Laser system and method for detecting and processing information - Patents.com

Abstract

To provide a laser system suitable for changing an intraocular pressure (IOP) of an eye, for the normalization of the intraocular pressure (IOP) in eyes with glaucoma.SOLUTION: A laser system comprises: a laser source 101; a feedback controller 106 configured to regulate a dosimetry of the laser source to produce spatially and / or temporally modulated laser light; a first optical delivery element 102 configured to guide the spatially and / or temporally modulated laser light to irradiate a first area 202a on an eye 201; and a detecting element 105 configured to detect one or more physical, chemical, mechanical and / or structural characteristics in a second area 202b on the eye in a real-time during the change of the IOP, wherein the feedback controller is configured to regulate the dosimetry of the laser source in a real-time on the basis of the real-time detected information pertaining to the one or more physical, chemical, mechanical and / or structural characteristics in the second area.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present disclosure is in the field of medical laser technology. In particular, the present disclosure relates to a laser system that can be applied for normalizing intraocular pressure (IOP) in eyes with glaucoma. [Background technology]

[0002] Glaucoma is characterized by optic nerve damage that often results in irreversible vision loss. Glaucoma is the leading cause of irreversible blindness worldwide. Glaucoma affects more than 80 million people worldwide, and this number is expected to increase to 110 million by 2040. Glaucoma is estimated to cost the U.S. economy $2.86 billion annually in direct costs and lost productivity.

[0003] A key component in the pathophysiology of glaucoma is the secretion, transport, and eventual outflow of aqueous humor from the anterior chamber of the eye. Elevated intraocular pressure (IOP) is a significant risk factor for developing glaucoma. IOP is balanced by the production of aqueous humor by the ciliary body of the eye and its drainage through several outflow pathways, including the traditional pathway, i.e., via the trabecular meshwork (TM) and Schlemm's canal, and the uveoscleral pathway, i.e., through the sclera.

[0004] Currently, glaucoma treatments aim to reduce IOP by limiting aqueous humor production or by increasing aqueous humor outflow. Treatments for glaucoma include medications, usually eye drops, laser surgery, and traditional surgery to help the eye drain fluid more effectively or to reduce fluid production.

[0005] Trabeculectomy has been the standard surgical procedure for 40 years, but it carries known risks of cataracts, intraocular hypotony, bleb loss, infection, and other complications. Various valuable procedures have been combined with trabeculectomy to shunt aqueous humor into the sub-Tenon space (e.g., Ahmed valves). Recently, microinvasive glaucoma procedures, such as the iStent (Glaukos, Laguna Hills, California) and Trabectome (NeoMedix, Tustin, California), have been introduced. CyPass (Transcend Medical, Menlo Park, California) operates on the suprachoroidal space and episcleral region. It allows for IOP reduction without utilizing traditional transport pathways. All of the above approaches to controlling IOP in glaucomatous eyes have problematic complications.

[0006] Currently, laser trabeculoplasty (LTP) and selective laser trabeculoplasty (SLT) are commonly performed, but these procedures may result in irreversible changes to Schlemm's canal and other secondary effects. SLT is a subclass of IOP-lowering laser procedures that target the TM and improve aqueous humor outflow.

[0007] Because the mechanism of action of SLT is not fully understood, it is difficult to predict success rates or prevent complications. SLT has a variable success rate, ranging from approximately 40% to 70%.

[0008] SLT is relatively safe and effective, but potential complications include elevated IOP 1 to 2 hours after the procedure (the duration of elevated IOP can last from 4 days to 3 months), corneal opacity, and shifts in refractive error (both myopia and hyperopia). Postoperative inflammation after SLT usually occurs 2 to 3 days after the procedure. This has been seen in 83% of eyes undergoing SLT. TM cell death and retinal side effects have been reported.

[0009] Another common procedure is laser cyclocoagulation (LCC), which is based on local coagulation (destruction) of the ciliary body, which reduces aqueous humor production and decreases IOP. It is often difficult to accurately predict the outcome of LCC. Furthermore, this method can have serious complications, particularly including excessive reduction in IOP and / or some increase in central corneal thickness, which can lead to decompensation of the corneal endothelium. LCC is currently reserved mostly for cases of patients with highly advanced glaucoma and poor vision.

[0010] Therefore, existing treatment modalities for glaucoma, including pharmacological treatment, laser, surgery, and shunt, all have certain drawbacks. Furthermore, all available methods and devices have been developed and used to reduce IOP. None of the above methods can treat low IOP glaucoma.

[0011] The prior art and knowledge is summarized in the following patents and publications: Non-Patent Document 1 provides the scientific background of this disclosure. It shows a mechanism that allows the formation of stabilized microporous structures on the sclera in vivo using a temporally and spatially modulated laser.

[0012] Patent document 1 discloses a controlled laser for prophylactic treatment to prevent bleeding from the incision made thereafter.

[0013] Patent document 2 discloses a method for adjusting a laser system in a cyclophotocoagulation procedure.

[0014] Non-patent document 2 discloses a DSLT system, an automatic gaze tracking system.

[0015] Further technical background of the present disclosure can be found in the review article: Non-Patent Document 3 and the review article: Non-Patent Document 4. [Prior art documents] [Patent documents]

[0016] [Patent Document 1] US Patent Application Publication No. 2022 / 0175580 [Patent Document 2] U.S. Patent No. 1,105,8890 [Non-patent literature]

[0017] [Non-Patent Document 1] Baum, O. et al. “Laser-induced hypotensive effect in treatment of the resistant open-angle glaucoma”, Optical Interactions with Tissue and Cells XXXII.Vol.11640.SPIE,2021 [Non-patent document 2] Goldenfeld, Mordechai et al. “Automated direct selective laser trabeculoplasty: first prospective clinical trial”, Translational Vision Science&Technology 10.3(2021):5-5 [Non-patent document 3] Song, Julia “Complications of selective laser trabeculoplasty: a review”, Clinical Ophthalmology (2016): 137-143 [Non-patent document 4] Radcliffe, Nathan et al. “Energy Dose-Response in Selective Laser Trabeculoplasty: A Review”, Journal of Glaucoma 31.8 (2022): e49 Summary of the Invention

[0018] It is an object of the present disclosure to provide an apparatus and method that overcomes one or more of the above-mentioned problems of the prior art. The present disclosure is defined by the appended claims.

[0019] A first aspect of the present disclosure provides a laser system suitable for altering intraocular pressure (IOP) in an eye, comprising: a laser source; a feedback controller configured to adjust dosimetry of the laser source to generate spatially and / or temporally modulated laser light; a first light delivery element configured to direct the spatially and / or temporally modulated laser light to irradiate a first region of the eye; and a detection element configured to detect one or more physical, chemical, mechanical and / or structural properties in a second region on the eye in real time during alteration of the IOP, wherein the feedback controller is configured to adjust dosimetry of the laser source in real time based on real-time detected information regarding the one or more physical, chemical, mechanical and / or structural properties in the second region.

[0020] In an operating scenario of the laser system, a doctor or practitioner can manually introduce a first light-delivering element near a first region. The doctor or practitioner can then select a function of the laser system, for example, to determine the first region or to determine whether the IOP needs to be increased or decreased. The doctor or practitioner can then set one of the preset laser modes (dosimetry parameters) and begin the laser treatment. After the laser treatment begins, it can be automatically performed until the detection information reaches a predetermined threshold, for example, when the IOP reaches a predetermined value. When such a threshold is reached, the controller can stop or pause the laser treatment and wait for the doctor's or practitioner's next command.

[0021] In the context of the present disclosure, "real-time" may generally refer to the timescale over which one or more physical, chemical, mechanical and / or structural properties on the eye are detected and subsequently processed, the timescale being short enough to allow for intentional adjustment of the dosimetry of the laser source via feedback based on the detected and processed information during ongoing treatment of the eye, particularly during changes in IOP.

[0022] In the context of the present disclosure, "real-time" may refer to a time scale of less than a few minutes. For example, detecting in real time may refer to detecting continuously over a period of several minutes, or detecting minutes after an external effect (such as a laser effect) to evaluate such an effect. Real-time processing may refer to processing in which a result can be calculated minutes after the start of the calculation. Nevertheless, smaller time scales are possible as well.

[0023] In particular, real time may refer to a time scale of less than 20 minutes, in particular less than 10 minutes or less than 3 minutes or less than 1 minute or less than 30 seconds or less than 10 seconds or less than 1 second.

[0024] In the context of the present disclosure, "adjusting the dosimetry of the laser" or "adjusting the laser" may refer to adjusting the laser during operation. However, they may also include selecting appropriate initial parameters of the laser for starting laser treatment. In this case, detecting in real time may refer to a situation in which the characteristics are detected within a time span of up to several minutes before the laser begins to function. The laser may start with different initial conditions depending on the exact condition of the eye being treated.

[0025] In an implementation of the laser system of the first aspect, the laser can be tuned by adjusting at least one of the following laser parameters: laser pulse repetition rate, laser pulse duration, shape of the laser signal in the time domain, shape of the laser signal in the frequency domain, laser wavelength, pulse energy, intensity of the laser signal, number of pulses in a pulse sequence, interval duration between sequences, number of total sequences, spatial distribution of laser illumination intensity, dimensions of the irradiated area, distance between adjacent irradiated regions, and distance shift due to propagation within the first light delivering element.

[0026] Adjusting one or more of these parameters can facilitate fine tuning based on environmental characteristics, which can enhance the precision and range of laser light modulation.

[0027] The real-time adjustment of the dosimetry of the laser source may correspond to a constant adjustment of the laser dosimetry, an adjustment of the laser dosimetry upon receiving a signal from a feedback controller, or an update of the laser dosimetry after a certain number of pulses in the sequence. The real-time adjustment may further include ceasing irradiation when real-time detected information regarding the property in the region reaches a predetermined or calculated threshold.

[0028] In further implementations of the laser system of the first aspect, the detection element may comprise at least one of the following: a pneumatic device, an IR radiometer, a photoacoustic detector, an OCE device, an OCT device, and a device for detecting backlight scattering.

[0029] These types of sensing elements can provide high-resolution monitoring of an area or local environment, but can generate large amounts of data. By combining multiple different types of sensing elements with a powerful (on-board or external) computer, such as a quantum computer, the present disclosure can facilitate precise real-time control of laser modulation.

[0030] In further implementations of the laser system of the first aspect, the characteristics may include one or more of the following: IOP of the eye, temperature, temperature distribution, pressure, pressure distribution, Young's modulus, speed of sound, chemical composition, thickness, e.g., scleral thickness, dimensions, e.g., dimensions of the ciliary body, Schlemm's canal and / or TM, dimensions of unobstructed luminal areas, e.g., dimensions of unobstructed luminal areas in fluid drainage pathways, pore size, pore size distribution.

[0031] In an embodiment, due to the complexity of the laser system as well as the complex environment within the human body, the desired results may be achieved by simultaneously adjusting multiple dosimetry parameters of the laser source based on calculation of real-time detected information regarding multiple characteristics in the area by specially designed algorithms.

[0032] Due to the large number of input and output parameters of the algorithm, a large feedback lag can lead to deviations from the desired effect. Real-time control can be achieved by high-performance computing capabilities. In embodiments, such computers can be (remote) high-performance computers, (remote) hybrid quantum-classical computing facilities, and / or (remote) quantum computers.

[0033] Real-time spatially and / or temporally modulated laser light targeted to the eye based on real-time detected information regarding one or more physical, chemical, mechanical and / or structural properties of the eye can facilitate controllable non-invasive procedures for regulating IOP.

[0034] In an implementation of the laser system of the first aspect, the first region may include a portion on the sclera of the eye, and the laser source may be adjusted to modify a porous structure on the sclera.

[0035] Conventional laser systems for altering the IOP of the eye focus on coagulating the vitreous pathway or the ciliary body. The importance of the uveoscleral pathway is usually overlooked. By modifying the porous structure on the sclera, the present disclosure provides a novel solution for adjusting aqueous humor outflow. This may be particularly useful when options for treating other parts of the eye are no longer available, for example, when Schlemm's canal and TM have been previously treated and can no longer be treated again. Furthermore, the formation and adjustment of the porous structure on the sclera largely maintains the integrity and mechanical stability of the eye, resulting in few adverse effects.

[0036] In the context of this disclosure, a porous structure may refer to a structure with multiple distributed structural defects. The pores of such a porous structure do not necessarily have to be rounded in the conventional sense; they may be creeks, microcavities, gaps, or other forms of structural defects that facilitate the movement of aqueous humor through the tissue matrix. Furthermore, porous structures should also be distinguished from aggregates of macroscopic defects that impair the mechanical properties of tissue. In a typical configuration, a porous structure may be a microporous structure, i.e., the structural defects may have a size of less than 5 micrometers. In the early stages of the formation of such microporous structures, the formation may only modify the physical and chemical properties of the affected area and may not significantly change the macroscopic appearance and mechanical properties of the tissue.

[0037] In some embodiments, the tissue and / or object in which the porous structure is formed may already be porous prior to laser-induced porosity formation. In these embodiments, the porous structure refers to a structure that is more porous than the untreated tissue or object. In some embodiments, the formation of a porous structure may refer to an increase in porosity and / or an increase in pore size. In other embodiments, the formation of a porous structure may refer to the unclog of an existing clogged porous structure. Because clogging can often occur in unstable porous structures, controlled porous structure formation according to the present disclosure may be applied to unclog clogged, unstable porous structures and form stabilized porous structures for long-term stability.

[0038] In some embodiments, the size of the pores or the porosity of the porous structure can be controlled according to the desired aqueous humor outflow, hi other embodiments, the size of the pores can be made small enough to maintain the structural integrity of the sclera and / or maximize the stability of the pores.

[0039] In a further implementation of the laser system of the first aspect, the detecting element may comprise a receiving element.

[0040] In a further implementation of the laser system of the first aspect, the light receiving element may be configured to receive scattered light.

[0041] Scattered light can result from spatially and / or temporally modulated laser light. Light scattering can be sensitive to the formation of microporous structures or other defects at the microscopic level. Detecting and analyzing scattered light of different wavelengths allows for the use of Mie and Rayleigh scattering laws to determine the size distribution of pores, defects, or potential bubbles on the sclera that may be generated during porous structure formation.

[0042] In a further implementation of the laser system of the first aspect, the detection element may comprise a second light delivering element.

[0043] In a further implementation of the laser system of the first aspect, the second light delivering element may be configured to deliver a probe light signal for light scattering analysis.

[0044] The scattered light can also result from a probe light signal, which does not need to interact with the tissue or object to form a pore and can be used prior to laser operation to determine the initial state of the laser. This can facilitate initializing the laser with little or no disruptive side effects to the tissue or object or their environment.

[0045] In a further implementation of the laser system of the first aspect, the first light delivering element comprises a bundle of optical fibers and / or is configured to multiplex multiple laser outputs of the laser source into one fiber at the input of the first light delivering element.

[0046] This may increase the flexibility of the spatial modulation of the laser light and the scattered light detection described above.

[0047] In a further implementation of the laser system of the first aspect, the sensing element may comprise a conductivity sensing element.

[0048] In a further implementation of the laser system of the first aspect, the conductivity sensing element may be configured to sense the conductivity on the tissue or object.

[0049] In some embodiments, it may be beneficial to form a stabilized porous structure. This can be achieved by stable bubble generation. Spatially and / or temporally modulated laser light can generate microbubbles from gas dissolved in the liquid in the environment. These bubbles can be stabilized by positive charges on their surfaces. Therefore, conductivity information can reflect the state of bubble formation. Modulating the laser light taking this information into account can facilitate the controlled generation of stabilized bubbles, which can further facilitate the controlled formation of stabilized porous structures.

[0050] The characteristics of the porous structure, such as the width and length of the pores, can be important parameters when optimizing one or more other processes, such as laser treatment of the ciliary body, because these characteristics can reflect the overall mechanical properties of the eye, which can be used to optimize other processes. Therefore, controlled formation and accurate detection of the corresponding properties can be important for achieving the effects of one or more other treatments. In particular, a real-time feedback controller can realize such controlled interaction between the porous structure formation and one or more other processes.

[0051] In a further implementation of the laser system of the first aspect, the modulated laser light may be suitable for achieving and / or maintaining a first temperature range and / or a second temperature range within the first region, wherein the porous structure is stabilized within the first temperature range and the porous structure is destabilized within the second temperature range.

[0052] For the formation of a stabilized porous structure, the parameters can be adjusted so that the detected temperature can be maintained below a first temperature threshold and / or within a predetermined first temperature range. At lower temperatures, bubbles can be stabilized. In a typical configuration, the first temperature threshold can be determined to be a value above 40°C and / or below 80°C. In an embodiment, the first temperature range can be 40-80°C, particularly 45-65°C.

[0053] In another embodiment, the bubbles may be destabilized at a higher temperature range. Accordingly, the parameters may be adjusted so that the detected temperature exceeds a second temperature threshold and / or is maintained within a predetermined second temperature range to destabilize the porous structure. In a typical configuration, the second temperature threshold may be determined to be a value above 40°C and / or below 80°C. In an embodiment, the second temperature range may be 55-100°C, preferably 70-90°C.

[0054] In a further implementation of the laser system of the first aspect, when the IOP of the eye needs to be lowered, the laser source can be adjusted to form and / or stabilize one or more pores on the sclera.

[0055] In a further implementation of the laser system of the first aspect, if the IOP of the eye needs to be increased, the laser source can be adjusted to close and / or destabilize one or more pores on the sclera.

[0056] The present disclosure provides a laser device that can reversibly change IOP. This can be achieved by opening and closing pores to increase and decrease aqueous humor outflow depending on the desired effect. The opening and closing of pores can be achieved by stabilizing and destabilizing the pores using a laser source. In other words, the solution provided by the present disclosure provides an opportunity to correct IOP changes, increasing flexibility, adaptability, and precision of IOP changes.

[0057] The formation and / or destabilization of one or more pores can be achieved by adjusting the laser source. For example, the temperature in the first region can be maintained in a first temperature range and the laser source can be adjusted to stabilize the porous structure, and / or the temperature in the first region can be maintained in a second temperature range and the laser source can be adjusted to destabilize the porous structure. The porous structure can also be stabilized / destabilized by other mechanisms, such as non-laser heating.

[0058] In a further implementation of the laser system of the first aspect, the feedback controller may be configured to calculate a flow rate of fluid through the porous structure on the sclera based on the detected information.

[0059] The detected information may include the size distribution of pores, defects, or potential bubbles on the sclera, as described above. The calculation may be based on a fluid dynamics model constructed in consideration of the mass transfer theory of fluid through the porous structure according to the detected information.

[0060] In a further implementation of the laser system of the first aspect, the second region may be outside the first region.

[0061] By detecting one or more physical, chemical, mechanical, and / or structural properties in a region outside the first region, the secondary effects of the laser light on the surrounding area can be considered, rather than just the primary effects of the laser light directly directed at the irradiated region. Furthermore, since the second region in this case is not directly affected by the laser light, noise in the detection information can be reduced. This can increase the accuracy of the feedback controller.

[0062] In a further implementation of the laser system of the first aspect, the second region may include two portions each having a different distance relative to the first region, and the detected information may each relate to one or more physical, chemical, mechanical and / or structural properties of the two portions of the second region.

[0063] For more precise feedback control, the sensing element may sense the property of two portions, each at a different distance to the first region, which may reflect, for example, the gradient of the property.

[0064] In a further implementation of the laser system of the first aspect, the second region may include a portion on the cornea.

[0065] For example, during operation of the laser system, the laser light may not directly affect the cornea, but the cornea may be coupled to other portions that are irradiated, such as the sclera, ciliary body, Schlemm's canal, and / or TM, and the laser effect on those portions may change the properties of the cornea.

[0066] In a further implementation of the laser system of the first aspect, the detected information may relate to one or more mechanical properties of the cornea.

[0067] The mechanical connection between the cornea and the rest of the eye is rigid. Therefore, the cornea may be sensitive to mechanical changes in the rest of the eye, and the mechanical response of the cornea to mechanical changes in the rest of the eye may be rapid. Therefore, information about the mechanical properties of the cornea may be a good input parameter for accurate feedback control.

[0068] In a further implementation of the laser system of the first aspect, the feedback controller may be configured to obtain overall mechanical properties of the eye, including mechanical properties of the trabecular meshwork, mechanical properties of the superficial layer of Schlemm's canal, mechanical properties of the ciliary body and / or mechanical properties of the sclera.

[0069] For example, the overall mechanical properties of the eye may include the IOP of the eye.

[0070] In further implementations of the laser system of the first aspect, the overall mechanical properties of the eye, the mechanical properties of the trabecular meshwork, the mechanical properties of the superficial layer of Schlemm's canal, the mechanical properties of the ciliary body and / or the mechanical properties of the sclera may be related to the mechanical response of the eye and / or sclera to the modulated laser light.

[0071] In a further implementation of the laser system of the first aspect, the detection element may include an OCE device and a pneumatic device combined with the OCE device, and the detection element continuously measures one or more mechanical properties of the cornea.

[0072] In a further implementation of the laser system of the first aspect, the OCE device continuously measures one or more mechanical properties of the cornea.

[0073] Conventional pneumatic devices for measuring one or more mechanical properties of the cornea operate in a pulsed mode, performed before or after ocular laser treatment. The present disclosure provides a solution in which an OCE can be used continuously to measure one or more mechanical properties of the cornea, so that the pneumatic device can be operated in a continuous mode. For example, after an air pressure pulse is applied to the cornea, OCE measurements can be performed on the cornea in real time during laser irradiation. In another example, OCE measurements can be performed on the depression formed by the air pressure pulse. In this way, air pressure measurements can be performed during laser treatment, facilitating accurate real-time feedback control.

[0074] In a further implementation of the laser system of the first aspect, the first region may include a portion on the ciliary body of the eye, and the laser source may be adjusted to activate one or more cells on the ciliary body.

[0075] Conventional laser systems applied to the ciliary body to change IOP are typically used for cyclophotocoagulation procedures, in which portions of the ciliary body are destructively coagulated, reducing aqueous humor production. This is only applied to reduce IOP and is destructive in nature. The present disclosure provides a laser system that can regenerate or heal the ciliary body by activating one or more cells on the ciliary body with modulated laser light. Thus, in this implementation, IOP can also be increased and damage to the ciliary body can be reversed.

[0076] In a further implementation of the laser system of the first aspect, the modulated laser light may be adapted to generate temperature and / or pressure conditions for activating one or more cells.

[0077] In a further implementation of the laser system of the first aspect, the temperature and / or pressure conditions may be defined over a temperature range and / or a pressure range.

[0078] Cells can be activated to differentiate or regenerate when placed under specific heat and / or pressure conditions. Such conditions can be achieved by modulated laser light. For example, absorption of laser energy can increase the temperature of local tissue and / or fluid, which can further result in thermal pressure. By spatially and temporally modulating the laser light, desired temperature and / or pressure conditions for activation can be achieved.

[0079] For example, typical temperatures on the ciliary body in cyclophotocoagulation procedures can be higher than 55°C, particularly in the range of 60-110°C. Typical temperature ranges on the ciliary body for cell activation can be in the range of 30-70°C, for example, 40-60°C, particularly 45-55°C. Typical pressure ranges on the ciliary body for cell activation can be less than 50 KPa, for example, 3-30 KPa, particularly 5-25 KPa.

[0080] In a further implementation of the laser system of the first aspect, the modulated laser light may be adapted to generate thermomechanical waves capable of propagating to a third region outside the first region, and the one or more cells may be within the third region.

[0081] The healing effect of the laser treatment or each laser treatment session can be achieved by localized temporally and spatially modulated laser light by activating distant cells. In some embodiments, the localized laser light is 0.01 to 10 mm. 3 , especially 0.1 to 1 mm 3 The laser beam can be absorbed in a tissue region of a volume of 1000 nm. A small irradiated area can reduce tissue damage from direct laser irradiation and facilitate more energy-efficient and controllable modulation of the laser light. Although the direct irradiated area according to the present disclosure can be small in some embodiments, larger areas can be treated by laser-induced effects by generating thermomechanical waves.

[0082] Controlled thermomechanical activation of one or more cells can be achieved by stress waves (waves due to the oscillating thermomechanical properties of the medium) resulting from non-uniform heating waves resulting from laser-induced coordinated rotational oscillations of water dipoles. The stress waves can propagate to one or more cells and activate the one or more cells by generating specific thermal and / or mechanical conditions for the one or more cells.

[0083] In a further implementation of the laser system of the first aspect, the feedback controller may be configured to adjust the dosimetry of the laser source such that the generated modulated laser light changes the temperature and / or pressure of the first region in a particular sequence and / or simultaneously.

[0084] In a further implementation of the laser system of the first aspect, the feedback controller may be configured to adjust the dosimetry of the laser source such that the generated modulated laser light changes the temperature and / or pressure field, in particular the temperature and / or pressure distribution, of the first region in a specific sequence and / or simultaneously.

[0085] Varying the temperature and / or pressure of the first region in a particular sequence can promote the generation of stress waves.

[0086] In an embodiment, the temperature and / or pressure at which the stress waves are generated can be varied and controlled by modulated laser light depending on the desired reach of the stress waves and the behavior of the stress wave dissipation in the environment relative to the eye.

[0087] Varying the temperature and / or pressure of the first region in a particular sequence and / or simultaneously can also facilitate the controlled formation of a porous structure.

[0088] In a further implementation of the laser system of the first aspect, the feedback controller may be configured to control the position of the first light delivering element during irradiation in real time based on the real-time detected information.

[0089] For example, the feedback controller may be configured to control the first light delivering element to direct the laser light to a fourth region different from the first region in real time based on the real-time detection information.

[0090] The first light-delivering element may comprise a single or bundle of optical fibers. The first light-delivering element may comprise multiple outcoupling elements. Changing the irradiation area may involve switching between different outcoupling elements and / or controlling individual outcoupling elements, such as tilting the angle of the outcoupling elements. The first light-delivering element may comprise a servo element configured to change the physical position of the first light-delivering element to change the irradiation area. The irradiation area may be changed after cell activation and / or porous structure formation to activate additional cells and / or foam additional porous structures. The change in irradiation area may be performed while activating the same cells or while forming the same porous structure. In the latter case, changing the irradiation area as part of the spatial modulation of the laser light may facilitate the generation of desired stress waves.

[0091] In a further implementation of the laser system of the first aspect, the first region may include at least two of the following: a) the episcleral part of the eye; b) in and / or near the Schlemm's canal and / or trabecular meshwork of the eye; and c) The part of the eye above the ciliary body.

[0092] The laser system according to the present disclosure may apply laser effects to different regions or portions of an eye region during a laser treatment. The laser effects may occur simultaneously or closely spaced or temporally, resulting in a complex final effect on the eye region. For example, the final effect on the eye region may include a superposition of a primary effect of laser light delivered directly to the region with a secondary effect of laser light delivered to another portion of the eye, or a superposition of two secondary effects of laser light delivered to two other portions of the eye. The controller may adjust the laser source so that the laser light delivered to different portions of the eye can be simultaneously modulated for an optimal overall healing effect.

[0093] Among the various parts of the eye, the above three types a) to c) may be important for IOP. Laser treatment that considers at least two of the three parts, or all three parts simultaneously, may result in improved healing effects compared to conventional laser treatment that usually only treats b) or c).

[0094] In a further implementation of the laser system of the first aspect, the feedback controller may be configured to calculate the desired relative contribution of the two portions in normalizing the IOP.

[0095] In a further implementation of the laser system of the first aspect, the dosimetry of the laser source may be adjusted to achieve a desired relative contribution.

[0096] In an example, the relative contribution can be the relative contribution in increasing / decreasing aqueous humor outflow and / or production.

[0097] Considering multiple portions of the eye simultaneously can contribute to the accurate determination of real-time laser effects on those portions, as well as the accurate determination of the desired result. By considering multiple portions on the eye to achieve the final desired result, each portion on the eye may require fewer modifications compared to treating only one of the portions, which may result in less overall trauma.

[0098] For example, in a first laser treatment session, a porous structure may be formed and stabilized in an episcleral portion of the eye using a first modulated laser light, while the luminal area of ​​Schlemm's canal in another portion of the eye may be increased using a second modulated laser light to reduce the IOP of the eye. The relative contribution of the two portions in normalizing IOP may be 1:1. In an example, this value may be calculated by dividing the increase in aqueous humor outflow through the uveoscleral pathway by the increase in aqueous humor outflow through the conventional pathway.

[0099] In another example, some time after a first laser treatment session, it may be determined that the IOP of the eye is too low and a second laser session may be necessary. In the second laser session, the porous structure formed and stabilized in the first laser session in the suprascleral region may be destabilized and closed using a third laser beam, while in the suprascleral region, one or more cells may be healed and activated using a fourth laser beam. The relative contribution of the two regions in normalizing IOP may be 1:2. In an example, this value may be calculated by dividing the decreased aqueous humor outflow through the uveoscleral pathway by the increased aqueous humor production by the ciliary body.

[0100] In another example, the desired relative contributions of three, more, or all segments in normalizing IOP may be calculated. For example, a laser treatment session may include applying a laser effect to three segments on the sclera and two segments on the ciliary body, with respective contributions to IOP normalization of 25%, 25%, 30%, 10%, and 10%, respectively.

[0101] In a further implementation of the laser system of the first aspect, the feedback controller may be configured to determine, based on the detection information, whether one of the portions has been previously treated.

[0102] Portions of the eye that have been previously treated may be more sensitive to additional laser effects, which may result in greater trauma in such portions than in other portions. By determining whether one of the portions has been previously treated, the controller may be further configured to adjust the laser source accordingly to reduce the real-time laser effect on the treated portion or to reduce the overall laser dose applied to the treated portion.

[0103] In a further implementation of the laser system of the first aspect, if the feedback controller determines that one of the portions has been previously treated, the feedback controller is configured to correct the desired relative contribution by reducing the desired contribution of the treated portion.

[0104] Such a correction can be achieved by multiplying the desired contribution by a predetermined coefficient. For example, the predetermined coefficient can be 0.25. The desired relative contribution of the episcleral portion and the TM portion in reducing IOP can be 1:1 before correction. For example, it can be determined that the TM has previously been treated by conventional selective laser trabeculoplasty. The desired relative contribution after correction can be 1:0.25 = 4:1. If these are the only two portions irradiated by laser light, this means that after a laser treatment session, the laser system can operate such that 80% instead of 50% of the increased aqueous humor outflow can be achieved through the newly formed porous structure in the episcleral portion, while 20% instead of 50% of the increased aqueous humor outflow can be achieved through the laser effect on the TM portion.

[0105] In an embodiment, the coefficients may depend on which portions have been previously treated, the results of the previous treatments, other patient-related characteristics and / or diagnoses.

[0106] In an embodiment, the desired contributions of two or more portions may be compensated for.

[0107] In a further implementation of the laser system of the first aspect, two or more portions may be irradiated simultaneously, sequentially, and / or repeatedly.

[0108] In a further implementation of the laser system of the first aspect, the first region may include multiple portions positioned along the limbus of the eye.

[0109] By placing multiple sections along the annulus, the treatment may be more symmetrical and therefore more balanced.

[0110] In an embodiment, multiple portions on the same organ of the eye, for example, multiple portions on the sclera, may be illuminated with laser light from the same laser source.

[0111] In another example, multiple portions of the eye may be illuminated with laser light that is correlated with one another, for example, laser light illuminating adjacent regions of the eye may have a particular phase shift.

[0112] In further implementations of the laser system of the first aspect, the feedback controller may comprise and / or be coupled to a (remote) high performance computer, a (remote) hybrid quantum-classical computing facility, and / or a (remote) quantum computer.

[0113] In a further implementation of the system of the first aspect, the feedback controller may comprise and / or be connected to a storage device that stores offline configuration tables, the configuration tables being calculated by a (remote) high performance computer, a (remote) hybrid quantum-classical computing facility, and / or a (remote) quantum computer.

[0114] The real-time adjustment of a laser based on feedback detection information of the laser affected area according to the present disclosure is a complex feedback optimization problem. Better evaluation of the laser effect and accurate adjustment of the laser may depend on a large amount of detection information, which may be enormous. Quantum algorithms or hybrid quantum algorithms such as variational quantum eigensolvers may be used in this context and may outperform conventional algorithms in optimizing systems with multidimensional parameters. Therefore, using high-performance and / or hybrid and / or quantum computers and / or hybrid computing capabilities may facilitate better control of the laser system.

[0115] In a further implementation of the method of the first aspect, the remote high performance computer, the remote hybrid quantum-classical computing facility, and / or the remote quantum computer may be located on a central server.

[0116] In a further implementation of the method of the first aspect, the central server may be configured to coordinate multiple laser systems.

[0117] A second aspect of the present disclosure is a method, comprising: a) detecting one or more physical, chemical, mechanical and / or structural properties in a first region of the eye; b) processing the detected information regarding the physical, chemical, mechanical and / or structural properties of a first region on the eye; c) acquiring characteristics of the porous structure changes of the eye and / or activation of ciliary body regeneration in real time during the porous structure changes and / or activation of ciliary body regeneration.

[0118] In implementations of the method of the second aspect, characterizing the porous structure changes and / or activating ciliary body regeneration may include real-time aqueous humor outflow calculated based on the porous structure changes and / or real-time aqueous humor production calculated based on ciliary body production.

[0119] In a further implementation of the method of the second aspect, the characteristics may include one or more of the following: IOP of the eye, temperature, temperature distribution, pressure, pressure distribution, Young's modulus, speed of sound, chemical composition, thickness, e.g., scleral thickness, dimensions, e.g., dimensions of the ciliary body, Schlemm's canal and / or TM, dimensions of unobstructed luminal areas, e.g., dimensions of unobstructed luminal areas in fluid drainage pathways, pore size, pore size distribution, scattered light properties.

[0120] In a further implementation of the method of the second aspect, the method steps may be performed in real time during laser irradiation of the second region of the eye.

[0121] The laser light used for irradiation may have an invasive effect on the second region, for example, in a laser procedure, or may have no essentially invasive effect on the second region, for example, for diagnostic purposes. For example, the irradiated laser light may be a probing light used for light scattering analysis. In another example, light scattering analysis may be used to obtain characteristics of the porous structure.

[0122] In a further implementation of the method of the second aspect, the detected and processed information may be used to adjust the laser source in real time to optimize the change in porous structure and / or ciliary body regeneration.

[0123] While the present disclosure may provide an automatic feedback controlled laser system, such as a laser system according to the first aspect, it is understood that the method according to the second aspect need not involve adjustment of the laser system itself. For example, the method according to the second aspect may provide the necessary information to a physician or practitioner operating the laser based on which the physician or practitioner can subsequently assess aqueous humor outflow / production in a first region of the eye and / or the expected laser effect in this region.

[0124] An evaluation system configured to carry out the method according to the second aspect may comprise an indicator, for example an indicator LED bulb.

[0125] In an embodiment, if the evaluation system determines that aqueous humor outflow / production in the area needs to be altered, it may instruct the physician or practitioner to perform laser treatment, for example, by indicating a green light, which may further indicate to the physician or practitioner where to perform the laser treatment, for example, by displaying corresponding information on a screen.

[0126] In another example, if the evaluation system determines that the detected information regarding the treated eye has reached a predetermined value, for example, if the porosity of the porous structure of the eye is large enough or if the temperature is too high, it may instruct the doctor or practitioner to stop the laser treatment, for example, by displaying a red light.

[0127] The method may also provide instructions to the physician to perform other actions, for example, to change the dosimetry of the laser. The predetermined values ​​and / or other evaluation criteria may be predetermined by the physician or practitioner based on a specific case, or may be stored in an offline setting table for the procedure, which may be calculated by a remote high-performance computer, a remote hybrid quantum-classical computing facility, and / or a remote quantum computer. The predetermined values ​​and / or other evaluation criteria may be predetermined based on the laser used by the physician or practitioner, which may be a laser in a laser system according to the first aspect of the present disclosure. The laser may also be a laser whose dosimetry can be manually adjusted.

[0128] In a further implementation of the method of the second aspect, processing the detection information may include generating dosimetry of the laser source in real time based on the detection information during the change in porous structure and / or activation of ciliary body regeneration.

[0129] In an automated laser system, such as the laser system according to the first aspect of the present disclosure, the generated laser dosimetry value may be directly used by a feedback controller to adjust the laser dosimetry without human intervention. The value may also be transmitted to a physician or practitioner, who can then use it to determine whether to manually adjust the laser dosimetry or terminate the laser treatment. As long as the information detection and processing can be performed in real time, e.g., within minutes, the physician or practitioner may have sufficient time to react to change the laser dosimetry in time for real-time laser effects, even if the physician or practitioner chooses to manually change the laser dosimetry. Compared to conventional monitoring and evaluation systems, the evaluation system employing the method according to the second aspect provides more useful and accurate feedback to a physician or practitioner operating a laser system for treating an eye with abnormal IOP.

[0130] In a further implementation of the method of the second aspect, detecting physical, chemical, mechanical and / or structural properties within the region may include determining a temperature or temperature field within the region, wherein dosimetry of the laser source is generated when the temperature and / or its distribution is within a predetermined range.

[0131] In a further implementation of the method of the second aspect, no dosimetry of the laser source may be generated if the temperature is not within a predetermined range.

[0132] In a further implementation of the method of the second aspect, processing the detection information may be performed in accordance with a current task to provide a physician or practitioner with supplemental information on how to operate the laser system.

[0133] The task may be one of alteration of the porous structure on the sclera, alteration of the luminal area in and / or near Schlemm's canal and / or trabecular meshwork, ciliary body coagulation, ciliary body regeneration.

[0134] In a further implementation of the method of the second aspect, processing the detected information regarding the physical, chemical, mechanical and / or structural properties in the eye may further include consideration of the effect of the detected temperature on the thermodynamic parameters of the medium, in particular the nonlinearity of the thermodynamic parameters.

[0135] During laser treatment, laser light can be absorbed by the medium. Current diagnostic techniques based on laser treatment ignore the effects of local temperature increases on the medium's thermodynamic parameters (e.g., thermal conductivity, density, thermal expansion coefficient, and isobaric specific heat capacity) due to such laser light absorption. Conventional diagnostic techniques assume that the thermodynamic parameters are constant. However, even small increases in local temperature can change the values ​​of the medium's thermodynamic parameters, potentially requiring consideration of the nonlinearity of thermal parameters in the heat diffusion thermomechanical equation. The most significant changes in parameters can be attributed to structural and phase transformations that occur in the tissue during laser irradiation.

[0136] In a further implementation of the method of the second aspect, the first region may include a portion outside the second region.

[0137] In a further implementation of the method of the second aspect, the second region may be illuminated by spatially and / or temporally modulated laser light generated by a laser source.

[0138] In a further implementation of the method of the second aspect, the first region may include two portions, each having a different distance to the second region, and the detected information may relate to one or more physical, chemical, mechanical and / or structural properties of the two portions of the first region, respectively.

[0139] In a further implementation of the method of the second aspect, the detected pressure distribution may be mapped to a detected temperature distribution within the first region.

[0140] The spatially resolved distribution can provide more information about the laser effect, which can increase the accuracy of the laser adjustment.

[0141] The combination of temperature sensing and mechanical pressure sensing may reflect different characteristics of regions of the eye and may facilitate accurate assessment of laser effectiveness.

[0142] In a further implementation of the method of the second aspect, the first region may include a portion on the cornea of ​​the eye.

[0143] In a further implementation of the method of the second aspect, the detected information may relate to mechanical properties of the cornea.

[0144] In a further implementation of the method of the second aspect, acquiring characteristics of the porous structure changes of the eye and / or activation of ciliary body regeneration of the eye in real time during the activation of the porous structure changes and / or ciliary body regeneration may further include acquiring overall mechanical properties of the eye, including mechanical properties of the trabecular meshwork, mechanical properties of the superficial layer of Schlemm's canal, mechanical properties of the ciliary body, and / or mechanical properties of the sclera.

[0145] In a further implementation of the method of the second aspect, the overall mechanical properties of the eye, the mechanical properties of the trabecular meshwork, the mechanical properties of the superficial layers of Schlemm's canal, the mechanical properties of the ciliary body and / or the mechanical properties of the sclera may be related to the mechanical response of the eye and / or sclera to the spatially / temporally modulated laser light.

[0146] In further implementations of the method of the second aspect, processing the detection information may be performed in a high performance computer (on-board or remote), a hybrid quantum-classical computing facility (on-board or remote), and / or a quantum computer (on-board or remote).

[0147] In further implementations of the method of the second aspect, the method of the second aspect may be encompassed in an algorithm designed for a high performance computer, a hybrid quantum-classical computing facility, and / or a quantum computer.

[0148] In a further implementation of the method of the second aspect, the remote high performance computer, the remote hybrid quantum-classical computing facility, and / or the remote quantum computer may be located on a central server.

[0149] In a further implementation of the method of the second aspect, the central server may be configured to coordinate multiple laser systems.

[0150] A third aspect of the present disclosure is a method for altering IOP of an eye using temporally and / or spatially modulated laser light comprising a treatment step, the treatment step comprising: a) detecting one or more physical, chemical, mechanical and / or structural properties of a first region of the eye in real time during changes in IOP; b) modulating in real time the laser light illuminating the second portion of the region based on the real-time detected information.

[0151] In implementations of the method of the third aspect, the characteristics may include one or more of the following: IOP of the eye, temperature, temperature distribution, pressure, pressure distribution, Young's modulus, speed of sound, chemical composition, thickness, e.g., scleral thickness, dimensions, e.g., dimensions of the ciliary body, Schlemm's canal and / or TM, dimensions of unobstructed luminal areas, e.g., dimensions of unobstructed luminal areas in fluid drainage pathways, pore size, pore size distribution.

[0152] In a further implementation of the method of the third aspect, the second region may include a portion of the episclera of the eye.

[0153] In a further implementation of the method of the third aspect, the laser light may be modulated to modify the porous structure on the sclera.

[0154] In a further implementation of the method of the third aspect, the modulated laser light may be suitable for achieving and / or maintaining a first temperature range and / or a second temperature range within the second region, wherein the porous structure is stabilized in the first temperature range and the porous structure is destabilized in the second temperature range.

[0155] In a further implementation of the method of the third aspect, the laser light may be modulated to form and / or stabilize one or more pores on the sclera when needed to lower the IOP of the eye.

[0156] In a further implementation of the method of the third aspect, when the IOP of the eye needs to be increased, the laser light may be modulated to close and / or destabilize one or more pores on the sclera.

[0157] In a further implementation of the method of the third aspect, the method may further include calculating a flow rate of fluid through the porous structure on the sclera based on the detected information.

[0158] In a further implementation of the method of the third aspect, the first region may be outside the second region.

[0159] In a further implementation of the method of the third aspect, the first region may include two portions, each having a different distance to the second region, and the detected information may relate to one or more physical, chemical, mechanical and / or structural properties in the two portions of the first region, respectively.

[0160] In a further implementation of the method of the third aspect, the first region may include a portion on the cornea.

[0161] In a further implementation of the method of the third aspect, the detected information may relate to one or more mechanical properties of the cornea.

[0162] In a further implementation of the method of the third aspect, the method may further comprise obtaining overall mechanical properties of the eye, including mechanical properties of the trabecular meshwork, mechanical properties of the superficial layer of Schlemm's canal, mechanical properties of the ciliary body and / or mechanical properties of the sclera.

[0163] In a further implementation of the method of the third aspect, the overall mechanical properties of the eye, the mechanical properties of the trabecular meshwork, the mechanical properties of the superficial layer of Schlemm's canal, the mechanical properties of the ciliary body and / or the mechanical properties of the sclera may be related to the mechanical response of the eye and / or sclera to the modulated laser light.

[0164] In a further implementation of the method of the third aspect, the second region may include a portion on the ciliary body of the eye.

[0165] In a further implementation of the method of the third aspect, the laser source may be adjusted to activate one or more cells on the ciliary body.

[0166] In a further implementation of the method of the third aspect, the modulated laser light may be adapted to generate temperature and / or pressure conditions for activating one or more cells.

[0167] In a further implementation of the method of the third aspect, the modulated laser light may be adapted to generate thermomechanical waves capable of propagating to a third region outside the second region, and the one or more cells may be within the third region.

[0168] In a further implementation of the method of the third aspect, the second region may include at least two of the following: a) the episcleral part of the eye; b) in and / or near the Schlemm's canal and / or trabecular meshwork of the eye; and c) The part of the eye above the ciliary body.

[0169] In a further implementation of the method of the third aspect, the feedback controller may be configured to calculate the desired relative contribution of the two portions in normalizing the IOP.

[0170] In a further implementation of the method of the third aspect, the laser light may be modulated to achieve a desired relative contribution.

[0171] In a further implementation of the method of the third aspect, the method may further include determining, based on the detection information, whether one of the portions has been previously treated.

[0172] In a further implementation of the method of the third aspect, if the feedback controller determines that one of the portions has been previously treated, the desired relative contribution may be corrected by reducing the desired contribution of the treated portion.

[0173] In a further implementation of the method of the third aspect, the two portions may be irradiated simultaneously, sequentially and / or repeatedly.

[0174] In a further implementation of the method of the third aspect, the second region may include multiple portions positioned along the limbus of the eye.

[0175] In a further implementation of the method of the third aspect, the method may be performed by a high performance computer, a hybrid quantum-classical computing facility, and / or a quantum computer.

[0176] In a further implementation of the method of the third aspect, the method may be performed by a feedback controller comprising and / or connected to a storage device, the storage device storing the offline configuration table, the configuration table being calculated by a high performance computer, a hybrid quantum-classical computing capability, and / or a quantum computer. [Brief explanation of the drawings]

[0177] In order to more clearly describe the technical features of the embodiments of the present disclosure, the accompanying drawings illustrating the embodiments are briefly introduced in the following description. The accompanying drawings in the following description are only some embodiments of the present disclosure, and modifications of these embodiments are possible without departing from the scope of the present disclosure defined in the claims. [Figure 1] 1 is a schematic diagram of the anterior part of the eye. [Figure 2] 1 is a schematic diagram of a laser system according to an embodiment. [Figure 3] 1 is a schematic diagram of a laser system according to an embodiment. [Figure 4] 1 is a flowchart illustrating a method for detecting and processing information according to an embodiment. [Figure 5] 1 is a flowchart illustrating a method for altering the IOP of an eye using temporally and / or spatially modulated laser light. [Figure 6] 1 is a schematic diagram of an eye under laser treatment or diagnosis according to an embodiment. [Figure 7] 1 is an example of the calculated trabecular meshwork pore size distribution as a result of laser irradiation of a rabbit eye. [Figure 8] 1 is a graphical representation of the calculated kinetics of porous structure formation in the sclera of a human eye treated with a laser. [Figure 9] 1 is a histological image of laser-induced pores in the sclera of a rabbit eye. [Figure 10] 1 is an ultrasound image of the illuminated sclera of a rabbit eye. [Figure 11] 1 is a graphical representation of the calculated spatial distribution of trabecular meshwork temperature during laser irradiation of a rabbit eye. [Figure 12] 1 is a histological image of laser-induced coagulation of the ciliary body of a rabbit eye. [Figure 13] 1 is a graphical representation of the measured dynamics of temperature and backscattered light during laser irradiation of the sclera of a human eye. DETAILED DESCRIPTION OF THE INVENTION

[0178] The following description provides examples of implementation of the present disclosure and the scope of the present disclosure, but the present disclosure is not limited to the provided examples. Any modifications or substitutions can be easily made by those skilled in the art. Therefore, the scope of protection of the present disclosure is defined by the appended claims.

[0179] FIG. 1 is a schematic diagram of the anterior segment of an eye 201. In the anterior segment, several organs related to intraocular pressure (IOP) of the eye 201 are located within or near the limbus, which surrounds the outer edge of the iris 203f or the outer edge of the lens 203g, and the sclera 203a meets the cornea 203c. IOP is balanced by the production and outflow of aqueous humor. Aqueous humor is produced in the ciliary body 203e and drains along two typical outflow pathways: the conventional pathway 205a or the uveoscleral pathway 205b. In both types of outflow pathways 205a and 205b, aqueous humor produced by the ciliary body 203e flows through the posterior chamber between the iris 203f, the ciliary body 203e, and the lens 203g, then flows through the anterior chamber between the iris 203f, the lens 203g, and the cornea 203c, and then flows toward the limbal region of the anterior chamber. In the conventional pathway 205a, the aqueous humor ultimately drains through the trabecular meshwork 203b and Schlemm's canal 203d. In the uveoscleral pathway 205b, instead of draining through the trabecular meshwork 203b and Schlemm's canal 203d, the aqueous humor ultimately drains through the sclera 203a, which is located near or away from the trabecular meshwork 203b or Schlemm's canal 203d.

[0180] In human infant eyes, the sclera 203a is porous and the uveoscleral pathway 205b contributes significantly to the total drainage of aqueous humor. In adult human eyes, the sclera 203a is porous and the uveoscleral pathway 205b contributes significantly to the total drainage of aqueous humor.

[0181] Typical System FIG. 2 is a schematic diagram of a laser system disclosed by the present disclosure.

[0182] The laser system is suitable for altering the IOP of the eye 201. The laser system comprises a laser source 101, a feedback controller 106 configured to adjust the dosimetry of the laser source 101 to generate spatially and / or temporally modulated laser light, a first light delivery element 102 configured to direct the spatially and / or temporally modulated laser light to irradiate a first region 202a on the eye 201, and a detection element 105 configured to detect one or more physical, chemical, mechanical, and / or structural properties in a second region 202b on the eye 201 in real time during an IOP change, wherein the feedback controller 106 is configured to adjust the dosimetry of the laser source 101 in real time based on real-time detected information regarding the one or more physical, chemical, mechanical, and / or structural properties in the second region 202b.

[0183] FIG. 3 is a schematic diagram of a laser system according to an embodiment.

[0184] The laser system may include an electronics unit 106a. The electronics unit 106a may include a diagnostic element configured to receive and process the detected information. The diagnostic element includes a user interface configured to present the detected information to a user, such as a researcher or physician. For example, the user interface may be configured to present stress and temperature distributions within region 202b. The diagnostic element may transmit the raw detected information to a remote high-performance computer, a remote hybrid computing facility, and / or a remote quantum computer 106c. The diagnostic element may further be configured to preprocess the detected information. For example, the diagnostic element may be configured to analyze the detected information regarding scattered light and determine the size distribution of pores within the porous structure.

[0185] The electronic unit 106a may comprise a radiation modulation element configured to temporally and spatially modulate the radiation of the laser 101 source. The radiation modulation element may be configured to receive commands generated to modulate the radiation of the laser source 101 and adjust the dosimetry of the laser source 101, or the radiation modulation element may be configured to receive dosimetry directly from an external high performance computer, a remote hybrid computing facility, and / or a remote quantum computer 106c.

[0186] The laser system may further comprise a feedback control element 106b configured to manage data flow within the laser system. The data flow may include a flow of real-time detected information regarding one or more physical, chemical, mechanical, and / or structural properties within region 202b, a flow of processed / preprocessed detected information, and generated commands to adjust the dosimetry of laser source 101. Feedback control element 106b may be configured to control the direction and sequence of the data flow such that the irradiation of laser source 101 can be modulated in real time based on the real-time detected information.

[0187] The laser system may further include an external high performance computer, a remote hybrid computing facility, and / or a remote quantum computer 106c configured to process the detection information or pre-processed detection information to generate commands for modulating the radiation of the laser source 101 or adjusting the dosimetry of the laser source 101.

[0188] The external high performance computer, remote hybrid computing facility, and / or remote quantum computer 106c may be configured to solve equations defining thermomechanical problems, such as heat propagation problems, mechanical problems, such as problems involving medium deformation, etc. The solutions may help to optimize the control of porous structure changes and / or cell activation.

[0189] The external high performance computer, the remote hybrid computing facility, and / or the remote quantum computer 106c may be configured to solve equations that define a chemical process problem, such as a chemical bond breaking problem.

[0190] An external high performance computer, a remote hybrid computing facility, and / or a remote quantum computer 106c can be configured to calculate the dynamics of pore shape and size. This solution can help optimize the controlled formation of porous structures.

[0191] The external high performance computer, remote hybrid computing facility, and / or remote quantum computer 106c can be configured to solve hydrodynamic problems, such as equations defining the mass transfer of aqueous humor through a porous structure. The solution can help control real-time IOP and optimize the sensitivity of the feedback control of the laser source.

[0192] An external high performance computer, a remote hybrid computing facility, and / or a remote quantum computer 106c may be configured to use the solution of the above inverse problem to establish optimal dosimetry for each step of the laser procedure. The calculations may be performed within a small time interval, e.g., within milliseconds to minutes, such that a method for treating an eye 201 according to the present disclosure may be performed continuously.

[0193] The diagnostic element, feedback control element 106b, radiation modulation element, and high-performance computer, remote hybrid computing facility, and / or remote quantum computer 106c may be part of the feedback controller 106 of Figure 1. While Figure 2 shows a separation of the electronic unit 106a, feedback control element 106b, and high-performance computer, remote hybrid computing facility, and / or remote quantum computer 106c, this separation should not be interpreted as a physical separation, but rather as a separation of their logical functions. The feedback controller 106 may also refer to one or more combinations of the diagnostic element, feedback control element 106b, radiation modulation element, and high-performance computer, remote hybrid computing facility, and / or remote quantum computer 106c.

[0194] For example, if the feedback controller 106 is configured only to process detected information regarding physical, chemical, mechanical and / or structural properties within region 202b and obtain characteristics of porous structure changes on the eye 201 and / or activation of ciliary body regeneration in the eye 201, the diagnostic element alone or a combination of the diagnostic element with a high-performance computer, remote hybrid computing facility, and / or remote quantum computer 106c can be considered as the feedback controller 106, in which case the feedback controller 106 facilitates evaluation of porous structure changes on the sclera of the eye 201 and / or activation of ciliary body regeneration in the eye 201 within region 202b, and initialization of parameters of the laser source 101.

[0195] For example, if the feedback controller 106 is further configured to process detection information in real time during the change in porous structure and / or activation of ciliary body regeneration induced by the temporally and spatially modulated radiation of the laser source 101, the combination of the feedback control element 106b and the diagnostic element 106a can be considered as the feedback controller 106, in which case the feedback controller 106 facilitates monitoring of the laser-induced change in porous structure and / or activation of ciliary body regeneration. For example, a physician can decide when to discontinue laser irradiation depending on whether the pore size distribution of the porous structure reaches a predetermined threshold.

[0196] The feedback controller 106 may be configured to adjust the laser source 101 in real time based on both diagnostic data obtained before the laser treatment session and real-time detected information during the laser treatment session.

[0197] The laser system may include a laser 101 configured to have its radiation spatially and temporally modulated by a feedback controller 106. Spatial modulation may refer to changing the location, shape, and specific intensity distribution of the laser beam and laser-irradiated area of ​​the laser, as well as the specific intensity distribution of the laser-induced light within the laser-irradiated area. To achieve such spatial modulation, the laser system may include one or more laser sources 101. The laser light delivered by the laser source 101 may be coherent or non-coherent. Multiple lasers 101 may facilitate complex spatial modulation of the laser irradiation.

[0198] The laser system may include a light-converting element 104. The light-converting element 104 may include active or passive elements such as LEDs, lasers, lenses, mirrors, light splitters, and other optical devices. The light-converting element may facilitate or supplement spatial modulation. In an embodiment, the conversion element is adapted to direct modulated laser light into multiple portions aligned along the annulus.

[0199] Each of the lasers 101 may implement independent temporally modulated illumination. Temporally modulated laser illumination is typically a series of pulses of laser illumination with variable pulse repetition rate, pulse duration, pulse intensity, or other variable attributes of the laser pulses. Temporally modulated laser illumination can also refer to non-pulsed laser radiation with variable shape in the time domain and variable shape in the frequency domain.

[0200] The illumination of the laser source 101 may be modulated in real time, which may include constantly adjusting the dosimetry of the laser source 101, adjusting the dosimetry upon receiving a signal from the feedback controller 106, or updating the laser dosimetry after a certain number of pulses in a sequence.

[0201] The laser source 101 in this disclosure may be a combination of several types of lasers, including solid state lasers, fiber lasers, and / or diode lasers.

[0202] Each of the laser sources 101 may further be assigned to different tasks. For example, during a procedure, a first laser source 101 may generate modulated laser light to close holes on the sclera, and a second laser source 101 may generate modulated laser light to activate ciliary body regeneration.

[0203] The laser system may further include one or more light delivering elements 102 configured to deliver modulated laser radiation or laser light to a target. The light delivering element 102 may be an optical fiber, a bundle of optical fibers, or another type of light delivering element. The light delivering element 102 may also be configured to deliver other laser signals, such as a probing laser signal for detecting specific characteristics within the eye 201. In a typical embodiment, the imposed laser modulation may account for possible distortions of the laser signal due to propagation within the laser delivery system 102 and implement corresponding compensation. The light delivering element 102 may include an optical out-coupler for delivering the laser signal to the target in the form of laser radiation. The out-coupler may be coupled to the conversion element 104.

[0204] The laser system may further comprise one or more detection elements 105. The detection element 105 is configured to detect one or more physical, chemical, mechanical, and / or structural properties within region 202b on eye 201. The one or more physical, chemical, mechanical, and / or structural properties may include one or more of the following: IOP of the eye, temperature, temperature distribution, pressure, pressure distribution, Young's modulus, speed of sound, chemical composition, thickness, e.g., scleral thickness, dimensions, e.g., dimensions of the ciliary body, Schlemm's canal, and / or TM, dimensions of unobstructed luminal areas, e.g., dimensions of unobstructed luminal areas in fluid drainage pathways, pore size, pore size distribution.

[0205] The properties can be detected in direct and indirect ways. In an example, the detecting element 105 may comprise a light receiving element configured to receive the scattered light. The scattered light can be fed back as an optical signal and processed to deliver information about temperature, pressure, bubble size distribution, and size distribution of pores and other structural defects based on properties of the optical signal, such as, but not limited to, wavelength distribution and angular intensity distribution. In a typical embodiment, the detecting element 105 may comprise a diagnostic device such as one of the following: an IR radiometer, a photoacoustic detector, an OCE device, an OCT device, and a device for detecting backlight scattering.

[0206] The sensing element 105 may further comprise a pneumatic device for delivering air pulses and / or controlling air pressure. In an embodiment, the pneumatic element may be used for IOP measurement. In another embodiment, the pneumatic element may be used in combination with OCE measurements of mechanical properties such as Young's modulus and pressure distribution at or near the cornea, sclera, and trabecular meshwork. In another embodiment, the mechanical properties may be measured in real time in a continuous mode during a laser procedure.

[0207] The laser system may comprise a work tool 103. The work tool may be connected to a laser source 101 via one or more light delivering elements 102. A portion of the light delivering element 102, one or more detection elements 105, the light converting element 104, and / or (part of) the electronic unit 106a may be incorporated into or integrated into the work tool 103. The work tool 103 may further be connected to a feedback control element 106b.

[0208] Typical Method FIG. 4 is a flow chart illustrating a method for detecting and processing information according to an embodiment.

[0209] In this embodiment, the method comprises: a) detecting one or more physical, chemical, mechanical and / or structural properties in a first region of the eye; b) processing the detected information regarding the physical, chemical, mechanical and / or structural properties of a first region on the eye; c) acquiring characteristics of the pore structure change of the eye and / or activation of ciliary body regeneration in real time during the pore structure change and / or activation of ciliary body regeneration.

[0210] The method shown in Figure 3 can be used to evaluate porous structure, temperature distribution, pressure distribution, and / or other characteristics related to aqueous humor production or outflow. This structural evaluation can be performed to initialize the operating state of the laser. This method can further be used to monitor and evaluate the effects of modulated laser radiation on the eye. This laser effect evaluation can be performed to control laser effects or prevent laser-induced damage to the eye.

[0211] FIG. 5 illustrates a method for altering the IOP of an eye using temporally and / or spatially modulated laser light including a treatment step, the treatment step comprising: a) detecting one or more physical, chemical, mechanical and / or structural properties of a first region of the eye in real time during changes in IOP; b) modulating in real time the laser light illuminating the second portion of the area based on the real-time detected information.

[0212] Application scenario Below is presented an example of a method for altering the IOP of an eye using temporally and / or spatially modulated laser light, which corresponds to the method shown in Figure 5 with additional optional steps.

[0213] 6 is a schematic diagram of an eye 201 undergoing laser treatment or diagnosis according to an embodiment. This diagram corresponds to a front view of the eye 201, with the cornea 203c located in the center of the diagram and the sclera 203a located on the outside of the cornea 203c. The dotted line indicates the limbus 204 located at the boundary between the cornea 203c and the sclera 203a. The trabecular meshwork 203b is located at the limbus.

[0214] The laser system generates temporally and / or spatially modulated light to irradiate a first region 202a of the eye. As shown in FIG. 6, the first region 202a may include several portions distributed across the eye. According to FIG. 6, eight portions of the first region 202a are located on the sclera and two portions are located on the TM. Other numbers of portions may be used depending on the specific treatment scenario. The portions may be separated from each other, connected to each other, or overlapping each other.

[0215] Illumination of different parts can be achieved by different angles of incidence. For example, illumination of the ciliary body can be achieved by a small angle of incidence. In this example, the incident laser light can pass through the sclera and the light can be modulated taking into account both the sclera and the ciliary body. In another example, illumination of the ciliary body can be achieved by a large angle of incidence. For example, the incident laser light can come from the side through the cornea. In this case, the laser effect on the sclera may no longer be considered.

[0216] In the example shown in FIG. 6, the eight segments of the first region on the sclera are arranged along the limbus. In the present disclosure, the arrangement of the segments along the limbus can be understood as a circumferential arrangement along the limbus. The segments may have a fixed distance from the limbus. They may be located outside or inside the limbus. They may be arranged in a circle confocal with the limbus, an ellipse surrounding the limbus, and / or another pattern.

[0217] The positioning of each portion of the first region may be achieved via the light-converting element 104. In another embodiment, the light-converting element 104 may further provide a ring illumination with a controlled annular diameter and width and / or a modulated spatial distribution of radiation along the annulus.

[0218] In this example, an improved approach for the treatment of glaucoma is based on enhancing both conventional uveoscleral outflow by creating permeable pathways for water transport through both the sclera and / or Schlemm's canal / trabecular meshwork as a result of porous structure formation using laser radiation.

[0219] Laser normalization of IOP in eyes of patients with elevated IOP The present disclosure provides a laser system suitable for forming a stabilized porous structure on the sclera and / or superficial Schlemm's canal / trabecular meshwork. In embodiments, the porous structure may be formed on the sclera and / or Schlemm's canal / trabecular meshwork without stabilization. Forming a porous structure on the sclera instead of / in addition to Schlemm's canal / TM effectively increases the availability of the uveoscleral pathway and reduces IOP, especially when treating Schlemm's canal / TM alone is no longer sufficient.

[0220] However, if the pores are closed (healed), the IOP-lowering effect can last for a short period of time. Therefore, in embodiments of the present disclosure, the laser system is further suited to stabilizing the porous structure, for example, by stabilizing ions that coat the surfaces of the bubbles within the porous structure.

[0221] It has been demonstrated that small, submicron-sized, stable bubbles form in the sclera in response to laser irradiation. The stabilization of the bubbles is due to the repulsion of ions that coat the bubble surface, which can stabilize the pores and prevent their collapse.

[0222] In embodiments of the present disclosure, the laser system may further be adapted to destabilize the porous structure, for example, by overheating.

[0223] Overheating above 70°C can anneal stabilizing ions from the bubble surface, thus causing the collapse of bubbles and pores within the tissue. This phenomenon can be used to normalize IOP in eyes with excessively low IOP.

[0224] Therefore, to ensure the long-term clinical efficacy of laser healing of glaucoma, and other techniques involving laser tissue modification, more precise control over the laser heating regimen may be beneficial.

[0225] In another embodiment, simultaneous (or sequential) laser irradiation is performed on the ciliary body, the trabecular region of Schlemm's canal, and / or the sclera.

[0226] In an embodiment, the percentage of the ciliary body that has solidified is determined using OCT during the course of exposure to the ciliary body, and the change in fluid flow, e.g., aqueous humor flow, at each instant is calculated for experimental changes in the intensity of fluid release, e.g., aqueous humor production, due to partial solidification of the ciliary body.

[0227] The dimensions of Schlemm's canal and pores in the trabecular region are controlled by OCT before and / or during laser irradiation.

[0228] In an embodiment, the calculation of the desired size distribution of the pores is performed by a computer based on the measured volume of the ciliary body and the calculated change in fluid release by the ciliary body.

[0229] As a result, the desired porosity during exposure is calculated.

[0230] Figure 7 is a graphical representation of the calculated size distribution of trabecular meshwork pores as a result of laser irradiation of a rabbit eye. Pores with an average size of 12 μm occur in a 160 μm area of ​​the irradiated trabecular meshwork, resulting in a 2 mmHg reduction in IOP.

[0231] Figure 8 is a graphical representation of the calculated kinetics of porous structure formation in the sclera of a laser-treated human eye. The laser has a wavelength of 1560 nm, a laser spot diameter of 600 µm, a pulse duration of 200 ms, an average power of 0.8 W, a pulse repetition rate of 2.5 Hz, and an exposure time of 42 seconds. The calculated maximum temperature is 59 °C, the average pore size is 9 µm, and the desired reduction in IOP is 6 mmHg.

[0232] Monitoring the increase in porosity during irradiation is done by measuring backscattered light during changes in scleral thickness and / or using OCT.

[0233] If the desired value and the monitored porosity value match, then the IOP can be measured by the pneumatic device. In a typical IOP measurement with a pneumatic device, a depression is created on the cornea by the action of an air pressure pulse. The depression size is measured using OCT. When the IOP reaches a predetermined value, the irradiation is stopped.

[0234] Figure 9 shows histological images of laser-induced pores in the sclera of a rabbit eye. The average width of the pores is 10 μm, which allows for an 80% increase in water transport through the sclera. The spatial size distribution and formation kinetics of the pores resulting from laser irradiation of the sclera and / or trabecular meshwork region are calculated by computer before laser irradiation and then measured in real time using backscattered light measurements and / or OCT or ultrasound devices.

[0235] Figure 10 shows an ultrasound image of the irradiated sclera of a rabbit eye. Pore formation in the sclera is evidenced in real time by an increase in scleral thickness in the laser-irradiated area. Scleral thickness increased by 220 μm, representing an 80% increase in water permeability through the irradiated area of ​​the sclera. IOP decreased by 3.2 mmHg.

[0236] During the typical laser procedure described above, the temperature of the sclera can be monitored (e.g., by an IR radiation measuring instrument or a photoacoustic sensor) and the laser parameters (power and / or time of laser exposure) can be controlled so that the temperature is within a specific range (e.g., between 45 and 65°C).

[0237] Figure 11 is a graphical representation of the calculated spatial distribution of trabecular meshwork temperature during laser irradiation of a rabbit eye. The maximum temperatures within the irradiation zone are 68°C and 55°C at the center and boundary of the 400 μm diameter laser spot, respectively.

[0238] If laser-induced formation of porous structures in the sclera and / or Schlemm's canal / trabecular meshwork does not result in sufficient IOP reduction, focal laser coagulation of the ciliary body may be performed. Laser-induced coagulation of the ciliary body may be performed in real time during porous structure formation. However, due to the destructive nature of ciliary body coagulation, the laser system may be configured to minimize coagulation of the ciliary body.

[0239] Figure 12 shows a histological image of laser-induced coagulation of the ciliary body of a rabbit eye. The desired coagulation volume was 3.3 mm. 3 The 1320 nm transscleral laser was adjusted to achieve the desired coagulation volume. The final coagulation zone size was 1.5 mm, which was calculated as 3.4 mm. 3 It represents the final coagulation volume of 100 μg, which allows for a reduction in IOP of 3 mmHg.

[0240] Laser normalization of IOP in eyes of patients with low IOP There are two approaches to achieving this goal.

[0241] 1) Partial closure of the stabilized pores in the scleral and trabecular regions of Schlemm's canal by increasing the temperature above 70°C. In an embodiment, a calculation of a desired distribution of pore sizes is performed based on changes in permeability of fluids, such as aqueous humor, through the sclera and trabecular meshwork.

[0242] Monitoring of porosity reduction during irradiation is performed by measuring backscattered light and / or using OCT during changes in scleral thickness and trabecular meshwork dimensions.

[0243] Figure 13 is a graphical representation of the measured temperature and backscattered light dynamics during laser irradiation of the sclera of a human eye. The x-axis represents irradiation time. Triangular data points represent temperature, and circular data points represent backscattered light intensity. The laser had a wavelength of 1560 nm, a power output of 1.8 W, a spot diameter of 1 mm, a pulse duration of 200 ms, and a pulse repetition rate of 2.5 Hz. At an exposure time of 27.5 s, indicated by the dashed line, a temperature of 83 °C and a two-fold decrease in backscattered light intensity compared to the initial value were observed. This decrease in backscattered light intensity is attributed to the partial closure of pores in the irradiated region of the sclera that provide aqueous humor transport through the sclera. The pores were stabilized by positive ions coating the pore surface. The pores were closed by heating above 70 °C, which resulted in the release of ions from the pore surface and local coagulation of tissue near the pore surface. The exposure time value was established by a feedback system based on calculations of aqueous humor transport in the porous structure and real-time data on temperature and IOP dynamics.

[0244] If the desired value and the monitored porosity value match, then the IOP can be measured by the pneumatic device. In a typical IOP measurement with a pneumatic device, a depression is created on the cornea by the action of an air pressure pulse. The depression size is measured using OCT. When the IOP reaches a predetermined value, the irradiation is stopped.

[0245] During the typical laser procedure described above, the temperature of the sclera can be monitored (e.g., by an IR radiation measuring instrument or a photoacoustic sensor) and the laser parameters (power and / or time of laser exposure) can be controlled so that the temperature is within a specific range (e.g., between 70 and 90°C).

[0246] 2) Laser revitalization and partial regeneration of excessively damaged ciliary bodies. In an embodiment, the laser system may be adapted to generate temperature and / or pressure conditions to activate and / or regenerate the damaged ciliary body. For better healing effects, activation / regeneration may be followed by IOP measurement and (if necessary) further laser treatment after 2 or 3 months.

[0247] Typical Algorithms A typical algorithm can be characterized through mathematical problems and sub-problems that need to be solved by a large remote high performance computer connected to a feedback controller for real-time adjustment of the laser system. The mathematical problems, sub-problems, and tasks may include: 1. 3D unsteady thermal problem for spatial and temporal modulation of a laser heat source. 2.3D thermomechanical problems. 3. 3D kinetics of laser-induced bond cleavage. 4. Kinetics of porous structure formation, including pore branching and merging. Figure 8 shows an example of pore size dynamics calculated in real time. 5. Kinetics of tissue degeneration. 6. Kinetics of aqueous transport in porous structured systems.

[0248] The calculation of the ratio between the effect of IOP changes due to laser exposure on the sclera, trabecular region, and ciliary body is based on preoperative diagnostic data regarding IOP, scleral and trabecular meshwork aperture dimensions, and ciliary body size and condition.

[0249] The algorithm used in this disclosure should solve the inverse problem of determining the dosimetry of a laser source to achieve a positive effect such as a desired IOP. The algorithm is based on diagnostic data obtained before and during ocular laser treatment with variations in the following parameters: laser wavelength, laser power, pulse duration, pulse repetition rate, laser spot diameter, distance between laser spots, volume of train of pulses, time interval between train of pulses, and total exposure time.

[0250] Because people with thicker, stiffer corneas tend to have a higher measured IOP than their actual IOP, the calculation algorithm may include an adjustment based on measurements of corneal thickness and its Young's modulus.

[0251] The efficiency and safety of the laser exposure is ensured by the selection and real-time control of the laser dosimetry, which provides a specific temperature range, a specific size distribution of pores within the irradiation zone, and a specific range of thermomechanical stress amplitude during irradiation of the ciliary body.

[0252] Laser dosimetry for irradiating the sclera and trabecular meshwork is calculated to heat the pores of the sclera and / or trabecular meshwork to temperatures ranging from 65 to 90°C for several seconds, closing the pores and reducing water transport in the irradiated area. Laser dosimetry for irradiating the ciliary body is calculated to provide a thermomechanical action with a frequency ranging from 0.2 to 5.0 Hz and an amplitude of oscillatory pressure ranging from 3 to 20 kPa, resulting in the activation of regenerative processes in the irradiated area of ​​the ciliary body.

[0253] For patients with elevated IOP, the ratio between the desired effects of irradiation of the sclera, Schlemm's canal, trabecular meshwork, and ciliary body can be calculated based on diagnostic information obtained from all of these targets and the cornea. Laser dosimetry for irradiation is calculated to result in the formation of pores of the desired dimensions. The desired dimensions can range from 5 to 20 μm in width and 10 to 100 μm in length for the irradiated areas of the sclera and trabecular meshwork, and from 30 to 300 μm for Schlemm's canal.

[0254] The calculated temperature of the irradiated area can range from 45 to 65°C in the sclera and trabecular meshwork, and from 60 to 90°C in Schlemm's canal.

[0255] Examples of successful procedures The present disclosure has been embodied in certain preliminary experiments disclosed below. Although the present disclosure has been embodied in these examples, these examples may include additional steps, which should not be construed as limiting the present disclosure.

[0256] First Example: Decreased IOP in rabbit eyes. An example of this involves the formation of porous structures in the sclera and trabecular meshwork, followed by local coagulation of the ciliary body.

[0257] Experiments were performed in two eyes of male New Zealand rabbits (weight 3.1 kg).

[0258] Preoperative evaluation was performed to determine IOP, Young's modulus, and stress distribution in the cornea, sclera, and trabecular meshwork. The corneal Young's modulus was determined to be 0.30 + / - 0.05 MPa.

[0259] The mean pore size of the sclera and trabecular meshwork was 3 microns measured by OCT.

[0260] Intraocular pressure in rabbits was measured using a pneumatic tonometer calibrated for rabbit eyes. Measurements were performed in restrained animals without topical anesthesia.

[0261] The rabbit's IOP was found to be 21.6 mmHg in the left eye and 21.7 mmHg in the right eye.

[0262] The desired reduction in IOP was calculated to be 5 mmHg. The desired relative contributions of IOP change due to laser exposure to the trabecular meshwork, sclera, and ciliary body were calculated to be 25%, 38%, and 37%, respectively.

[0263] The irradiation was carried out in three steps.

[0264] Step 1. Laser irradiation of the trabecular meshwork and IOP measurement. This step was performed using a Tm fiber laser with a wavelength of 1920 nm, a laser spot diameter of 400 μm, a pulse duration of 5 ms, an average power of 2.0 W, and a pulse repetition rate of 20 Hz.

[0265] OCT images demonstrate through-channels in the trabecular meshwork measuring 420 μm and 460 μm in diameter in the left and right eyes, respectively.

[0266] IOP was measured to be 19.6 (left eye) and 19.2 (right eye) mmHg, a decrease of 2.0 and 2.5 mmHg, respectively.

[0267] Step 2. Laser irradiation of the sclera. In this step, a laser with a wavelength of 1440 nm, a laser spot diameter of 400 μm, a pulse duration of 200 ms, an average power of 0.7 W, a pulse repetition rate of 2 Hz, a series of 10 pulses, a period of 5 s between the series, and an exposure time of 50 s was irradiated.

[0268] Figures 11 and 7 demonstrate the calculated temperature field and spatial distribution of pores in the laser-irradiated sclera.

[0269] Photoacoustic techniques were used to measure the actual temperature field during laser irradiation: the maximum temperature at the center of the laser spot was 62°C, and the maximum temperature at the boundary of the laser spot was 50°C.

[0270] After irradiation, IOP was measured at 16.3 mmHg (left eye) and 16.5 mmHg (right eye). Ultrasound imaging demonstrated an increase in scleral thickness, indicating the formation of pores in the irradiated sclera (Figure 10).

[0271] Step 3. Local coagulation of the ciliary body. In this step, a laser with a wavelength of 1320 nm, a laser spot diameter of 200 μm, a pulse duration of 1 ms, an average power of 1.4 W, a pulse repetition rate of 5 Hz, a series of 20 pulses, a period of 5 s between the series, and an exposure time of 40 s was irradiated.

[0272] The calculated desired size of the solidified ciliary body was 65 μm. The estimated reduction in IOP was 3 mmHg. The actual reduction after this step was 2.8 (left eye) and 3.3 mmHg (right eye), respectively.

[0273] IOP was measured in the rabbits 1 hour and 1 month after all three stages of treatment. After 1 hour, IOP was 13.5 (left eye) and 13.2 (right eye) mmHg, a decrease of 8.1 and 8.5 mmHg, respectively.

[0274] The final IOP values ​​one month after irradiation were 13.6 (left eye) and 13.6 (right eye) mmHg, respectively. Therefore, the final IOP reduction was 8.0-8.1 mmHg (including contributions of 24% after the first step, 39% after the second step, and 37% after the third step).

[0275] OCT images show channels in the trabecular meshwork measuring approximately 380 + / - 30 μm in diameter, and pores in the sclera with an average size of 9 μm.

[0276] The rabbits were then sacrificed for histological analysis. The results demonstrate the formation of pores in the irradiated sclera with an average pore size of 10 μm (FIG. 9), and the formation of coagulation areas of 60 + / - 10 μm in the ciliary body (FIG. 12).

[0277] Thus, this first example demonstrates a predictable reduction in IOP in living rabbit eyes due to subsequent irradiation and the formation of pores in the trabecular meshwork and sclera and local coagulation of the ciliary body. In living rabbit eyes, the stability of IOP reduction was maintained for at least 2 months.

[0278] Second Example: Lowering IOP in human eyes by laser irradiation of the sclera and ciliary body of both eyes. Preoperative diagnosis showed an initial IOP of 32 mmHg (left eye) and 31 mmHg (right eye), respectively. Optical Coherence Tomography (OCT) of the sclera showed a mean pore diameter of 4 μm. Corneal thickness was measured by OCT. Mechanical properties, including Young's modulus and stress distribution, of the cornea, sclera, and trabecular meshwork at or near the cornea were measured using OCE with a pneumatic device.

[0279] The irradiation was carried out in two steps.

[0280] Step 1. Irradiation of the sclera. In this step, a laser with a wavelength of 1560 nm, a laser spot diameter of 600 μm, a pulse duration of 200 ms, an average power of 0.8 W, a pulse repetition rate of 2.5 Hz, a series of 10 pulses, a 5-second period between the series, and an exposure time of 42 seconds was used. The light delivery element 102 and the light conversion element 104 enabled the formation of eight irradiated areas, each with a diameter of 600 μm, at a distance of 1 mm from the limbus of the eye (FIG. 6).

[0281] The following properties were calculated: a maximum temperature of 59°C, a mean pore size that increased with time (Figure 8) and reached 9 μm at 45 seconds of irradiation, and a desired reduction in IOP of 6.2 mmHg.

[0282] Temperature measurements were taken during laser irradiation using an IR radiometer, and the maximum temperature was 59 + / - 0.5°C.

[0283] The IOP after scleral irradiation was 26.2 mmHg (left eye) and 26.0 mmHg (right eye), and the mean pore size was 8 μm (left eye) and 9 μm (right eye).

[0284] Step 2. Irradiation of the ciliary body. In this step, a laser with a wavelength of 1320 nm, a laser spot diameter of 200 μm, a pulse duration of 1 ms, an average power of 1.5 W, a pulse repetition rate of 5 Hz, a series of 20 pulses, a period of 5 s between the series, and an exposure time of 45 s was irradiated.

[0285] The following characteristics were calculated: a coagulation ciliary zone of 90 μm, an estimated reduction in IOP of 10 mmHg, and a maximum temperature of 82° C. Temperature measurements during irradiation showed a temperature of 82+ / -1° C.

[0286] IOP was controlled several times after the procedure: for the left eye, IOP was 15.5 mmHg immediately after the procedure, 16.5 mmHg at 6 months, and 16.8 mmHg at 12 months. For the right eye, IOP was 15.2 mmHg immediately after the procedure, 16.1 mmHg at 6 months, and 16.4 mmHg at 12 months.

[0287] This example demonstrates a long-term, predictable reduction in IOP in humans following irradiation and the formation of pores in the sclera and local coagulation of the ciliary body. Normal IOP stability was maintained for at least 12 months in both human eyes.

[0288] Third Example: IOP normalization in human eyes with low IOP. Treatment was performed on right human eyes following glaucoma surgery with chronic ocular inflammation.

[0289] The initial IOP in the right eye was measured at 8 mm Hg.

[0290] Diagnosis (OCT) shows large pores in the sclera (mean pore diameter 27 microns) and marked inflammation of the ciliary body.

[0291] OCE measurements show reduced Young's modulus values, eg, 0.1 MPa and 0.3 MPa for the cornea and sclera, respectively.

[0292] IOP measurements showed an IOP of 15 mmHg in the left eye with no visible inflammation. The mean pore size in the left eye was approximately 10 microns.

[0293] Temperature measurements were taken using an IR radiometer.

[0294] Light scattering measurements were performed using a photodetector.

[0295] Thermomechanical vibration measurements were performed using a photoacoustic detector.

[0296] Right eye irradiation. The dosimetry of the laser source was calculated to achieve a desired positive effect, such as IOP.

[0297] The algorithm is based on diagnostic data obtained before and during laser irradiation of the eye with variations in the following parameters: laser wavelength, power, pulse duration, pulse repetition rate, laser spot diameter, amount of series of pulses, time interval between series, total exposure time.

[0298] The laser irradiation was carried out in two steps.

[0299] Step 1. Closure of the scleral hole. This step involved irradiating the sclera with a laser having a wavelength of 1560 nm, a power of 1.8 W, a laser spot diameter of 1 mm, a pulse width of 200 ms, a pulse repetition rate of 2.5 Hz, and an exposure time of 32 seconds. The laser parameters were established by a feedback controller based on measurements of backscattered light during irradiation of the sclera (Figure 13).

[0300] The light delivery element 102 and the light conversion element enabled the formation of six illuminated areas, each 1 mm in diameter, 2 mm from the limbus of the eye (FIG. 6).

[0301] Temperature measurements show heating of the sclera to 82 + / - 1°C.

[0302] After transscleral laser irradiation, IOP was measured at 11.5 mmHg, and a mean pore diameter of 9 μm was measured by OCT.

[0303] The Young's modulus of the sclera measured by OCE was 0.45 MPa (meaning it had returned to the normal range).

[0304] Step 2: Modulated laser light is applied to the ciliary body to activate the regenerative process and reduce inflammation. In this step, the laser was irradiated with a wavelength of 1320 nm, a pulse duration of 200 ms, a laser spot diameter of 1.0 mm, a laser power of 0.4 W, a pulse repetition rate of 1 Hz, four series of laser pulses with 10 pulses in each series, a period of 10 seconds between series, and an exposure time of 70 seconds.

[0305] Temperature measurements during irradiation indicate a maximum temperature of 48°C. Oscillatory pressure measurements indicate pressures in the range of 8-12 kPa. These result in the activation of regenerative processes in the irradiated area of ​​the ciliary body.

[0306] The IOP in the right eye was measured as 11.7 mmHg immediately after laser treatment, 15.2 mmHg 1 year after treatment, 15.4 mmHg 2 years after treatment, and 15.5 mmHg 3 years after treatment.

[0307] Examination using OCT revealed a mean pore size of 9 μm. After laser treatment, no inflammation was observed and no large pores were observed.

[0308] The IOP in the left eye was measured as 15 mmHg immediately after the laser procedure, 15.4 mmHg at 1 year after the procedure, 15.6 mmHg at 2 years after the procedure, and 15.7 mmHg at 3 years after the procedure.

[0309] This example demonstrates the restoration of normal IOP in human eyes due to a reduction in the mean scleral pore size (closure of large pores), cessation of ciliary body inflammation, and activation of regenerative processes. Long-term stability of normal IOP was maintained for at least 3 years after treatment.

[0310] Method and laser system embodiments according to the present disclosure may exhibit the following advantages: 1. Several (three) targets can be treated simultaneously: the ciliary body, the sclera, and Schlemm's canal with the trabecular meshwork. The distinct mechanism of laser action is an advantage of this method. The goal is to control IOP in patients with abnormal (elevated or low) IOP through the laser effect on (i) the volume and productivity of the ciliary body, (ii) the permeability of the sclera, and (iii) the permeability of Schlemm's canal and trabecular meshwork.

[0311] 2. Reversible IOP reduction due to closure of scleral and / or trabecular meshwork pores by transient temperature increases above 70°C.

[0312] 3. A feedback control system based on the measurement of several parameters (temperature, electrical impedance, water permeability, scleral and / or trabecular meshwork micropore formation, corneal and scleral mechanical properties, light backscatter, and ciliary body coagulation zone dimensions). Information on the corneal mechanical properties is used to estimate the final desired characteristics (size distribution) of the micropores, because lower corneal mechanical properties can increase the amount of intraocular fluid and potentially lead to the development of glaucoma. Furthermore, a small number of large pores and a large number of small pores with the same total cross-sectional area will give different IOP values ​​and different IOP stabilities. Therefore, control of the pore size distribution and temperature range is very important to provide long-term normalization of IOP.

[0313] 4. An automated system with real-time control of laser dosimetry is controlled by a remote high performance computer.

[0314] 5. The present methods and devices can be used for both elevated and / or low IOP.

[0315] The description of specific embodiments and drawings merely serves to illustrate the technology of the present disclosure and its associated advantageous effects, and should not imply any limitations. The scope of the present disclosure should be inferred from the appended claims. [Explanation of symbols]

[0316] 101 Laser Source 102 Light Delivery Element 103 Work Tools 104 Light conversion element 105 Detection Elements 106 Feedback Controller 106a Electronic Unit 106b Feedback control element 106c Remote Hybrid Computing Facilities and / or Remote Quantum Computers 201 Eye 202a First Area 202b Second Area 203a Sclera 203b Trabecular meshwork 203c cornea 203d Schlemm's canal 203e Ciliary body 203f Iris 203g crystalline lens 204 Corneal limbus 205a Traditional Route 205b Uveoscleral pathway

Claims

1. 1. A laser system suitable for altering the IOP of an eye (201), comprising: a laser source (101); a feedback controller (106) configured to adjust the dosimetry of the laser source (101) to generate spatially and / or temporally modulated modulated laser light; a first light delivery element (102) configured to direct the modulated laser light, which is spatially and / or temporally modulated, to illuminate a first area (202a) on the eye (201); a detection element (105) configured to detect one or more physical, chemical, mechanical and / or structural properties at a second region (202b) on the eye (201) in real time during said change in IOP; The feedback controller (106) provides real-time information regarding the one or more physical, chemical, mechanical and / or structural properties within the second region (202b). and adjusting the dosimetry of the laser source (101) in real time based on the detected information of the system; the feedback controller (106) is configured to calculate a fluid flow rate through a porous structure on the sclera (203 a) of the eye (201) based on the detected information. Laser system.

2. the first region (202a) includes a portion on the sclera (203a); The laser source (101) is adjusted to modify the porous structure on the sclera (203a).

10. The laser system of claim 1.

3. the modulated laser light is suitable for achieving and / or maintaining a first temperature range and / or a second temperature range in the first region (202a); the porous structure is stabilized in the first temperature range and the porous structure is destabilized in the second temperature range; 3. The laser system of claim 2.

4. the second region (202b) includes a portion on the cornea (203c); the detected information relates to one or more mechanical properties of the cornea (203c); the feedback controller (106) is configured to obtain overall mechanical properties of the eye (201), including mechanical properties of the trabecular meshwork (203b), mechanical properties of the surface of Schlemm's canal (203d), mechanical properties of the ciliary body (203e), and / or mechanical properties of the sclera (203a); 10. The laser system of claim 1.

5. the sensing element (105) comprises an OCE device and a pneumatic device combined with the OCE device, and the sensing element (105) continuously measures the one or more mechanical properties of the cornea (203c); 5. The laser system of claim 4.

6. the first region (202a) includes a portion on the ciliary body (203e) of the eye (201); The laser source (101) is adjusted to activate one or more cells on the ciliary body (203e).

4. The laser system according to claim 1.

7. the modulated laser light is adapted to generate temperature and / or pressure conditions for activating the one or more cells; 7. The laser system of claim 6.

8. the modulated laser light is adapted to generate a thermomechanical wave capable of propagating to a third region outside the first region (202 a); the one or more cells are in the third region.

7. The laser system of claim 6.

9. The first region (202a) a) a portion of the eye (201) over the sclera (203a); b) at and / or near the Schlemm's channel and / or trabecular meshwork (203b) of said eye (201); and c) a portion on the ciliary body (203e) of said eye (201); the feedback controller (106) is configured to calculate the desired relative contributions of the two portions in normalizing the IOP; the dosimetry of the laser source (101) is adjusted to achieve a desired relative contribution; 4. The laser system according to claim 1.

10. the feedback controller (106) is configured to determine, based on the detection information, whether one of the portions has been previously treated; if the feedback controller (106) determines that the one of the portions has been previously treated, the feedback controller (106) is configured to correct the desired relative contribution by reducing the desired contribution of the treated portion.

10. The laser system of claim 9.

11. the feedback controller (106) comprises a high performance computer, a hybrid quantum-classical computing facility, and / or a quantum computer (106c) and / or is coupled to the high performance computer, the hybrid quantum-classical computing facility, and / or the quantum computer (106c); and / or the feedback controller (106) comprises and / or is connected to a storage device, the storage device stores an offline configuration table, the configuration table being calculated by a high performance computer, a hybrid quantum-classical computing facility, and / or a quantum computer (106c); 4. The laser system according to claim 1.

12. A method performed by a rating system, comprising: a) detecting one or more physical, chemical, mechanical and / or structural properties in a first region (202b) of the eye (201); b) processing the detected information regarding the physical, chemical, mechanical and / or structural properties of the first area (202b) on the eye (201); c) obtaining characteristics of porous structure changes on the eye (201) and / or characteristics of activation of ciliary body (203e) regeneration of the eye (201) in real time during the porous structure changes and / or activation of ciliary body (203e) regeneration; d) calculating a flow rate of a fluid through a porous structure on the sclera (203a) based on the detected information; does not involve adjusting the laser system; method.

13. the first region (202b) includes a portion on the cornea (203c) of the eye (201); the detected information relates to mechanical properties of the cornea (203c); acquiring characteristics of porous structure changes on the eye (201) and / or characteristics of activation of ciliary body (203e) regeneration of the eye (201) in real time during the porous structure changes and / or activation of ciliary body (203e) regeneration; obtaining overall mechanical properties of the eye (201), including mechanical properties of the trabecular meshwork (203b), mechanical properties of the superficial layer of Schlemm's canal (203d), mechanical properties of the ciliary body (203e), and / or mechanical properties of the sclera (203a); The method of claim 12.

14. processing the detected information is performed in real time using a high performance computer, a hybrid quantum-classical computing facility, and / or a quantum computer (106c); 14. The method of claim 12 or 13.

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