1. Field of the Invention
The invention pertains to systems and methods for stabilizing corneal tissue, and more particularly, systems and methods for applying and activating a cross-linking agent in corneal tissue and monitoring the activation of the cross-linking agent.
2. Description of Related Art
A variety of eye disorders, such as myopia, keratoconus, and hyperopia, involve abnormal shaping of the cornea. Laser-assisted in-situ keratomileusis (LASIK) is one of a number of corrective procedures that reshape the cornea so that light traveling through the cornea is properly focused onto the retina located in the back of the eye. During LASIK eye surgery, an instrument called a microkeratome is used to cut a thin flap in the cornea. The cornea is then peeled back and the underlying cornea tissue ablated to the desired shape with an excimer laser. After the desired reshaping of the cornea is achieved, the cornea flap is put back in place and the surgery is complete.
In another corrective procedure that reshapes the cornea, thermokeratoplasty provides a noninvasive procedure that applies electrical energy in the microwave or radio frequency (RF) band to the cornea. In particular, the electrical energy raises the corneal temperature until the collagen fibers in the cornea shrink at about 60° C. The onset of shrinkage is rapid, and stresses resulting from this shrinkage reshape the corneal surface. Thus, application of energy according to particular patterns, including, but not limited to, circular or annular patterns, may cause aspects of the cornea to flatten and improve vision in the eye.
The success of procedures, such as LASIK or thermokeratoplasty, in addressing eye disorders, such as myopia, keratoconus, and hyperopia, depends on the stability of the changes in the corneal structure after the procedures have been applied.
Aspects of the present disclosure further provide a system for applying a controlled amount of cross-linking in corneal tissue of an eye. The system includes an applicator adapted to apply a cross-linking agent to the eye. The system also includes a light source adapted to emit a photoactivating light. The system also includes a targeting system adapted to create targeting feedback information indicative of a position of a cornea of the eye. The system also includes a mirror array having a plurality of mirrors arranged in rows and columns. The plurality of mirrors are adapted to selectively direct the photoactivating light toward the eye according to a pixelated intensity pattern having pixels corresponding to the plurality of mirrors in the mirror array. The system also includes an interferometer adapted to monitor an amount of cross-linking in the corneal tissue. The interferometer monitors the amount of cross-linking in the corneal tissue by interfering a beam of light reflected from a surface of the eye with a reference beam of light reflected from a reference surface. The interferometer monitors the amount of cross-linking in the corneal tissue by also capturing, via an associated camera, a series of images of interference patterns due to optical interference between the beam of light and the reference beam of light. The series of images are indicative of a plurality of profiles of the surface of the eye. The system also includes a head restraint device for restraining a position of a head associated with the eye. The head restraint device thereby aligns the eye with respect to the interferometer. The system also includes a controller. The controller is adapted to receive the targeting feedback information and receive the generated series of intensity patterns. The controller is also adapted to analyze the generated series of intensity patterns to determine the plurality of profiles of the surface of the eye associated therewith. The controller is also adapted to determine an amount of cross-linking of the corneal tissue based on a dynamic deformation of the surface of the eye. The dynamic deformation of the eye is indicated by the plurality of profiles of the surface of the eye. The controller is also adapted to adjust the pixelated intensity pattern according to data. The data includes at least one of: the targeting feedback information and the determined amount of cross-linking
These and other aspects of the present disclosure will become more apparent from the following detailed description of embodiments of the present disclosure when viewed in conjunction with the accompanying drawings.
As described below in connection with
Although eye therapy treatments may initially achieve desired reshaping of the cornea 2, the desired effects of reshaping the cornea 2 may be mitigated or reversed at least partially if the collagen fibrils within the cornea 2 continue to change after the desired reshaping has been achieved. Indeed, complications may result from further changes to the cornea 2 after treatment. For example, a complication known as post-LASIK ectasia may occur due to the permanent thinning and weakening of the cornea 2 caused by LASIK surgery. In post-LASIK ectasia, the cornea 2 experiences progressive steepening (bulging).
Aspects of the present disclosure provide approaches for initiating molecular cross-linking of corneal collagen to stabilize corneal tissue and improve its biomechanical strength. For example, embodiments may provide devices and approaches for preserving the desired corneal structure and shape that result from an eye therapy treatment, such as LASIK surgery or thermokeratoplasty. In addition, aspects of the present disclosure may provide devices and approaches for monitoring the shape, molecular cross-linking, and biomechanical strength of the corneal tissue and providing feedback to a system for providing iterative initiations of cross-linking of the corneal collagen. As described herein, the devices and approaches disclosed herein may be used to preserve desired shape or structural changes following an eye therapy treatment by stabilizing the corneal tissue of the cornea 2. The devices and approaches disclosed herein may also be used to enhance the strength or biomechanical structural integrity of the corneal tissue apart from any eye therapy treatment.
Therefore, aspects of the present disclosure provide devices and approaches for preserving the desired corneal structure and shape that result from an eye treatment, such as LASIK surgery or thermokeratoplasty. In particular, embodiments may provide approaches for initiating molecular cross-linking of the corneal collagen to stabilize the corneal tissue and improve its biomechanical strength and stiffness after the desired shape change has been achieved. In addition, embodiments may provide devices and approaches for monitoring cross-linking in the corneal collagen and the resulting changes in biomechanical strength to provide a feedback to a system for inducing cross-linking in corneal tissue.
Some approaches initiate molecular cross-linking in a treatment zone of the cornea 2 where structural changes have been induced by, for example, LASIK surgery or thermokeratoplasty. However, it has been discovered that initiating cross-linking directly in this treatment zone may result in undesired haze formation. Accordingly, aspects of the present disclosure also provide alternative techniques for initiating cross-linking to minimize haze formation. In particular, the structural changes in the cornea 2 are stabilized by initiating cross-linking in selected areas of corneal collagen outside of the treatment zone. This cross-linking strengthens corneal tissue neighboring the treatment zone to support and stabilize the actual structural changes within the treatment zone.
With reference to
The optical elements 112 can be used to focus the light emitted by the light source 110 to a particular focal plane within the cornea 2, such as a focal plane that includes the mid-depth region 2B. In addition, according to particular embodiments, 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 heat sinks for absorbing light emitted by the light source 110. The optical elements 112 may further include filters for partially blocking wavelengths of light emitted by the light source 110 and for advantageously selecting particular wavelengths of light to be directed to the cornea 2 for activating the cross-linking agent 130. The controller 120 can also be adapted to control the light source 110 by, for example, toggling a power switch of the light source 110.
In an implementation, the controller 120 may include hardware and/or software elements, and may be a computer. The controller 120 may include a processor, a memory storage, a microcontroller, digital logic elements, software running on a computer processor, or any combination thereof. In an alternative implementation of the delivery system 100 shown in
Referring to
As the example embodiment 200B of
According to one approach, the Riboflavin may be applied topically to the corneal surface, and transepithelial delivery allows the Riboflavin to be applied to the corneal stroma. In general, the application of the cross-linking agent sufficiently introduces Riboflavin to mid-depth regions of the corneal tissue where stronger and more stable structure is desired.
Where the initiating element is UV light, the UV light may be generally applied to the corneal surface 2A (e.g. the epithelium) of the cornea 2 to activate cross-linking However, regions of the cornea 2 requiring stabilization may extend from the corneal surface 2A to a mid-depth region 2B in the corneal stroma 2C. Generally applying UV light to the corneal surface 2A may not allow sufficient penetration of the UV light to activate necessary cross-linking at a mid-depth region of the cornea. Accordingly, embodiments according to aspects of the present disclosure provide a delivery system that accurately and precisely delivers UV light to the mid-depth region 2B where stronger and more stable corneal structure is required. In particular, treatment may generate desired changes in corneal structure at the mid-depth region 2B.
By rapidly scanning the beam of light 341 over the mirrors in the mirror array 344, the mirror array 344 outputs a light pattern 345, which has a two dimensional intensity pattern. The two dimensional intensity pattern of the light pattern 345 is generated by the mirror array 344 according to, for example, the length of time that the beam of light 341 is scanned over each mirror in the mirror array 344. In particular, the light pattern 345 can be considered a pixilated intensity pattern with each pixel represented by a mirror in the mirror array 344 and the intensity of the light in each pixel of the light pattern 345 proportionate to the length of time the beam of light 341 scans over the mirror in the mirror array 344 corresponding to each pixel. In an implementation where the beam of light 341 scans over each mirror in the mirror array 344 in turn to create the light pattern 345, the light pattern 345 is properly considered a time-averaged light pattern, as the output of the light pattern 345 at any one particular instant in time may constitute light from as few as a single pixel in the pixelated light pattern 345. In an implementation, the laser scanning technology of the delivery system 300 may be similar to the technology utilized by Digital Light Processing™ (DLP®) display technologies.
The mirror array 344 can include an array of small oscillating mirrors, controlled by mirror position motors 347. The mirror position motors 347 can be servo motors for causing the mirrors in the mirror array 344 to rotate so as to alternately reflect the beam of light 341 from the light source 340 toward the cornea 2. The controller 120 can control the light pattern 345 generated in the mirror array 344 using the mirror position motors 347. In addition, the controller 120 can control the depth within the cornea 2 that the light pattern 345 is focused to by controlling the location of the focal depth of the objective lens 346 relative to the corneal surface 2A. The controller can utilize an objective lens position motor 348 to raise and/or lower the objective lens 346 in order to adjust the focal plane 6 of the light pattern 345 emitted from the mirror array 344. By adjusting the focal plane 6 of the light pattern 345 using the objective lens motor 348, and controlling the two-dimensional intensity profile of the light pattern 345 using the mirror position motors 347, the controller 120 is adapted to control the delivery of the light source 110 to the cornea 2 in three dimensions. The three-dimensional pattern is generated by delivering the UV light to selected regions 5 on successive planes (parallel to the focal plane 6), which extend from the corneal surface 2A to the mid-depth region 2B within the corneal stroma. The cross-linking agent 130 introduced into the selected regions 5 is then activated as described above.
By scanning over selected regions 5 of a plane 6 at a particular depth within the cornea 2, the controller 120 can control the activation of the cross-linking agent 130 within the cornea 2 according to a three dimensional profile. In particular, the controller 120 can utilize the laser scanning technology of the laser scanning device 300 to strengthen and stiffen the corneal tissues by activating cross-linking in a three-dimensional pattern within the cornea 2. In an implementation, the objective lens 346 can be replaced by an optical train consisting of mirrors and/or lenses to properly focus the light pattern 345 emitted from the mirror array 344. Additionally, the objective lens motor 348 can be replaced by a motorized device for adjusting the position of the eye 1 relative to the objective lens 346, which can be fixed in space. For example, a chair or lift that makes fine motor step adjustments and adapted to hold a patient during eye treatment can be utilized to adjust the position of the eye 1 relative to the objective lens 346.
Advantageously, the use of laser scanning technologies allows cross-linking to be activated beyond the corneal surface 2A of the cornea 2, at depths where stronger and more stable corneal structure is desired, for example, where structural changes have been generated by an eye therapy treatment. In other words, the application of the initiating element (i.e., the light source 110) is applied precisely according to a selected three-dimensional pattern and is not limited to a two-dimensional area at the corneal surface 2A of the cornea 2.
Although the embodiments described herein may initiate cross-linking in the cornea according to an annular pattern defined, for example, by a thermokeratoplasty applicator, the initiation pattern in other embodiments is not limited to a particular shape. Indeed, energy may be applied to the cornea in non-annular patterns, so cross-linking may be initiated in areas of the cornea that correspond to the resulting non-annular changes in corneal structure. Examples of the non-annular shapes by which energy may be applied to the cornea are described in U.S. patent Ser. No. 12/113,672, filed on May 1, 2008, the contents of which are entirely incorporated herein by reference.
Some embodiments may employ Digital Micromirror Device (DMD) technology to modulate the application of initiating light, e.g., UV light, spatially as well as a temporally. Using DMD technology, a controlled light source projects the initiating light in a precise spatial pattern that is created by microscopically small mirrors laid out in a matrix on a semiconductor chip, known as a (DMD). Each mirror represents one or more pixels in the pattern of projected light. The power and duration at which the light is projected is determined as described elsewhere.
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 delivery system (e.g., 100 in
Referring again to
Aspects of the present disclosure, e.g., adjusting the parameters for delivery and activation of the cross-linking agent, can be employed 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 initiating element (i.e., the light source 110) at a flux dose of 5 J/cm2, aspects of the present disclosure allow larger doses of the initiating element, e.g., multiples of 5 J/cm2, to be applied to reduce the time required to achieve the desired cross-linking Highly accelerated cross-linking is particularly possible when using laser scanning technologies (such as in the delivery system 300 provided in
To decrease the treatment time, and advantageously generate stronger cross-linking within the cornea 2, the initiating element (e.g., the light source 110 shown in
Treatment of the cornea 2 by activating cross-linking produces structural changes to the corneal stroma. In general, the optomechanical properties of the cornea changes under stress. Such changes include: straightening out the waviness of the collagen fibrils; slippage and rotation of individual lamellae; and breakdown of aggregated molecular superstructures into smaller units. In such cases, the application of the cross-linking agent 130 introduces sufficient amounts of cross-linking agent to mid-depth regions 2B of the corneal tissue where stronger and more stable structure is desired. The cross-linking agent 130 may be applied directly to corneal tissue that have received an eye therapy treatment and/or in areas around the treated tissue.
To enhance safety and efficacy of the application and the activation of the cross-linking agent, aspects of the present disclosure provide techniques for real time monitoring of the changes to the collagen fibrils with a feedback system 400 shown in
Moreover, real time monitoring with the feedback system 400 may be employed to identify when further application of the initiating element (e.g., the light source 110) yields no additional cross-linking Where the initiating element is UV light, determining an end point for the application of the initiating element protects the corneal tissue from unnecessary exposure to UV light. Accordingly, the safety of the cross-linking treatment is enhanced. The controller 120 for the cross-linking delivery system can automatically cease further application of UV light when the real time monitoring from the feedback system 400 determines that no additional cross-linking is occurring.
The feedback system 400 can be a video eye-tracking system as shown in
The real time video image data 504 (e.g., the series of images captured by the video camera 510) are sent to the controller 120, which may include processing hardware, such as a conventional personal computer or the like. The controller 120 analyzes the data from the video camera 10, for example, according to programmed instructions on computer-readable storage media, e.g., data storage hardware. In particular, the controller 120 identifies the image of the cornea 2 in the video image data 504 and determines the position of the cornea 2 relative to the delivery system 500, and particularly relative to the laser scanning device 300. The controller 120 sends instructions 506 to the laser scanning device 300 to direct a pattern of UV light 508 to the position of the cornea 2. For example, the instructions 506 can adjust optical aspects of the laser scanning device 300 to center the pattern of UV light 508 output from the laser scanning device 300 on the cornea 2. The pattern of UV light 508 activates the cross-linking agent 130 in desired areas and depths of corneal tissue according to aspects of the present disclosure described herein.
In addition, the video image data 504 can optionally include distance information and the controller 130 can be adapted to further analyze the video image data 504 to determine the distance to the cornea 2 from the laser scanning device 508 and can adjust the focal plane of the pattern of UV light 508 directed to the cornea 2. For example, the distance to the cornea 2 may be detected according to an auto-focus scheme that automatically determines the focal plane of the cornea 2, or may be determined according to an active ranging scheme, such as a laser ranging or radar scheme. In an implementation, the video image data 504 can be a series of images, and the controller 120 can be adapted to analyze the images in the series of images individually or in combination to detect, for example, trends in the movement of the cornea 2 in order to predict the location of the cornea 2 at a future time.
In general, the system 500 shown in
In sum, implementations of aspects of the present disclosure stabilize a three-dimensional structure of corneal tissue through controlled application and activation of cross-linking in the corneal tissue. For example, the cross-linking agent 130 and/or the initiating element (e.g., the pattern of UV light 508) are applied in a series of timed and controlled steps to activate cross-linking incrementally. Moreover, the delivery and activation of the cross-linking agent 130 at depths in the cornea 2 depend on the concentration(s) and diffusion times of the cross-linking agent 130 as well as the power(s) and bandwidths of the initiating element. Furthermore, systems may employ laser scanning technologies in combination with a video eye-tracking system to achieve accurate application of the initiating element 222 to the cornea 2.
Another technique for real time monitoring of the cornea 2 during cross-linking treatment employs interferometry with a specialized phasecam interferometer (e.g., manufactured by 4dTechnology, Tucson, Ariz.). The interferometer takes up to 25 frames per second with a very short exposure so as to substantially minimize motion during an exposure duration. In an example, the exposure time can be less than one millisecond. As the heart beats, the intraocular pressure (IOP) in the eye 1 increases and causes the corneal surface to extend outwardly by a slight amount. The deflection of the cornea 2 is determined by developing a difference map between the peaks and valleys of the cardiac pulsate flow cycles. The deflection of the cornea provides an indicator for the strength of the corneal tissue. The deflection of the cornea 2 may be used to measure changes in the biomechanical strength, rigidity, and/or stiffness during cross-linking treatment. Additionally, comparisons of an amount of deflection observed before and after cross-linking treatment is applied to a cornea 2 may be used to determine a change in biomechanical strength, rigidity, and/or stiffness of the corneal tissue. In general, however, interferometry may be employed to measure corneal strength before and after an eye surgery, before and after any eye treatment, or to monitor disease states. Thus, aspects of the present disclosure employ interferometry as a non-contact technique to determine the surface shape of the cornea 2 and develop a difference map to measure the deflection from IOP. The deflection of the cornea can then be used to determine changes in corneal strength during cross-linking treatment.
To provide control over cross-linking activity, aspects of the present disclosure provide techniques for real time monitoring of the changes in the strength of the corneal tissue. These techniques may be employed to confirm whether appropriate doses of the cross-linking agent have been applied during treatment. Moreover, real time monitoring may be employed to identify when further application of the initiating element yields no additional cross-linking Where the initiating element is UV light, determining an end point for the application of the initiating element protects the corneal tissue from unnecessary exposure to UV light. Accordingly, the safety of the cross-linking treatment is enhanced. The controller 120 for the cross-linking delivery system (e.g., the delivery system 100 in
In addition the video systems and interferometry systems discussed above, still further examples of systems suitable to be included in the feedback system 400 of
The beam conditioning system 1420 can generally include lenses, mirrors, apertures, and/or other optical elements to condition the beam of light such that the resulting output light 1422 has a non-uniform time-averaged intensity profile. The output light 1422 can activate cross-linking in the eye 1 according to a non-uniform pattern that is related to the non-uniform time-averaged intensity profile. For example, regions of the eye 1 illuminated by portions of the output light 1422 having a relatively greater energy flux can experience more cross linking than regions of the eye 1 illuminated by portions of the output light 1422 having a relatively lesser energy flux.
Aspects of the beam conditioning system 1420 can be similar to the system 300 such that the non-uniform time-averaged intensity profile of the output light 1422 can be generated at least in part by scanning the laser light over an array of selectively alignable mirrors to create a pixelated intensity profile. Additionally or alternatively, the laser light can be diverged or converged and directed to a digital micro mirror device having an array of selectively alignable mirrors to generate a pixelated intensity profile with the digital micro mirror device being imaged to the eye 1.
The laser light may also be passed through one or more fixed or moving apertures to selectively block portions of the beam of light thereby generating the non-uniform time-averaged intensity profile of the output light 1422 imaged on the eye 1. Dynamic adjustments to the non-uniform time-averaged intensity profile can be provided in part by translating and/or rotating apertures adapted to be programmatically positioned to generate the non-uniform time averaged intensity profile. In an implementation, the positions, translations, and/or rotations of the apertures may be carried according to instructions from a controller. Generally, the apertures can be manipulated such that greater amounts of light are blocked, on a time-averaged basis, from regions of the beam corresponding to low-intensity areas of the desired intensity profile, and vice versa. For example, light-blocking portions of the apertures can move relatively more rapidly through regions of the beam corresponding to high-intensity areas of the desired intensity profile and relatively more slowly through regions of the beam corresponding to low-intensity areas of the desired intensity profile. The apertures can include rotating screens having cut-out portions shaped as wedges, shapes similar to a nautilus shell pattern, and/or other shapes. The screens can be rotated in an optical path of the beam of light from the laser 1410. As the cut-out portion of the screen sweeps through regions of the beam of light corresponding to relatively high intensity regions of the non-uniform intensity profile, the angular rotation of the screen can be slowed to a low rate, and while the cut-out portion sweeps through regions of the beam of light corresponding to relatively low intensity regions of the non-uniform time-averaged intensity profile, the angular rotation of the screen can be slowed to a high rate. The same principal can be applied to translating apertures with high rates of motion of a cut-out portion corresponding to low intensity regions of a resulting intensity profile and vice versa.
The beam conditioning system may also have a set of beam steering optics that can scan a converging or diverging beam of light with a specific spot size imaged on the eye 1. The spot intensity distribution, size and shape being modified by the methods described herein.
In implementations, the beam conditioning system 1420 can be programmatically adjusted and controlled by a controller (such as the controller 120 described herein). Generally, similar to aspects described herein in reference to iterative approaches for activating cross-linking, the output light 1422 can be delivered to the eye 1 in one or more doses characterized by a power, bandwidth, duration, and/or intensity profile. Furthermore, aspects of the beam conditioning system 1420 can be automatically adjusted to modify, for example, the overall intensity or power, the non-uniform intensity pattern, the duration, and/or the bandwidth of the output light 1422 for each dose of the output light 1422 delivered to the eye 1. In implementations, the automatic adjustment of each dose of the output light 1422 can be carried out according to feedback information, such as the feedback information provided by the interferometry systems, polarimetry systems, and multi-slit lamp configurations described herein for providing feedback.
Furthermore, ocular coherence tomography (OCT) systems can be employed to provide feedback to the controller (e.g., 120). An OCT system generally utilizes low coherence interferometry of white optical light or near-infrared light interfered with light from a reference surface to characterize regions of interest within a narrow coherence length. OCT systems can employ time domain or frequency domain scanning to generate a high resolution (micrometer scale), three-dimensional (to millimeter depths) profile of the corneal tissue. Examples of OCT systems providing feedback for an eye therapy system are disclosed, for example, in U.S. Provisional Patent Application No. 61/542,269, filed Oct. 2, 2011; and U.S. Provisional Patent Application No. 61/550,576, filed Oct. 24, 2011, each of which is hereby incorporated herein by reference in its entirety.
Aspects of the present disclosure also provide systems and methods for treating myopia (i.e., near-sightedness) and/or astigmatism of a patient by activating cross-linking in the patient's corneal tissue. Clinical observations have revealed that myopia can be treated by applying a cross-linking agent (e.g., Riboflavin) to an eye with an applicator, and then activating cross-linking in the corneal tissue of the eye by applying an initiating element, such as UV light. The resulting cross-lining activity in the corneal tissue of the eye has been observed to flatten the shape of the eye, thereby advantageously reducing the corneal power of the cornea so as to correct for myopia. Furthermore, asymmetric flattening of an eye has been observed in patients suffering from astigmatism. In an example clinical treatment, which is discussed next in connection with
As shown in
The present disclosure provides techniques for addressing astigmatism that contrast with LASIK techniques for correcting astigmatism. LASIK techniques treat astigmatism by removing corneal tissue from bulging regions of the cornea (i.e., from regions having high corneal power) in order to flatten those regions of the cornea. The removal of corneal tissue from the bulging regions further weakens those regions and undesirably thins those regions of the cornea, making them potentially more susceptible to bulging in the future. In contrast, the cross-linking therapy described herein corrects astigmatism by flattening (and strengthening) bulging regions of the cornea by activating cross-linking therapy in those regions. According to aspects of the present disclosure, corneal thickness and corneal strength is not sacrificed in order to provide optical corrections to the cornea. Aspects of the present disclosure provide for strengthening weakened regions of the cornea (e.g., regions of the cornea that are bulging so as to cause non-uniformities in corneal power) through cross-linking Furthermore, it has been observed that cross-linking therapy applied to an eye in a uniform treatment zone results in preferential flattening of regions of the treatment zone having relatively greater corneal power (e.g., regions of the cornea with greater axial curvature). This effect of preferential cross-linking activity in higher curvature regions of the corneal tissue results in a partial correction of corneal astigmatism even when cross-linking therapy is initiated according to a uniformly applied pattern within the treatment zone.
While particular clinical results are described in connection with
According to aspects of the present disclosure, cross-linking therapy treatments applied to an eye 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. Based on the received one or more biomechanical properties, (e.g., corneal thickness), the cross-linking treatment is accordingly adjusted to provide treatment based on the received biomechanical properties. For example, the amount of cross-linking agent and/or dosage of cross-linking activation can be increased for patients having larger corneal thickness. Generally optical correction and/or strengthening of the cornea is applied similar to the descriptions of iterative cross-linking therapy treatments discussed above where the cross-linking agent and/or cross-linking initiating element are each applied in one or more iterations with adjustable characteristics for each iteration. Furthermore, the treatment can be adapted based on feedback information of the biomechanical properties of the cornea that is gathered in real-time during treatment or during breaks in treatment. Generally the developed treatment plan can include a number of applications of the cross-linking agent (e.g., the cross-linking agent 130 shown in
Additionally and/or alternatively, the non-uniform pattern of the initiating element can also be realized by applying the initiating element to the eye in separate treatment zones with different doses sequentially or continuously applied. For example, one treatment zone can turn off (i.e., ceases to receive the initiating element) while another stays on (i.e., continues to receive the initiating element). The zones can be, for example, annularly shaped about a center point of the eye. There can also be discontinuous zones where no initiating element is applied (e.g., a central zone surrounded by an annulus of no light surrounded by an annulus of light, etc.). The widths of the annular zones (“rings”) can be of different dimensions, such as where one annular zone has a width of 1 mm and another has a width of 2 mm. Applying the initiating element in rings on the periphery of the eye without a central spot can result in a hyperopic correction by causing the central region of the eye to have an increased curvature while the periphery is strengthened. Furthermore, the central and surrounding annular treatment zones can be elliptical in shape to correct for astigmatism by preferentially initiating cross-linking 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)). The elliptically shaped treatment zones can also be dictated by the biomechanical properties of the cornea, for example, the corneal topography, the corneal thickness, and/or the corneal strength. These zones may also be defined by the irregular and translating shaped apertures as described herein.
Furthermore, the distribution of the cross-linking agent can be adjusted prior to or during initiation of the cross-linking agent according to the techniques and systems described in commonly assigned U.S. patent application Ser. No. 13/086,019, filed Apr. 13, 2011, the contents of which is incorporated entirely herein by reference.
The one or more biomechanical properties of the eye can be observed pre-treatment or can be actively observed during treatment by a feedback system, such as the interferometric feedback system, Oculus Pentacam, 4 slit lamp apparatus, OCT system, and other feedback systems described herein. Additionally and/or alternatively, biomechanical properties of the cornea may be provided according to information from a Supersonic Shear Imaging (“SSI”) corneal elasticity measurement system, such as described in, for example, M. Tanter et al., High-Resolution Quantitative Imaging of Cornea Elasticity Using Supersonic Shear Imaging, IEEE Transactions on Medical Imaging, vol. 28, no. 12, December 2009, pp. 1881-1893, the contents of which is hereby incorporated entirely herein by reference. Additionally or alternatively, biomechanical properties of the cornea may be provided according to information from an Ocular Response Analyzer for measuring corneal hysteresis in response to a changing optical pressure, available from Reichert, Inc., and as described in Michael Sullivan-Mee, The Role of Ocular Biomechanics In Glaucoma Management, Review of Optometry, Oct. 15, 2008, pp. 49-54, the contents of which is hereby incorporated entirely herein by reference.
The cross-linking agent 122 may be applied to the corneal tissue in an ophthalmic solution, e.g., in the form of eye drops. In some cases, the cross-linking agent 122 is effectively applied to the corneal tissue by removing the overlying epithelium before application. However, in other cases, the cross-linking agent 122 is effectively applied in a solution that transitions across the epithelium into the underlying corneal tissue, i.e., without removal of the epithelium. For example, a transepithelial solution may combine Riboflavin with approximately 0.1% benzalkonium chloride (BAC) in distilled water. Alternatively, the transepithelial solution may include other salt mixtures, such as a solution containing approximately 0.4% sodium chloride (NaCl) and approximately 0.02% BAC. Additionally, the transepithelial solution may contain methyl cellulose, dextran, or the like to provide a desired viscosity that allows the solution to remain on the eye for a determined soak time.
Although embodiments of the present disclosure may describe stabilizing corneal structure after treatments, such as LASIK surgery and thermokeratoplasty, it is understood that aspects of the present disclosure are applicable in any context where it is advantageous to form a stable three-dimensional structure of corneal tissue through cross-linking Furthermore, while aspects of the present disclosure are described in connection with the re-shaping and/or strengthening of corneal tissue via cross-linking the corneal collagen fibrils, it is specifically noted that the present disclosure is not limited to cross-linking corneal tissue, or even cross-linking of tissue. Aspects of the present disclosure apply generally to the controlled cross-linking of fibrous matter and optionally according to feedback information. The fibrous matter can be collagen fibrils such as found in tissue or can be another organic or inorganic material that is arranged, microscopically, as a plurality of fibrils with the ability to be reshaped by generating cross-links between the fibrils. Similarly, the present disclosure is not limited to a particular type of cross-linking agent or initiating element, and it is understood that suitable cross-linking agents and initiating elements can be selected according to the particular fibrous material being reshaped and/or strengthened by cross-linking
The present disclosure includes systems having controllers for providing various functionality to process information and determine results based on inputs. Generally, the controllers (such as the controller 120 described throughout the present disclosure) 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 120 may be a programmable processing device, such as 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, 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), digital signal processors (DSP's), micro-controllers, and the like, programmed according to the teachings of the exemplary 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 exemplary embodiments, as is appreciated by those skilled in the software art. In addition, the devices and subsystems of the exemplary 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 exemplary 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 exemplary embodiments of the present disclosure may include software for controlling the devices and subsystems of the exemplary embodiments, for driving the devices and subsystems of the exemplary embodiments, for enabling the devices and subsystems of the exemplary 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 exemplary 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 exemplary 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 in connection with a number of exemplary embodiments, and implementations, the present disclosure is not so limited, but rather covers various modifications, and equivalent arrangements. In addition, although aspects of the present invention may be described in separate embodiments, it is contemplated that the features from more than one embodiment described herein may be combined into a single embodiment.
This application is a continuation-in-part of U.S. patent application Ser. No. 13/051,699, filed Mar. 18, 2011, which claims priority to U.S. Provisional Application No. 61/315,840, filed Mar. 19, 2010; U.S. Provisional Application No. 61/319,111, filed Mar. 30, 2010; U.S. Provisional Application No. 61/326,527, filed Apr. 21, 2010; U.S. Provisional Application No. 61/328,138, filed Apr. 26, 2010; U.S. Provisional Application No. 61/377,024, filed Aug. 25, 2010; U.S. Provisional Application No. 61/388,963, filed Oct. 1, 2010; U.S. Provisional Application No. 61/409,103, filed Nov. 1, 2010; and U.S. Provisional Application No. 61/423,375, filed Dec. 15, 2010, the contents of these applications being incorporated entirely herein by reference. This Application also claims the benefit of, and priority to, U.S. Provisional Patent Application No. 61/477,505, filed Apr. 20, 2011; U.S. Provisional Patent Application No. 61/521,261, filed Aug. 8, 2011; U.S. Provisional Patent Application No. 61/542,269, filed Oct. 2, 2011; and U.S. Provisional Patent Application No. 61/550,576, filed Oct. 24, 2011, the contents of these applications being incorporated entirely herein by reference.
Number | Date | Country | |
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61315840 | Mar 2010 | US | |
61319111 | Mar 2010 | US | |
61326527 | Apr 2010 | US | |
61328138 | Apr 2010 | US | |
61377024 | Aug 2010 | US | |
61388963 | Oct 2010 | US | |
61409103 | Nov 2010 | US | |
61423375 | Dec 2010 | US | |
61477505 | Apr 2011 | US | |
61521261 | Aug 2011 | US | |
61542269 | Oct 2011 | US | |
61550576 | Oct 2011 | US |
Number | Date | Country | |
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Parent | 13051699 | Mar 2011 | US |
Child | 13438705 | US |