WO2018203930A1 - Système et procédé de traitement de la myopie - Google Patents

Système et procédé de traitement de la myopie Download PDF

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Publication number
WO2018203930A1
WO2018203930A1 PCT/US2017/064708 US2017064708W WO2018203930A1 WO 2018203930 A1 WO2018203930 A1 WO 2018203930A1 US 2017064708 W US2017064708 W US 2017064708W WO 2018203930 A1 WO2018203930 A1 WO 2018203930A1
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WIPO (PCT)
Prior art keywords
eye tissue
eye
tissue
myopia
pulsed energy
Prior art date
Application number
PCT/US2017/064708
Other languages
English (en)
Inventor
Jeffrey K. LUTTRULL
David B. Chang
Benjamin W. L. Margolis
Original Assignee
Ojai Retinal Technology, Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US15/583,096 external-priority patent/US10953241B2/en
Priority claimed from US15/629,002 external-priority patent/US10278863B2/en
Application filed by Ojai Retinal Technology, Llc filed Critical Ojai Retinal Technology, Llc
Priority to AU2017412681A priority Critical patent/AU2017412681B2/en
Priority to EP17908615.2A priority patent/EP3618923A4/fr
Priority to BR112019023061A priority patent/BR112019023061A2/pt
Priority to CN201780090319.XA priority patent/CN110582238A/zh
Priority to SG11201909214Y priority patent/SG11201909214YA/en
Priority to JP2019554563A priority patent/JP2020518317A/ja
Priority to CA3058891A priority patent/CA3058891A1/fr
Publication of WO2018203930A1 publication Critical patent/WO2018203930A1/fr
Priority to JP2022143131A priority patent/JP2022184907A/ja

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/0622—Optical stimulation for exciting neural tissue
    • 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
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/0625—Warming the body, e.g. hyperthermia treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/067—Radiation therapy using light using laser light
    • 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
    • A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
    • A61F2007/0001—Body part
    • A61F2007/0002—Head or parts thereof
    • A61F2007/0004—Eyes or part of the face surrounding the eyes
    • 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
    • A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0635—Radiation therapy using light characterised by the body area to be irradiated
    • A61N2005/0642—Irradiating part of the body at a certain distance
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0659—Radiation therapy using light characterised by the wavelength of light used infrared

Definitions

  • the present invention generally relates to systems and processes for treating eye disorders. More particularly, the present invention resides in systems and processes for preventing or treating myopia by applying pulsed energy to tissue of an eye having myopia or a risk of having myopia to raise the temperature of the eye tissue sufficiently to provide treatment benefits while not permanently damaging the eye tissue.
  • Myopia is the condition known as "near-sightedness", where the image in front of the eye is focused in front of the retina rather than exactly on the retina. This focus of the image on the retina is also referred to as
  • the image in myopia may be focused in front of the retina for one or both of the following reasons: either the refractive strength of the front of the eye at the cornea and lens is excessive; and/or the axial length of the eye is too long, such that the retina is posterior to the image focal point, causing blurred vision. To counteract this visual blurring, those affected move closer to the object to be viewed. This moves the focal point of the image back and closer to the retina, causing the vision to become more clear.
  • Myopia is epidemic by usual medical definitions, affecting as many as 50% of adults, with increases in incidents in school-aged children in recent generations by 200% or more. This rapid increase and prevalence has been attributed to improved educational opportunities with increased reading time, as well as increased use of electronic devices and media.
  • the causes of typical myopia appear to be genetic and environment. Higher education and greater time spent doing close work and reading are known to be risk factors for myopia.
  • the stimulus for near work causing myopia suggests that this influences, possibly in part via accommodation of the crystalline lens, neurologic and/or chemical mediators of eye growth to increase the axial length of the eye. Evidence for this phenomenon is that paralyzation of accommodation with topical atropine in children is able to reduce the degree and incidence of acquired myopia.
  • Retinal dysfunction and alteration of retinal autoregulation in response to environmental factors is a common phenomenon and a common finding in most chronic progressive retinopathies, including age-related macular degeneration and diabetic retinopathy, ocular neurologic diseases such as chronic open angle glaucoma, and inherited retinopathies including retinitis pigmentosa and Stargardt's Disease.
  • ocular neurologic diseases such as chronic open angle glaucoma
  • inherited retinopathies including retinitis pigmentosa and Stargardt's Disease.
  • glaucoma a setting analogous to the development of myopia, selective complimentary sparing of visual field defects has demonstrated direct and neurologic and/or chemical communication between fellow eyes mediated by the central nervous system to minimize total visual disability.
  • optic nerve tissue is sacrificed in such a way as to increase the probability of preserved visual field in one eye, covering lost visual field in the other eye, maximizing total visual function when both eyes are used together.
  • retinal signaling which alters retinal and neurologic structure to accommodate the quality of visual stimuli and maximize visual function.
  • myopia While typical axial or refractive myopia can be corrected by glasses, contact lenses or refractive surgery, myopia is also often associated with reduced visual function and increases risks of vision loss due to retinal detachment, choroidal neovascularization, macular atrophy, and glaucoma. Together, the need for refractive correction of myopia, and medical
  • the present invention resides in a process for preventing or treating myopia.
  • a pulsed energy source having energy parameters, including wavelength or frequency, duty cycle and pulse duration is provided.
  • the energy parameters are selected so as to raise an eye tissue temperature up to 1 1 ° C to achieve a therapeutic or prophylactic effect.
  • the average temperature rise of the eye tissue over several minutes is maintained at or below a predetermined level so as not to permanently damage the eye tissue. It may be determined that the eye has myopia or is at a risk of having myopia.
  • the pulsed energy is applied to tissue of an eye having a myopia or a risk of having myopia to stimulate heat shock protein activation in the eye tissue.
  • the pulsed energy may comprise a pulsed light beam having a wavelength between 530 nm to 1 300 nm, and more particularly between 80 nm and 1 000 nm.
  • the light beam may have a duty cycle of less than 1 0%, and more preferably between 2.0% and 5%.
  • the pulsed light beam may have a power between 0.5 and 74 watts.
  • the pulsed light beam may have a pulse train duration between 0.1 and 0.6 seconds.
  • the eye tissue to which the pulsed energy is applied comprises retinal and/or foveal tissue.
  • the pulsed energy source energy parameters are selected so that the eye tissue temperature is raised between 6° C to 1 1 ° C at least during application of the pulsed energy source. However, the average temperature rise of the eye tissue is maintained at approximately 1 ° C or less over several minutes, such as over a six-minute period of time.
  • the pulsed energy may be applied to a plurality of eye tissue areas, wherein adjacent eye tissue areas are separated by at least a predetermined distance to avoid thermal tissue damage.
  • the pulsed energy may be applied to a first eye tissue area and, after a predetermined period of time within a single treatment session, the pulsed energy is reapplied to the first eye tissue area.
  • the pulsed energy is applied to a second eye tissue area.
  • FIGURE 1 is a graph illustrating an average power of a laser source having a wavelength compared to a source radius and pulse train duration of the laser;
  • FIGURE 2 is a graph similar to FIG. 1 , illustrating the average power of a laser source of a higher wavelength compared to a source radius and a pulse train duration of the laser;
  • FIGURE 3 is a diagrammatic view illustrating a system used for treating an eye in accordance with the present invention.
  • FIGURE 4 is a diagrammatic view of an exemplary optical lens or mask used to generate a geometric pattern, in accordance with the present invention
  • FIGURE 5 is a diagrammatic view illustrating an alternate
  • FIGURE 6 is a diagrammatic view illustrating yet another alternate embodiment of a system used for treating eye tissue in accordance with the present invention.
  • FIGURE 7 is a front view of a camera including an iris aperture of the present invention.
  • FIGURE 8 is a front view of a camera including an LCD aperture, in accordance with the present invention.
  • FIGURE 9 is a top view of an optical scanning mechanism, used in accordance with the present invention.
  • FIGURE 1 0 is a partially exploded view of the optical scanning mechanism of FIG. 9, illustrating various component parts thereof;
  • FIGURE 1 1 is a diagrammatic view illustrating controlled offset of exposure of an exemplary geometric pattern grid of laser spots to treat the eye tissue, in accordance with the present invention
  • FIGURE 1 2 is a diagrammatic view illustrating units of a geometric object in the form of a line controllably scanned to treat an area of eye tissue, in accordance with the present invention
  • FIGURE 1 3 is a diagrammatic view similar to FIG. 1 2 , but illustrating the geometric line or bar rotated to treat an area of the retina, in accordance with the present invention
  • FIGURES 1 4A - FIGURE 1 4D are diagrammatic views illustrating the application of laser light to different treatment areas during a predetermined interval of time, within a single treatment session, and reapplying the laser light to previously treated areas, in accordance with the present invention.
  • FIGURES 1 5- 1 7 are graphs depicting the relationship of treatment power and time in accordance with embodiments of the present invention.
  • the present invention is directed to a process for preventing or treating myopia. This is accomplished by providing a pulsed energy source having energy parameters selected so as to raise an eye tissue temperature sufficiently to achieve a therapeutic or prophylactic effect, while maintaining the average temperature rise of the eye tissue over time at or below a pulsed energy source having energy parameters selected so as to raise an eye tissue temperature sufficiently to achieve a therapeutic or prophylactic effect, while maintaining the average temperature rise of the eye tissue over time at or below a pulsed energy source having energy parameters selected so as to raise an eye tissue temperature sufficiently to achieve a therapeutic or prophylactic effect, while maintaining the average temperature rise of the eye tissue over time at or below a
  • predetermined level so as not to permanently damage the eye tissue.
  • SDM subthreshold diode micropulsed laser
  • RPE retinal pigment epithelium
  • SDM homeotropic therapy by restoring normal retinal physiology and autoregulation should then slow, stop or even reverse progression of myopia, and particularly pediatric myopia, in the same way that it does other chronic progressive retinopathies and glaucoma.
  • Various parameters of the light beam must be taken into account and selected so that the combination of the selected parameters achieve the therapeutic effect while not permanently damaging the tissue. These parameters include laser wavelength, radius of the laser source, average laser power, total pulse duration, and duty cycle of the pulse train. Although a laser light beam is used in a particularly preferred embodiment, other pulsed energy sources including ultrasound, ultraviolet frequency, microwave frequency and the like having energy parameters appropriately selected may also be used, but are not as convenient in the treatment of eye disorders and diseases, including myopia, as other diseases and disorders.
  • Arrhenius integrals are used for analyzing the impacts of actions on biological tissue. See, for instance, The CRC Handbook of Thermal Engineering, ed. Frank Kreith, Springer Science and Business Media (2000). At the same time, the selected parameters must not permanently damage the tissue. Thus, the Arrhenius integral for damage may also be used, wherein the solved Arrhenius integral is less than 1 or unity.
  • tissue temperature rises of between 6° C and 1 1 ° C can create therapeutic effect, such as by activating heat shock proteins, while maintaining the average tissue temperature over a prolonged period of time, such as over several minutes, such as six minutes, below a predetermined temperature, such as 6° C and even 1 ° C or less in certain circumstances, will not permanently damage the tissue.
  • the subthreshold retinal photocoagulation is defined as retinal laser applications biomicroscopically invisible at the time of treatment.
  • Truste subthreshold photocoagulation, as a result of the present invention, is invisible and includes laser treatment non-discernible by any other known means such as FFA, FAF, or even SD-OCT.
  • Truste subthreshold photocoagulation is therefore defined as a laser treatment which produces absolutely no retinal damage detectable by any means at the time of treatment or any time thereafter by known means of detection.
  • “true subthreshold” is the absence of lesions and other tissue damage and destruction.
  • the invention may be more accurately referred to as photostimulation than photocoagulation due to the absence of typical photocoagulation damage.
  • True subthreshold laser applications can be applied singly or to create a geometric object or pattern of any size and configuration to minimize heat accumulation, but assure uniform heat distribution as well as maximizing heat dissipation such as by using a low duty cycle.
  • the inventor has discovered how to achieve therapeutically effective and harmless true subthreshold retinal laser treatment.
  • the inventor has also discovered that placement of true subthreshold laser applications confluently and contiguously to the retinal surface improves and maximizes the therapeutic benefits of treatment without harm or retinal damage.
  • the exposure envelope duration is a duration of time where the micropulsed laser beam would be exposed to the same spot or location of the retina, although the actual time of exposure of the tissue to the laser is much less as the laser light pulse is less than a millisecond in duration, and typically between 50
  • Invisible phototherapy or true subthreshold photocoagulation in accordance with the present invention can be performed at various laser light wavelengths, such as from a range of 532 nm to 1 300 nm. Use of a different wavelength can impact the preferred intensity or power of the laser light beam and the exposure envelope duration in order that the retinal tissue is not damaged, yet therapeutic effect is achieved.
  • Another parameter of the present invention is the duty cycle (the frequency of the train of micropulses, or the length of the thermal relaxation time in between consecutive pulses). It has been found that the use of a 1 0% duty cycle or higher adjusted to deliver micropulsed laser at similar irradiance at similar MPE levels significantly increase the risk of lethal cell injury, particularly in darker fundi. However, duty cycles less than 1 0%, and preferably approximately 5% duty cycle or less have demonstrated adequate thermal rise and treatment at the level of the RPE cell to stimulate a biologic response, but remained below the level expected to produce lethal cell injury, even in darkly pigmented fundi. Moreover, if the duty cycle is less than 5%, the exposure envelope duration in some instances can exceed 500 milliseconds.
  • the use of small retinal laser spots is used. This is due to the fact that larger spots can contribute to uneven heat distribution and insufficient heat dissipation within the large retinal laser spot, potentially causing tissue damage or even tissue destruction towards the center of the larger laser spot. In this usage, "small” would generally apply to retinal spots less than 3 mm in diameter. However, the smaller the retinal spot, the more ideal the heat dissipation and uniform energy application becomes. Thus, at the power intensity and exposure duration described above, small spots, such as 25-300 micrometers in diameter, or small geometric lines or other objects are preferred so as to maximize even heat distribution and heat dissipation to avoid tissue damage.
  • the laser light beam should have a wavelength greater than 532 nm to avoid cytotoxic photochemical effects, such as a wavelength between 550 nm and 1 300 nm, and in a particularly preferred embodiment between 81 0 nm and 1 000 nm.
  • the duty cycle should be less than 1 0%, and preferably between 2.5%- 5%.
  • the pulse train duration or exposure time should be between 1 00 and 600 milliseconds.
  • the intensity or power of the laser light beam should be between 1 00-590 watts per square centimeter at the retina or approximately 1 watt per laser spot for each treatment spot at the retina. This is sufficient power to produce retinal laser exposures between 1 8-55 times Maximum Permissible Exposure (MPE) and retinal irradiance of between 1 00-590 W/cm 2 .
  • MPE Maximum Permissible Exposure
  • small spot size is used to minimize heat accumulation and assure uniform heat distribution within a given laser spot so as to maximize heat dissipation.
  • a harmless yet therapeutically effective "true subthreshold" or invisible phototherapy treatment can be attained in which retinal photostimulation of all areas of the RPE may be exposed to the laser radiation and preserved and available to contribute therapeutically.
  • the present invention has been found to produce the benefits of conventional photocoagulation and phototherapy while avoiding the drawbacks and complications of conventional phototherapy.
  • the physician may apply the laser light beam to treat the entire retina, including sensitive areas such as the macula and even the fovea, without creating visual loss or other damage. This is not possible using conventional phototherapies as it could create damage to the eye or even blindness.
  • the present invention spares the neurosensory retina and is selectively absorbed by the RPE.
  • Current theories of the pathogenesis of retinal vascular disease especially implicate cytokines, potent extra cellular vasoactive factors produced by the RPE, as important mediators of retinal vascular disease.
  • the present invention both selectively targets and avoids lethal buildup within RPE.
  • the capacity for the treated RPE to participate in a therapeutic response is preserved and even enhanced rather than eliminated as a result their destruction of the RPE in conventional photocoagulation therapies.
  • HSPs heat shock proteins
  • temperature thermal spikes at a very steep rate of change ( ⁇ 7° C elevation with each 1 00 MS micropulse, or 70,000 °C/sec) produced by each SDM exposure is especially effective in stimulating production of HSPs, particularly compared to non-lethal exposure to subthreshold treatment with continuous wave lasers, which can duplicate only the low average tissue temperature rise.
  • SDM produces prompt clinical effects, such as rapid and significant improvement in retinal electrophysiology, visual acuity, contrast visual acuity and improved macular sensitivity measured by
  • microperimetry as well as long-term effects, such as reduction of DME and involution of retinal neovascularization.
  • SDM may cause direct photothermal effects such as entropic protein unfolding and disaggregation
  • SDM appears optimized for clinically safe and effective stimulation of HSP- mediated retinal repair.
  • DME diabetic macular edema
  • PDR proliferative diabetic retinopathy
  • BRVO branch retinal vein occlusion
  • CSR chorioretinopathy
  • prophylactic treatment of progressive degenerative retinopathies such as dry age-related macular degeneration, Stargardts' disease, cone dystrophies, and retinitis pigmentosa.
  • SDM chorioretinopathy
  • SDM treatment of patients suffering from age-related macular degeneration can slow the progress or even stop the progression of AMD.
  • Most of the patients have seen significant improvement in dynamic functional logMAR mesoptic visual acuity and mesoptic contrast visual acuity after the SDM treatment. It is believed that SDM works by targeting, preserving, and "normalizing" (moving toward normal) function of the retinal pigment epithelium (RPE).
  • RPE retinal pigment epithelium
  • SDM has also been shown to stop or reverse the manifestations of the diabetic retinopathy disease state without treatment-associated damage or adverse effects, despite the persistence of systemic diabetes mellitus.
  • SDM might work by inducing a return to more normal cell function and cytokine expression in diabetes-affected RPE cells, analogous to hitting the "reset" button of an electronic device to restore the factory default settings.
  • SDM treatment may directly affect cytokine expression via heat shock protein (HSP) activation in the targeted tissue.
  • HSP heat shock protein
  • the energy source to be applied to the target tissue will have energy and operating parameters which must be determined and selected so as to achieve the therapeutic effect while not permanently damaging the tissue.
  • a light beam energy source such as a laser light beam
  • the laser wavelength, duty cycle and total pulse train duration parameters must be taken into account.
  • Other parameters which can be considered include the radius of the laser source as well as the average laser power. Adjusting or selecting one of these parameters can have an effect on at least one other parameter.
  • FIGURES 1 and 2 illustrate graphs showing the average power in watts as compared to the laser source radius (between 0.1 cm and 0.4 cm) and pulse train duration (between 0.1 and 0.6 seconds).
  • FIG. 1 shows a wavelength of 880 nm
  • FIG. 2 has a wavelength of 1 000 nm. It can be seen in these figures that the required power decreases monotonically as the radius of the source decreases, as the total train duration increases, and as the
  • the preferred parameters for the radius of the laser source is 1 mm-4 mm.
  • the minimum value of power is 0.55 watts, with a radius of the laser source being 1 mm, and the total pulse train duration being 600 milliseconds.
  • the maximum value of power for the 880 nm wavelength is 52.6 watts when the laser source radius is 4 mm and the total pulse drain duration is 1 00 milliseconds.
  • the minimum power value is 0.77 watts with a laser source radius of 1 mm and a total pulse train duration of 600 milliseconds, and a maximum power value of 73.6 watts when the laser source radius is 4 mm and the total pulse duration is 1 00 milliseconds.
  • corresponding peak powers, during an individual pulse are obtained from the average powers by dividing by the duty cycle.
  • the volume of the tissue region to be heated is determined by the wavelength, the absorption length in the relevant tissue, and by the beam width.
  • the total pulse duration and the average laser power determine the total energy delivered to heat up the tissue, and the duty cycle of the pulse train gives the associated spike, or peak, power associated with the average laser power.
  • the pulsed energy source energy parameters are selected so that approximately 20 to 40 joules of energy is absorbed by each cubic centimeter of the target tissue.
  • the target tissue can be heated to up to approximately 1 1 ° C for a short period of time, such as less than one second, to create the therapeutic effect of the invention while maintaining the target tissue average temperature to a lower temperature range, such as less than 6° C or even 1 ° C or less over a prolonged period of time, such as several minutes.
  • the selection of the duty cycle and the total pulse train duration provide time intervals in which the heat can dissipate.
  • a duty cycle of less than 1 0%, and preferably between 2.5% and 5%, with a total pulse duration of between 1 00 milliseconds and 600 milliseconds has been found to be effective.
  • Arrhenius integral being less than 1 .
  • the average temperature rise of the target tissue over any six-minute period is 1 ° C or less.
  • the temperature decay time is 1 07 seconds when the source diameter is 4 mm.
  • the temperature decay time is 1 8 seconds when the source diameter is 1 mm and 1 36 seconds when the source diameter is 4 mm.
  • the relatively low duty cycle provides relatively long periods of time between the pulses of energy applied to the tissue and the relatively short pulse train duration ensure sufficient temperature diffusion and decay within a relatively short period of time comprising several minutes, such as 6 minutes or less, that there is no permanent tissue damage.
  • the pulse train mode of energy delivery has a distinct advantage over a single pulse or gradual mode of energy delivery, as far as the activation of remedial HSPs and the facilitation of protein repair is concerned.
  • FIG. 3 a schematic diagram is shown of a system for realizing the process of the present invention.
  • the system generally referred to by the reference number 30, includes a laser console 32, such as for example the 81 0 nm near infrared micropulsed diode laser in the preferred embodiment.
  • the laser generates a laser light beam which is passed through optics, such as an optical lens or mask, or a plurality of optical lenses and/or masks 34 as needed.
  • the laser projector optics 34 pass the shaped light beam to a coaxial wide-field non-contact digital optical viewing
  • system/camera 36 for projecting the laser beam light onto the eye 38 of the patient.
  • box labeled 36 can represent both the laser beam projector as well as a viewing system/camera, which might in reality comprise two different components in use.
  • the viewing system/camera 36 provides feedback to a display monitor 40, which may also include the necessary computerized hardware, data input and controls, etc. for
  • the laser light beam 42 is passed through a collimator lens 44 and then through a mask 46.
  • the mask 46 comprises a diffraction grating.
  • the mask/diffraction grating 46 produces a geometric object, or more typically a geometric pattern of simultaneously produced multiple laser spots or other geometric objects. This is represented by the multiple laser light beams labeled with reference number 48.
  • the multiple laser spots may be generated by a plurality of fiber optic wires.
  • Either method of generating laser spots allows for the creation of a very large number of laser spots simultaneously over a very wide treatment field, such as consisting of the entire retina.
  • a very high number of laser spots perhaps numbering in the hundreds, even thousands or more could cover the entire ocular fundus and entire retina, including the macula and fovea, retinal blood vessels and optic nerve.
  • the intent of the process in the present invention is to better ensure complete and total coverage and treatment, sparing none of the retina by the laser so as to improve vision.
  • wavelength of the laser employed for example using a diffraction grating
  • the individual spots produced by such diffraction gratings are all of a similar optical geometry to the input beam, with minimal power variation for each spot.
  • the result is a plurality of laser spots with adequate irradiance to produce harmless yet effective treatment application, simultaneously over a large target area.
  • the present invention also contemplates the use of other geometric objects and patterns generated by other diffractive optical elements.
  • the laser light passing through the mask 46 diffracts, producing a periodic pattern a distance away from the mask 46, shown by the laser beams labeled 48 in FIG. 4.
  • the single laser beam 42 has thus been formed into multiple, up to hundreds or even thousands, of individual laser beams 48 so as to create the desired pattern of spots or other geometric objects.
  • These laser beams 48 may be passed through additional lenses, collimators, etc. 50 and 52 in order to convey the laser beams and form the desired pattern on the patient's retina. Such additional lenses, collimators, etc. 50 and 52 can further transform and redirect the laser beams 48 as needed.
  • Arbitrary patterns can be constructed by controlling the shape, spacing and pattern of the optical mask 46.
  • the pattern and exposure spots can be created and modified arbitrarily as desired according to application requirements by experts in the field of optical engineering. Photolithographic techniques, especially those developed in the field of semiconductor
  • manufacturing can be used to create the simultaneous geometric pattern of spots or other objects.
  • the number of simultaneous spots generated and used could number from as few as 1 and up to approximately 1 00 when a 0.04 (4%) duty cycle and a total train duration of 0.3 seconds (300 milliseconds) is used for panretinal coverage.
  • the water absorption increases as the
  • the absorption coefficient in the RPE's melanin can be higher, and therefore the laser power can be lower.
  • the power can be lowered by a factor of 4 for the invention to be effective. Accordingly, there can be as few as a single laser spot or up to approximately 400 laser spots when using the 577 nm wavelength laser light, while still not harming or damaging the eye.
  • the present invention can use a multitude of simultaneously generated therapeutic light beams or spots, such as numbering in the dozens or even hundreds, as the parameters and methodology of the present invention create therapeutically effective yet non-destructive and non-permanently damaging treatment, allowing the laser light spots to be applied to any portion of the retina, including the fovea, whereas conventional techniques are not able to use a large number of simultaneous laser spots, and are often restricted to only one treatment laser beam, in order to avoid accidental exposure of sensitive areas of the retina, such as the fovea, as these will be damaged from the exposure to conventional laser beam methodologies, which could cause loss of eyesight and other complications.
  • FIGURE 5 illustrates diagrammatically a system which couples multiple light sources into the pattern-generating optical subassembly described above.
  • this system 30' is similar to the system 30 described in FIG. 3 above.
  • the primary differences between the alternate system 30' and the earlier described system 30 is the inclusion of a plurality of laser consoles 32 , the outputs of which are each fed into a fiber coupler 54.
  • the fiber coupler produces a single output that is passed into the laser projector optics 34 as described in the earlier system.
  • the coupling of the plurality of laser consoles 32 into a single optical fiber is achieved with a fiber coupler 54 as is known in the art.
  • Other known mechanisms for combining multiple light sources are available and may be used to replace the fiber coupler described herein.
  • a sequential offsetting to achieve complete coverage will be different for each wavelength.
  • This sequential offsetting can be accomplished in two modes. In the first mode, all wavelengths of light are applied simultaneously without identical coverage. An offsetting steering pattern to achieve complete coverage for one of the multiple wavelengths is used. Thus, while the light of the selected wavelength achieves complete coverage of the retina, the application of the other wavelengths achieves either incomplete or overlapping coverage of the retina.
  • the second mode sequentially applies each light source of a varying or different wavelength with the proper steering pattern to achieve complete coverage of the retina for that particular wavelength. This mode excludes the possibility of simultaneous treatment using multiple wavelengths, but allows the optical method to achieve identical coverage for each wavelength.
  • FIGURE 6 illustrates diagrammatically yet another alternate embodiment of the inventive system 30".
  • This system 30" is configured generally the same as the system 30 depicted in FIG. 3. The main difference resides in the inclusion of multiple pattern-generating subassembly channels tuned to a specific wavelength of the light source.
  • Multiple laser consoles 32 are arranged in parallel with each one leading directly into its own laser projector optics 34.
  • the laser projector optics of each channel 58a, 58b, 58c comprise a collimator 44, mask or diffraction grating 48 and recollimators 50, 52 as described in connection with FIG. 4 above - the entire set of optics tuned for the specific wavelength generated by the corresponding laser console 32.
  • the output from each set of optics 34 is then directed to a beam splitter 56 for combination with the other wavelengths. It is known by those skilled in the art that a beam splitter used in reverse can be used to combine multiple beams of light into a single output.
  • the system 30" may use as many channels 58a, 58b, 58c, etc. and beam splitters 56a, 56b, 56c, etc. as there are wavelengths of light being used in the treatment.
  • each channel begins with a light source 32 , which could be from an optical fiber as in other embodiments of the pattern- generating subassembly.
  • This light source 32 is directed to the optical assembly 34 for collimation, diffraction, recollimation and directed into the beam splitter which combines the channel with the main output.
  • the invention described herein is generally safe for panretinal and/or trans-foveal treatment.
  • a user i.e., surgeon, preparing to limit treatment to a particular area of the retina where disease markers are located or to prevent treatment in a particular area with darker pigmentation, such as from scar tissue.
  • the camera 36 may be fitted with an iris aperture 72 configured to selectively widen or narrow the opening through which the light is directed into the eye 38 of the patient.
  • FIG. 7 illustrates an opening 74 on a camera 36 fitted with such an iris aperture 72.
  • the iris aperture 72 may be replaced or supplemented by a liquid crystal display (LCD) 76.
  • the LCD 76 acts as a dynamic aperture by allowing each pixel in the display to either transmit or block the light passing through it.
  • Such an LCD 76 is depicted in FIG. 8.
  • any one of the inventive systems 30, 30', 30" includes a display on a user interface with a live image of the retina as seen through the camera 36.
  • the user interface may include an overlay of this live image of the retina to select areas where the treatment light will be limited or excluded by the iris aperture 72 and/or the LCD 76.
  • the user may draw an outline on the live image as on a touch screen and then select for either the inside or the outside of that outline to have limited or excluded coverage.
  • the surgeon may use the fundus monitor to outline an area of the retina to be treated or avoided; and the designated area then treated or avoided by software directing the treatment beams to treat or avoid said areas without need or use of an obstructing LCD 76 diaphragm.
  • the system of the present invention incorporates a guidance system to ensure complete and total retinal treatment with retinal photostimulation.
  • This guidance system is to be distinguished from traditional retinal laser guidance systems that are employed to both direct treatment to a specific retinal location; and to direct treatment away from sensitive locations such as the fovea that would be damaged by conventional laser treatment, as the treatment method of the present invention is harmless, the entire retina, including the fovea and even optical nerve, can be treated.
  • protection against accidental visual loss by accidental patient movement is not a concern. Instead, patient movement would mainly affect the guidance in tracking of the application of the laser light to ensure adequate coverage.
  • Fixation/tracking/ registration systems consisting of a fixation target, tracking mechanism, and linked to system operation are common in many ophthalmic diagnostic systems and can be incorporated into the present invention.
  • the geometric pattern of simultaneous laser spots is sequentially offset so as to achieve confluent and complete treatment of the retinal surface.
  • a segment of the retina can be treated in accordance with the present invention, more ideally the entire retina will be treated within one treatment session. This is done in a time- saving manner by placing a plurality of spots over the entire ocular fundus at once. This pattern of simultaneous spots is scanned, shifted, or redirected as an entire array sequentially, so as to cover the entire retina in a single treatment session.
  • FIGS. 9 and 1 0 illustrate an optical scanning mechanism 60 which may be used in the form of a MEMS mirror, having a base 62 with electronically actuated controllers 64 and 66 which serve to tilt and pan the mirror 68 as electricity is applied and removed thereto. Applying electricity to the controller 64 and 66 causes the mirror 68 to move, and thus the
  • the optical scanning mechanism may also be a small beam diameter scanning galvo mirror system, or similar system, such as that distributed by Thorlabs. Such a system is capable of scanning the lasers in the desired offsetting pattern.
  • the geometric pattern of laser spots can be overlapped without destroying the tissue or creating any permanent damage.
  • the pattern of spots are offset at each exposure so as to create space between the immediately previous exposure to allow heat dissipation and prevent the possibility of heat damage or tissue destruction.
  • the pattern illustrated for exemplary purposes as a grid of sixteen spots, is offset each exposure such that the laser spots occupy a different space than previous exposures.
  • micromachined mirror as illustrated in FIGS. 9 and 1 0.
  • Another example would be a 3 cm x 3 cm area, representing the entire human retinal surface.
  • a much larger secondary mask size of 25 mm by 25 mm could be used, yielding a treatment grid of 1 90 spots per side separated by 1 33 m with a spot size radius of 6 m. Since the secondary mask size was increased by the same factor as the desired treatment area, the number of offsetting operations of approximately 98, and thus treatment time of approximately thirty seconds, is constant. These treatment times represent at least ten to thirty times reduction in treatment times compared to current methods of sequential individual laser spot applications. Field sizes of 3 mm would, for example, allow treatment of the entire human macula in a single exposure, useful for treatment of common blinding
  • diabetic macular edema diabetic macular edema
  • age-related macular diabetic macular edema
  • FIGS. 1 2 and 1 3 instead of a geometric pattern of small laser spots, the present invention contemplates use of other geometric objects or patterns.
  • a single line 70 of laser light formed by the continuously or by means of a series of closely spaced spots, can be created.
  • An offsetting optical scanning mechanism can be used to
  • the pulsed laser light beam of an 81 0 nm diode laser should have an exposure envelope duration of 500 milliseconds or less, and preferably approximately 300 milliseconds.
  • the exposure duration should be lessened accordingly.
  • duty cycle or the frequency of the train of micropulses, or the length of the thermal relaxation time between consecutive pulses. It has been found that the use of a 1 0% duty cycle or higher adjusted to deliver micropulsed laser at similar irradiance at similar MPE levels significantly increase the risk of lethal cell injury, particularly in darker fundi. However, duty cycles of less than 1 0%, and preferably 5% or less demonstrate adequate thermal rise and treatment at the level of the MPE cell to stimulate a biological response, but remain below the level expected to produce lethal cell injury, even in darkly pigmented fundi. The lower the duty cycle, however, the exposure envelope duration increases, and in some instances can exceed 500 milliseconds.
  • Each micropulsed lasts a fraction of a millisecond, typically between 50 microseconds to 1 00 microseconds in duration. Thus, for the exposure envelope duration of 300-500 milliseconds, and at a duty cycle of less than 5%, there is a significant amount of wasted time between micropulses to allow the thermal relaxation time between consecutive pulses. Typically, a delay of between 1 and 3 milliseconds, and preferably approximately 2 milliseconds, of thermal relaxation time is needed between consecutive pulses.
  • the retinal cells are typically exposed or hit by the laser light between 50-200 times, and preferably between 75- 1 50 at each location.
  • the total time in accordance with the embodiments described above to treat a given area, or more particularly the locations on the retina which are being exposed to the laser spots is between 200 milliseconds and 500 milliseconds on average.
  • the thermal relaxation time is required so as not to overheat the cells within that location or spot and so as to prevent the cells from being damaged or
  • the present invention may utilize the interval between consecutive laser light applications to the same location (typically between 1 to 3 milliseconds) to apply the laser light to a second treatment area, or additional areas, of the retina and/or fovea that is spaced apart from the first treatment area.
  • the laser beams are returned to the first treatment location, or previous treatment locations, within the predetermined interval of time so as to provide sufficient thermal relaxation time between consecutive pulses, yet also sufficiently treat the cells in those locations or areas properly by sufficiently increasing the temperature of those cells over time by repeatedly applying the laser light to that location in order to achieve the desired therapeutic benefits of the invention.
  • milliseconds at least one other area, and typically multiple areas, can be treated with a laser light application as the laser light pulses are typically 50 microseconds to 1 00 microseconds in duration.
  • the number of additional areas which can be treated is limited only by the micopulse duration and the ability to controllably move the laser light beams from one area to another.
  • approximately four additional areas which are sufficiently spaced apart from one another can be treated during the thermal relaxation intervals beginning with a first treatment area.
  • multiple areas can be treated, at least partially, during the 200-500 millisecond exposure envelope for the first area.
  • approximately 500 light spots can be applied during that interval of time in different treatment areas.
  • each location has between 50-200, and more typically between 75- 1 50, light applications applied thereto over the course of the exposure envelope duration (typically 200-500 milliseconds) to achieve the desired treatment.
  • the laser light would be reapplied to previously treated areas in sequence during the relaxation time intervals for each area or location. This would occur repeatedly until a predetermined number of laser light applications to each area to be treated have been achieved.
  • FIGS. 1 4A- 1 4D This is diagrammatically illustrated in FIGS. 1 4A- 1 4D.
  • FIG. 1 4A illustrates with solid circles a first area having laser light applied thereto as a first application.
  • the laser beams are offset or microshifted to a second exposure area, followed by a third exposure area and a fourth exposure area, as illustrated in FIG. 1 4B, until the locations in the first exposure area need to be retreated by having laser light applied thereto again within the thermal relaxation time interval.
  • the locations within the first exposure area would then have laser light reapplied thereto, as illustrated in FIG. 1 4C. Secondary or subsequent exposures would occur in each exposure area, as illustrated in FIG.
  • Adjacent exposure areas must be separated by at least a
  • Such distance is at least 0.5 diameter away from the immediately preceding treated location or area, and more preferably between 1 -2 diameters away.
  • Such spacing relates to the actually treated locations in a previous exposure area. It is contemplated by the present invention that a relatively large area may actually include multiple exposure areas therein which are offset in a different manner than that illustrated in FIG. 1 4.
  • the exposure areas could comprise the thin lines illustrated in FIGS. 1 2 and 1 3, which would be
  • this can comprise a limited area of the retina, the entire macula or panmacular treatment, or the entire retina, including the fovea.
  • the time required to treat that area of the retina to be treated or the entire retina is significantly reduced, such as by a factor of 4 or 5 times, such that a single treatment session takes much less time for the medical provider and the patient need not be in discomfort for as long of a period of time.
  • the lower curve is for panmacular treatment and the upper curve is for panretinal treatment. This would be for a laser light beam having a micropulse time of 50 microseconds, a period of 2 milliseconds period of time between pulses, and duration of train on a spot of 300
  • each retinal spot requires a minimum energy in order for its reset mechanism to be adequately activated, in accordance with the present invention, namely, 38.85 joules for panmacular and 233.1 joules for panretinal. As would be expected, the shorter the treatment time, the larger the required average power. However, there is an upper limit on the allowable average power, which limits how short the treatment time can be.
  • FIGS. 1 6 and 1 7 show how the total power depends on treatment time. This is displayed in FIG. 1 6 for panmacular treatment, and in FIG. 1 7 for panretinal treatment.
  • the upper, solid line or curve represents the embodiment where there are no microshifts taking advantage of the thermal relaxation time interval, such as described and illustrated in FIG. 1 1 , whereas the lower dashed line represents the situation for such microshifts, as described and illustrated in FIG. 1 4.
  • FIGS. 1 6 and 1 7 show that for a given treatment time, the peak total power is less with microshifts than without microshifts. This means that less power is required for a given treatment time using the microshifting
  • the allowable peak power can be advantageously used, reducing the overall treatment time.
  • the product of the treatment time and the average power is fixed for a given treatment area in order to achieve the therapeutic treatment in accordance with the present invention.
  • the parameters of the laser light are selected to be therapeutically effective yet not destructive or permanently damaging to the cells, no guidance or tracking beams are required, only the treatment beams as all areas of the retina, including the fovea, can be treated in
  • the entire retina, including the fovea is treated in accordance with the present invention, which is simply not possible using conventional techniques.
  • a simplified user interface is permitted. While the operating controls could be presented and function in many different ways, the system permits a very simplified user interface that might employ only two control functions. That is, an "activate" button, wherein a single depression of this button while in
  • a depression of this button during treatment would allow for premature halting of the treatment, and a return to "standby” mode.
  • the activity of the machine could be identified and displayed, such as by an LED adjacent to or within the button.
  • a second controlled function could be a "field size” knob.
  • a single depression of this button could program the unit to produce, for example, a 3 mm focal or a "macular” field spot.
  • a second depression of this knob could program the unit to produce a 6 mm or "posterior pole” spot.
  • a third depression of this knob could program the unit to produce a "pan retinal” or approximately 1 60°-220° panoramic retinal spot or coverage area. Manual turning of this knob could produce various spot field sizes therebetween. Within each field size, the density and intensity of treatment would be identical. Variation of the field size would be produced by optical or mechanical masking or apertures, such as the iris or LCD apertures described below.
  • Fixation software could monitor the displayed image of the ocular fundus. Prior to initiating treatment of a fundus landmark, such as the optic nerve, or any part or feature of either eye of the patient (assuming orthophoria), could be marked by the operator on the display screen. Treatment could be initiated and the software would monitor the fundus image or any other image- registered to any part of either eye of the patient (assuming orthophoria) to ensure adequate fixation. A break in fixation would automatically interrupt treatment. A break in fixation could be detected optically; or by interruption of low energy infrared beams projected parallel to and at the outer margins of the treatment beam by the edge of the pupil. Treatment would automatically resume toward completion as soon as fixation was established. At the establishment of a fundus landmark, such as the optic nerve, or any part or feature of either eye of the patient (assuming orthophoria), could be marked by the operator on the display screen. Treatment could be initiated and the software would monitor the fundus image or any other image- registered to any part of either eye of the patient (assuming orthophoria) to ensure adequate
  • the unit would automatically terminate exposure and default to the "on” or “standby” mode. Due to unique properties of this treatment, fixation interruption would not cause harm or risk patient injury, but only prolong the treatment session.
  • the laser could be projected via a wide field non-contact lens to the ocular fundus. Customized direction of the laser fields or particular target or area of the ocular fundus other than the central area could be accomplished by an operator joy stick or eccentric patient gaze.
  • the laser delivery optics could be coupled coaxially to a wide field non-contact digital ocular fundus viewing system.
  • the image of the ocular fundus produced could be displayed on a video monitor visible to the laser operator. Maintenance of a clear and focused image of the ocular fundus could be facilitated by a joy stick on the camera assembly manually directed by the operator. Alternatively, addition of a target registration and tracking system to the camera software would result in a completely automated treatment system.
  • a fixation image could be coaxially displayed to the patient to facilitate ocular alignment. This image would change in shape and size, color, intensity, blink or oscillation rate or other regular or continuous modification during treatment to avoid photoreceptor exhaustion, patient fatigue and facilitate good fixation.
  • results or images from other retinal diagnostic modalities might be displayed in parallel or by superimposition on the display image of the patient's fundus to guide, aid or otherwise facilitate the treatment.
  • This parallel or superimposition of images can facilitate identification of disease, injury or scar tissue on the retina.
  • RPE retinal pigment epithelium
  • SDM treatment may directly affect cytokine expression and heat shock protein (HSP) activation in the targeted tissue, particularly the retinal pigment epithelium (RPE) layer.
  • HSP heat shock protein
  • Panretinal and panmacular SDM has been noted by the inventors to reduce the rate of progression of many retinal diseases, including severe non-proliferative and proliferative diabetic retinopathy, AMD, DME, etc.
  • the reset theory also suggests that the invention may have application to many different types of RPE-mediated retinal disorders.
  • panmacular treatment can significantly improve retinal function and health, retinal sensitivity, and dynamic logMAR visual acuity and contrast visual acuity in dry age-related macular degeneration, retinitis pigmentosa, cone-rod retinal degenerations, and Stargardt's disease where no other treatment has previously been found to do so.
  • SDM normal retinal physiology and autoregulation as well to slow, stop or even reverse the progression of myopia, and particularly pediatric myopia in the same way that it does other chronic progressive retinopathies.
  • a laser light beam that is sublethal and creates true subthreshold photocoagulation or photostimulation of retinal tissue, is generated and at least a portion of the retinal tissue is exposed to the generated laser light beam without damaging the exposed retinal or foveal tissue, so as to provide preventative and protective treatment of the retinal tissue of the eye.
  • the treated retina may comprise the fovea, foveola, retinal pigment epithelium (RPE), choroid, choroidal neovascular membrane, subretinal fluid, macula, macular edema, parafovea, and/or perifovea.
  • the laser light beam may be exposed to only a portion of the retina, or substantially the entire retina and fovea, or other eye tissue. This procedure is applied to tissue of the eye, such as retinal and/or foveal tissue, of an eye having myopia or a risk of having myopia.
  • the retina is periodically retreated. This may be done according to a set schedule or when it is determined that the retina of the patient is to be retreated, such as by periodically monitoring visual and/or retinal function or condition of the patient.

Abstract

Un procédé de prévention ou de traitement de la myopie comprend l'application d'une énergie pulsée, telle qu'un faisceau laser pulsé, au tissu d'un oeil présentant une myopie ou un risque de myopie. La source d'énergie pulsée présente des paramètres d'énergie comprenant la longueur d'onde ou la fréquence, le rapport cyclique et la durée du train d'impulsions, qui sont sélectionnés de façon à élever une température de tissu oculaire jusqu'à onze degrés Celsius pour obtenir un effet thérapeutique ou prophylactique, tel que la stimulation de l'activation de la protéine de choc thermique dans le tissu oculaire. L'élévation de température moyenne du tissu oculaire pendant plusieurs minutes est maintenue à un niveau prédéterminé ou en-dessous de façon à ne pas endommager de façon permanente le tissu oculaire.
PCT/US2017/064708 2017-05-01 2017-12-05 Système et procédé de traitement de la myopie WO2018203930A1 (fr)

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AU2017412681A AU2017412681B2 (en) 2017-05-01 2017-12-05 System and process for treatment of myopia
EP17908615.2A EP3618923A4 (fr) 2017-05-01 2017-12-05 Système et procédé de traitement de la myopie
BR112019023061A BR112019023061A2 (pt) 2017-05-01 2017-12-05 processo para prevenir ou tratar miopia
CN201780090319.XA CN110582238A (zh) 2017-05-01 2017-12-05 用于治疗近视的系统及方法
SG11201909214Y SG11201909214YA (en) 2017-05-01 2017-12-05 System and process for treatment of myopia
JP2019554563A JP2020518317A (ja) 2017-05-01 2017-12-05 近視の治療のためのシステムおよびプロセス
CA3058891A CA3058891A1 (fr) 2017-05-01 2017-12-05 Systeme et procede de traitement de la myopie
JP2022143131A JP2022184907A (ja) 2017-05-01 2022-09-08 近視の治療のためのシステムおよびプロセス

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US15/583,096 2017-05-01
US15/629,002 2017-06-21
US15/629,002 US10278863B2 (en) 2016-03-21 2017-06-21 System and process for treatment of myopia

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BR112019023061A2 (pt) 2020-06-09
AU2017412681B2 (en) 2019-11-14
AU2017412681A1 (en) 2019-10-31
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CN110582238A (zh) 2019-12-17
EP3618923A4 (fr) 2020-03-11

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