Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
  • A61F2/02—Prostheses implantable into the body
  • A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
  • A61F2/16—Intraocular lenses
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/28—Materials for coating prostheses
  • A61L27/34—Macromolecular materials
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2430/00—Materials or treatment for tissue regeneration
  • A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea

Definitions

• the field of the invention is intraocular lenses and their construction. More particularly, the invention is directed to lenses that have modified surface properties that substantially improve their suitability as intraocular implants.
• the intraocular lens is composed of the optical lens body and a haptic device or element for positioning and securing the optical 'lens body in proper position within the eye.
• the lens body portion of IOLs in recent years has been formed of glass or polymeric materials that possess the appropriate optical qualities and that remain chemically and mechanically stable after implantation over a long period of time.
• the exact design of the haptic device depends upon the location within the eye at which the optic lens is to be placed. Three general designs are posterior chamber lenses, anterior chamber lenses, and iris plan lenses. The wide variety of IOL haptic
• SUBSTITUTESHE element designs is shown in the literature, examples of which are Hoffer U.S. 4,244,060; Sheets U.S. 4,328,595; Feaster U.S. 4,418,431; Bayers U.S. 4,316,293; and Kel an U.S. 4,174,543 and U.S. 41,340,979.
• a major difficulty with IOLs has been that the implantation process can cause serious injury to the corneal endothelium, which may result in corneal edema.
• Adhesive contact between the most commonly used intraocular lens body optical material, poly(methyl methacrylate) (PMMA) , and the corneal endothelium during surgical implantation results in losses of endothelial cells that do not regenerate. Cell loss has been directly related to the number of times the intraocular lens contacts the endothelium during surgery, with approximately 20% loss resulting from each contact.
• the investigator constructed and employed an instrument directly measuring the force of adhesion between rabbit corneal endothelium and intraocular material samples.
• the average stress calculated for PMMA was 0.66 g/cm ⁇ which was shown to be the highest of all materials studied.
• a plasma-deposited VP coating on PMMA and a conventional coating of Healon (manufactured by Pharmacia Inc.) on PMMA each lowered the stress to 0.19 g/cm .
• Two hydrogels poly (HEMA) and Duragel (Soflex) exhibited the lowest stresses, 0.09 and 0.14 g/cm 2 , respectively, of the materials tested.
• the best state-of-the-art coatings discovered prior to the present invention appear to result from surfaces that are soft, hydrophilic hydrogels.
• hydrogel surfaces such as HEMA and VP
• HEMA and VP while demonstrating lower cell damage relative to the PMMA substrate and other coatings tried, exhibit a number of disadvantages.
• the coatings are soft and easily damaged. Also, they are difficult to package and difficult to hydrate properly at surgery. Further, hydrogels are prone to calcification and bacterial contamination.
• the IOL constructions known prior to the present invention may still cause significant damage during implantation or may be otherwise unsuitable for general use.
• the improved intraocular lens of the invention includes an optical lens body formed from a material having suitable optical qualities and coated with a fluorocarbon polymer coating that is bound covalently to lens body surfaces.
• the intraocular lens also includes a haptic element portion that secures the lens body in position in the eye.
• the fluorinated coating on the lens body is a dense, impermeable, cross-linked film that reduces the degree of endothelial cell adhesion damage during the implantation procedure. It may also protect the lens body from degradation caused by environmental conditions. In addition, the fluorinated film may prevent leaching of defusible components from the lens material into the eye.
• the fluorinated coating can be deposited on the haptic element as well as the lens body. Because any area of the IOL might contact corneal endothelial cells as the IOL is implanted, coating all exposed surfaces is advantageous to cell damage reduction. Reduced iris abrasion may also result.
• a preferred intraocular lens body is a poly(methyl methacrylate) material shaped to perform
• the fluorocarbon polymer surface coating is preferably deposited onto the lens body by exposing it to a gaseous fluorocarbon monomer and an electrical field. The field ionizes the monomer gas, creating a fluorocarbon plasma. The plasma reacts with the optic material, resulting in the simultaneous polymerization of the fluorocarbon groups and their attachment onto the lens body surfaces.
• a preferred process for making the lens body includes selecting an optically suitable material such as poly (methyl methacrylate) and shapin it to perform its optical task.
• the shaped optic is placed in a chamber containing a gaseous fluorocarbon monomer, such as pe-rfluoropropane.
• a radio-frequency generator induces an oscillating electric field within the chamber, polymerizing the monomer and attaching the polymer film to the surface of the substrate.
• Figure 1 is a schematic view of an intraocular lens that is coated according to the invention and positioned within the • anterior chamber of the human eye.
• Figure 2 is a sectional view of the intraocular lens of Figure 1 in which all IOL surfaces, including the haptic element, are coated.
• Figure 3 is a schematic diagram of an instrument for contacting an intraocular lens body with corneal tissue to determine potential corneal endothelium damage.
• Figure 4 presents percent corneal cell damage as a function of initial force of contact with tested intraocular lens bodies.
• An intraocular lens (IOL) 10 of the invention is shown in Figure 1 positioned in the anterior chamber 11 of the human eye after surgical implantation to replace the natural lens that had been removed from the posterior chamber 12.
• the lens 10 is shown in cross- sectional view in Figure 2.
• the IOL includes a lens body 20 that substantially performs the visual focusing functions of a removed natural lens.
• the lens body 20 may be any material that is optically satisfactory and remains chemically and mechanically stable indefinitely.
• a preferred conventional lens material, as noted ' above, is poly(methyl methacrylate) (PMMA). This material transmits more than 90% of incident light and is easily machined, molded and polished to the appropriate optical shape.
• PMMA poly(methyl methacrylate)
• the IOL of the invention also includes a haptic element or device 21 that functions to secure the optic lens body in proper position within the eye.
• a haptic element or device 21 that functions to secure the optic lens body in proper position within the eye.
• the exact design of the haptic 21 depends upon where within the eye the lens is to be located.
• an IOL may be positioned in the posterior chamber.
• the IOL may include a clip-like haptic device that positions the IOL adjacent to the iris.
• the haptic device may be bonded or otherwise fastened to the optic.
• the haptic device may be formed as an extension of the lens itself.
• the IOL of the invention includes a fluorocarbon polymer coating 22 that covers all surfaces of the optic portion of the IOL that might contact the corneal endothelium during surgical implantation.
• a lens having the fluorocarbon polymer coating of the invention causes substantially less damage to corneal endothelial cells which it may contact during implantation than a conventional lens.
• fluoropolymer coated lenses represent a substantial advantage over uncoated IOLs or those coated with materials other than a fluorocarbon polymer.
• the fluorinated plasma coating can be deposited on all optic and haptic surfaces or only on specific areas, such as optic only, depending on the design of the holder which secures the IOL in the reach on chamber.
• the preferred fluorocarbon polymer coating is a thin film c ⁇ valently bonded to the lens surfaces.
• the film is highly cross-linked and substantially impermeable but does hot adversely affect the optical qualities of - the optic portion of the IOL.
• the film is of a thickness that presents a uniform and distinct modification of surface properties of the optic material.
• the film is not so thick a layer that internal stresses can destroy the coating. For example, in coating a series PMMA lenses in a perfluoropropane plasma, film thicknesses on the order of 200-500 Angstroms were found to be satisfactory.
• the fluorinated coating is preferably applied by exposing the IOL to a gas plasma formed from a fluorocarbon monomer.
• a fluorocarbon monomer for example, a conventional PMMA IOL may be coated by exposing it to a gas plasma of perfluoropropane. Any fluorocarbon or fluorinated hydrocarbon monomer that forms a polymer film of similar composition is suitable. Gaseous fluorocarbon monomers and mixtures thereof are preferred.
• the plasma reactor may be of conventional design.
• a reactor may include a glass chamber for holding the IOLs to be treated.
• the chamber is surrounded by capacitance plates or rings ' coupled to a radio-frequency generator which establishes an oscillating electric field within the chamber.
• IT TE T surfaces to be coated are first etched by exposure to an argon plasma, then the IOLs are exposed to a plasma containing the monomer to be polymerized and deposited on the IOL surfaces.
• System parameters of RF power, gas mixture, chamber pressure and reaction time may be varied to control the rate of the reaction and depth of deposition. The parameters selected depend on the character of the monomers employed.
• the following examples further describe the fluorocarbon polymer surface coatings of the IOL optic that result in reduced corneal endothelial cell damage during implantation, the plasma gas deposition process for forming such coatings and a comparison of the IOL surface of the invention with surfaces previously known in the art.
• EO ethylene oxide
• NDP N-vinyl-2- pyrrolidone
• HEMA hydroxyethyl methacrylate
• the resulting products were characterized in terms of surface chemistry and surface energy.
• Cell damage resulting from contact of the lens coated optical material of the invention with corneal tissue was measured and compared with the untreated PMMA lens material substrate and the other treated surfaces.
• the measured surface characteristics of the material of the invention as a function of cell damage were compared with measurements of the same properties for the other surfaces.
• the "critical surface energy” was determined using the method of Zisman, as described in "Relation of the Equilibrium Contact Angle to Liquid and Solid Constitution", Advances in Chemistry Series No. 43, Fowkes, Editor, American Chemical Society, Washington, D.C. pp. 1-51 (1964).
• the analysis required measuring contact angles of various purified liquids on each type of surface at atmospheric conditions. Cosines of the measured angles were then plotted as a function of the surface tensions of the test liquids, resulting in a Zisman plot from which the critical surface energy was calculated.
• Actuil interaction of the modified surface of the invention' with corneal endothelium was determined by employing an -apparatus which produced consistent and quantitatively comparable- results between samples.
• a disk 30 of the material to be tested is secured in a holder 31 mounted on the lever arm 32 of a microforce detector 37.
• a freshly excised rabbit cornea 33 is mounted in a holder 34 on a base 35 opposed to the disk 30 to be tested.
• a micrometer 36 is provided to advance the lever arm 32 and the disk sample 30 into contact with the corneal button 33 at a measurable force.
• An electronic circuit of the microforce detector 37 measures the contact force, reporting the measurement on a chart recorder 38.
• the test disk 30 was brought into contact with the corneal tissue by means of the micrometer 36 for a period of 40-60 seconds. The initial maximum force under which contact was made was recorded.
• the corneal buttons were then removed, stained and examined under a low power microscope. The percent damaged cells were counted and recorded.
• Example 2 PMMA lens material, PERSPEX disks fabricated by CooperVision of Seattle, Washington, in the form of 10mm diameter disks was selected. Monomers of perfluoropropane and ethylene oxide both manufactured- by Matheson Chemical Company of Newark, California, N-vinyl-2-pyrrolidone manufactured by Alfa Products of Danver ' s, Massachusetts, and hydroxyethyl methacrylate manufactured by Hydron Industries were prepared.
• Spectra from the HP-5950-B were resolved using a DuPo ⁇ t 310 curve resolver, while spectra from the SSX-100 were resolved with a peak-fitting routine on an HP-9836-C computer.
• the C(ls) hydrocarbon peak was assigned to 285eV and used as a reference peak to correct for any energy shifts.
• the ESCA results of the samples measured appear in section 2 of the following table.
• Example 2 The samples produced and characterized in Example 2 were contacted with corneal tissue by means of the apparatus of Figure 3.
• Each cornea rimmed by 2-3 mm of sclera, was excised form a 2-3 kg New Zealand white rabbit and immediately placed in RPMI 1640 media with HEPES buffer, L-Glutamine, and penicillin-streptomycin (Grans- Island Biological) .
• the cornea in solution was placed in a Forma Scientific Hydrojac C0 incubator for at least 30 minutes. In preparation for a test, the cornea was removed from this solution, rinsed in a 0.9%
• NaCl solution placed on a concave Teflon block, and trephined to form a 9-mm-diameter button.
• the cornea was then placed endothelial side up, in a convex stainless steel holder of the apparatus of Figure 3.
• a circle of endothelium 7 mm in diameter was exposed with the center projected 2 mm above the level of the holder edge.
• a 0.9% NaCl solution was dropped intermittently onto the cornea to keep the cells continuously moist.
• a 10-mm-diameter sample disk was mounted in the stainless steel holder of the apparatus which clamped the edges, leaving a 9-mm-diameter exposed planar surface.
• This holder was then attached to the micro-force detector 32, Deflection Sensor Cartridge, Model DSC3, manufactured by Imperial Controls.
• the system was calibrated using 1-20 gram weights, depending on the force anticipated for each test. The test range was 4000-20,000 dynes.
• the corneal holder was placed directly beneath the lens sample, and the two surfaces were brought into contact with the micrometer attachment. After 40-60 seconds, the cornea and the sample were separated. The cornea was immediately placed in a 0.9% NaCl solution. The initial and maximum force with which contact was made was recorded. Controls for the test were corneal buttons which remained in the holder for 20- minutes and were kept moist with 0.9% NaCl solution. These corneas were subjected to all handling except for actual contact with a sample disk.
• the PMMA substrate and the treated disks were measured for cell damage over a range of contact forces. The results were then plotted showing cell damage as a function of contact force. Table III reports the best fit curves for the data for each sample. The data are also plotted in Figure 4.
• the ESCA results of both conventional ana plasma-deposited polymers are -compared with stoichiometry of the monomers.
• the untreated PMMA disk exhibits C/O ratios close to the expected ratio from stoichiometry.
• the types of bonding present in the sample also compare closely.
• Each of the HEMA and NVP plasma-deposited coatings shows a close resemblance in composition and bonding to the stoichiometry and to the model poly (HEMA) and poly(NVP) conventional films spun on glass.
• the peaks comprising the ESCA spectra of the conventional HEMA and NVP polymer surfaces are more distinct then those in the spectral envelopes ' of the plasma-deposited films. The more ill-defined spectra of the plasma-deposited films reflect the wider
• Coatings deposited by ethylene oxide and perfluoropropane plasmas are vastly altered from the monomer structures. These plasmas undergo complex reactions involving "atomic polymerization", a type of deposition in which the molecular structure- of the monomer is not retained in the polymer. As a result, a regularity in the structure of the ethylene oxide plasma coating is not likely to occur because the bonding environments noted by ESCA are so dissimilar to those in conventional poly(ethylene oxide).
• the plasma-altered surfaces exhibit definite changes in wettability compared to the PMMA substrate.
• the fluorinated plasma rendered the disk nonwettable.
• the other three plasma-deposited surfaces show an increase in wettability as the critical surface tension increases.
• the solid horizontal line at 3.5*2.7% represents the average damage associated with the control corneas.
• the lines shown for the other samples are the best curves for the force-damage data, representing either a least squares fit or an average of cell damage where damage appears independent of force. Table III reports the parameters and errors of the fits of these data.
• the fluorinated surface of the invention induced the lowest endothelial damage over the entire force range investigated. Damage appears to be independent of force.
• the HEMA and NVP surfaces were also associated with decreased cell damage, compared to the unmodified PMMA.
• both HEMA and NVP surfaces induced increasing cell damage with increasing force.
• the ethylene oxide coating caused significantly greater adhesion damage to the cornea than PMMA.
• the degree of cell adhesion damage is significantly ' changed by modifying the PMMA surface. Changes in the surface chemistry and surface energy have been documented by the ESCA and contact angle studies reported in Example 2.
• the data demonstrate a change in surface properties of poly (methyl methacrylate) material modified by RF plasma deposition.
• the degree of endothelial cell adhesion to the surface is considerably altered.
• the percent cell damage as a function of the initial force of contact for each modified surface was significantly different than that induced by PMMA.
• the results suggest that a rigid, low-energy fluorinated surface is desirable for reduced cell adhesion.
• any glass or polymeric substrate for which low cell adhesion properties are desired and upon which a fluorocarbon monomer may be plasma deposited can be improved by modifying its surfaces according to this invention.
• substrates include glass, polypropylene, poly (methyl methacrylate) and silicone polymers, for example.
• Fluorocarbon monomers or mixtures thereof which can be deposited on a substrate using the gas plasma technique are within the scope of the invention.
• Preferred monomers include perfluoropropane, perfluoropropene, hexafluoroethane, and tetrafluoroethylene.
• the presents ' invention includes other treatments that might superficially create a surface similar to the one heretofore and in the parent U.S. application. These include:
• Textiles are. contacted with a gaseous mixture of fluoroolefins in an inert diluent gas in the presence of UV light.
• a fluo ine-rich surface film will be formed that will more closely resemble that produced in reference 2, above, than to what the RF-plas method synthesizes.

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• 1987
  • 1987-04-24 JP JP50348387A patent/JPH01503443A/ja active Pending
  • 1987-04-24 AU AU74886/87A patent/AU606068B2/en not_active Ceased
  • 1987-04-24 WO PCT/US1987/000931 patent/WO1988008287A1/en not_active Application Discontinuation
  • 1987-04-24 EP EP19870903764 patent/EP0311611A4/de not_active Withdrawn

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