Abstract:
A device is disclosed for separating the epithelial layer of a cornea from the eye. The device includes a separator having an edge to remove the epithelial layer as the separator moves across the eye. The edge includes a thickness thicker than the thickness of at least one epithelial cell and less thick than the thickness of the epithelial layer. Separation can be performed mechanically, without the use of chemicals, so that the shape and integrity of the separated epithelial layer is preserved. The device can also be used with a polymer film that adheres to the epithelial layer to help preserve an integrity of the epithelial layer.

Description:
REFERENCE TO EARLIER FILED APPLICATION  
       [0001]    The present application claims the benefit as a Continuation-in-Part of U.S. patent application Ser. No.09/911,356 filed Jul. 23, 2001, which is incorporated by reference herein. 
     
    
     
       BACKGROUND  
         [0002]    LASIK (Laser-Assisted In Situ Keratomileusis) is a surgical procedure intended to reduce a person&#39;s dependency on glasses or contact lenses. LASIK permanently changes the shape of the cornea, the clear covering of the front of the eye, using an excimer laser. A device, called a microkeratome, is used to cut a flap in the cornea. A hinge is left at one end of this flap. The flap is folded back revealing the stroma, the middle section of the cornea. Pulses from a computer-controlled laser vaporize a portion of the stroma and the flap is replaced. It is important that the knife used during the LASIK procedure is sharp, otherwise the quality of the procedure and the healing time are poor. Additionally the knife has to be sharp in order to produce consistent and reproducible flaps. There are some complications related to the use of microkeratomes. Common complications include the creation of an irregular flap, for example, a half flap, a buttonhole, or a total cup. These complications represent irregular incisions of the cornea, a situation that can permanently degrade visual performance.  
           [0003]    Alternatively, PRK (Photo-Refractive Keratectomy) which is a technique developed earlier than LASIK may be used to correct the curvature of the cornea. In PRK a physician scrapes away the superficial layer, e.g., the epithelium, of the cornea. After the superficial layer is removed, laser treatment is applied on to the exposed surface of the cornea. A drawback of PRK, however, is that the healing period for the eye typically lasts for a week, much longer than the healing period of LASIK. Also, the patient experiences some pain during healing. Typically in PRK a disposable contact lens is used to cover the treated area of the cornea and help reduce postoperative pain.  
           [0004]    In another technique, LASEK (Laser Epithelial Keratomileusis) the epithelial layer is separated from the surface of the cornea in a manner that the separated epithelial layer can be preserved. First, the epithelium is treated with and alcohol solution to partially devitalize it. Once the exact surface area of treatment is determined, a few drops of a weak alcohol solution is applied to the surface of the cornea and allowed to stay in contact with the epithelium for a few seconds. This weak alcohol solution is then rinsed off the surface of the eye. The function of the weak alcohol solution is to loosen the epithelial layer (50 microns) and to allow it to be peeled back in a sheet of epithelial cells, thereby exposing the underlying cornea. This is not to be confused with LASIK, which actually uses a microkeratome instrument to create a flap of both epithelium and the front part of the stromal tissue measuring anywhere between 130 to 180 microns.  
           [0005]    In LASEK, the epithelium-only layer is laid back in a similar fashion to LASIK, but consists of only epithelium, not corneal stroma. Once the epithelial cells have been laid out of the way, the laser is applied to the surface of the cornea in the exact same fashion as in PRK. Once the laser treatment has been completed, the epithelial layer is laid back into place and a soft contact lens is placed over the eye as in PRK. The epithelial cells, which were partly devitalized by the weak alcohol solution, are laid over the treatment area and may serve as a facilitator of new epithelium healing underneath. The alcohol-devitalized epithelium falls off the eye, similar to a scab, in 5-10 days. These devitalized epithelial cells do not become the new surface of the eye, but simply serve as a protective agent in addition to the contact lens to facilitate comfort and healing of the new underlying epithelium. Alcohol treatment of the epithelium results in a severe amount of epithelial cell loss, a fact that may render the epithelial disk not usable, due to the reduced durability and adhesion on to the cornea.  
           [0006]    Thus, there is a need for an automated corneal epithelium separator that addresses the above problems by separating the epithelial layer as a whole in a mechanical way, not chemical.  
         BRIEF SUMMARY  
         [0007]    To help correct an imperfect vision of a patient&#39;s eye, an automated mechanical device separates the epithelial layer from the cornea of a patient&#39;s eye from the cornea. After the epithelial layer is separated from the cornea, a laser is used to help correct imperfections in the cornea. Thereafter, the epithelial layer is placed back on the cornea to reduce the visual rehabilitation period and reduce postoperative pain.  
           [0008]    In one aspect, the device includes a separator such as a plate, wire or dull blade. The device can preserve a separated epithelial layer as a disk without rupturing the disk and without substantial epithelial cell loss. The epithelial layer is separated from the cornea without cutting the cornea.  
           [0009]    The device includes a separator having an edge to remove the epithelial layer as the separator moves across the eye. The edge includes a thickness thicker than the thickness of at least one epithelial cell and less thick than the thickness of the epithelial layer. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]    [0010]FIG. 1 is a diagram showing a side view of an eye and a epithelial separator with a separator located in a first position according to the preferred embodiments.  
         [0011]    [0011]FIG. 2 is a diagram showing a top view of the eye and the separator located in a first position according to the preferred embodiments.  
         [0012]    [0012]FIG. 3 is a diagram showing a side view of the eye and the separator located in a second position according to the preferred embodiments.  
         [0013]    [0013]FIG. 4 is a diagram showing a top view of the eye and the separator located in a second position according to the preferred embodiments.  
         [0014]    [0014]FIG. 5 is a diagram showing a side view of the eye and the separator located in a third position according to the preferred embodiments.  
         [0015]    [0015]FIG. 6 is a diagram showing a top view of the eye and the separator located in a third position according to the preferred embodiments.  
         [0016]    [0016]FIG. 7 is a diagram showing a side view of the eye and the separator located in a fourth position according to the preferred embodiments.  
         [0017]    [0017]FIG. 8 is a diagram showing a top view of the eye and the separator located in a fourth position according to the preferred embodiments.  
         [0018]    [0018]FIG. 9 is a diagram showing a top view of the eye and the separator located in a fifth position according to the preferred embodiments, the separator is retracted after epithelial separation.  
         [0019]    [0019]FIG. 10 is a diagram showing a top view of the eye with the separator removed.  
         [0020]    [0020]FIG. 11 is a diagram showing a top view of the eye after ablations is performed with a laser.  
         [0021]    [0021]FIG. 12 is a diagram showing a top view of the eye with the epithelium replaced on the eye.  
         [0022]    [0022]FIG. 13. is a diagram showing a top view of the eye with the epithelium smoothly stretched into place.  
         [0023]    [0023]FIG. 14 is a diagram showing a side view of the eye and the epithelial separator device including a rotating drum.  
         [0024]    [0024]FIG. 15 is a diagram showing a front view of the eye and the epithelial separator device including the rotating drum.  
         [0025]    [0025]FIG. 16 is a diagram showing a top view of the eye and the epithelial separator device including the rotating drum.  
         [0026]    [0026]FIG. 17 is a diagram showing a drum according to one embodiment.  
         [0027]    [0027]FIG. 18 is a diagram showing a drum according to another embodiment.  
         [0028]    [0028]FIG. 19 is a diagram representing a side view of a separator removing the epithelial layer from the Basal membrane of the eye.  
         [0029]    [0029]FIG. 20 is a diagram showing a perspective view of a known blade.  
         [0030]    [0030]FIG. 21 is a diagram showing a side view of a separator&#39;s leading edge according to an embodiment.  
         [0031]    [0031]FIG. 22 is a diagram showing a side view of a separator&#39;s leading edge according to another embodiment.  
         [0032]    [0032]FIG. 23 is a diagram showing a side view of a separator&#39;s leading edge according to yet another embodiment.  
         [0033]    [0033]FIG. 24 is a diagram showing a perspective view of a wire that could be used as a separator according to a preferred embodiment.  
         [0034]    [0034]FIG. 25 shows a perspective view of an exemplary machine that is used to condition a separator according to one embodiment.  
         [0035]    [0035]FIG. 26 shows a front view of the machine of FIG. 25 including the separator.  
         [0036]    [0036]FIG. 27 shows a side view of one embodiment of a device for separating and preserving an epithelial layer.  
         [0037]    [0037]FIG. 28 shows a top view of the device of FIG. 27. 
     
    
     DETAILED DESCRIPTION  
       [0038]    To help correct an imperfect vision of a patient&#39;s eye, an automated mechanical device separates the epithelial layer from the cornea of a patient&#39;s eye from the cornea. A separator, such as a plate, wire or dull blade is used to separate the epithelial layer of the cornea from the basal membrane. In this way, the automated mechanical device can preserve the separated epithelial layer as a disk without rupturing the disk and without substantial epithelial cell loss, less than 5-10% loss, to ensure viability and stability of the epithelial disk after replacement on the surface of the cornea. After the epithelial layer is separated from the cornea, a laser is used to help correct imperfections in the cornea. Thereafter, the epithelial layer is placed back on the cornea to aid in the healing process of the eye.  
         [0039]    [0039]FIG. 1 is a diagram showing a side view of an eye  10  of a patient and a epithelial separator device  12 . The epithelial separator device  12  includes a separator  14 , shown here in a first position located away from the eye  10 . The separator  14  includes a device that can scrape the epithelium from the cornea such as a plate, a wire or a knife with a dull edge. The separator  14  removes an epithelium layer  16  located above a corneal surface  18  of the eye  10 . The separator  14  is not sharp enough to excise corneal tissue during operation of the epithelial separator device  12 .  
         [0040]    Referring also to FIG. 2, the epithelial separator device  12  includes a ring  20  that sits on the eye  10  with its plane parallel to a limbus of the eye. The ring  20  includes an internal diameter  22  ranging from about 10 to about 12 mm and external diameter  24  from about 13 to about 16 mm and including a groove  26  (best seen in FIG. 15). The groove  26  is dimensioned wider than the internal diameter  22 . A separator support  28  fits in the groove  26  to carry the separator  14  on a determined travel.  
         [0041]    An oscillation device  30  provides motion and vibration to the separator  14 . The oscillation device  30  can oscillate the separator  14  either transversely or longitudinally with frequency ranging from about 10 Hz to about 10 KHz. Electromagnetic or piezoelectric forces on the separator  14  can provide the oscillation, or external rotating or vibrating wires can provide the oscillation. To maintain the ring  20  on the eye  10 , for example during oscillation, the ring  20  can include a circumferential groove  32  positioned on a side of the eye  10 . Suction can be applied to the circumferential groove  32  to ensure stable mounting of the ring  20  to the eye  10 .  
         [0042]    [0042]FIGS. 3 and 4 are diagrams showing a side and a top view, respectively, of the eye  10  and the separator  14  located in a second position with respect to the eye. As the separator  14  travels to contact the eye  10 , the corneal surface  18  is flattened. To accommodate the travel of the separator  14 , the separator support  28  freely slides in the groove  26 , for example, when driven by the oscillation device  30 .  
         [0043]    [0043]FIGS. 5 and 6 are diagrams showing a side and a top view of the eye  10  and the separator  14  located in a third position. As the separator  14  travels along the cornea  10 , the epithelium layer  16  is separated from the cornea.  
         [0044]    The separator  14  separates the epithelium layer  16  without cutting the cornea  18 .  
         [0045]    [0045]FIGS. 7 and 8 are diagrams showing a side and a top view of the eye  10  and the separator  14  located in a fourth position. In one embodiment, the travel of the separator  14  is controlled to produce an epithelial disk  34  hinged at an edge  36  of the epithelial disk  34 . In another embodiment the epithelial disk  34  is completely detached for the corneal surface  18 , for example, as described below.  
         [0046]    [0046]FIG. 9 is a diagram showing a top view of the eye  10  and the separator  14  located in a retracted position after the epithelial disk  34  as been formed. After the separator  14  is retracted, suction to the circumferential groove  32  is turned off and the epithelial separator device  12  is removed from the eye  10 . Referring also to FIG. 10, after the epithelial separator device  12  is removed, a deepithelialized area  38  is exposed that corresponds to a shape and size of the area that the separator  14  contacted during travel.  
         [0047]    [0047]FIG. 11 shows a top view of the eye  10  after laser ablation is performed. The laser ablation forms an irradiated area  40  on the eye  10 . Referring to FIG. 12, thereafter, the epithelium disk  34  is replaced on the corneal surface  18  of the eye  10  to aid in the healing process. Referring to FIG. 13, once replaced on the corneal surface  18 , the epithelium disk  34  is preferably smoothly stretched into place.  
         [0048]    [0048]FIG. 14 is a diagram showing a side view of the eye  10  and the epithelial separator device  12  including rotating drum  42 . To rotate the drum  42 , the epithelial separator device  12  may include a rotating gear  44 . The gear  44  could also be used to provide movement to the separator support  28 . Referring also to FIGS. 15 and 16, front and top views, respectively, of the epithelial separator device  12 , the rotating gears  44  could be bilaterally placed on the separator support  28 . The oscillating device  30  can provide for rotation of the gears  44  and the gears  44  can travel on rails, for example toothed rails, which run parallel to the groove  26 .  
         [0049]    Since a typical thickness of an epithelial disk  36  includes about 50 microns, to preserve an epithelial disk  36 , a separated epithelial disk  36  is rolled onto the drum  42 . The drum  42  can include a diameter ranging from about 3 to about 9 mm and a length of about 12 mm. Referring also to FIG. 17, in one embodiment, to maintain integrity of the epithelial disk  36 , the drum  42  can be coated with a hydrating and/or a conditioning substrate. The hydrating and/or conditioning substrate can include, for example, HEMA contact lenses, tissue culture media, silicone and biocompatible hydrogels. The hydrating and/or conditioning substrate can be removed from the drum after the epithelial disk  36  attaches on to the drum. Thereafter, the epithelial disk  36  can be removed from the drum  46  and replaced on the corneal surface  16 , as described above.  
         [0050]    [0050]FIG. 18 shows another embodiment of the drum  42  includes apertures  46  and a connector  48  that connects to a suction source (not shown). By applying suction to the apertures  46  of the drum  42 , the epithelial disk  36  can be rolled onto the drum  42 . Thereafter, the epithelial disk  36  can be removed from the drum  46  and replaced on the corneal surface  16 , as described above.  
         [0051]    [0051]FIG. 19 is a diagram representing a side view of the separator  14  removing the epithelial layer  16  from a Basal membrane  1900  of the eye  10 . The epithelial layer  16  is made up of epithelial cells  1902 . The epithelial layer  16  overlies the Basal membrane  1900 . The Basal membrane  1900  is formed from a lamina densa  1904  of about 50 nm in thickness and an underlying lamina lucida  1906  of about 25 nm in thickness. The lamina densa  1906  overlies a Bowman&#39;s layer  1908 . The epithelial layer  16  anchors to the Bowman&#39;s layer via a complex mesh of anchoring fibrils (type VlI collagen) and anchoring plaques (type VI collagen) that interact with the lamina densa  1904  and the collagen fibrils of the Bowman&#39;s layer  1908 . The Bowman&#39;s layer  1908  overlies a corneal stroma  1910 .  
         [0052]    The epithelial layer  16  is stratified, possessing 5 to 6 layers of epithelial cells  1902 . The epithelial layer  16  is typically about 50 to 60 micrometers in thickness. Adjacent epithelial cells  1902  are held together by desmosomes  1912 . The epithelial cells  1902  are held to the underlying basal membrane  1900  by hemidesmosomes  1914  and anchoring filaments. A bottom surface of the epithelial layer  16  includes numerous microvilli and microplicae, i.e., ridges, whose glycocalyx coat interacts with, and helps to stabilize, a precorneal tear film. New epithelial cells  1902  are derived from mitotic activity in the basal membrane  1900  layer. New epithelial cells  1902  displace existing cells both superficially and centripetally.  
         [0053]    The separator  14  includes a blunt leading edge to push the epithelial cells  1902  as the separator  14  moves across the epithelial layer  16 . The separator  14  has a thickness that is preferably between one cell layer thick and the thickness of the epithelial layer  16 . More preferably, the separator has a thickness between two to three cell layers in thickness. The separator  14  preferably pushes the epithelial cells  1902  and does not exert a force that could disrupt the intercellular bonds such as the desmosomes  1912 . The point of separating the epithelial layer  16  has been found to often occur at the border between the lamina densa  1904  and the lamina lucida  1906 . The separator  14  preferably pushes the bottom two to three layers of epithelial cells  1902  which probably contain a majority of the shear strength of the epithelial layer  16 .  
         [0054]    [0054]FIG. 20 is a diagram showing a perspective view of a known blade  2000 . A leading edge  2002  of the blade  2000  is sharp and thus would not work well as a separator. The blade  2000  risks cutting the cornea.  
         [0055]    [0055]FIG. 21 is a diagram showing a side view of a leading edge  2100  of a separator  14  according to an embodiment. The leading edge  2100  of the separator  14  should not be too wide such that it will reduce the consistency with which the epithelial layer  16  is penetrated. The leading edge  2100  preferably includes a 5 to 25 micrometer width, and more preferably includes about a 15 micrometers width.  
         [0056]    [0056]FIG. 22 is a diagram showing a side view of a separator&#39;s leading edge  2100  according to another embodiment. The leading edge  2100  is rounded instead of flat.  
         [0057]    [0057]FIG. 23 is a diagram showing a side view of a separator&#39;s leading edge  2100  according to yet another embodiment. The separator  14  is constructed, for example, by bending the leading edge  2002  of the blade  2000  shown in FIG. 20. The leading edge  2001  preferably includes a diameter of about 5 to 25 micrometers, or a radius between about 2 to 13 micrometers, and more preferably includes a diameter of 15 micrometers.  
         [0058]    [0058]FIG. 24 is a diagram showing a perspective view of a wire  2400  that could be used as the separator  14  according to a preferred embodiment. The wire  2400  includes a generally elliptical or circular cross-sectional shape. The wire  2400  includes a leading edge with a width of about 5 to 25 micrometers. The wire  2400  is preferably manufactured from a material that is strong enough to push the epithelium without breaking. Exemplary wire materials include titanium and its alloys, tungsten and its alloys, steel alloys and carbon fibers.  
         [0059]    [0059]FIG. 25 shows a perspective view of an exemplary machine  2500  that is used to condition a separator  14  according to one embodiment. The machine  2500  conditions the separator  14  by changing a sharp edged separator to include a generally bent edge, for example, like the front edge of the separator  14  shown in FIG. 23.  
         [0060]    [0060]FIG. 26 shows a front view of the machine  2500  and separator  14 . Referring to FIGS. 25 and 26, the machine  2500  includes a motor  2510 , a rotating cylinder  2520 , a weight  2530 , or other way to hold the blade down, and a blade holder  2540 . The motor  2510  and a housing  2544  of the cylinder  2520  rest on a platform  2546 . The blade is held by, for example, a clamp. The blade&#39;s edge is substantially parallel to the axis of rotation of cylinder  2520 . The blade&#39;s plane forms an angle between 0 and 20 degrees with the is plane defined by the axis of the cylinder  2520  and the blade&#39;s edge. The motor  2510  connects to the cylinder  2520  via a belt  2550  to rotate the cylinder  2520 . In another embodiment, the motor  2510  connects directly to the cylinder  2520  to rotate the cylinder.  
         [0061]    The cylinder  2520  includes a helical wire  2560 . The helical wire  2560  and the cylinder  2520  are manufactured from steel. This helical wire serves as a helical protrusion of the rotating drum. This helix has a pitch equal to the length of the blade&#39;s edge. The helix causes only one point of the blade to be conditioned at any given moment (the point of contact between the blade&#39;s edge and the helical wire). As the helical wire  2560  rotates along with drum  2520 , the point of contact travels along the blade&#39;s edge, but the amount of conditioning is equal across the blade&#39;s length. The weight  2530 , and the running time and rotations of the cylinder  2520  vary the shape and width of the leading edge  2100  of the separator  14 . In one embodiment, a preferred separator  14  has been conditioned by asserting 20 mN of force on the separator  14  to the cylinder  2520  and operating the cylinder for about 45 second at 0.7 (seven-tenths) rotations/second.  
         [0062]    [0062]FIG. 27 shows a side view of one embodiment of a device  2700  for separating and preserving an epithelial layer  16 . The device  2700  includes a body  2705 , a first drum  2720  and a second drum  2730 , and a belt  2730  connecting the first drum  2720  to the second drum  2730 . The device  2700  accommodates a substrate, such as film  2740 . Film  2740  is used to substantially preserve the epithelial layer  16  when the epithelial layer  16  is removed from the eye  10 . The film  2740  can be held to the drum  2710  with a bar or clip  2750 . Alternatively, the film  2740  can serve to connect the drums  2720  and  2730  and therefore eliminate the use of belt  2730 .  
         [0063]    [0063]FIG. 28 shows a top view of the device  2710  and how the device  2700  is used with the clip  2750 . In one embodiment, the film  2740  is rolled on to the drum  2710  and under the clip  2750  (see also FIG. 27). The first drum  2710  turns as the second drum  2720  turns since they are connected by the belt  2730 . The film  2740  lays on the belt  2730  and moves as the first drum  2710  and the second drum  2720  move. The film  2740  preferably removably adheres to the belt  2730  through cohesion.  
         [0064]    The film  2740  includes an outer surface  2760 . The outer surface  2760  is constructed to adhere to the epithelial layer  16  to provide mechanical stability to the epithelial layer  16  when the epithelial layer  16  is separated from the eye  10 . The film  2740  includes a natural or synthetic polymer. An exemplary polymer includes HEMA (poly-2hydroxy-ethyl-methacrylate). The film  2740  includes a thickness from about 20 to about 100 micrometers. If the film  2740  is in the shape of a strip of film, a length (a) and a width (b) of the film  2740  is preferably longer and wider than the diameter of a separated epithelium layer  16 .  
         [0065]    The film  2740  is preferably hydrated to adhere the epithelial layer  16  to the film  2740 . The level of hydration of the film  2740  controls adhesion to the film  2740 . The hydrated film  2740  also helps to keep cracks from forming in the removed epithelial layer  16 , and to help avoid the removed epithelial layer  16  from being torn or shrinking. In one embodiment, a surface of the epithelial layer  16  is dried, for example, with a sponge or with a compressed air flow. Thereafter, the film  2740  is placed on the epithelial layer  16 . The epithelial layer  16  adheres to the film  2740  because of the difference in hydration levels between the epithelial layer and the film.. Thereafter, the separator  14  is used to separate the epithelial layer  16 . The film  2740  and the epithelial layer  16  are rolled onto the first and second drums  2710 ,  2720 .  
         [0066]    It should be appreciated that the strip of film  2740  does not have to be applied with the device  2700  and that the strip does not need to include a coating. Moreover, the film  2740  can be applied before or after removal of the epithelial layer  16 , and can be manually applied instead of using the device  2700 .  
         [0067]    The film  2740  can include other shapes such as the shape of a disc. A way to attach the epithelial layer  16  to a disc, such as a contact lens, is to separate the epithelial layer  16  and remove the epithelial layer  16  to the side. The epithelial layer  16  is then smoothed with a sponge and dried with the sponge, compressed air or both. Thereafter, the removed epithelial layer  16  is placed on the film  2740 . The epithelial layer  16  and the film  2740  are then dried, for example, with compressed air. After about 30 seconds of drying, the epithelial layer  16  is adhered to the film  2740  and can be more easily manipulated with a reduced risk of damage.  
         [0068]    While the invention has been described above by reference to various embodiments, it will be understood that many changes and modifications can be made without departing from the scope of the invention. It is therefore intended that the foregoing detailed description be understood as an illustration of the presently preferred embodiments of the invention, and not as a definition of the invention. It is only the following claims, including all equivalents, which are intended to define the scope of this invention.