Systems for eye tracking 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-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 62 / 638,621, filed March 5, 2018, the contents of which are incorporated herein by reference in their entirety.

[0002] Technical Field The present disclosure relates to systems and methods for eye treatment, and more particularly, to systems and methods for tracking eye movements to deliver treatment to desired areas of the eye. [Background technology]

[0003] Cross-linking treatments (also called cross-linking treatments) can be used to treat eyes suffering from diseases such as keratoconus. In particular, keratoconus is a degenerative disease of the eye in which structural changes within the cornea weaken it and cause it to deform into an abnormal conical shape. Cross-linking treatments can strengthen and stabilize the areas weakened by keratoconus, preventing undesirable shape changes.

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

[0005] Cross-linking treatments may also be used to induce refractive changes in the cornea to correct disorders such as myopia, hyperopia, nearsightedness, hyperopia, astigmatism, irregular astigmatism, and presbyopia. Summary of the Invention [Problem to be solved by the invention]

[0006] For example, an effective cross-linking procedure for treating keratoconus or for performing refractive correction involves applying photoactivating light (hereinafter referred to as "photoactivating light") as precisely as possible to the specific area of ​​the cornea to be treated with a cross-linking agent. Applying photoactivating light outside of the specific area may cause undesirable structural changes in the cornea and adversely affect the treatment outcome. However, applying photoactivating light precisely can be difficult to achieve due to eye movements that may occur during surgery. Such eye movements may include, for example, corneal translation along a plane (transverse to the corneal depth), changes in gaze angle, and / or septum movement. Because cross-linking procedures require the cornea to be exposed to photoactivating light for at least one minute (e.g., 1-20 minutes), eye movements are highly likely to occur during surgery. To address the occurrence of eye movements, the systems and methods may use an active eye tracking system to determine any changes in the position of the cornea, and the application system may be adjusted accordingly to precisely apply photoactivating light to the specific area of ​​the cornea. [Means for solving the problem]

[0007] According to one exemplary embodiment, a system for administering a cross-linking treatment to a cornea of ​​an 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 a pixelated illumination with the photoactivating light. The spatial light modulator defines a maximum area of ​​the pixelated illumination. The system includes a controller configured to cause the spatial light modulator to project a first pixelated illumination onto the cornea to generate crosslinking activity within the treatment area by photoactivating a crosslinking agent administered to the treatment area. The first pixelated illumination has an area smaller than the maximum area defined by the spatial light modulator. The controller is further configured to determine a movement of the cornea. In response to the movement of the cornea, the controller controls the spatial light modulator to project a second pixelated illumination onto the treatment area based on at least one of a translation or a deformation of the first pixelated illumination to continue the photoactivation of the crosslinking agent administered to the treatment area.

[0008] In the above exemplary embodiment, the use of smaller pixelated illumination can provide a wider range of positioning adjustments to the spatial light modulator. However, smaller pixelated illumination patterns are composed of fewer pixels. Reducing the size (dimension) of the pixelated illumination can degrade the smallest resolvable spatial feature that can be projected onto the eye, creating "pixelation" defects. To address such effects, a system for administering cross-linking treatment to a cornea of ​​an 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 a pixelated illumination with the photoactivating light. The system includes a controller configured to cause the spatial light modulator to project a first pixelated illumination and a second pixelated illumination onto the cornea to photoactivate a crosslinking agent administered to the desired treatment area, thereby creating crosslinking activity in the desired treatment area. The desired treatment area includes at least one portion not illuminated by the first pixelated illumination. The second pixelated illumination includes one or more pixels that illuminate at least one portion of the desired treatment area not illuminated by the first pixelated illumination. The spatial light modulator projects a first pixelated illumination and a second pixelated illumination onto the cornea according to different temporal parameters, for example, the first pixelated illumination includes all complete pixels that may be projected within a desired treatment area, and the second pixelated illuminated one or more pixels include the remaining pixels that combine with the first pixelated illuminated pixels to illuminate the entire desired treatment area. [Brief description of the drawings]

[0009] [Figure 1] FIG. 1 illustrates one exemplary system for administering a crosslinking agent and photoactivating light to the cornea of ​​an eye to generate crosslinks in corneal collagen, according to an embodiment of the present disclosure. [Figure 2A] FIG. 1 illustrates one exemplary therapeutic system with an active eye tracking system, according to an embodiment of the present disclosure. [Figure 2B] FIG. 2B illustrates one irradiation pattern of the exemplary treatment system of FIG. 2A. [Figure 3A] FIG. 1 illustrates one exemplary therapeutic system with an alternative active eye tracking system, according to an embodiment of the present disclosure. [Figure 3B] FIG. 3B illustrates one irradiation pattern of the exemplary treatment system of FIG. 3A. [Figure 4A] FIG. 3B illustrates one exemplary irradiation pattern of the exemplary treatment system of FIG. 3A. [Figure 4B] FIG. 4B illustrates another exemplary illumination pattern based on a deformation of the illumination pattern of FIG. 4A in response to a rotational change of the subject eye. [Figure 5A] FIG. 3B illustrates an exemplary irradiation pattern for the exemplary treatment system of FIG. 3A. [Figure 5B] FIG. 5B illustrates another exemplary illumination pattern based on deformation of the illumination pattern of FIG. 5A in response to geometric distortions produced by changes in eye gaze angle and / or head movement by a subject. [Figure 6A] FIG. 3B illustrates one exemplary pixel activation corresponding to a desired irradiation pattern for the exemplary treatment system of FIG. 3A. [Figure 6B] FIG. 6B illustrates one exemplary approach for resolving pixelation defects resulting from pixel activation illustrated by FIG. 6A. [Figure 6C] FIG. 6B illustrates another exemplary approach for solving the pixelation defects resulting from pixel activation illustrated by FIG. 6A. [Figure 7A] FIG. 1 illustrates a substantially circular UV illumination pattern (diameter=4 mm) defined by pixels 25 μm×25 μm in size, according to an embodiment of the present disclosure. [Figure 7B] FIG. 1 illustrates a substantially circular UV illumination pattern (diameter=4 mm) defined by pixels 100 μm×100 μm in size, according to an embodiment of the present disclosure. [Figure 7C] FIG. 1 illustrates a substantially circular UV illumination pattern (diameter=4 mm) defined by pixels 200 μm×200 μm in size, according to an embodiment of the present disclosure. [Figure 7D]FIG. 1 illustrates a substantially circular UV illumination pattern (diameter=4 mm) defined by pixels 400 μm×400 μm in size, according to an embodiment of the present disclosure. [Figure 7E] FIG. 1 illustrates a substantially circular UV illumination pattern (diameter=4 mm) defined by pixels 750 μm×750 μm in size, according to an embodiment of the present disclosure. [Figure 7F] FIG. 1 illustrates a substantially circular UV illumination pattern (diameter=4 mm) defined by pixels 1000 μm×1000 μm in size, according to an embodiment of the present disclosure. [Figure 8A] FIG. 7B shows the modeled change in anterior corneal curvature (pre- to post-treatment) following cross-linking treatment using the UV irradiation pattern prescribed in FIG. 7A. [Figure 8B] FIG. 7C shows the modeled change in anterior corneal curvature following cross-linking treatment using the UV irradiation pattern prescribed in FIG. 7B. [Figure 8C] FIG. 7D shows the modeled change in anterior corneal curvature following cross-linking treatment using the UV irradiation pattern prescribed in FIG. 7C. [Figure 8D] FIG. 7D shows the modeled change in anterior corneal curvature following cross-linking treatment using the UV irradiation pattern prescribed in FIG. 7D. [Figure 8E] FIG. 7C shows the modeled change in anterior corneal curvature following cross-linking treatment using the UV irradiation pattern prescribed in FIG. 7E. [Figure 8F] FIG. 8C shows the modeled change in anterior corneal curvature following cross-linking treatment using the UV irradiation pattern prescribed in FIG. 8F. [Figure 9A] FIG. 13 illustrates the modeled difference in anterior corneal height (μm) resulting from two cross-linking treatments using larger pixels (750 μm×750 μm) and smaller pixels (10 μm×10 μm), respectively, to deliver a substantially circular UV irradiation pattern, according to an embodiment of the present disclosure. [Figure 9B]FIG. 9B shows the modeled difference in anterior corneal curvature (D) resulting from the two cross-linking treatments of FIG. 9A. [Figure 10A] FIG. 1 illustrates a substantially annular UV illumination pattern defined by pixels 25 μm×25 μm in size (inner diameter=4 mm, outer diameter=8.5 mm), according to an embodiment of the present disclosure. [Figure 10B] FIG. 1 illustrates a substantially annular UV illumination pattern defined by pixels 100 μm×100 μm in size (inner diameter=4 mm, outer diameter=8.5 mm), according to an embodiment of the present disclosure. [Figure 10C] FIG. 1 illustrates a substantially annular UV illumination pattern defined by pixels 200 μm×200 μm in size (inner diameter=4 mm, outer diameter=8.5 mm), according to an embodiment of the present disclosure. [Figure 10D] FIG. 1 illustrates a substantially annular UV illumination pattern defined by pixels 400 μm×400 μm in size (inner diameter=4 mm, outer diameter=8.5 mm), according to an embodiment of the present disclosure. [Figure 10E] FIG. 1 illustrates a substantially annular UV illumination pattern defined by pixels 750 μm×750 μm in size (inner diameter=4 mm, outer diameter=8.5 mm), according to an embodiment of the present disclosure. [Figure 10F] FIG. 1 illustrates a substantially annular UV illumination pattern defined by pixels 1000 μm×1000 μm in size (inner diameter=4 mm, outer diameter=8.5 mm), according to an embodiment of the present disclosure. [Figure 11A] FIG. 10B shows the modeled change in anterior corneal curvature following cross-linking treatment using the UV irradiation pattern prescribed in FIG. 10A. [Figure 11B] FIG. 10C shows the modeled change in anterior corneal curvature following cross-linking treatment using the UV irradiation pattern prescribed in FIG. 10B. [Figure 11C] FIG. 10D shows the modeled change in anterior corneal curvature following cross-linking treatment using the UV irradiation pattern defined in FIG. 10C. [Figure 11D]FIG. 10D shows the modeled change in anterior corneal curvature following cross-linking treatment using the UV irradiation pattern prescribed in FIG. [Figure 11E] FIG. 10F shows the modeled change in anterior corneal curvature following cross-linking treatment using the UV irradiation pattern defined in FIG. 10E. [Figure 11F] FIG. 10C shows the modeled change in anterior corneal curvature following cross-linking treatment using the UV irradiation pattern defined in FIG. 10F. [Figure 12A] FIG. 13 illustrates the modeled difference in anterior corneal height (μm) resulting from two cross-linking treatments using larger pixels (750 μm×750 μm) and smaller pixels (10 μm×10 μm), respectively, to deliver a substantially annular UV radiation pattern, according to an embodiment of the present disclosure. [Figure 12B] FIG. 12B shows the modeled difference in anterior corneal curvature (D) resulting from the two cross-linking treatments of FIG. 12A. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] While the disclosure is susceptible to various modifications and alternative forms, specific embodiments thereof have been shown by way of example in the drawings and are herein described in detail. It is to be understood, however, that it is not intended to limit the disclosure to the particular forms disclosed, but on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit of the disclosure.

[0011] FIG. 1 illustrates an exemplary treatment system 100 for generating collagen cross-linking in a cornea 2 of an eye 1. The treatment system 100 includes an applicator 132 for applying a cross-linking agent 130 to the cornea 2. In an exemplary embodiment, the applicator 132 can be an eye dropper, syringe, or the like that applies the photosensitizer agent 130 as droplets to the cornea 2. Exemplary systems and methods for applying the cross-linking agent are described in U.S. Patent Application Publication No. 2017 / 0296383, entitled "Systems and Methods for Delivering Drugs to an Eye," filed April 13, 2017, the contents of which are incorporated herein by reference in their entirety.

[0012] The cross-linking agent 130 may be provided in a formulation that allows for passage of the cross-linking agent 130 through the corneal epithelium 2a to the underlying region within the corneal stroma 2b. Alternatively, the corneal epithelium 2a may be removed or otherwise incised so that the cross-linking agent 130 may be applied more directly to the underlying tissue.

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

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

[0015] The optical element 112 may include one or more mirrors or lenses to direct and focus the photoactivating light emitted by the light source 110 in a particular pattern on the cornea 2. The optical element 112 may further include filters to partially block wavelengths of light emitted by the light source 110 and to select particular wavelengths of light directed to the cornea 2 to photoactivate the crosslinking agent 130. Furthermore, the optical element 112 may include one or more beam splitters to split the beam of light emitted by the light source 110 and may include one or more heat sinks to absorb the light emitted by the light source 110. The optical element 112 may also accurately and precisely focus the photoactivating light to a particular focal plane within the cornea 2 (e.g., at a particular depth within the lower region 2b where crosslinking activity is desired).

[0016] Additionally, the specific characteristics of the photoactivating light may be altered to achieve a desired degree of crosslinking in selected regions of the cornea 2. One or more controllers 120 may control the operation of the light source 110 and / or optics 112 to precisely dispense the photoactivating light according to any combination of wavelength, bandwidth, intensity, power, location, depth of penetration, and / or treatment duration (duration of exposure cycles, duration of dark cycles, and ratio of duration of exposure cycles to dark cycles).

[0017] Parameters for light activation of the cross-linking agent 130 can be adjusted, for example, to reduce the time required to achieve the desired cross-linking. In one implementation, the time can be reduced from minutes to seconds. Some configurations use 5 mW / cm 2Although the photoactivating light can be applied at an irradiance of 1000 nm to 1000 nm, in order to reduce the time required to achieve the required crosslinking, the photoactivating light can be applied at a greater irradiance (e.g., 5 mW / cm 2 The total dose of energy absorbed by the cornea 2 can be described as an effective dose, which is the amount of energy absorbed through an area of ​​the corneal epithelium 2a. For example, the effective dose for an area of ​​the corneal surface 2a can be, for example, 5 J / cm 2 , or 20 J / cm 2 or 30 J / cm 2 The effective doses listed can be from a single application of energy or from repeated applications of energy.

[0018] The optical element 112 of the present treatment system 100 may include a microelectromechanical system (MEMS) device, such as a digital micro-mirror device (DMD), to spatially and temporally modulate the illumination of the photoactivating light. With DMD technology, the photoactivating light from the light source 110 is projected in a precise spatial pattern created by extremely small mirrors arranged in an array on a semiconductor chip. Each mirror represents one or more pixels of the projected light pattern. With the DMD, topograph-guided crosslinking can be performed. Control of the DMD by topography can use several different spatial and temporal irradiance and dose profiles. These spatial and temporal dose profiles can be created using continuous wave illumination, but can be adjusted via pulsed illumination by pulsing the illumination source under varying frequency and duty cycle. Alternatively, the DMD can be adjusted to have different pixel frequencies and duty cycles on a pixel-by-pixel basis to provide ultimate flexibility using continuous wave illumination. Alternatively, both pulsed illumination and a combination of adjusted DMD frequency and duty cycle may be combined. This spatially determined crosslinking may be combined with dosimetry, interferometry, optical coherence tomography (OCT), corneal topography, etc. for pre-treatment planning and / or real-time monitoring and adjustment of corneal crosslinking during treatment. Aspects of the dosimetry system are described in more detail below. Additionally, pre-clinical patient information may be combined with finite element biomechanical computer modeling to generate patient-specific pre-treatment plans.

[0019] To control the aspect of the projection of the photoactivating light, the embodiment may also employ aspects of multi-photon excitation microscopy. Specifically, rather than irradiating the cornea 2 with a single photon of a particular wavelength, the present treatment system 100 may irradiate multiple photons of longer wavelengths (i.e., lower energy) that combine to initiate cross-linking. Advantageously, longer wavelengths are scattered less in the cornea 2 than shorter wavelengths, which allows longer wavelength light to penetrate the cornea 2 more efficiently than shorter wavelength light. The shadowing effect of incident illumination deeper in the cornea is also reduced compared to conventional short wavelength illumination, because the absorption of light by the photosensitizer is much less at longer wavelengths. This allows for enhanced control over depth-specific cross-linking. For example, in some embodiments, two photons may be used, where each photon carries approximately half the energy required to excite molecules in the cross-linking agent 130 to generate a photochemical reaction, which will be further described below. When the crosslinker 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 crosslinker molecule must absorb, for example, 3, 4, or 5 photons simultaneously to release reactive radicals. It is unlikely that multiple photons will be absorbed at nearly the same time, thus requiring a high flux of excitation photons, which may be provided through a femtosecond laser.

[0020] A number of conditions and parameters affect the cross-linking of corneal collagen by the cross-linking agent 130. For example, the irradiance and dose of the photoactivating light affect the amount and rate of cross-linking.

[0021] When the cross-linking agent 130 is specifically riboflavin, the UVA light may be applied continuously (CW) or as a pulsed light, the choice of which affects the amount, rate, and extent of cross-linking. When the UVA light is applied as a pulsed light, the duration of the exposure cycle, the dark cycle, and the ratio of the exposure cycle to the dark cycle duration will affect the resulting corneal stiffening. Pulsed light exposure can be used to stiffen the corneal tissue more or less than can be achieved with continuous wave exposure delivering 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 treatment, the on / off duty cycle can be between about 1000 / 1 to about 1 / 1000. The irradiance can be about 1 mW / cm2 average irradiance. 2 to about 1000mW / cm 2 and the pulse rate can be between about 0.01 Hz and about 1000 Hz, or between about 1000 Hz and about 100,000 Hz.

[0022] The present treatment system 100 may generate pulsed light by employing a DMD (electronically turning the light source 110 on and off) and / or by using mechanical or optoelectronic (e.g., Pockels cell) shutters or mechanical choppers or rotating apertures. Due to the inherent modulation capabilities of the DMD's pixels and subsequent stiffening based on the modulated frequency, duty cycle, irradiance, and dose delivered to the cornea, complex biomechanical stiffening patterns are imparted to the cornea, allowing for various degrees of refractive correction. These refractive corrections may include, for example, a combination of myopia, hyperopia, astigmatism, irregular astigmatism, presbyopia, and complex corneal surface corrections due to ocular conditions (e.g., keratoconus, clear peripheral disease, post-LASIK ectasia, and other conditions such as corneal biomechanical changes / degeneration). A particular advantage of the DMD system and method is that it allows for the generation of non-periodic, uniform appearing illumination that, due to the randomized asynchronous pulse topography patterning, eliminates the possibility of inducing photosensitive epileptic seizures or flicker vertigo for pulse frequencies between 2 Hz and 84 Hz.

[0023] Although the exemplary embodiment may use a stepped on / off pulsed light function, it is understood that other functions of applying light to the cornea may be used to achieve a similar effect. For example, light may be applied to the cornea according to a sinusoidal function, a sawtooth 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 more gradual transition between the on / off values. Furthermore, it will be understood that the illuminance need not decrease to a value of zero during the off cycle, but may exceed zero during the off cycle. The desired effect may be achieved by applying light to the cornea according to a curve that varies the illuminance between two or more values.

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

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

[0026] Riboflavin undergoes photoactivation upon absorption of radiation energy, specifically light. There are two photochemical kinetic pathways for riboflavin photoactivation: Type I and Type II. The reactions involved in both Type I and Type II mechanisms, as well as other aspects of the photochemical kinetic reactions that generate cross-linking 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," the contents of which are incorporated herein by reference in their entirety.

[0027] For example, to treat keratoconus or to achieve refractive correction, an effective cross-linking procedure applies photoactivating light as precisely as possible to the specific area of ​​the cornea that is to be treated with a cross-linking agent. Applying photoactivating light outside of the specific area may cause undesirable structural changes in the cornea, adversely affecting the treatment outcome. However, precise application of photoactivating light may be difficult to achieve due to eye movements that may occur during the procedure. Such eye movements may include, for example, translational movement along the xy plane, changes in gaze angle, and / or septum movement, as shown in FIG. 1. (In FIG. 1, the depth of the cornea 2 may be measured along the z-axis, and the pattern of photoactivating light may be projected in the lateral xy plane.) Because cross-linking procedures require the cornea to be exposed to photoactivating light for at least 1 minute, e.g., 1-20 minutes, it is highly likely that some eye movement will occur during the procedure.

[0028] To address the occurrence of eye movements, embodiments may use an active eye tracking system to determine changes in the position of the cornea, and in response, the illumination system may be adjusted to precisely illuminate specific areas of the cornea with photoactivating light. FIG. 2A illustrates an exemplary treatment system 200 with an active eye tracking system. The treatment system 200 includes an illumination system for directing photoactivating light to the cornea 2 of the eye 1. The illumination system includes a light source 110 and an optical element 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. The optical element 112, including a Digital Micromirror Device (DMD) 212, illuminates the photoactivating light along the xy plane on the cornea 2 in a precise spatial pattern. Additionally, the treatment system 200 includes one or more controllers 120 for controlling aspects of the treatment system 200.

[0029] With respect to an active eye tracking system, the treatment system 200 includes a camera (image capture device) 252 that dynamically captures images of the eye 1 during surgery. The one or more controllers 120 may process the images to detect the position of a reference point (e.g., pupil) of the eye 1 relative to the treatment system 200. Using the position of the reference point as a reference, the one or more fiducial point controllers 120 may determine the location of a particular area of ​​the cornea 2. In this manner, the one or more controllers 120 may adjust the treatment system 200 to irradiate the photoactivating light to the location of the particular area. The camera 252 and software (e.g., computer readable instructions stored on a non-transitory medium) for processing the images and adjusting the treatment system 200 may collectively be known as a vision system.

[0030] 2B, the entire mirror array of the DMD 212 defines a maximum area 202 for applying photoactivating light. The maximum area 202 includes boundaries 202a-d. Any portion of the array of the DMD 212 may be activated to apply photoactivating light from any portion of the maximum area 202. For example, as shown in FIG. 2B, a portion of the array of the DMD 212 may be substantially circular and aligned at positions (x c , y c ) and has a diameter D1. 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 small distance within the region 202 while maintaining the same shape with diameter D1. For example, if a different portion of the array of DMDs 212 is located at a different position (x c +δ x1 , y c +δ y1 ), where δ x1 represents the possible translation along the x-axis, and δ y1 represents a possible translational movement along the y-axis. Translational movement of illumination pattern 204 within region 202 changes the position of the corresponding photoactivating light as it illuminates cornea 2. In this manner, in response to eye movements detected via camera 252, one or more controllers 120 may control DMD 212 to adjust illumination of the photoactivating light to reach designated regions of cornea 2 to achieve desired results.

[0031] However, the adjustments that the one or more controllers 120 can make with the DMD 212 are limited by the small amount of free space between the illumination pattern 204 and the boundaries 202a-d. With the DMD 212 alone, the one or more controllers 120 may not be able to make large enough adjustments to the position of the illumination pattern 204 within the region 202 to respond to larger eye movements. In other words, the illumination pattern 204 may reach one of the boundaries 202a-d before it has been moved the desired distance. To make larger adjustments that the DMD 212 cannot make, the treatment system 200 includes an electromechanical XY motion system 254 coupled with the one or more optical elements 112. The one or more controllers 120 can control the XY motion system 254 to move the one or more optical elements 112 to better mechanically align with the cornea 2 in response to larger eye movements. For example, the XY motion system 254 can include an electromechanical stage operable to move one or more optical elements 112 and corresponding photoactivating lights along the x-axis and / or y-axis. In this manner, the treatment system 200 can use 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] FIG. 3A illustrates one exemplary treatment system 300 with an alternative active eye tracking system. In contrast to the treatment system 200 illustrated in FIG. 2A, the treatment system 300 does not employ an XY motion system 254. Rather, the treatment system 300 uses a DMD 312 to perform substantially all desired adjustments digitally. Similar to the DMD 212 described above, the entire mirror array in the DMD 312 defines the same maximum area 202 for dispensing photoactivating light, as illustrated in FIG. 3B. The maximum area 202 includes the same boundaries 202a-d. Any portion of the array of the DMD 312 can be actuated to dispense light from any portion of this maximum area 202. To eliminate the need for the XY motion system 254 employed for the irradiation pattern 204 illustrated in FIG. 2A, the DMD 312 illuminates an illumination pattern 304 that is significantly smaller than the illumination pattern 204.

[0033] A comparison of Figures 2B and 3B clearly shows the difference between the respective illumination patterns 204, 304 within the same maximum area 202. The smaller area illumination pattern 304 is generated by activating fewer DMD arrays. The illumination pattern 304 is substantially circular and has a smaller area at the location (x c , y c ), but has a diameter D2 that is smaller than diameter D1 of illumination pattern 204. Thus, there is more free space between illumination pattern 304 and boundaries 202a-d than between illumination pattern 204 and boundaries 202a-d. This larger space allows the center of illumination pattern 304 to be translated along the x-axis and / or y-axis within region 202 to a greater extent than the center of illumination pattern 204. In other words, if a different portion of the array of DMD 312 is located at a different position (x c +δ x2 , y c +δ y2 ), where δ x2 is δ x1 is larger than δ y2 is δ y1 and δ x1 and δy1 represents the possible translational movements along each axis that the treatment system 200 has.

[0034] Translation of the illumination pattern 304 within the region 202 changes the position of the corresponding photoactivating light when applied to the cornea 2. The greater potential translation of the illumination pattern 304 by the DMD 312 allows for a greater range of adjustments for the application of the photoactivating light along the x-axis and / or y-axis. In this manner, in response to eye movements detected via the camera 252, the one or more controllers 120 can use the DMD 312 to make substantially any desired adjustments so that the photoactivating light reaches a particular region of the cornea 2 to achieve a desired result.

[0035] The treatment system 200 relies on an electromechanical XY motion system 254 that may use slower motors. In contrast, the DMD 312 can digitally respond to commands at a rate of approximately 60 Hz, allowing the treatment system 300 to more quickly make position adjustments to the administration of photoactivating light.

[0036] By using the DMD 312, the treatment system 300 can also perform other position corrections that are not possible with the X-Y motion system 254. For example, the treatment system 300 can respond more effectively to rotational changes in the eye position by applying a rotational deformation corresponding to the rotational change in the eye position to the irradiation pattern irradiated to the eye via the DMD 312. FIG. 4A shows an initial irradiation pattern 404a generated by activating a portion of the array of the DMD 312. The irradiation pattern 404a has an initial rotation state. When the treatment system 300 detects a rotational change in the eye position via the camera 252, another portion of the array of the DMD 312 can be activated to generate an irradiation pattern 404b shown in FIG. 4B. The irradiation pattern 404b provides a geometric deformation of the initial irradiation pattern 404a with a different rotation state than the initial state in response to the rotational change in the eye position.

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

[0038] By using a smaller illumination pattern, a wider range of positioning is provided for the DMD 312. As described above, the DMD provides an illumination pattern that is pixelated according to an array of mirrors. Since the illumination pattern from the DMD is composed of a discrete number of pixels, a smaller illumination pattern is composed of fewer pixels. In this way, reducing the size of the illumination pattern can degrade the smallest resolvable spatial feature that can be projected onto the eye, resulting in "pixelation" artifacts. As shown in FIG. 6A, the DMD 312 provides a maximum illumination area 602 defined by a number of pixels 602a. The treatment system 300 can activate a subset of these pixels to generate a smaller illumination pattern that allows a wider range of positioning. For example, 602a in FIG. 6A shows the boundary (contour) of a desired illumination pattern 606. However, due to the size of the desired illumination pattern 606, only pixel 604a substantially fits within the desired illumination pattern 606. If only pixel 604a is actuated, a portion of the desired illumination pattern 606 remains unfilled. However, if pixel 604b is actuated to fill the remaining portion of the desired illumination pattern 606, the resulting illumination pattern does not have the desired shape. In either case, the resulting illumination pattern does not have smooth edges corresponding to the desired illumination pattern 606. In general, the example of FIG. 6A illustrates the tradeoff between the range of adjustments possible for active eye tracking on the DMD and the resolution to obtain the desired illumination pattern for a given DMD array size.

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

[0040] FIG. 6C illustrates another approach to smooth the pixelation defects illustrated by FIG. 6A. Specifically, dithering may be applied by shifting the primitive shape defined by pixel 604a illustrated in FIG. 6A by alternating + / -1 pixel along the x-axis or y-axis at interleaved points in time. For example, in one update cycle, DMD 312 is operated to translate the primitive shape by one pixel in the positive y-direction (from the position illustrated in FIG. 6A) to include a boundary defined in part by pixel 608a. In the next update cycle, DMD 312 is operated to translate the primitive shape by one pixel in the positive x-direction (from the position illustrated in FIG. 6A) to include a boundary defined in part by pixel 608b. In the next update cycle, DMD 312 is operated to translate the primitive shape by one pixel in the negative y-direction (from the position illustrated in FIG. 6A) to include a boundary defined in part by pixel 608c. In the next update cycle, DMD 312 is operated to translate the primitive shape one pixel in the negative x-direction (from the position shown in FIG. 6A) so that it includes the boundary defined in part by pixel 608d. This series of steps is repeated to provide a smoother illumination pattern that more closely approximates the desired illumination pattern 606 and corresponding dose of photoactivating light.

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

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

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

[0044] 9A-B show the modeled difference in the results of two crosslinking processes 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. FIG. 9A shows the anterior corneal surface height (μm) obtained after using the larger pixels minus the anterior corneal surface height (μm) obtained after using the smaller pixels. FIG. 9B shows the anterior corneal surface curvature (D) obtained after using the larger pixels minus the anterior corneal surface curvature (D) obtained after using the smaller pixels.

[0045] 8A-F and Table 1 show, however, that the changes in tangent and corneal curvature are effectively similar for treatments using pixel sizes up to 250 μm×250 μm (or 400 μm×400 μm) for a substantially circular illumination pattern. Similar results with larger pixel sizes (compared to smaller 10 μm×10 μm pixels, for example) enable effective implementation of the eye tracking approach of the exemplary system 300 described above.

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

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

[0048] 12A-B show the modeled difference between the results of two cross-linking treatments using larger and smaller pixels, respectively, to deliver a substantially annular UV radiation pattern. Specifically, the larger pixels are 750 μm×750 μm in size and the smaller pixels are 10 μm×10 μm in size. FIG. 12A shows the anterior corneal surface height (μm) obtained after using the larger pixels minus the anterior corneal surface height (μm) obtained after using the smaller pixels. FIG. 12B shows the anterior corneal surface curvature (D) obtained after using the larger pixels minus the anterior corneal surface curvature (D) obtained after using the smaller pixels.

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

[0050] While the above embodiment may include the use of a DMD device, alternative embodiments may use any type of programmable spatial light modulator to achieve similar results. For example, embodiments may use a liquid crystal microdisplay, either transmissive or reflective. A spatial light modulator that provides polarization variation may be used in combination with a fixed polarizer to achieve similar results. A transmissive implementation may have additional advantages in terms of overall system size.

[0051] In view of the foregoing, the embodiments employ a purely digital means for eye tracking that can be used in conjunction with an illumination system to perform corneal crosslinking. In particular, the embodiments do not require an electromechanical motion system (e.g., for adjustment along the xy plane) to keep the photoactivating light beam aligned with the desired region of the subject's eye. 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 compared to other systems, adjustment for rotational movements of the eye, and correction of geometric distortions caused by changes in gaze angle and / or head movements.

[0052] As mentioned above, according to some aspects of the present disclosure, some or all of the steps of the above-described and illustrated procedures may be automated or guided under the control of a controller (e.g., controller 120). In general, the controller may be implemented as a combination of hardware and software elements. The hardware aspects may include a combination of operatively coupled hardware components including a microprocessor, logic circuitry, communication / network ports, digital filters, memory, or logic circuitry. The controller may be adapted to perform operations specified by computer-executable code (which may be stored on a computer-readable medium).

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

[0054] Exemplary embodiments of the present disclosure may include software stored on any one or combination of computer readable media for controlling the devices and subsystems of the exemplary embodiments, for driving the devices and subsystems of the exemplary embodiments, and for enabling the devices and subsystems of the exemplary embodiments 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, application software, and the like. Such computer readable media may further include computer program products of the embodiments of the present disclosure for performing all or a portion (if the processing is distributed) of the processing performed in the implementation. Computer code devices of the exemplary embodiments of the present disclosure may include any suitable interpretable or executable code mechanism, including, but not limited to, scripts, interpretable programs, dynamic link libraries (DLLs), Java classes and applets, complete executable programs, and the like. Additionally, portions of the processing of the exemplary embodiments of the present disclosure may be distributed for better performance, reliability, cost, and the like.

[0055] Common forms of computer readable media may include, for example, a floppy disk, a flexible disk, a hard disk, magnetic tape, other suitable magnetic media, CD-ROM, CDRW, DVD, other suitable optical media, punch cards, paper tape, optical mark sheets, other suitable physical media with a pattern of holes or other optically recognizable indicia, RAM, PROM, EPROM, FLASH-EPROM, other suitable memory chips or cartridges, a computer readable carrier wave, or other suitable medium.

[0056] Although the present disclosure has been described with reference to one or more specific embodiments, those skilled in the art will recognize that many modifications may be made thereto without departing from the spirit and scope of the present disclosure. Each of these embodiments and their obvious variations are considered to be within the spirit and scope of the present disclosure. It is also contemplated that additional embodiments according to aspects of the present disclosure may combine any number of features of any of the embodiments described herein.

Claims

1. 1. A system for administering a cross-linking treatment to a cornea of ​​an eye, comprising: 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 a pixelated illumination using the photoactivating light, the spatial light modulator defining a maximum area of ​​the pixelated illumination; and a controller configured to cause the spatial light modulator to project a first pixelated illumination onto the cornea to generate crosslinking activity in the treatment area by photoactivating a crosslinking agent applied to the treatment area, the first pixelated illumination having an area smaller than the maximum area defined by the spatial light modulator; Including, the controller is further configured to determine a movement of the cornea, and in response to the movement of the cornea, the controller controls the spatial light modulator to project a second pixelated illumination to the treatment area based on at least one of a translation or a deformation of the first pixelated illumination to continue photoactivation of the crosslinking agent applied to the treatment area. The above system

2. 2. The system of claim 1, wherein the spatial light modulator is a digital micro-mirror device (DMD), the DMD including a plurality of mirrors arranged in an array configured to selectively reflect the photoactivating light from the light source to provide the pixelated illumination, the plurality of mirrors defining a maximum area of ​​the pixelated illumination, and the controller determines a first subset of the plurality of mirrors to provide the first pixelated illumination and a second subset of the plurality of mirrors to provide a second pixelated illumination.

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

4. 2. The system of claim 1, wherein the spatial light modulator includes a boundary defining a maximum area of ​​the pixelated illumination, the first pixelated illumination being centered at a first location within the boundary and the second pixelated illumination being centered at a second location within the boundary, the second location being different from the first location.

5. The system of claim 4 , wherein the first pixelated illumination and the second pixelated illumination have the same shape and size.

6. The system of claim 1 , wherein the first pixelated illumination and the second pixelated illumination have different shapes.

7. The system of claim 1 , wherein the controller controls the spatial light modulator to geometrically transform the first pixelated illumination to generate the second pixelated illumination.

8. The system of claim 7 , wherein the geometric transformation rotates the first pixelated illumination to generate the second pixelated illumination.

9. 8. The system of claim 7, wherein the controller controls the spatial light modulator to project the first pixelated illumination onto the plane of the cornea according to a desired shape and size, the movement of the cornea including movement of the plane of the cornea, and the controller controls the spatial light modulator to project the second pixelated illumination onto the plane of the cornea to generate the desired shape and size.

10. 1. A system for administering a cross-linking treatment to a cornea of ​​an eye, comprising: 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 a pixelated illumination using the photoactivating light; and a controller configured to cause the spatial light modulator to project a first pixelated illumination and a second pixelated illumination onto the cornea to photoactivate a crosslinking agent applied to a desired treatment area, thereby generating crosslinking activity in the desired treatment area; Including, the desired treatment area includes at least one portion not projected by the first pixelated illumination, the second pixelated illumination includes one or more pixels that project at least one portion of the desired treatment area not projected by the first pixelated illumination, and the spatial light modulator projects the first pixelated illumination and the second pixelated illumination to the cornea according to different temporal parameters. The above system

11. 11. The system of claim 10, wherein the first pixelated illumination includes all complete pixels that may be projected within the desired treatment area, and the second pixelated illuminated one or more pixels include remaining pixels that combine with the first pixelated illuminated pixels to project the entire desired treatment area.

12. 11. The system of claim 10, wherein the first pixelated illumination is projected substantially inside the desired treatment area and the second pixelated illuminated one or more pixels are projected inside and outside the desired treatment area.

13. 11. The system of claim 10, wherein the one or more pixels of the second pixelated illumination are disposed along a boundary of the desired treatment area.

14. 11. The system of claim 10, wherein the first pixelated illumination is projected onto the cornea for a predetermined period of time and the second pixelated illumination is dithered onto the cornea at a fast rate during said period.

15. 11. The system of claim 10, wherein the first pixelated illumination is projected onto the cornea every update cycle for the spatial light modulator and the second pixelated illumination is projected onto the cornea every update cycle for the spatial light modulator.

16. 11. The system of claim 10, wherein the controller is configured to cause the spatial light modulator to project one or more additional pixelated illuminations onto the cornea, the additional pixelated illuminations projecting different respective portions of the desired treatment area not projected by the first pixelated illumination, and the spatial light modulator projects the first pixelated illumination, the second pixelated illumination, and the one or more additional pixelated illuminations according to different temporal parameters.

17. 11. The system of claim 10, wherein the first pixelated illumination and the second pixelated illumination are projected onto a plane defined by two axes, the first pixelated illumination and the second pixelated illumination have the same shape and size, and the first pixelated illumination and the second pixelated illumination are spatially offset along at least one of the two axes.

18. the controller is configured to cause the spatial light modulator to further project a third pixelated illumination and a fourth pixelated illumination; the first pixelated illumination, the second pixelated illumination, the third pixelated illumination, and the fourth pixelated illumination have the same shape and size; the first pixelated illumination, the second pixelated illumination, the third pixelated illumination, and the fourth pixelated illumination are spatially offset from one another along at least one of the two axes; 20. The system of claim 17, wherein the first pixelated illumination, the second pixelated illumination, the third pixelated illumination, and the fourth pixelated illumination are alternately projected onto the cornea to collectively illuminate the entire desired treatment area.

19. 11. The system of claim 10, wherein the spatial light modulator is a DMD including a plurality of mirrors arranged in an array configured to selectively reflect the photoactivating light from the light source to provide the pixelated illumination.

20. 11. The system of claim 10, wherein the controller is further configured to determine a movement of the cornea, and in response to the movement, the controller controls the spatial light modulator to at least one of translate or transform the first pixel illumination to continue to photoactivate the crosslinking agent applied to the desired treatment area.

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