WO2003011194A1 - Lentilles intraoculaires permettant un reglage de puissance in vivo - Google Patents

Lentilles intraoculaires permettant un reglage de puissance in vivo Download PDF

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Publication number
WO2003011194A1
WO2003011194A1 PCT/US2002/023623 US0223623W WO03011194A1 WO 2003011194 A1 WO2003011194 A1 WO 2003011194A1 US 0223623 W US0223623 W US 0223623W WO 03011194 A1 WO03011194 A1 WO 03011194A1
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WO
WIPO (PCT)
Prior art keywords
implant
optical
stimulus
exposing
optical element
Prior art date
Application number
PCT/US2002/023623
Other languages
English (en)
Inventor
Jagdish M. Jethmalani
Robert K. Maloney
Robert H. Grubbs
Julia A. Kornfield
Christian A. Sandstedt
Daniel M. Schwartz
Original Assignee
California Institute Of Technology
University Of California, San Francisco
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by California Institute Of Technology, University Of California, San Francisco filed Critical California Institute Of Technology
Publication of WO2003011194A1 publication Critical patent/WO2003011194A1/fr

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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
    • 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

Definitions

  • the FPMC monomer may itself either be a homopolymer or copolymer) which may be linked together to form a polymer containing repeating units of the same. If the FPMC monomer is a copolymer, it may be comprised of the same type of monomers (e.g., two different siloxanes) or it may be comprised of different types of monomers (e.g., a siloxane and an acrylic).
  • the one or more monomers that form the first polymer matrix are polymerized and cross-linked in the presence of the macromer.
  • polymeric starting material that forms the first polymer matrix is cross-linked in the presence of the macromer.
  • the macromer components must be compatible with and not appreciably interfere with the formation of the first polymer matrix.
  • the formation of the second polymer matrix should also be compatible with the existing first polymer matrix. Put another way, the first polymer matrix and the second polymer matrix should not phase separate and light transmission by the optical element should be unaffected.
  • the macromer may be a single component or multiple components so long as (i) it is compatible with the formation of the first polymer matrix; (ii) it remains capable to stimulus-induced polymerization after the formation of the first polymer matrix; and (iii) it is freely diffusable within the first polymer matrix.
  • the stimulus-induced polymerization is photo-induced polymerization.
  • inventive optical elements have numerous applications in the electronics and data storage industries.
  • Another application for the present invention is as medical lenses, particularly as intraoccular lenses.
  • IOLs intraoccular lenses
  • the first type of an intraoccular lens replaces the eye's natural lens. The most common reason for such a procedure is cataracts.
  • the second type of intraoccular lens supplements the existing lens and functions as a permanent corrective lens.
  • This type of lens (sometimes referred to as a phakic intraoccular lens) is implanted in the anterior or posterior chamber to correct any refractive errors of the eye.
  • the power for either type of intraoccular lenses required for emmetropia i.e., perfect focus on the retina from light at infinity
  • the inventive intraoccular lens comprises a first polymer matrix and a macromer dispersed therein.
  • the first polymer matrix and the macromer are as described above with the additional requirement that the resulting lens be biocompatible.
  • Illustrative example of a suitable first polymer matrix include: poly- acrylates such as poly-alkyl acrylates and poly-hydroxyalkyl acrylates; poly-methacrylates such as poly-methyl methaacrylate (“PMMA”), poly-hydroxyethyl methacrylate (“PHEMA”), and poly-hydroxypropyl methacrylate (“HPMA”); poly- vinyls such as poly-styrene and poly- vinylpyrrolidone (“PNVP”); poly-siloxanes such as poly-dimethylsiloxane; poly- phosphazenes,and copolymers of thereof.
  • PMMA poly-methyl methaacrylate
  • PHEMA poly-hydroxyethyl methacrylate
  • HPMA poly-hydroxypropyl methacrylate
  • poly- vinyls such as poly-styrene and poly- vinylpyrrolidone
  • PNVP poly-siloxanes
  • poly-dimethylsiloxane poly-phospha
  • the first polymer matrix generally possesses a relatively low glass transition temperature (“T g ”) such that the resulting IOL tends to exhibit fluid-like and/or elastomeric behavior, and is typically formed by crosslinking one or more polymeric starting materials wherein each polymeric starting material includes at least one crosslinkable group.
  • T g glass transition temperature
  • suitable crosslinkable groups include but are not limited to hydride, acetoxy, alkoxy, amino, anhydride, aryloxy, carboxy, enoxy, epoxy, halide, isocyano, olefinic, and oxime.
  • each polymeric starting material includes terminal monomers (also referred to as endcaps) that are either the same or different from the one or more monomers that comprise the polymeric starting material but include at least one crosslinkable group.
  • the terminal monomers begin and end the polymeric starting material and include at least one crosslinkable group as part of its structure.
  • the mechanism for crosslinking the polymeric starting material preferably is different than the mechanism for the stimulus-induced polymerization of the components that comprise the Macromer. For example, if the Macromer is polymerized by photo-induced polymerization, then it is preferred that the polymeric starting materials have crosslinkable groups that are polymerized by any mechanism other than phot- induced polymerization.
  • An especially preferred class of polymeric starting materials for the formation of the first polymer matrix is poly-siloxanes (also known as "silicones") endcapped with a terminal monomer which includes a crosslinkable group selected from the group consisting of acetoxy, amino, alkoxy, halide, hydroxy, and mercapto. Because silicone IOLs tend to be flexible and foldable, generally smaller incisions may be used during the IOL implantation procedure.
  • An example of an especially preferred polymeric starting material is bis(diacetoxymethylsilyl)-polydimethylsiloxane (which is poly-dimethylsiloxane that is endcapped with a diacetoxymethylsilyl erminal monomer).
  • the macromer that is used in fabricating IOLs is as described above except that it has the additional requirement of biocompatibility.
  • the macromer is capable of stimulus- induced polymerization and may be a single component or multiple components so long as (i) it is compatible with the formation of the first polymer matrix; (ii) it remains capable of stimulus- induced polymerization after the formation of the first polymer matrix; and (iii) it is freely diffusable within the first polymer matrix.
  • the same type of monomers that is used to form the first polymer matrix may be used as a component of the macromer.
  • Macromer may include other components such as initiators and sensitizers that facilitate the formation of the second polymer matrix.
  • the stimulus-induced polymerization is photo- polymerization.
  • the one or more monomers that comprise the macromers each preferably includes at least one group that is capable of photopolymerization.
  • Illustrative examples of such photopolymerizable groups include but are not limited to acrylate, allyloxy, cinnamoyl, methacrylate, stibenyl, and vinyl.
  • the macromer includes a photoinitiator (any compound used to generate free radicals) ether alone or in the presence of a sensitizer.
  • photinitiators examples include acetophenones (e.g., - substituted haloacetophenones, and diethoxyacetophenone); 2,4-dichloromethyl-l,3,5-triazines; benzoin methyl ether; and o-benzoyl oximino ketone.
  • suitable sensitizers include p- (dialkylamino)aryl aldehyde; N-alkylindolyidene Check sp; and bis[p- (dialkylamino)benzylidene] ketone.
  • an especially preferred class of macromer monomers is poly-siloxanes endcapped with a termination siloxane moiety that includes a photopolymerizable group.
  • An illustrative representation of such a monomer is
  • adjustable optical implants are those optical implants such as IOLs whose properties can be manipulated or adjusted post implantation by non-invasive measures.
  • the adjustable implant's contain macromers which are capable of inducing change in the implant when the implant is exposed to an external stimulus.
  • Y is a siloxane which may be a monomer, a homopolymer or a copolymer formed from any number of siloxane units, and X and X 1 may be the same or different and are each independently a terminal siloxane moiety that includes a photopolymerizable group.
  • Y include
  • R , R , and R are independently each hydrogen, alkyl (primary, secondary, tertiary, cyclo), aryl, or heteroaryl.
  • R 1 , R 2 , R 3 , and R 4 is a C ⁇ C 10 alkyl or phenyl. Because Macromer monomers with a relatively high aryl content have been found to produce larger changes in the refractive index of the inventive lens, it is generally preferred that at least one R 1 , R 2 , R 3 , and R 4 is an aryl, particularly phenyl. In more preferred embodiments, R , R , and R are the same and are methyl, ethyl or propyl and R 4 is phenyl.
  • R 5 and R 6 are independently each hydrogen, alkyl, aryl, or heteroaryl
  • Z is a photopolymerizable group.
  • R 5 and R 6 are independently each a Ci-C 10 or phenyl and Z is a photopolymerizable group that includes a moiety selected from the group consisting of acrylate, allyloxy, connamoyl, methaacrylate, stibenyl, and vinyl.
  • R 5 and R 6 is methyl, ethyl, or propyl and Z is a photopolymerizable group that includes an acrylate or methacrylate moiety.
  • an macromer monomer if of the following formula
  • Macromer monomers include dimethylsiloxane-diphenylsiloxane copolymer endcapped with a vinyl dimethylsilane group; dimethylsiloxane- methylphenylsiloxane copolymer endcapped with a methacryloxypropyl dimethylsilane group; and dimethylsiloxane endcapped with a methacryloxypropyldimethylsilane group.
  • a ring-opening reaction of one or more cyclic siloxanes in the presence of triflic acid has been found to be a particularly efficient method of making one class of inventive macromers. Briefly, the method comprises contacting a cyclic siloxane with a compound of the formula
  • the cyclic siloxane may be a cyclic siloxane monomer, homopolymer, or copolymer. Alternatively, more than one cyclic siloxane may be used.
  • a cyclic dimethylsiloxane tetramer and a cyclic methyl-phenylsiloxane trimer are contacted with bis- methacryloxypropyltetramethyldisiloxane in the presence of triflic acid to form a dimethylsiloxane methyl-phenylsiloxane copolymer that is endcapped with a methacryloxypropyl- dimethylsilane group, an especially preferred macromer.
  • the adjustable IOLs may be fabricated with any suitable method that results in a first polymer matrix with one or more components which comprise the Macromer dispersed therein, and where the Macromer is capable of stimulus-induced polymerization to form a second polymer matrix.
  • the method for making an inventive IOL is the same as that for making an inventive optical element.
  • the method comprises
  • the type of mold that is used will depend on the optical element being made. For example, if the optical element is a prism, then a mold in the shape of a prism is used. Similarly, if the optical element is an intraoccular lens, then an intraoccular lens mold is used and so forth.
  • the first polymer matrix composition comprises one or more monomers for forming the first polymer matrix and optionally includes any number of formulation auxiliaries that either modulate the polymerization reaction or improve any property (whether or not related to the optical characteristic) of the optical element.
  • the Macromer comprises one or more components that together are capable of stimulus-induced polymerization to form the second polymer matrix. Because flexible and foldable intraoccular lenses generally permit smaller incisions, it is preferred that both the first polymer matrix composition and the Macromer iniclude one or more silicone-based or low T g acrylic monomers when the inventive method is used to make IOLs.
  • the adjustable optical element is then implanted in a non-human test subject. Implantation entails removal of the existing lens by phaecoemulsification and extraction of the lens debries. This is followed by implantation of the element using standard surgical procedures.
  • Operability testing involves attempting to manipulate the properties of the implant in vivo followed by an evaluation as to whether the desired changes have occurred.
  • this entails exposing at least a portion of the implant to an external stimulus so as to induce a change in the properties of the implant.
  • ultraviolet light is said to induce photopolymerization of macromers in at least a portion of an adjustable IOL polymerization of the macromers causes change in the shape of the IOL and/or the refractive index of the IOL. The extent of the changes is then evaluated to see if the desired optical properties have been achieved.
  • Determination of biocompatibility can be accomplished either in vivo or ex vivo or both. Physical examination of the eye can be used to determine the presence of inflammation and their biocompatibility. In some cases, however, it may be necessary to explant the lens and conduct histopatho logical studies of the eye tissue to determine biocompatibility.
  • the determination of operability requires that at least the adjustment phase be done in vivo followed by examination of the lens in vivo or ex vivo.
  • In vivo examination of the lens can be done using an autoretractometer or a Scheimpfiug imaging device to determine change in refraction and/or shape.
  • the lens may be explanted after an ajustment lens has been attempted and the changes in the lens can be determined ex vivo.
  • Sterilized, adjustable IOLs were implanted in albino rabbit eyes. After clinically following the eyes for one week, the rabbits were sacrificed. The extracted eyes were evaluated, placed in familiar and studied histopathologically. There was no evidence of corneal toxicity, anterior segment inflammation or other signs of lens toxicity.
  • a series of adjustable IOLs were prepared for implantation.
  • the IOLs comprised a silicon based polymer matrix with dimethylsiloxane macromer dispersed therein.
  • the safety and operability of the lenses was evaluated in four rabbits. The rabbits were first anesthetized and the existing lens was removed using phaecoemulsification. The IOLs were then implanted into the rabbits.
  • the rabbit eyes were exposed to ultraviolet light for 60 to 120 seconds to induce localized polymerization of macromer in the center of the lens.
  • the lenses were then examined to determine if the desired changes in optical properties had taken place. This was accomplished by explanting the lenses and then evaluating the change in lens power achieved. In this case the power of the lenses increased an average of 0.72 diopters.

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  • Health & Medical Sciences (AREA)
  • Ophthalmology & Optometry (AREA)
  • Cardiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne un procédé destiné à évaluer l'efficacité d'implants optiques réglables. Ce procédé consiste d'abord à introduire des implants chez un sujet testé, à exposer chaque implant à un stimulus externe, tel qu'une lumière, afin d'y induire des changements de propriétés, puis à réaliser une évaluation desdits implants en vue de déterminer la nature et la portée de ces changements de propriétés.
PCT/US2002/023623 2001-07-27 2002-07-26 Lentilles intraoculaires permettant un reglage de puissance in vivo WO2003011194A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US30837401P 2001-07-27 2001-07-27
US60/308,374 2001-07-27

Publications (1)

Publication Number Publication Date
WO2003011194A1 true WO2003011194A1 (fr) 2003-02-13

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/023623 WO2003011194A1 (fr) 2001-07-27 2002-07-26 Lentilles intraoculaires permettant un reglage de puissance in vivo

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WO (1) WO2003011194A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5968095A (en) * 1995-05-09 1999-10-19 Pharmacia & Upjohn Groningen Bv Method of selecting an intraocular lens to be implanted into an eye
WO2000041650A1 (fr) * 1999-01-12 2000-07-20 California Institute Of Technology Lentilles a puissance modifiable apres fabrication

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5968095A (en) * 1995-05-09 1999-10-19 Pharmacia & Upjohn Groningen Bv Method of selecting an intraocular lens to be implanted into an eye
WO2000041650A1 (fr) * 1999-01-12 2000-07-20 California Institute Of Technology Lentilles a puissance modifiable apres fabrication

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