WO2007112130A2

WO2007112130A2 - Automatic epithelial delaminator and lens inserter

Info

Publication number: WO2007112130A2
Application number: PCT/US2007/007847
Authority: WO
Inventors: Edward Perez; Jay Daulton; Paul Hsei; Matthew Mcdonald
Original assignee: Tissue Engineering Refraction, Inc.
Priority date: 2006-03-28
Filing date: 2007-03-28
Publication date: 2007-10-04
Also published as: WO2007112130A3; TW200808282A

Abstract

The described devices and methods are useful in the field of ophthalmology. Described herein are epithelial delaminators, applicators, lens inserters, and methods of using those devices for introducing an ocular device beneath a corneal epithelium. Typically, the devices would be used to lift a section or portion of the corneal epithelium and insert a lens or other ocular correction device beneath the lifted epithelium in a single stroke. The described devices and methods for using them involve separating or lifting corneal epithelium from the eye in a substantially continuous layer to form a flap or pocket. In particular, the devices and methods generally utilize a combined epithelial delaminator and ocular device inserter. The combined delaminator and inserter is configured to separate the epithelium from the cornea, e.g., between the epithelium and the corneal stroma (Bowman's membrane) in the region of the lamina lucida, and also to introduce an ocular device on the eye without the need for an additional inserter or an additional insertion step. The devices and methods described herein may be used as part of an ocular therapy including ocular corrective surgery and laser eye corrective surgery.

Description

AUTOMATIC EPITHELIAL DELAMINATOR AND LENS INSERTER

FIELD

(0001] The described devices and methods are useful in the field of ophthalmology.

Described herein are epithelial delaminators, applicators, lens inserters, and methods of using those devices for introducing an ocular device beneath a corneal epithelium. Typically, the devices would be used to lift a section or portion of the corneal epithelium and insert a lens or other ocular correction device beneath the lifted epithelium in a single stroke. The described devices and methods for using them involve separating or lifting corneal epithelium from the eye in a substantially continuous layer to form a flap or pocket. In particular, the devices and methods generally utilize a combined epithelial delaminator and ocular device inserter. The combined delaminator and inserter is configured to separate the epithelium from the cornea, e.g., between the epithelium and the corneal stroma (Bowman's membrane) in the region of the lamina lucida, and also to introduce an ocular device on the eye without the need for an additional inserter or an additional insertion step. The devices and methods described herein may be used as part of an ocular therapy including ocular corrective surgery and laser eye corrective surgery.

BACKGROUND

(0002) Refractive surgery refers to a set of surgical procedures that change the native optical or focusing power of the eye. The result of these procedures often alleviates the need for glasses or contact lenses that an individual might otherwise be dependent on for clear sight. The majority of the focusing power in the human eye is dictated by the curvature of the air-liquid interface, where there is the greatest change in the index of refraction. This curved interface is the outer surface of the cornea. The refractive power of this interface accounts for approximately 70% of the total magnification of the eye. Light rays making up seen images pass through the cornea, the anterior chamber, the crystalline lens, and the vitreous humor before being focused on the retina to form an image. It is the magnifying power of this curved, air-corneal interface that provided the field of refractive surgery with the opportunity to surgically correct visual deficiencies. |0003] Early refractive surgical procedures corrected nearsightedness by flattening the curvature of the cornea. The first procedure having a measure of success was called radial keratotomy (RK). RK was widely used during the 1970's and early 1980's and involved providing radially oriented incisions in the periphery of the cornea. These incisions reformed the peripheral cornea by causing it to bow outwards, consequently flattening the central optical zone of the cornea. Such a procedure was fairly easy and thus, popular, but it rarely did more than lessen one's dependency on glasses or contract lenses. |0004J A largely flawed and failed procedure called epikeratophakia was developed in the era of RK. It is now essentially an academic anomaly. Epikeratophakia provided a new curvature to the outer curvature of the cornea by grafting onto the cornea a thin layer of preserved corneal tissue. The processed corneal tissue was freeze-dried and during the process of freeze drying, the cornea was also ground to a specific curvature. The resulting lens was surgically placed into the eye. An annular 360° incision was made in the cornea after the epithelium was completely removed from the site where the epikeratophakic lens would eventually reside. The perimeter of this lens would be inserted into the annular incision and held in place by a running suture. There were several problems with epikeratophakia: 1) the lenses remained cloudy until host stromal fibroblasts colonized the lens, which colonization possibly would take several months; 2) until migrating epithelium grew over the incision site onto the surface of the lens, the interrupted epithelium was a nidus for infection; and 3) epithelium healing onto the surgical site sometimes moved into the space between the lens and the host cornea. Currently, epikeratophakia is limited in its use. It is now used in pediatric aphakic patients who are unable to tolerate very steep contact lenses. [0005] Around the mid- 1990's, procedures that sculpt the cornea with lasers were sufficiently successful that they began to replace radial keratotomy. The first generation of laser ablation of the cornea was called photorefractive keratectomy (PRK). In PRK, an ablative laser (e.g., an excimer laser) is focused on the cornea to sculpt a new curvature into the surface. In PRK, the epithelium is destroyed when achieving a new outer surface curve. Over the ensuing post-operative days, the epithelium grows or heals back into place. This epithelial healing phase was problematic for most patients since the epithelially denuded and ablated cornea was painful. The patient often found initial difficulties with sight following PRK, and this "recuperative time" could last for periods of time extending from days to a week or more. 10006] A subsequent variation of PRK corneal laser ablation, LASIK, has become very popular. The LASIK procedure, also known as laser in situ keratomileusis, is currently synonymous in the public mind with laser vision correction. In LASIK, an outer portion (or chord-like lens-shaped portion) of the cornea (80 to 150 microns thick) is surgically cut from the corneal surface. This step is performed by a device known as a microkeratome. The microkeratome cuts a circular flap from the surface of the cornea, leaving the flap (made up of both epithelial and corneal tissue) hinged at one edge. This flap is folded or reflected back and an ablative laser (e.g., an excimer laser) is used to remove or to reform a portion of the exposed surgical bed. The flap is laid back into place. When this flap is laid back into place, the cornea achieves a new curvature because the flap conforms to the laser-modified corneal surface. In this procedure, epithelial cells are not removed nor harmed. The epithelial cells have simply been incised at the edge of this flap. When the flap is placed back onto the corneal bed, the epithelium heals back at the incision site. There is essentially no recuperative time and the results perceived by the patient are almost immediate. Because there is very little surgical time (often about 15 minutes for each eye) and because there are lasting and very accurate results, LASIK is currently considered the premier manner of performing refractive surgery.

[0007] A newer technique being evaluated in high volume refractive surgical practices and in some academic centers is a procedure called Laser Assisted Subepithelial Keratomileusis (LASEK). In LASEK, a "flap" is made of only epithelium. This layer of epithelium is lifted off the cornea in a manner similar to LASIK but is created by using an ethanolic wash on that epithelium. The ablative laser is focused just on the surface of the denuded cornea (in the same manner as was done with PRK). However, this epithelial flap is left intact, i.e., the epithelium physical structure is not destroyed even though cellular viability is largely destroyed. The epithelium is simply rolled back into place after formation of the re-curved anterior portion of the cornea, resulting in much less recuperative time than with PRK. Current methods of LASEK are not as good as LASIK but the results are better than with PRK.

[0008] The corneal epithelium is a multilayered epithelial structure typically about 50 μm in thickness. It is non-cornified. The outer cells are living, although they are squamous in nature. The basal epithelial cells are cuboidal and sit on the stromal surface on a structure known as Bowman's membrane. The basal cell layer is typically about 1 mil thick (0.001"). The basal cells produce the same keratins that are produced in the integument, i.e., skin. The basal epithelial cells express keratins 5 and 14 and have the potential to differentiate into the squamous epithelial cells of the corneal epithelium that produce keratins 6 and 9. The corneal epithelium has a number of important properties: 1) it is clear; 2) it is impermeable; 3) it is a barrier to external agents; and 4) it is a highly innervated organ. Nerves from the cornea directly feed into the epithelium, and thus, defects of this organ produce pain. [0009J Epithelial cells are attached side-to-side by transmembrane molecules called desmosomes. Another transmembrane protein, the hemidesmosome, connects to collagen type 7 and is present on the basolateral surface of basal epithelial cells. Hemidesmosomes anchor epithelium to the underlying collagenous portion of the stroma. The junction between the epithelium and corneal stroma is referred to as basement membrane zone (BMZ). [001 OJ When LASEK is performed, a physical well is placed or formed on the epithelium and filled with a selection of 20% ethanol and balanced salt solution. Contact with the solution causes the epithelial cells to lose their adherence at the BMZ, most likely by destroying a portion of that cell population. The epithelium is then raised by pushing the epithelium back in a manner similar to chemically stripping a wall of paint. The exposed collagenous portion of the corneal stroma is then ablated to reshape its surface. A weakened epithelium is then rolled back into place to serve as a bandage. However, this "bandage" fails to restore the epithelium to its original state, i.e., it does not preserve the integrity of the epithelium, thereby reducing its clarity, impermeability to water, and barrier function. Furthermore, the ability of the epithelium to adhere to the corneal stromal surface is impaired.

REFERENCES

(0011] Kiistala, U. (1972). "Dermal-Epidermal Separation. II. External Factors in

Suction Blister Formation with Special Reference to the Effect of Temperature," Ann Clin

Res 4(4):236-246. [0012] Azar et al. (2001). "Laser Subepithelial Keratomileusis: Electron Microscopy and Visual Outcomes of Flap Photorefractive Keratectomy," Curr Opin Ophthalmol

12(4):323-328. [00.13] Beerens et al. (1975). "Rapid Regeneration of the Dermal-Epidermal Junction

After Partial Separation by Vacuum: An Electron Microscopic Study,"J/m>es/ Dermatol

65(6):513-521. (00141 Willsteed et al. (1991). "An Ultrastructural Comparison of Dermo-Epidermal

Separation Techniques," J Cutan Pathol 18(1):8-12. [0015J Van der Leun et al. (1974). "Repair of Dermal-Epidermal Adherence: A Rapid

Process Observed in Experiments on Blistering with Interrupted Suction," J Invest Dermatol

63(5):397-401. [0016| Katz SI. (1984). "The Epidermal Basement Membrane: Structure, Ontogeny and Role in Disease," Ciba Found Symp 108:243-259. [0017] Green et al. (1996). "Desmosomes and Hemidesmosomes: Structure and

Function of Molecular Components," FASEBJ 10(8): 871-881.

[0018[ None of the cited references shows or suggests our devices and procedures as described herein.

SUMMARY

[0019] The written description here includes description of devices for separating a portion of the corneal epithelium from the cornea and inserting a lens or other medical device beneath that lifted corneal epithelium. This written description includes description of certain components (and combinations of components with the applied or appliable lenses) forming the integrated system. The integrated system may comprise a complete or automated system for introducing the lens or other medical device beneath the lifted epithelium, although the description is not so limited in its scope. The component device inserters for introducing an ocular device beneath a corneal epithelium may include a) an edge configured to mechanically separate a layer of the corneal epithelium from a cornea while maintaining the epithelial layer in at least partial attachment to the cornea and b) an ocular device holder configured to hold an ocular device. The ocular device holder often is also configured place the ocular device onto the cornea, beneath the separated layer of the corneal epithelium. The ocular device holder secures the ocular device in the inserter until the ocular device is placed on the cornea. The ocular device holder may be further configured to replace the epithelial layer over the implanted ocular device after the ocular device has been placed onto the cornea: In one version of the ocular device inserter described herein, the ocular device holder comprises a recessed region into which all or a part of the ocular device may fit.

[0020J Examples of ocular devices that may be inserted using the devices and methods described herein include any biocompatible ocular device, such as lenses (e.g. contact lenses, implantable lenses, etc. of various compositions including hydrophilic and hydrophobic polymers and their mixtures), filters (polarizers, diffraction filters, etc), inserts, and the like. The ocular device may also be included as part of the inserter-delaminator, variously as an implant to be released or as an edge of the inserter-delaminator situated to provide delamination of the epithelium from the cornea.

[0021] The integrated devices (and the inserter-delaminator component) may be used to introduce non-ocular implants that comprise or release, for instance, medical treatment or diagnostic compositions beneath the corneal epithelium. The devices may be used to provide a single application of such compositions in a liquid, gel, or other form, to the separated region beneath the corneal epithelium.

J0022] The integrated devices may comprise the following components: a.) inserter/delaminator for separating the corneal epithelium from the cornea, for carrying the lens to the sub-epithelial region so-created, for controllably releasing the lens in that site, and for withdrawing from the site without removing the lens; b.) an eye-indexing component or assembly for fixing the position of the inserter/delaminator with respect to the cornea so that it separates the corneal epithelium from the cornea and forms an acceptable sub-epithelial delivery site as a result of the generally movement of the inserter/delaminator, c.) a track component for providing translational movement to the inserter/delaminator, d.) an optional applanator for providing a consistent epithelial surface ahead of the inserter/delaminator as it passes along the cornea, e.) an oscillator for vibrating the inserter/delaminator in a way that provides acceptable epithelial delamination, and f.) various ancillary equipment and fluid or vacuum sources as appropriate for operating the integrated device, e.g., vacuum sources to maintain the lens on the inserter/delaminator during delivery and fluid sources to release the lens from the inserter/delaminator after its proper siting in the separated sub-epithelial region.

(0023] At least one edge of the component inserter/delaminator may be adapted to delaminate the epithelial layer from the cornea. This edge may be substantially blunt or dull. In one version, the edge is rounded. In general, the inserter lifts the epithelial layer without cutting. Functionally speaking, the delaminating edge is sufficiently dull that it does not cut the cornea in use. The edge is sufficiently sharp to separate the epithelium from the limn of the Bowman's layer without leaving substantial (or, preferably, any) epithelial tissue on the corneal bed or surface. In one version, at least part of the delaminating edge is formed by at least part of an ocular device to be inserted. In one version, at least part of the edge is stainless steel. In one version, the inserter is spatula shaped, so that the edge configured to delaminate the cornea is located at the end region of the spatula shape. The inserter/delaminator may be comprised of one or more sub-components that may be assembled to form a thin device having fluid flow channels or regions for communicating vacuum from a remote source (e.g., for holding the lens) or passing fluids to the distal area of the inserter/delaminator for releasing the lens or promoting epithelial delamination. [0024] The inserter/delaminator may be configured to create a loose epithelial flap, so that the portion of the corneal epithelial layer mechanically separated by the inserter remains attached to the cornea for 10% to 50% of the edge of the separated epithelial layer. The inserter may be configured to create an epithelial flap, so that the portion of the corneal epithelial layer mechanically separated by the inserter remains attached to the cornea for 50% to 75% of the edge of the separated epithelial layer. The inserter/delaminator may be configured to create an epithelial pocket, so that the portion of the corneal epithelial layer mechanically separated by the inserter/delaminator remains attached to the cornea for 50% to 95% of the edge of the separated epithelial layer,

[0025 j The inserter/delaminator is configured so that the edge oscillates. Oscillation may help in separating the epithelial layer from the cornea. For example, the inserter may oscillate the separating (or leading) edge side to side, backwards and forwards, in a circular (or partially circular) motion, or some combination thereof. Oscillation may be in the plane of the inserter edge, or out of the plane of the inserter edge. [0026] In some versions of the device, one or more selected regions of the inserter/delaminator comprise at least one low-friction surface. In particular, placing a low- friction surface on any portion of the inserter/delaminator that contacts either the delaminated epithelial layer or the lens often provides some advantage in quality of the delaminated region and in the predictability of the lens displacement from the inserter/delaminator onto the cornea. A low-friction surface is also considered to reduce the potential for damage (e.g. tearing) to the deiaminated epithelium as the inserter is used. For example, the pertinent surface or surfaces may be coated with friction-reducing substances such as lubricious polymers (e.g., a suitable polyfluoroethylene (e.g., PTFE) or polyxyxylene (e.g., Paralene) or polyurethanes or polysilicone), biocompatible lubricants such as silicones or hyaluronic acids, and slick inorganic coatings such as diamond. Other low-friction surfaces include polished surfaces.

10027] The ocular device is releasably held in the inserter/delaminator. In one version, the ocular device is releasably held in the device holder by a releasable adhesive, such as a water-soluble material (e.g. a biocompatible soluble polymer such as polyvinylalcohol). In one version, the ocular device holder surface of the inserter is configured to apply positive or negative force to an ocular (or other medical-) device. For example, the inserter/delaminator may include one or more channel fluidly connected to the holder so that positive or negative force (such pressure from gas or liquid) may be applied through the channel(s) to secure or release an ocular device from the ocular device holder surface of the inserter. The inserter/delaminator may have a plurality of openings from the channels to enhance secure placement of, e.g., a lens, to the surface during translation of the inserter/delaminator during epithelium separation, or to enhance release of the lens at the desired time and corneal site.

10028] The inserter/delaminator may be indexed to the eye with an indexing component in such a way that when the inserter/delaminator is axially moved across the eye, the edge of the inserter/delaminator separates the epithelium from the cornea as otherwise described here. One such indexing device is a vacuum device, e.g., a ring or column or other device perhaps having a "view" window for the cornea and cooperatively adapted to place the inserter/delaminator edge in a specific physical relationship to the eye. Such a vacuum device may comprise a ring with an opening that allows the user to view the cornea during operation. It may comprise a column with a similar opening. The vacuum device may be sealed with a window, as mentioned just above, situated opposite the eye or in the distance from the eye to the remote and or section of the device.

|0029] The indexing device may comprise non-vacuum fixation devices involving friction or barbs to maintain relative positioning between the eye and inserter/delaminator. [0030 J The integrated device may also comprise tracking components, perhaps in conjunction with or affixed to the indexing components (e.g., a vacuum ring), configured to ' allow axial movement of the inserter/delaminator with respect to the eye during the step of separating the epithelium from the cornea and also configured to index that movement to the desired delamination site. In particular, the tracking components may be configured to provide a specific linear motion to the inserter/delaminator as it transverses the eye, whether the inserter/delaminator oscillates or not.

(0031] Driving components, such as an oscillator for oscillating the blade during separation and a motor to move the inserter/delaminator axially during separation may also be included in the integrated device.

[0032] An applanator having a form such as a roller, a flat plate, or having a curved surface may be included in a position tending to provide a smoothed epithelium surface leading the moving edge of the inserter/delaminator.

[0033] Finally, sources for or specific components for supplying vacuum to hold the lens to the inserter/delaminator and for supplying liquids to release the lens from the inserter/delaminator may also form a portion of the described integrated device.

10034] Also described herein are kits for inserting an ocular device beneath a corneal epithelium. The kits contain a combined delaminating and inserting device for delaminating the corneal epithelium having an edge configured to delaminate an epithelial layer of an eye while maintaining the epithelial layer in at least partial attachment, and a holder configured to hold an ocular device. The kit also contains an ocular device held within the holder.

[0035] Also described here are methods for delaminating an epithelial layer from an eye using the described combined delaminating and inserting devices. The method includes: lifting from the anterior corneal surface of an eye, a substantially continuous epithelial layer using a combined delaminating and inserting device. The combined epithelial delaminating and inserting device (also referred to as an ocular device inserter) has an edge and a holder, wherein the holder is configured to hold an ocular device.

|0036] Also described herein are methods of inserting an ocular device beneath a corneal epithelium using an ocular device inserter. The method includes: lifting from the anterior corneal surface of an eye a substantially continuous epithelial layer by inserting below the epithelium an ocular device inserter and inserting onto the anterior corneal surface an ocular device from the holder of the ocular device inserter. The ocular device inserter has an edge and a holder configured to hold an ocular device. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 shows a stylized procedure for placing a lens beneath the corneal epithelium using the devices described herein. |0038] Figures 2A-2G show, respectively, for one variation, a lens and inserter/del aminator side view cross-section, a top view of the inserter/delaminator, a top lens view, a top view of the sealing plate component, a bottom view of the inserter/delaminator, a top view of an alternative sealing plate, and an end view of the alternative sealing plate component. 10039] Figures 3A-3D show, respectively, for another variation, a lens and inserter/delaminator side view cross-section, a bottom view of an inserter/delaminator, a top lens view, and a bottom view of an inserter/delaminator. [0040] ^' Figures 4A-4C show, respectively, for another variation, a top view of an inserter/delaminator, a side view of an inserter/delaminator, and a bottom view of an inserter/delaminator. [0041 ] Figures 5 A-5C show, respectively, for another variation, a top view of an inserter/delaminator, a bottom view of an inserter/delaminator, and a side view of an i nserter/delam i nator. [0042] Figures 6A-6B show, respectively, for another variation, a top view of an inserter/delaminator and an end view of an inserter/delaminator. [0043] Figures 7A and 7B show, respectively, schematic depictions of the "before" and "after" cross sections of an effective inserter/delaminator leading edge. [0044] Figure 8 is a close-up cross-section of the leading edge of the Fig. 2A inserter/delaminator. [0045] Figures 9-13 show various views of the vacuum ring assembly and its components. [0046] Figure 14 is an exploded view of the components comprising an integrated device. [0047] Figure 15 is an end view of the integrated device situated on an eye during introduction of a lens. DETAILED DESCRIPTION

[0048] Described here are devices that may be used to raise a portion of the epithelial layer found on the surface of the eye's cornea by cleaving the margin between that epithelium and the cornea and to place an ocular device between that raised epithelial layer and the cornea. One typical use would involve the placement of a corrective lens beneath the raised epithelium in the same trip the device makes in raising the epithelium. This component is termed in this description as an "inserter/delaminator." The described devices may be used in other ways, of course. The various devices, components, and subcomponents described here generally center around the convenient and accurate use of a specific component in an otherwise integrated contact lens placement apparatus. The inserter/delaminator typically has a multiple utility in that it functions variously to separate the epithelium from the eye and to carry a corrective lens while doing so and then to release that lens at the chosen site and finally to retreat from the eye without substantially disturbing the lens placement.

[0049] Moreover, the described integrated devices may comprise the following components: a.) an inserter/delaminator for separating the corneal epithelium from the cornea, for carrying the lens to the sub-epithelial region so-created, for controllably releasing the lens in that site, and for withdrawing from the site without removing the lens; b.) an eye- indexing component or assembly for fixing the position of the inserter/delaminator with respect to the cornea so that it separates the corneal epithelium from the cornea and forms an acceptable sub-epithelial delivery site as a result of the generally movement of the inserter/delaminator, c.) a track component for providing translational or linear movement to the inserter/delaminator across the front of the eye, d.) an optional applanator, e.g., for providing a "plane" or at least a consistent epithelial surface ahead of the inserter/delaminator as it passes along the cornea, e.) an oscillator for vibrating the inserter/delaminator in a way that provides acceptable epithelial delamination, and f.) various ancillary equipment and fluid or vacuum sources as appropriate for operating the integrated device, e.g., vacuum sources to maintain the lens on the inserter/delaminator during delivery and fluid sources to release the lens from the inserter/delaminator after its proper siting in the separated sub-epithelial region. The components may have utility independent of the integrated device as used by a person introducing a corrective contact lens beneath an epithelial layer. [0050J As will be explained at intervals elsewhere in this description, the inserter/delaminator may be used for purposes and for procedures other than for the placement of a corrective lens. The mention of a particular use or of a particular benefit in this description, whether specific to the inserter/delaminator or not, is not to be taken as a waiver of or the abandonment of other rights that the inventors may have, based upon this description.

|0051] By way of background: a continuous layer of corneal epithelium may be separated from or lifted from the anterior surface of the eye by applying various mechanical forces to this anterior surface, or to the basal cell layer, or to the junction between the basal cell layer and the Bowman membrane (the "lamina lucida")- The term "continuous" as used herein means "uninterrupted". More or less epithelium may be separated from the cornea. For example, the devices and methods disclosed herein may be used to create a loose flap of corneal epithelium, leaving less than 50% (e.g., between 10% and 50%) of the edge of the delaminated epithelium attached to the cornea. Similarly, a flap of corneal epithelium may be made from the corneal epithelium, leaving between 50% and 75 % of the edge of the delaminated epithelium attached to the cornea. A half flap or less, a pocket or tight pocket, of delaminated corneal epithelium may also be formed by leaving between 50% and 95% of the edge of the delaminated epithelium attached to the cornea.

10052] The inserter/delaminators described herein may be used to insert an ocular device onto the region of the cornea that has been delaminated of epithelium from the corneal stroma. In particular, the inserter/delaminators described herein allow an ocular device to be placed onto the delaminated cornea, beneath the epithelium that was separated from the cornea. The separated epithelium can then be placed or situated atop the inserted ocular device.

[0053] The term "ocular device" is intended to include any implantable ocular device, preferably ocular devices intended to modify, improve, or correct vision in a patient in need thereof. One such suitable ocular device is described in U.S. Pat. No. 6,544,286, entitled "Pre-fabricated Corneal Lens and Method of Corneal Overlay to Correct Vision" by Perez, issued April 8, 2003, which is herein incorporated by reference in its entirety. Examples of ocular devices include: lenses (such as contact lenses, implantable lenses, etc.), filters (e.g. diffraction gratings, polarizers, etc.), implants (e.g. implants to reshape the eye surface), and the like. 10054) Figure 1 shows a stylized version of a typical procedure for inserting a corrective lens using the inserter/delaminator component described herein. This depiction is used to allow a functional explanation of one important use of the device.

[0055] Shown in Fig. 1 is an eye (100) having a cornea (102) and an epithelial layer

(104). In step (a) of Fig. 1 may be seen an inserter/delaminator (106) with a distal end (108) with a leading edge (110) configured initially to pass through the epithelial layer (104) and then to separate the epithelial layer (104) from the Bowman's layer of the eye. The inserter/delaminator (106) shown also includes a more-proximal shaft (112) that connects it to whatever mechanical drivers, motors, oscillators, or other motion-providing translators that may be utilized.

[0056] The lens (114) to be implanted or released upon the corneal surface beneath the lifted and separated epithelial layer (104) is shown to be situated on the upper surface of the inserter/delaminator (106). As is discussed elsewhere, the lens (114) may be held in position during the step of forming a region beneath the separated epithelial layer (104) via the assistance of releasable vacuum, temporary releasable adhesives, or the like upon the lens (1 14) or with the inclusion of modest insets or chamfers or the like on the surface of the inserter/delaminator (106).

|0057] In step (a), the inserter/delaminator (106) approaches the eye (100). In step

(b), the inserter/delaminator (106) has penetrated the epithelial layer (104) and begun its traverse across the cornea (102) separating the epithelium (104) from that surface while carrying the lens (1 14) toward its desired destination.

(0058] Step (c) depicts the stage in this procedure where the inserter/delaminator

(106) and its attendant lens (114) have reached the desired site, the site on the eye where the user wishes to release the lens (114). The epithelium (104) remains atop the lens (1 14) and may be seen as being situated within an "epithelial pocket" on the eye (100). At this point, the lens (114) is freed from the grasp of the inserter/delaminator (106) via, e.g., release of the holding vacuum or adhesive and perhaps introduction of a fluid such as saline or water into the inserter/delaminator (106).

[0059] Step (d) of Fig. 1 shows completion of the procedure. The inserter/delaminator

(106) has been withdrawn from the separated region beneath the epithelium (104) leaving the lens (1 14) in position upon the cornea (102). [0060] As noted elsewhere, the procedure shown in Fig. 1 may be used to situate other solid and gel devices, e.g., implants that deliver medicines, drugs, diagnostics, etc., or may be used to deliver materials in the form of gels, oils, waxes, liquids, etc. for various reasons beneath the epithelium (104).

|0061 ] Figs. 2A-2D show a variation of the inserter/delaminator (200), its subcomponent parts, and the carried lens (202).

|0062] Fig. 2A shows, in cross-section, the inserter/delaminator (200) and the carried lens (202). The lens (202) is shown in slight separation from the face of the inserter/delaminator (200) for clarity of explanation and portrayal. The inserter/delaminator (200) shown comprises a domed section (204) and a sealing plate (206). Top and bottom views of the domed section (204) are shown respectively in Figs. 2B and 2E₅ the former drawing with the lens (202) removed and the latter with the sealing plate (206) removed. The lens (202) is shown in isolation, in top view in Fig. 2C. The sealing plate (206) is shown in isolation in top view in Fig. 2D.

J0063] Returning to the domed section (204) in Fig. 2A, this variation is adapted to carry the lens on the upper surface (208). The upper surface (208) may be formed to at least approximately replicate the under surface (210) of the lens (202). Passageways (212) of various sizes and positions are shown allowing communication of vacuum from the lower surface (214) to the upper surface (208) and to the lens (202). The vacuum may be used to hold the lens (202) in position until delivery. As is shown with more detail in Fig. 5, the upper surface (208) may include an inset (500) to allow the edge of lens (202) to pass more easily across the underside of the epithelium during insertion. Additionally, the upper surface (208) may include a lubricious covering or coating (502) on at least the surfaces contacting the lens (202) and those surfaces contacting the epithelium during introduction of the inserter/delaminator (200) and during its withdrawal. The remainder of the inserter/delaminator (200) may also be treated to be lubricious, but we have found such treatment to be of limited added benefit.

|0064] Figs. 2A, 2B, and 2E each show a leading edge (232) that has the function of initially penetrating the epithelium and then separating the epithelium from the cornea's Bowman's layer. The shape of the edge, the cross-section and the adjacent ramp, is discussed below. |0065] Again returning to Fig.2 A, the chamber (216) formed between the sealing plate (206) and the underside (214) of domed section (200) may also be used to allow passage of fluid such as saline or water (and medicaments, if desired) to push the lens (202) from the upper surface (208) as a portion of the release step.

[0066J As shown in Figs. 2F and 2G, the chamber (216) may be separated into a number of independent chambers, if so desired, and accessed by independent passages through the drive leg (220). The independent passages (222, 224) in the drive leg (220) may be placed there by machining, casting, etc. Similarly, the chamber (216) may be separated into independent chambers (226, 228) by a wall or walls (230) projecting upwardly from sealing plate (206). Figs. 2F and 2G show top and end views of such a variation. Tn this variation, a single meandering wall (230) provides two chambers (226, 228), in this example accessing separate sets of passageways (210) through the domed section. One chamber (228) accesses the outer circle of openings (210) and the central opening (210). The other chamber accesses the other four openings (212) in the domed section (204) shown in Figs. 2B and 2E. The passageways and chambers may be isolated to permit separate access by, e.g., the vacuum or the saline, to separate passageways (210) in the domed section (204). We have found that such separate access is sometimes desirable. Distributed vacuum at the edge of the lens, provided by numerous passageways at the edge of domed section (204), appears to help with lens stability during insertion of the inserter/delaminator (200). A large passageway (210) at the center of the domed section (204) for passage of water or saline appears to assist in releasing the lens when desired.

|0067] Fig. 2B shows a top view of the domed section (204) of Fig. 2A. The inset edge (500) (as seen in Fig. 8) may be seen, as well as the various open passageways (210).

{0068] Fig. 2C shows a top view of the selected lens (202). The lenses suitable for use with this device are not limited in any way. They may be soft, flexible or they may be hard lenses as that term is used in ophthalmology. The lenses may be of hydrophilic or hydrophobic polymers or of their mixtures, block or random copolymers of those materials, composites, multi-layer constructs, and the like. One variation of the device involves the use of a lens as a leading edge in the domed section. The material properties of a lens chosen to serve as a leading edge would necessarily be selected to be adequate to perform such a task, e.g., by choice of appropriate stiffness. The lenses typically applied using this device are normally in the range of 6- 12mm in diameter for humans. 10069] Fig. 2D shows the top view of a sealing plate (206).

|0070] Fig. 2E shows a bottom view of the domed section (204) with the sealing plate

(206 in Fig. 2D) removed. The rabbet (226) for supporting the edge of the sealing plate (226) may be seen. The various passageways (210) through the domed section (204) may also be seen.

[0071 ] Figs. 3A-3D show another variation of the inserter/delaminator (250), in particular, a domed section (252) and its attendant lens (254). This variation carries the lens (254) beneath the domed section (252).

[0072] Fig. 3 A shows a side-view cross section of the inserter/delaminator (250), the domed section (252), a sealing plate (256), and its attendant lens (254). The chamber (258) beneath the domed section (252) may be adapted or configured to retain the lens (254) during delivery and to controllably release the lens (254) when the desired deployment site is attained, generally as shown in Fig. 1.

|0073] One way to retain the lens (254) within the domed section (252) during delivery is depicted in the bottom view shown in Fig. 3B. Various recesses (260) may be placed in the underside (262) of the domed section (252). The recesses (260) may be connected to a passageway (264) found in the arm (268) beneath the sealing plate (256) for passage of vacuum to the recesses (260). Those same passageways and recesses may be used to apply fluids such as water or saline to release the lens (254 in Figs. 3A and 3C).

[0074] Fig. 3C shows a top view of lens (254).

[0075] Fig. 3D shows a top view of domed section (252).

[0076| Figs. 3 A and 3B show the leading edge (270) of the inserter/delaminator (250) that has the function of initially penetrating the epithelium and then separating the epithelium from the cornea, the Bowman's layer. The shape of the edge, the cross-section and the adjacent ramp, is discussed below.

[0077] Figs. 4A-4C show another variation of the inserter/delaminator (300). In general, these inserter/delaminators have an elongated shape terminating in an edge region (302). Overall, this version of the inserter/delaminator (300) is shown to be substantially flat, as shown in the side-view of the inserter/delaminator (300) in Figure 4B. This inserter/delaminator (300) includes a top, or upper, surface (304) and a lower, or bottom, surface (306). Fig. 4C shows the bottom surface (306). The inserter/delaminator (300) is shown to be substantially flat, and having a uniform thickness (310) across and along its length, although other shapes (e.g. non-uniform thicknesses, "wedge" shapes, etc) are also intended to be encompassed by this description. Figure 4C also shows an ocular device holding region, shown as a cavity (320) in the bottom surface (306) into which at least a portion of an ocular device may be placed.

[0078) Although the inserter/delaminator may be described herein as flat or planar, these terms should be understood to specifically include shapes having a curvature in one axis (e.g. side to side) and in another axis (e.g. front to back) as appropriate to ease the mechanical separation of the epithelium from the corneal surface.

[0079| The top surface (304) and the bottom surface (306) (including the shaft region

(314)) of the inserter/delaminator may also be adapted to enhance the function of the inserter decreasing the rubbing friction of the respective surfaces. In particular, the top surface (304) of the inserter/delaminator may be adapted to reduce friction between the inserter/delaminator and the delaminated corneal epithelial layer by smoothing the top surface (304) via polishing or by coating with a lubricious material as discussed elsewhere herein.

[008Oj Friction between the top of the inserter/delaminator and the delaminated epithelium may also be reduced by decreasing the overall bulk or volume of the device or decreasing the size of the surface area that contacts the delaminated epithelium. [0081] Figs. 5A and 5B show an inserter/delaminator (330) in which a ring (334) comprises the edge (332). In this version, friction is reduced because the opening (310) in the top surface (304) of the top of the inserter/delaminator (330) effectively reduces the surface area with respect to an inserter/delaminator such as is shown in Fig. 2A. The surfaces of this version may also be corrected with a lubricant material. [0082] Figures 5 A and 5B also show an attachment site (314) by which the inserter/delaminator (330) may be connected to an inserter mount. In one version the inserter is attached to an inserter mount at the end of the inserter furthest from the delaminating edge of the inserter. In this version, a driver is connected to the attachment site (314) that is configured to oscillate either the entire inserter/delaminator, i.e., oscillating in two or more axes, or predominantly the edge region (332) of the inserter/delaminator (330), i.e., oscillating only in one axis.

[0083] Figure 6A shows the top view of another version of an inserter/delaminator

(360). This version includes a recess (362) in the bottom surface (364) of the inserter/delaminator (360) configured to act as a holding region for the lens to be delivered. In general, the holder recess (362) releasably secures an ocular device on (or in) the inserter/delaminator (360). The holder recess (362) is adapted to release a secured ocular device once the inserter/delaminator (360) has sufficiently separated the epithelium from the cornea so that the ocular device fits into the delaminated region. (0084] In general, there are benefits to conforming the shape of the inserter/delaminator region holding the ocular device holder to at least a portion of the ocular device. In the version shown in Figs. 6A and 6B, the ocular device is completely enclosed in the ocular device holder of the inserter/delaminator (360). Said another way, in the Fig. 6A device, a lens would fit into the holder recess (362) formed in inserter/delaminator (360) so that the lens would project beyond the plane of the bottom side (364). |0085] In Figs. 4A and 6A, the ocular device holding regions (320 and 362, respectively) comprise cavities in the bottom of the inserter/delaminator into which the ocular device fits. The ocular device holding regions (320 and 362, respectively) are shown adjacent the delaminating edges (302) of the inserter/delaminators, and is surrounded by the edge on at least three sides.

[0086] The ocular device holding regions do not necessarily comprise recesses in the bottom of the inserter/delaminators. For instance, the ocular device holding region may project from the bottom surface of the inserter/delaminators. The ocular device holding region may comprise cooperating cavities in both the top and bottom of the inserter/delaminators (for example, in Figs. 5A, 5B, and 5C). In particular, Fig. 5C shows a lens (315) situated within the holding region but extending from the top of the ring (334). {0087] As was the case with the other inserter/delaminators discussed elsewhere herein, the ocular device holding region is adapted or configured to hold the ocular device before and during epithelial separation, and to release the ocular device after delamination is substantially complete. The ocular device may be held and/or released from the inserter/delaminator by applying force to the ocular device, or by using a releasable adhesive, or by a combination of both.

10088] In the version shown in Fig. 6A, the ocular device is held in the inserter/delaminators (360) by applying a vacuum to the lens through one or more channels (365). That vacuum secures the ocular device in the inserter/delaminators (360); a positive force may be applied through the same channel(s) (365) to release the ocular device. For example, air (or other gas) may be applied through the channel to release the ocular device. Fluid, e.g., water or saline or other suitable fluid, may be pushed through the channel to release the ocular device. Further, the channel may be used to apply useful substances (e.g. liquids such as saline, medicaments, etc.).

|0089] The ocular device may be held in the holder by a releasable adhesive. In particular, a dissolvable adhesive may be used. For example, a water-soluble material may be used to secure the ocular device until it is ready to be released after insertion. Examples of water-soluble materials having adhesive properties include, but are not limited to: polymers such as polyvinylalcohol, biopolymers such as hyaluronic acid (HA), and polysaccharides. Application of a fluid that releases the adhesive (e.g., saline or other beneficial fluid) causes the adhesive to dissolve or otherwise release, allowing implantation of the ocular device. Such a solution may be applied locally (e.g. through a channel (365)) or over a larger area of the cornea.

(0090] The various leading edge regions mentioned above (232 in Figs. 2A, 2B, and

2E; 270 in Figs. 3A and 3B; 302 in Figs. 4A and 6A; 332 in Figs. 5A and 5B) of the inserter/delaminator is the region which mechanically interacts with the cornea to cleave or to delaminate and to separate some portion of the epithelium from the surface of the cornea, the Bowman's layer. Functionally, the edge is one that performs such a function. The edge is of a shape that is sufficiently blunt to permit and to cause separation of the epithelium from the cornea but does not cut any corneal tissue during such a procedure.

[0091] Functionally, the edge may be considered as having a bluntness appropriate to separate the epithelium from the cornea and produce a delaminated epithelial layer without substantial corneal tissue attached. The edge may be sufficiently blunt to produce a separated epithelial layer has only an insignificant amount of corneal tissue attached. Best is an edge that produces a separated epithelium layer having no corneal tissue attached.

|0092] Fig. 7B shows an edge profile or cross section that has proven to result in epithelial pockets of comparatively higher quality, i.e., having little extraneous epithelial tissue on the corneal surface after passage of the inserter/delaminator. It is quite blunt to touch by hand. It is produced by electropoHshing an edge blank (400) having a profile such as is shown in Fig. 7A and producing the blunt, but rounded, edge shown in Fig 7B. Such an edge profile (232) is also shown in Fig. 8. [0093] Electropolishing the edge blank (400) to achieve the blunt leading edge (402 in

Fig. 7B) is accomplished by placing the blank (400) in an appropriate solution and apply a direct or pulsed voltage to the blank (400). The technique is well known.

|0094] The cross-sectional profile of the edge may also vary over the length of the edge. The region just adjacent the edge, i.e., the ramp (404 in Fig. 7B) may be generally wedge-shaped. The angle of such ramp may also vary over a reasonable range. For example, in FIG. 4B, the ramp is shown having an angle of about 20° from the horizontal (70° from the vertical). The ramp angle may range from about 5° to greater than 45°. That angle may be constant over the entire device or may vary. For example, the portion of the ramp closest to the bottom surface may be around 20°, while the angle decreases as the edge approaches the upper surface.

J0095] In some variations, the ramp angle may be chosen so that there is no visible transition from the edge to the upper surface. The transition between the edge region and the lower and upper surface may be blunt (e.g. smooth), or sharp (e.g. angular).

(0096J The leading edge of the inserter/delaminator may comprise any material suitable to carry out the specified function, i.e., the leading edge delaminates the epithelial layer from the cornea without cutting into the Bowman's layer as the inserter/delaminator passes over the eye. The edge region of the leading edge may comprise metals, alloys, ceramics, or polymers, composites of one or more of these classes and may further be coated or otherwise treated with other materials to enhance some property of the leading edge. For instance, other materials or coatings may be included to enhance the ability of the edge to delaminate the epithelium from the cornea without damaging either the cornea or the epithelial cells. The edge may comprise stainless steel, perhaps polished (e.g., electropolished) or coated. The edge material may also be made of the same material as the shaft region of the inserter, or it may be made from a different material. Inserter/delaminators intended for use with living tissue maybe made of a material which can be sterilized. The edge may also include a material which incorporates therapeutic properties (e.g. medicaments, growth factors, etc.) to assist the healing process, reduce pain, or to help the cornea in accepting an optical implant. For example, the edge region (or any region of the inserter) may be configured to release a medicament from a polymeric matrix while in contact with the eye. |0097) The leading edge of the inserter/delaminator may comprise at least a region of the ocular device to be implanted. For example, the edge may be part of a lens made from a relatively stiff material (e.g., PMMA), or a hydrophilic lens that is not yet fully hydrated. The lens is held by the ocular device holder and at least of region of the lens projects from the inserter and is used to delaminate the epithelial layer from the corneal surface. The lens is released from the inserter and secured into place after delaminating and positioning the lens above the corneal stroma. The inserter is then removed, leaving the lens in place (and re-hydrating the lens, if necessary).

[0098] Fig. 8 shows a close-up cross section of a leading edge and adjacent structures of the device shown in Fig. 2 A.

|0099] Figs. 9-11 show components that may be affixed to the eye and may be used as a stable site to, in effect, to index the position and movement of the inserter/delaminator and its attached lens during the lens introduction procedure outlined with regard to Fig. 1. The depicted components comprise a vacuum ring made up of a softer elastomeric skirt subcomponent ((502) shown in perspective in Fig. 10 and in partial cross-section in Fig. 12) and an indexing ring ((500) shown in perspective in Fig. 9 and in partial cross-section in Fig. 11). In this variation, the skirt is designed to fit over the outside perimeter of the indexing ring to provide an assembled ring with a soft skirt sealing the lower side of a vacuum containing volume and an upper stiffer ring configured to sit on the eye (usually outside the periphery of the cornea, near the sclera) forming the upper and lower walls of an annular- shaped vacuum-containing volume.

100100] Shown in Figs. 9 and 11 is an indexing ring (500). Uppermost in the indexing ring (500) are a set of rails or tracks (504) that contain grooves (506) that cooperate with a driven carriage (described below) that carries a blade holder and an inserter/delaminator. The driven carriage slides within the grooves and moves in a predictable motion, typically linear, with respect to the cornea held by the vacuum ring assembly (500 and 502). [001011 The indexing ring includes an upper contact surface (508) that sits upon the eye. Exterior to the indexing ring (500) are one or more positioned grooves (510) that match the interior protrusions (512) on the interior of the skirt (502) and hold it in position to the skirt (502). The indexing ring (500) also includes a lower contact surface (514) that also sits upon the eye. [00102] Fig. 13 shows the position of the resulting vacuum-containing volume (514) within the assembled vacuum ring of the indexing ring (500) and the skirt (502). Fig. 9 shows a connection (516) to a vacuum source controlled by the user.

|00103] Fig. 14 shows an exploded view of the integrated device and the constituent components and the eye (520) to be treated.

{00104] First, the lens (522) is fitted to the inserter/delaminator (524). The passageway openings (526) in the end of the inserter/delaminator (524) for vacuum and saline supply to the lens holding region may also be seen. The inserter/delaminator (524) is attached to the underside of a blade-holder (528). Openings for connection to fluid or vacuum passageways in the inserter/delaminator (524) are provided, but are not shown in this view.

[00105] The bladeholder (528) may be designed to be disposable (along with the attached inserter/delaminator (524)) and may be designed to be sold with a preselected lens. In any case, the depicted bladeholder (528) shown to include mounting slots (530 and 532) that cooperate with matching mounting sites in the carriage (534). Openings (536) for connection to vacuum and fluid sources are shown, those openings passing to the inserter/delaminator (524) for (at least) retention and release of the lens during the lens placement procedure.

[00106] In the depicted variation, the bladeholder (528) is introduced into the carriage

(or carriage head) (534). The carriage head (534) has two major functions: a.) it is linearly driven along its tracks (540) riding in the cooperating grooves (504) in the indexing ring (500) ultimately causing passage of the inserter/delaminator (524) across the cornea and b.) it forms the other portion of the indexing function of the integrated device. As the carriage head (534) is axially or linearly driven across the indexing ring, it is also oscillated along the path in the manner discussed above. The mounted position of the bladeholder (528) is shown (in shadow) in the depiction of the carriage head (534). Also shown in the drawing is a roller applanator (542). The applanator (542) precedes the leading edge of the inserter/delaminator (524) and helps to present a consistent epithelial surface to that edge. The approximate position of the applanator (542) is also shown (in shadow) in the carriage head (534).

[00107] The carriage head (534) with these included components is then introduced into the vacuum ring (500) for placement on the eye (520). As mentioned just above, the rails (540) found on the carriage head (534) are placed into the grooves (504). The beginning and end of the travel of the carriage may be controlled by the user in this variation or limited via the use of limit switches. Not shown in this depiction are the various motors and oscillators as may be needed to move the carriage as specified above. The vacuum and liquid sources used in this variation are also not shown here.

[00] 08] Finally, Fig. 15 shows a cross-sectional end view of the integrated device (600) on an eye (520) during the procedure of introducing the lens. This view is intended only to show the relative positioning of the carriage head, the cooperating indexing rails (540) and grooves (504), and the inserter/delaminator (524) with respect to the eye (520) during the procedure. The cornea of that eye (520) is above the upper vacuum surface (508) of the indexing ring (500) and between the rails (504). The inserter/delaminator (524) has a clear path across the cornea for placement of the lens.

[00109] The integrated device may be fabricated either from separate parts (e.g. the edge, the holder, etc.) and assembled. For example, the inserter/delaminator may be injection molded and/or micro-stamped into shape. The size of the inserter/delaminator is chosen by the designer and depends in large part upon the intended use of the inserter/delaminator, e.g., dependent upon the size of the device to be implanted. However, the inserter/delaminator may have an overall thickness similar to the thickness of the basal cell layer, e.g., about 1/2 mil to 3.5 mils. (0.0005 to 0.0035"), but often about 1.0 mil to 3.0 mils (0.001 to 0.003"). For example, the edge of the inserter may have a thickness around 2.0 mils.

[00110] Although the procedure here is normally used to insert an ocular device beneath a substantially intact sheet of the epithelium, i.e., the portion of the epithelium that passes to the anterior side of the dissector is continuous, the device may be used in less elegant ways. For instance, the inserter/delaminator may be used to remove selected portions of that membrane. Indeed, when this device is used in conjunction with a LASEK-type procedure, the epithelium may be removed in the form of a soft flap allowing for ease of replacement or re-positioning once any corneal laser remodeling is completed. In some instances it may be desirable to also apply heat to the anterior surface of the eye to enhance the mechanical epithelial delamination or to apply cooling fluids to the device and to the epithelium to enhance the viability of the epithelium after the conclusion of the procedure. |00Il 1 J The devices described here may be used to delaminate epithelium during the described procedure into the shape of a pocket, i.e., a structure having more than 50% of the periphery of the separated epithelium remains attached to the cornea. The pocket remains above and surrounding the inserted ocular device. The devices may also be used to produce epithelial flaps that may be at least partly folded away from the surface of the eye. After placement of the ocular device (or after completion of a procedure such as laser corrective surgery), the delaminated epithelium is replaced.

(00.112] The epithelial delaminating and devices methods described here may also be used in conjunction with corneal reshaping procedures or procedures that do not involve placement of ocular lens devices on the surface of the eye. Specifically, the disclosed procedure may be used to prepare an epithelial pocket or a flap, often with an attached hinge. For example, a corneal reshaping procedure may be performed and the corneal flap replaced. (00113] The structure and physiologic properties for our devices and methods, as well as certain of the benefits particular to the specific variations of this epithelial delaminating device, have been described. This manner of describing the device should not, however, be taken as limiting its scope in any way.

Claims

WE CLAIM:

1. An ocular device inserter for introducing an ocular device beneath a corneal epithelium comprising: an edge configured to mechanically separate a layer of the corneal epithelium from a cornea while maintaining the epithelial layer in at least partial attachment to the cornea; and an ocular device holder configured to place the ocular device beneath the layer of the corneal epithelium upon the cornea, and to hold the ocular device with the inserter until such placement.

2. The inserter of claim 1 wherein the inserter is configured to replace the epithelial layer onto the ocular device after placement of the ocular device onto the cornea.

3. The inserter of claim 1 wherein the ocular device holder further comprises a recessed region.

4. The inserter of claim 3 wherein the recessed region is configured to hold the entire ocular device.

5. The inserter of claim 1 wherein the inserter is spatula-like in shape.

6. The inserter of claim 1 wherein the inserter is further configured to produce an attached epithelial layer having an epithelial edge that is attached to the cornea for 10% to 50% of the length of the epithelial edge.

7. The inserter of claim 1 wherein the inserter is further configured to produce an attached epithelial layer having an epithelial edge that is attached to the cornea for 50% to 75% of the length of the epithelial edge.

8. The inserter of claim 1 wherein the inserter is further configured to produce an attached epithelial layer having an epithelial edge that is attached to the cornea for 50% to 95% of the length of the epithelial edge.

9. The inserter of claim 1 wherein the inserter is further configured to oscillate the edge.

10. The inserter of claim 9 wherein the inserter is configured to circularly oscillate the edge.

1 1. The inserter of claim 1 wherein the edge is rounded.

12. The inserter of claim 1 wherein the edge is substantially dull.

13. The inserter of claim 1 wherein at least a portion of the inserter comprises a low-friction surface.

14. The inserter of claim 13 wherein at least a portion of the inserter has a low-friction coating.

15. The inserter of claim 14 wherein the low-friction coating comprises a diamond coating.

16. The inserter of claim 1 wherein the ocular device holder is configured to allow positive and/or negative force to be applied to an ocular device held in the ocular device holder.

17. The inserter of claim 1 wherein the ocular device holder is fluidly connected to a channel configured to pass positive and/or negative force to the ocular device holder.

18. The inserter of claim 17 wherein the ocular device holder is further configured to release an ocular device by applying a positive force through the channel.

19. The inserter of claim 17 wherein the ocular device holder is further configured to secure an ocular device in the ocular device holder by applying a negative force though the channel.

20. The inserter of claim 17 wherein the channel allows pressure to be applied to an ocular device held in the ocular device holder.

21. The inserter of claim 20 wherein the pressure is air pressure.

22. The inserter of claim 1 wherein the edge has a rounded tip.

23. The inserter of claim 1 wherein the edge is substantially blunt.

24. The inserter of claim 1 wherein the edge is rounded.

25. The inserter of claim 1 wherein the edge is stainless steel.

26. The inserter of claim 1 further comprising an ocular device secured in the ocular device holder.

27. The inserter of claim 26 wherein the edge comprises at least a region of the ocular device

28. The inserter of claim 26 wherein the ocular device is secured in the ocular device holder by a releasable adhesive.

29. The inserter of claim 28 wherein the releasable adhesive is a water-soluble polymer.

30. The inserter of claim 29 wherein the releasable adhesive is polyvinylalcohol.

31. A combined delaminating and inserting device for delaminating at least a portion of the corneal epithelium from a cornea and placing an ocular device on the cornea comprising: an edge configured to delaminate an epithelial layer of an eye; an upper surface adjacent to the edge, wherein the upper surface comprises a low- friction surface; and, an ocular device holder configured to hold an ocular device.

32. A combined delaminating and inserting device for delaminating at least a portion of the corneal epithelium and placing an ocular device on the delaminated cornea comprising: an ocular device holder configured to releasably hold the ocular device; an edge configured to mechanically separate a layer of the corneal epithelium from a cornea while maintaining the epithelial layer in at least partial attachment to the cornea; and, an ocular device held within the holder.

33. The delaminating and inserting device of claim 32 wherein the edge is comprised of at least a region of the ocular device.

34. An ocular device inserter for introducing an ocular device beneath a corneal epithelium comprising: an edge configured to mechanically separate a layer of the corneal epithelium from a cornea while maintaining the epithelial layer in at least partial attachment to the cornea; an ocular device holder configured to place the ocular device beneath the layer of the corneal epithelium upon the cornea, and to hold the ocular device with the inserter until such placement; and said ocular device held within the ocular device holder.

35. A kit for inserting an ocular device beneath a corneal epithelium comprising: a combined delaminating and inserting device for delaminating the corneal epithelium and placing an ocular device on the delaminated cornea comprising an edge configured to delaminate an epithelial layer of an eye while maintaining the epithelial layer in at least partial attachment, and a holder configured to hold an ocular device; and an ocular device held within the holder.

36. A method for delaminating an epithelial layer from an eye using a combined delaminating and inserting device comprising: lifting from the anterior corneal surface of an eye a substantially continuous epithelial layer using a combined delaminating and inserting device comprising an edge and a holder, wherein the holder is configured to hold an ocular device.

37. A method of inserting an ocular device beneath a corneal epithelium using a combined delaminating and inserting device comprising: lifting from the anterior corneal surface of an eye a substantially continuous epithelial layer by inserting below the epithelium a combined delaminating and inserting device comprising an edge and a holder configured to hold an ocular device; and inserting onto the anterior corneal surface an ocular device from the holder of the combined delaminating and inserting device.

38. The method of claim 37 further comprising replacing the epithelial layer over the inserted ocular device.

39. The method of claim 37 further comprising removing the delaminating and inserting device.

40. The method of claim 37 wherein the step of lifting from the anterior corneal surface a substantially continuous epithelial layer further comprises maintaining at least a portion of the epithelial layer attached to the cornea.

41. The method of claim 37 wherein the step of lifting from the anterior corneal surface of a substantially continuous epithelial layer further comprises the step of inserting below the epithelium an oscillating combined delaminating and inserting device.