1. Field of the Invention
The disclosure pertains to systems and methods for stabilizing corneal tissue, and more particularly, systems and methods for conveying a cross-linking agent to regions of the cornea where the cross-linking agent is activated by an initiating element.
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.
According to aspects of the present disclosure provide systems and methods for stabilizing corneal tissue and improving its biomechanical strength, particularly after desired structural changes have been achieved in the corneal tissue. For example, the embodiments help to preserve the desired reshaping of the cornea produced by LASIK surgery, thermokeratoplasty, or other similar treatments.
According to aspects of the present disclosure, after a treatment produces a desired change to the shape of a cornea, a cross-linking agent is activated in the treated region of the cornea. The cross-linking agent prevents the corneal fibrils in the treated regions from moving and causing undesired changes to the shape of the cornea. An initiating element may be applied to the treated corneal fibrils to activate the cross-linking agent.
In some embodiments, for example, the cross-linking agent may be Riboflavin and the initiating element may be photoactivating light, such as ultraviolet (UV) light. In these embodiments, the photoactivating light initiates cross-linking activity by irradiating the applied cross-linking agent to release reactive oxygen radicals in the corneal tissue. In particular, the cross-linking agent, e.g., Riboflavin, acts as a sensitizer to convert O2 into singlet oxygen which causes cross-linking within the corneal tissue.
The initiating element may be applied according to a selected pattern to stabilize and strengthen the regions of the cornea where structural changes have been generated by the treatment. Accordingly, aspects of the present disclosure may include a delivery system that accurately and precisely delivers the initiating element to corneal fibrils according to a selected pattern. In embodiments where the initiating element is UV light, the delivery system may deliver the UV light in the form of a laser.
According to an aspect of the present disclosure a method is disclosed for activating cross-linking in at least one eye component. The method includes delivering ultrasound waves to the at least one eye component such that a permeability of the at least one eye component to the cross-linking agent is increased. The method also includes conveying the cross-linking agent to the at least one eye component. The method also includes activating the cross-linking agent by delivering an initiating element to the at least one eye component.
According to another aspect of the present disclosure a method is disclosed for treating an eye. The method includes: delivering heat energy to at least one eye component of the eye; generating a structural change in the at least one eye component; and lowering an intraocular pressure of the eye due to the generated structural change.
According to another aspect of the present disclosure a method is disclosed for activating cross-linking in at least one eye component. The method includes delivering heat energy to the at least one eye component such that a permeability of the at least one eye component to a cross-linking agent is increased. The method also includes conveying a cross-linking agent to the at least one eye component. The method also includes activating the cross-linking agent by delivering an initiating element to the at least one eye component.
According to yet another aspect of the present disclosure a method is disclosed for activating cross-linking in at least one eye component. The method includes conveying a charged cross-linking agent to the at least one eye component. The method also includes urging the charged cross-linking agent to a depth of the at least one eye component using iontophoresis. The method also includes activating the cross-linking agent by delivering an initiating element to the at least one eye component.
According to still another aspect of the present disclosure a method is disclosed for activating cross-linking in at least one eye component of an eye. The method includes conveying the cross-linking agent to a surface of the at least one eye component. The method also includes allowing a time to pass to allow the cross-linking agent to diffuse within the at least one eye component. The method also includes applying a reverse osmotic fluid to the surface of the at least one eye component to draw out the cross-linking agent at or near the surface of the at least one eye component. The method also includes activating the cross-linking agent by delivering an initiating element to the at least one eye component.
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.
For the sake of clarity, the non-limiting embodiments disclosed herein describe the operation of aspects of the present disclosure in conveying the cross-linking agent 130 to regions of the cornea 2. However, the system 100, and the embodiments disclosed herein for conveying the cross-lining agent 130 to regions of the eye 1, refer to systems and methods for directing the cross-linking agent 130 to regions of at least one eye component, and it is understood that the at least one eye component may include a cornea, a limbus, a sclera, and/or a retina.
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 initiating cross-linking at depths of the cornea 2 below the epithelium 2A by first conveying the cross-linking agent 130 to regions of the cornea 2 below the epithelium 2A. Advantageously, aspects of the present disclosure allow for conveying the cross-linking agent 130 to regions below the epithelium 2A of the cornea 2 without requiring removal of the epithelium 2A. 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.
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 delivery system 100 also includes a controller 120 for controlling the operation of the optical elements 112 or the conveyor 132, or both. By controlling aspects of the operation of the optical elements 112 and the conveyor 132, the controller 120 can control the regions of the cornea 2 that receive the cross-linking agent 130 and that are exposed to the light source 110. By controlling the regions of the cornea 2 that receive the cross-linking agent 130 and the light source 110, the controller 120 can control the particular regions of the cornea 2 that are strengthened and stabilized through cross-linking of the corneal collagen fibrils. Furthermore, by controlling the depth region that the cross-linking agent 130 is conveyed to, the controller 120 can control the depth of cross-linking activity within the corneal tissue. In an implementation, the cross-linking agent 130 can be applied generally to the eye 1, without regard to a particular region of the cornea 2 requiring strengthening, but the light source 110 can be directed to a particular region of the cornea 2 requiring strengthening, and thereby control the region(s) of the cornea 2 wherein cross-linking is initiated by controlling the regions of the cornea 2 that are exposed to the light source 110. In another implementation, the light source 110 can be directed generally to the eye 1, and the cross-linking agent 130 can be conveyed to particular region(s) of the cornea 2, and thereby control the region of the cornea 2 wherein cross-linking is initiated. In yet another implementation, both the cross-linking agent 130 and the initiating element 110 can be conveyed and/or directed to particular regions of the cornea 2, and thereby jointly control the region(s) of the cornea 2 wherein cross-linking is initiated.
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, the controller 120 may be replaced by two or more separate controllers or processors. For example, one controller may be used to control the operation of the conveyor 132, and thereby control the precise rate of delivery, location of conveyance, depth of penetration, and/or concentration of the cross-linking agent 130 to the cornea 2. Another controller may be used to control the operation of the optical elements 112, and thereby control with precision the delivery of the light source 110 (i.e. the initiating element) to the cornea 2 by controlling any combination of wavelength, bandwidth, intensity, power, location, depth of penetration, and duration of treatment. In addition, the function of the controller 120 can be partially or wholly replaced by a manual operation. For example, the conveyor 132 can be manually operated to deliver the cross-linking agent 130 to the cornea 2 without the assistance of the controller 120. In addition, the controller 120 can operate the conveyor 132 and the optical elements 112 according to inputs dynamically supplied by an operator of the delivery system 100 in real time, or can operate according to a pre-programmed sequence or routine.
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.
According to aspects of the present disclosure, a treatment is employed to produce a desired change to the shape of the cornea 2. For example, thermokeratoplasty applies energy to the cornea 2 to reshape the cornea 2.
As further illustrated in
With the concentric arrangement of conductors 311A and 311B, a substantially annular gap 311C of a selected distance is defined between the conductors 311A and 311B. The annular gap 311C extends from the proximal end 310A to the distal end 310B. A dielectric material 311D may be used in portions of the annular gap 311C to separate the conductors 311A and 311B. The distance of the annular gap 311C between conductors 311A and 311B determines at least partially the penetration depth of microwave energy into the cornea 2 according to established microwave field theory. Thus, the energy conducting element 311 receives, at the proximal end 310A, the electrical energy generated by the electrical energy source 320, and directs microwave energy to the distal end 311B, where the cornea 2 is positioned.
In general, the outer diameter of the inner conductor 311B may be selected to achieve an appropriate change in corneal shape, i.e., keratometry, induced by the exposure to microwave energy. Meanwhile, the inner diameter of the outer conductor 311A may be selected to achieve a desired gap between the conductors 311A and 311B. For example, the outer diameter of the inner conductor 311B ranges from about 2 mm to about 10 mm while the inner diameter of the outer conductor 311A ranges from about 2.1 mm to about 12 mm. In some systems, the annular gap 311C may be sufficiently small, e.g., in a range of about 0.1 mm to about 2.0 mm, to minimize exposure of the endothelial layer of the cornea (posterior surface) to elevated temperatures during the application of energy by the applicator 310.
A controller 340 may be employed to selectively apply the energy any number of times according to any predetermined or calculated sequence. In addition, the heat may be applied for any length of time. Furthermore, the magnitude of heat being applied may also be varied. Adjusting such parameters for the application of heat determines the extent of changes that are brought about within the cornea 2. Of course, the system 300 can limit the changes in the cornea 2 to an appropriate amount of shrinkage of collagen fibrils in a selected region and according to a selected pattern. When employing microwave energy to generate heat in the cornea 2, for example with the applicator 310, the microwave energy may be applied with low power (of the order of 40 W) and in long pulse lengths (of the order of one second). However, other systems may apply the microwave energy in short pulses. In particular, it may be advantageous to apply the microwave energy with durations that are shorter than the thermal diffusion time in the cornea 2. For example, the microwave energy may be applied in pulses having higher power in the range of 500 W to 3 kW and pulse duration in the range of about 10 milliseconds to about one second.
Referring again to
In general, an interposing layer, such as the dielectric layer 310D, may be employed between the conductors 311A and 311B and the cornea 2 as long as the interposing layer does not substantially interfere with the strength and penetration of the microwave radiation field in the cornea 2 and does not prevent sufficient penetration of the microwave field and generation of a desired heating pattern in the cornea 2. The dielectric material may be elastic, such as polyurethane and silastic, or nonelastic, such as Teflon® and polyimides. The dielectric material may have a fixed dielectric constant or varying dielectric constant by mixing materials or doping the sheet, the variable dielectric being spatially distributed so that it may affect the microwave hearing pattern in a customized way. The thermal conductivity of the material may have fixed thermal properties (thermal conductivity or specific heat), or may also vary spatially, through mixing of materials or doping, and thus provide a means to alter the heating pattern in a prescribed manner. Another approach for spatially changing the heating pattern is to make the dielectric sheet material of variable thickness. The thicker region will heat less than the thinner region and provides a further means of spatial distribution of microwave heating.
During operation, the distal end 310B of the applicator 310 as shown in
The system 300 of
As further illustrated in
Treatment of the cornea 2 produces structural changes to the stroma 2C. As described previously with reference to
Thus, aspects of the present disclosure provide techniques that promote the effective delivery of the cross-linking agent 130 across the epithelium 2A to the corneal tissue below, without requiring removal of the overlying epithelium 2A.
Studies have been directed at the effects of conveying a cross-linking agent to a cornea after thermokeratoplasty. The studies have discovered distinct enhancement in the uptake, i.e., movement, of the cross-linking agent (Riboflavin) into the regions that are treated with energy. In particular, fluorescence indicating the presence of the cross-linking agent in the cornea is brighter in the regions that receive energy. In other words, the pattern of brighter fluorescence matches the pattern of energy application. The pattern of energy application generally depends on the shape of the thermokeratoplasty applicator and the contact between the applicator and the cornea. For example, using the applicator 310, the regions of the cornea exhibiting an enhanced capacity to receive the cross-linking agent correspond closely to the annular pattern defined by the outer conductor 311A and inner conductor 311B. In addition, the fluorescence is bigger and brighter when the intended correction via thermokeratoplasty is greater, i.e., greater amounts of energy are applied. Correspondingly, the greater uptake of the cross-linking agent in these treated regions should result in greater cross-linking when the cross-linking agent is appropriately activated. According to the studies, the delivery of the cross-linking agent is enhanced where cross-linking activation is particularly desired, i.e., where the energy is applied to treat the eye according to thermokeratoplasty.
As discussed previously with reference to
In some embodiments, the dosage of the cross-linking agent and other aspects of its application are modified to account for the increased capacity of treated regions to accommodate greater amounts of cross-linking agent after the application of energy. For example, referring to the example embodiment 500A shown in
In other embodiments, another treatment, such as LASIK, may be employed. In LASIK surgery, an instrument called a microkeratome is used to cut a thin flap in the cornea. The flap is peeled back and the underlying corneal tissue is 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 to complete the surgery. In such treatments, energy may not be applied to the cornea in the same manner as thermokeratoplasty. However, the application of energy may be employed as an additional step to enhance the movement of the cross-linking agent 130 into regions that are treated. For example, referring to the example embodiment 500B shown in
In general, energy may be applied to selected regions of the cornea 2 according to any pattern, for example, with an applicator similar to the applicator 310 described previously. Although the pattern defined by the applicator 310 may be annular, the pattern may have any non-annular and/or asymmetric shape. The pattern determines the regions of the cornea 2 that will have enhanced permeability to receive the cross-linking agent 130 and that will experience greater cross-linking relative to the other regions of the cornea 2. Thus, the application of energy provides a technique for achieving patterned activation of cross-linking in the cornea 2. 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.
In one example, a lower concentration of the cross-linking agent is broadly applied to the cornea, e.g., in the form of a drip, after a pattern of energy is applied. The lower concentration of the cross-linking agent is effective in activating cross-linking in the regions treated with energy, because these regions receive more cross-linking agent. Meanwhile, the effect on the other regions of the cornea may be insignificant due to the low concentration and the lower amount of cross-linking agent received by these other regions.
Referring to the embodiment 600A shown in
Referring to the embodiment 600B shown in
While the embodiments 600A and 600B each provide for increasing the permeability of the corneal tissues, in some embodiments, the cross linking agent 130 may be dissolved in a different carrier to promote delivery across the corneal surface 2A. For example, the cross-linking agent 130 may be combined in varying concentrations with another agent, such as EDTA, benzalkonium chloride, or an alcohol, to promote further delivery across the corneal surface 2A.
Referring to embodiment 700A shown in
Referring to embodiment 700B shown in
Referring to the embodiment 800A shown in
To achieve greater concentrations of Riboflavin farther below the surface, in step 810, the reverse osmotic fluid 812, such as distilled water, is applied to the corneal surface 2A. The reverse osmotic fluid 812 at the surface acts to draw the cross-linking agent 130 out from regions of corneal tissue closer to the corneal surface 2A. The concentration of the cross-linking agent 130 in the regions closer to the corneal surface 2A is then reduced relative to the regions farther below. Thus, the use of the reverse osmotic fluid 812 can produce a “reverse gradient” of the amount of the cross-linking agent 130 along a path moving deeper into the cornea 2.
The resulting distribution of the cross-linking agent 130 is then activated by the application of an initiating element 222, e.g., UV light, in step 220 to initiate cross-linking in the corneal regions treated with the cross-linking agent 130. The cross-linking activity generally corresponds to the distribution of cross-linking agent 130, which is produced in part by the application of the reverse osmotic fluid 812 in step 810.
Referring to the embodiment 800B shown in
Referring to
The cross-linking agent 912 is then activated in step 220 with an initiating element 922. Activation of the cross-linking agent 912 is triggered by the application of microwaves or light. As such, the initiating element 922 is applied with a power P. The power P of the initiating element 922 determines the extent to which the distribution of cross-linking agent 912 is activated. For example, an initiating element applied with a greater power P may reach greater depths below the epithelium 2A and allow the cross-linking agent to be activated at these depths. The parameters C, P, and T may be selected as independent variables to achieve the appropriate amount of cross-linking at desired depths of the cornea.
As the example embodiment 900B of
While the embodiment 1000 shown in
Further, in an iterative implementation of the embodiment 1000, one or more of the steps (508, 604, 720, 820, 902, 810) can be adjusted according to feedback information indicative of the progress of cross-linking in strengthening the corneal tissue. In an example embodiment, feedback information can be supplied by a feedback system configured to dynamically monitor cross-linking in the corneal tissue and provide an output signal indicative of a biomechanical strength of the corneal tissue. The feedback system can include an interferometer dynamically monitoring a three-dimensional surface profile of the surface of an eye and determining a biomechanical strength of the corneal tissue based on an amount of dynamic deformation of the surface profile of the eye due to, for example, changes in intraocular pressure corresponding to a cardiac cycle.
In sum, embodiments 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 and/or the initiating element 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 at depths in the cornea 2 depend on the concentration(s) of the cross-linking agent and the power(s) of the initiating element.
Although cross-linking agents, such as Riboflavin, may be effectively applied to the stroma by removing the overlying epithelium before application, it has been shown that cross-linking agents can chemically transition across the epithelium into the stroma. Indeed, Riboflavin may also be delivered to the stroma by applying it topically on the epithelium. Moreover, in some cases, the epithelium may be treated to promote the transition of the cross-linking agent through the epithelium. Accordingly, in the embodiments described herein, no removal of the epithelium is required. Advantageously, this eliminates the post-operative pain, healing period, and other complications associated with the removal of the epithelium.
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.
The embodiments above may be described with respect to treatment of the cornea and the application of a cross-linking agent. In general, however, embodiments according to the present disclosure take advantage of the increase in the permeability of eye tissue caused by the application of energy. It is further understood that aspects of the present disclosure may be employed with other eye features, such as the limbus, sclera, and retina. Thus, for example, the increased permeability may be advantageous in treating retinal membrane problems. In addition, the application of energy may be employed to produce changes in permeability in the structure of the limbus and the sclera. For example, energy may be applied to form a 6 mm to 8 mm arc at the limbus overlying Schlemm's canal. The corresponding structural changes may result in lowering intraocular pressure, for example, in the treatment of glaucoma. Increased scleral permeability without the induction of fibroblastic elements may be an effective way to lower intraocular pressure. With the increased fluid movement after energy application, significant lowering of intraocular pressure may occur. Advantageously, the amount of energy may be applied with precision.
Aspects of the present disclosure provide for lowering intraocular pressure by generating structural changes in at least one eye component of an eye. The at least one eye component may be a cornea, a limbus, a sclera, and/or a retina. According to aspects providing treatment methods for glaucoma, the cross-linking agent is not necessarily conveyed to the cornea. Aspects provide for treating glaucoma or other eye conditions by decreasing intraocular pressure with or without cross-linking also taking place. Conventional glaucoma treatments provide for decreasing intraocular pressure by regulating the flow of aqueous humor through use of, for example, prescription medications or surgical interventions. Conventional treatments to decrease intraocular pressure may decrease capillary size, or surgically redirect a flow of aqueous humor. However, aspects of the present disclosure provide for decreasing intraocular pressure to treat glaucoma by generating a structural change of an eye component by application of energy to the eye component. For example, heat energy can be applied to the eye component using the applicator 310 shown in
In other embodiments, additional techniques are employed to control the amount of cross-linking agent that is delivered to the treated regions. For example, systems and methods for controlling the activation of the cross-linking agent 130 by precisely delivering the initiating element both spatially and temporally, and optionally according to information received from a feedback system are provided in U.S. patent Ser. No. 13/051,699, filed Mar. 18, 2011, and 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. These and other techniques may be combined with the application of energy to enhance the movement of the cross-linking agent into selected corneal regions.
The use of Riboflavin as the cross-linking agent and UV light as the initiating element in the embodiments above is described for illustrative purposes only. In general, other types of cross-linking agents may be alternatively or additionally employed according to aspects of the present disclosure. Thus, for example Rose Bengal (4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein) may be employed as the cross-linking agent 130, or as the cross-linking agent delivered in varying concentrations 912, 1022. Rose Bengal has been approved for application to the eye as a stain to identify damage to conjunctival and corneal cells. However, Rose Bengal can also initiate cross-linking activity within corneal collagen to stabilize the corneal tissue and improve its biomechanical strength. Like Riboflavin, photoactivating light may be applied to initiate cross-linking activity by causing the Rose Bengal to convert O2 in the corneal tissue into singlet oxygen. The photoactivating light may include, for example, UV light or green light. The photoactivating light may include photons having energy levels sufficient to individually convert O2 into singlet oxygen, or may include photons having energy levels sufficient to convert O2 into singlet oxygen in combination with other photons, or any combination thereof.
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 controllers 120, 140 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 controllers 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 (FPGAs), digital signal processors (DSPs), 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 image capture device(s), or may be integrated to reside within an 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.
This application claims priority to: U.S. Provisional Application No. 61/323,388, filed Apr. 13, 2010; U.S. Provisional Application No. 61/326,527, filed Apr. 21, 2010; U.S. Provisional Application No. 61/345,873, filed May 18, 2010; U.S. Provisional Application No. 61/378,281, filed Aug. 30, 2010, the contents of each of these applications being incorporated entirely herein by reference.
Number | Date | Country | |
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61323388 | Apr 2010 | US | |
61326527 | Apr 2010 | US | |
61345873 | May 2010 | US | |
61378281 | Aug 2010 | US |