Patent Publication Number: US-2019175333-A1

Title: Corneal implant systems and methods

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority to, and benefit of, U.S. Provisional Patent Application Ser. No. 62/598,099, filed Dec. 13, 2017, the contents of which are incorporated entirely herein by reference. 
    
    
     FIELD OF THE INVENTION 
     The present disclosure relates generally to systems and methods for correcting vision, and more particularly, to systems and methods relating to implants to reshape the cornea in order to correct vision. 
     BACKGROUND 
     A variety of eye disorders, such as myopia, hyperopia, astigmatism, and presbyopia, involve abnormal shaping of the cornea. This abnormal shaping prevents the cornea from properly focusing light onto the retina in the back of the eye (i.e., refractive error). A number of treatments attempt to reshape the cornea so that the light is properly focused. For instance, a common type of corrective treatment is LASIK (laser-assisted in situ keratomileusis), which employs a laser to reshape the cornea surgically. 
     SUMMARY 
     According to aspects of the present disclosure, embodiments provide implants for reshaping the cornea in order to correct vision. For instance, such implants may address the refractive errors associated with eye disorders such as myopia, hyperopia, astigmatism, and presbyopia. The implants may be formed from natural tissue, such as donor corneal tissue. 
     According to aspects of the present disclosure, a storage/delivery device includes a first wall defining a well configured to receive a corneal tissue. The storage/delivery device includes a second wall configured to be positioned over the first wall and to seal the well. The second wall includes a recess configured to extend into the well to define a chamber between the first wall and the second wall. The chamber is configured to hold the corneal tissue when the second wall seals the well. 
     According to other aspects of the present disclosure, a system includes the storage/delivery device above and a measurement system configured to measure the corneal tissue disposed in the well. In one embodiment, the measurement system is an optical coherence tomography (OCT) system, where the OCT system is positioned to direct incident light to the corneal tissue in the well and to receive optical scattering from the corneal tissue in response to the incident light, the optical scattering indicating a measurement of the corneal tissue. In another embodiment, the measurement system is a second-harmonic generation (SHG) or third-harmonic generation (THG) microscopy system, the SHG or THG microscopy system including: a light source positioned to direct incident light to the corneal tissue; and a detector positioned to receive a respective 2nd or 3rd harmonic light respectively from the corneal tissue in response to the incident light, the respective 2nd or 3rd harmonic light indicating a measurement of the corneal tissue, where the light source and the detector are positioned on opposite sides of the first wall and the first wall is transmissive to allow the detector to receive the respective 2nd or 3rd harmonic light. 
     According to further aspects of the present disclosure, a method for processing corneal tissue includes receiving a corneal tissue and placing the corneal tissue in a well defined by a first wall. The method also includes filling the well with a fluid medium to keep the corneal tissue hydrated in the well. Additionally, the method includes sealing the corneal tissue and the fluid medium in the well by positioning a second wall over the first wall and coupling the second wall to the first wall. The second wall includes a recess configured to extend into the well to define a chamber between the first wall and the second wall, the chamber configured to hold the corneal tissue when the well is sealed. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates an example storage/delivery device for holding corneal tissue, according to aspects of the present disclosure. 
         FIG. 2  illustrates the use of an example optical coherence tomography (OCT) system to measure corneal tissue disposed in a storage/delivery device, according to aspects of the present disclosure. 
         FIG. 3  illustrates the use of an example second-harmonic generation (SHG) or third-harmonic generation (THG) microscopy system to measure corneal tissue disposed in a storage/delivery device, according to aspects of the present disclosure. 
         FIG. 4  illustrates an example approach for producing implants, where the approach accounts for swelling and deswelling of corneal tissue, according to aspects of the present disclosure. 
         FIG. 5  illustrates an example approach for producing a plurality of lenticules from a donor cornea and accounting for deswelling associated with each lenticule, according to aspects of the present disclosure. 
         FIG. 6  illustrates an example approach for producing a corneal implant by reshaping a lenticule from a donor cornea, where the approach accounts for swelling of the lenticule, according to aspects of the present disclosure. 
     
    
    
     DESCRIPTION 
     Example systems and methods employ implants to reshape the cornea in order to correct vision. For instance, such embodiments may address the refractive errors associated with eye disorders such as myopia, hyperopia, astigmatism, and presbyopia. Example systems and methods employ implants that are formed from natural tissue, such as donor corneal tissue. 
     Implants formed from donor cornea can be employed to reshape the cornea in order to correct a variety of eye disorders, such as myopia, hyperopia, astigmatism, and presbyopia. Approaches for producing and implementing such implants are described, for instance, in U.S. Patent Application Publication No. 2014/0264980, filed Jan. 10, 2014, U.S. Patent Application Publication No. 2017/0027754, filed Feb. 28, 2016, and U.S. Patent Application Publication No. 2017/0319329, filed May 5, 2017, the contents of these applications being incorporated entirely herein by reference. 
     An implant can be formed by shaping a lenticule that is cut from a donor cornea. In some cases, the single donor cornea is cut to maximize the number of lenticules, thereby maximizing the number of implants from the single donor cornea. According to one approach, the lenticule may be prepared and packaged (e.g., by a supplier) for delivery and subsequent reshaping (e.g., by a practitioner) at or near the time of actual implantation into the cornea. As such, the lenticule may provide a more general shape (e.g., a blank) that can be subsequently reshaped into an implant according to any specific shape. The specific shape may cause a change in refractive power when implanted. In addition, the shape may include desired edge characteristics and other features that allow the structure of the implant to blend or transition smoothly into the surrounding eye structure, for instance, to improve optics and/or promote epithelial growth over the implant. 
     If a separate supplier packages and delivers a lenticule as a blank to a practitioner, the practitioner may need to know the starting measurements of the lenticule so that the proper amount of tissue can be accurately removed from the lenticule to obtain a precisely shaped corneal implant. The supplier may take the measurements of the lenticule and may provide the measurements to the practitioner. 
     Embodiments provide a storage/delivery device (e.g., container) for holding a lenticule for delivery to a practitioner. Advantageously, the storage/delivery device allows the lenticule to maintain its shape and holds a fluid medium to maintain hydration for the lenticule during delivery. Furthermore, the storage/delivery device allows optical measurement techniques to be applied to the lenticule while it is in the device. 
       FIG. 1  illustrates an example storage/delivery device  100  for holding a lenticule  10 . Aspects of the storage/delivery device  100 , for instance, may be formed from glass, plastic, or similarly suitable material. The storage/delivery device  100  includes a first wall  102  that defines a well  104  that is configured to receive the lenticule  10 . The well  104  can be filled with a medium  20 , including albumin for instance, to keep the lenticule  10  hydrated in the well  104 . The lenticule  10  may have a diameter in the x-y plane of up to approximately 10 mm, but more typically a diameter of approximately 3 mm to approximately 7 mm. In addition, the lenticule  10  may have a thickness along the z-axis of approximately 10 μm to approximately 50 μm. ( FIG. 1  provides a simplified illustration of the storage/delivery device  100  and the lenticule  10 ; the storage/delivery device  100  and the lenticule  10  as shown in  FIG. 1  are not to-scale.) Although the lenticule  10  may have a generally circular profile in the x-y plane, the lenticule  10  may have other shapes and dimensions. 
     The first wall  102  includes a bottom portion  102   a  that defines the bottom of the well  104 . When the lenticule  10  is received into the well  104 , the lenticule  10  is situated along the bottom portion  102   a . In some embodiments, the portion  102   a  may be contoured or otherwise shaped to accommodate the lenticule  10  and keep the lenticule  10  in place. For instance, the bottom portion  102   a  may define a depression that receives the lenticule  10 . 
     The storage/delivery device  100  also includes a second wall  106  that is configured to be positioned over the first wall  102  and to seal the well  104 . In particular, the second wall  106  defines a recess  108  that can extend into the well  104  to define a chamber  110  between the first wall  102  and the second wall  106 . The lenticule  10  and the medium  20  are sealed within the chamber  110 . The first wall  102  includes a top portion  102   b  that defines a periphery at the top of the well  104 . The second wall  106  includes a top portion  106   b  that defines a periphery at the top of the recess  108 . Once the lenticule  10  and the medium  20  are placed in the well  104 , the second wall  106  is placed over the first wall  102  with the recess  108  extending into the well  104 . The top portion  106   b  of the second wall  106  can then be coupled to the top portion  102   a  of the first wall  102  to seal the well  104  and form the chamber  110 . The coupling can be achieved, for instance, with an adhesive, mechanical coupling (e.g., threaded coupling, fasteners, clips, etc.), or other similarly suitable approach. 
     The second wall  106  includes a bottom portion  106   a  that defines the bottom of the recess  108 . When the second wall  106  seals the well  104 , the lenticule  10  is positioned between the bottom portion  102   a  of the first wall  102  and the bottom portion  106   a  of the second wall  106 . To accommodate the lenticule  10  and to keep the lenticule  10  in place, the distance along the z-axis between the bottom portions  102   a ,  106   a  may be approximately 100 μm (though other suitable dimensions are possible). Additionally, the diameter in the x-y plane of the bottom portion  106   a  may be approximately equal to the diameter of the lenticule  10 . In some embodiments, the bottom portion  106   a  of the second wall  106  may also be contoured or otherwise shaped to keep the lenticule  10  in place. When positioned between the bottom portions  102   a ,  106   a , the lenticule  10  can maintain its desired shape. For instance, the lenticule  10  can avoid rolling up or experiencing external forces that might affect its shape. 
     The example storage/delivery device  100 , for instance, provides significant advantages over an approach that holds a lenticule in a plastic pouch. In a plastic pouch, it might be difficult to determine identify and locate the lenticule relative to the pouch, and the lenticule might also be susceptible to undesired changes in shape, e.g., due to squeezing of the pouch. In contrast, the lenticule  10  can be easily located within the well  104  of the storage/delivery device  100 , and the storage/delivery device  100  allows the lenticule  10  to maintain the desired shape. 
     After the lenticule  10  is cut from the donor cornea (e.g., with a keratome, cryo-microtome, etc.), further preparation may include sterilizing the lenticule  10 , shaping aspects of the lenticule  10  with a laser, and/or measuring the lenticule  10 . The storage/delivery device  100  may be implemented at any point during the preparation process. According to an example implementation, after the lenticule  10  is cut from the donor cornea, the lenticule  10  may be placed in the well  104  of the storage/delivery device  100  (while in a humidified chamber) where it can be further shaped with a laser. While the lenticule  10  remains in the well  104 , dimensions and/or other characteristics of the lenticule  10  can be measured and the lenticule  10  can be sterilized. The well  104  may then be filled with a fluid medium, including such as albumin, prior to sealing the well with the second wall  106 . Other additional or alternative implementations and/or steps may be employed. For instance, in alternative implementations, the lenticule  10  might not undergo any further shaping with a laser while in the well  104 . In yet other implementations, the sterilization may occur after the well  104  is filled with the fluid. 
     In some embodiments, the lenticule  10  may adhere to a surface of the storage/delivery device  100 , e.g., the bottom portion  102   a  of the first wall  102 . When the lenticule  10  adheres to such a surface, it can maintain the desired shape and remain in place for shaping with a laser, measurements, and/or other operations or manipulations. In some implementations, a pressure may be applied to the lenticule  10 , e.g., with a fluid or a device, to cause it to adhere to the surface when in the well  104 . As discussed above, aspects of the storage/delivery device  100  may be contoured to accommodate the lenticule  10 ; such contours may also help the lenticule  10  to adhere to a surface. 
     The dimensions and/or other characteristics of the lenticule  10  can be measured by employing optical techniques, such as optical coherence tomography (OCT), second-harmonic generation (SHG) microscopy, or third-harmonic generation (THG) microscopy. OCT involves low-coherence interferometry using light of relatively long wavelengths (e.g., near-infrared light) to capture micrometer-resolution, three-dimensional images based on the optical scattering by the corneal tissue. SHG or THG microscopy involves detecting, with a microscope, variations in optical density, path length, refractive index, etc., in the corneal tissue based on variations in the corneal tissue&#39;s ability to generate second- or third-harmonic light from incident light (i.e., light having half or one-third the incident wavelength), respectively. 
       FIG. 2  illustrates the use of an example OCT system  200  to measure the lenticule  10  disposed in the well  104 . In particular, the OCT system  200  is positioned to direct incident light (e.g., near-infrared light) to the lenticule  10  and to receive optical scattering (e.g., reflection) from the lenticule  10  in response to the incident light. 
       FIG. 3  illustrates the use of an example SHG/THG microscopy system  300  to measure the lenticule  10  disposed in the well  104 . In particular, the SHG/THG microscopy system  300  includes a light source  302  that is positioned to direct incident light to the lenticule  10 . The SHG/THG microscopy system  300  also includes a detector  304  positioned to receive the 2 nd /3 rd  harmonic light from the lenticule  10  in response to the incident light. As shown in  FIG. 3 , the light source  302  and the detector  304  are positioned on opposite sides of the first wall  102 . As such, aspects of the first wall  102  are transmissive to allow the detector  304  to receive the 2 nd /3 rd  harmonic light. 
     Although  FIGS. 2 and 3  illustrate specific optical measurement techniques, the storage/delivery device  100  may be employed with any suitable optical or non-optical measurement system. 
     In general, tissue from donor cornea may experience swelling when placed in a fluid medium. While a volume of corneal tissue remains in an eye of a living donor, the volume of corneal tissue experiences physiological hydration conditions and maintains an initial size. When the volume of corneal tissue is removed from the living donor and stored in a fluid medium, however, the volume of corneal tissue experiences different hydration conditions. Thus, when stored in the medium, the volume of corneal tissue may swell from its initial size, resulting for instance in an increase in thickness. When the volume of corneal tissue is removed from the medium and placed in the physiological hydration conditions of a living recipient, the volume of corneal tissue shrinks from the swollen size back to its initial size. This phenomenon is referred hereinafter as deswelling. The corneal tissue shrinks by substantially the same factor by which it swells in the medium. 
     When forming an implant from a donor cornea, embodiments according to the present disclosure can account for the swelling that the corneal tissue experiences when stored in in a medium and the deswelling that the corneal tissue experiences when implanted into a living recipient. For instance, if a corneal implant of thickness 50 μm is needed in the living recipient, corneal tissue that has swelled in a medium can be cut into an implant with a thickness that is greater than 50 μm to accommodate anticipated deswelling. In particular, if the corneal tissue swells by a factor of two in the medium, the corneal tissue may be cut into an implant with a thickness of 100 μm, so that when deswelling occurs, the implant attains the desired thickness of 50 μm in the living recipient. 
       FIG. 4  illustrates an example approach  400  for producing implants, where the approach  400  accounts for swelling and deswelling of corneal tissue. In act  402 , a cornea is extracted from a donor in an operation. Immediately after the cornea is extracted from the donor, a post-operation thickness TC POST-OP  of the cornea is measured in act  404 . The thickness TC POST-OP  provides a good approximation of the thickness of the cornea while still residing in the donor (i.e., prior to act  402 ). In act  406 , OCT is employed to obtain a three-dimensional map of the cornea, which can be used for further processing of the corneal tissue. In act  408 , the cornea is placed in a medium in a pouch where it swells. When the cornea is received in the pouch for further processing, a swollen thickness TC SWELL  for the cornea is measured in act  410 . The swollen thickness TC SWELL  reflects the amount of swelling resulting from act  408 . 
     In act  412 , the cornea is cut into lenticules with a cryo-microtome or similar cutting device. Aspects of implementing a cryo-microtome are described, for instance, in U.S. Patent Application Publication No. 2017/0319329. The cryo-microtome can be set to cut the lenticules to a particular cut thickness TL CUT  corresponding to a percentage P of the swollen thickness TC SWELL  measured in act  410 . Additionally, the cryo-microtome can be employed to determine the thickness TC CUT  of the cornea at the time of cutting in act  412 . 
     In an example scenario, the cornea is measured in act  404  to have a post-operation thickness TC POST-OP  of 500 μm and the cornea swells to a swollen thickness TC SWELL  of 1000 μm as measured in act  410 . If the cornea does not experience any further changes in thickness after swelling in act  408 , the measured thickness TC′ CUT  of the cornea at the time of cutting in act  412  is 1000 μm. The cryo-microtome is set to make a series of cuts at a selected thickness TL CUT  of 100 μm. Based on the setting for the cryo-microtome (TL CUT =100 μm) and the thickness of the cornea measured at the time of cutting (TC CUT =1000 μm), each lenticule is P=(TL CUT /TC CUT )=10% of the cornea. 
     As described above, lenticules may provide a more general shape (e.g., a blank) that can be subsequently reshaped to form an implant that causes a desired change in refractive power. Thus, in act  418 , the lenticules are reshaped with a laser to produce implants of desired shapes. Prior to act  418 , however, the lenticules may experience drying, freezing, and/or other manipulation in act(s)  414 , which cause the lenticules to experience additional changes in thickness. The lenticules are measured in act  416 , e.g., with an OCT system, to determine the changed thickness TL CHANGE . Act  418  can then use the measurements to account for the additional changes in thickness prior to reshaping. 
     For instance, in the example scenario above, a lenticule has a thickness TL CUT  of 100 μm when cut from the cornea in act  412 , but after some events  414 , the lenticule may be measured in act  416  to have a changed thickness TL CHANGE  of 75 μm. Even though there is a changed thickness TL CHANGE , it is known that the lenticule, from the time of its cutting in act  412 , is still P=10% of the cornea. The cornea in physiological hydration conditions deswells to the thickness of 500 μm as measured in act  404 . Correspondingly, P=10% of the cornea will deswell to 10% of 500 μm, i.e., 50 μm. Thus, the lenticule will deswell from 75 μm as measured in act  416  to 50 μm. Accordingly, the reshaping in act  418  can take into account that the implant will deswell by a factor of 1.5. If the final implant should have a thickness of 40 μm, the reshaping in act  418  would cut the lenticule to 60 μm in thickness prior to deswelling. The deswell factor used in act  418  can be calculated as the changed thickness TL CHANGE  of the lenticule as measured in act  416  divided by the product of the percentage P of the lenticule relative to the cornea as determined in act  412  multiplied by the thickness TC POST-OP  of the cornea as measured in act  404 . 
     In the example scenario above, the cornea does not experience any further changes in thickness after swelling in act  408 . In other scenarios, however, the measured thickness TC CUT  of the cornea at the time of cutting in act  412  can change from the swollen thickness TC SWELL  measured in act  410 . For instance, the thickness TC CUT  of the cornea at the time of cutting in act  412  may be 800 μm. If the lenticules should be P=10% of the cornea, the cryo-microtome lenticules can be set to make a series of cuts separated by a selected thickness TL CUT  of 80 μm. The acts  414 ,  416 ,  418  apply as described above. Even though the selected thickness TL CUT  is 80 μm, the percentage P remains the same and the deswell factor in act  418  is still calculated as the changed thickness TL CHANGE  of the lenticule as measured in act  416  divided by the product of the percentage P as determined in act  412  multiplied by the post-operation thickness TC POST-OP  of the cornea as measured in act  404 . 
     As described above, in the act  412 , the cornea can be cut into lenticules with a cryo-microtome (or similar cutting device). Once the percentage P for the lenticules relative to the cornea has been determined (e.g., P=10%), the cryo-microtome can be set to make series of cuts that are spaced by a thickness TL CUT  corresponding to the percentage P.  FIG. 5  illustrates an example approach for making the series of cuts by the cryo-microtome and determining the deswelling associated with each lenticule produced by the cuts. In act  502 , the cryo-microtome makes a first cut in the cornea at a starting depth d 1  in act  502 . The starting depth d 1  of the first cut may be a few microns deep into the cornea. In act  504 , the cryo-microtome proceeds to make a series of cuts at increasing depths d 2 . . . n  into the cornea, where the depths d 1 . . . n  are spaced by the selected thickness TL CUT . The cryo-microtome ceases the series of cuts at depth d n , because the cornea is not sufficiently thick to allow the cryo-microtome to make another cut at a depth d n+1 =d n +TL CUT . The series of cuts at depths d 1 . . . n  produce n−1 lenticules of selected thickness TL CUT . The n th  lenticule, however, is defined in act  506  by the remaining corneal tissue beyond the cut at the depth d n . The n th  lenticule does not have the selected thickness TL CUT . Although one may attempt to cut the entire cornea evenly into n lenticules with the selected thickness TL CUT , errors in cutting the n−1 lenticules and the starting depth d 1  of the first cut may result in a final volume of corneal tissue with less than thickness TL CUT  for the n th  lenticule. 
     Unlike the first n−1 lenticules, the percentage P n  of the n th  lenticule relative to the cornea is not immediately known. Without the percentage P n , further processing of the n th  lenticule cannot accurately account for the effect of deswelling. Thus, to determine the percentage P n  of the n th  lenticule accurately, the n th  lenticule and the previous lenticule produced by the cuts at depths d n−1  and d n  can be hydrated in act  508  to a substantially similar state. In act  510 , the n th  lenticule and the previous lenticule can be measured, e.g., with an OCT system, while in similar hydration states. With the measurements from act  510 , the size of the n th  lenticule can be properly compared to the previous lenticule in act  512 . Because the percentage P of the previous lenticule relative to the cornea is known, the percentage of the n th  lenticule relative to the cornea can then be determined in act  514 . With this percentage P n , acts  414 ,  416 , and  418  apply as described above. Specifically, the reshaping of the n th  lenticule in act  418  can account for the deswelling that will occur during physiological hydration conditions (i.e., when the resulting implant is received by the living recipient). 
     The present inventors have also determined that for a given hydration state, tissue from more anterior portions of the cornea may be denser than tissue from more posterior portions of the cornea. As such, the swelling of a given volume of corneal tissue may also depend on the portion of the cornea from which the given volume of corneal tissue is taken. For instance, the given volume of corneal tissue may swell more if it is taken from a more posterior portion of the cornea. As such, embodiments can further account for the portion of the cornea from which the given volume of tissue is taken. By considering differences in swelling based on anterior/posterior regions, swollen corneal tissue can be cut more accurately to achieve an implant with a desired thickness in the living recipient. For instance, referring to  FIG. 4 , when the series of cuts are made at increasing depths into the cornea (e.g., from anterior cornea to posterior cornea) to produce a plurality of lenticules in act  412 , the respective anterior/posterior regions from which the lenticules are cut can be recorded and subsequently used in act  418  to account for deswelling that may depend on the respective anterior/posterior regions. 
       FIG. 6  illustrates an example approach  600  for reshaping lenticules to produce implants while accounting for any swelling. In particular, one or more calibrated weights  602  are placed on a lenticule  10  to squeeze the corneal tissue down to a thickness that corresponds more closely to the thickness it attains when it deswells in physiological hydration conditions. The calibrated weight(s)  602  are placed to apply uniform pressure across the lenticule  10 , particularly to avoid folding or rolling at the periphery. The calibrated weight(s)  602  may be applied to provide varying amounts of pressure at different times and for different durations. Once the desired thickness is achieved, a cutting device  604  (e.g., a trephine) can be applied to the lenticule  10 . During the cutting process, the lenticule  10  can be positioned on a device  606  (e.g., a mandrel) with a contoured surface that approximates the curvature of a cornea. 
     In other approaches, a donor cornea can be squeezed with pressure and frozen when the donor cornea reaches a thickness that corresponds more closely to its thickness in physiological hydration conditions. 
     In the embodiments above, the hydration state and corresponding aspects of corneal tissue can be evaluated via raman spectroscopy, 2 nd  harmonic measurements, holography or the like. 
     Aspects of the embodiments above may be implemented with computer-based controllers that can execute programmed instructions stored on computer-readable storage media. For instance, such controllers can be implements to control the disclosed measurement systems and/or process signals and information from the measurement systems. 
     While the present disclosure has been described with reference to one or more particular embodiments, those skilled in the art will recognize that many changes may be made thereto without departing from the spirit and scope of the present disclosure. Each of these embodiments and obvious variations thereof is contemplated as falling within the spirit and scope of the invention. It is also contemplated that additional embodiments according to aspects of the present disclosure may combine any number of features from any of the embodiments described herein.