PHOTOACTIVATION SYSTEMS AND METHODS FOR CORNEAL CROSS-LINKING TREATMENTS
A system for treating an eye includes a laser light source providing photoactivating light. The system includes a scanning system to receive the photoactivating light as a laser beam and to move the laser beam over a cornea treated with a cross-linking agent. The system includes a controller that provides control signal(s) to programmatically control the laser light source and the scanning system. The control signal(s) cause the laser beam to visit region(s) of the cornea more than once according to a scan pattern and expose the region(s) to the photoactivating light. The photoactivating light causes the cross-linking agent in the exposed region(s) to react with oxygen to generate cross-linking activity in the exposed region(s). The scan pattern causes a predetermined period of time to pass between visits by the laser beam to the exposed region(s), the predetermined period of time allowing oxygen in the exposed region(s) to replenish.
This application is a continuation of U.S. patent application Ser. No. 16/987,370, filed Aug. 6, 2020, claiming priority to, and the benefit of, U.S. Provisional Patent Application No. 62/883,197, filed Aug. 6, 2019, the contents of which are incorporated entirely herein by reference and relied upon.
BACKGROUND FieldThe present disclosure pertains to systems and methods for eye treatments, and more particularly, to systems and methods for photoactivating a cross-linking agent.
Description of Related ArtCross-linking treatments may be employed to treat eyes suffering from disorders, such as keratoconus. In particular, keratoconus is a degenerative disorder of the eye in which structural changes within the cornea cause it to weaken and change to an abnormal conical shape. Cross-linking treatments can strengthen and stabilize areas weakened by keratoconus and prevent undesired shape changes.
Cross-linking treatments may also be employed after surgical procedures, such as Laser-Assisted in situ Keratomileusis (LASIK) surgery. For instance, a complication known as post-LASIK ectasia may occur due to the thinning and weakening of the cornea caused by LASIK surgery. In post-LASIK ectasia, the cornea experiences progressive steepening (bulging). Accordingly, cross-linking treatments can strengthen and stabilize the structure of the cornea after LASIK surgery and prevent post-LASIK ectasia.
Cross-linking treatments may also be employed to induce refractive changes in the cornea to correct disorders such as myopia, hyperopia, astigmatism, irregular astigmatism, presbyopia, etc.
SUMMARYEmbodiments include systems and methods for photoactivating a cross-linking agent in corneal cross-linking treatments. Using a laser light source to achieve a scanned light pattern can provide advantages for photoactivating a cross-linking agent. In particular, scanning parameters for the laser can be optimized to increase the efficacy of individual treatments. For instance, treatment time, total dose, intensity/irradiance of the laser beam, pulsing of the laser beam, size of the spot defined by the laser beam (laser spot size), velocity or duration of application of the laser spot, and/or frequency of repetition of portions of the scan pattern can be controlled to enhance cross-linking activity. Such parameters can be optimized according to the photochemical kinetic reactions involved in cross-linking activity as described above. These reactions determine the consumption and replenishment of oxygen during cross-linking activity, supply and photo-degradation of the cross-linking agent molecules, and depth of effect.
According to an example embodiment, a system for treating an eye includes a laser light source configured to provide photoactivating light. The system includes a scanning system configured to receive the photoactivating light as a laser beam and to move the laser beam over a cornea treated with a cross-linking agent. The system includes a controller configured to provide control signals to programmatically control the laser light source and the scanning system. The one or more control signals causing the laser beam to visit one or more regions of the cornea more than once according to a scan pattern and expose the one or more regions to the photoactivating light. The photoactivating light causes the cross-linking agent in the one or more exposed regions to react with oxygen to generate cross-linking activity in the one or more exposed regions. The scan pattern causes a predetermined period of time to pass between visits by the laser beam to the one or more exposed regions, the predetermined period of time allowing oxygen in the one or more exposed regions to replenish and allow a desired amount of the cross-linking activity to be generated with sufficient oxygen during each visit to the one or more exposed regions.
According to another example embodiment, a method for treating an eye includes generating photoactivating light with a laser light source. The method includes directing the photoactivating light as a laser beam to a scanning system. The method includes operating the scanning system to cause the laser beam to move over the cornea and visit one or more regions of the cornea more than once according to a scan pattern and expose the one or more regions to the photoactivating light. The photoactivating light causes the cross-linking agent in the one or more exposed regions to react with oxygen to generate cross-linking activity in the one or more exposed regions. The method includes optimizing the scan pattern to cause a predetermined period of time to pass between visits by the laser beam to the one or more exposed regions, the predetermined period of time allowing oxygen in the one or more exposed regions to replenish and allow a desired amount of the cross-linking activity to be generated with sufficient oxygen during each visit to the one or more exposed regions.
While the present disclosure is susceptible to various modifications and alternative forms, a specific embodiment thereof has been shown by way of example in the drawings and will herein be described in detail. It should be understood, however, that it is not intended to limit the present 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 present disclosure.
DESCRIPTIONThe cross-linking agent 130 may be provided in a formulation that allows the cross-linking agent 130 to pass through the corneal epithelium 2a and to underlying regions in the corneal stroma 2b (also known as an “epi-on” procedure). Alternatively, the corneal epithelium 2a may be removed or otherwise incised to allow the cross-linking agent 130 to be applied more directly to the underlying tissue (also known as an “epi-off” procedure).
The treatment system 100 includes an illumination system with a light source 110 and optical elements 112 for directing light to the cornea 2. In some embodiments, the light source 110 may include a light emitting diode (LED). In other embodiments, the light source 110 may provide a laser. The light causes photoactivation of the cross-linking agent 130 to generate cross-linking activity in the cornea 2. For example, the cross-linking agent may include riboflavin and the photoactivating light may include ultraviolet A (UVA) (e.g., approximately 365 nm or 375 nm, or a wavelength falling within the band of 315 nm to 400 nm) light. Alternatively, the photoactivating light may include another wavelength, such as a visible wavelength (e.g., approximately 452 nm) or any other wavelength selected to activate a photosensitizing agent. As described further below, corneal cross-linking improves corneal strength by creating chemical bonds within the corneal tissue according to a system of photochemical kinetic reactions.
Riboflavin and the photoactivating light may be applied to stabilize and/or strengthen corneal tissue to address corneal ectatic disorders, such as keratoconus or post-LASIK ectasia. The application of riboflavin and the photoactivating light may also allow for various amounts of refractive correction, which for instance, may involve combinations of myopia, hyperopia, astigmatism, irregular astigmatism, presbyopia and complex corneal refractive surface corrections due to corneal ectatic disorders as well as other conditions of corneal biomechanical alteration/degeneration, etc.
The treatment system 100 includes one or more controllers 120 that control aspects of the treatment system 100, including the light source 110 and/or the optical elements 112. In an implementation, the cornea 2 can be more broadly treated with the cross-linking agent 130 (e.g., with an eye dropper, syringe, etc.), and the photoactivating light from the light source 110 can be selectively directed to regions of the treated cornea 2 according to a particular pattern.
The optical elements 112 may include one or more mirrors, lenses, or other optical components for directing and focusing the photoactivating light emitted by the light source 110 to a particular pattern on the cornea 2. The optical elements 112 may further include filters for partially blocking wavelengths of light emitted by the light source 110 and for selecting particular wavelengths of light to be directed to the cornea 2 for photoactivating the cross-linking agent 130. In addition, the optical elements 112 may include one or more beam splitters for dividing a beam of light emitted by the light source 110, and may include one or more optical sinks for absorbing light emitted by the light source 110. The optical elements 112 may also accurately and precisely focus the photo-activating light to particular focal planes within the cornea 2, e.g., at a particular depths in the underlying region 2b where cross-linking activity is desired.
According to some aspects, optical elements of an example treatment system may employ fiber-optic elements. The use of fiber-optic elements can eliminate the need for free space optical elements as well as opto-mechanical mounts in a treatment system. Advantageously, the use of fiber-optics can reduce the size and footprint of a treatment system, reduce design and manufacturing complexity and cost, and enhance reliability.
Moreover, specific regimes of the photoactivating light can be modulated to achieve a desired degree of cross-linking in the selected regions of the cornea 2. The one or more controllers 120 may be used to control the operation of the light source 110 and/or the optical elements 112 to precisely deliver the photoactivating light according to any combination of: wavelength, bandwidth, intensity, power, location, depth of penetration, and/or duration of treatment (the duration of the exposure cycle, the dark cycle, and the ratio of the exposure cycle to the dark cycle duration).
The parameters for photoactivation of the cross-linking agent 130 can be adjusted, for example, to reduce the amount of time required to achieve the desired cross-linking. In an example implementation, the time can be reduced from minutes to seconds. While some configurations may apply the photoactivating light at an irradiance of 5 mW/cm2, larger irradiance of the photoactivating light, e.g., multiples of 5 mW/cm2, can be applied to reduce the time required to achieve the desired cross-linking. The total dose of energy absorbed in the cornea 2 can be described as an effective dose, which is an amount of energy absorbed through an area of the corneal epithelium 2a. For example the effective dose for a region of the corneal surface 2A can be, for example, 5 J/cm2, or as high as 20 J/cm2 or 30 J/cm2. The effective dose described can be delivered from a single application of energy, or from repeated applications of energy.
The optical elements 112 of the treatment system 100 may include a microelectromechanical system (MEMS) device, e.g., a digital micro-mirror device (DMD), to modulate the application of photoactivating light spatially and temporally. Using DMD technology, the photoactivating light from the light source 110, e.g., an LED, is projected in a precise spatial pattern that is created by microscopically small mirrors laid out in an array on a semiconductor chip. Each mirror represents one or more pixels in the pattern of projected light. With the DMD one can perform topography guided cross-linking. The control of the DMD according to topography may employ several different spatial and temporal irradiance and dose profiles. As described further below, these spatial and temporal dose profiles may be created using continuous wave (CW) illumination but may also be modulated via pulsed illumination by pulsing the illumination source under varying frequency and duty cycle regimes. Alternatively, the DMD can modulate different frequencies and duty cycles on a pixel by pixel basis to give ultimate flexibility using continuous wave illumination. Or alternatively, both pulsed illumination and modulated DMD frequency and duty cycle combinations may be combined. This allows for specific amounts of spatially determined corneal cross-linking. This spatially determined cross-linking may be combined with dosimetry, interferometry, optical coherence tomography (OCT), corneal topography, etc., for pre-treatment planning and/or real time monitoring and modulation of corneal cross-linking during treatment. Additionally, pre-clinical patient information may be combined with finite element biomechanical computer modeling to create patient specific pre-treatment plans.
To control aspects of the delivery of the photoactivating light, embodiments may also employ aspects of multiphoton excitation microscopy. In particular, rather than delivering a single photon of a particular wavelength to the cornea 2, the treatment system 100 may deliver multiple photons of longer wavelengths, i.e., lower energy, that combine to initiate the cross-linking. Advantageously, longer wavelengths are scattered within the cornea 2 to a lesser degree than shorter wavelengths, which allows longer wavelengths of light to penetrate the cornea 2 more efficiently than light of shorter wavelengths. Shielding effects of incident irradiation at deeper depths within the cornea are also reduced over conventional short wavelength illumination since the absorption of the light by the photosensitizer is much less at the longer wavelengths. This allows for enhanced control over depth specific cross-linking. For example, in some embodiments, two photons may be employed, where each photon carries approximately half the energy necessary to excite the molecules in the cross-linking agent 130 to generate the photochemical kinetic reactions described further below. When a cross-linking agent molecule simultaneously absorbs both photons, it absorbs enough energy to release reactive radicals in the corneal tissue. Embodiments may also utilize lower energy photons such that a cross-linking agent molecule must simultaneously absorb, for example, three, four, or five, photons to release a reactive radical. The probability of the near-simultaneous absorption of multiple photons is low, so a high flux of excitation photons may be required, and the high flux may be delivered through a femtosecond laser.
A large number of conditions and parameters affect the cross-linking of corneal collagen with the cross-linking agent 130. For example, the irradiance and the dose of photoactivating light affect the amount and the rate of cross-linking. The UVA light may be applied continuously (CW) or as pulsed light, and this selection has an effect on the amount, the rate, and the extent of cross-linking. If the UVA light is applied as pulsed light, the duration of the exposure cycle, the dark cycle, and the ratio of the exposure cycle to the dark cycle duration have an effect on the resulting corneal stiffening. Pulsed light illumination can be used to create greater or lesser stiffening of corneal tissue than may be achieved with continuous wave illumination for the same amount or dose of energy delivered. Light pulses of suitable length and frequency may be used to achieve more optimal chemical amplification. For pulsed light treatment, the on/off duty cycle may be between approximately 1000/1 to approximately 1/1000; the irradiance may be between approximately 1 mW/cm2 to approximately 1000 mW/cm2 average irradiance, and the pulse rate may be between approximately 0.01 HZ to approximately 1000 Hz or between approximately 1000 Hz to approximately 100,000 Hz.
The treatment system 100 may generate pulsed light by employing a DMD, electronically turning the light source 110 on and off, and/or using a mechanical or opto-electronic (e.g., Pockels cells) shutter or mechanical chopper or rotating aperture. Because of the pixel specific modulation capabilities of the DMD and the subsequent stiffness imparted based on the modulated frequency, duty cycle, irradiance and dose delivered to the cornea, complex biomechanical stiffness patterns may be imparted to the cornea. A specific advantage of the DMD system and method is that it allows for randomized asynchronous pulsed topographic patterning, creating a non-periodic and uniformly appearing illumination which eliminates the possibility for triggering photosensitive epileptic seizures or flicker vertigo for pulsed frequencies between 2 Hz and 84 Hz.
Although example embodiments may employ stepwise on/off pulsed light functions, it is understood that other functions for applying light to the cornea may be employed to achieve similar effects. For example, light may be applied to the cornea according to a sinusoidal function, sawtooth function, or other complex functions or curves, or any combination of functions or curves. Indeed, it is understood that the function may be substantially stepwise where there may be more gradual transitions between on/off values. In addition, it is understood that irradiance does not have to decrease down to a value of zero during the off cycle, and may be above zero during the off cycle. Desired effects may be achieved by applying light to the cornea according to a curve varying irradiance between two or more values.
Examples of systems and methods for delivering photoactivating light are described, for example, in U.S. Patent Application Publication No. 2011/0237999, filed Mar. 18, 2011 and titled “Systems and Methods for Applying and Monitoring Eye Therapy,” U.S. Patent Application Publication No. 2012/0215155, filed Apr. 3, 2012 and titled “Systems and Methods for Applying and Monitoring Eye Therapy,” and U.S. Patent Application Publication No. 2013/0245536, filed Mar. 15, 2013 and titled “Systems and Methods for Corneal Cross-Linking with Pulsed Light,” the contents of these applications being incorporated entirely herein by reference. Embodiments may generate cross-linking activity in the cornea according to circular and/or annular patterns defined by the delivery of photoactivating light (e.g., via the DMD described above). Additionally or alternatively, embodiments may generate cross-linking activity in the cornea according to non-circular and/or non-annular patterns defined by the delivery of photoactivating light (e.g., via the DMD).
Patterns of photoactivating light can be applied (e.g., via the DMD) to the eye in separate treatment zones with different doses sequentially or continuously applied. For instance, one treatment zone can be “turned off” (i.e., delivery of the corresponding photoactivating light ceases) while another “stays on” (i.e., delivery of the corresponding photoactivating light continues). The treatment zones can be, for instance, annularly shaped about a center point of the eye. There may also be discontinuous zones where no the photoactivating light is applied (e.g., a central treatment zone surrounded by an annulus of no light surrounded by an annular treatment zone of light, etc.). The widths of the annular zones can be of different dimensions, e.g., one annular zone has a width of 1 mm and another has a width of 2 mm. Applying the photoactivating light in annular treatment zones on the periphery of the eye without a central treatment zone can result in a hyperopic correction, for instance, by causing the central region of the eye to have an increased curvature while the periphery is strengthened. In some cases, central and surrounding treatment zones can be elliptical in shape, for instance to address astigmatism, by preferentially generating cross-linking activity in regions of the cornea to correct the astigmatism. Such elliptically shaped annular treatment zones are preferentially oriented with the axis of the annular treatment zones aligned according to the orientation of the astigmatism. The elliptically shaped treatment zones can also be irregularly asymmetric (i.e., having major and minor axis that are not perpendicular and can be situated with distinct center points (centers of mass)).
Cross-linking treatments can be tuned according to one or more biomechanical properties of the eye, such as the corneal topography (i.e., shape), corneal strength (i.e., stiffness), and/or corneal thickness. Optical correction and/or strengthening of the cornea can be achieved by applying the cross-linking agent and/or photoactivating light in one or more iterations with adjustable characteristics for each iteration. Generally, a developed treatment plan can include a number of applications of the cross-linking agent, the amount and concentration of the cross-linking agent for each application, the number of applications of photoactivating light, and the timing, duration, power, energy dosage, and pattern of the photoactivating light for each application. Furthermore, the cross-linking treatments can be adapted based on feedback information relating to the biomechanical properties gathered in real time during treatment or during breaks in treatments.
When riboflavin absorbs radiant energy, especially light, it undergoes photoactivation. There are two photochemical kinetic pathways for riboflavin photoactivation, Type I and Type II. The reactions involved in both the Type I and Type II mechanisms and other aspects of the photochemical kinetic reactions generating cross-linking activity are described in U.S. Pat. No. 10,350,111, filed Apr. 27, 2016 and titled “Systems and Methods for Cross-Linking Treatments of an Eye,” the contents of which are incorporated entirely herein by reference.
Corneal cross-linking reactions are rate limited by oxygen concentrations in the corneal tissue. Thus, the addition of oxygen also affects the amount of corneal cross-linking. In human tissue, O2 content is very low compared to the atmosphere. The rate of cross-linking in the cornea, however, is related to the concentration of O2 when it is irradiated with photoactivating light. Therefore, it may be advantageous to increase or decrease the concentration of O2 actively during irradiation to control the rate of cross-linking until a desired amount of cross-linking is achieved. Oxygen may be applied during the cross-linking treatments in a number of different ways. One approach involves supersaturating the riboflavin with O2. Thus, when the riboflavin is applied to the eye, a higher concentration of O2 is delivered directly into the cornea with the riboflavin and affects the reactions involving O2 when the riboflavin is exposed to the photoactivating light. According to another approach, a steady state of O2 (at a selected concentration) may be maintained at the surface of the cornea to expose the cornea to a selected amount of O2 and cause O2 to enter the cornea. As shown in
As described above, the treatment system 100 includes optical elements 112 that direct light (e.g., UV light) from a light source 110 to photoactivate the cross-linking agent 130 (e.g., riboflavin) applied to the cornea 2 and thus generate cross-linking activity. In particular, the photoactivating light can be selectively directed to regions of the cornea 2 according to a particular spatial treatment pattern. In some embodiments, a treatment system can provide an adjustable treatment pattern so that different ophthalmic conditions can be treated with the same treatment system.
Example treatment systems that treat different ophthalmic conditions by providing different treatment patterns are described in U.S. Patent Application Publication No. 2020/0107953, filed Oct. 9, 2019 and titled “Photoactivation Systems and Methods for Corneal Cross-Linking Treatments,” the contents of these application being incorporated entirely herein by reference.
Scanning Treatment SystemsOptical elements of an example treatment system include a XY scanning mirror pair (e.g., instead of a DMD) that can scan a UV light beam to form a UV light pattern with a small, high-quality spot. (The depth of the cornea is measured along a z-axis and patterns of photoactivating light may be projected on transverse x-y planes.) For instance,
The laser beam from the laser source 310 produces a small, high-quality spot on the galvanometer mirror system 312. The galvanometer mirror system 312 includes a X mirror 312a that can scan the UV light beam in the x-direction and a Y mirror 312b that can scan the UV light beam in the y-direction. The controller 320 can control the galvanometer mirror system 312 to scan the laser beam in the x- and y-directions according to a predefined scan pattern 10. The scan pattern 10 can be translated to cause the X mirror 312a and the Y mirror 312b to scan the laser beam in the x- and y-directions, respectively. In particular, the controller 320 can transmit a X position signal to the X mirror 312a to control a tilt angle of the X mirror 312a and direct the laser beam to a desired position along the x-axis. Correspondingly, controller 320 can transmit a Y position signal to the Y mirror 312b to control a tilt angle of the Y mirror 312b and direct the laser beam to a desired position along the y-axis. The treatment system 300 also includes a lens 314 (e.g., a telecentric, f-theta, or other scanning lens) that transmits the scanned laser beam to the cornea 2. Additionally or alternatively, a lens may be positioned between the laser 310 and the X mirror 312a. Light from the laser source 310 may be transmitted via free space or may be coupled to an optical fiber for transmission to the vicinity of the galvanometer mirror system 312 or lens 314. Fiberoptic transmission has the added benefit of allowing the laser source 310 to be positioned remotely from the other system elements, simplifying system design. The speed of the first mirror and/or second mirrors of the galvanometer mirror system 312 can be adjusted during part of the scan in order to increase or decrease dwell time over a portion of the scan pattern, thereby adjusting the corresponding dose of UV light applied in portions of the scan pattern.
The treatment system 300 also includes an eye tracking system. In particular, the treatment system 300 includes an eye position and orientation detecting system 316 (e.g., a camera that captures images of the eye 1). The controller 320 can receive and process the information (e.g., images) from the eye position detecting system 316 to determine the position of the cornea 2 relative to the treatment system 300. To compensate for changes in the position of the cornea 2, the controller 320 can control the galvanometer mirror system 312 to adjust the scanned laser beam and cause the scan pattern 10 to be applied to the desired areas of the cornea 2. As such, the detecting system 316 and the controller 320 combine to provide an eye tracking system.
In general, scanning treatment systems can apply photoactivating light according to a pattern to achieve a predefined treatment zone (e.g., circular, annular, or other shape) at the corneal surface. Aspects of a scan pattern may be defined by a continuous line. As shown with the example patterns 200a, 200b of
Alternatively, a continuous line may formed by scanning the laser without interruption. For instance, as shown in
Additionally or alternatively, aspects of a scan pattern may be defined by a plurality of unconnected straight or curved lines. For instance, a scan pattern may include lines defined by a series of dashes.
Additionally or alternatively, aspects of a scan pattern may be defined by a plurality of discrete dots. For instance, a scan pattern may include lines defined by a series of discrete dots. In some embodiments, a sequence of discrete dots can be applied with an optical element, such as a diffractive element as described further below, to simultaneously form multiple laser spots which are individually scanned to define the treatment zone.
Various types of patterns of photoactivating light for cross-linking treatments are described herein. The choice of pattern may depend on different optimization criteria including, but not limited to, uniformity of photoactivating light dose over the treatment zone, desired maximum cross-linking efficiency, and maximum correction (e.g., refractive correction) for the eye. Furthermore, the choice of pattern may be constrained by considerations including, but not limited to, compliance to eye safety standards, predefined treatment time, predefined light dose, limits on scan velocity imposed by optical elements and other components of the treatment system, and laser power specifications.
Laser Scanning OptimizationUsing a laser light source to achieve a scanned light pattern can provide benefits for corneal cross-linking treatments over approaches that employ a LED light source. In particular, scanning parameters for the laser can be optimized to increase the efficacy of individual treatments. For instance, treatment time, total dose, intensity/irradiance of the laser beam, pulsing of the laser beam, size of the spot defined by the laser beam (laser spot size), velocity or duration of application of the laser spot, and/or frequency of repetition of portions of the scan pattern can be controlled to enhance cross-linking activity. Such parameters can be optimized according to the photochemical kinetic reactions involved in cross-linking activity as described above. These reactions determine the consumption and replenishment of oxygen during cross-linking activity, supply and photo-degradation of the cross-linking agent molecules, and depth of effect.
For instance, laser spot size can be optimized to achieve the desired treatment.
Additionally or alternatively, frequency of repetition for portions of the scan pattern can be optimized to achieve the desired treatment. For instance, the laser beam may travel over portions of a given scan pattern more than once. Furthermore, the laser beam may be scanned over these portions in different sequences. For instance, a scan pattern may include portions A, B, and C. In an initial pass, the laser beam may travel over portion A, then portion B, and then portion C. During a subsequent pass, the laser beam may travel over portion C, then portion B second, and then portion A. The laser beam may also transform aspects of the scan pattern as it travels over portions of the given scan more than once. For instance, during a subsequent pass by the laser beam, the scan pattern or portions thereof may be rotated and/or shifted laterally relative to the first pass. Optimizing the frequency of repetition of the scan pattern has the effect of preventing depletion of oxygen within the treated spots, which is advantageous for maintaining an aerobic state in the treated spots and therefore increasing crosslinking efficiency.
Additionally or alternatively, characteristics of the laser beam delivered to the XY scanning system can be optimized to achieve desired treatment. For instance, the laser beam may be delivered according to particular pulsing parameters as described above. In some cases, a pulsed laser beam may be delivered to the XY scanning system while the XY scanning system travels continuously over selected portions of the scan pattern, so that a pattern of dashes is generated over those portions.
The intensity and/or duration of the laser beam delivered to the XY scanning system at different portions of the scan pattern can be optimized to provide desired doses of photoactivating light at desired areas of the treatment zone. For instance, the intensity of the laser beam may be modulated for selected portions of the scan pattern to apply different irradiances at different locations on the cornea. The laser beam may also be applied with particular durations and irradiance for selected portions of the scan pattern.
If a continuous scan pattern such as spiral pattern is applied, the pitch between spiral lines can additionally be optimized. If a discontinuous scan pattern such as a random, semi-random, or matrix-based pattern is applied, the dwell time on each spot, distance between spots, and travel time between spots can additionally be optimized.
Certain scanning parameters may be related. For instance, if the total dose is kept constant, increasing the laser power decreases the treatment time, or vice versa. Experimental data indicates that longer treatment times and higher repetition rates usually result in a significant increase in flattening of the cornea, while the change in the laser power does not significantly affect flattening. (It is noted, however, extremely high laser powers, in addition raising safety concerns, can adversely affect flattening by degrading drug molecules to by-products that produce less efficient cross-linking.)
Experimental results indicate that increasing repetition rate, thus increasing the number of visits to the same location by the laser beam, can significantly enhance cross-linking activity. To achieve greater flattening, the repetition rate, or equivalently the number of visits, can be increased until the time for oxygen replenishment is on the order of the off-duty duration for each location. This allows sufficient time between two consecutive visits for the oxygen to replenish at each location.
Correspondingly,
As described above, the rate of corneal cross-linking activity is limited by oxygen concentrations in the corneal tissue. Thus, embodiments can optimize parameters for laser scanning to achieve scan patterns that affect depletion/replenishment of oxygen for cross-linking activity. In an example implementation, a pulsed laser beam is scanned over corneal tissue with a 50% duty cycle and a fixed pulse frequency. As the laser beam scans a pattern, the laser beam leaves unexposed regions of corneal tissue before and after each exposed region along the scan. The exposed regions receive photoactivating light from the laser beam, and the resulting cross-linking activity depletes oxygen in the exposed region. Advantageously, the adjacent unexposed regions enhance the diffusion of oxygen back into an exposed region after the laser beam leaves the exposed region. The pattern scanned by the laser beam can be dithered back and forth to ensure that cross-linking activity is generated over the entire desired treatment area. In some cases, the pulse may be selected based on the scan velocity to expose a region of corneal tissue approximately equal to the diameter of the laser beam at a time.
To produce the patterns 1900a, b, the formulas relating to scan parameters may be given by the following:
-
- Input:
- Dmin—inner diameter of annular treatment pattern
- Dmax—outer diameter of annular treatment pattern
- Pr—pitch in radial direction
- fupd—update frequency
- θ0—initial spiral angle (changing θ0 rotates the spiral)
- Formulas:
- spiral update time:
- Input:
-
-
- spiral length:
-
-
-
- linear velocity:
-
V=fupd·Lsp (3)
-
-
- time constant (for spiral formula below):
-
-
-
- spiral angle (for spiral formula below):
-
-
-
- number of loops:
-
NLps=(Dmax−Dmin)/(2·Pr) (6)
-
-
- spiral formula (t∈[0, tupd]):
-
-
-
- wave formula:
-
x(t)=r(t)·cos(θ(t)) (13)
y(t)=r(t)·sin(θ(t)) (14)
In another example implementation, a pulsed laser beam may be scanned over corneal tissue with a 50% duty cycle and a variable pulse frequency so that the laser beam leaves unexposed regions of corneal tissue on all four sides of each exposed region in the resulting pattern. The resulting pattern resembles a checkerboard. Advantageously, compared to the laser beam with fixed pulsed frequency described above, the adjacent unexposed regions of corneal tissue on all four sides of an exposed region promotes greater diffusion of oxygen back into the exposed region after the laser beam leaves the exposed region. The pulse frequency can be varied between predefined minimum and maximum values, resulting in corresponding minimum and maximum exposure regions.
To produce the patterns 2000a, b, the formulas relating to scan parameters may be given by the following:
-
- Input:
- DC—duty cycle
- Nsct—number of sectors over 2π rad angle
- Formulas:
- angular pitch:
- Input:
Δθ=2π/Nsct (15)
-
-
- number of spots:
-
-
-
- sot counter:
-
nsp=1,2, . . . ,Nspt (17)
-
-
- meridional angles:
-
θmnsp=θ0+(nsp−1)·Δθ (18)
-
-
- loop numbers (may be fractional):
-
-
-
- even/odd loop index (in the range from −1 to 1):
-
iinsp=rem(nLpnsp,2)−1 (20)
-
-
- laser on angle:
-
θonnsp=θmnsp+iinsp·Δθ/2 (21)
-
-
- laser off angle:
-
θoffnsp=θonnsp+Δθ·DC (22)
-
-
- laser on time:
-
-
-
- laser off time:
-
-
-
- instantaneous laser modulation frequency:
-
Implementations of the laser beam with variable pulse frequency may employ a laser modulation signal that sets laser on/off times to coincide with a predefined number of meridians in the treatment pattern.
The size of the exposed regions is determined by pulse frequency and scan velocity, but the pulse frequency may vary in relation to the radial position of the laser beam. In particular, the modulation signal may have a variable frequency that increases toward the center of the spiral. The instantaneous laser modulation frequency is given by equation (25), where the linear velocity is given by equation (3). The radial pitch of the laser modulation is not constant.
When implementing the laser beam with variable pulse frequency, the exposed regions may become smaller and smaller as the laser beam approaches the center of the treatment pattern.
The laser modulation signal is synchronized with the drive signal for the galvanometer—the laser modulation signal can reset and alternate at each spiral restart.
To overcome the potential problem of undesirably high laser modulation frequencies near the center of the treatment pattern, the checkerboard angular pattern can be split into multiple radial zones based on the instantaneous laser modulation frequency.
TABLE 1 illustrates example output data for an annular pattern produced by (i) a pulsed laser beam scanned with fixed laser modulation frequency, (ii) a pulsed laser beam scanned with variable laser modulation frequency not implementing the auto zone approach, and (iii) a pulsed laser beam scanned with variable laser modulation frequency employing the auto zone approach.
The common input parameters for the patterns in TABLE 1 include:
-
- inner diameter of pattern: 100 μm
- outer diameter of patter: 9 mm
- laser beam (spot) diameter: 100 μm
- radial pitch: 100 μm
- update frequency: 16 Hz
- duty cycle: 50%
For the pulsed laser beam scanned with fixed laser modulation frequency, the input further includes a tangential pitch equal to 100 μm. For the pulsed laser beam scanned with variable laser modulation frequency not implementing the auto zone approach, the input further includes a number of sectors equal to 25. For the pulsed laser beam scanned with variable laser modulation frequency implementing the auto zone approach, the input further includes an initial number of sectors equal to 128 and a modulation frequency limit equal to 100 kHz.
The input parameters for the pattern 2400a include:
-
- inner diameter of pattern: 85 μm
- outer diameter of pattern: 4 mm
- radial pitch: 85 μm
- update frequency: 16 Hz
- maximum number of meridians: 64
- maximum modulation frequency: 22 kHz
The output data for the pattern 2400a include:
-
- number of zones: 6
- spiral length: 147.8 mm
- scan velocity: 2.3644 m/s
- minimum modulation length: 52.4 μm
- maximum modulation length: 107.2 μm
- minimum laser modulation frequency: 11.014 kHz
- maximum laser modulation frequency: 22.139 kHz
The input parameters for the pattern 2500a include:
-
- inner diameter of pattern: 85 μm
- outer diameter of pattern: 9 mm
- radial pitch: 85 μm
- update frequency: 16 Hz
- maximum number of meridians: 128
- maximum modulation frequency: 75 kHz
The output data for the pattern 2500a include:
-
- number of zones: 7
- spiral length: 748.37 mm
- scan velocity: 11.9739 m/s
- minimum modulation length: 74.37 μm
- maximum modulation length: 159.60 μm
- minimum laser modulation frequency: 37.507 kHz
- maximum laser modulation frequency: 76.225 kHz
The input parameters for the pattern 2600a include:
-
- inner diameter of pattern: 5 mm
- outer diameter of pattern: 9 mm
- radial pitch: 85 μm
- update frequency: 16 Hz
- maximum number of meridians: 128
- maximum modulation frequency: 75 kHz
The output data for the pattern 2600a include:
-
- number of zones: 1
- spiral length: 517.4 mm
- scan velocity: 8.279 m/s
- minimum modulation length: 61.34 μm
- maximum modulation length: 110.45 μm
- minimum laser modulation frequency: 37.47 kHz
- maximum laser modulation frequency: 67.47 kHz
Although the auto zone approach is employed, the pattern includes only one zone.
The following parameters may be employed to produce a pattern with an outer diameter of 9 mm, for instance:
-
- scan velocity VSC: 10.2 m/s
- laser spot diameter Dsp: 100 μm
- radial pitch: 100 μm
- duty cycle: 50%
- spot profile: flattop and Gaussian
- laser power: 8 mW
The modulation frequency can be optimized. In the case of a Gaussian laser beam, the modulation frequency is preferably less than 50 kHz to maintain sufficient contrast in dose between treated and untreated spots in a single scan. For instance, at 50 kHz, the contrast ((max−min)/mean) is approximately 50%. This estimate depends on spot profile (inner and outer diameters) and galvanometer velocity.
TABLE 2A provides input parameters for producing various annular treatment patterns A-F via pulsed laser scanning implementing the auto zone approach. Correspondingly, TABLE 2B provides output data for the various treatment patterns A-F. The requirement imposed onto the patterns A-F is a minimum modulation length of 85 μm.
As described above, aspects of a scan pattern may be defined by a plurality of discrete dots. A treatment pattern may be defined by scanning discrete dots in randomized manner or a semi-randomized manner based on continuous x, y variables.
According to some embodiments, a point and shoot technique may be employed to apply a sequence of discrete dots and achieve a desired treatment zone. As shown in
After the grid of the scan pattern has been defined, the order for shooting the laser beam spots into the cells of the grid can be optimized. The order of shots, duration of shots, intensity of shots, and the number of repeated shots into each cell may affect the efficiency of cross-linking activity and the desired amount of corneal shape change. According to one approach, each cell is sampled at least once in a random order. According to another approach, the treatment system tracks the total dose delivered to each cell based on the accumulation of shots received. In other words, the treatment system maintains a dose map as treatment progresses and determines where to deliver the next shot according to this dose map. During the treatment, the treatment system may deliver the next shot to the cell with the lowest total dose (which may be the cell that has received the fewest number of shots). If more than one cell has the lowest total dose, the treatment system may also select, for the next shot, a cell that is located the greatest distance from the cell receiving the previous shot. Selecting cells based on greatest distance between consecutive shots may provide more efficient and uniform cross-linking activity across the scan pattern. In particular, greater distance between shots may improve the local supply of oxygen for cross-linking at the next cell. Additionally, the effect of activity at the previous cell (cross-talk) is less likely to affect the activity at a next cell that is a greater distance away from the previous cell.
A possible downside of selecting cells to maximize distance between consecutive shots is the increased time between the applications of the consecutive shots due to the time to move across the distance (transit time). Accordingly, to address this possible downside, the treatment system may constrain the distance between consecutive shots, e.g., the distance is maximized but does not exceed a predefined maximum travel distance (MTD). Thus, the treatment system may choose a cell with the minimum total dose within the MTD. Where all cells have received the same dose or the same number of shots, the treatment system may select the next cell randomly.
In general, the point and shoot technique can be optimized according to various parameters to achieve the desired treatment. Such parameters include, but are not limited to: (i) size of the laser beam spot; (ii) pitch of the grid; (iii) number of shots per cell across the scan pattern (also known as visits); (iv) total treatment time; (v) irradiance of the laser beam; (vi) amount of time between application of consecutive dots; and/or (vi) the order in which the spots are applied. For instance,
As described above, the treatment system 300 shown in
As shown in the timeline 1300 of
Rapid eye movements, in particular, can cause location error in the delivery of the photoactivating light due to this delay. With the point and shoot approach above, the location error can be significant if the laser spot size is comparable to the amount of eye movement during the delay time.
A motion model (e.g., linear model, Kalman filter, or FIR filter) is employed to model eye motion between consecutive frames and to determine the cells that receive photoactivating light between consecutive frames. The dose map can then be updated to indicate that each of such cells has received a dose of photoactivating light proportional to the area covered by the photoactivating light in the frames. Thus, as shown in
Although
Referring to the treatment system 300 of
x=X sin(ωxt+δ) (26)
y=Y sin(ωyt) (27)
-
- where X and Y correspond to the maximum laser beam movement on the eye surface.
As a specific example, when X=Y=A, ωx=ωy=ω, and δ=90°, the Lissajou curve is a circle. The beam position and the scanning velocity at any moment can be described as
- where X and Y correspond to the maximum laser beam movement on the eye surface.
s=x+jy=A cos ωt+jA sin ωt=Aejωt (28)=
{dot over (s)}=jωAejωt (29)
In order to cover the entire scanning area, multiple scanning paths are involved. The amplitude A is a variable to fit the entire scanning area. In the case of uniform scanning speed:
ωA=constant (30)
Very dense Lissajou scanning paths may be employed to achieve proper cross-linking effect. The process of cross-linking in a region of corneal tissue requires a local supply of oxygen as well as cross-linking agent, e.g., riboflavin. As such, the cross-linking efficiency might decrease if consecutive scanning paths are too close to each other. To minimize a decrease in cross-linking efficiency, a scanning of n total paths can be interlaced by scanning the n total scan paths in a sequence defined by an interval m. For instance, if the scan pattern includes n=20 total scan paths (e.g., circular paths) and an interval m=5 is selected, the scan sequence can start with scan path 1 and proceeds to scan paths at every fifth interval after scan path 1, i.e., scan paths 6, 11, 16. The sequence can then move to scan path 2 and proceed to scan paths at every fifth interval after scan path 2, i.e., scan paths 7, 12, 17, and so on. The order for the total sequence is then scan paths 1, 6, 11, 16, 2, 7, 12, 17, 3, 8, 13, 18, 4, 9, 14, 19, 5, 10, 15, 20. Alternatively, a sequence can start with scan path 20 and proceed in reverse to scan paths at every fifth interval, i.e., the order for the total sequence is scan paths 20, 15, 10, 5, 19, 14, 9, 4, 18, 13, 8, 3, 17, 12, 7, 2, 16, 11, 6, 1.
The scanning of each path can start at any portion of the path. For instance, if circular paths are scanned according to the previous sequence, scanning of paths 20, 15, 10, 5 can start at 45° on the circles; scanning of paths 19, 14, 9, 4 can start from at 40° on the circles; scanning of paths 18, 13, 8, 3 can start at 35° on the circles; and so on. Because the scan pattern for the entire treatment may involve a large number of scan paths, many start angles may be employed to achieve a uniform distribution of start angles.
Dead Zone DwellingIn some cases, very high linear scanning speed might be employed for effective cross-linking. For instance, if linear scanning speed is 3.14 mm/ms, a 0.1 mm diameter scanning circle is completed in 0.1 ms and the galvanometer function frequency ω is 10 kHz. This function frequency is very difficult to achieve with most commercially available galvanometer mirror systems. Indeed, it is common practice to apply one or more notch filters on a galvanometer servo board to avoid issues associated with resonance in that range. As such, there is a scanning dead zone due to the limitations of conventional galvanometer performance. Moreover, this dead zone may create issues for achieving peak power for the photoactivating light for cross-linking treatment.
The laser beam, however, can move into the dead zone and stay (dwell) in the dead zone for a short period of time when, for each scan path, the laser beam scans the portion closest to the dead zone. For instance, if a cross-linking treatment lasts for a total of 1000 seconds and scans interlaced paths (e.g., circular scan paths) ten times for each scan pattern at 10 Hz repetition frequency, there are 100,000 opportunities to move into the dead zone. If the dead zone size is one percent of the total scanning area, the total dwelling time may be 10 seconds, and 100 μs for each move into the dead zone (dwelling).
Uniform dead zone dwelling positions can be generated with deterministic equations, but dead zone dwelling can also be achieved randomly. For instance, with two 0 to 1 uniformly distributed numbers r1 and r2, and dead zone radius is R, random dead zone dwelling position may be:
x=R√{square root over (r1)}cos(2πr2) (31)
y=R√{square root over (r1)}cos(2πr2) (32)
Laser power is synchronized with laser beam position during cross-linking treatments. Additionally, synchronizing a laser modulation signal with a position sensor may be employed to maintain precise control over the temporal and spatial characteristics of the scan pattern.
Such synchronization may be necessary because a scan pattern, e.g., with Lissajous scan paths, may not correspond exactly with the desired treatment area. For instance, the scan pattern may be defined by a circular boundary and circular scan paths, but the zone for cross-linking treatment may not be correspondingly circular. As such, it may be necessary to turn the laser power on when the laser beam is inside the treatment zone and to turn the laser power off when the laser beam is outside the treatment zone. Such synchronization may also be necessary because non-uniform laser power is needed for portions of the treatment zone.
Modulated CW laser output power can be manipulated via triggering signals from an acousto-optic modulator or an electro-optic modulator, manipulated directly via diode current, etc. A time delay, also known as rise and fall time, generally occurs when the laser is turned on or off. High quality synchronization accounts for this time delay via calibration.
The triggering signals for modulation of laser output power can be provided via an open or closed loop control system. A closed loop control system employs a feedback signal for position. An open loop control system involves careful pre-calibration of time delay associated with the triggering signal.
TTL (Transistor-Transistor Logic) generally involves a short rise and fall time and may be employed for digital modulation. Other differential signaling such as PECL (Positive Emitter coupled Logic), LV-PECL (Low-Voltage Positive Emitter coupled Logic), and LVDS (Low-Voltage Differential Signaling) are also able to modulate at high frequencies with minimal noise.
Stochastic Model, Estimation, and Control for Eye TrackingKalman Filter
An algorithm based on the Kalman filter may be employed to remove errors from eye tracking measurements. The Kalman filter is a set of mathematical equations that implement a predictor-corrector type of estimator for a stochastic system. It is optimal in the sense of minimizing the estimated error when some presumed conditions are met. With the Kalman filter, eye tracking accuracy can be significantly improved, in contrast to approaches that use direct measurements of eye position. Such eye tracking can effectively estimate eye movement with a regular position-velocity-acceleration component and occasional random component. To implement such eye tracking in a two-dimensional space, two independent filters are employed, i.e., one filter for each spatial dimension.
State-Space Model for Kalman Filter
The Kalman filter addresses the general problem of estimating the state x∈ of a discrete-time controlled process that is governed by the linear stochastic difference equation:
xk=Axk-1+Buk+wk-1 (33)
With the measurement z∈,
zk=Hxk+vk (34)
The random variables wk and vk represent the process and measurement noise. They are assumed to be independent, with normal probability distribution:
p(w)˜N(0,Q) (35)
p(v)˜N(0,R) (36)
One defines {circumflex over (x)}
P
Pk=E[ekekT] (38)
Discrete Kalman Filter Algorithm
The equations of Kalman filter fall into two groups: time update equations and measurement update equations:
The time update equations are responsible for projecting forward the current state and error covariance estimates to obtain a priori estimates of the next time step:
Project the state ahead: {circumflex over (x)}
Project the error covariance: P
The measurement update equations are responsible for the feedback. They incorporate a new measurement into the a priori estimate to obtain an improved a posteriori estimate.
Compute the Kalman gain: Kk=P
Update estimate with measurement: {circumflex over (x)}k={circumflex over (x)}
Update the error covariance: Pk=(I−KkH)P
Raster Scan with Polygon Scanner
A polygon scan can typically run faster because there is no dead zone as with a Lassajou curve scan. The vertical movement of a raster scan is much slower, and it can be implemented with simple, slow scanning, e.g., MEMS-based scanning.
Zig-Zag Scan with Resonant Scanner
As described above, using a laser light source to deliver a photoactivating light pattern can provide benefits for corneal cross-linking treatments over approaches that employ a LED light source. LED light sources may provide light beams of lower optical quality, including low coherence, poor collimation, and/or large diameters. With light beams of such low quality, the choice of available patterns for the delivery of photoactivating light may be more limited and may require more complex and expansive aspherical optics for pattern formation.
In addition to the laser-based approaches employing XY scanners as described above,
The treatment system 1700 shown in
The treatment system 1700 includes a controller 1720 that may control aspects of the treatment system 1700. Additionally, the treatment system 1700 includes an imaging system 1716 (e.g., a camera) that captures images of the eye 1. The controller 1720 can receive and process the images from the imaging system 1716 to determine the position of the cornea 2 relative to the treatment system 1700. To compensate for changes in the position of the cornea 2, the controller 1720 can control the laser beam deflector 1713 to adjust the scanned laser beam and cause the spot pattern to be applied to the desired areas of the cornea 2. As such, the imaging system 1716 and the controller 1720 combine to provide an eye tracking system.
Meanwhile, the treatment system 1800 shown in
Like the treatment system 1700, the treatment system 1800 includes a controller 1820 that may control aspects of the treatment system 1800. Additionally, the treatment system 1800 includes an imaging system 1816 (e.g., a camera) that captures images of the eye 1. The controller 1820 can receive and process the images from the imaging system 1816 to determine the position of the cornea 2 relative to the treatment system 1800. To compensate for changes in the position of the cornea 2, the controller 1820 can control the laser beam deflector 1814 to adjust the scanned laser beam and cause the spot pattern to be applied to the desired areas of the cornea 2. As such, the imaging system 1816 and the controller 1820 combine to provide an eye tracking system.
In general, cross-linking treatment systems employing a laser light source can deliver more sophisticated and sharper photoactivating light patterns. As described above, embodiments can employ XY scanners, diffractive multi-beam splitters, and diffractive beam shapers to achieve the desired patterns.
As also described above, photoactivating light patterns from laser-based treatment systems can be optimized to achieve clinical efficacy and a desired treatment objective (e.g., refractive correction) based on particular eye parameters for individual subjects. Optimized laser-based treatment system can precisely control the shape of a treatment zone and local strength for a patient-specific treatment pattern. Advantageously, optimized laser-based treatment systems can enhance cross-linking by efficiently use cross-linking agent and ambient oxygen based on photochemical kinetic reactions. Indeed, such treatment systems can make it unnecessary to have hyperoxic condition during treatment, i.e., an external gas source, treatment masks, etc. are not required to supply supplemental concentrated oxygen.
As described above, according to some aspects of the present disclosure, some or all of the steps of the above-described and illustrated procedures can be automated or guided under the control of a controller. Generally, the controllers may be implemented as a combination of hardware and software elements. The hardware aspects may include combinations of operatively coupled hardware components including microprocessors, logical circuitry, communication/networking ports, digital filters, memory, or logical circuitry. The controller may be adapted to perform operations specified by a computer-executable code, which may be stored on a computer readable medium.
As described above, the controller may be a programmable processing device, such as an external conventional computer or an on-board field programmable gate array (FPGA), application specific integrated circuits (ASIC), or digital signal processor (DSP), that executes software, or stored instructions. In general, physical processors and/or machines employed by 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's), application specific integrated circuits (ASIC), digital signal processors (DSP's), micro-controllers, and the like, programmed according to the teachings of the example embodiments of the present disclosure, as is appreciated by those skilled in the computer and software arts. The physical processors and/or machines may be externally networked with the image capture device(s), or may be integrated to reside within the image capture device. Appropriate software can be readily prepared by programmers of ordinary skill based on the teachings of the example embodiments, as is appreciated by those skilled in the software art. In addition, the devices and subsystems of the example embodiments can be implemented by the preparation of application-specific integrated circuits or by interconnecting an appropriate network of conventional component circuits, as is appreciated by those skilled in the electrical art(s). Thus, the example embodiments are not limited to any specific combination of hardware circuitry and/or software.
Stored on any one or on a combination of computer readable media, the example embodiments of the present disclosure may include software for controlling the devices and subsystems of the example embodiments, for driving the devices and subsystems of the example embodiments, for enabling the devices and subsystems of the example embodiments to interact with a human user, and the like. Such software can include, but is not limited to, device drivers, firmware, operating systems, development tools, applications software, and the like. Such computer readable media further can include the computer program product of an embodiment of the present disclosure for performing all or a portion (if processing is distributed) of the processing performed in implementations. Computer code devices of the example embodiments of the present disclosure can 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. Moreover, parts of the processing of the example embodiments of the present disclosure can be distributed for better performance, reliability, cost, and the like.
Common forms of computer-readable media may include, for example, a floppy disk, a flexible disk, hard disk, magnetic tape, any other suitable magnetic medium, a CD-ROM, CDRW, DVD, any other suitable optical medium, punch cards, paper tape, optical mark sheets, any other suitable physical medium with patterns of holes or other optically recognizable indicia, a RAM, a PROM, an EPROM, a FLASH-EPROM, any other suitable memory chip or cartridge, a carrier wave or any other suitable medium from which a computer can read.
While the present disclosure has been described with reference to one or more particular embodiments, those skilled in the art will recognize that many changes may be made thereto without departing from the spirit and scope of the present disclosure. Each of these embodiments and obvious variations thereof is contemplated as falling 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 from any of the embodiments described herein.
Claims
1. A system for treating an eye, comprising:
- a laser light source configured to provide photoactivating light;
- a scanning mirror system configured to receive the photoactivating light as a laser beam and to move the laser beam over a cornea treated with a cross-linking agent; and
- a controller configured to provide control signals to programmatically control the laser light source and the scanning mirror system, the one or more control signals causing the laser beam to visit one or more regions of the cornea via linear scanning and retracement to constitute a scan pattern,
- wherein the photoactivating light causes the cross-linking agent in the one or more exposed regions to react with oxygen to generate cross-linking activity in the one or more exposed regions,
- wherein the one or more control signals programmatically control the laser light source, such that a predetermined period of time passes between visits by the laser beam to the one or more exposed regions, and
- wherein the scan pattern includes unexposed regions on all four sides of each exposed region, such that the scan pattern is a checkerboard pattern.
2. The system of claim 1, wherein the light source is operable to adjust a power associated with the laser beam, and the scan pattern is optimized according to the power associated with the laser beam.
3. The system of claim 1, wherein the scanning mirror system is operable to adjust a speed of the laser beam as the laser beam moves over the cornea, and the scan pattern is optimized according to the speed of the laser beam.
4. The system of claim 1, further comprising one or more optical elements configured to receive the photoactivating light and determine a spot size associated with the laser beam, wherein the scan pattern is optimized according to the spot size associated with the laser beam.
5. The system of claim 1, wherein the scanning mirror system includes a galvanometer pair, the galvanometer pair including a first mirror configured to move the laser beam along a first axis and a second mirror configured to move the laser beam along a second axis.
6. The system of claim 1, wherein the scan pattern causes the laser beam to visit the one or more exposed regions while keeping one or more adjacent regions unexposed to the photoactivating light, and the one or more adjacent unexposed regions provide oxygen for diffusion into the one or more exposed regions.
7. The system of claim 1, wherein the scan pattern is defined by a pulsing of the laser beam according to a duty cycle, wherein, as the scanning mirror system scans the laser beam over the cornea, the pulsing causes the laser beam to visit the one or more exposed regions when the laser beam is on during the duty cycle while adjacent regions are unexposed to the photoactivating light when the laser beam is off during the duty cycle, and the adjacent unexposed regions provide oxygen for diffusion into the one or more exposed regions.
8. The system of claim 7, wherein the pulsing of the laser beam has a frequency that varies according to a position of the laser beam in the scan pattern.
9. The system of claim 1, wherein the one or more exposed regions correspond to a plurality of discrete dots defining the scan pattern.
10. The system of claim 1, wherein linear scanning and retracement comprises at least a first horizontal scan line and a second horizontal scan line, the second horizontal scan line disposed parallel to and vertically below the first horizontal scan line.
11. A method for treating an eye, comprising:
- generating photoactivating light with a laser light source;
- directing the photoactivating light as a laser beam to a scanning mirror system;
- operating the scanning mirror system to cause the laser beam to move over a cornea and visit one or more regions of the cornea via linear scanning and retracement to constitute a scan pattern, wherein the photoactivating light causes a cross-linking agent in the one or more exposed regions to react with oxygen to generate cross-linking activity in the one or more exposed regions,
- optimizing the scan pattern by programmatically controlling the laser light source, such that a predetermined period of time passes between visits by the laser beam to the one or more exposed regions, and.
- wherein the scan pattern includes unexposed regions on all four sides of each exposed region, such that the scan pattern is a checkerboard pattern.
12. The method of claim 11, wherein optimizing the scan pattern includes adjusting a power associated with the laser beam.
13. The method of claim 11, wherein optimizing the scan pattern includes adjusting a speed of the laser beam, and the scan pattern is optimized according to the speed of the laser beam.
14. The method of claim 11, wherein optimizing the scan pattern includes determining a spot size associated with the laser beam.
15. The method of claim 11, wherein the scanning mirror system includes a galvanometer pair, the galvanometer pair including a first mirror configured to move the laser beam along a first axis and a second mirror configured to move the laser beam along a second axis.
16. The method of claim 11, wherein optimizing the scan pattern includes defining the scan pattern to cause the laser beam to visit the one or more exposed regions while keeping one or more adjacent regions unexposed to the photoactivating light, the one or more adjacent unexposed regions provide oxygen for diffusion into the one or more exposed regions.
17. The method of claim 11, wherein optimizing the scan pattern includes defining the scan pattern to pulse the laser beam according to a duty cycle, wherein, as the scanning mirror system scans the laser beam over the cornea, the pulsing causes the laser beam to visit the one or more exposed regions when the laser beam is on during the duty cycle while adjacent regions are unexposed to the photoactivating light when the laser beam is off during the duty cycle, the adjacent unexposed regions provide oxygen for diffusion into the one or more exposed regions.
18. The method of claim 17, wherein the pulsing of the laser beam has a frequency that varies according to a position of the laser beam in the scan pattern.
19. The method of claim 11, wherein the one or more exposed regions correspond to a plurality of discrete dots defining the scan pattern.
20. The system of claim 1, wherein linear scanning and retracement comprises at least a first horizontal scan line and a second horizontal scan line, the second horizontal scan line disposed parallel to and vertically below the first horizontal scan line.
Type: Application
Filed: May 5, 2023
Publication Date: Nov 2, 2023
Inventors: Desmond C. Adler (Bedford, MA), Mikhail Smirnov (North Andover, MA), David Usher (Waltham, MA), Behrouz Tavakol (Lexington, MA), Jason Hill (Auburndale, MA), Jie Zhang (Andover, MA), Amit Mukherjee (Acton, MA), Alex Yildizyan (Lexington, MA)
Application Number: 18/313,078