System and method

Abstract

The present invention relates generally to systems for two-photon or multi-photon irradiation of an intraocular lens, preferably an intraocular lens, preferably disposed within an eye of a patient, and methods for locally adjusting the degree of polarization and / or refractive index of an intraocular lens, preferably an intraocular lens, preferably disposed within an eye of a patient. The method relates in particular to the manufacture of optical properties by adjusting the degree of polarization in a non-destructive manner by a bi-or multi-photon method.

Description

Invention Field

[0001] This invention generally relates to a system for two-photon or multi-photon irradiation of an intraocular lens, preferably an intraocular lens, preferably disposed within a patient's eye, and a method for locally adjusting the polarization degree and / or refractive index of the intraocular lens, preferably an intraocular lens, preferably disposed within a patient's eye. The method particularly relates to creating optical profiles by non-destructively adjusting the polarization degree using a two- or multi-photon approach. Background of the Invention

[0002] Photoinduced changes in material properties have applications in several technological fields, such as microfabrication, 3D printing, nanostructuring, or two-photon lithography. These changes can occur in various ways, such as photopolymerization, photoinduced material degradation, or photochemical crosslinking. The result of these methods is a change in the properties of the irradiated material. This can be alteration of mechanical properties, solubility, transparency, refractive index, or other aspects.

[0003] In 3D printing, typically photolithography, femtosecond lasers can be used to polymerize specific arrays. This can be accomplished through a photopolymerization reaction. To make the formulation curable, a photosensitizer can be added. This allows printing at micrometer resolution, which may not be possible with conventional 3D printing techniques. Multi-beam arrays can be used to increase manufacturing speed.

[0004] Nanostructuring is also used in the biomedical field. In eye care, structural applications are used to modify ophthalmic polymers (such as contact lenses or intraocular lenses (IOLs)) and eye tissue (see, for example, US2018243082 A1). When working with IOLs, photosensitivity in the material is typically utilized, for example, by absorbing ultraviolet light. Two or more photonic processes can allow targeting voxels within the internal material without affecting the IOL surface. When irradiated, the photosensitizer absorbs light and transfers energy to the surrounding material. In WO2017221068 A1, the emitted light is provided to the hydrogel material as heat. This can lead to polymer degradation and changes in refractive index. Another approach is to form non-visually degrading crystallites in the material through femtosecond laser irradiation. As shown in US2010228345 A1, the higher molecular order of the crystallites can lead to a localized increase in density within the material, resulting in a localized increase in refractive index.

[0005] US2009143858 describes a method for altering the refractive index of an optical polymer material, comprising destructively irradiating a selected region of the optical polymer material with a focused, visible, or near-infrared laser with a pulse energy of 0.05 nJ to 1000 nJ, thereby forming a refractive optical structure. The refractive optical structure is characterized by a change in refractive index relative to the unirradiated optical polymer material exhibiting little or no scattering loss and no significant difference in Raman spectroscopy.

[0006] US2016081852 describes a method for altering the refractive properties of an eye, the method comprising applying a photosensitizer to the internal tissues of the cornea of ​​the eye, the photosensitizer promoting cross-linking of the internal tissues of the cornea, irradiating the cornea to activate the cross-linking agents in the internal tissues of the cornea, and altering the cornea to change the refractive properties of the eye.

[0007] US2008004610 describes a specific refractive index-tunable lens and the refractive index measurement performed by a refractometer. The described adjustment is a destructive method.

[0008] Cataracts are clouding of the eye's lens that can obstruct the passage of light. Most cataract cases are related to the aging process. However, children may be born with cataracts or develop them at a very young age. Furthermore, cataracts can occur after eye injury, inflammation, or other eye diseases. According to the World Health Organization, more than 50 million people worldwide currently have cataracts, making them the cause of approximately half of all blindness globally. Although cataracts can be removed surgically, the lack of access to surgery in many countries means that cataracts remain a leading cause of blindness. With increasing life expectancy, the number of people developing cataracts is also rising. Therefore, cataracts are a significant cause of poor vision in both developed and developing countries. Comprehensive prevention of cataract formation is not yet fully understood.

[0009] Cataract surgery can successfully restore vision. The opaque lens is removed and replaced with an artificial lens.

[0010] An intraocular lens is implanted as a modern lens through a small incision after the natural lens has been removed, into the remaining capsular bag, or into the sulcus if the capsular bag is lost.

[0011] A typical problem associated with IOL implantation is that, in terms of best visual acuity, the results obtained are far from optimal in most cases. Prior to IOL implantation, the eye's biometric data, including corneal curvature radius and eyeball length, cannot be determined with the required precision. IOL positioning during surgery, the unpredictable impact on wound healing, and postoperative IOL displacement occurring weeks and months after cataract surgery are currently difficult to predict. Several methods and formulas exist for predicting IOL refractive power before cataract surgery, but a satisfactory solution has not yet been found.

[0012] Clinical trials of cataract surgery outcomes have shown that over 80% of patients fall within 1 diopter (D) of the desired refractive index. However, many people have refractive errors and therefore require some correction to provide optimized vision. It has been shown that refractive errors after cataract surgery are virtually unavoidable, even if the magnitude of the refractive error has been reduced. Problems can also arise if certain eye conditions are present, such as if the axial length of the eye is significantly longer or shorter than average. Pediatric cases are often prone to complications related to refractive power prediction. Errors in intraocular lens power due to manufacturing tolerances can also contribute to the total error, especially for high-power IOLs. It is worth noting that the applicable ISO 11979 standard allows for an in-plane tolerance of ±0.33D for IOLs above 25.00D and even ±0.66D for IOLs above 30.00D.

[0013] Refractive error is defined as a mistake in the eye's ability to focus light, and it is a common cause of decreased visual acuity. When viewing distant objects, the eye is normal (emmetropic) and there is no refractive error.

[0014] An eye that has a refractive error when viewing distant objects is called a refractive error.

[0015] Refractive errors can be classified as spherical or cylindrical. Spherical errors occur when the eye's optical power is too high or too low to focus light onto the retina. Cylindrical errors occur when the curvature of the two meridians is different. People with refractive errors experience blurred vision.

[0016] Nearsightedness, also known as myopia or near-sightedness, is a refractive error of the eye where collimated light focuses in front of the retina when the eye is relaxed. Nearsighted people can see nearby objects clearly, while distant objects appear blurry. In nearsightedness, the eyeball is too long, or the cornea is too steep—meaning the optics are too strong for the length of the eyeball. As a result, the image focuses inside the vitreous humor of the eye rather than on the retina.

[0017] Farsightedness, also known as hyperopia or hyperopia (farsightedness or long-sightedness), is a visual impairment caused by a defect in the eye. Optics that are too weak for a given length of eyeball can cause the eye to be unable to focus on nearby objects. In extreme cases, a person may be unable to focus on objects at any distance. As an object moves toward the eye, the eye must increase its refractive power to keep the image focused on the retina. If the refractive power of the cornea and lens is insufficient, as in farsightedness, the image appears blurry.

[0018] Astigmatism is an optical defect in which vision may be blurred because the eye's optical system is unable to focus point objects into a clear, focused image on the retina. Irregularities or complex curvatures of the cornea or lens can cause astigmatism. The curvature of two different meridians refracts light differently. In other words, the eye has different focal points in different planes. For example, an image may focus clearly on the retina in a horizontal plane, but not in front of the retina in a vertical plane. People may see blurry outlines in certain directions, but can see clearly outlines in right-angled directions. People with astigmatism may have difficulty seeing details. In some cases, vertical lines (such as walls) may appear tilted to the patient. Astigmatism can usually be corrected with eyeglasses, rigid contact lenses, or contact lenses with compensating optics.

[0019] There are approximately six different types of cataracts, and more than twenty causes have been identified. Therefore, once cataracts are diagnosed, drug treatment is currently not an option. The only current treatment is to replace the natural lens with an artificial IOL (intraocular lens). Today, the standard of care is for foldable IOLs.

[0020] The IOL can thus be immersed in the fluid of the eye chamber. The diameter of the optically active portion of the IOL is typically between 5 mm and a maximum of 7 mm. Depending on the specific model, elastic rings or supports are attached to the edge of the IOL's optical portion. These rings, called haptics, place the lens in the center of the capsular bag and hold the IOL in place. The total diameter of the intraocular lens is approximately 12 mm, and its thickness depends on its refractive power, typically varying between 0.7 mm and a maximum of 2 mm. The weight of an intraocular lens is approximately 50 mg.

[0021] Polymers that can be used to manufacture foldable IOLs can be divided into two groups. IOLs can be made from (1) acrylic or methacrylic polymers or (2) silicone-based polymers. Furthermore, hydrophobic and hydrophilic materials can be used for IOLs. Hydrophilic materials can be softened by absorbing approximately 10-30% water, while hydrophobic materials can be designed to be soft without absorbing water. Many IOL variants and IOLs with different optical properties (such as multifocality, tortuosity, and extended depth of focus) have been studied and marketed. However, it is currently difficult to determine the biometric data required for IOLs to provide the promised results.

[0022] Examples of silicon-containing polymers that can be used as optical materials are described in WO2018149857.

[0023] Examples of acrylate- or methacrylate-containing polymers that can be used as optical materials are described in WO2017032442, WO2017032443, WO2017032444, WO2018149850, WO2018149852, WO2018149853, WO2018149855 and WO2018149856.

[0024] For example, the [2+2] cycloaddition reaction between coumarins can be carried out using light. A coumarin is photochemically excited and can react with ground-state molecules within its range. According to the Yablonski diagram, the absorption of a photon causes the organic molecule to enter an excited singlet state. This can be converted to a triplet state through intersystem crossing. Compared to the singlet state, which can be reduced by fluorescence decay, the triplet state can only be reduced by non-irradiation decay. Therefore, the lifetime of the triplet state in organic molecules such as coumarins is much longer than that of the singlet state. Thus, for the intermolecular [2+2] cycloaddition reaction of coumarins, the triplet state and its quantity are most relevant [T. Wolff et al., Phys. Chem. Chem. Phys., 2004, 6, 368-376], because its long lifetime allows for multiple collisions with other molecules and the high specific mobility leads to a higher probability of cyclodimerization reactions.

[0025] Aside from errors due to biometric data measurements, accurate prediction of refractive error after surgery / surgical procedures is virtually impossible. This is primarily due to unpredictable effects that can occur during the healing process, which can last for weeks or months after cataract surgery. These effects include, for example, changes in the anterior chamber depth of the intraocular lens (IOL), i.e., the nominal distance between the corneal apex and the effective master surface of the IOL. Furthermore, changes in corneal shape may occur during healing. The exact values ​​of these changes can depend on a variety of factors, including the originality of the eye, the type of IOL, and the surgeon and instruments used. Uncertainties in IOL specifications can also make it difficult to predict the correct refractive index.

[0026] After the wound heals, individual treatments can be administered, such as adjusting the optical properties of the IOL, or patients who have received IOL treatment may need prescription glasses to achieve ideal vision.

[0027] Alternatively, patients may need appropriate contact lenses to correct for ideal vision in their natural lens.

[0028] Because preoperative IOL refractive power prediction currently has insurmountable drawbacks, the purpose of the systems and methods according to this disclosure is to provide a solution for non-invasively adjusting the optical properties of an implanted IOL by altering the polarization degree of the organic molecules used to manufacture the IOL. Furthermore, the purpose of the systems and methods according to this disclosure is to provide a solution for preparing and / or modifying an intraocular lens (which may or may not be placed in the patient's eye) particularly by using a two-photon (or generally multiphoton) process, especially modifying the polarization degree of the IOL.

[0029] Multiphoton excitation is a nonlinear phenomenon that requires high intensity to enable the simultaneous absorption of photons. In the case of two-photon excitation, the probability of excitation occurring is proportional to the square of the excitation light intensity. On the other hand, the excitation light collected by the microscope objective has an intensity inversely proportional to the square of the distance from the focal plane.

[0030] N. Yonezawa et al., Bull. Chem. Soc. Jpn., 1984, 57, 1608-1611, described how heat has been shown to induce thermal ring-cracking reactions, which negatively affect the yield of photo-reacted cyclic dimers. Invention Overview

[0031] The inventors have now discovered that the above-mentioned objectives can be achieved individually or in any combination using the systems and methods of this application.

[0032] This invention relates to a system for irradiating an intraocular lens, the system comprising:

[0033] One or more illumination sources for illuminating the artificial lens with a two-photon or multi-photon illumination beam, the illumination beam being focused by an optical device and having a first wavelength and / or a second wavelength different from the first wavelength.

[0034] A scanner, connected to the one or more illumination sources and configured to scan the illumination beam across the intraocular lens, and

[0035] An input unit, connected to the one or more illumination sources and the scanner, wherein the input unit is configured to input data to process the intraocular lens by scanning the illumination beam across the intraocular lens based on the input data, and

[0036] The first wavelength is between 600 nm and 800 nm to locally reduce the polarization degree of the intraocular lens based on the treatment of the intraocular lens, and the second wavelength is between 400 nm and 590 nm to locally increase the polarization degree of the intraocular lens based on the treatment of the intraocular lens.

[0037] The present invention further relates to a system for irradiating an intraocular lens preferably disposed within a patient's eye, the system comprising:

[0038] One or more illumination sources are used to illuminate the artificial lens with a two-photon or multi-photon beam focused by an optical device and having a wavelength between 600 nm and 800 nm.

[0039] A scanner, connected to the one or more illumination sources and configured to scan the illumination beam across the intraocular lens, and

[0040] An input unit, connected to the one or more illumination sources and the scanner, wherein the input unit is configured to input data to process the intraocular lens by scanning the illumination beam across the intraocular lens based on the input data, and

[0041] The wavelength is used to locally reduce the polarization degree of the intraocular lens based on the treatment of the intraocular lens.

[0042] The present invention further relates to a system for irradiating an intraocular lens preferably disposed within a patient's eye, the system comprising:

[0043] One or more illumination sources are used to irradiate the artificial lens with two-photon or multi-photon beams focused by an optical device and having wavelengths between 400 nm and 590 nm.

[0044] A scanner, connected to the one or more illumination sources and configured to scan the illumination beam across the intraocular lens, and

[0045] An input unit, connected to the one or more illumination sources and the scanner, wherein the input unit is configured to input data to process the intraocular lens by scanning the illumination beam across the intraocular lens based on the input data, and

[0046] The wavelength is used to locally increase the polarization degree of the intraocular lens based on the treatment of the intraocular lens.

[0047] Figure 1 and 2 A schematic diagram of the system as described above is shown.

[0048] Figure 1 This is a schematic diagram of a system for irradiating an intraocular lens, such as a contact lens or an intraocular lens placed inside a patient's eye. The irradiation beam (2) emitted by the irradiation source (1) is redirected by the scanner (4) and focused by the optics (16) to adjust the desired polarization of the intraocular lens (3). The positioning system (20) determines the working position of the focal point within the intraocular lens (3). The positioning information, along with the refractive power and existing optical characteristics of the intraocular lens (3), is part of the input data (8) associated with the intraocular lens (3). Lens data (10) and processing plan data (12) are further described below. The temperature management unit (14) predicts and / or measures the temperature in the material of the intraocular lens (3) before and / or during irradiation.

[0049] Figure 2 This is a schematic diagram of a system for irradiating an intraocular lens placed inside a patient's eye.

[0050] Figure 2 This is a schematic diagram of a system for irradiating an intraocular lens placed inside a patient's eye. An irradiation beam (2) emitted from an irradiation source (1) is redirected by a scanner (4) and focused by an optics device (16) to adjust the polarization of the desired intraocular lens (3) within the patient's eye. The optics device (16) is connected to an eye interface system (18) that holds the patient's eye in a fixed position. A positioning system (20) determines the working position of the focal point within the intraocular lens (3). Positioning information, along with the refractive power and existing optical characteristics of the intraocular lens (3), is part of the input data (8) associated with the intraocular lens (3). Lens data (10) and processing plan data (12) are further described below. A temperature management unit (14) predicts and / or measures the temperature in the material of the intraocular lens (3) before and / or during irradiation.

[0051] The present invention further relates to a method for adjusting the polarization of an artificial lens comprising a body formed of polymer optical material based on a two- or multi-photon absorption process, the method comprising the following steps:

[0052] Provide the lens; and

[0053] By irradiating the lens with the system of the present invention as described above or preferably as described below, the polarization degree of the lens is adjusted, thereby changing the polymer optical material relative to the unirradiated polymer optical material of the artificial lens, resulting in a significant difference in the UV / Vis spectrum.

[0054] The present invention further relates to a method for locally adjusting the polarization of an intraocular lens comprising polymeric optical material disposed within a patient's eye, the method comprising:

[0055] The intraocular lens was exposed to an illumination beam with wavelengths between 600 nm and 800 nm to locally reduce the polarization of the intraocular lens, or

[0056] The intraocular lens was exposed to an illumination beam with wavelengths between 400 nm and 590 nm to locally increase the polarization degree of the intraocular lens.

[0057] The present invention further relates to a method for correcting the vision of a patient by modifying the refractive index of the intraocular lens of the patient's eye, comprising:

[0058] Confirm and measure the patient's corrected visual acuity.

[0059] Determine the location and type of the refractive structure to be implanted into the intraocular lens to correct the patient's vision; and

[0060] The intraocular lens is then exposed to two-photon or multi-photon irradiation with wavelengths between 600 nm and 800 nm to locally reduce the polarization of the intraocular lens or to expose the intraocular lens, or

[0061] The intraocular lens is then exposed to two-photon or multi-photon irradiation with wavelengths between 400 nm and 590 nm to locally increase the polarization degree of the intraocular lens.

[0062] The present invention further relates to a component kit comprising a system as described above or preferably as described below, and at least one artificial lens suitable for said system. Invention Details

[0063] It should be noted that throughout this disclosure, any reference to an entity / component / part of the system being connected to another entity / component / part (and potentially further entities / components / parts) may require that an entity / component / part be directly and / or indirectly connected to another entity / component / part.

[0064] The disclosed lens or intraocular lens is defined as a contact lens or intraocular lens. The intraocular lens according to the invention is an implantable lens for replacing the natural lens of the eye when it is damaged.

[0065] There are no restrictions on the type of lens, and it may include a contact lens or an intraocular lens. Most preferably, such an intraocular lens is an intraocular lens (IOL), which may be, for example, a posterior chamber intraocular lens or an anterior chamber intraocular lens.

[0066] There are no restrictions on the type of intraocular lens. For example, it can be a pseudophakic intraocular lens or a phakic intraocular lens. The former type replaces the eye's natural lens, typically replacing a removed cataract lens. The latter type is used to supplement an existing lens and serve as a permanent corrective lens, implanted in the anterior or posterior chamber to correct refractive errors. The intraocular lens to be processed according to the invention may, for example, include one or more optical components and one or more tactile components, wherein the one or more optical components serve as the lens and the one or more tactile components are attached to the one or more optical components and fix the one or more optical components in the eye. The intraocular lens to be processed according to the invention can be a one-piece design or a multi-piece design, depending on whether the one or more optical components and the one or more tactile components are formed from a single piece of material (one-piece design) or fabricated separately and then assembled (multi-piece design).

[0067] The intraocular lens, preferably an IOL, may comprise polymeric optical materials, wherein the optical properties of the lens can be noninvasively altered using this system. This system can be used to change the degree of polarization and thus the refractive index, particularly based on multiphoton processes.

[0068] Preferably, the intraocular lens (contact lens or IOL) comprises a polymerized optical material, more preferably as described below, wherein the optical properties of the IOL can be noninvasively altered using the system.

[0069] Particularly preferably, the intraocular lens (contact lens or IOL) is composed of a polymerized optical material, more preferably as described below. Typically, the optical properties of the lens are a diameter of 5 mm to 7 mm and a thickness typically between 0.2 mm and 2.0 mm.

[0070] In this application, input data refers to all types of data used to create a treatment plan, defined as translating ophthalmic needs into control commands for the writing process, as further described in detail below. During the writing process, an optical pattern is written by irradiation through the intraocular lens.

[0071] The term "control command" refers to a command that directly controls the writing process as defined above or preferably as described below. Control commands can control, for example, the movement of a scanner.

[0072] The term "scanner" as used herein is not part of the input unit according to the invention. As described herein, "scanner" is a component of the system according to the invention that controls the movement of an illumination beam.

[0073] Ophthalmic requirements refer to desired optical properties that must be achieved in the intraocular lens using the system and method according to the invention.

[0074] Optical properties are the desired changes defined by the surgeon based on the results of examinations of the patient before or after intraocular lens implantation; such as, but not limited to, spherical total refractive power changes, toric properties, EDOF properties, or bifocal, trifocal, or multifocal properties. Alternatively, optical properties are adjustments to the optical properties of the contact lens.

[0075] Optical patterning is a necessary change in polarization that causes a change in the refractive index of each voxel in an artificial lens.

[0076] The previously defined input data is intended to include common input data, individual input data, or in-process input data.

[0077] Common input data is intended to include generic data that is used by default due to system limitations. An example of such common input data is described below.

[0078] Individually entered data consists of all data specifically relevant to ophthalmological needs. An example of such individually entered data is described below.

[0079] The input data during the process is the data created and used during the writing process.

[0080] The term "positioning system" used in this instruction manual refers to the location of the laser focus in the eye.

[0081] The term "locating system," used as part of the positioning system in this manual, determines the position of the artificial lens relative to the system and the patient's eye.

[0082] The term "irradiation beam" exit defines the position where the irradiation beam leaves the optical element of the system according to the invention.

[0083] As used herein as part of the system according to the invention, the term "optical device" includes all optical means required to control the spatial distribution of the illumination source (focal point) on an intraocular lens. Key parameters of the focal point include the lateral focal size (or beam waist) and the focal length (or Rayleigh range). The optical device includes all elements that define the focal point along the beam path, such as beam expanders, aperture stops, shutters, and especially focusing optics, such as microscope objectives or single aspherical lenses.

[0084] The illumination within the focal volume is characterized by a refractive optical structure that alters the degree of polarization / refractive index relative to the main body of the intraocular lens or, alternatively, the unilluminated portion of the intraocular lens.

[0085] In other words, changes in polarization degree / refractive index can be used to form patterned desired refractive structures in an intraocular lens, as described below or preferably.

[0086] Preferably, a refractive structure is provided that displays changes in refractive index and exhibits little or no scattering loss, so that ablation, removal, or destruction of the intraocular lens material is not observed in the irradiated area. The previously described irradiated area can take the form of a two-dimensional or three-dimensional, area- or volume-filled refractive structure, which can provide spherical, non-spherical, toroidal, or cylindrical correction. In fact, any optical structure can be formed to produce refractive power correction in two physical directions. Furthermore, the optical structure can be vertically stacked or written in a separate plane within the artificial lens, which will be further described below as serving as a single lens element.

[0087] Multiphoton excitation occurs only near the focal point and is preferably performed using ultrashort laser pulses. The average refractive power is limited by a sample damage threshold, which is part of the common input data defined previously and below.

[0088] The system described above, or preferably as described below, advantageously allows for postoperative and non-invasive adjustment of the optical properties / characteristics of the implanted IOL to remove visual impairments such as refractive errors. Furthermore, the system advantageously allows for gentle preparation of the IOL during manufacturing (e.g., a contact lens or, for example, before inserting an intraocular lens into a patient's eye), thereby particularly allowing for refractive structures that can provide spherical, aspherical, annular, or cylindrical correction and / or maintain the flexibility of the lens once preparation is complete. The polarization degree of the IOL is modified based on a two-photon (or generally multiphoton) process, which allows for adjustment of the optical properties / characteristics of the IOL or allows for adjustment of optical properties in different planes of the IOL. Furthermore, polarization degree modification based on two-photon or multiphoton processes allows for improved maintenance of the lens's flexibility when processed with wavelengths from 400 nm to 590 nm. The IOL is preferably an IOL.

[0089] Criteria for system parameter selection and optimization:

[0090] A key objective of this invention is to produce local refractive index modification of the IOL post-implantation, as prescribed by a physician, to improve the patient's visual acuity. A crucial criterion for refractive index modification procedures is the total treatment time required to achieve the desired results. It is generally accepted that such a procedure should not take more than a few minutes to be considered feasible. Existing systems capable of local refractive index modification do not include methods for obtaining the actual treatment time for IOL applications.

[0091] Discussion of system trade-offs and limitations:

[0092] In order to achieve truly high-performance systems for general intraocular lenses, or especially IOLs, after implantation, it is recognized that their sub-components must be considered as a system and therefore must be jointly optimized, as there are many interdependencies and trade-offs among the sub-components. Sub-components include the irradiation source, optics, scanner, and processing plan.

[0093] A key requirement for any system / parameter optimization is that, in the case of intraocular lenses (IOLs) used as contact lenses, the lens material is kept within safe limits, or, in the case of IOLs used as intraocular lenses (IOLs), the lens material and the eye and its components (e.g., the retina) are kept within safe limits. These requirements form the basis for the common input data described earlier. Specifically, two main damage mechanisms from irradiation sources (preferably pulsed laser sources) can be distinguished: single-pulse damage (dielectric breakdown and avalanche breakdown), and thermal damage, where the temperature of the lens material and / or the eye is subsequently heated and then used to repeat the pulses to the same volume. For example, the average power of the pulsed irradiation source is related to heating and therefore to potential damage to the lens material and / or the eye. Therefore, while keeping the average power of the irradiation source below a threshold that would overheat the lens material and / or the eye, pulse energy and pulse repetition rate are inversely proportional; the product of pulse energy and the number of pulses per second (= the reciprocal of the repetition rate) equals the average power.

[0094] Average power is defined as pulse energy multiplied by the number of pulses per second and is expressed in watts (W).

[0095] Irradiance equals flux density (W / cm²) 2 ).

[0096] Radiation exposure equals flux (J / cm²) 2 ).

[0097] A general objective is to minimize the processing time for IOL conditioning after implantation. Theoretically, increasingly higher pulse energies with higher frequency pulses (i.e., higher repetition rates) can be applied; however, above the typical average power of 1 watt, overheating begins to create unsafe conditions for the IOL material and the retina. Therefore, to remain within safe operating limits while completing the treatment of the entire IOL volume within a few minutes, a preferred radiation exposure can be defined. The preferred radiation exposure is ≤5 kJ / cm². 2 Especially preferred is <1kJ / cm 2 And a very special preference <0.3kJ / cm 2 The radiation exposure thus described is also applied to the processes and methods further described below according to the present invention.

[0098] In cases where the processing plan is too extensive and would exceed laser safety limits related to overheating, the process can be interrupted to allow all affected intraocular lens material and tissue to cool down. Once cooled, the positioning system can compare the processed voxels in the intraocular lens with the optical pattern, and then processing can continue.

[0099] The process of adjusting the optical properties / characteristics of the artificial lens through the system and according to the requirements described above will proceed according to the processing plan as described above. Depending on the processing plan, characteristics such as toric, spherical, multifocal, or EDOF (extended depth of focus) can be incorporated into the lens. Algorithms can be used to incorporate characteristics such as toric, spherical, multifocal, or EDOF (extended depth of focus).

[0100] By combining information about the desired optical properties with common and individual input data, the required optical pattern and control commands for the irradiation source, optics, and scanner of the system as described above or preferably below can be calculated. Individual input data include, for example, lens data, such as the laser energy required for a specific refractive index change of each voxel of the artificial lens material, and further patient data, such as the precise position and orientation of the artificial lens in the patient's eye as part of the processing plan data.

[0101] Control commands can be updated and modified during the writing process by input data such as temperature data of the patient's eye obtained by means of, for example, IR temperature measurement, illumination beam obtained by OCT (Optical Coherence Tomography), intraocular lens or eye positioning data during the process, and / or refraction data obtained from Scheimpflug images.

[0102] In a further embodiment of the input data, the input data includes lens data of the intraocular lens, preferably the intraocular lens, and / or processing plan data related to the processing plan for the processing of the intraocular lens. For example, the lens data may include data related to the degree of polarization and / or refractive index of the intraocular lens as a function of the position of a corresponding volume or portion of the intraocular lens, and one or more of its shape, refractive power, cylindrical and spherical shape, and / or individual aberrations in said dimension. Therefore, based on the current degree of polarization (or refractive index) and the degree of polarization (or refractive index) to be obtained through processing, the degree of polarization can be increased or decreased at a specific location or volume in one or more planes of the intraocular lens.

[0103] Alternatively or additionally, the lens data may include data relating to one or more of the following: the dimensions of the intraocular lens (e.g., diameter and / or thickness), its shape, refractive power, cylindrical and spherical shape and / or individual aberrations in said dimensions, and data relating to the material in which the intraocular lens, preferably an intraocular lens, is contained.

[0104] Preferably, the lens data includes data related to one or more of the following: the dimensions (e.g., diameter and / or thickness) of the intraocular lens or IOL, or data related to one or more of the following: the polarization degree and / or refractive index of the intraocular lens as a function of the position of the corresponding volume or portion of the intraocular lens, the lens shape, refractive power, cylindrical and spherical shape and / or its individual aberrations in said dimensions, and data related to the material contained in the intraocular lens as part of the input data set.

[0105] The materials of the intraocular lens, preferably those contained in the intraocular lens, are described below.

[0106] In some examples, the processing plan calculation can generate control commands that produce one or more processing plan data, including: scan strategy control command data for the scanning strategy of the scan of the illumination beam across the first and / or second wavelength of the intraocular lens (e.g., scan mode and / or scan sequence and / or scan speed and / or scan duration of the scan mode and / or scan duration of the scan sequence and / or pulse duration of the pulses of the first and / or second wavelength illumination beams (e.g., nanosecond, picosecond, or femtosecond pulses) and / or illumination beam characteristics of the first and / or second wavelength illumination beams and / or illumination (photon) density and / or illumination intensity and / or illumination power). The data input during the exposure process includes, for example, temperature data of the current and / or predicted temperature of the intraocular lens during the exposure, refractive index / polarization data of the intraocular lens to be obtained based on the exposure, which is particularly related to the mapping of the refractive index / polarization to be obtained to a specific location / coordinate of the intraocular lens, fracture dimension data, and individual input data, such as eye data related to the dimension and / or shape of the patient's eye, positioning data related to the position and / or orientation of the intraocular lens relative to the eye, and registration data related to the patient's identity and / or the patient's specific eye.

[0107] Preferably, the scanning strategy control command data of the scanning strategy is the scanning mode and / or scanning speed and / or pulse duration and / or irradiation intensity, as further described below.

[0108] The parameters of the illumination beam can then be adjusted based on the lens data and / or treatment plan data defined herein, so as to precisely (locally) change the polarization degree / refractive index of the artificial lens when needed.

[0109] Preferably, the parameters of the irradiation beam are adjusted based on lens data and / or treatment plan data as previously described or preferably described herein.

[0110] Those skilled in the art will understand that optimal illumination focusing conditions are achieved when the depth of field (Rayleigh range) of the irradiating beam matches the required thickness of the optical structure of the intraocular lens to be written.

[0111] Those skilled in the art will understand that optimal focusing conditions are achieved when the depth of field (Rayleigh range) of the irradiated beam is matched with the local thickness of the intraocular lens.

[0112] In a further embodiment, the lens data includes data related to the illumination absorption performance of the intraocular lens (e.g., absorption and / or light attenuation coefficients, which may depend on the wavelength of light), and wherein the system is configured to adjust a first wavelength and / or a second wavelength for the intraocular lens to locally change the polarization degree based on a multiphoton absorption process. For example, based on the material used for the intraocular lens, a specific wavelength or wavelength range can be input to make a precise local change in the polarization degree of the intraocular lens.

[0113] As part of the system according to the invention as described above and further as described below, the input unit is configured to input the aforementioned input data to process the intraocular lens, which may be on a sample holder to process a contact lens, or the intraocular lens may be in the patient's eye for non-invasive adjustment of the intraocular lens.

[0114] Therefore, the present invention further relates to a system as described above or below, wherein the input data includes lens data of the intraocular lens and / or processing plan data related to the processing plan for the treatment of the intraocular lens.

[0115] Therefore, the present invention further relates to a system as described above or below, wherein the lens data includes data related to the irradiation absorption performance of the intraocular lens, and wherein the system is configured to adjust the first wavelength and / or the second wavelength for the intraocular lens to locally change the polarization degree based on the multiphoton absorption process.

[0116] One or more irradiation sources, as part of the system according to the invention, may comprise one or more pulsed lasers, which can be used to generate nanosecond pulses, preferably picosecond pulses, and more preferably femtosecond pulses. Preferably, a single irradiation source is used. Particularly preferably, the one or more irradiation sources comprise one or more pulsed lasers for generating femtosecond pulses. Particularly preferably, a single pulsed laser is used to generate femtosecond pulses, which are used for irradiation in the system according to the invention or in the process and method according to the invention.

[0117] In one embodiment of the invention, the one or more illumination sources include lasers tunable to emit laser beams having first and second wavelengths, respectively. This can be particularly advantageous because, as desired, a single laser can be used to (locally) increase or decrease the polarization degree / refractive index of the intraocular lens.

[0118] Different types of pulsed lasers are suitable as the irradiation source within the system according to the invention. Both MHz and kHz lasers are suitable and have their specific advantages. For example, although MHz laser systems operate, for instance, at lower pulse energies, the focused laser spot can be maintained in the μm range (<1 μm to several μm), thus allowing for precise local refractive index modification in all three dimensions, for example, to generate diffraction structures. A preferred MHz irradiation source is an 80 MHz laser with a pulse energy range of 0.1 to 10 nJ.

[0119] On the other hand, kHz lasers operate with relatively high pulse energies, typically from 0.1 to 10 μJ, thus requiring larger spot sizes, such as 10 to 100 μm, to avoid damaging the lens material. However, a larger laser spot size implies a large depth of field (= long Rayleigh range), which can be equal to or even exceed the thickness of the intraocular lens material. With such a long Rayleigh range, it may not be possible to modify the refractive index in the IOL layer by layer, but only uniformly along a line around the focal point. Preferred kHz illumination sources are lasers with a repetition rate of 100 to 500 kHz.

[0120] The average power of the irradiation source described above or preferably previously is preferably between 300 and 600 mW, and particularly preferably between 400 and 500 mW.

[0121] In a further embodiment of the invention, an illumination beam with wavelengths exceeding a given range of the first and second wavelengths is generated by doubling the frequency of the feed laser, using an optical power amplifier, or using another laser source to use the same laser source as the illumination source.

[0122] The irradiation source, as part of the system according to the invention, preferably comprises a tunable laser providing a variable wavelength in the range of approximately 680-1080 nm, such as a Ti:sapphire laser (e.g., Chameleon Ultra II, Coherent, Santa Clara, CA, USA). The system may also comprise an optical parametric oscillator (e.g., frequency-doubled Chameleon Compact OPO-Vis, Coherent, Santa Clara, CA, USA).

[0123] The irradiation source, as part of the system according to the invention, particularly preferably comprises a femtosecond pumped laser with an optical parametric amplifier. The pumped laser emits an average power of >10 watts of irradiation at 1030 nm with pulses of <350 fs and a repetition rate of 0.1 to 700 kHz. The irradiation from the pumped laser is directed to the optical parametric amplifier, wherein the pumped laser output is frequency-doubled and optically mixed to produce a final tunable output in the wavelength range of 600 nm to 800 nm. A preferred repetition rate is between 50 and 600 kHz. A particularly preferred repetition rate is between 100 and 500 kHz.

[0124] The irradiation source, as part of the system according to the invention, particularly preferably comprises a femtosecond pumped laser with an average power >10 watts at 1030 nm, combined with an optical parametric amplifier, which emits irradiation pulses of <350 fs at a repetition rate of 1 to 700 kHz. The irradiation from the pump laser is directed to an optical parametric amplifier having one or more second harmonic stages, thereby producing a final optical output with a wavelength range of 400 nm to 590 nm. A preferred repetition rate is between 50 and 600 kHz. A particularly preferred repetition rate is between 100 and 500 kHz.

[0125] The laser type described above, or preferably previously described, produces a collimated beam a few millimeters in diameter, which is then guided to optics and a scanner. The beam quality (measured in millimeters) is ideally between 1.0 and 1.5, and more ideally between 1.0 and 1.3.

[0126] Multiphoton excitation occurs only near the focal point and is preferably generated using ultrashort laser pulses as described above. The average power is limited by a sample damage threshold, which is part of the previously defined common input data.

[0127] The ideal parameters for two-photon induced cyclodimerization are related to the pulse duration and repetition frequency of the system and the characteristic time constants of the intraocular lens material capable of cyclodimerization, as further described or preferably described below, and in short, include the molecular S1 state lifetime (about a few ns), the lifetime of the long-lived triplet state (many ns to > μs), and the characteristic thermal diffusion time (about 1 μs).

[0128] Given the long lifetime of the triplet state, a longer pulse interval is advantageous. The lifetime of the triplet state in photochemically active groups (many ns to > μs) is much longer than the repetition frequency (12.5 ns) in an 80 MHz system. Therefore, it is advantageous to use the kHz laser described previously, or preferably the one described previously, because most of the triplet state is cleared before the next pulse is initiated. This effect results in a significant increase in the efficiency of the cyclodimerization reaction of the intraocular lens material, as further preferredly described below.

[0129] The temperature rise within the focal zone caused by linear absorption, as indicated by the characteristic thermal diffusion time, will ease within one microsecond, approximately 79 times slower than the separation of a typical 80 MHz pulse. Therefore, the temperature rise is significant. This is not the case for kHz pulses. Here, the thermal diffusion time is 9 times faster than the separation of a typical 100 kHz pulse. Therefore, with constant laser energy density irradiation, the localized temperature rise due to laser heating is more pronounced at higher repetition frequencies.

[0130] The first wavelength of the irradiation beam in the system according to the invention is between 600 nm and 800 nm, preferably between 650 nm and 750 nm, more preferably between 670 nm and 720 nm, and even more preferably between 680 nm and 710 nm, so as to (locally) reduce the polarization degree of the IOL (and thus reduce the refractive index).

[0131] According to the invention, the second wavelength of the irradiated beam in the system is between 400 nm and 590 nm, preferably between 500 nm and 580 nm, and more preferably between 530 nm and 570 nm, so as to (locally) increase the polarization degree of the IOL (and thus increase the refractive index).

[0132] This allows for particularly precise local changes in polarization.

[0133] By locally altering the polarization degree of the intraocular lens, the refractive index of the lens can be locally changed. Further details of this correlation are described below.

[0134] Typical laser parameters are a wavelength of 680 nm, a pulse duration of 180 fs, and an average power of 500 mW, as described in one of the examples mentioned below.

[0135] Optical devices within the system according to the present invention:

[0136] The primary function of the optics is to focus the illumination beam emitted from the illumination source and controlled by the scanner onto the intraocular lens. As previously mentioned, key considerations are spot size and depth of focus to minimize processing time while remaining within limits given by laser safety requirements and material damage, as commonly included as input data. The most important characteristics of the optics are determined by their numerical aperture (NA), effective focal length (EFL), and the diameter of the illumination beam at the entrance aperture of the focusing optics. Furthermore, all optical elements within the system according to the invention should be selected for diffraction-limited or near-diffraction-limited characteristics to avoid significantly degrading beam quality.

[0137] Different ophthalmic needs will require different spot sizes, as the spot size determines the achievable spatial resolution. Ideally, the spot size is between 1 and 100 μm, and more ideally between 50 and 100 μm, to minimize processing time while keeping the possibility of material damage low.

[0138] Scanner within the system according to the present invention:

[0139] The scanner used in the system according to the invention may include a Galvano scanner, a piezoelectric scanner, a rotary scanner, or an acousto-optic modulator, or it may be digital, such as a spatial light modulator, a digital micromirror device, or a stereolithography apparatus. Preferably, the scanner used as part of the system according to the invention is selected from Galvano scanners, piezoelectric scanners, rotary scanners, acousto-optic modulators, spatial light modulators, digital micromirror devices, or stereolithography apparatus. A preferred Galvano scanner is a single pivot-point scanner.

[0140] Preferably, the scanner is configured to operate at a scanning speed greater than 50 mm / s. This allows for short treatment times. As a general rule, the treatment time should not exceed a few minutes per treatment session, and preferably less than 10 minutes, more preferably less than 5 minutes, and particularly preferably less than 3 minutes.

[0141] The treatment area can be defined as the volume and size of the intraocular lens. Typically, the diameter of the lens's optics is 5 mm to 7 mm and the thickness is usually between 0.2 mm and 2.0 mm.

[0142] The optimal exposure is <1 kJ / cm². 2 Ideally <0.3kJ / cm 2 To maintain low overall irradiation exposure and short treatment time, while addressing the full volume of the intraocular lens.

[0143] Particularly preferred is to use a random scanning pattern or interlaced scanning lines to spread the irradiation energy of the irradiation beam.

[0144] Three modes can be used to perform a scan. In a bottom-up scan, the laser can travel from one point to another with a specific dwell time at each point ("bottom-up, point-to-point"). Alternatively, in a bottom-up scan, the laser may stop at points that overlap with each other ("bottom-up, point coverage"). Alternatively, the laser can travel at a fixed speed without stopping at any point ("fly-by, constant speed"). Figure 3 A schematic diagram (1500) of this scanning strategy as described above is shown.

[0145] In one implementation of the scanning mode, the IOL is scanned by irradiation through the pupil using the previously described or preferably previously described irradiation source. During scanning, the IOL, contained within the capsular bag, is pre-inserted through a corneal incision using a conventional surgical procedure. In such an implementation, the entire volume of the IOL is scanned and the scan is performed in a bottom-up manner (i.e., first scanning the portion of the IOL furthest from the cornea), thus creating optical properties to avoid unwanted refractive index changes in the light path.

[0146] As mentioned earlier, a key consideration when selecting a scanning procedure is minimizing local heating of the intraocular lens and / or the patient's eye; therefore, various variables are used in the scanning procedure. Laser procedures with specific scanning speeds and sequences are created, taking into account anatomical features (such as rupture and pupil size) and optical features (such as numerical aperture and laser pulse characteristics). In such cases, the relationship between the lens coordinate system and the eye coordinate system is automatically considered. Figure 4 A schematic diagram (1600) shows the variables used in the scanning procedure as described above, taken into account when irradiating the lens inside the patient's eye.

[0147] The parameters of the scanning procedure and / or processing plan are preferably the first and second wavelengths, scanning speed and sequence, lens positioning relative to the eye (e.g., in Cartesian coordinates), scanning strategy, refractive index change to be obtained (optical pattern), numerical aperture of the objective lens, break, optical diameter of the pupil and / or lens (approximately 6 mm in some examples), pulse duration of the laser beam (shape, intensity, and xy positioning), laser safety when operating the laser, and centripetal orientation relative to the lens and eye positioning.

[0148] In one embodiment of the system according to the invention, photons generated in the laser are preferably guided by a mirror (e.g., optical element 1) to a beam expander, for example, to prepare the beam for subsequent scanning and focusing optics. After passing through the beam expander, the photons are directed to a scanner (e.g., a Galvano-scanner, a piezoelectric scanner, a rotary scanner, an acousto-optic modulator, or digitally using a spatial light modulator, a digital micromirror device, or a stereolithography apparatus).

[0149] After passing through the scanner, the laser beam passes through another optics, such as a divider mirror. In such an embodiment, the divider mirror splits the beam into a main imaging beam for irradiating the intraocular lens and a beam for monitoring beam characteristics and for positioning feedback. After the divider mirror, the beam is focused onto the intraocular lens by an imaging group or focusing optics. In one embodiment, the imaging group includes microscope objectives to obtain high numerical aperture (for μm-level spatial resolution) or low-NA optics to allow higher pulse energies in the μJ range.

[0150] In another embodiment of the previously described or preferred system, a microscope objective is further included, connected to a scanner, for focusing the illumination beam onto the artificial lens via the microscope objective. The microscope objective has a numerical aperture between 0.1 and 0.8, preferably between 0.2 and 0.5, and more preferably between 0.2 and 0.4. Providing a microscope objective with such a numerical aperture allows for high illumination beam quality, particularly in terms of the focusing and resolution characteristics of the beam used to process the artificial lens.

[0151] Microscope objectives include typical lens configurations to allow, for example, correction of chromatic aberration. Microscope objectives are preferably connected to an eye interface system, typically a suction system that holds the patient's eye in a fixed position, as further described below.

[0152] In another embodiment of the objective lens used in the system according to the invention as described above, the objective lens is an Olympus LUCPLFLN objective lens for focusing the illumination beam onto the intraocular lens.

[0153] Therefore, the present invention also relates to a system as described above, the system further comprising a microscope objective connected to a scanner for focusing the illumination beam onto the intraocular lens via the microscope objective, wherein the microscope objective has a numerical aperture between 0.1 and 0.8, preferably between 0.2 and 0.5, and more preferably between 0.2 and 0.4.

[0154] The alternative focusing optics / imaging assembly is configured with a single aspherical lens, the effective focal length of which is preferably in the range of 50 to 150 mm and the numerical aperture is preferably in the range of 0.025 to 0.1.

[0155] Therefore, the present invention further relates to a system as described above that further includes a focusing optics / imaging group, the focusing optics / imaging group being configured with a single aspherical lens having an effective focal length preferably in the range of 50 to 150 mm and a numerical aperture preferably in the range of 0.025 to 0.1.

[0156] The previously described, or preferably previously described, system in another embodiment further includes a positioning system for determining the location of the focal point of the illumination beam within the patient's eye, wherein the positioning system is connected to the scanner and wherein a scan by the scanner of the illumination beam across the intraocular lens is based on the location of the focal point of the illumination beam within the eye. The positioning system may include a positioning system, such as an optical coherence tomography system, a confocal microscope, or a Scheimpflug camera. The positioning system may be directly or indirectly connected to the scanner. In some examples using a confocal microscope, the confocal microscope may be directly connected to the scanner.

[0157] The positioning system described above is used to provide the positioning system with topographic data of the eye, which is used to determine the position of the laser focus based on the eye and the artificial lens.

[0158] For confocal microscopy, partially transparent mirrors are used for video imaging.

[0159] The system as described above, or preferably previously described, is preferably further configured to determine the position and / or orientation of the intraocular lens relative to the eye and the exit of the illumination beam, wherein the illumination beam is scanned across the intraocular lens by a scanner based on the position and / or orientation of the intraocular lens relative to the eye. This can be particularly advantageous because the position of the intraocular lens may not be concentric with respect to the eye, and such misalignment can be taken into account when the intraocular lens is treated with the illumination beam.

[0160] Regarding the location of the IOL, at least two coordinate systems can be considered relevant: the coordinate system of the eye and the coordinate system of the lens inside the eye, since the two may not be centered relative to each other.

[0161] Regarding the position of the intraocular lens, at least two coordinate systems can be considered relevant: the x, y, z coordinates of the eye and the x, y, z coordinates of the lens inside the eye, since the two may not be centered relative to each other.

[0162] In one implementation, the positioning system creates separate input data. This separate input data includes, for example, data regarding the position and / or orientation of the intraocular lens within the eye and relative to the laser beam exit, and / or the refractive index mapping of the eye and / or the intraocular lens. This data is used to calculate an optical pattern or for further processing.

[0163] Furthermore, the positioning system can create input data during the writing process. This input data includes, for example, data regarding the position and / or orientation of the intraocular lens within the eye and relative to the laser beam exit, and / or the refractive index mapping of the eye and / or the intraocular lens. This data is used to modify the control commands used to generate the optical pattern during the process.

[0164] Therefore, the present invention also relates to a system as described above, which further includes a positioning system for determining the focal position of the irradiation beam within the patient's eye, wherein the positioning system is connected to a scanner, and wherein the irradiation beam is scanned across the intraocular lens by the scanner based on the focal position of the irradiation beam within the eye.

[0165] Therefore, the present invention further relates to a system as described above, wherein the system is configured to determine the position and / or orientation of the intraocular lens relative to the eye and the exit of the irradiation beam, and wherein the irradiation beam is scanned across the intraocular lens by the scanner based on the position and / or orientation of the intraocular lens relative to the eye.

[0166] In another embodiment, the system as described above, or preferably previously described, further includes a temperature management unit connected to (i) one or more irradiation sources and (ii) one or both of a scanner, wherein the temperature management unit is configured to determine a portion of the temperature of the intraocular lens during the treatment performed by the scan based on the irradiation beam performance and the intraocular lens performance of the intraocular lens, and wherein the system is configured to control (i) the one or more irradiation sources and (ii) one or both of the scanners based on the temperature determination. This allows for ensuring that the eye and / or the intraocular lens are not adversely affected by the treatment with the irradiation beam.

[0167] Furthermore, the temperature management unit is preferably configured to predict the temperature during the treatment of the intraocular lens, and the input data includes the predicted temperature. This allows for preventative measures to ensure that the eye and / or intraocular lens are not adversely affected by the treatment with the irradiated light beam.

[0168] Alternatively, the temperature management unit is an infrared camera that records eye temperature and correlates the measurement data with general data carrying calibration data to calculate the true temperature in the eye.

[0169] In another implementation, the temperature dependence of the refractive index is used for temperature control. In these examples, the system includes a refractive mapping device. Based on the deviation of the measured refractive map and the progress of writing the predicted refractive map, the temperature in the lens can be calculated during the process.

[0170] In another embodiment, the temperature dependence of the emission spectrum is used for temperature control. In these examples, the system includes a UV-Vis spectrometer. Based on the deviation of the measured emission peak wavelength and / or peak width, the temperature at the focal point can be calculated during the process.

[0171] Therefore, the present invention also relates to a system as described above, comprising a temperature management unit connected to one or both of (i) one or more irradiation sources and (ii) a scanner, wherein the temperature management unit is configured to determine a temperature of a portion of the intraocular lens during the processing of the intraocular lens through the scan, based on the irradiation beam characteristics and the intraocular lens characteristics of the intraocular lens, and wherein the system is configured to control one or both of (i) one or more irradiation sources and (ii) a scanner based on the temperature determination.

[0172] Therefore, the present invention further relates to a system as described above, wherein a temperature management unit is configured to predict the temperature during the treatment of the intraocular lens, and wherein the input data includes the predicted temperature.

[0173] In another embodiment, the system as described above, or preferably previously described, further includes an eye interface system configured to hold the patient's eye in a fixed position. The eye interface system may include a suction system for fixing the position of the patient's eye during treatment.

[0174] Patients can "docked" into the system in a lying or standing position.

[0175] Therefore, the present invention also relates to a system as described above, comprising an eye interface system configured to hold the patient's eye in a fixed position.

[0176] In another embodiment, the previously described or preferred system further includes a wireless or wired receiver and / or transceiver for one or more of the following: (i) sending control commands to one or more illumination sources, (ii) sending control commands to a scanner, and (iii) inputting control command data required to create an optical pattern into the scanner.

[0177] Therefore, one or more irradiation sources and / or scanners can be remotely controlled. Additionally or alternatively, data relating to one or both of the lens data and processing plan data can be stored externally to the system and made available to the system when needed. In some examples, a wired receiver or transceiver may preferably be provided for at least controlling one or more irradiation sources and / or for controlling the scanner, in order to reduce (or avoid) any delays in sending control signals to one or more irradiation sources and / or scanners.

[0178] In another example, the receiver / transceiver sends processing plan data and lens data to a central computing unit, which calculates the optical pattern and sends it back to the receiver as input data, which then provides it to the system.

[0179] In a further embodiment, the previously described, or preferably previously described, system further includes means for locally measuring the refractive power of the intraocular lens during the treatment of the intraocular lens. Adjustments to one or more of the illumination source, scanner, and input data may be made during the treatment process.

[0180] In a further embodiment, the previously described, or preferably previously described, system further includes a refractometer for locally measuring the refractive index of the intraocular lens during the treatment of the intraocular lens. Adjustments to one or more of the illumination source, scanner, and input data may be made during the treatment process.

[0181] Other components of the system that provides photons may optionally be the cover for all the devices built into it, the power unit that provides sufficient energy for the system and all subsystems, and subsystems such as the suction system and / or the refrigeration unit.

[0182] In addition to the components mentioned above, a controller, firmware, graphical user interface (GUI), and processing algorithms may also be provided. Connection to the system can be established via Bluetooth, Wi-Fi, or other ports such as RS-232.

[0183] Figure 5 A further schematic diagram of a system (100) for irradiating an intraocular lens disposed within the eye of a patient (136) is shown. The system (100) generally relates to a laser system comprising at least one femtosecond laser source (102, 104) capable of generating at least one, preferably two, different wavelengths. The system (100) also includes a focal or Z-shifter optics (106), a scanner (110) (Galvano-scanner, piezoelectric scanner, rotating scanner, acousto-optic modulator, spatial light modulator, digital micromirror device, or stereolithography apparatus), and optics (108) for delivering laser pulses to a predetermined area. The system (100) is capable of delivering the same level of energy to a target area of ​​a polymer material comprising photochemically active units forming an intraocular lens disposed within the eye of the patient (136). The system in Figure 5 It also includes an eye interface (112) for securing the patient's (136) eye. Figure 5In this configuration, the laser system is connected to a computer controller (116) incorporating the corresponding device firmware (118) and a front-end graphical user interface (GUI) (120). An algorithm (122) is used to calculate the energy level delivered to the target region of the polymer material contained in the photochemically active unit that forms the intraocular lens in the processing planning system. System parameters and process planning (134) are monitored via the GUI (120). Inputs and adjustments from the patient (136), such as lens data (130) and refractive index shaping plans (132), can be input via the GUI (120). The laser source, subsystem, and body fixation device (124) can be integrated into a single module connected to a power supply (126) sealed with a cover (128).

[0184] Figure 6 and Figure 7 A schematic diagram of the components of the system according to the invention described herein is shown.

[0185] exist Figure 6 In the example, photons generated in the illumination source (202) are guided through a mirror (optical system 1, such as a beam shaper (204), a focus shifter / Z-shifter (206)) to a scanner (208) (e.g., a Galvano-scanner, a piezoelectric scanner, a rotary scanner, an acousto-optic modulator, or digitally coupled with a spatial light modulator (SLM)). Connected to the scanner (208) are a microscope objective (optical system 2) and a patient interface (210).

[0186] like Figure 7 As shown, the Z-shifter (302) includes a first lens (304), a second lens (306), and a third lens (308). The illumination beam then travels to a scanner (310), which includes multiple mirrors (312), (314), and (316) that allow for alteration of the position of the illumination beam in the xy direction on the IOL. After passing through the scanner (310), the illumination beam is imaged by passing through a beam splitter (318) before passing through the imaging group (320). The system also includes an illumination unit (322) and a patient interface (324).

[0187] This application further describes a method for adjusting the polarization of an intraocular lens (preferably at one or more specific locations on the lens) based on a two- or multi-photon absorption process, comprising a body formed of polymer optical material. The method includes the steps of: providing the lens; and adjusting the polarization of the lens by using the system described herein or preferably as described throughout this disclosure, thereby altering the polymer optical material relative to the unirradiated polymer optical material of the intraocular lens to exhibit significant differences in the UV / Vis spectrum. The intraocular lens preferably comprises a contact lens or IOL of the polymer optical material described herein or preferably as described below. The method for adjusting polarization according to the invention as described above or preferably as described below is performed in a non-destructive manner with respect to the intraocular lens material.

[0188] Ultraviolet-visible spectroscopy or ultraviolet-visible spectrophotometry (UV-Vis or UV / Vis) is known to those skilled in the art. It refers to the absorption or reflectance spectrum of a portion of the ultraviolet light and the entire adjacent visible spectral region. Suitable UV / Vis spectrometers are commercially available. The choice of UV / Vis spectrometer is not critical for comparing the UV / Vis spectrum of the initial intraocular lens with the UV / Vis spectrum of the irradiated intraocular lens prepared according to the present invention. This is known to those skilled in the art, as long as both measurements are performed under comparable conditions so that the results can be compared. A suitable spectrometer is the Lambda 900 UV / Vis spectrometer from Perkin Elmer.

[0189] In some examples, the artificial lens can then be introduced into the patient's eye. In some examples, the lens may include an intraocular lens, allowing the polarization of the lens to be adjusted as it is positioned within the patient's eye.

[0190] In the aforementioned method, the adjustment of the polarization degree of the intraocular lens includes reducing the polarization degree by irradiating the intraocular lens with an illumination beam having a wavelength between 600 nm and 800 nm, thereby altering the polymer optical material relative to the unirradiated polymer optical material of the intraocular lens to have a significant difference in UV / Vis spectra, i.e., a peak absorption loss in the range of 300 nm to 400 nm.

[0191] Therefore, the present invention further relates to the method as described above, wherein the adjustment of the polarization degree of the intraocular lens comprises reducing the polarization degree by irradiating the intraocular lens with an irradiation beam having a wavelength between 600 nm and 800 nm, thereby altering the polymer optical material relative to the unirradiated polymer optical material of the intraocular lens to have a significant difference in UV / Vis spectra, i.e., a peak absorption loss in the range of 300 nm to 400 nm.

[0192] In the aforementioned method, the adjustment of the polarization degree of the intraocular lens includes increasing the polarization degree by irradiating the intraocular lens with an illumination beam having a wavelength between 400 nm and 590 nm, thereby altering the polymer optical material relative to the unirradiated polymer optical material of the intraocular lens to have a significant difference in UV / Vis spectra, i.e., an increase in peak absorption in the range of 300 nm to 400 nm.

[0193] Therefore, the present invention further relates to the method as described above, wherein the adjustment of the polarization degree of the intraocular lens comprises increasing the polarization degree by irradiating the intraocular lens with an illumination beam having a wavelength between 400 nm and 590 nm, thereby altering the polymer optical material relative to the unirradiated polymer optical material of the intraocular lens to have a significant difference in the UV / Vis spectrum, i.e., an increase in peak absorption in the range of 300 nm to 400 nm.

[0194] Therefore, the present invention further relates to a method (preferably at one or more specific locations of the lens) for adjusting the polarization of an artificial lens comprising a body formed of a polymer optical material based on a two- or multi-photon absorption process, the method comprising the following steps:

[0195] Provide the lens; and

[0196] The polarization degree of the lens is adjusted by using a system comprising the following:

[0197] One or more illumination sources are used to illuminate the artificial lens with a two-photon or multi-photon beam of light focused by an optical device and having a first wavelength and / or a second wavelength different from the first wavelength.

[0198] A scanner, connected to the one or more illumination sources, and configured to scan the illumination beam across the intraocular lens, and

[0199] An input unit, connected to the one or more illumination sources and the scanner, wherein the input unit is configured to input data to process the intraocular lens by scanning the illumination beam across the intraocular lens based on the input data, and

[0200] The first wavelength, between 600 nm and 800 nm, is used to locally reduce the polarization degree of the intraocular lens based on the treatment, thereby altering the polymer optical material relative to the unirradiated polymer optical material of the intraocular lens, resulting in a significant difference in UV / Vis spectra, i.e., a peak absorption loss in the range of 300 nm-400 nm.

[0201] The second wavelength is between 400 nm and 590 nm. Based on the treatment of the intraocular lens, the polarization degree of the intraocular lens is locally increased, thereby changing the polymer optical material relative to the unirradiated polymer optical material of the intraocular lens, resulting in a significant difference in the UV / Vis spectrum, namely an increase in peak absorption in the range of 300 nm to 400 nm.

[0202] The specific wavelength used to reduce and / or increase the polarization of the intraocular lens may depend on which particular material or composition is available for the intraocular lens. Any one or more polymeric optical materials described in this disclosure may be used to prepare and / or provide the lens.

[0203] The special polymers described below are preferred, as they are suitable for manufacturing artificial lenses, preferably IOLs, whose optical properties can be altered later (non-invasively) by utilizing their ability to change the degree of polarization and thus the refractive index by applying a two-photon or multi-photon process.

[0204] The special polymers described below are preferably processed using the system according to the invention and / or preferably used using the method according to the invention.

[0205] Two-photon or multi-photon processes are generated using a system described in detail earlier.

[0206] The applicable wavelength range of the irradiation source is preferably 600nm-800nm, more preferably 650nm-750nm, particularly preferably 670nm-720nm, and very particularly preferably 680-710nm, as described above for pulsed lasers, thereby reducing the polarization degree of the artificial lens and thus reducing its refractive index.

[0207] The applicable wavelength range of the irradiation source is preferably the pulsed laser range of 400nm-590nm, more preferably 500nm-580nm, and particularly preferably 530nm-570nm, as described above, thereby increasing the polarization degree of the artificial lens and thus increasing its refractive index.

[0208] This allows for highly precise local changes in polarization.

[0209] In the following, the optical materials used for the intraocular lens according to the method of the invention, preferably polymeric optical materials for contact lenses or IOLs, are further and preferably described for the following wavelength regions: 600nm-800nm, preferably 650nm-750nm, particularly preferably 670nm-720nm, and very particularly preferably 680-710nm, to locally reduce the polarization of the material.

[0210] To apply such adjustment, the refractive index of polymer optical materials is in the range of 1.45–1.60.

[0211] The polymer optical material of an artificial lens (contact lens or IOL) may optionally contain an ultraviolet light blocker or a blue light absorber.

[0212] The polymeric optical material of the intraocular lens used for the adjustment according to the method of the present invention comprises a polymer matrix containing covalently bonded photoactive units, preferably in an amount of at least 2 wt% to 100 wt%, preferably 5 wt% to 90 wt%, and most preferably 7 wt% to 80 wt%.

[0213] The photoactive units within the polymer matrix may be the same or different.

[0214] The polymer matrix for the adjustment of the polymer optical material of the intraocular lens and / or IOL can be derived from homopolymers or copolymers, preferably copolymer matrices.

[0215] The polymer matrix containing photoactive units can be derived from silicon-containing polymers, acrylic polymers, methacrylic polymers, or mixtures thereof.

[0216] A photoactive unit refers to a photochemically active unit that is photochemically active in the applicable wavelength region described above or preferably previously as an effect of a two-photon or multi-photon process.

[0217] The photoactive unit preferably contains a non-aromatic double bond, preferably a carbon-carbon double bond, which can dimerize by forming a cyclobutane ring through [2π+2π] cycloaddition under the effect of a two-photon or multi-photon process.

[0218] Therefore, the present invention further relates to a method for adjusting the polarization of an intraocular lens comprising a body formed of a polymer optical material (preferably at one or more specific locations in the lens), wherein the optical material of the intraocular lens comprises a polymer matrix containing covalently bonded photoactive units comprising non-aromatic double bonds, preferably carbon-carbon double bonds, which are dimerizable by forming a cyclobutane ring via [2π+2π] cycloaddition under the effect of a two-photon or multi-photon process. In such embodiments, the photoactive units within the polymer optical material of the intraocular lens used according to the method of the present invention may be the same or different, but are the only photoactive units in the polymer optical material and are classified in that they contain non-aromatic double bonds, preferably carbon-carbon double bonds, which are dimerizable by forming a cyclobutane ring via [2π+2π] cycloaddition under the effect of a two-photon or multi-photon process as described above or further preferably as described below.

[0219] Alternatively, the polymer matrix may contain the photoactive units as described above or below, together with the already dimerized photoactive units. Therefore, the polymer matrix may still contain photoactive units capable of dimerization. The polymer optical material (polymer matrix) may be partially dimerized.

[0220] In the embodiments of the optical material used in the intraocular lens according to the method of the invention, polymeric optical materials for contact lenses or IOLs are preferred. Such materials can be irradiated with a first or second region of wavelength as described above to reduce or increase the polarization of the intraocular lens containing the polymeric optical material, thereby reducing or increasing the refractive index. Using such polymeric optical materials, the polarization of the intraocular lens can be adjusted.

[0221] Therefore, the present invention further relates to adjusting the polarization of an intraocular lens comprising a body formed of a polymer optical material (preferably a method at one or more specific locations in the lens), wherein the optical material of the intraocular lens comprises a polymer matrix containing covalently bonded photoactive units comprising non-aromatic double bonds, preferably carbon-carbon double bonds, which are capable of dimerizing together with already dimerized photoactive units by forming a cyclobutane ring via [2π+2π] cycloaddition under the effect of a two-photon or multi-photon process. In such embodiments, the photoactive units within the polymer optical material of the intraocular lens for use according to the method of the present invention may be the same or different, but are the only photoactive units in the polymer optical material and are classified in that they contain non-aromatic double bonds, preferably carbon-carbon double bonds, which are capable of dimerizing by forming a cyclobutane ring via [2π+2π] cycloaddition under the effect of a two-photon or multi-photon process as described above or further preferably as described below, or the photoactive units are their dimerized photoactive units.

[0222] The photoactive unit within the polymeric optical material of the intraocular lens used according to the method of the invention particularly preferably comprises a non-aromatic carbon-carbon double bond conjugated with at least one aromatic ring system, which is capable of dimerizing by forming a cyclobutane ring via [2π+2π] cycloaddition under the effect of a two-photon or generally multiphoton process.

[0223] Preferably, the non-aromatic double bond and the aromatic ring system conjugated with the non-aromatic double bond form a fused ring system as part of the photoactive unit as described above, preferably a bicyclic or tricyclic ring system, and particularly preferably a bicyclic ring system.

[0224] Examples of such fused-ring systems conjugated with non-aromatic carbon double bonds, as previously described, that are part of the photoactive unit within the polymeric optical material of an artificial lens used according to the method of the invention, are chromone-2-one, chromone-2-thione, thiochromone-2-one, thiochromone-2-thione, quinoline-2-one, quinoline-2-thione, benzo[b]furan, benzo[b]thiophene, benzo[b]pyrrole, indene, 1,2-dihydronaphthalene, 6,7-dihydro-5H-benzo[7]cycloarbutin, (Z)-5,6,7,8-tetrahydrobenzo[8]cycloarbutin.

[0225] The [2π+2π] ring addition can be visualized according to the following scheme 1. Figure 8 The specific [2π+2π] cycloaddition reaction of poly(M-14) is shown; the representative material will be further described in Examples 1 and 2. Scheme 1 further visualizes the ring splitting. Figure 9 The specific poly(M-14)-dimer is shown to be split through ring cleavage, which is further described in Examples 3 and 5.

[0226] Option 1:

[0227]

[0228] R p It refers to the polymer / polymer backbone covalently attached to the fused ring system via a linker;

[0229] X′-X′ are independent of each other as CH=CH, CR′=CH, CH=CR′ or CR′=CR′;

[0230] Y′ represents O, S, NR′, CH2, CHR′, and C(R′)2;

[0231] m is 1 when Y′ is O, S or NR′, and m is 1, 2, 3 or 4 when Y′ is independently selected from CH2, CHR′ and C(R′)2 each time it appears;

[0232] Z′ is either C=O or C=S;

[0233] n is 0 or 1

[0234] R′ is an organic substituent.

[0235] Examples of silicon-containing polymers that can be used as optical materials for intraocular lenses according to the method of the present invention are described in WO2018149857.

[0236] Examples of acrylate- or methacrylate-containing polymers that can be used as optical materials for intraocular lenses used in the method according to the invention are described in WO2017032442, WO2017032443, WO2017032444, WO2018149850, WO2018149852, WO2018149853, WO2018149855, and WO2018149856.

[0237] All references are incorporated into this application by reference.

[0238] In a preferred embodiment of the invention, the polymeric optical material comprises a polymer matrix containing covalently bonded photoactive units of an intraocular lens to be used in the method according to the invention, the polymeric optical material containing polymerized monomers according to formula (1).

[0239]

[0240] The symbols used are as follows:

[0241] u is 0 or 1,

[0242] Y is either the same or different each time it appears, and is O, S, NR. 0 or X 1 ,

[0243] X 1 CH2, CHR 0 ,C(R 0 )2, [CH2]2, [CHR 0 ]2, [C(R 0 )2]2,[CH2]3,[CHR 0 ]3, [C(R 0 )2]3,[CH2]4,[CHR 0 ]4 or [C(R 0 )2]4;

[0244] Z is either the same or different each time it appears, and is either O or S;

[0245] X1 is O, S, or SO2;

[0246] a is 0 or 1;

[0247] Sp is an alkyl diel, alkenyl diel, or ynyl diel, which may be substituted by one or more R groups;

[0248] R 0 It is a straight-chain or branched alkyl group having 1-10 carbon atoms;

[0249] R 1 R2 R 3 and R 4 The compounds are independently selected from H, F, Cl, Br, I, straight-chain or branched alkyl groups having 1-20 C atoms, partially or fully halogenated straight-chain or branched alkyl groups having 1-20 C atoms, and aryl or heteroaryl groups having 5-40 cyclic atoms.

[0250] R 5 R 6 R 7 R 8 and R 9 Each time it appears, it is independently selected from F, straight-chain or branched, non-halogenated, partially or fully halogenated alkyl groups having 1-20 carbon atoms, non-halogenated, partially or fully halogenated cycloalkyl groups having 3-6 carbon atoms, straight-chain or branched, non-halogenated, partially or fully halogenated alkoxy groups having 1-20 carbon atoms, and straight-chain or branched, non-halogenated, partially or fully halogenated thioalkyl groups having 1-20 carbon atoms;

[0251] X 11 Selected from O, S, O-SO2, SO2-O, C(=O), OC(=O), C(=O)O, S(C=O) and (C=O)S;

[0252] c is 0 or 1;

[0253] R 10 R 11 R 12 The compounds are independently selected from H, F, partially or fully halogenated straight-chain or branched alkyl groups having 1-20 carbon atoms, and aryl groups having 6-14 carbon atoms;

[0254] R may be the same or different each time it appears, and is selected from F, OH, straight-chain or branched alkyl with 1-10 carbon atoms, partially or fully halogenated straight-chain or branched alkyl with 1-10 carbon atoms, straight-chain or branched alkoxy with 1-10 carbon atoms, and partially or fully halogenated straight-chain or branched alkoxy with 1-10 carbon atoms.

[0255] In a preferred embodiment of the invention, the polymeric optical material comprises a polymer matrix containing covalently bonded photoactive units of an intraocular lens to be used in the method according to the invention, the polymeric optical material containing polymerized monomers according to formula (2).

[0256]

[0257] The symbols used are as follows:

[0258] u is 0 or 1,

[0259] Y is either the same or different each time it appears, and is O, S, NR. 0 or X 1 ,

[0260] X 1 CH2, CHR 0 ,C(R 0 )2, [CH2]2, [CHR 0 ]2, [C(R 0 )2]2,[CH2]3,[CHR 0 ]3, [C(R 0 )2]3,[CH2]4,[CHR 0 ]4 or [C(R 0 )2]4;

[0261] Z is either the same or different each time it appears, and is either O or S;

[0262] X1 is O, S, or SO2;

[0263] a is 0 or 1;

[0264] Sp is an alkyl diel, alkenyl diel, or ynyl diel, which may be substituted by one or more R groups;

[0265] R 0 It is a straight-chain or branched alkyl group having 1-10 carbon atoms;

[0266] R 1 R 2 R 3 and R 4 The compounds are independently selected from H, F, Cl, Br, I, straight-chain or branched alkyl groups having 1-20 C atoms, partially or fully halogenated straight-chain or branched alkyl groups having 1-20 C atoms, and aryl or heteroaryl groups having 5-40 cyclic atoms.

[0267] R 5 R 6 R 7 R 8 and R 9 Each time it appears, it is independently selected from F, straight-chain or branched, non-halogenated, partially or fully halogenated alkyl groups having 1-20 carbon atoms, non-halogenated, partially or fully halogenated cycloalkyl groups having 3-6 carbon atoms, straight-chain or branched, non-halogenated, partially or fully halogenated alkoxy groups having 1-20 carbon atoms, and straight-chain or branched, non-halogenated, partially or fully halogenated thioalkyl groups having 1-20 carbon atoms, but...

[0268] The condition is that R 5 R 6 R7 R 8 Or R 9 One corresponds to equation (2-1), where * indicates a connection to the rest of equation (2).

[0269]

[0270] R 10 R 11 R 12 The compounds are independently selected from H, F, partially or fully halogenated straight-chain or branched alkyl groups having 1-20 carbon atoms, and aryl groups having 6-14 carbon atoms;

[0271] X 11 Selected from O, S, O-SO2, SO2-O, C(=O), OC(=O), C(=O)O, S(C=O) and (C=O)S;

[0272] c is 0 or 1;

[0273] R may be the same or different each time it appears, and is selected from F, OH, straight-chain or branched alkyl groups having 1-10 carbon atoms, partially or fully halogenated straight-chain or branched alkyl groups having 1-10 carbon atoms, straight-chain or branched alkoxy groups having 1-10 carbon atoms, and partially or fully halogenated straight-chain or branched alkoxy groups having 1-10 carbon atoms.

[0274] Halogenation refers to the preferred methods of fluorination, chlorination, or bromination, with fluorination being particularly preferred.

[0275] Straight-chain or branched alkyl groups having 1-10 carbon atoms represent alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, such as methyl, ethyl, isopropyl, n-propyl, isobutyl, n-butyl, tert-butyl, n-pentyl, 1-, 2-, or 3-methylbutyl, 1,1-, 1,2-, or 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, n-heptyl, n-octyl, ethylhexyl, n-nonyl, or n-decyl. Alkyl groups having 1-20 carbon atoms include all examples of straight-chain or branched alkyl groups having 1-10 carbon atoms, including any alkyl group having 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20 carbon atoms, such as n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecanyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n-nonadecanyl, and n-eicosyl.

[0276] The term "partially halogenated alkyl" means that at least one H atom of the alkyl group is replaced by F, Cl, Br, or I. Preferably, the alkyl group is partially fluorinated, meaning that at least one H atom of the alkyl group is replaced by F.

[0277] The term fully halogenated alkyl means that all the H atoms of the alkyl group are replaced by F, Cl, Br, and / or I. Preferably, the alkyl group is fully fluorinated, meaning that all the H atoms of the alkyl group are replaced by F. A preferred fully fluorinated alkyl group is trifluoromethyl.

[0278] The terms halogenation or preferred fluorination also correspond to other groups, such as halogenated cycloalkyl, halogenated alkoxy, or halogenated thioalkyl.

[0279] Cycloalkyl groups having 3-6 carbon atoms include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, which may be partially or completely halogenated or fluorinated as previously described.

[0280] A straight-chain or branched alkoxy group having 1-20 carbon atoms represents an O-alkyl group having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, such as methoxy, ethoxy, isopropoxy, n-propoxy, isobutoxy, n-butoxy, tert-butoxy, n-pentoxy, 1-, 2-, or 3-methylbutoxy, 1,1-, 1,2-, or 2,2-dimethylpropoxy, 1-ethylpropoxy, n-hexyloxy, n-heptoxy, n-octyloxy, ethylhexyloxy, n-nonyloxy, n-decyloxy, n-undecyloxy, n-dodecyloxy, n-tridecyloxy, n-tetradecyloxy, n-pentadecanyloxy, n-hexadecyloxy, n-heptadecyloxy, n-octadecyloxy, n-nonadecanyloxy, and n-eicosyloxy, which may be partially or completely halogenated or preferably partially or completely fluorinated. The preferred fully fluorinated alkoxy group is trifluoromethoxy.

[0281] Straight-chain or branched thioalkyl groups having 1-20 carbon atoms represent S-alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, such as thiomethyl, 1-thioethyl, 1-thio-isopropyl, 1-thio-n-propyl, 1-thio-isobutyl, 1-thio-n-butyl, 1-thio-tert-butyl, 1-thio-n-pentyl, 1-thio-1-,-2-, or-3-methylbutyl, 1-thio-1,1-,-1,2-, or-2,2-dimethylpropyl. 1-Thio-1-ethylpropyl, 1-thio-n-hexyl, 1-thio-n-heptyl, 1-thio-n-octyl, 1-thio-ethylhexyl, 1-thio-n-nonyl, 1-thio-n-decyl, 1-thio-n-undecyl, 1-thio-n-dodecyl, 1-thio-n-tridecyl, 1-thio-n-tetradecyl, 1-thio-n-pentadecanyl, 1-thio-n-hexadecyl, 1-thio-n-heptadecyl, 1-thio-n-heptadecanyl, 1-thio-n-octadecyl, 1-thio-n-nonadecanyl, and 1-thio-n-eicosyl, which may be partially or fully halogenated or preferably partially or fully fluorinated. The preferred fully fluorinated sulfide group is trifluoromethyl sulfide.

[0282] Preferred alkyl and alkoxy groups have 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms.

[0283] In the context of this invention, aryl groups contain 6-40 ring atoms, and heteroaryl groups contain 5-40 ring atoms, including at least one heteroatom. The heteroatom is preferably selected from N, O, and / or S. Aryl or heteroaryl groups herein refer to simple aromatic rings, i.e., phenyl, or simple heteroaryl rings, such as pyridyl, pyrimidinyl, thiophenyl, etc., or fused (anellated) aryl or heteroaryl groups, such as naphthyl, anthracene, phenanthryl, quinolinyl, or isoquinolinyl.

[0284] The aryl or heteroaryl groups are preferably derived from benzene, naphthalene, anthracene, phenanthrene, pyrene, benzo[a]anthracene, [unspecified], perylene, fluoranthene, tetraphenyl, pentaphenyl, benzo[a]pyrene, biphenyl, biphenylene, terphenyl, benzo[a]phenanthrene, fluorene, spirodifluorene, dihydrophenanthrene, dihydropyrene, tetrahydropyrene, cis or trans indo[a]fluorene, cis or trans indo[a]carbazole, cis or trans indo[a]carbazole, trimer indene, isotrimer indene, spirotrimer indene, spiroisotrimer indene, furan, benzo[a]furan, isobenzo[a]furan, dibenzo[a]furan, thiophene, benzo[a]thiophene, isobenzene Thiophene, dibenzothiophene, pyrrole, indole, isoindole, carbazole, pyridine, quinoline, isoquinoline, acridine, phenanthridine, benzo-5,6-quinoline, benzo-6,7-quinoline, benzo-7,8-quinoline, phenothiazine, phenothiazine, pyrazole, indazole, imidazole, benzimidazole, naphthiamidazole, phenanthrenemidazole, pyridinium pyrazinium pyridimazole, quinoxaline pyridimazole, oxazole, benzoxazole, naphthiamidazole, anthraquinoxazole, phenanthrenemidazole, isoxazole, 1,2-thiazole, 1,3-thiazole Zyrazole, benzothiazole, pyridazine, hexaazabenzophenanthrene, benzopyridazine, pyrimidine, benzopyrimidine, quinoxaline, 1,5-diazathane, 2,7-diazapyrene, 2,3-diazapyrene, 1,6-diazapyrene, 1,8-diazapyrene, 4,5-diazapyrene, 4,5,9,10-tetraazaperylene, pyrazine, phenazine, phenoxazine, phenothiazine, fluorescein ring, naphthidine, azacarbazole, benzocarbline, phenanthroline, 1,2,3-triazole, 1,2,4-triazole, benzotriazole 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,3,5-triazine, 1,2,4-triazine, 1,2,3-triazine, tetrazolium, 1,2,4,5-tetraazine, 1,2,3,4-tetraazine, 1,2,3,5-tetraazine, purine, pteridine, indazine, and benzothiadiazole.

[0285] The aryl group having 6-14 carbon atoms is preferably an aryl group, selected from phenyl, naphthyl or anthracene, with phenyl being particularly preferred.

[0286] In a particularly preferred embodiment of the invention, the polymeric optical material comprises a polymer matrix containing covalently bonded photoactive units of an intraocular lens to be used in the method according to the invention, the polymeric optical material containing monomers polymerized according to formula (3).

[0287]

[0288] Where X1, a, R 5 -R 9 and R 10 -R 12 It has the meaning described above.

[0289] In a particularly preferred embodiment of the invention, the polymeric optical material comprises a polymer matrix containing covalently bonded photoactive units of an intraocular lens to be used in the method according to the invention, the polymeric optical material containing polymerized monomers according to formula (4).

[0290]

[0291] in

[0292] u is 0, Y is X 1 X 11 The suffixes are selected from O-SO2, SO2-O, OC(=O), C(=O)O, S(C=O), and (C=O)S, where c is 1.

[0293] and X 1 X1, a, Sp, R 0 R 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 10 R 11 R 12 , and R has the meaning as described above.

[0294] In a particularly preferred embodiment of the invention, the polymeric optical material comprises a polymer matrix containing covalently bonded photoactive units of an intraocular lens to be used in the method according to the invention, the polymeric optical material containing polymerized monomers according to formula (5).

[0295]

[0296] in

[0297] u is 0, Y is X 1 X 11 Selected from, O-SO2, SO2-O, OC(=O), C(=O)O, S(C=O)

[0298] And (C=O)S, where c is 1,

[0299] and X 1 X1, a, Sp, R 0 R 1 R 2 R 3 R 4 R 5 R 6 R7 R 8 R 9 R 10 R 11 R 12 , and R has the meaning as described above.

[0300] For compounds according to formula (1) or (3), R 5 R 6 R 7 R 8 and R 9 Preferably, the compounds are independently selected from H, F, Cl, Br, I, straight-chain or branched alkyl groups having 1-20 carbon atoms, straight-chain or branched alkoxy groups having 1-20 carbon atoms, partially or fully halogenated straight-chain or branched alkyl groups having 1-20 carbon atoms, partially or fully halogenated straight-chain or branched alkoxy groups having 1-20 carbon atoms, and aryl or heteroaryl groups having 5-40 ring atoms, wherein at least one of them is selected from R. 5 -R 9 The groups are straight-chain or branched alkyl or alkoxy groups having 1-20 C atoms, which may be partially or completely halogenated.

[0301] For compounds according to formulas (2), (4) or (5), R 5 R 6 R 7 R 8 and R 9 Preferably, the compounds are independently selected from H, F, Cl, Br, I, straight-chain or branched alkyl groups having 1-20 C atoms, straight-chain or branched alkoxy groups having 1-20 C atoms, partially or fully halogenated straight-chain or branched alkyl groups having 1-20 C atoms, partially or fully halogenated straight-chain or branched alkoxy groups having 1-20 C atoms, and aryl or heteroaryl groups having 5-40 cyclic atoms.

[0302] In compounds of formula (1), (2), (3), (4) or (5), Sp is preferably unsubstituted.

[0303] In compounds of formula (1), (2), (3), (4) or (5), R 11 and R 12 H is preferred.

[0304] In compounds of formula (1), (2), (3), (4) or (5), R 10 H or methyl is preferred.

[0305] In compounds of formula (1) or (2), R 5 H is preferred.

[0306] In compounds of formula (1) or (2), R 6 H is preferred.

[0307] In compounds of formula (1) or (2), R 8 H is preferred.

[0308] In compounds of formula (1) or (2), R 9 Preferably, they are straight-chain or branched alkyl or alkoxy groups having 1-6 carbon atoms, which may be partially or completely fluorinated, and X1, a, R 5 -R 8 and R 10 -R 12 It has the meaning as described above or preferably as previously stated.

[0309] In compounds of formula (1) or (2), R 7 Preferably, they are straight-chain or branched alkyl groups having 2 to 8 carbon atoms, which may be partially or completely fluorinated, and X1, a, R 5 -R 6 R 9 and R 10 -R 12 It has the meaning as described above or preferably as previously stated.

[0310] In compounds of formula (2), (4) or (5), R 1 R 2 R 3 and R 4 H is preferred.

[0311] In compounds of formula (2) or (4), R 5 R 6 R 7 R 8 and R 9 Preferably, the compounds are independently selected from H, F, straight-chain or branched alkyl groups having 1-20 C atoms, straight-chain or branched alkoxy groups having 1-20 C atoms, partially or fully halogenated straight-chain or branched alkyl groups having 1-20 C atoms, and partially or fully halogenated straight-chain or branched alkoxy groups having 1-20 C atoms.

[0312] In the compound of formula (4), R 5 R 6 R 7 R 8 and R 9 H or R are preferred. 5 R 6 R 7 R 8 and R 9One or two of them are F or alkyl groups having 1-8 C atoms, which may be partially or completely fluorinated, and the other substituents are H.

[0313] In the compound of formula (5), R 5 R 6 R 7 R 8 and R 9 H is preferred, except for one substituent which is as described above or preferably the previously described formula (2-1).

[0314] In a further embodiment of the invention, the polymeric optical material comprising the polymeric matrix of the intraocular lens to be used according to the method of the invention contains monomers selected from polymerized compounds (M-1) to (M-68) and (A-01) to (A-16):

[0315]

[0316]

[0317]

[0318]

[0319]

[0320]

[0321]

[0322]

[0323]

[0324]

[0325]

[0326] In a further embodiment of the invention, the polymer optical material comprising the polymer matrix contains polymeric monomers selected from compounds (M-12), (M-14), (M-15), (M-18), (M-53), (M-55), (M-67), (A-01) to (A-16).

[0327] In a further very preferred embodiment of the invention, the polymer matrix of the polymer optical material to be used in the method according to the invention is a copolymer matrix comprising a polymeric monomer comprising the aforementioned or preferably previously described photoactive unit, or a polymeric compound of formulas (1) to (5) as described above, or polymeric compounds (M-1) to (M-68) and (A-01) to (A-16) and other polymeric monomers known in the art.

[0328] Examples of monomers copolymerized with the monomers comprising photoactive units described above or preferably previously described, for constructing polymeric optical materials for artificial lenses (e.g., contact lenses or IOLs), may be selected from styrene, ethoxyethyl methacrylate (EOEMA), methyl methacrylate (MMA), methyl acrylate, n-alkyl acrylate (containing 2-20 carbon atoms), n-alkyl methacrylate (containing 2-20 carbon atoms), isoalkyl acrylate (containing 3-20 carbon atoms), isoalkyl methacrylate (containing 3-20 carbon atoms), ethoxyethyl acrylate (EEEA), 2-hydroxyethyl methacrylate (HEMA), tetrahydrofuran methacrylate (THFMA), glycidyl methacrylate (GMA), propylene 16-Hydroxyhexadecyl acrylate, 16-Hydroxyhexadecyl methacrylate, 18-Hydroxyoctadecyl acrylate, 18-Hydroxyoctadecyl methacrylate, 2-phenoxyethyl acrylate (EGPEA), heptafluorobutyl acrylate, heptafluorobutyl methacrylate, hexafluorobutyl acrylate, hexafluorobutyl methacrylate, hexafluoroisopropyl acrylate, hexafluoroisopropyl methacrylate, octafluoropentyl acrylate, octafluoropentyl methacrylate, pentafluoropropyl acrylate, pentafluoropropyl methacrylate, tetrafluoropropyl methacrylate, trifluoroethyl acrylate, trifluoroethyl methacrylate, bisphenol A diacrylate-1EO / phenol (BPADA), 2-[3′-2′H-benzotriazol-2′-yl)-4′-hydroxyphenyl]ethyl methacrylate (BTPEM) or ethylene glycol dimethacrylate.

[0329] Preferred examples of monomers copolymerized with the monomers comprising photoactive units described above or preferably previously described are selected from methyl methacrylate, 2-hydroxyethyl methacrylate, 2-phenoxyethyl acrylate, ethoxyethoxyethyl acrylate, 8-methylnonyl methacrylate, n-butyl methacrylate, 2-ethylhexyl methacrylate, or mixtures thereof.

[0330] Suitable UV absorbers include 2-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2-benzotriazolyl)phenoxy)ethyl methacrylate, 3-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2-benzotriazolyl)phenoxy)propyl methacrylate, 3-(3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl)propyl methacrylate, 3-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)phenoxy)propyl methacrylate, and 2-(2-hydroxy-5-vinylphenyl)-2H- Benzotriazole, allyl-2-hydroxybenzophenone, 2-allyl-6-(2H-benzotriazole-2-yl)-p-cresol, 4-methacryloyl-2-hydroxybenzophenone, 2-(2′-hydroxy-3′-methylallyl-5′-methylphenyl)benzotriazole, 2-hydroxy-4-methacryloyloxybenzophenone, 4-acryloylethoxy-2-hydroxybenzophenone, 2-[3-(2H-benzotriazole-2-yl)-4-hydroxyphenyl]ethyl methyl acrylate, 2-(2′-hydroxy-5′-methacryloylamidophenyl)-5-methoxybenzotriazole, 2-(2′-hydroxy-5′-methacryloylamidophenyl) 2-(2′-hydroxy-5′-methacryloyloxypropylphenyl)benzotriazole, 2-(2′-hydroxy-5′-methacryloylpropyl-3′-tert-butyl-phenyl)-5-methoxy-2H-benzotriazole, 2-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)phenoxy)ethyl methacrylate, 2-[3′-tert-butyl-2′-hydroxy-5′-(3′-methacryloyloxypropyl)phenyl]-5-chlorobenzotriazole, 2-{2′-hydroxy-3′-tert-butyl-5′-[3′-methacryloyl] [Oxypropoxy]phenyl}-5-methoxy-2H-benzotriazole, 2-[3′-tert-butyl-5′-(3″-dimethylvinylsilylpropoxy)-2′-hydroxyphenyl]-5-methoxybenzotriazole, 2-(tert-butyl)-6-(5-chloro-2H-benzo[d][1,2,3]triazol-2-yl)-4-vinylphenol, 2-(2H-1,2,3-benzotriazol-2-yl)-4-methyl-6-(2-methylprop-2-enyl)phenol, 2-(3-acetyl-2-aminophenoxy)ethyl methacrylate, 2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate, or combinations thereof.

[0331] Preferred UV absorbers are selected from 2-[3′-2′H-benzotriazol-2′-yl)-4′-hydroxyphenyl]ethyl methacrylate (BTPEM), 2-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2-benzotriazolyl)phenoxy)ethyl methacrylate, 3-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2-benzotriazolyl)phenoxy)propyl methacrylate, and 3-(3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl)propyl methacrylate, which can be polymerized with monomers according to formula (1), (2), (3), (4) or (5).

[0332] The suitable crosslinking agent for the polymeric optical material used to construct the artificial lens (contact lens or IOL) is selected from copolymers containing monomers of formula (1), (2), (3), (4), or (5) of polyethylene glycol diacrylate, poly(ethylene glycol) dimethacrylate, ethylene glycol dimethacrylate (EGDMA), ethylene glycol diacrylate, 1,3-propanediol diacrylate, 1,6-hexanediol diacrylate, 1,8-octanediol diacrylate, 1,11-undecanediol diacrylate, 1,12-dodecyl Diacrylates, 1,15-pentadecanediol diacrylate, 1,16-hexadecanediol diacrylate, 1,18-octadecanediol diacrylate, 1,3-propanediol dimethacrylate, 1,6-hexanediol dimethacrylate, 1,8-octanediol dimethacrylate, 1,11-undecanediol dimethacrylate, 1,12-dodecyl dimethacrylate, 1,15-pentadecanediol dimethacrylate, 1,16-hexadecanediol dimethacrylate, 1,18-octadecanediol dimethacrylate.

[0333] If a higher refractive index is required, a wavelength from another region can be applied to an artificial lens (contact lens or IOL) made of one or more polymers capable of altering polarization. 400-590 nm can be used, preferably 500-580 nm, and most preferably 530-570 nm.

[0334] In the following, the optical material to be used in the artificial lens according to the method of the present invention, preferably a polymeric optical material for contact lenses or IOLs, is further and preferably described in the wavelength region of 400nm-590nm, preferably 500nm-580nm, and particularly preferably 530nm-570nm to locally improve the polarization of the material.

[0335] To apply such adjustment, the refractive index of polymer optical materials is in the range of 1.45–1.60.

[0336] The polymer optical material (contact lens or IOL) of the intraocular lens used for the adjustment may optionally contain ultraviolet light blocking agents or blue light absorbers as described above.

[0337] The polymeric optical material for the artificial lens used in the method according to the invention comprises a polymer matrix containing covalently bonded dimerized photoactive units, preferably in an amount of at least 2 wt% to 100 wt%, preferably 5 wt% to 90 wt%, and most preferably 7 wt% to 80 wt%.

[0338] The dimerized photoactive units within the polymer matrix can be the same or different.

[0339] The polymer matrix of the polymeric optical material used for the adjustment of the intraocular lens and / or IOL can be derived from homopolymers or copolymers, preferably copolymer matrices.

[0340] The polymer matrix containing the dimerized photoactive unit may be a matrix derived from a silicon-containing polymer, an acrylic polymer, a methacrylic polymer, or a mixture thereof.

[0341] Dimerized photoactive units refer to photochemically active units that are photochemically active in the 400nm-590nm wavelength region described above or preferably previously as described, under two-photon or multi-photon process effects.

[0342] The polymer matrix of the polymer optical material used for the adjustment of the lens and / or IOL contains dimerized photoactive units that are capable of separation under the effects of two-photon or generally multiphoton processes.

[0343] Therefore, the present invention further relates to a method for adjusting the polarization of an intraocular lens (preferably at one or more specific locations of the lens) comprising a body formed of a polymer optical material, wherein the polymer optical material of the intraocular lens comprises a polymer matrix containing covalently bonded dimerized photoactive units as the sole photoactive units capable of being separated under the effects of two-photon or generally multiphoton processes.

[0344] Preferably, the dimerized photoactive unit comprises a cyclobutane ring, which will split under the effect of a two-photon or generally multiphoton process.

[0345] Alternatively, the dimerized photoactive unit particularly preferably comprises a cyclobutane ring, which is capable of splitting under the effect of a two-photon or generally multiphoton process.

[0346] Therefore, the present invention further relates to a method for adjusting the polarization of an intraocular lens (preferably at one or more specific locations of the lens) comprising a body formed of a polymer optical material, wherein the polymer optical material of the intraocular lens comprises a polymer matrix containing covalently bonded dimerized photoactive units, which contain a cyclobutane ring as the sole photoactive unit, capable of splitting under the effect of a two-photon or generally multiphoton process.

[0347] The splitting of the dimerized photoactive unit containing the cyclobutane ring is visualized in Scheme 1 as described above.

[0348] In a preferred embodiment of the invention, the polymeric optical material containing a polymer matrix comprising a dimerized photoactive unit of an intraocular lens to be used in the method according to the invention is derived from monomers of formula (1), (2), (3), (4) or (5) as described above or preferably previously described.

[0349] In a further embodiment of the invention, the polymeric optical material containing a polymer matrix comprising a dimerized photoactive unit of an intraocular lens to be used in the method according to the invention is derived from monomers selected from compounds (M-1) to (M-68) and (A-01) to (A-16) as described above.

[0350] In a further very preferred embodiment of the invention, the polymer matrix of the polymer optical material to be used in the method according to the invention is a copolymer matrix of monomers containing dimerized photoactive units as described above or preferably previously described, or a compound derived from the polymers of formulas (1) to (5) as described above, or a monomer derived from polymers (M-1) to (M-68) and (A-01) to (A-16) and other polymers known in the art.

[0351] Examples of monomers, UV absorbers, and crosslinking agents are as described above and are therefore applicable to polymeric optical materials containing dimerized photoactive units as described above or preferably described above.

[0352] In manufacturing an artificial lens intended for use in the method according to the invention, the polymer matrix comprising partially or fully dimerized photoactive units may be formed via single-photon or two-photon or generally multi-photon absorption of photoactive units that are dimerized by forming cyclobutane rings via [2π+2π] cycloaddition, as previously described or preferably previously described.

[0353] If the method according to the invention is applied to the eye, two-photon (or usually multi-photon) absorption can be used.

[0354] In order to produce an artificial lens comprising a polymer optical material containing a polymer matrix for use in the method according to the invention, the polymer matrix comprises partially or fully dimerized photoactive units that can be absorbed by two-photon (or generally multi-photon) or single-photon irradiation by any means of illumination (e.g., a UV lamp with a special wavelength filter, a UV LED with one of the wavelengths given above, or a laser with the wavelengths given above).

[0355] In order to produce an artificial lens comprising a polymer optical material containing a polymer matrix for use in the method according to the invention, the polymer matrix comprises partially or fully dimerized photoactive units, preferably using single-photon absorption by any irradiation method (e.g., a UV lamp with a specific wavelength filter, a UV LED having one of the wavelengths given above, or a laser having one of the wavelengths given above).

[0356] To manufacture an intraocular lens comprising a polymer optical material containing a polymer matrix, which contains partially or fully dimerized photoactive units, for use in the method according to the invention, the same irradiation source as previously described for the system according to the invention can be used, by doubling the frequency of the feed laser, or an optical power amplifier can be used, or another irradiation source can be used. Preferably, the other irradiation source is used to manufacture the intraocular lens.

[0357] The present invention further relates to a method for adjusting the polarization degree of an artificial lens comprising a body formed of a polymer optical material based on a two- or multi-photon absorption process, the method comprising the following steps:

[0358] Provide the aforementioned intraocular lens; and

[0359] The polarization degree of the lens is adjusted by irradiating the lens using a system as described above or preferably previously described.

[0360] The provided intraocular lens comprises a polymer matrix containing covalently bonded photoactive units, which contain non-aromatic double bonds capable of dimerizing via [2π+2π] cycloaddition to form a cyclobutane ring, as described above or preferably previously.

[0361] as well as

[0362] The provided intraocular lens is irradiated with an illumination beam of the first wavelength, the irradiation causing dimerization of the photoactive units, thereby reducing the polarization degree of the intraocular lens and thus modifying the provided intraocular lens, wherein the modified intraocular lens comprises a polymer matrix containing partially or fully dimerized photoactive units derived from the [2π+2π] cycloaddition, and

[0363] Optionally, the modified intraocular lens is irradiated with the second wavelength of the irradiation beam to locally increase the polarization degree of the modified intraocular lens by partially splitting the dimerized photoactive units.

[0364] The present invention further relates to a method for adjusting the polarization degree of an artificial lens comprising a body formed of a polymer optical material based on a two- or multi-photon absorption process, the method comprising the following steps:

[0365] Provide the aforementioned intraocular lens; and

[0366] The polarization degree of the lens is adjusted by irradiating the lens using a system as described above or preferably previously described.

[0367] The provided intraocular lens comprises a polymer matrix containing covalently bonded dimerized photoactive units, which are the sole photoactive units capable of being separated under the effects of two-photon or generally multiphoton processes as described above or preferably previously.

[0368] The provided intraocular lens is irradiated with the second wavelength of the irradiation beam, which causes the separation of the dimerized photoactive units, thereby increasing the polarization degree of the intraocular lens and thus modifying the provided intraocular lens, wherein the modified intraocular lens comprises a polymer matrix containing photoactive units capable of re-dimerization and

[0369] Optionally, the modified intraocular lens is irradiated with the first wavelength of the irradiation beam to locally reduce the polarization degree of the modified intraocular lens by partially dimerizing the photoactive unit.

[0370] The present invention further relates to a method for adjusting the polarization degree of an artificial lens comprising a body formed of a polymer optical material based on a two- or multi-photon absorption process, the method comprising the following steps:

[0371] Provide the aforementioned intraocular lens; and

[0372] The polarization degree of the lens is adjusted by irradiating the lens using a system as described above or preferably previously described.

[0373] The provided intraocular lens comprises a polymer matrix containing covalently bonded photoactive units. These photoactive units contain non-aromatic double bonds capable of dimerizing with the previously described or preferably previously described pre-dimerized photoactive units through a two-photon or multi-photon process via [2π+2π] cycloaddition to form a cyclobutane ring.

[0374] The provided intraocular lens is irradiated with an illumination beam of the first wavelength, which causes the photoactive units to dimerize, thereby reducing the polarization degree of the intraocular lens and thus modifying the provided intraocular lens in that the modified intraocular lens comprises a polymer matrix containing more dimerized photoactive units derived from the [2π+2π] cycloaddition, or

[0375] The provided intraocular lens is irradiated with the second wavelength of the irradiation beam, which causes the separation of the dimerized photoactive units, thereby increasing the polarization degree of the intraocular lens and thus modifying the provided intraocular lens, wherein the modified intraocular lens comprises a polymer matrix containing more photoactive units that can dimerize by forming cyclobutane rings via [2π+2π] cycloaddition.

[0376] The present invention further relates to a method for locally adjusting the polarization of an intraocular lens comprising, as described above or preferably previously described, a polymer optical material disposed within a patient's eye, the method comprising:

[0377] The intraocular lens was exposed to an illumination beam with wavelengths between 600 nm and 800 nm to locally reduce the polarization of the intraocular lens.

[0378] The intraocular lens is exposed to an illumination beam with wavelengths between 400 nm and 590 nm to locally increase the polarization of the intraocular lens, preferably using the system and / or method described above.

[0379] The present invention further relates to a method for locally adjusting the polarization of an intraocular lens comprising, as described above or preferably previously described, a polymer optical material disposed within a patient's eye, the method comprising:

[0380] The intraocular lens is exposed to a first illumination beam having a first wavelength between 600 nm and 800 nm to locally reduce the polarization of the intraocular lens; and

[0381] The intraocular lens is exposed to a second illumination beam having a second wavelength between 400 nm and 590 nm to locally increase the polarization of the intraocular lens, thereby preferably using the system and / or method as described above.

[0382] The present invention further relates to a method for locally adjusting the polarization of an intraocular lens disposed within a patient's eye, comprising a polymer optical material as described above or preferably previously described, wherein the exposure of the intraocular lens comprises scanning the illumination beam across the intraocular lens based on input data, the input data being related to: lens data associated with the intraocular lens, particularly related to the polymer optical material, and / or processing plan data related to a processing plan for processing the intraocular lens based on the exposure of the intraocular lens to the illumination beam.

[0383] The present invention further relates to a method for locally adjusting the polarization of an intraocular lens disposed within a patient's eye and comprising a polymer optical material as described above or preferably previously described, wherein the lens data includes data relating to one or more of the following: the dimensions of the intraocular lens (e.g., diameter and / or thickness), the material comprising the intraocular lens as described above or preferably previously described, particularly a polymer optical material, the refractive index of the intraocular lens, and a mapping of the refractive index of the specific location / coordinates of the intraocular lens.

[0384] The present invention further relates to a method for locally adjusting the polarization of an intraocular lens disposed within a patient's eye, comprising a polymer optical material as described above or preferably previously described, wherein the processing plan data comprises one or more of the following:

[0385] Scanning strategy control command data for the scanning strategy of the illumination beam used to scan across the intraocular lens (e.g., scan mode and / or scan sequence and / or scan speed and / or scan duration of the scan mode and / or scan duration of the scan sequence and / or pulse duration of the pulses of the first and / or second wavelength illumination beam and / or illumination beam characteristics and / or illumination (photon) density and / or illumination intensity and / or illumination power and / or illumination wavelength).

[0386] Temperature data of the current and / or predicted temperature of the intraocular lens during the exposure period.

[0387] The refractive index data to be obtained based on the exposure of the intraocular lens, the refractive index to be obtained being particularly related to the mapping of the refractive index of the specific location / coordinates of the intraocular lens,

[0388] Breakage dimension data of the breakage dimension.

[0389] Eye data related to the dimensions and / or shape of the patient's eyes.

[0390] Positioning data related to the position and / or orientation of the intraocular lens relative to the eye, and

[0391] Registration data related to the patient's identity and / or the patient's specific eye.

[0392] The present invention further relates to a method for locally adjusting the polarization of an intraocular lens comprising a polymer optical material as described above or preferably previously described, disposed within a patient's eye, wherein the exposure of the intraocular lens to the irradiation beam comprises exposing a first volume of the intraocular lens and then exposing a second volume of the intraocular lens, wherein the first volume is further away from the cornea of ​​the patient's eye than the second volume.

[0393] The present invention further relates to a method for locally adjusting the polarization of an intraocular lens comprising a polymer optical material as described above or preferably previously described, disposed within a patient's eye, wherein the (first) wavelength is between 650 nm and 750 nm, preferably between 670 nm and 720 nm, and more preferably between 680 nm and 710 nm.

[0394] The present invention further relates to a method for locally adjusting the polarization of an intraocular lens comprising a polymer optical material as described above or preferably previously described, disposed within a patient's eye, wherein the (second) wavelength is between 500 nm and 580 nm, preferably between 530 nm and 570 nm.

[0395] In the above entries, the initial step of the method may be to provide the intraocular lens.

[0396] In one example, the exposure of the intraocular lens to the irradiation beam comprises exposing a first volume and / or plane and / or location of the intraocular lens, followed by exposing a second volume and / or plane and / or location of the intraocular lens, wherein the first volume and / or plane and / or location is more distant from the cornea of ​​the patient's eye than the second volume and / or plane and / or location, and the volume and / or plane and / or location irradiated at a later time point in the irradiation sequence may be closer to the cornea than the volume and / or plane and / or location irradiated at an earlier time point. Here, the volume may be associated with one or more planes of the intraocular lens.

[0397] The lens data and processing plan data are preferably those described above and are part of a system preferred for use in a method described above for locally adjusting the polarization of an intraocular lens containing the polymer optical material described above or preferably described above, disposed within a patient's eye.

[0398] The present invention further relates to a method for correcting the vision of a patient by modifying the refractive index of an intraocular lens comprising a polymer optical material as described above or preferably previously described, including...

[0399] Confirm and measure the degree of visual correction for the patient;

[0400] Determine the location and type of the refractive structure to be implanted into the intraocular lens to correct the patient's vision; and

[0401] The intraocular lens is then exposed to two-photon or multi-photon irradiation with wavelengths between 600 nm and 800 nm to locally reduce the polarization of the intraocular lens, and / or

[0402] The intraocular lens is then exposed to two-photon or multi-photon irradiation with wavelengths between 400 nm and 590 nm to locally increase the polarization of the intraocular lens, preferably by using the system and / or method described above to expose the intraocular lens to the irradiation.

[0403] As mentioned above, a change in polarization leads to a change in refractive index, as will be described in more detail below.

[0404] The speed of light in a vacuum, c0, is a fundamental constant and describes the speed of electromagnetic waves in a vacuum. According to the solutions to Maxwell's equations, the speed of light in a vacuum can be related to the electrical constant ε0 and the magnetic constant μ0. These are also fundamental constants.

[0405]

[0406] When light passes through a transparent medium c m Its speed in time is less than its speed in a vacuum. The electrical constant needs to be replaced by the permittivity ε and the magnetic constant needs to be replaced by the permeability μ.

[0407]

[0408] Relative permittivity ε r (Also known as dielectric constant) is a dimensionless, material-dependent parameter that gives the permittivity relative to the electrical constant. Therefore, the relative permittivity ε of vacuum... r =1, which can also be seen by comparing the two equations above. The actual permittivity is obtained by multiplying the relative permittivity by ε0.

[0409] ε=ε0ε r =(1+χ) e )ε0

[0410] Where χ e Let be the polarizability of the material, a property related to ε. r Closely related values ​​and defined as

[0411] χ e =ε r -1

[0412] Relative permittivity describes how the strength of an electric field decreases when a material (also called a dielectric) is placed in an electric field. Relative permittivity depends on the material's ability to polarize in response to an electric field, thus reducing the overall electric field within the material. Most materials have a relative permittivity between 1 and 100, but ε is also known. r Dielectrics with a relative permittivity as high as 10,000. For example, the relative permittivity of polystyrene, cellulose, and water are 2.5, 4.5, and 81, respectively. The relative permittivity of air can be considered as 1 (a good approximation). Generally, relative permittivity is not constant because it varies with the frequency of the applied electric field, humidity, temperature, and other parameters. In nonlinear media, permittivity can depend on the electric field strength. Therefore, ε... r The outdated term "dielectric constant" is vague and should no longer be used.

[0413] For magnetic field values ​​μ0, μ r The definition of μ is similar to that of the corresponding electric field value. Magnetic permeability is...

[0414] μ=μ0μ r

[0415] And the magnetic susceptibility is

[0416] χ m =μ r -1

[0417] By definition, the relative permeability μ of vacuum r =1. Relative permittivity varies with magnetic field strength and is generally a function of frequency. The relative permeability of a material can also be negative. Distinguishing diamagnetic materials (μ... r <1), paramagnetic substances (μ r >1) and ferromagnetic materials (μ r >>1). Most organic materials, such as polymers, are diamagnetic and their relative permeability is very close to 1.

[0418] The refractive index *n* is a material constant that characterizes the refractive properties of a medium. As previously introduced, the refractive index is the ratio of the speed of light in a vacuum to the speed of light in a given medium. Therefore, the refractive index of a vacuum is 1. The refractive index of water is 1.333. The refractive indices of commercially available glassware range from 1.4 to 1.9. Most organic polymers have refractive indices between 1.4 and 1.6, with specially modified high-refractive-index polymers having refractive indices greater than 1.7. The refractive index largely depends on the frequency of light, a phenomenon known as dispersion. Since the refractive index of dry air (n) is... air (≈1.0003) differs only slightly from 1 and can be measured relative to air to obtain a good approximation. In technical optics, the refractive index n is used. 0 It is defined as

[0419]

[0420] The following relation can be obtained.

[0421]

[0422] Because for organic polymers, μ in the visible part of the electromagnetic spectrum r ≈1, this equation can be further simplified to

[0423]

[0424] This indicates that the refractive index of the polymer / copolymer is related to its relative permittivity ε. r Changes occur when the refractive index changes. To understand how the relative permittivity of polymers / copolymers and thus their refractive index can be modified, it is necessary to observe more closely what happens when light waves interact with matter. If an electric field is present, in this case, the electric component of the light wave... Acting on the medium, it induces a dipole moment. polarity Defined as the electric dipole density per unit volume.

[0425]

[0426] vector The norm of the region density σ of polar charge is p .

[0427]

[0428] polar vector and external electric field vector Pointing in the same direction. Polar charges. The induced electric flux lines travel from the positive to the negative surface charges of the dielectric. Therefore, the electric flux lines within the dielectric travel to the point where they interact with the external electric field. The electric flux lines are in the opposite direction. Polarity in the electric field. Given from the following

[0429]

[0430] Electroscalability was defined earlier. It is necessary to distinguish between two types of polarity: displacement polarity and orientation polarity. Displacement polarity arises from the displacement of charges in neutral atoms or molecules relative to each other. It is the relative tendency of charge distribution, like the electron cloud of an atom or molecule being deformed from its normal shape by an external electric field, i.e., the electric field induces an electric dipole moment. Orientation polarization arises from the orientation of permanent dipoles along electric field lines. These dipoles are present in the medium even before the electric field is applied. In the visible spectrum, only the orientation polarization of electrons should be considered. Visible light has relatively high frequencies, ranging from about 10⁻⁶ Hz.14 Hz to 10 15 Hz. Therefore, the factors affecting the overall polarization caused by the displacement of atoms and the orientation of permanent dipoles are so small that they can be ignored. Only electrons can "obey" the rapidly oscillating electric field. For displacement polarity, the equation...

[0431]

[0432] This provides the relationship between the number of particles per unit volume, *x*, and polarization. The proportionality constant α in this equation is called the polarizability. Polarizability is a molecular parameter. Quantum particles are not rigidly connected to each other; they are bound to their rest positions by a force of first approximation elasticity. Therefore, Newton's law F = -kx applies. External electric field A force Q·E is applied to a charge Q. This force causes the charge to deflect a distance x = F / k = QE / k.

[0433] Such displacement produces an induced dipole moment.

[0434]

[0435] It is easy to see by comparison that α must be proportional to ε. r .

[0436] α∝(ε r -1)ε0

[0437] This means that changing the polarization of molecules containing a given medium results in a change in the refractive index of that medium.

[0438] It should be noted that variations of the embodiments described in this invention are all included within the scope of protection of this invention. Unless expressly excluded, any feature disclosed in this invention may be interchanged with a substitute feature for the same, equivalent, or similar purpose. Therefore, any feature disclosed in this invention, unless otherwise stated, should be considered as an example of a general series or an equivalent or similar feature.

[0439] All features of this invention can be combined with each other in any way, unless certain features and / or steps are mutually exclusive. This is especially true for preferred features of the invention. Similarly, features that are not necessarily combined can be used alone (rather than in combination).

[0440] It should also be noted that many features of the present invention, especially those of the preferred embodiments, are inventive in themselves and should not be considered merely as embodiments of the present invention. Independent protection may be sought for these features, in addition to or as an alternative to any currently claimed invention.

[0441] The technical teachings disclosed in this invention can be extracted and combined with other examples.

[0442] Undoubtedly, those skilled in the art will conceive of many other effective alternatives. It should be understood that the invention is not limited to the described embodiments and includes modifications that are obvious to those skilled in the art and fall within the scope of the appended claims. Example

[0443] The present invention is described in detail through the following embodiments, but is not intended to limit the invention.

[0444] The following embodiments are also included in this disclosure and may be incorporated, in whole or in part, into the embodiments and general disclosure of the present invention.

[0445] In single-photon experiments, UV / Vis spectroscopy is performed by placing a cuvette containing a dissolved sample on a sample holder and then irradiating the cuvette. Changes in the UV / Vis spectrum over time are monitored by UV / Vis measurements, for example, using a Lambda 900 UV / Vis spectrometer (manufactured by Perkin Elmer).

[0446] The refractive index manipulation in the single-photon experiment described below is performed by placing the sample on a sample holder and preferably irradiating the sample for 30 seconds. The resulting change in refractive index over time is monitored by refractive index measurements. The change in refractive index is measured using a multi-wavelength refractometer (ATR-L from Schmidt & Haensch).

[0447] Single-photon experiments demonstrate the ability of the described polymeric optical material to be used in an artificial lens according to the method of the invention to locally alter the initial polarization by irradiating it with specific first and second wavelengths to induce, for example, [2π+2π] cycloaddition or ring splitting as described above or below.

[0448] Alternatively, the intraocular lens may be treated using a multiphoton (e.g., two-photon) based process, as further described in Examples 14 to 19 below.

[0449] Example:

[0450] Example 1: Preparation of poly(M-14):

[0451] 1 g of M-14 was first dissolved in 10 mL of chloroform. The solution was then degassed and 1.33 mg of AIBN was added. The mixture was then stirred at 60 °C for 14 h. The polymer was then precipitated in 250 mL of methanol. The resulting polymer (M-14) was then dried.

[0452] Example 2:

[0453] In the second embodiment, a solution of 75.4 mg of poly(M-14) in 10 mL of THF was prepared. This solution was diluted 500-fold. The diluted solution was then filled into a quartz glass cuvette (32 / GL14 / S / Q / 10, obtained from STARNA, with a path length of 10 mm). UV / Vis spectra were obtained using a Lambda 900 UV / Vis spectrometer (obtained from Perkin Elmer). The sample was alternately irradiated at 340 nm, and UV / Vis spectra were obtained. The results were plotted on... Figure 12 The diagram shows absorption as a function of the wavelength used in the single-photon process.

[0454] Figure 12 There are three isoextinction points. This indicates a controlled transformation. The photochemical reaction exhibited by the transformation is a [2π+2π] cycloaddition, as shown in... Figure 8 This resulted in cross-linked polymers. The dimerization of the photoactive units was indicated by a decreasing signal at 332 nm. The signal intensity increased in the range of 260 nm–275 nm.

[0455] The reaction mixture was dried and analyzed by NMR.

[0456] 1 H NMR (500MHz, CDCl3) δ7.45, 7.17, 7.08-7.03, 7.01-6.96, 6.84, 6.75, 6.61, 6.52, 4.96, 4.72, 4.0 6, 3.95-3.87, 2.58, 2.54-2.47, 2.36, 1.76, 1.71-1.56, 1.49-1.44, 1.37-1.24, 1.14, 0.93-0.84.

[0457] The 1 The singlet states at 4.72 and 4.96 ppm in the 1H NMR spectrum are attributed to the cyclobutane ring formed via the aforementioned photochemical [2π+2π] cycloaddition reaction. Both signals are attributed to the formation of a photodimer mixture consisting of cis and trans arrangements, respectively, head-to-head and head-to-tail. The NMR signals and conclusions are consistent with those in the literature [Rao et al., Chem. Ber., 1973, 106(2), 388].

[0458] Example 3:

[0459] In the third embodiment, poly(M-14) prepared according to Example 2 was used for irradiation. UV / Vis spectra were taken. Samples were alternately irradiated at 275 nm and with UV / Vis spectra. The results were plotted on... Figure 13 The diagram shows absorption as a function of the wavelength used in the single-photon process.

[0460] The experiment demonstrated the ability of representative polymer optical materials to split dimerized photoactive units.

[0461] The amount of cyclobutane moiety within the crosslinked poly(M-14) is reduced. The mechanism of this splitting is shown in... Figure 9 The return conversion is indicated by an increased signal at 332nm.

[0462] The reaction mixture was dried and analyzed by NMR.

[0463] 1 H NMR (500MHz, CDCl3) δ7.67, 7.40, 7.20-7.14, 6.86, 4.11-4.00, 2.69-2.62, 2.36, 1.87-1.78, 1.65, 1.53-1.41, 1.40-1.26, 1.14, 0.91.

[0464] As can be further seen, as in Example 2 1 The disappearance of the singlet state at 4.74 and 4.98 ppm, previously attributed to a photoinduced photochemical [2π+2π] cycloaddition reaction, as confirmed by 1H NMR spectroscopy, records a splitting, as shown in the image. Figure 9 As shown.

[0465] Example 4:

[0466] In the fourth embodiment, a polymer optical material having a copolymer matrix is ​​prepared.

[0467] A molten mixture of 2.00 g M-14, 10.36 mg 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate, 220.00 mg poly(ethylene glycol) diacrylate (average Mn250), and 247.60 mg n-butyl methacrylate was first degassed. Then, 25.57 mg 1,1′-(3,3,5-trimethylcyclohexylene)bis[2-(1,1-dimethylethyl)peroxide was added. The mixture was filtered to form a 1 mm thick sheet. Polymerization occurred thermally under conditions deemed suitable by those skilled in the art. After polymerization, the process was terminated, and the polymer was demolded to produce a 1 mm thick polymer sheet.

[0468] Example 5:

[0469] In the fifth embodiment, a cylindrical blank of the polymer optical material prepared according to Example 4 is stamped into a sheet. A multi-wavelength refractometer with a heating stage is used to determine the refractive index. Before measurement, the blank is heated to 80°C in the apparatus to release stress from the material. In this embodiment, the refractive index measurement is performed at 546 nm and 35°C. The blank outside the refractometer is shown as shown in [the image / image / etc.]. Figure 10 The sample was irradiated at 340 nm in the apparatus. The sample was then transferred back to the refractometer, heated to 80 °C, and the refractive index was measured at 546 nm and 35 °C. Figure 14 The change in refractive index as a function of the applied energy is shown for the single-photon process.

[0470] As the applied energy increases, the refractive index of the irradiated polymer optical material decreases. This is due to the following... Figure 8 This is caused by a cross-linking reaction. (As shown in...) Figure 8 The cycloaddition reaction produces a photoactive unit with lower polarization (cyclobutane ring), which reduces the refractive index.

[0471] The sample irradiated at 340 nm was further used in the procedure described herein, but with an irradiation wavelength of 275 nm.

[0472] Shown Figure 15 The effect is caused by the splitting or reversion of the cyclobutane moiety (see [link]). Figure 9 This results in a higher degree of polarization and an increased refractive index. Figure 15 The change in refractive index as a function of the applied energy is shown for the single-photon process.

[0473] Figure 10 The system (400) associated with the illumination setup using an LED system for single-photon experiments as described above is shown.

[0474] The system (400) includes an irradiation source (402), a beam collimator (404), and a sample holder (408) on which a sample (406) is mounted.

[0475] In this embodiment 5, the irradiation source (402) is Thorlabs' Mounted LED M340L4-340nm, 53mW.

[0476] Examples 6-10 were carried out in a similar manner to Examples 1-5 described above.

[0477] Example 6: Preparation of poly(M-18).

[0478] Dissolve 1 g of M-18 in 10 mL of chloroform. Degas the solution and add 1.33 mg of AIBN. Stir the mixture at 60 °C for 14 h. Allow the polymer to precipitate in 250 mL of methanol. Dry the resulting polymer (M-18).

[0479] Example 7:

[0480] In the seventh embodiment, a solution of 12.67 mg of poly(M-18) in 25 mL of THF was prepared. This solution was diluted 20-fold. The diluted solution was then poured into a quartz glass cuvette. UV / Vis spectra were obtained. The sample was alternately irradiated at 340 nm, and UV / Vis spectra were acquired. The results are shown below. Figure 16 . Figure 16 The absorption of the single-photon process as a function of wavelength is shown.

[0481] Example 8:

[0482] In the eighth embodiment, an irradiated sample of poly(M-18) according to Example 7 was used. UV / Vis spectra were obtained. The sample was further irradiated at 275 nm, and UV / Vis spectra were obtained alternately. The results are shown in... Figure 17 . Figure 17 The absorption of the single-photon process as a function of wavelength is shown.

[0483] Example 9:

[0484] In the ninth embodiment, a second polymer optical material having a copolymer matrix is ​​prepared.

[0485] A molten mixture of 2.00 g M-18, 9.08 mg 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate, 65.8 mg ethylene glycol diacrylate, 211.7 mg 2-hydroxyethyl methacrylate, and 173.92 mg octadecyl 2-methacrylate was degassed. Then, 26.42 mg 1,1′-(3,3,5-trimethylcyclohexylene)bis[2-(1,1-dimethylethyl)peroxide was added. The mixture was filtered to form a 1 mm thick sheet. Polymerization was carried out thermally under conditions deemed suitable by those skilled in the art. After polymerization, the process was terminated, and the polymer was demolded to produce a 1 mm thick polymer sheet.

[0486] Example 10:

[0487] In the tenth embodiment, a cylindrical blank of ophthalmic material prepared according to Example 9 was stamped into a sheet. A multi-wavelength refractometer with a heating stage was used to determine the refractive index. Before measurement, the sample was heated to 80°C in the apparatus to release stress from the material. The refractive index was measured at 546 nm and 35°C. The sample was alternately irradiated at 340 nm, returned to the refractometer, heated to 80°C, and the refractive index was measured at 546 nm and 35°C. The results are shown in... Figure 18 .therefore, Figure 18 The change in refractive index as a function of the applied energy is shown for the single-photon process.

[0488] The sample irradiated at 340 nm was further used in the procedure described herein, but with an irradiation wavelength of 275 nm. (Shown...) Figure 19 The effect arises from the splitting or reversion of the cyclobutane moiety (see [link]). Figure 9 ). Figure 19 The change in refractive index as a function of the applied energy is shown for the single-photon process.

[0489] Examples 11-13:

[0490] Examples 11-13 below illustrate the refractive index changes of polymeric optical materials having the amounts shown in the table below and based on the formulation described in Example 9, after single-photon process irradiation:

[0491]

[0492] Examples of irradiation using two-photon / multiphoton absorption:

[0493] Example 14:

[0494] The experimental apparatus used in Example 14 is shown in Figure 11 .

[0495] For Figure 11 The system (410) for the two-photon experiment incorporates a tunable laser (412) (Ti: sapphire laser (Chameleon Ultra II, obtained from Coherent, Santa Clara, CA, USA) as the irradiation source, which is configured to generate pulsed laser irradiation. The irradiation beam is spread in a beam shaper (414).

[0496] The pulsed laser generated by the laser source (412) is then transmitted to the microscope objective (416) (LUCPLFLN, obtained from Olympus) to produce a focused laser output.

[0497] The region of the polymer optical material (sample 418) whose refractive index to be changed is transmitted via a voice coil driven linear stage (422) (obtained from...). ) is designated as the target, which is used to position the sample holder (420).

[0498] The polymer sample (418) here is a flat button with a diameter of 6.0 mm, which is described below as a polymer optical material.

[0499] All polymers in the polymer samples are copolymers containing at least a crosslinking agent. The main monomers for each button material used in the manufacture of polymeric optical materials comprising a copolymer matrix are summarized in the table below:

[0500]

[0501]

[0502] During the irradiation process, the flat button, which is the polymer material as described above, serving as the polymer sample (418), is positioned in a fixed location within the sample holder (420). A coupling gel (Vidisic [Bausch & Lomb]) is applied to the button. The sample holder (420) is mounted horizontally, and a laser pulse is focused onto the material using a high numerical aperture microscope objective. This approximately creates a refractive index profile near the surface. This mimics a bottom-up and point-to-point process.

[0503] The sample holder (420) is driven by a voice coil linear stage (422) as described above. This mimics the movement of a scanner.

[0504] Typical laser parameters are a 680 nm wavelength, a 180 fs pulse duration, and an average power of 500 mW. The varying parameters are the scan rate and the x-spacing between the layers. These three parameters are adjusted to produce a uniform solid-state refractive index profile. Changes in refractive index are measured using a multi-wavelength refractometer (ATR-L, from Schmidt & Haensch).

[0505] The results of the two-photon laser experiment are related to the refractive index of the electromagnetic energy input dependent on the refractive index diagram of the single-photon experiment.

[0506] Example 15:

[0507] In the fifteenth embodiment, a solution of 288 mg of poly(M-14) (Example 1) in 4 mL of acetonitrile was prepared. The solution was filled into a quartz glass cuvette (32 / GL14 / S / Q / 10, obtained from STARNA, with a path length of 10 mm). The cuvette containing the poly(M-14) liquid solution was irradiated with a 1 μJ pulse at a wavelength of 680 nm with a repetition rate at 100 kHz using an NA 0.1 microscope objective. The fluorescence generated by two photons of the solution was measured as a function of irradiation time using the pulsed irradiation source described earlier. Fluorescence was measured at 90-degree geometry using a fiber-coupled spectrometer with a sensitivity of 350 to 1050 nm and a diffraction grating-based spectrometer. The fluorescence spectra with increasing irradiation time were compiled in […]. Figure 20 The two-photon-induced [2π+2π] ring dimerization of the photoactive unit is represented by a decreasing signal between 400 and 500 nm. The emission peak decreases due to the conversion to a non-fluorescent dimer in poly(M-14).

[0508] The reaction mixture was dried and analyzed by NMR in d-chloroform. Singlet states at 4.74 and 4.98 ppm were attributed to the cyclobutane ring formed via the two-photon-induced photochemical [2π+2π] cycloaddition reaction. The NMR spectra were correlated with those of Example 2. Both the single-photon and two-photon-induced photochemical [2π+2π] cycloaddition reactions produced the same product.

[0509] Example 16:

[0510] In the sixteenth embodiment, the irradiated poly(M-14) prepared according to Example 14 was used as an acetonitrile solution (4 mL) in a quartz glass cuvette (32 / GL14 / S / Q / 10, obtained from STARNA, with a path length of 10 mm). The solution was irradiated with a 1 μJ pulse at a wavelength of 532 nm using a NA 0.1 microscope objective at a repetition rate of 100 kHz. The amount of cyclobutane moiety in the substrate decreased over time during laser irradiation, which was attributed to a two-photon-induced photochemical [2π+2π] ring-breaking reaction.

[0511] The reaction mixture was dried and analyzed by NMR in d-chloroform. The singlet state loss of the cyclobutane ring at 4.74 and 4.98 ppm in Experiment 14 was attributed to the formation of the cyclobutane ring via a two-photon-induced photochemical [2π+2π] cycloaddition reaction. The results of the two-photon-induced photochemical [2π+2π] ring-breaking were correlated with the single-photon-induced photochemical [2π+2π] ring-breaking experiment in Example 3.

[0512] Example 17:

[0513] In the seventeenth embodiment, a solution of 288 mg of poly(M-14) from Example 1 in 4 mL of acetonitrile was prepared. The solution was filled into a quartz glass cuvette (32 / GL14 / S / Q / 10, derived from STARNA, with a path length of 10 mm). In this embodiment, the fluorescence generated by two photons from the solution was measured as a function of the irradiation wavelength using a pulsed irradiation source as described earlier. The cuvette containing the liquid solution of poly(M-14) was irradiated with a 1 μJ pulse at a repetition rate of 100 kHz using an NA 0.1 microscope objective. The fluorescence was measured at a 90-degree geometry using a fiber-coupled, diffraction grating-based spectrometer with a sensitivity of 350 to 1050 nm. The peak value of the fluorescence spectrum in the 420–430 nm range was determined for each irradiation wavelength, and then... Figure 21 The value can be plotted as a function of the illumination wavelength. For example, it can be... Figure 21 As observed, two-photon-induced fluorescence exhibits a high value of approximately 680 nm and decreases with increasing irradiation wavelength. Excitation is maximized at a wavelength approximately twice the maximum wavelength of single-photon excitation (340 nm). Such observations are typical for two-photon absorption methods.

[0514] Example 18:

[0515] In the eighteenth embodiment, a polymeric optical material having a copolymer matrix was prepared. A molten mixture of 4.1 g M-14, 21 mg 2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate, 143.6 mg 1,18-octadecanediol diacrylate, and 506.7 mg 2-hydroxyethyl methacrylate was first degassed. Then, 52 mg 1,1′-(3,3,5-trimethylcyclohexylene)bis[2-(1,1-dimethylethyl)peroxide was added. The mixture was filtered to form a 1 mm thick sheet. Polymerization occurred thermally under conditions known in the art. After polymerization, the process was completed, and the polymer was demolded to produce a 1 mm thick polymer sheet. A cylindrical preform of the optical material was punched from the sheet.

[0516] Example 19:

[0517] In the nineteenth embodiment, a cylindrical blank of the optical material prepared according to Example 18 was used. The two-photon-induced photochemical crosslinking reaction of the optical material was demonstrated. Figure 11 The setup shown uses two different illumination sources as described above. One illumination source is in Figure 22 The term "kHz" indicates a femtosecond laser operating at 680 nm and emitting μJ pulses with a repetition rate of 100 kHz. The second irradiation source is... Figure 22 The term "MHz" indicates a femtosecond laser operating at a wavelength of 680 nm and emitting nJ pulses with a repetition rate of 80 MHz. Cylindrical blanks were treated with an average power of 400 mW. After irradiation, for each measurement, the optical path difference across the entire sample was measured using an optical phase-sensitive camera. The refractive index of the material in the irradiated region was derived from the optical path difference and the sample thickness. Figure 22 The refractive index change (Δn) depicted is obtained by comparing the irradiated and unirradiated regions.

[0518] Subsequent data points for radiation exposure values ​​(i.e., applied energy) from low to high were followed by increasing exposure durations, thus demonstrating the cumulative effect of the irradiation treatment. This cumulative effect allows for the accurate translation of physician requirements into appropriate treatment plans.

[0519] Figure 22 The study also revealed a difference in overall system efficiency between kHz and MHz irradiation sources. With all system settings identical, the kHz system exhibited a significantly improved write speed, resulting in shorter and more desirable processing times. These results indicate that the two-photon-induced photochemical [2π+2π]-cyclodimerization reaction is more efficient for the kHz system, consistent with the conclusions drawn from the excited-state lifetimes above.

[0520] Example 20:

[0521] In this embodiment, a cylindrical blank of the optical material prepared according to Example 18 was used. Two-photon-induced photochemical crosslinking of the optical material using different irradiation wavelengths is shown. The irradiation source used was a femtosecond laser tunable between 666 and 722 nm and emitting μJ pulses with a repetition rate of 100 kHz. Figure 11 The setup is shown in the figure. For each measurement, a 1 mm x 6 mm area on the optical material is treated with the same total radiation exposure at an average power of 400 mW. The refractive index of the material in the irradiated area is derived from the optical path difference and the sample thickness. Figure 23 The refractive index change (Δn) shown was obtained by comparing the irradiated and unirradiated regions. Figure 23 The data presented in the paper indicate that the 680-720 nm range can be effectively used to generate refractive index changes in optical materials.

[0522] Figure 24 A selected example of the refractive index distribution written into the optical material during this experiment is shown. In this embodiment, the irradiation source operated at a repetition rate of 100 kHz with 5 μJ pulses at 710 nm. A rectangular area of ​​0.6 mm x 6 mm on the optical material was irradiated with spatially overlapping optical pulses using an optical scanner. Data were collected at 10x magnification using a phase-sensitive camera system mounted on a microscope. The phase-sensitive camera recorded the optical phase difference at a lateral resolution of 30 μm. By taking into account the sample thickness, the recorded values ​​were then converted into refractive index changes. Figure 24 The results show that the refractive index of the irradiated area is reduced by approximately 0.011 compared to the surrounding unirradiated material.

[0523] Attached Figure Index:

[0524] Figure 1 This is a schematic diagram of a system used to irradiate an artificial lens, such as a contact lens or intraocular lens not placed inside a patient's eye.

[0525] Figure 2 This is a schematic diagram of a system for illuminating an intraocular lens placed inside a patient's eye.

[0526] Figure 3 A schematic diagram of the scanning strategy is shown (1500).

[0527] Figure 4 A schematic diagram (1600) shows the variables considered for the scanning procedure when irradiating the lens inside a patient's eye.

[0528] Figure 5A further schematic diagram of a system for illuminating an intraocular lens placed inside a patient's eye is shown.

[0529] Figure 6 A schematic diagram of the components of a system for illuminating an intraocular lens placed inside a patient's eye is shown.

[0530] Figure 7 A schematic diagram of the components of a system for illuminating an intraocular lens placed inside a patient's eye is shown.

[0531] Figure 8 This demonstrates a specific [2π+2π] cycloaddition reaction of poly(M-14).

[0532] Figure 9 This shows the specific splitting of the poly(M-14)-dimer through ring cleavage.

[0533] Figure 10 The irradiation settings for Example 5 are shown.

[0534] Figure 11 An irradiation setup for, for example, Example 14 is shown.

[0535] Figure 12 Absorption as a function of wavelength for single-photon processes is shown, as further described in the experimental section, such as Example 2.

[0536] Figure 13 The absorption as a function of wavelength for a single-photon process, as described in Example 3, is shown.

[0537] Figure 14 The change in refractive index as a function of applied energy is shown in Example 5 for a single-photon process.

[0538] Figure 15 The change in refractive index as a function of applied energy is shown in Example 5 for a single-photon process.

[0539] Figure 16 Absorption as a function of wavelength for a single-photon process is shown, as further described in Example 7.

[0540] Figure 17 The absorption of the solution from Example 7 as a function of wavelength for the single-photon process described in Example 8 is shown.

[0541] Figure 18 The change in refractive index of the bulk polymer of Example 9, which is described in Example 10 for use with respect to a single-photon process as a function of the applied energy, is shown.

[0542] Figure 19 The change in refractive index of the crosslinked dimer of the bulk polymer of Example 9, which includes the polymerized M18, as described in Example 10, is shown as a function of the applied energy in relation to a single-photon process.

[0543] Figure 20 The fluorescence spectrum according to Example 15 under increased irradiation time is shown.

[0544] Figure 21 The peak values ​​of the fluorescence spectrum at 420-430 nm, as a function of the irradiation wavelength, as described in Example 17, are shown.

[0545] Figure 22 The change in refractive index (Δn) as a function of radiation exposure is shown according to Example 19.

[0546] Figure 23 The change in refractive index (Δn) as a function of radiation exposure is shown according to Example 20.

[0547] Figure 24 Selected examples of refractive index distributions written into optical materials during the experiments of Example 20 are shown.

Claims

1. A system for irradiating an intraocular lens, the system comprising: One or more irradiation sources (1) for irradiating the artificial lens (3) with a two-photon or multi-photon beam (2), the irradiation beam (2) being focused by an optical device (16) and having a first wavelength and / or a second wavelength different from the first wavelength. A scanner (4), which is connected to one or more irradiation sources (1) and configured to scan the irradiation beam (2) across the intraocular lens (3), and An input unit (6) connected to the one or more irradiation sources (1) and the scanner (4), wherein the input unit (6) is configured to input data to process the intraocular lens (3) by scanning the irradiation beam (2) across the intraocular lens (3) based on the input data (8), and The first wavelength is between 600 nm and 800 nm to locally reduce the polarization degree of the intraocular lens based on the treatment of the intraocular lens, and The second wavelength is between 400 nm and 590 nm to locally increase the polarization degree of the artificial lens (3) based on the treatment of the artificial lens.

2. The system according to claim 1, wherein the artificial lens (3) is a contact lens or an intraocular lens.

3. The system according to claim 1 or 2, wherein the artificial lens (3) is disposed in the patient's eye.

4. The system according to one or more of claims 1-3, wherein the input data (8) includes lens data (10) of the intraocular lens (3) and / or processing plan data (12) related to the processing plan for the processing of the intraocular lens (3).

5. The system of claim 4, wherein the lens data (10) includes data relating to the irradiation absorption performance of the artificial lens (3), and wherein the system is configured to adjust the first wavelength and / or the second wavelength for the artificial lens to locally change the polarization degree based on a two-photon or multi-photon absorption process.

6. The system according to one or more of claims 2-5, further comprising a positioning system (20) for determining the position of the focal point of the irradiating beam (2) within the patient's eye, The positioning system (20) is connected to the scanner (4), and the scanning of the irradiation beam (2) across the artificial lens (3) by the scanner is based on the position of the focal point of the irradiation beam within the eye.

7. The system according to one or more of claims 2-6, wherein the system is configured to determine the position and / or orientation of the artificial lens (3) relative to the eye and the exit of the irradiated beam, and The scanning of the illumination beam (2) across the artificial lens (3) by the scanner (4) is based on the position and / or orientation of the artificial lens (3) relative to the eye.

8. The system according to one or more of claims 1-7, further comprising a temperature management unit (14) connected to (i) one or more irradiation sources (1) and (ii) one or both of the scanner (4), The temperature management unit (14) is configured to determine, during the processing of the scanned intraocular lens (3), a portion of the temperature of the intraocular lens (3) based on the performance of the irradiation beam (2) and the performance of the intraocular lens (3). The system is configured to control (i) one or more irradiation sources (1) and (ii) one or both of the scanner (4) based on the determination of the temperature.

9. The system of claim 8, wherein the temperature management unit (14) is configured to predict the temperature during the treatment of the intraocular lens (3), and wherein the input data (8) includes the predicted temperature.

10. The system according to one or more of claims 2-9, further comprising an eye interface system (18) configured to hold the patient's eye in a fixed position.

Images