Systems and methods for applying and monitoring eye therapy

Abstract

Devices and approaches for activating cross-linking within corneal tissue to stabilize and strengthen the corneal tissue following an eye therapy treatment. A feedback system is provided to acquire measurements and pass feedback information to a controller. The feedback system may include an interferometer system, a corneal polarimetry system, or other configurations for monitoring cross-linking activity within the cornea. The controller is adapted to analyze the feedback information and adjust treatment to the eye based on the information. Aspects of the feedback system may also be used to monitor and diagnose features of the eye 1 . Methods of activating cross-linking according to information provided by a feedback system in order to improve accuracy and safety of a cross-linking therapy are also provided.

1 . A system for controlling activation of a cross-linking agent applied to an eye, comprising:
 a feedback system for providing feedback information indicative of a biomechanical strength of corneal tissue of the eye;   a controller for receiving the feedback information and automatically determining an indication of an amount of cross-linking in the corneal tissue based on the received feedback information; and   a cross-linking activation system for initiating cross-linking in the corneal tissue according to one or more control signals generated by the controller, the one or more control signals generated according to a function including the determined indication of the amount of cross-linking in the corneal tissue.   
     
     
         2 . The system of  claim 1 , wherein the feedback system comprises an interferometer adapted to interfere a beam of light reflected from a surface of the eye with a reference beam of light reflected from a reference surface, the interfered with beams of light passing through a polarizing filter and creating an intensity pattern detected by a camera associated with the feedback system, and wherein the feedback information comprises an output from the associated camera. 
     
     
         3 . The system of  claim 2 , wherein the polarizing filter includes a pixelated polarizing filter for simultaneously capturing, via the associated camera, intensity patterns associated with four polarization states. 
     
     
         4 . The system of  claim 2 , wherein the associated camera is adapted to capture one or more intensity patterns indicative of a plurality of polarized interference patterns in an exposure having a duration less than one millisecond. 
     
     
         5 . The system of  claim 2 , wherein the feedback system further comprises a distance measurement system for monitoring a distance between the eye and the interferometer and providing an indication of the monitored distance to the controller. 
     
     
         6 . The system of  claim 3 , wherein the associated camera is adapted to detect a plurality of intensity patterns and wherein the controller is further adapted to:
 receive the plurality of detected intensity patterns,   determine a plurality of surface profiles of the surface of the eye associated with the plurality of detected intensity patterns based on the plurality of detected intensity patterns and based on the monitored distance, and   determine an amount of dynamic deformation of the surface of the eye based on the determined plurality of surface profiles.   
     
     
         7 . The system of  claim 3 , wherein the associated camera is adapted to detect a plurality of intensity patterns and wherein the controller is further adapted to:
 receive the plurality of detected intensity patterns,   determine a plurality of surface profiles of the surface of the eye associated with the plurality of detected intensity patterns based on the plurality of detected intensity patterns and based on the monitored distance, and   estimate a volume of tear-film associated with the eye based on a difference between a first and second profile of the surface of the eye taken from the plurality of surface profiles of the surface of the eye.   
     
     
         8 . The system of  claim 1 , wherein the feedback system is adapted to direct light emitted by a light source to complete a double-pass of the corneal optics, direct emerging light that emerges from the eye through a polarizing filter, and capture an intensity pattern indicative of a degree of polarization of the emerging light. 
     
     
         9 . The system of  claim 1 , wherein the cross-linking activation system includes:
 a light source for emitting light suitable for activating cross-linking in the corneal tissue by exciting the cross-linking agent to produce a reactive singlet oxygen from oxygen content in the corneal tissue; and   corneal optics for conveying the emitted light to the eye according to the one or more control signals.   
     
     
         10 . The system of  claim 7 , wherein the corneal optics are operable to convey the emitted light to the eye according to a non-uniform intensity pattern, and wherein the one or more control signals specify the non-uniform intensity pattern. 
     
     
         11 . The system of  claim 7 , wherein the emitted light is conveyed to the eye via a laser scanning device. 
     
     
         12 . The system of  claim 7 , wherein the emitted light is conveyed to the eye according to a multi-photon technology. 
     
     
         13 . The system of  claim 1 , wherein the feedback system comprises:
 one or more lamps emitting narrow slits of light directed toward the eye,   a video camera adapted to monitor the eye, and   a distance measurement system adapted to monitor a distance from the eye to the video camera,   wherein the feedback information comprises an output of the video camera.   
     
     
         14 . The system of  claim 13 , wherein the one or more lamps include:
 a first lamp and a second lamp are situated above and below the eye, respectively, and illuminate the eye with light emitted at a downward and an upward angle, respectively, and   a third lamp and a fourth lamp are situated on opposing sides of the eye, respectively, and emit light angled toward the eye from the respective opposing sides.   
     
     
         15 . The system of  claim 13 , wherein the video camera is adapted to begin capturing video images of the eye responsive to the eye blinking. 
     
     
         16 . The system of  claim 1 , wherein one or more of the feedback system or the cross-linking activation system includes a head restraint device to rigidly align the eye. 
     
     
         17 . The system of  claim 16 , wherein the head restraint device comprises a bite plate. 
     
     
         18 . The system of  claim 1 , wherein the cross-linking agent is Riboflavin or Rose Bengal and the cross-linking activation system includes an ultraviolet light source. 
     
     
         19 . A method of controllably activating a cross-linking agent applied to an eye, comprising:
 receiving feedback information comprising electronic signals output from a feedback system adapted to monitor the eye, the feedback information indicative of a biomechanical strength of corneal tissue of the eye;   automatically analyzing the feedback information to determine a dosage of light to be applied to the eye; and   activating the cross-linking agent by conveying light to the eye according to the determined dosage.   
     
     
         20 . The method of  claim 19 , further comprising:
 receiving targeting information indicative of an alignment of the eye with respect to the conveyed light; and   automatically adjusting the alignment of the eye with respect to the conveyed light according to the received targeting information.   
     
     
         21 . The method of  claim 19 , wherein the feedback system comprises an interferometer adapted to interfere a beam of light reflected from a surface of the eye with a reference beam of light reflected from a reference surface, the interfered with beams of light passing through a polarizing filter and creating an intensity pattern detected by a camera associated with the feedback system, the feedback system adapted to allow the associated camera to detect a plurality of intensity patterns, and wherein the feedback information comprises the plurality of detected intensity patterns, and wherein the automatically analyzing the feedback information is carried out by:
 receiving the plurality of detected intensity patterns,   determining a plurality of surface profiles of the surface of the eye associated with the plurality of detected intensity patterns based on the plurality of detected intensity patterns and based on a distance between the surface of the eye and the interferometer, and   determining an amount of dynamic deformation of the surface of the eye based on the determined plurality of surface profiles, the amount of dynamic deformation related to the dosage of light to be applied to the eye.   
     
     
         22 . The method of  claim 21 , wherein the polarizing filter includes a pixelated polarizing filter for capturing intensity patterns associated with four polarization states, and wherein intensity patterns associated with four different polarizations states are simultaneously detected by the associated camera. 
     
     
         23 . The method of  claim 21 , further comprising:
 capturing, via a photosensitive detector, a specular reflection related to the plurality of intensity patterns detected by the associated camera;   analyzing the specular reflection to determine targeting information associated with the alignment of the eye with respect to the conveyed light;   adjusting the alignment of the eye with respect to the conveyed light according to the determined targeting information.   
     
     
         24 . The method of  claim 22 , wherein targeting information is determined by solving for a centroid position of the captured specular reflection. 
     
     
         25 . The method of  claim 22 , wherein the targeting information is determined by solving for an energy distribution of the captured specular reflection. 
     
     
         26 . The method of  claim 22 , wherein the adjusting the alignment and the receiving the targeting information are carried out in real time to stabilize an initial fringe pattern captured by the associated camera. 
     
     
         27 . The method of  claim 19 , wherein the feedback system is adapted to direct light emitted by a light source to complete a double-pass of the corneal optics, direct emerging light that emerges from the eye through a polarizing filter, and capture an intensity pattern indicative of a degree of polarization of the emerging light, and wherein the feedback information comprises the degree of polarization. 
     
     
         28 . The method of  claim 19 , wherein the receiving feedback information, the automatically analyzing the feedback information, and the activating the cross-linking agent are carried out repeatedly. 
     
     
         29 . The method of  claim 28 , wherein the repeated carrying out of the activating the cross-linking agent is ceased responsive to the biomechanical strength of the cornea indicated by the feedback information attaining a desired value. 
     
     
         30 . The method of  claim 19 , wherein the light is conveyed to the eye via a laser scanning device. 
     
     
         31 . The method of  claim 19 , wherein the light is conveyed to the eye according to a multi-photon technology. 
     
     
         32 . The method of  claim 19 , wherein the cross-linking agent is Riboflavin or Rose Bengal and the light conveyed to the eye is ultraviolet light. 
     
     
         33 . A method for activating cross-linking in corneal tissue of an eye, comprising:
 applying a cross-linking agent having a first concentration to the eye;   allowing, during a first diffusion time, the cross-linking agent having the first concentration to diffuse within the eye;   activating the cross-linking agent with a photoactivating light applied according to a first dose, the first dose specified by a first power and a first bandwidth;   activating the cross-linking agent with the photoactivating light applied according to a second dose, the second dose specified by a second power and a second bandwidth.   
     
     
         34 . The method of  claim 33 , wherein the second dose is applied responsive to monitoring the corneal tissue with a feedback system to determine an amount of cross-linking of the corneal tissue. 
     
     
         35 . The method of  claim 33 , further comprising:
 applying a cross-linking agent having a second concentration to the eye; and   allowing, during a second diffusion time, the cross-linking agent having the second concentration to diffuse within the eye.   
     
     
         36 . The method of  claim 33 , wherein the applying, the allowing, and one or more of the activating the cross-linking agent are carried out repeatedly. 
     
     
         37 . The method of  claim 33 , wherein the first dose or the second dose is applied such that an amount of energy of the photoactivating light is applied to a surface of the eye exceeding 5 J/cm 2 . 
     
     
         38 . A system for activating a cross-linking agent applied to a cornea of an eye, comprising:
 a light source for emitting photoactivating light;   a minor array having a plurality of minors arranged in rows and columns, the plurality of minors 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 plurality of mirrors alignable according to one or more control signals; and   a controller for providing the one or more control signals to programmatically align the plurality of minors in the array of mirrors such that the pixelated intensity pattern emerges from the mirror array responsive to the photoactivating light scanning across the plurality of minors.   
     
     
         39 . The system of  claim 38 , further comprising:
 a camera for capturing an image of the eye, wherein the captured image of the eye includes pixels that are mapped to the pixels corresponding to the plurality of minors.   
     
     
         40 . The system of  claim 38 , wherein the plurality of mirrors in the mirror array are selectively alignable to reflect light from the light source alternately toward the eye or toward a heat sink for controlling an amount of energy of light applied to a corresponding plurality of locations of the eye. 
     
     
         41 . The system of  claim 38 , wherein an intensity of each pixel in the pixelated intensity pattern is proportionate to an amount of time each corresponding minor in the mirror array is aligned to direct the photoactivating light toward the eye while the photoactivating light scans across the corresponding mirror. 
     
     
         42 . The system of  claim 38 , further comprising:
 an objective lens for focusing the pixelated intensity pattern to a focal plane at least partially within the corneal tissue of the eye.   
     
     
         43 . The system of  claim 42 , further comprising:
 a camera for capturing video images of the eye;   a head restraint device for restraining a head associated with the eye; and   a motorized mount adapted to adjust a position of the objective lens according to a targeting signal, the targeting signal generated according to the captured video images.   
     
     
         44 . The system of  claim 38 , wherein the pixelated intensity pattern is non-uniform over the surface of the eye. 
     
     
         45 . The system of  claim 38 , wherein the cross-linking agent is Riboflavin or Rose Bengal and the photoactivating light is an ultraviolet laser light source. 
     
     
         46 . The system of  claim 38 , wherein the light source is an ultraviolet laser light source and the photoactivating light is sufficient for activating cross-linking in the corneal tissue by exciting the cross-linking agent to produce a reactive singlet oxygen from oxygen content in corneal tissue of the eye. 
     
     
         47 . A method of activating a cross-linking agent applied to an eye, comprising:
 emitting photoactivating light;   directing the photoactivating light to be scanned across a mirror array having a plurality of minors arranged in rows and columns, the plurality of minors 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 minor array, the plurality of mirrors alignable according to one or more control signals; and   generating the one or more control signals for programmatically aligning the plurality of minors in the mirror array according to the pixelated intensity pattern.   
     
     
         48 . The method of  claim 47 , further comprising:
 receiving, from a feedback system, feedback information indicative of an amount of cross-linking in the corneal tissue; and   adjusting the one or more control signals based on the feedback information to thereby modify the pixelated intensity pattern applied to the eye via the minor array.   
     
     
         49 . The method of  claim 47 , further comprising:
 receiving video images of the eye from a video camera, the video images having pixels mapped to the pixels corresponding to the plurality of mirrors.   
     
     
         50 . The method of  claim 47 , further comprising:
 conveying the pixelated intensity pattern to the surface of the eye via one or more optical elements;   receiving an image of the eye from a camera;   analyzing the received video images to determine targeting information; and   adjusting an alignment of the eye to the one or more optical elements according to the determined targeting information.   
     
     
         51 . The method of  claim 47 , wherein the photoactivating light activates cross-linking in the corneal tissue by exciting the cross-linking agent to produce a reactive singlet oxygen from oxygen content in corneal tissue of the eye. 
     
     
         52 . A system for activating a cross-linking agent applied to an eye, comprising:
 a light source for emitting photoactivating light; and   a mask adapted to selectively allow the photoactivating light to be transmitted therethrough, the regions of the mask allowing the photoactivating light to be transmitted defining a pattern of activation of the cross-linking agent.   
     
     
         53 . The system of  claim 52 , wherein the mask comprises a circular lens adapted to be placed on a surface of the eye, the circular lens having a coating applied to at least a portion of the circular lens, the coating substantially blocking the photoactivating light from being transmitted through the circular lens to the eye. 
     
     
         54 . The system of  claim 52 , wherein the photoactivating light has sufficient energy to activate cross-linking in the corneal tissue by exciting the cross-linking agent to produce a reactive singlet oxygen from oxygen content in corneal tissue of the eye. 
     
     
         55 . A method of activating a cross-linking agent applied to an eye, comprising:
 emitting photoactivating light; and   directing the photoactivating light to pass through a mask adapted to selectively allow the photoactivating light to be transmitted therethrough, the regions of the mask allowing the photoactivating light to be transmitted defining a pattern of activation of the cross-linking agent.   
     
     
         56 . The method of  claim 55 , wherein the mask comprises a circular lens adapted to be placed on a surface of the eye, the circular lens having a coating applied to at least a portion of the circular lens, the coating substantially blocking the photoactivating light from being transmitted through the circular lens to the eye. 
     
     
         57 . The method of  claim 56 , wherein the coating is applied according to a predetermined or prescribed pattern. 
     
     
         58 . The method of  claim 55 , wherein the photoactivating light activates cross-linking in the corneal tissue by exciting the cross-linking agent to produce a reactive singlet oxygen from oxygen content in corneal tissue of the eye. 
     
     
         59 . A system for monitoring an eye, comprising:
 an interferometer comprising:
 a light source for providing a beam of light having a reference polarization state, 
 a corneal imaging lens for directing a beam of light from the light source toward a surface of the eye and collimating light reflected from the surface of the eye, 
 a reference surface for providing a reference surface to compare with a surface of the eye, 
 one or more beam splitters adapted to:
 split the beam of light and direct a first portion to be reflected from the surface of the eye, and direct a second portion to be reflected from the reference surface, and 
 combine the reflected first portion and the reflected second portion to form a superimposed beam, 
 
 a polarizing filter, and 
 a camera for capturing an intensity pattern of the superimposed beam emerging from the polarizing filter; and 
   a controller for analyzing the intensity pattern by:
 determining a phase offset, for a plurality of points in the captured intensity pattern, between the reflected first portion and the reflected second portion based on the captured intensity pattern, 
 determining an optical path length difference between the reflected first portion and the reflected second portion for the plurality of points from the phase offsets determined for the plurality of points, and 
 determining a surface profile of the eye by comparing a profile of the reference surface to the optical path length differences determined for the plurality of points. 
   
     
     
         60 . The system of  claim 59 , wherein the polarizing filter includes a pixelated polarizing filter for simultaneously capturing, via the associated camera, intensity patterns associated with four polarization states. 
     
     
         61 . The system of  claim 59 , further comprising:
 a distance measurement system for providing an indication of a distance between the surface of the eye and the interferometer.   
     
     
         62 . The system of  claim 59 , further comprising:
 a head restraint device for restraining a position of a head associated with the eye, the head restraint device thereby aligning a position of the eye with respect to the interferometer.   
     
     
         63 . The system of  claim 59 , wherein the camera is adapted to detect a plurality of intensity patterns in sequence, and wherein the controller is further adapted to:
 receive the plurality of detected intensity patterns,   determine a plurality of surface profiles of the surface of the eye associated with the plurality of detected intensity patterns, and   determine an amount of dynamic deformation of the surface of the eye based on the determined plurality of surface profiles.   
     
     
         64 . The system of  claim 59 , further comprising a photosensitive detector for capturing a specular reflection of a fringe pattern of the superimposed beam, and wherein the controller is further adapted to:
 analyze the captured specular reflection and solve for a centroid position of the captured specular reflection,   determine an amount of adjustment desirable between an alignment of the interferometer and the eye, and   provide alignment control signals to a motorized adjustment device adapted to align the interferometer with the eye in real time.   
     
     
         65 . The system of  claim 64 , further comprising:
 a head restraint device for restraining a position of a head associated with the eye, the head restraint device thereby aligning a position of the eye with respect to the interferometer.   
     
     
         66 . The system of  claim 65 , wherein the head restraint device comprises a bite plate. 
     
     
         67 . A method of monitoring an eye, comprising:
 emitting a beam of light from a light source having a known polarization;   splitting the beam and directing a first portion to be reflected from a surface of the eye, and directing a second portion to be reflected from a reference surface;   interfering the first portion of the beam and second portion of the beam to create a superimposed beam;   directing the superimposed beam through a polarizing filter;   capturing an intensity pattern of the superimposed beam emerging from the polarizing filter;   analyzing the captured intensity pattern to determine a surface profile of the surface of the eye.   
     
     
         68 . The system of  claim 67 , wherein the polarizing filter includes a pixelated polarizing filter for simultaneously capturing, via an associated camera, intensity patterns associated with four polarization states. 
     
     
         69 . The method of  claim 67 , wherein the analyzing the captured intensity pattern includes:
 determining a phase offset, for a plurality of points in the captured intensity pattern, between the reflected first portion and the reflected second portion based on the captured intensity pattern;   determining an optical path length difference between the reflected first portion and the reflected second portion for the plurality of points from the phase offsets determined for the plurality of points; and   determining a surface profile of the eye by comparing a profile of the reference surface to the optical path length differences determined for the plurality of points.   
     
     
         70 . The method of  claim 67 , further comprising:
 capturing a plurality of sequential intensity patterns;   determining a plurality of surface profiles of the surface of the eye associated with the plurality of detected intensity patterns; and   determining an amount of dynamic deformation of the surface of the eye based on the determined plurality of surface profiles.   
     
     
         71 . A system for applying a controlled amount of cross-linking in corneal tissue of an eye, comprising:
 an applicator adapted to apply a cross-linking agent to the eye;   a light source for emitting photoactivating light;   a targeting system adapted to create targeting feedback information indicative of a position of a cornea of the eye;   a minor array having a plurality of minors arranged in rows and columns, the plurality of minors 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 minor array;   an interferometer adapted to monitor an 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, and 
 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 being indicative of a plurality of profiles of the surface of the eye; 
   a head restraint device for restraining a position of a head associated with the eye, thereby aligning the eye with respect to the interferometer; and   a controller adapted to:
 receive the targeting feedback information, 
 receive the generated series of intensity patterns, 
 analyze the generated series of intensity patterns to determine the plurality of profiles of the surface of the eye associated therewith, 
 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 indicated by the plurality of profiles of the surface of the eye, and 
 adjust the pixelated intensity pattern according to data comprising at least one of:
 the targeting feedback information and the determined amount of cross-linking. 
 
   
     
     
         72 . The system of  claim 71 , wherein the series of images comprise fringe patterns having fringes, the fringes defining continuous bands of relatively uniform intensity and corresponding to regions of the surface of the eye equidistant from the camera.