processor, cause the apparatus to adjust one or more laser parameters during the treatment in response to the detected surface temperature.
  • the apparatus of claim 132 wherein the instructions are configured to: compare the measured surface temperature to a predetermined thermal model relating scleral surface temperature change produced by laser beam to tissue damage of the conjunctiva or sclera; and reduce the surface temperature in response to the comparison by reducing laser power or powering down the laser.
  • the instructions are configured to: compare the measured surface temperature to a predetermined thermal model relating eye surface temperature change produced by the laser beam to a temperature change of the underlying sub-scleral biological structures; and maintain a temperature of the sub-scleral biological structures within a temperature range that provides the nonlethal hyperthermia without photocoagulation by dynamically adjusting the one or more laser parameters during the treatment duration. 135.
  • the one or more laser parameters include one or more of: irradiance, duration, laser power, laser duty cycle, irradiance profile, annulus mean diameter, annulus thickness, annulus inner diameter, annulus outer diameter. 9900-108824-02 FILED VIA EFS ON JUNE 26, 2024 136.
  • the apparatus of any of claims 113-136, wherein the irradiance is at least 0.1 W/cm 2 and at most 2.0 W/cm 2 . 138.
  • any of claims 113-137 wherein the wavelength or the second wavelength is between 1.4 ⁇ m and 1.6 ⁇ m. 139.

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Abstract

Un appareil comprend un système optique conçu pour produire un premier espace annulaire et un second espace annulaire au niveau d'une cible avec des premier et second diamètres respectifs, le premier espace annulaire ayant une première longueur d'onde et le second espace annulaire ayant une seconde longueur d'onde plus longue que la première longueur d'onde, le système optique comprenant un système axicon comprenant un premier élément axicon et un second élément axicon, le système axicon étant conçu pour définir une relation entre les premier et second diamètres. Des exemples peuvent comprendre un dispositif de commande qui comprend un processeur, et une mémoire comprenant des instructions lisibles par ordinateur stockées qui, en réponse à l'exécution par le processeur, amènent l'appareil à former le second espace annulaire sur la surface externe de l'œil avec un éclairement énergétique et pendant une durée qui produit une hyperthermie non létale géographique large à des structures biologiques sous-sclérales sous-jacentes fournissant des voies de sortie primaires et non classiques sans provoquer de photocoagulation du tissu oculaire.
PCT/US2024/035662 2023-06-26 2024-06-26 Thérapie laser pour traitement et prévention de maladies oculaires à l'aide de faisceaux annulaires Pending WO2025006635A1 (fr)

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Family Cites Families (9)

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Publication number Priority date Publication date Assignee Title
RU94030810A (ru) * 1991-11-06 1996-06-20 Т.Лай Шуй Импульсный лазерный аппарат, способ для обеспечения гладкой абляции вещества, лазерный аппарат и способ роговичной хирургии
US6319274B1 (en) 1998-06-22 2001-11-20 John H. Shadduck Devices and techniques for light-mediated stimulation of trabecular meshwork in glaucoma therapy
US8945103B2 (en) 2007-10-30 2015-02-03 Iridex Corporation Contact probe for the delivery of laser energy
PT2797493T (pt) 2011-12-28 2018-07-27 Wavelight Gmbh Processo para tomografia de coerência ótica e aparelho para tomografia de coerência ótica
US9962291B2 (en) 2012-05-25 2018-05-08 Ojai Retinal Technology, Llc System and process for neuroprotective therapy for glaucoma
WO2018067864A1 (fr) 2016-10-05 2018-04-12 Aleyegn Technologies Llc Systèmes, procédés et kits pour réduire le chauffage de surface pendant un traitement de tissu
US20180104508A1 (en) * 2016-10-13 2018-04-19 Ronald Michael Kurtz Optical system for nonpharmacologic constriction of a pupil
WO2019216364A1 (fr) * 2018-05-09 2019-11-14 国立研究開発法人理化学研究所 Dispositif optique et microscope photoacoustique
EP3749264B1 (fr) * 2018-11-02 2023-06-07 ALeyeGN Technologies LLC Thérapie au laser pour le traitement et la prévention de maladies oculaires

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