text: With the recent advances in small-incision cataract surgery, increased emphasis has been placed on developing soft, foldable materials suitable for use in artificial intraocular lenses (“IOL”). Materials that are commonly used for such lenses include hydrogels, silicones and acrylic polymers.
  Hydrogels have a relatively low refractive index which makes them less desirable materials because of the thicker lens optic that is necessary to achieve a given refractive power. Silicones have a higher refractive index than hydrogels, but tend to unfold explosively after being placed in the eye in a folded position. Explosive unfolding can potentially damage the corneal endothelium and/or rupture the natural lens capsule. Acrylic polymers are currently the material of choice since they typically have a high refractive index and unfold more slowly or controllably than silicone materials. U.S. Pat. No. 5,290,892 and U.S. Pat. No. 5,331,073, for example, disclose high refractive index, acrylic copolymers suitable for use as an IOL material.
  An important feature in the design of modern IOL's made of high refractive index material is that lenses can be made thinner which allows for a specific design of the lens being rolled in smaller dimensions. This consequently necessitates a smaller incision size in lens cataract surgery with the advantage of reduced risks for complications like astigmatism or complications related to incision healing.
  A further requirement for IOL material is that rolling the lens does not induce tears or wrinkles so that after release of the lens from the cartridge nozzle the lens unfolds in a controlled way to its pre-rolled dimensions without its optical quality being compromised. The material must also be stiff enough such that thin high refractive index lenses do not deform when residing in the eye. After all, lenses must remain flat to retain their optical properties.
  A known method for manufacturing IOL's comprises polymerization of the acrylic monomer composition in open moulds where after the raw IOL is further mechanically processed by lathing, drilling, grinding and the like. However, it is highly advantageous to polymerise the acrylic monomer composition in a closed castmould whereby a ready-to-use IOL is directly formed. Such methods wherein in particular closed castmoulds are employed, on the other hand, might give rise to the formation of vacuoles filled with air or gas in the polymerised material. Such vacuoles are in particular formed when thermal free radical initiators such as azo initiators are used that form gases as byproducts. Upon implantation of the IOL, these vacuoles are hydrated thereby giving rise to the formation of white dots due to reflection of light, a phenomenon known in the art as “glistenings”. In fact, these vacuoles containing moisture have a refractive index that is different from that of the IOL material.
  A solution for this problem that is provided by the prior art is employing an acrylate monomer composition comprising at least one hydrophobic, high refractive index IOL-forming monomer in conjunction with a small amount of a hydrophilic monomer. By the incorporation of the latter, the hydrophilicity of the IOL is improved so that any moisture is better dispersed within the IOL.
  For example, U.S. Pat. No. 5,693,095 discloses acrylic monomer compositions comprising a hydrophilic monomer, e.g. 2-hydroxyethyl acrylate, and a high refractive index, IOL-forming, hydrophobic aryl acrylic monomer having the general formula:
  wherein X is hydrogen or methyl, m is an integer of 0-6, Y is a direct bond, O, S or NR (R may be alkyl) and Ar is an optionally substituted aromatic group. The acrylic monomer compositions further comprise a crosslinker such as 1,4-butanediol diacrylate. The polymerization of the acrylic monomer composition is preferably thermally initiated by using peroxy free radical initiators. The polymerized materials are said to be substantially free of glistenings.
  Similarly, U.S. Pat. No. 6,140,438 and U.S. Pat. No. 6,326,448 disclose an acrylic monomer composition comprising an aromatic ring containing (meth)acrylate monomer (A) of the formula:
  wherein R1 is hydrogen or methyl, n is an integer of 0-5, X is a direct bond or oxygen, and R2 is an optionally substituted aromatic group, a hydrophilic monomer (B), an alkyl(meth)acrylate monomer (C) wherein the alkyl group has 1-20 carbon atoms, and a crosslinker (D). The polymerization can be conducted by any conventional method, i.e. thermally by using azo or peroxide initiators or by irradiation with electromagnetic waves such as UV. The polymerized material has a water absorptivity of 1.5 to 4.5 wt. % and has an improved transparency. The polymerized materials are further mechanically processed into IOL's.
  U.S. Pat. No. 6,329,485 and U.S. Pat. No. 6,657,032 disclose an acrylic monomer composition comprising a high refractive index aromatic acrylate monomer, a hydrophilic monomer in an amount higher than that of the high refractive index aromatic acrylate monomer, and a crosslinker. The polymerization is preferably conducted by thermal initiation in the presence of azo or peroxide initiators, preferably the azo initiator 2,2′-azobis(isobutyronitril). After polymerization, the polymerized materials are further mechanically processed as described above to form IOL's.
  The prior art discussed above all employ acrylic monomer compositions comprising at least two IOL-forming monomers, i.e. a hydrophobic monomer and a hydrophilic monomer, and a crosslinker not only to improve the hydrophilicity of the polymerised material, but also to adjust the glass transition temperature to around ambient temperature or below (as otherwise the lenses cannot be folded without damaging the lens). However, this has the disadvantage that the refractive index is also lowered which is obviously undesired.
  U.S. Pat. No. 6,653,422 discloses acrylic monomers having a very high refractive index which have the formula:
  wherein it is preferred that A is hydrogen or methyl, B is —(CH2)m— wherein m is an integer of 2-5, Y is a direct bond or oxygen, C is —(CH2)w— wherein w is an integer of 0 or 1 and Ar is phenyl. The IOL material is made from these monomers only and a cross-linking monomer. The refractive index is at least 1.50, de glass transition temperature is preferably below 25° C. and the elongation is at least 150%. According to the examples, the copolymer made of 3-benzoyloxypropyl methacrylate (B=3, Y═O, w=1, Ar=phenyl) and polyethylene glycol 1000 dimethyacrylate has the highest refractive index (dry state) which is 1.543 (Example 11).
  US 2005/0049376 discloses curable (meth)acrylate compositions suitable for optical articles and in particular for light management films. Apart from a high refractive index, these compositions when cured have desirably a high glass transition temperature for shape retention during storage and use of the light management films. Tables 7 and 8 disclose glass transition temperatures of 41°-62° C. The refractive index of a composition made of 1,3-bis(thiophenyl)propane-2-yl acrylate and the diacrylate of tetrabromo bisphenol A diepoxide has a refractive index as high as 1.6016 (Example 14). Although generally having a high refractive index, the compositions are obviously unsuitable for IOL applications because of their high glass transition temperatures.
  U.S. Pat. No. 6,015,842 discloses a method for preparing a foldable, acrylic, high refractive index ophthalmic material from a composition comprising a hydrophilic crosslinker, e.g. polyethyleneoxide di(meth)acrylate, one or more hydrophilic monomers, a UV absorbing chromophore and a benzoyl phosphine oxide photoinitiator which can be activated by blue light having a wave length in the range of 400-500 nm.
  US 2005/0055090 discloses an intraocular lens that is made from a high refractive index monomer, a photoinitiator that can be activated by blue light having a wave length of above 500 nm. The high refractive index monomer is for example 2-ethylphenoxy (meth)acrylate and 2-ethylthiophenyl (meth)acrylate.
  It is therefore an object of the invention to provide a method for manufacturing IOL's having a high refractive index as well as a low glass transition temperature, in particular a glass transition temperature of lower than 25° C.
  It is a further object of the invention to provide a method for manufacturing IOL's that are essentially free from glistenings.
  It is another object of the invention to provide a method for manufacturing IOL's that can be conducted in closed castmoulds.
  In addition, it is an object of the invention to provide a method for the manufacturing of IOL's wherein an acrylic monomer composition is used that contains a single IOL-forming monomer.