Biomacromolecules 2001, 2, 628-634
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Articles Injectable Intraocular Lens Materials Based upon Hydrogels Jacqueline H. de Groot,*,† Folkert J. van Beijma,† Henk J. Haitjema,† Keith A. Dillingham,† Kenn A. Hodd,‡ Steven A. Koopmans,†,§ and Sverker Norrby† Pharmacia Groningen BV, Van Swietenlaan 5, 9728 NX Groningen, The Netherlands; Polykendra Limited, Wrexham, LL12 9EW, U.K.; Department of Ophthalmology, University Hospital Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands Received October 9, 2000; Revised Manuscript Received December 1, 2000
The possibilities to develop an injectable hydrogel lens were investigated. Aqueous solutions of reactive polymers in combination with a water-soluble blue light photoinitiator were transformed into hydrogels by irradiation with blue light. Poly(ethylene glycol) diacrylates (PEGDA) with low molecular weights and an acrylate modified copolymer of N-vinylpyrrolidone and vinyl alcohol with a high molecular weight were used as reactive polymers. A copolymer of (4-vinyl-2,6-dimethylbenzoyl)diphenylphosphine oxide and dimethylacrylamide was used as a water-soluble blue light photoinitiator. PEGDA showed high reactivity and the hydrogels were more transparent than the natural lens. The mass loss and the additional swelling of the hydrogel were 1.0 and 4.0%, respectively. The refractive index of these hydrogels was 1.40, lower than that of natural lens. The viscosity of the solutions before cross-linking was too low for injection into the capsular bag. Hydrogels based upon the copolymer had a transmission comparable to a 25-year-old natural lens. The materials showed no mass loss and the additional swelling after curing was less than 1%. The refractive index was comparable to that of the natural lens (1.42). The viscosity of the polymer solutions was sufficient for injection into the capsular bag without leakage. Introduction The natural lens is a precisely formed structure of fiber cells containing about 65% water and 35% organic material, chiefly structural proteins. The proteins are responsible for the relatively high refractive index of 1.42 of the lens and are structured in such a way that there are negligible local variations in their density, resulting in a transparent lens.1 Aging or large stresses can change the morphology of the proteins, causing a progressive loss of transparency. This is termed cataract formation and is irreversible and can eventually result in blindness. Implantation of an intraocular lens (IOL) following cataract surgery is performed to replace the optical function of the natural lens. To remove the natural, cataractous lens, as well as to prepare for the introduction of the IOL, an incision is made into the eye. For many years most IOLs were made of poly(methyl methacrylate), a material with good optical characteristics and compatibility with the tissues of the eye. A disadvantage of PMMA is, however, that it is a very rigid material and the incision must be made big enough, at least 5-6 mm, for implantation of the IOL. With improved devices for less traumatic removal of the natural lens by phacoemulsification, requiring only a rather small incision * Corresponding author. E-mail:
[email protected]. Telephone: ++31 50 5296643. Fax: ++31 50 5276824. † Pharmacia Groningen BV. ‡ Polykendra Ltd. § University Hospital Groningen.
of 1.5 mm, there was a need for lenses with deformable optics. In such small incision surgery an opening of only 3-4 mm is required. Various silicone, acrylate, and hydrogel lenses have been commercialized. Although foldable lenses have been a great improvement, there is still a search for lenses than can be placed through an even smaller incision. By injection of the lens material into the capsular bag as a fluid, followed by formation of a solid, full size lens in situ in the eye, this is possible. Then the lens can then be implanted through a 1.2 mm opening. An additional advantage of this technique is that, due to the formation of a full size lens, it might overcome complications of conventional IOL implantation, namely decentration2,3 and posterior capsular opacification.4 Full size lenses show excellent centration, and there is evidence that they may prevent posterior opacification (PCO) depending on their size and their material.5,6 Dimethylsilicone-based systems either in the form of silicone oils or low-temperature vulcanizing (LTV) silicone elastomers have been used as injectable lens materials in rabbits.7-9 The LTVs systems suffer from a disadvantage in the context of refill lens formation in that they cure slowly. Up to 12 h may be needed to complete their setting, and their slow setting may result in material leakage out of the capsular bag through the surgical incision. Furthermore, the used silicones showed severe PCO. Hettlich et al. used a blue light photocurable dental resin in rabbit eyes.10 Advantages of this system were that the
10.1021/bm005622r CCC: $20.00 © 2001 American Chemical Society Published on Web 07/25/2001
Injectable Intraocular Lens Materials
material could be cured within 20 s of illumination with blue light (400-500 nm) and PCO was suppressed. A disadvantage of this material was that the refractive index was too high (1.51). Ravi et al. reported on an injectable hydrogel material made by thermally curing PEG monoacrylates and diacrylates. They were, however, not studied for possible lens refilling material but as potential probes to study the accommodation mechanism.11 The polymer content and, therefore, the refractive indices of the materials were very low (
