Eye tracking system during eye treatment

Abstract

To provide an eye tracking system such that an active eye tracking system can be employed to determine any changes in the position of a cornea and, in response, an illumination system can be adjusted to apply photoactivating light precisely to specified areas of the cornea.SOLUTION: A system 200 includes a spatial light modulator configured to receive photoactivating light from a light source 110 and provide pixelated illumination. The system includes a controller 120 configured to cause the spatial light modulator to project first pixelated illumination onto a cornea 2 to photoactivate a cross-linking agent applied to a treatment area. The first pixelated illumination has an area that is smaller than the maximum area defined by the spatial light modulator. The controller is configured to determine movement of the cornea. In response to the movement, the controller controls the spatial light modulator to project second pixelated illumination onto the treatment area based on a translation and / or transformation of the first pixelated illumination so as to continue photoactivating the cross-linking agent.SELECTED DRAWING: Figure 2A

Description

[Technical Field]

[0001] Cross-references to related applications This application claims priority to U.S. Provisional Application No. 62 / 638,621 (filed on 5 March 2018), the contents of which are incorporated herein by reference in their entirety.

[0002] Technical field This disclosure relates to a system and method for treating the eye, and more specifically, to a system and method for tracking eye movements in order to treat a desired area of ​​the eye. [Background technology]

[0003] Cross-linking therapy (also known as bridging therapy) can be used to treat eyes affected by diseases (such as keratoconus). In particular, keratoconus is a degenerative eye disease in which structural changes within the cornea weaken the cornea and cause it to deform into an abnormal cone shape. Cross-linking therapy can strengthen and stabilize the area weakened by keratoconus and prevent undesirable shape changes.

[0004] Cross-linking treatment may also be used after surgical procedures such as LASIK (Laser-Assisted in-site Keratomileusis). For example, a complication known as post-LASIK ectasia can occur due to corneal thinning and weakening caused by LASIK surgery. In post-LASIK ectasia, a progressive steepening (bulging) of the cornea occurs. Therefore, cross-linking treatment can strengthen and stabilize the corneal structure after LASIK surgery and prevent post-LASIK ectasia.

[0005] Cross-linking therapy can also be used to induce refractive changes in the cornea to correct disorders such as myopia, hyperopia, astigmatism, irregular astigmatism, and presbyopia. [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] To treat keratoconus or perform refractive correction, for example, effective cross-linking surgery involves irradiating a specific area of ​​the cornea to be treated with a cross-linking agent (crosslinking agent) with photoactivating light (hereinafter referred to as "photoactivating light") as precisely as possible. Irradiating areas outside the specific area with photoactivating light can cause undesirable structural changes in the cornea and adversely affect the treatment outcome. However, precisely irradiating with photoactivating light can be difficult due to eye movements that may occur during surgery. Such eye movements may include, for example, corneal translational movement along a plane (across the corneal depth), changes in line of sight angle, and / or septal movement. In cross-linking surgery, the cornea needs to be exposed to photoactivating light for at least one minute (e.g., 1 to 20 minutes), making it highly likely that eye movements will occur during surgery. To address the occurrence of eye movements, systems and methods may employ an active eye tracking system to determine any changes in corneal position, and the irradiation system may be adjusted accordingly to precisely irradiate a specific area of ​​the cornea with photoactivating light. [Means for solving the problem]

[0007] According to an exemplary embodiment of 1, a system for performing crosslinking therapy on the cornea of ​​the eye includes a light source configured to emit photoactivating light. The system includes a spatial light modulator configured to receive the photoactivating light from the light source and to provide a pixelating irradiation with the photoactivating light. The spatial light modulator defines the maximum area of ​​the pixelating irradiation. The system includes a controller configured to cause the spatial light modulator to project a first pixelating irradiation onto the cornea, thereby generating crosslinking activity within the treatment area by photoactivating a crosslinking agent applied to the treatment area. The first pixelating irradiation has an area smaller than the maximum area defined by the spatial light modulator. The controller is further configured to determine the movement of the cornea. In response to the movement of the cornea, the controller controls the spatial light modulator to project a second pixelating irradiation onto the treatment area based on at least one translational movement or deformation of the first pixelating irradiation, so as to continue the photoactivation of the crosslinking agent applied to the treatment area.

[0008] In the exemplary embodiments described above, using smaller pixelated irradiations can provide a wider range of positional adjustments for the spatial light modulator. However, smaller pixelated irradiation patterns consist of fewer pixels. Reducing the size (dimensions) of the pixelated irradiation can degrade the least resolvable spatial features that can be projected onto the eye, potentially generating “pixelated” defects. To address such effects, a system for performing crosslinking therapy on the cornea of ​​the eye includes a light source configured to emit photoactivating light. The system includes a spatial light modulator configured to receive the photoactivating light from the light source and provide pixelated irradiation with the photoactivating light. The system includes a controller configured to cause the spatial light modulator to project a first pixelated irradiation and a second pixelated irradiation onto the cornea, thereby generating crosslinking activity in the desired treatment area by photoactivating a crosslinking agent applied to the desired treatment area. The desired treatment area includes at least one portion that is not irradiated by the first pixelated irradiation. The second pixelated irradiation includes one or more pixels that irradiate at least one portion of the desired treatment area that is not irradiated by the first pixelated irradiation. The spatial light modulator projects a first pixelating irradiation and a second pixelating irradiation onto the cornea according to different temporal parameters. For example, the first pixelating irradiation includes all complete pixels that can be projected within the desired treatment area, and the second pixelating irradiation includes one or more pixels that, in combination with the pixels irradiated in the first pixelating irradiation, irradiate the entire desired treatment area. [Brief explanation of the drawing]

[0009] [Figure 1] This figure shows an exemplary system for applying a crosslinking agent and photoactivating light to the cornea of ​​the eye in order to generate crosslinks of corneal collagen, according to an aspect of the present disclosure. [Figure 2A] This figure shows an exemplary therapeutic system comprising an active eye-tracking system according to an aspect of the present disclosure. [Figure 2B] This figure shows one irradiation pattern of the exemplary treatment system in Figure 2A. [Figure 3A] FIG. 1 shows an exemplary treatment system with an alternative active eye tracking system according to aspects of the present disclosure. [Figure 3B] FIG. 5 shows an irradiation pattern of an exemplary treatment system of FIG. 3A. [Figure 4A] FIG. 8 shows an exemplary irradiation pattern of an exemplary treatment system of FIG. 3A. [Figure 4B] FIG. 11 shows another exemplary irradiation pattern based on the deformation of the irradiation pattern of FIG. 4A in response to rotational changes of the target eye. [Figure 5A] FIG. 14 shows an exemplary irradiation pattern for the exemplary treatment system of FIG. 3A. [Figure 5B] FIG. 17 shows another exemplary irradiation pattern based on the deformation of the irradiation pattern of FIG. 5A in response to geometric distortion generated by changes in the line-of-sight angle of the eye and / or movement of the head of the subject. [Figure 6A] FIG. 20 shows an exemplary pixel activation corresponding to a desired irradiation pattern for the exemplary treatment system of FIG. 3A. [Figure 6B] FIG. 23 shows an exemplary approach for resolving pixelation defects resulting from the pixel activation shown by FIG. 6A. [Figure 6C] FIG. 26 shows another exemplary approach for resolving pixelation defects resulting from the pixel activation shown by FIG. 6A. [Figure 7A] FIG. 29 shows a substantially circular UV irradiation pattern (diameter = 4 mm) defined by pixels of size 25 μm × 25 μm according to aspects of the present disclosure. [Figure 7B] FIG. 32 shows a substantially circular UV irradiation pattern (diameter = 4 mm) defined by pixels of size 100 μm × 100 μm according to aspects of the present disclosure. [Figure 7C] FIG. 35 shows a substantially circular UV irradiation pattern (diameter = 4 mm) defined by pixels of size 200 μm × 200 μm according to aspects of the present disclosure. [Figure 7D]This figure shows a substantially circular UV irradiation pattern (diameter = 4 mm) defined by pixels having a size of 400 μm × 400 μm, according to an aspect of this disclosure. [Figure 7E] This figure shows a substantially circular UV irradiation pattern (diameter = 4 mm) defined by pixels having a size of 750 μm × 750 μm, according to an aspect of this disclosure. [Figure 7F] This figure shows a substantially circular UV irradiation pattern (diameter = 4 mm) defined by pixels having a size of 1000 μm × 1000 μm, according to an aspect of this disclosure. [Figure 8A] Figure 7A shows the modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern defined in Figure 7A (from before treatment to after treatment). [Figure 8B] Figure 7B shows a modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern defined in Figure 7B. [Figure 8C] Figure 7C shows a modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern defined in Figure 7C. [Figure 8D] Figure 7D shows a modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern defined in Figure 7D. [Figure 8E] Figure 7E shows a modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern defined in Figure 7E. [Figure 8F] Figure 8F shows a modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern specified. [Figure 9A] This figure shows the modeled difference in corneal anterior surface height (μm) as a result of two cross-linking treatments using larger pixels (750 μm × 750 μm) and smaller pixels (10 μm × 10 μm), respectively, to apply a substantially circular UV irradiation pattern according to an aspect of the present disclosure. [Figure 9B]Figure 9A shows the modeled difference in tangent curvature (D) of the anterior surface of the cornea as a result of the two cross-linking processes. [Figure 10A] This figure shows a substantially annular UV irradiation pattern (inner diameter = 4 mm, outer diameter = 8.5 mm) defined by pixels of size 25 μm × 25 μm, according to an aspect of the present disclosure. [Figure 10B] This figure shows a substantially annular UV irradiation pattern (inner diameter = 4 mm, outer diameter = 8.5 mm) defined by pixels of size 100 μm × 100 μm, according to an aspect of the present disclosure. [Figure 10C] This figure shows a substantially annular UV irradiation pattern (inner diameter = 4 mm, outer diameter = 8.5 mm) defined by pixels with a size of 200 μm × 200 μm, according to an aspect of the present disclosure. [Figure 10D] This figure shows a substantially annular UV irradiation pattern (inner diameter = 4 mm, outer diameter = 8.5 mm) defined by pixels with a size of 400 μm × 400 μm, according to an aspect of the present disclosure. [Figure 10E] This figure shows a substantially annular UV irradiation pattern (inner diameter = 4 mm, outer diameter = 8.5 mm) defined by pixels with a size of 750 μm × 750 μm, according to an aspect of the present disclosure. [Figure 10F] This figure shows a substantially annular UV irradiation pattern (inner diameter = 4 mm, outer diameter = 8.5 mm) defined by pixels with a size of 1000 μm × 1000 μm, according to an aspect of the present disclosure. [Figure 11A] This figure shows a modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern specified in Figure 10A. [Figure 11B] Figure 10B shows a modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern specified. [Figure 11C] Figure 10C shows a modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern specified. [Figure 11D]Figure 10D shows a modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern specified. [Figure 11E] Figure 10E shows a modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern specified. [Figure 11F] Figure 10F shows a modeled change in the tangent curvature of the anterior surface of the cornea after cross-linking treatment using the UV irradiation pattern specified. [Figure 12A] This figure shows the modeled difference in corneal anterior surface height (μm) as a result of two cross-linking treatments using larger pixels (750 μm × 750 μm) and smaller pixels (10 μm × 10 μm), respectively, to apply a substantially annular UV irradiation pattern according to an aspect of the present disclosure. [Figure 12B] Figure 12A shows the modeled difference in tangent curvature (D) of the anterior corneal surface as a result of two cross-linking treatments. [Modes for carrying out the invention]

[0010] While various modifications and alternative forms are possible with respect to this disclosure, specific embodiments are shown in the drawings as examples and described in detail herein. However, it should be understood that this disclosure is not intended to limit itself to any specific form disclosed, but rather to encompass all modifications, equivalents, and alternatives that are in line with the spirit of this disclosure.

[0011] Figure 1 shows one exemplary therapeutic system 100 for generating collagen cross-linking in the cornea 2 of an eye 1. The therapeutic system 100 includes an applicator 132 for administering a cross-linking agent 130 to the cornea 2. In the exemplary embodiment, the applicator 132 may be an eye dropper, syringe, etc., for administering the photosensitizer 130 as a droplet to the cornea 2. Exemplary systems and methods for administering the cross-linking agent are described in U.S. Patent Application Publication No. 2017 / 0296383 (filed April 13, 2017), entitled "Systems and Methods for Delivering Drugs to an Eye," which is incorporated herein by reference in whole.

[0012] The crosslinking agent 130 may be provided in a formulation that allows the crosslinking agent 130 to pass through the corneal epithelium 2a to the lower region within the corneal matrix 2b. Alternatively, the corneal epithelium 2a may be removed or otherwise incised so that the crosslinking agent 130 can be more directly administered to the lower tissue.

[0013] The treatment system 100 includes an irradiation system having a light source 110 and an optical element 112 for directing the light onto the cornea 2. This light causes photoactivation of the crosslinking agent 130, generating crosslinking activity in the cornea 2. For example, the crosslinking agent may include riboflavin, and the light for photoactivation (hereinafter referred to as photoactivating light) may include ultraviolet A (UVA) light (e.g., about 365 nm). Alternatively, the photoactivating light may include another wavelength, for example, a visible wavelength (e.g., about 452 nm). As will be further described below, corneal crosslinking improves corneal strength by generating chemical bonds within the corneal tissue according to a photochemical reaction mechanism. For example, riboflavin and photoactivating light may be applied to stabilize and / or strengthen the corneal tissue to address a disease (e.g., keratoconus or post-LASIK ectasia).

[0014] The treatment system 100 includes one or more controllers 120 that control the configuration of the system 100 (including a light source 110 and / or an optical element 112). In one embodiment, the cornea 2 can be broadly treated with a crosslinking agent 130 (e.g., using an eye dropper, syringe, etc.), and the photoactivating light from the light source 110 can be selectively directed to the area of ​​the cornea 2 being treated according to a specific pattern.

[0015] The optical element 112 may include one or more mirrors or lenses for directing and focusing the photoactivating light emitted by the light source 110 onto a specific pattern on the cornea 2. The optical element 112 may further include filters for partially blocking wavelengths of light emitted by the light source 110 and for selecting specific wavelengths of light directed onto the cornea 2 to photoactivate the crosslinking agent 130. Furthermore, the optical element 112 may include one or more beam splitters for splitting the beam of light emitted by the light source 110, and one or more heat sinks for absorbing light emitted by the light source 110. The optical element 112 can also accurately and precisely focus the photoactivating light onto a specific focal plane in the cornea 2 (for example, at a specific depth in the lower region 2b where crosslinking activity is desired).

[0016] Furthermore, the inherent properties of the photoactivating light can be modified to achieve a desired degree of crosslinking in a selected area of ​​the cornea 2. One or more controllers 120 can control the operation of the light source 110 and / or optical element 112 to precisely deliver the photoactivating light according to any combination of wavelength, bandwidth, intensity, output, position, penetration depth, and / or treatment duration (exposure cycle duration, dark cycle duration, and ratio of exposure cycle to dark cycle duration).

[0017] The parameters for photoactivation of the crosslinking agent 130 can be adjusted, for example, to shorten the time required to achieve the desired crosslinking. In one implementation example, the time can be reduced from minutes to seconds. Some configurations use 5 mW / cm². 2While photoactivating light can be irradiated at a certain irradiance, to shorten the time required to achieve the necessary crosslinking, the photoactivating light can be irradiated at a higher irradiance (e.g., 5 mW / cm²). 2 It can be irradiated at multiples of . The total energy dose absorbed by the cornea 2 can be described as the effective dose, which is the amount of energy absorbed through the region of the corneal epithelium 2a. For example, the effective dose to the region of the corneal surface 2a is, for example, 5 J / cm². 2 , or 20 J / cm 2 or 30 J / cm 2 This can be the height. The stated effective dose can be obtained from a single application of energy or from repeated applications of energy.

[0018] The optical elements 112 of this treatment system 100 may include a microelectromechanical system (MEMS), such as a digital micro-mirror device (DMD), to spatially and temporally modulate the irradiation of photoactivating light. Using DMD technology, photoactivating light from the light source 110 is projected in a precise spatial pattern created by an array of extremely small mirrors on a semiconductor chip. Each mirror represents one or more pixels in the projected light pattern. Using DMD, topographically guided bridging can be performed. Topographically controlled DMD can use several different spatial and temporal illuminance and dose profiles. These spatial and temporal dose profiles can be created using continuous wave irradiation, but can also be adjusted via pulsed irradiation by pulsed irradiation, which is achieved by changing the frequency and duty cycle of the irradiation source. Alternatively, the DMD can be tuned so that the frequency and duty cycle of each pixel differ, providing ultimate flexibility using continuous wave irradiation. Alternatively, both pulsed irradiation and a combination of adjusted DMD frequencies and duty cycles may be used. This spatially determined crosslinking can be combined with dosimetry, interferometry, optical coherence tomography (OCT), corneal topography, etc., for pretreatment planning and / or real-time monitoring and adjustment of corneal crosslinking during treatment. The embodiments of the dosimetry system will be described in more detail below. Furthermore, preclinical patient information can be combined with finite-element biomechanical computer modeling to create patient-specific pretreatment plans.

[0019] To control the projection of photoactivating light, embodiments may also employ multiphoton excitation microscopy techniques. Specifically, rather than irradiating the cornea 2 with a single photon of a specific wavelength, the treatment system 100 may irradiate with multiple photons of longer wavelengths (i.e., lower energy) that bind to initiate crosslinking. Advantageously, longer wavelengths are scattered less within the cornea 2 than shorter wavelengths, which allows longer wavelength light to penetrate the cornea 2 more efficiently than shorter wavelength light. The shielding effect of incident irradiation at deeper points in the cornea is also reduced compared to conventional short-wavelength irradiation, because light absorption by the photosensitizer is much less at longer wavelengths. This allows for enhanced control over depth-specific crosslinking. For example, in some embodiments, two photons may be used, each carrying approximately half the energy required to excite molecules in the crosslinking agent 130 to produce the photochemical reactions described further below. If the crosslinking molecule absorbs both photons simultaneously, it absorbs enough energy to release reactive radicals in the corneal tissue. Embodiments may also utilize lower-energy photons, such that the crosslinking molecule must absorb, for example, three, four, or five photons simultaneously to release reactive radicals. The likelihood of multiple photons being absorbed nearly simultaneously is low, and therefore a high flux of excitation photons is required, which can be provided through a femtosecond laser.

[0020] Numerous conditions and parameters affect the crosslinking of corneal collagen by the crosslinking agent 130. For example, the illuminance and dose of photoactivating light affect the amount and rate of crosslinking.

[0021] When the crosslinking agent 130 is specifically riboflavin, UVA light may be irradiated continuously (CW) or as pulsed light, and this choice affects the amount, rate, and degree of crosslinking. When UVA light is irradiated as pulsed light, the exposure cycle, the duration of the dark cycle, and the ratio of the exposure cycle to the dark cycle duration affect corneal hardening. Pulsed light irradiation can be used to strengthen or weaken corneal tissue hardening more than can be achieved with continuous wave irradiation applying the same amount or dose of energy. Light pulses of appropriate length and frequency can be used to achieve more optimal chemical amplification. For pulsed light therapy, the on / off duty cycle can be between approximately 1 / 1000 and approximately 1 / 1000. The illuminance is an average illuminance of approximately 1 mW / cm². 2 From approximately 1000 mW / cm² 2 It can be between approximately 0.01 Hz and approximately 1000 Hz, or between approximately 1000 Hz and approximately 100,000 Hz.

[0022] The treatment system 100 can generate pulsed light by employing a DMD (electronically turning the light source 110 on and off) and / or by using a mechanical or photoelectronic (e.g., Pockels cell) shutter or a mechanical chopper or rotary aperture. Due to the modulation capabilities inherent in the pixels of the DMD, and subsequent stiffening based on the modulated frequency, duty cycle, illuminance, and dose irradiated to the cornea, complex biomechanical stiffness patterns are imparted to the cornea, enabling refractive correction of various degrees. These refractive corrections may include combinations of myopia, hyperopia, astigmatism, irregular astigmatism, presbyopia, and complex corneal refractive corrections due to the condition of the eye (e.g., keratoconus, perior optica, post-LASIK ectasia, and other conditions such as biomechanical changes / degeneration of the cornea). A specific advantage of the DMD system and method is that it allows for the generation of non-periodic and uniform-looking irradiations, eliminating the possibility of causing photosensitive epileptic seizures or flicker vertigo to pulse frequencies between 2 Hz and 84 Hz, for the patterning of randomized asynchronous pulse topography.

[0023] Although exemplary embodiments may utilize a stepped on / off pulsed light function, it is understood that other functions for irradiating the cornea with light may be used to achieve a similar effect. For example, light may be irradiated onto the cornea according to a sinusoidal function, a sawtooth wave function, or other complex functions or curves, or any combination of functions or curves. In fact, it will be understood that the function may be substantially stepped if it has a gentler transition between on / off values. Furthermore, it will be understood that the illuminance does not need to decrease to zero during the off-cycle, and may even exceed zero during the off-cycle. The desired effect may be achieved by irradiating the cornea with light according to a curve that varies the illuminance between two or more values.

[0024] Examples of systems and methods for applying photoactivating light are described, for example, in U.S. Patent Application Publication No. 2011 / 0237999 (filed March 18, 2011), entitled "Systems and Methods for Applying and Monitoring Eye Therapy," U.S. Patent Application Publication No. 2012 / 0215155 (filed April 3, 2012), entitled "Systems and Methods for Applying and Monitoring Eye Therapy," and U.S. Patent Application Publication No. 2013 / 0245536 (filed March 15, 2013), entitled "Systems and Methods for Corneal Cross-Linking with Pulsed Light." The contents of these applications are incorporated herein by reference in their entirety.

[0025] The addition of oxygen also affects the degree of corneal hardening. In human tissue, the O2 content is extremely low compared to air. However, the rate of crosslinking in the cornea is related to the concentration of O2 when irradiated with photoactivating light. Therefore, it may be advantageous to actively increase or decrease the O2 concentration during irradiation to control the crosslinking rate until the desired degree of crosslinking is achieved. Oxygen may be administered during crosslinking therapy in several different ways. One approach is to supersaturate riboflavin with O2. In this way, when riboflavin is administered to the eye, a high concentration of O2 is directly administered into the cornea along with the riboflavin, influencing the O2-involved reaction when riboflavin is exposed to photoactivating light. According to another approach, a steady state of O2 (at a selected concentration) is maintained on the surface of the cornea, and the cornea is exposed to a selected amount of O2, allowing the O2 to enter the cornea. As shown in Figure 1, for example, the treatment system 100 also includes an oxygen source 140 and an oxygen supply device 142 that optionally supplies oxygen to the cornea 2 at an optionally selected concentration. Exemplary systems and methods for administering oxygen during cross-linking therapy are described, for example, in U.S. Patent No. 8,574,277, titled "Eye Therapy" (filed October 21, 2010) and U.S. Patent Application Publication 2013 / 0060187, titled "Systems and Methods for Corneal Cross-Linking with Pulsed Light" (filed October 31, 2012). The contents of these applications are incorporated herein by reference in their entirety. Furthermore, an exemplary mask device for administering oxygen concentration and photoactivating light in eye treatment is described in U.S. Patent Application Publication No. 2017 / 0156926 (filed December 3, 2016), entitled "Systems and Methods for Treating an Eye with a Mask Device," which is incorporated herein by reference in its entirety.For example, a mask may be positioned to cover the eyes in order to provide a consistent and known oxygen concentration on the surface of the eyes.

[0026] Riboflavin undergoes photoactivation upon absorbing irradiation energy, specifically light. There are two photochemical dynamic pathways for riboflavin photoactivation: Type I and Type II. The reactions involved in both Type I and Type II mechanisms, along with other aspects of the photochemical dynamic reactions that generate crosslinking activity, are described in U.S. Patent Application Publication No. 2016 / 0310319 (filed April 27, 2016), entitled "Systems and Methods for Cross-Linking Treatments of an Eye." Its contents are incorporated herein by reference in their entirety.

[0027] For example, to treat keratoconus or achieve refractive correction, effective cross-linking surgery involves irradiating a specific area of ​​the cornea to be treated with a crosslinking agent with photoactivating light as precisely as possible. Irradiating areas outside the specific area with photoactivating light can cause undesirable structural changes in the cornea and negatively affect the treatment outcome. However, precise irradiation with photoactivating light can be difficult to achieve due to eye movements that may occur during the procedure. Such eye movements may include translational movement along the xy plane, changes in line of sight angle, and / or septal movement, as shown in Figure 1. (In Figure 1, the depth of the cornea 2 is measured along the z axis, and the pattern of photoactivating light may be projected onto the lateral xy plane.) Since cross-linking surgery requires exposing the cornea to photoactivating light for at least one minute, e.g., 1 to 20 minutes, there is a very high probability that some eye movement will occur during the procedure.

[0028] To address the occurrence of eye movements, embodiments may employ an active eye-tracking system to determine changes in corneal position, and in response, the irradiation system may be adjusted to precisely irradiate a specific area of ​​the cornea with photoactivating light. Figure 2A shows an exemplary treatment system 200 with an active eye-tracking system. The treatment system 200 includes an irradiation system for directing photoactivating light onto the cornea 2 of eye 1. The irradiation system includes a light source 110 and optical elements 112, as described above. For example, the light source 110 may include one or more LEDs that emit UV light to photoactivate riboflavin applied to the cornea 2. Optical elements 112, including a DMD (Digital Micromirror Device) 212, irradiate the photoactivating light onto the cornea 2 along the xy plane in a precise spatial pattern. Furthermore, the treatment system 200 includes one or more controllers 120 for controlling embodiments of the treatment system 200.

[0029] Regarding active eye-tracking systems, the treatment system 200 includes a camera (image capture device) 252 that dynamically captures images of the eye 1 during surgery. One or more controllers 120 may process the images to detect the position of a reference point (e.g., the pupil) of the eye 1 relative to the treatment system 200. Using the position of the reference point as a reference, one or more reference point controllers 120 may determine the location of a specific region of the cornea 2. In this way, one or more controllers 120 can adjust the treatment system 200 to irradiate the specific region with photoactivating light. The camera 252 and software for processing the images and adjusting the treatment system 200 (e.g., computer-readable instructions stored on a non-temporary medium) may together be known as a visual system.

[0030] Referring to FIG. 2B, the entire mirror array of the DMD 212 defines a maximum area 202 for irradiating photoactivation light. The maximum area 202 includes boundaries 202a - d. Any part of the array of the DMD 212 can be activated to impart photoactivation light from any part of the maximum area 202. For example, as shown in FIG. 2B, a part of the array of the DMD 212 can be activated to generate an irradiation pattern 204 that is substantially circular and has a diameter D1 centered at position (x c , y c ). The diameter D1 of the irradiation pattern 204 may be slightly smaller than the distance along the y-axis between the opposing boundaries 202a, b and the distance along the x-axis between the opposing boundaries 202c, d. Thus, there may be a space between the irradiation pattern 204 and the boundaries 202a - d. This space allows the center of the irradiation pattern 204 to be translated a short distance within the area 202 while maintaining the same shape with a diameter D1. For example, another part of the array of the DMD 212 can be activated to generate an irradiation pattern 204 centered at a different position (x c s +δ x1 , y c +δ y1 ). Here, δ x1 represents the possible translational movement along the x-axis, and δ y1 represents the possible translational movement along the y-axis. The translational movement of the irradiation pattern 204 within the area 202 changes the position of the corresponding photoactivation light when irradiating the cornea 2. In this way, in response to the movement of the eye detected via the camera 252, one or more controllers 120 can control the DMD 212 and adjust the irradiation of the photoactivation light to reach a specified area of the cornea 2 to obtain a desired result.

[0031] However, the adjustments that one or more controllers 120 can make using the DMD 212 are limited by the small amount of clearance between the irradiation pattern 204 and the boundaries 202a-d. With the DMD 212 alone, one or more controllers 120 may not be able to make sufficiently large adjustments within the region 202 to the position of the irradiation pattern 204 in response to larger eye movements. In other words, the irradiation pattern 204 may reach one of the boundaries 202a-d before it can be moved by the desired distance. To make larger adjustments that cannot be made with the DMD 212, the treatment system 200 includes an electromechanical XY motion system 254 coupled with one or more optical elements 112. One or more controllers 120 can control the XY motion system 254 to move one or more optical elements 112 to make better mechanical alignment with the cornea 2 in response to larger eye movements. For example, the XY motion system 254 may include an electromechanical stage capable of moving one or more optical elements 112 and corresponding photoactivating light along the x-axis and / or y-axis. In this way, the treatment system 200 uses the DMD 212 for smaller adjustments and the XY motion system 254 for larger adjustments, depending on the amount of variation in eye movement.

[0032] Figure 3A shows one exemplary treatment system 300 with an alternative active eye-tracking system. In contrast to the treatment system 200 shown in Figure 2A, the treatment system 300 does not employ an XY motion system 254. Rather, the treatment system 300 uses a DMD 312 to digitally perform virtually all desired adjustments. Similar to the DMD 212 described above, the entire mirror array within the DMD 312 defines the same maximum region 202 for applying photoactivating light, as shown in Figure 3B. The maximum region 202 includes the same boundaries 202a-d. Any part of the array in the DMD 312 can be operated to apply light from any part of this maximum region 202. To eliminate the need for the XY motion system 254 employed for the irradiation pattern 204 shown in Figure 2A, the DMD 312 irradiates an irradiation pattern 304 that is significantly smaller than the irradiation pattern 204.

[0033] A comparison of Figure 2B and Figure 3B clearly shows the difference between the respective irradiation patterns 204 and 304 within the same maximum area 202. The smaller area irradiation pattern 304 is generated by activating fewer DMD arrays. Irradiation pattern 304 is substantially circular, and the position (x c , y c It is centered at ) but has a diameter D2 smaller than the diameter D1 of the irradiation pattern 204. Therefore, there is more empty space between irradiation pattern 304 and boundary 202a~d than between irradiation pattern 204 and boundary 202a~d. This larger space allows the center of irradiation pattern 304 to be translated to a greater extent than the center of irradiation pattern 204 along the x and / or y axes within region 202. In other words, another part of the array of DMD312 can be translated to a different position (x c +δ x2 , y c +δ y2 It can be operated to generate an irradiation pattern 304 centered on ). Here, δ x2 is δ x1 Larger than δ y2 is δ y1 Larger than, and δ x1 and δy1 This represents the possible translational movements of the treatment system 200 along each axis.

[0034] Translational movement of the irradiation pattern 304 within region 202 alters the position of the corresponding photoactivating light when applied to the cornea 2. A greater potential translational movement of the irradiation pattern 304 by the DMD 312 allows for a wider range of adjustments for the application of photoactivating light along the x-axis and / or y-axis. In this way, in response to eye movements detected via the camera 252, one or more controllers 120 can use the DMD 312 to make substantially all desired adjustments so that the photoactivating light reaches a specific area of ​​the cornea 2 to achieve the desired result.

[0035] The treatment system 200 relies on an electromechanical XY motion system 254, which may use a slower motor. In contrast, since the DMD 312 can digitally respond to commands at a speed of approximately 60 Hz, the treatment system 300 can more quickly adjust its position for the application of photoactivating light.

[0036] By using the DMD312, the treatment system 300 can also perform positional corrections that are not possible with the X-Y motion system 254. For example, the treatment system 300 can respond more effectively to changes in the rotational position of the eye by applying a rotational deformation corresponding to the rotational change of the eye to the irradiation pattern irradiated onto the eye via the DMD312. Figure 4A shows the initial irradiation pattern 404a generated by activating a portion of the DMD312 array. Irradiation pattern 404a has an initial rotational state. When the treatment system 300 detects a change in the rotational position of the eye via the camera 252, another portion of the DMD312 array may be activated to generate the irradiation pattern 404b shown in Figure 4B. Irradiation pattern 404b provides a geometric deformation of the initial irradiation pattern 404a using a rotational state different from the initial state that responds to the change in the rotational position of the eye.

[0037] Furthermore, the treatment system 300 can respond more effectively to geometric distortions caused by changes in line of sight angle and / or head position. For example, Figure 5A shows the initial irradiation pattern 504a generated by activating a portion of the DMD 312 array. As illustrated, the irradiation pattern 504a is substantially circular. Preferably, the photoactivating light from the treatment system 300 is projected onto a desired plane (e.g., the xy plane) in the cornea 2 in a corresponding substantially circular shape, as predicted. However, changes in line of sight angle and / or head position can change the angle of the desired plane in the cornea 2 and geometrically distort the projection of the photoactivating light into a shape different from the initial irradiation pattern 504a. For example, changes in line of sight angle and / or head position can stretch the irradiation pattern 504a, resulting in an elliptical shape being projected onto the desired plane. When the treatment system 300 detects changes in line of sight angle and / or head position via the camera 252, another portion of the DMD 312 array may be activated to generate an irradiation pattern 504b as shown in Figure 5B. The irradiation pattern 504b provides a geometric deformation of the initial irradiation pattern 504a in a predetermined different shape that can compensate for geometric distortions caused by changes in line of sight angle and / or head position. When the irradiation pattern 504b is projected onto a desired plane of the cornea, the projection has exactly the desired shape. Specifically, in the example in Figures 5A-B, the projection has a substantially circular shape. However, in other applications, the projection may have another desired shape (e.g., an ellipse).

[0038] By using a smaller irradiation pattern, a wider range of position adjustment is provided to the DMD312. As described above, the DMD provides an irradiation pattern that is pixelated according to an array of mirrors. Since the irradiation pattern from the DMD consists of a discrete number of pixels, a smaller irradiation pattern consists of fewer pixels. Thus, reducing the size of the irradiation pattern can degrade the least resolvable spatial features that can be projected onto the eye, potentially resulting in "pixelation" defects (artifacts). As shown in Figure 6A, the DMD312 provides a maximum irradiation area 602 defined by multiple pixels 602a. The treatment system 300 can activate a subset of these pixels to generate a smaller irradiation pattern that allows for a wider range of position adjustment. For example, 602a in Figure 6A shows the boundary (contour) of a desired irradiation pattern 606. However, due to the size of the desired irradiation pattern 606, only pixel 604a substantially fits inside the desired irradiation pattern 606. If only pixel 604a is activated, a portion of the desired illumination pattern 606 remains unfulfilled. However, even if pixel 604b is activated to fulfill the remaining portion of the desired illumination pattern 606, the resulting illumination pattern does not have the desired shape. In both cases, the resulting illumination pattern lacks the smooth edges corresponding to the desired illumination pattern 606. Generally, the example in Figure 6A illustrates the trade-off between the range of possible adjustments for active eye tracking in the DMD and the resolution required to obtain the desired illumination pattern, given the size of the DMD array.

[0039] Figure 6B shows an approach to resolve the pixelation defects shown in Figure 6A (hereinafter referred to as pixelation defects) and to generate an irradiation pattern with smoother edges corresponding to the desired irradiation pattern 606. Specifically, one or more controllers 120 can operate the DMD 312 to rapidly dither pixels 604b during surgery. For example, pixels 604b may be activated alternately with a per-second update cycle for the DMD 312. The total dose of photoactivating light delivered by pixels 604b when dithered during surgery is less than if pixels 604b were activated for the entire duration of surgery. Therefore, dithering can be applied to provide a smoother irradiation pattern that more closely approximates the desired irradiation pattern 606 and the corresponding dose of photoactivating light.

[0040] Figure 6C shows another approach to smoothing the pixelation defects shown in Figure 6A. Specifically, dithering can be applied by alternately shifting the base shape defined by pixel 604a shown in Figure 6A by + / - 1 pixel along the x or y axis at interleaved time points. For example, in one update cycle, DMD312 is operated to translate the base shape by 1 pixel in the positive y direction (from the position shown in Figure 6A) so as to include the boundary partially defined by pixel 608a. In the next update cycle, DMD312 is operated to translate the base shape by 1 pixel in the positive x direction (from the position shown in Figure 6A) so as to include the boundary partially defined by pixel 608b. In the next update cycle, DMD312 is operated to translate the base shape by 1 pixel in the negative y direction (from the position shown in Figure 6A) so as to include the boundary partially defined by pixel 608c. In the next update cycle, the DMD312 is operated to translate the basic shape by one pixel in the negative x-direction (from the position shown in Figure 6A) so that it includes the boundary partially defined by pixel 608d. These steps are repeated to provide a smoother irradiation pattern that more closely approximates the desired irradiation pattern 606 and the corresponding dose of photoactivating light.

[0041] The maximum allowable pixel size of the DMD and the optimal parameters for the above embodiments can be determined by biomechanical modeling of the corneal response to cross-linking surgery.

[0042] Figures 7A-F show the use of pixels with increasing pixel size to apply a substantially circular UV irradiation pattern 706 having a diameter of approximately 4 mm. The irradiation pattern 706 may be used, for example, to generate a region of corresponding cross-linking activity within the cornea to treat myopia. In Figure 7A, the irradiation pattern 706 is defined by pixels 708a with a size of 25 μm × 25 μm. In Figure 7B, the irradiation pattern 706 is defined by pixels 708b with a size of 100 μm × 100 μm. In Figure 7C, the irradiation pattern 706 is defined by pixels 708c with a size of 200 μm × 200 μm. In Figure 7D, the irradiation pattern 706 is defined by pixels 708d with a size of 400 μm × 400 μm. In Figure 7E, the irradiation pattern 706 is defined by pixels 708e with a size of 750 μm × 750 μm. In Figure 7F, the illumination pattern 706 is defined by pixels 708f with a size of 1000 μm × 1000 μm. The effect of eye movement on the illumination pattern 706 is modeled in Figures 7A-F by a 100 μm blurring function along the edge of the illumination pattern 706.

[0043] Correspondingly, Figures 8A to 8F show the modeled change in the tangent curvature of the anterior corneal surface after crosslinking treatment (from before treatment to after treatment), using increasing pixel sizes for applying the UV irradiation pattern 706 as shown in Figures 7A to 7F, respectively. Figure 8A shows the results when the irradiation pattern 706 is defined by pixel 708a (25 μm × 25 μm). Figure 8B shows the results when the irradiation pattern 706 is defined by pixel 708b (100 μm × 100 μm). Figure 8C shows the results when the irradiation pattern 706 is defined by pixel 708c (200 μm × 200 μm). Figure 8D shows the results when the irradiation pattern 706 is defined by pixel 708d (400 μm × 400 μm). Figure 8E shows the results when the irradiation pattern 706 is defined by pixel 708e (750 μm × 750 μm). Figure 8F shows the results when the irradiation pattern 706 is defined by pixel 708f (1000 μm × 1000 μm). Table 1 shows the change (D) in corneal curvature measurement over the central 3 mm region of the cornea for various pixel sizes. [Table 1]

[0044] Figures 9A and 9B show the modeled differences between two crosslinking treatments using larger and smaller pixels, respectively, to apply a substantially circular UV irradiation pattern. Specifically, the larger pixels are 750 μm × 750 μm in size, and the smaller pixels are 10 μm × 10 μm in size. Figure 9A shows the difference between the corneal surface height (μm) obtained after using the smaller pixels and the corneal surface height (μm) obtained after using the larger pixels. Figure 9B shows the difference between the corneal surface tangent curvature (D) obtained after using the smaller pixels and the corneal surface tangent curvature (D) obtained after using the smaller pixels.

[0045] However, as shown in Figures 8A-F and Table 1, the changes in tangent curvature and corneal curvature are virtually similar to those observed with treatments using pixel sizes up to 250 μm × 250 μm (or 400 μm × 400 μm) for substantially circular irradiation patterns. Similar results with larger pixel sizes (e.g., compared to smaller 10 μm × 10 μm pixels) enable the effective implementation of the eye-tracking approach of the exemplary system 300 described above.

[0046] Figures 10A-F illustrate the use of increased pixel size to apply a substantially annular UV irradiation pattern 1006. The irradiation pattern 1006 has an inner diameter of approximately 4 mm and an outer diameter of approximately 8.5 mm. The irradiation pattern 1006 may be used, for example, to generate a corresponding area of ​​cross-linking activity in the cornea to treat hyperopia or presbyopia. In Figure 10A, the irradiation pattern 1006 is defined by pixels 1008a with a size of 25 μm × 25 μm. In Figure 10B, the irradiation pattern 1006 is defined by pixels 1008b with a size of 100 μm × 100 μm. In Figure 10C, the irradiation pattern 1006 is defined by pixels 1008c with a size of 200 μm × 200 μm. In Figure 10D, the irradiation pattern 1006 is defined by pixels 1008d with a size of 400 μm × 400 μm. In Figure 10E, the illumination pattern 1006 is defined by pixels 1008e with a size of 750 μm × 750 μm. In Figure 10F, the illumination pattern 1006 is defined by pixels 1008f with a size of 1000 μm × 1000 μm. The effect of eye movement on the illumination pattern 1006 is modeled in Figures 10A to F by a 100 μm blur function along the edge of the illumination pattern 1006.

[0047] Correspondingly, Figures 11A-F show the modeled changes (before and after treatment) in the tangent curvature of the anterior corneal surface after cross-linking treatment using increasing pixel sizes to apply the UV irradiation pattern 1006 as shown in Figures 10A-10F. Figure 11A shows the results when the irradiation pattern 1006 is defined by pixel 1008a (25 μm × 25 μm). Figure 11B shows the results when the irradiation pattern 1006 is defined by pixel 1008b (100 μm × 100 μm). Figure 11C shows the results when the irradiation pattern 1006 is defined by pixel 1008c (200 μm × 200 μm). Figure 11D shows the results when the irradiation pattern 1006 is defined by pixel 1008d (400 μm × 400 μm). Figure 11E shows the results when the illumination pattern 1006 is defined by pixel 1008e (750 μm × 750 μm). Figure 11F shows the results when the illumination pattern 1006 is defined by pixel 1008f (1000 μm × 1000 μm). Table 2 shows the change in corneal curvature measurement over the central 3 mm region of the cornea for various pixel sizes (D). [Table 2]

[0048] Figures 12A and 12B show the modeled differences between the results of two cross-linking treatments using larger and smaller pixels, respectively, to apply a substantially annular UV irradiation pattern. Specifically, the larger pixel size is 750 μm × 750 μm, and the smaller pixel size is 10 μm × 10 μm. Figure 12A shows the difference between the corneal anterior surface height (μm) obtained after using the smaller pixels and the corneal anterior surface height (μm) obtained after using the larger pixels. Figure 12B shows the difference between the corneal anterior surface tangent curvature (D) obtained after using the smaller pixels and the corneal anterior surface tangent curvature (D) obtained after using the larger pixels.

[0049] However, as shown in Figures 11A-F and Table 2, for substantially annular irradiation patterns, the changes in tangent curvature and corneal curvature are substantially similar for treatments using pixel sizes up to 200 μm × 200 μm (or 400 μm × 400 μm). Furthermore, similar results with larger pixel sizes (e.g., compared to smaller 10 μm × 10 μm pixels) enable the effective implementation of the eye-tracking approach of the exemplary system 300 described above.

[0050] While the above embodiments may involve the use of a DMD device, other embodiments may use any type of programmable spatial light modulator to obtain similar results. For example, embodiments may use a transmissive or reflective liquid crystal microdisplay. To obtain similar results, a spatial light modulator that provides a change in polarization may be used in combination with a fixed polarizer. Transmissive implementation may offer additional advantages in terms of the overall system size.

[0051] Considering the foregoing, the embodiments employ purely digital means for eye tracking that can be used in conjunction with an irradiation system for performing corneal crosslinking. Specifically, these embodiments do not require an electromechanical motion system (e.g., for adjustment along the xy plane) to hold a photoactivating light beam aligned to a desired area of ​​the target eyeball. Advantageously, this allows for a significant reduction in the cost and complexity of the treatment system. Furthermore, among other advantages, the system allows for increased response time, adjustment of rotational eye movements, and correction of geometric distortions caused by changes in gaze angle and / or head movements compared to other systems.

[0052] As described above, according to some aspects of this disclosure, some or all of the steps of the above-described and illustrated procedure may be automated or induced under the control of a controller (e.g., controller 120). Generally, the controller may be implemented as a combination of hardware and software elements. The hardware aspect may include a combination of operable-coupled hardware components, such as a microprocessor, logic circuits, communication / network ports, digital filters, memory, or logic circuits. The controller may be adapted to perform operations specified by computer executable code (which may be stored in a computer-readable medium).

[0053] As described above, the controller may be a programmable processing device that executes software or stored instructions (e.g., an external conventional computer, or an onboard field-programmable gate array (FPGA), or digital signal processor (DSP)). Generally, the physical processor and / or machine used by embodiments of the present disclosure for any processing or evaluation may include, as will be understood by those skilled in computer and software technology, one or more networked or unnetworked general-purpose computer systems, microprocessors, field-programmable gate arrays (FPGAs), digital signal processors (DSPs), microcontrollers, etc., programmed in accordance with the teachings of the exemplary embodiments of the present disclosure. The physical processor and / or machine may be externally networked with an image capture device (e.g., camera 252) or integrated to reside within the image capture device. As will be understood by those skilled in software technology, suitable software may be readily prepared by a programmer of ordinary skill based on the teachings of the exemplary embodiments. Furthermore, the devices and subsystems of the exemplary embodiments may be implemented by preparing application-specific integrated circuits or by interconnecting conventional component circuits in a suitable network, as can be understood by those skilled in electrical engineering. Thus, the exemplary embodiments are not limited to any particular combination of hardware circuits and / or software.

[0054] The exemplary embodiments of this disclosure may include software stored on any one or combination of computer-readable media for controlling the exemplary devices and subsystems, for driving the exemplary devices and subsystems, and for enabling the exemplary devices and subsystems to interact with a human user or the like. Such software may include, but is not limited to, device drivers, firmware, operating systems, development tools, and application software. Such computer-readable media may further include computer program products of the embodiments of this disclosure for performing all or part of the processing performed in the implementation (if the processing is distributed). The computer code devices of the exemplary embodiments of this disclosure may include, but are not limited to, any suitable interpretable or executable code mechanisms, including, but not limited to, scripts, interpretable programs, dynamic link libraries (DLLs), Java classes and applets, and complete executable programs. Furthermore, some of the processing of the exemplary embodiments of this disclosure may be distributed for better performance, reliability, cost, etc.

[0055] Common forms of computer-readable media may include, for example, floppy disks, flexible disks, hard disks, magnetic tapes, and other suitable magnetic media; CD-ROMs, CDRWs, DVDs, and other suitable optical media; punch cards, paper tapes, optical mark sheets, other suitable physical media with hole patterns or other optically recognizable markings; RAM, PROMs, EPROMs, FLASH-EPROMs, and other suitable memory chips or cartridges; computer-readable carrier waves or other suitable media.

[0056] While this disclosure has been described with reference to one or more specific embodiments, those skilled in the art will recognize that many modifications can be made without departing from the spirit and scope of this disclosure. Each of these embodiments and their obvious variations is considered to fall within the spirit and scope of this disclosure. Additional embodiments according to aspects of this disclosure are also envisioned to be able to combine any number of features of any of the embodiments described herein.

Claims

1. This is a system for performing cross-linking therapy on the cornea of ​​the eye. A light source configured to emit photoactivating light, A spatial light modulator configured to receive the photoactivating light from the light source and to provide pixelating irradiation using the photoactivating light, wherein the spatial light modulator defines the maximum area of ​​the pixelating irradiation, and A controller configured to generate crosslinking activity in a treatment area by projecting a first pixelating irradiation onto the cornea using the spatial light modulator, wherein the first pixelating irradiation has a region smaller than the maximum region defined by the spatial light modulator, Includes, The controller is further configured to determine the movement of the cornea, and in response to the movement of the cornea, the controller controls the spatial light modulator to project a second pixelating irradiation onto the treatment area based on at least one of the translational movement or deformation of the first pixelating irradiation in order to continue the photoactivation of the crosslinking agent applied to the treatment area. The spatial light modulator includes a boundary defining the maximum area of ​​the pixelation irradiation, the first pixelation irradiation is centered at a first position within the boundary, and the second pixelation irradiation is centered at a second position within the boundary, the second position being different from the first position. The above system.

2. The system according to claim 1, wherein the spatial light modulator is a digital micromirror device (DMD), the DMD comprising a plurality of mirrors arranged in an array, the plurality of mirrors configured to selectively reflect the photoactivating light from the light source to provide the pixelating illumination, the plurality of mirrors defining the maximum area of ​​the pixelating illumination, and the controller determining a first subset of the plurality of mirrors for providing the first pixelating illumination and a second subset of the plurality of mirrors for providing the second pixelating illumination.

3. The system according to claim 1, further comprising an image capture device configured to acquire an image of the cornea, wherein the controller is configured to (i) receive information from the image capture device regarding the image of the cornea, and (ii) determine the movement of the cornea according to the information from the image capture device.

4. The system according to claim 1, wherein the first pixelating irradiation and the second pixelating irradiation have the same shape and size.

5. The system according to claim 1, wherein the first pixelation irradiation and the second pixelation irradiation have different shapes.

6. The system according to claim 1, wherein the controller controls the spatial light modulator to geometrically deform the first pixelation irradiation to generate the second pixelation irradiation.

7. The system according to claim 6, wherein the geometric deformation rotates the first pixelating irradiation to generate the second pixelating irradiation.

8. The system according to claim 1, wherein the controller controls the spatial light modulator to project the first pixelation irradiation onto the plane of the cornea according to a desired shape and size, the movement of the cornea includes the movement of the plane of the cornea, and the controller controls the spatial light modulator to project the second pixelation irradiation onto the plane of the cornea to generate a desired shape and size.

9. The controller is further configured to project a first pixelation irradiation and a second pixelation irradiation onto the cornea to photoactivate the crosslinking agent applied to the desired treatment area, thereby generating crosslinking activity in the desired treatment area. The system according to claim 1.

10. The system according to claim 9, wherein the first pixelating irradiation includes all complete pixels that can be projected into the desired treatment area, and the one or more pixels to be second pixelating include the remaining pixels that, in combination with the first pixelating irradiation pixels, project the entire desired treatment area.

11. The system according to claim 10, wherein the first pixelating irradiation is projected substantially inside the desired treatment area, and one or more pixels that are secondly pixelated are projected both inside and outside the desired treatment area.

12. The system according to claim 10, wherein the one or more pixels to be irradiated in the second pixelation are arranged along the boundary of the desired treatment area.

13. The system according to claim 9, wherein the first pixelating irradiation is projected onto the cornea for a predetermined period of time, and the second pixelating irradiation is dithered onto the cornea at a high speed for the same period of time.

14. The system according to claim 9, wherein the first pixelating irradiation is projected onto the cornea for all of the update cycles for the spatial light modulator, and the second pixelating irradiation is projected onto the cornea alternately for each update cycle.

15. The system according to claim 9, wherein the controller is configured to cause the spatial light modulator to project one or more additional pixelating irradiations onto the cornea, the additional pixelating irradiations projecting onto each other portion of the desired treatment area not projected by the first pixelating irradiation, and the spatial light modulator projects the first pixelating irradiation, the second pixelating irradiation, and the one or more additional pixelating irradiations according to different temporal parameters.

16. The system according to claim 9, wherein the first pixelating irradiation and the second pixelating irradiation are projected onto a plane defined by two axes, the first pixelating irradiation and the second pixelating irradiation have the same shape and size, and the first pixelating irradiation and the second pixelating irradiation are spatially offset along at least one of the two axes.

17. The controller is configured to project a third pixelation irradiation and a fourth pixelation irradiation onto the spatial light modulator. The first pixelation irradiation, the second pixelation irradiation, the third pixelation irradiation, and the fourth pixelation irradiation have the same shape and size. The first pixelating irradiation, the second pixelating irradiation, the third pixelating irradiation, and the fourth pixelating irradiation are spatially offset from each other along at least one of the two axes. The system according to claim 16, wherein the first pixelating irradiation, the second pixelating irradiation, the third pixelating irradiation, and the fourth pixelating irradiation are projected alternately onto the cornea so as to irradiate the entire desired treatment area as a group.

18. The system according to claim 9, wherein the spatial light modulator is a DMD, the DMD includes a plurality of mirrors arranged in an array, and the plurality of mirrors are configured to selectively reflect the photoactivating light from the light source in order to provide the pixelated illumination.

19. The system according to claim 9, wherein the controller is further configured to determine the movement of the cornea, and in response to the movement, the controller controls the spatial light modulator to perform at least one of translating or deforming the first pixelating irradiation in order to continue photoactivating the crosslinking agent applied to the desired treatment area.

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