FR2627078A1 - OCULAR DEVICE - Google Patents

Abstract

The invention relates to an ocular device. According to the invention, it comprises lens means 110 which can be surgically associated with a cornea 114 to change the optical properties of the eye associated with the cornea and an effective amount of at least one added compound covalently linked to the eye. lens and serving to promote at least the growth of corneal epithelial cells on the lens means or the adhesion of the cornea to the lens means. The invention applies in particular to eye surgery.

Description

I 2627078

  The present invention relates to a device

  eyepiece that can be surgically associated that is

  say, for example, surgically implanted in a cor-

  born or, in another embodiment, is

  propria to placement near a damaged living cornea. More particularly, the invention relates to such ocular devices that promote at least one of the growth and adhesion of the living cornea, ie the corneal epithelium, to the ocular device after surgery. and serves to correct a vision problem or promotes healing of the damaged cornea and can be used to correct a vision problem, such as

refraction error.

  The cornea consists of five layers, comprising an outer layer of epithelial cells, a Bowman membrane immediately posterior to the cells, the stroma

  immediately posterior to Bowman's membrane, the mem-

  brane de Descémet immediately posterior to the stroma and the endothelium immediately posterior to the membrane of Descémet. A number of surgical operations

  consist in implanting a body lens structure

  in or on one or more of these components of the cornea. For example, in a form of eye surgery, the epithelial cell layer is removed and a correction lens structure is placed and

  where the cells have been removed.

  In another form of eye surgery, a portion of the epithelial cell layer is removed and a wedge-shaped ring of the Bowman's membrane and underlying Stroma is removed. An incision is then made of the posterior end of the resulting groove radially outward in an annular zone to define a

  shutter. A correction lens structure is attached

  by inserting the wing of the lens structure below the corneal flap and fixing it, for example by suturing it in place. In addition, a structure of

2 2627078

  Correction lens can be placed totally in the stroma. This surgical process consists of making a

  incision in the cornea to gain access to the stroma and

  is also to interrupt the stroma by placing a lens structure. In each of these surgical procedures, it is highly desirable, and even necessary, for the long-term viability of such incrustation or implant, that the cornea, i.e. the epithelial cells, grow

  on the lens structure and / or adhere to the structure

  lens. Obtaining such growth

  and such adhesion has been a significant problem

  bant the use of such incrustation processes and

implant in the cornea.

  A suggestion to overcome this problem has

  add drops of liquid fibronectin solution to the cornea after surgery to enhance epithelial cell growth. However, this attempt has not proved totally successful, for example, the drops must be introduced into the eye very frequently. This is annoying and can lead to discomfort. Even with the frequent addition of drops, it is very difficult to have an effective amount of

  fibronectin. The natural cleaning action, that is,

  say the crying action of the eye, tends to eliminate

fibronectin.

  Another situation that often arises is that the cornea is damaged, for example in

  incidents related to sport and other accidents.

  Since such degradation may cause relatively significant discomfort and / or adversely affect vision, it is highly desirable to heal this damage as soon as possible.

as possible.

  The present invention relates to an

  which effectively promotes growth and / or

  a living cornea to a lens structure

3 2627078

  and / or the healing of a damaged living cornea. So,

  using the present devices, we obtain a

  faster and more successful surgery of the eye or corneal degradation. Moreover, these beneficial results are obtained with little or no additional effort, treatment care, for example from the patient. For example, no droplets or other additive materials are added repeatedly in

the eyes.

  According to one embodiment, the present

  ocular means comprises a lens or structural means

  which can be surgically associated, preferably attached, to a living cornea and an effective amount of

  minus an added component associated with the lens structure.

  and to promote at least one of the growth of corneal epithelial cells on the structure of the lens and the adherence of the living cornea to the

  structure of the lens. The lens means, when

  that he is surgically associated, for example, with surgical

  stably implanted on or in the living cornea, serves to change the optical properties, such as deficiencies of

  correct vision, of the eye associated with the living cornea.

  By "promoting at least one of the growth of epithelial cells on the lens structure and

  of the adherence of the living cornea to the structure of the

  the present component added is ef-

  to encourage and / or facilitate at least one of the growth of epithelial cells on the structure of the lens, which is often synthetic in nature and

  adhesion of the corneal cells, i.e.

  newly formed epithelial cells, to the structure of the lens. This growth and adhesion is very desirable in order to obtain successful surgeries

  corneal implantation and establishment.

  The structure of the lens is preferably surgically attached, for example sutured and the like,

4 2627078

  to the living cornea, and the added component is effective

  to promote the adhesion of the living cornea to the structure

  the lens. After this adhesion, the corneal cells themselves serve to maintain the structure of the lens in place, for example after removal or dissolving.

elution of sutures.

  The added component can be associated, for example

  ply, attached or attached to, deposited on, and the like, the structure

  lens, on or near the outer surface thereof.

  However, it is preferable that the added component is

  placed in the structure of the lens, and better sensitive-

  uniformly in this structure. In one embodiment, the ocular device is adapted to be

  surgically associated with the cornea, for example chiropractic

  gically implanted in the cornea, the added component

  is preferably substantially non-degradable and non-lixi-

  viable or non-extractable from the lens structure to

  conditions of use, that is to say in the eye of the

  is holding. In a particularly useful embodiment, the added component is chemically bonded, in particular covalently bonded, to the lens structure. This covalent bond serves to maintain the added component in association with the lens structure and to minimize the amount of added component that is lost during

use.

  In another embodiment, the present invention relates to an ocular device comprising a lens means or structure that can be placed in proximity, for example substantially directly to a damaged living cornea and at least one added component.

  associated, for example, attached or attached to, deposited on,

  paired with, and the like, the lens structure. This composition

  added health is able to be released from the association with the structure of the lens over a period of time, preferably at least about 12 hours, better between 2 days and about 20 days or more to promote

-2627078

  the healing of the damaged living cornea. In this embodiment, the present ocular device can be

  regarded as a contact lens which is placed

  directly on the cornea. This attempt to provide a component added to a damaged living cornea is far superior to the repeated addition of drops of a material

  in the eye. For example, the release of the add-on component

  The structure of the lens may be more effectively controlled so that a useful amount of the added component is substantially continuously present to promote healing of the cornea. Similarly, it is not

  necessary to add repetitively and continuously

  your eyes damaged, a process that is often

and can cause discomfort.

  In this embodiment, the added component may be placed on or near the outer surface of the lens structure. In order to produce a more uniform release over time of the added component, it is

  it is preferable that the added component be placed in the structure

  the lens. Preferably, the added component is physically associated, i.e., not chemically related to the lens structure in the "contact lens" embodiment of the present invention. It is important that the added component be released from the lens structure over a period of time. As noted above, a chemical bond such as a covalent bond of the added component

  The structure of the lens is often used to eliminate

  this liberation, which liberation, in the embodiment of the "contact lens" of the present

  invention has proved to be very useful. -

  The structure of the lens in the mode of

  The use of "contact lens" may or may not be structured to change the optical properties, such as impairments of correct vision, of the eye associated with the damaged living cornea. A primary function of the structure of the

6 2627078

  lens of this embodiment is to provide a substrate

  for the useful release, over time, of the added component

  you. Another useful function of the lens structure

  is to offer protection to the damaged living cornea.

  Any appropriate added component can be used

  in the present invention provided that it functions

  describes me here and has no appreciable or unacceptable adverse effect on the eye or the patient being treated. By

  "added component" means a component or components

  which operate as described here and which have only

  that have not been incorporated into or with

  Lens tures as described here. Among the added components useful in the present invention, there are various

  growth factors and adhesion factors that favor

  the growth and adherence, respectively, of

  corneal lules as described here. In a mode of realization

  the added component is a protein. The components

  Useful added vitamins include those selected from the group consisting of enfibronectin, collagen cell attachment protein, anti-gelatin factor, cold insoluble globulin, chondronectin, laminin, epidermal growth factor (EGF), protein mussel,

  derivatives of each of these and mixtures thereof. Are parti-

  particularly useful fibronectin, fibro-

  nectin, EGF, EGF derivatives and mixtures thereof.

  The lens means or structure may be made of any suitable material or materials provided that the lens structure as well

  constructed works as described here and has no effect

  Negative or adverse sensitive fetus on the eye or patient who is being treated. The lens structure must be permeable

  to water and permeable to food so that the structure

  lens does not unduly restrict the flow of food to the corneal epithelium. Although the structure of the lens may be made of a natural material, it is preferable to use synthetic materials, and

7 2627078

  better synthetic polymeric materials. In addition, too

  many physical and chemical mixtures or combinations of

  Sounds of natural materials and synthetic materials can be used in the present lens structures. A large number of polymeric materials have been

  suggested for use in long-term structures

  daughter. Synthetic polymeric materials which are used

  in the present invention include homopolymers

  and copolymers derived from mono- and diolefins, mixtures

  such polymers, polystyrene, copolymers of styrene and ry-methylstyrene, graft copolymers of styrene, halogen-containing vinyl polymers,

  polymers derived from P-unsaturated acids and their derivatives.

  polymers derived from alcohols and unsaturated amines,

  homopolymers and copolymers derived from epoxides, poly-

  acetals, polyalkylene oxides, polyphenylene oxides, polyurethanes and polyureas, polycarbonates, polysulfones, polyamides and copolyamides, polyesters, cross-linked polymers

  which are derived from aldehydes plus phenols, ureas or

  mine, alkyd resins, unsaturated polyester resins, silicone

  cones, hydrogel-forming polymers and the like.

  The structure of the present ocular device is preferably made of polymers derived from β-unsaturated acids and their derivatives, polyurethanes, silicones and hydrogel-forming polymers. Hydrogel-forming polymers are particularly useful because of their

  outstanding characteristics permeability.

  In order to covalently link the component

  added to the lens structure, it may be necessary

  to derive either one or both of the added component and

  of the lens structure.The derivative or derivatives

  ployed depend for example on the specific material of the structure of the lens used and the added component

  specific used. In a particular embodiment

  Proudly useful, one of the material of the structure of the lens or the added component reacts with a component

8 2627078

  difunctional. One of the functional groups of the difunctional component reacts with and is covalently bonded to the lens structure material or added component and the other functional group is available to be covalently bonded to the other the

  structure of the lens or component added.

  Any suitable difunctional component can be employed provided it has the ability to covalently bond to both the specific material of the lens structure and the added component that is used. Of course, the difunctional component

  have no appreciable adverse effect on the

  or on its use. Examples of di-

  Some of the functional materials that can be employed with certain lens structure materials and added components include aldehydes, such as glutaraldehyde and the like, and

imides like carbodiimide.

  The difunctional component can be reacted with the lens structure material and the added component in separate reaction steps or in a reaction zone.

  single reaction step with all reagents present.

  In another embodiment, the covalent bonding of the structural material of the lens and the

  added component may be favored or induced in

  these materials and components to radiation, as

  gamma radiation, or plasma treatment.

  The invention will be better understood and other purposes, details and advantages thereof will become more apparent in the

  light of the explanatory description which will follow from

  various embodiments given by way of non-limiting examples only, with reference to the attached nonlimiting drawings in which: - Figure 1 is an enlarged axial cross-sectional view, showing an ocular device according to the present invention, attached to a cornea ; - Figure 2 is a cross-sectional view

9 2627078

  enlarged axial, showing another ocular device according to the present invention attached to a cornea; FIG. 3 is an enlarged axial cross-sectional view showing an ocular device according to the present invention inserted in the stroma of a cornea; and FIG. 4 is an enlarged axial cross-sectional view showing an ocular device according to FIG.

  present invention in contact with a cornea.

  Referring now to FIG.

  ocular positive in the form of an encrustation or "onlay" for the cornea, which can usually be seen in, is located on or attached (sutured) to the Bowman 111 membrane of a living cornea 114. In the cornea 114

  a layer 112 of epidermal cells is also incorporated

  theliales, stroma 113, Descémet membrane 115 and endothélium 117. Inlay 110, which is structured to correct one or more vision problems due to corneal defects 114 or one or more other components of the eye, is set up by extracting or surgically eroding a desired area of the epithelial cell layer 112, placing the inlay 110 on this area and fixing the inlay 110 in place by suturing to the membrane of Bowman 111. The inlay 110 is placed relative to the cornea 114 as shown

  FIG. 1, so that the incrustation 110 is co-

  axial with the optical axis of the eye.

  When this surgical process is accomplished, the epithelial cell layer 112 must grow on and

  attach to or adhere to the inlay 110.

  The inlay 110 is made of a material of a water-permeable, optically transparent polymer such as

  poly (hydroxyethyl) methacrylate, which is biocompatible

  tible and suitable for use in

  of the cornea. Fibronectin, or a derivative of fibro-

  nectin, is covalently bound to the polymeric material

  110. This fibronectin or derivative

2627078

  fibronectin is substantially uniformly distributed in the polymeric material and represents about 1%

weight of inlay 110.

  After attaching the key 110 to the mem-

  bran of Bowman 111, fibronectin or its derivative in the encrustation 110 serves to promote the growth of the epithelial cell layer 112 on. the incrustation 110 and the adhesion of the epithelial cell layer 112 to the incrustation 110. Finally, the layer 112 completely covers, by this growth, the inlay 110 and

  is firmly attached to it. The pace to which

  the this happens is noticeably faster when

  the incrustation 110 is used in relation to an incrustation

  which contains neither fibronectin nor

saddle.

  Of course, it can be understood that the fibronec

  tine or its derivative which covalently binds to the

  Corneal crustation 110 may be replaced, in whole or in part, by one or more other added components effective to promote the growth of the epithelial cell layer 112 over the inlay and / or

  adhesion or fixation of the epithelial cell layer

112 on the inlay 110.

  Referring now to FIG.

  ocular positive in the form of another encrustation for the cornea or lenticule for epikeratophakia, that

  one can usually see in 210, is located on or atta-

  (sutured) to the Bowman 211 membrane of a cornea vi-

  214. Each element of the cornea 214 of FIG. 2 which is also shown as an element of the cornea 114

  Figure 1 has an increased reference figure of 100

  to the same element shown in Figure 1. The incrusta-

  210 comprises a circular optical system 216 and a

  annular wing 218 surrounding the optical system. The incrus-

  210 is placed relative to the cornea 214 as shown in FIG. 2, the optical system 216 being coaxial with the optical axis of the eye with the annular wing 218 received in an abraded annular zone 220. 220 is obtained by extracting and / or abrading a portion of the epithelial cell layer 212 and the Bowman 211 membrane. An apparatus and process useful for accomplishing this operation is described in US Patent Application No. 102,344. filed on 29 September 1987 and assigned to

  applicant, which is incorporated here as a reference

  ence. The corneal inlay 210, and in particular the optical system 216, is structured to correct one or more problems due to defects of the cornea 214 or

  one or more other components of the eye.

  When the surgical process of fixing the inoculation 210 of the cornea in place as shown in FIG. 2 is accomplished, the epithelial cell layer 212 must grow on the inlay 210 and attach or

adhere to it.

  The incrustation or onlay 210 is made substantially

  of the same material as inlay or onlay 110.

  After attaching the inlay 210 to the cornea 214 as shown in FIG. 2, the fibronectin or its derivative in the inlay 210 serves to promote the growth of the epithelial cell layer 212 on the inlay 210 and the adhesion of the layer of epithelial cells

  212 on the inlay 210. Finally, the layer 212 overlies

  completely overlays the inlay 210 and is securely attached to the inlay 210. The rate at which this occurs is substantially faster when used.

  the inlay 210 for the cornea relative to an incrustation

  which contains neither fibronectin nor

  saddle. As with the incrustation 110, other added components effective to promote the growth of the epithelial cell layer 212 on the inlay 210 and / or

  adhesion or attachment of the epithelial cell layer

122627078

  lials 212 on inlay 210 can replace all

  or part of the fibronectin or its derivative.

  Referring now to FIG.

  The ocular positive in the form of an intrastromal lens, generally shown at 310, is located in the stroma 313 of the living cornea 314. Each element of the cornea 314 of Figure 3 which is also shown as part of the cornea 114 of Fig. 1 has a reference numeral

  increased by 200 in relation to the same element shown in

  1. The lens 310 is coaxial with the optical axis of

  the eye and is placed and fixed in the stroma 313 using

  conventional surgical processes. The lens 310 is structured to correct one or more vision problems caused by corneal defects 314 or

  one or more other components of the eye.

  The lens 310 is made substantially of the same

material as the inlay 110.

  After having surgically implanted the lens 310 into the stroma 313 as shown in FIG.

  fibronectin or its derivative in the lens 310 serves to promote

  riser the adhesion of the stroma tissue 313 to the lens 310.

  Finally, the stroma 313 is firmly attached to the len

  310. The pace at which this occurs is sensi-

  significantly faster when using the 310 lens in relation to an intrastromal lens that does not contain

  neither fibronectin nor comparable substance.

  Other components added effective to promote

  the adhesion or fixation to stroma 313 of the

  310 can be used instead, totally or

  partially, fibronectin or its derivative.

  Referring now to FIG.

  ocular positive in the form of a contact lens, gen-

Usually shown at 410, is located on the epithelial cell layer 412 of a living cornea 414. A thin film of natural lubrication or moisture, not shown,

  can exist between the contact lens 410 and the layer 412.

13 2627078

  In addition to the epithelial cell layer 412, the cornea 414 also contains the Bowman 411 membrane.

  and the stroma 413, the membrane of Descémet 415 and the endo-

Thelium 417.

  The contact lens 410 is made of a water-permeable poly (hydroxyethyl) methacrylate and optically

  transparent which is biocompatible and suitable for use

  in a contact lens construction. Of the

  fibronectin is physically mixed with and is sensi-

  uniformly distributed in the polymeric material,

  which represents about 1% by weight of the glass of

  tact 410. The contact lens 410 may or may not be structured to correct one or more problems of the

  vision due to defects in the cornea 414 or one or more

  sieurs other components of the eye. It is important that the fibronectin in the contact lens 410 is released from the contact lens 410 over a period of time

  to promote healing of the cornea 414.

  The epithelial cell layer 412 of the cornea 414 has been accidentally damaged and healing is required. The contact lens 410 is placed near the damaged portion of the layer 412. Over a period of time, fibronectin is released by the contact lens 410 and promotes the necessary healing of the layer 412. The application of the. fibronectin to the damaged layer 412 in this manner offers significant advantages over the use of drops of a solution containing fibronectin. With contact lens 410, fibronectin is supplied continuously to layer 412 rather than intermittently as with

  drops. Similarly, the gradual release of fibronectomy

  tine through the contact lens 410 gives a more efficient dosage.

  controlled creep of fibronectin and therefore a

  more efficient use of this growth factor.

  If desired, fibronectin may be microencapsulated

  in the contact lens 410 to better control the

14 2627078

  release, over time, of fibronectin. Of course, it will be understood that fibronectin

  in the contact lens 410 can be replaced, total-

  partially or partially, by one or more other added components effective to promote healing of the

epithelial cells 412.

2627078

R E V E ND I C A T I 0 N S

  1. An eye device characterized in that

  comprises a lens means (110) which can be

  rurgically associated with a living cornea (114) to change the optical properties of the eye associated with said cornea and an effective amount of at least one component

  added covalently bound to said means forming

  and promoting at least one of the growth of the corneal epithelial cells on the lens means and the adhesion of the cornea to the medium forming

lens.

  2. Device according to claim 1, characterized

  in that the lens means (110) is attached to the cornea (114) and the added component serves to promote

  adhesion of the cornea to the lens means.

  3. Device according to any one of the

  cations, characterized in that the component

  added is covalently bound to the

  (110) on or near the outer surface of said

medium forming a lens.

  4. Device according to any one of the

  1 or 2, characterized in that the added component is substantially uniformly placed in the forming means

lens (110).

  5. Device according to any one of the

  cations, characterized in that the lens means (110) comprises a synthetic polymeric material

which is permeable to water.

  6. Device according to claim 5, characterized in that the polymeric synthetic material is a polymer

forming a hydrogel.

  7. Device according to any one of the

  cations, characterized in that the component

  is selected from the group consisting of fibronectin,

16 2627078

  collagen cell binding tines, anti-gelatin factor, biologically active polypeptides, cold insoluble globulin, chondronectin, laminin, epidermal growth factor, mold adhesion protein, their derivatives and mixtures thereof.

  8. Device according to any one of the

  1 to 6, characterized in that the added component

  is selected from the group consisting of fibronectin, derived from

  fibronectin, epidermis growth factor,

  derived from this growth factor and their mixtures.