Recent advances in polymeric vitreous substitutes

Abstract

The vitreous humor occupies two thirds of the volume of the eye and is the major component behind the lens. The human vitreous is a gelatinous substance predominantly composed of water (98–99%). Its functions include holding the retina in place and circulating metabolites throughout the eye. The vitreous liquifies with age, facilitating posterior vitreous detachment, which can lead to retinal tears, intravitreal hemorrhage or retinal detachment. Vitreous substitutes are needed to tamponade the retina or during vitrectomies for treatment of retinal detachments. Gases, perfluorocarbon liquids and silicone or fluorosilicone oils are currently used as vitreous substitutes; however, none of these substitutes can be used long term due to the short retention time of the gaseous substitutes, cell toxicity or other complications, such as glaucoma or cataracts. Vitreous substitutes, both experimental and clinical, will be reviewed, along with promising experimental artificial vitreous; polymeric hydrogels.

Keywords::

• hydrogel
• in situ
• polymer
• vitrectomy
• vitreous
• vitreous substitute

Acknowledgements

This research was supported by a Veterans Affairs Merit Review Grant to Nathan Ravi. Additional awards to the Department of Ophthalmology and Visual Sciences were from Research to Prevent Blindness, Inc. and the National Institute of Health (P30 EY 02687) Core grant.

References

• Chirila TV, Tahija S, Hong Y, Vijayasekaran S, Constable IJ. Synthetic polymers as materials for artificial vitreous body: review and recent advances. J. Biomater. Appl.9, 121–137 (1994).
   PubMedGoogle Scholar
• Gloor BP. The vitreous. In: Adler’s Physiology of the Eye. Clinical Application. Moses RA, Hart WM (Eds). The CV Mosby Co., MO, USA 246–267 (1987).
   Google Scholar
• Snell R. Head and neck. In: Clinical Anatomy for Medical Students. Little, Brown, and Co., NY, USA 723–725 (1995).
   Google Scholar
• Nickerson CS, Karageozian HL, Park J, Kornfield JA. Internal tension: a novel hypothesis concerning the mechanical properties of the vitreous humor. Macromol. Symp.227, 183–189 (2005).
   Google Scholar
• Lee B, Litt M, Buchsbaum G. Rheology of the vitreous body. Part I: viscoelasticity of human vitreous. Biorheology29, 521–533 (1992).
   PubMed Web of Science ®Google Scholar
• Bettelheim FA, Wang TJY. Dynamic viscoelastic properties of bovine vitreous. Exp. Eye Res.23, 435–441 (1976).
   PubMed Web of Science ®Google Scholar
• Zimmerman RL. In vivo measurements of the viscoelasticity of the human vitreous humor. Biophys. J.29, 539–544 (1980).
   PubMed Web of Science ®Google Scholar
• Tokita M, Fujiya Y, Hikichi K. Dynamic viscoelasticity of bovine vitreous body. Biorheology21, 751–756 (1984).
   PubMed Web of Science ®Google Scholar
• Lee B, Litt M, Buchsbaum G. Rheology of the vitreous body. Part 2. Viscoelasticity of bovine and porcine vitreous. Biorheology31, 327–338 (1994).
   PubMed Web of Science ®Google Scholar
• Balazs EA. Functional anatomy of the vitreous. In: Biomedical Foundations of Ophthalmology. Tasman W, Jaeger EA (Eds). Lippincott, PA, USA 17, 1–16 (1989).
   Google Scholar
• Balazs EA. Fine structure and function of ocular tissues. The vitreous. Int. Ophthalmol. Clin.13, 169–187 (1973).
   PubMedGoogle Scholar
• Los LI, van der Worp RJ, van Luyn MJA, Hooymans JMM. Age-related liquefaction of the human vitreous body: LM and TEM evaluation of the role of proteoglycans and collagen. Invest. Ophthalmol. Vis. Sci.44, 2828–2833 (2003).
   PubMed Web of Science ®Google Scholar
• Colthurst MJ, Williams RL, Hiscott PS, Grierson I. Biomaterials used in the posterior segment of the eye. Biomaterials21, 649–665 (2000).
   PubMed Web of Science ®Google Scholar
• Giordano GG, Refojo MF. Silicone oils as vitreous substitutes. Prog. Polym. Sci.23, 509–532 (1998).
   Web of Science ®Google Scholar
• Jonas JB, Knorr HLJ, Rank RM, Budde WM. Retinal redetachment after removal of intraocular silicone oil tamponade. Br. J. Ophthalmol.85, 1203–1207 (2001).
   PubMed Web of Science ®Google Scholar
• Leaver PK, Billington BM. Vitrectomy and fluid/silicone-oil exchange for giant retinal tears: 5 years follow-up. Graefes Arch. Clin. Exp. Ophthalmol.227, 323–327 (1989).
   PubMed Web of Science ®Google Scholar
• Wolf S, Schon V, Meier P, Wiedemann P. Silicone oil-RMN3 mixture (“heavy silicone oil”) as internal tamponade for complicated retinal detachment. Retina23, 335–342 (2003).
   PubMed Web of Science ®Google Scholar
• Sparrow JR, Ortiz R, MacLeish PR, Chang S. Fibroblast behavior at aqueous interfaces with perfluorocarbon, silicone, and fluorosilicone liquids. Invest. Ophthalmol. Vis. Sci.31, 638–646 (1990).
   PubMed Web of Science ®Google Scholar
• Versura P, Cellini M, Torreggiani A et al. The biocompatibility of silicone, fluorosilicone and perfluorocarbon liquids as vitreous tamponades. Ophthalmologica215, 276–283 (2001).
   PubMed Web of Science ®Google Scholar
• Chan IM, Tolentino FI, Refojo MF, Fournier G, Albert DM. Vitreous substitute: experimental studies and review. Retina4, 51–59 (1984).
   PubMed Web of Science ®Google Scholar
• Chirila TV, Hong Y, Dalton PD, Constable IJ, Refojo MF. The use of hydrophilic polymers as artificial vitreous. Prog. Polym. Sci.23, 475–508 (1998).
   Web of Science ®Google Scholar
• Soman N, Banerjee R. Artificial vitreous replacements. Biomed. Mater. Eng.13, 59–74 (2003).
   PubMed Web of Science ®Google Scholar
• Deutschmann R. Zur operativen behandlung der netzhautablosung. Klin. Monastbl. Augenheilkd.44, 364–370 (1906).
   Google Scholar
• Cutler NL. Vitreous transplantation. Trans. Am. Acad. Ophthalmol. Otolaryngol.52, 253–259 (1947).
   Google Scholar
• Pruett RC, Calabria GA, Schepens CL. Collagen vitreous substitute: I. Experimental study. Arch. Ophthalmol.88, 540–543 (1972).
   PubMedGoogle Scholar
• Nakagawa M, Tanaka M, Miyata T. Evaluation of collagen gel and hyaluronic acid as vitreous substitutes. Ophthalmic Res.29, 409–420 (1997).
   PubMed Web of Science ®Google Scholar
• Nayak PL. Biodegradable polymers: opportunities and challenges. JMS Rev. Macromol. Chem. Phys.C39, 481–505 (1999).
   Web of Science ®Google Scholar
• Pruett RC, Schepens CL, Freeman HM. Collagen vitreous substitute: II. Preliminary clinical trials. Arch. Ophthalmol.91, 29–32 (1974).
   PubMedGoogle Scholar
• Liang C, Peyman GA, Serracarbassa P, Calixto N, Chow AA, Rao P. An evaluation of methylated collagen as a substitute for vitreous and aqueous humor. Int. Ophthalmol.22, 13–18 (1998).
   PubMed Web of Science ®Google Scholar
• Pruett RC, Schepens CL, Swann DA. Hyaluronic acid vitreous substitute: a six-year clinical evaluation. Arch. Ophthalmol.97, 2325–2330 (1979).
   PubMed Web of Science ®Google Scholar
• Oosterhuis JA, van Haeringen NJ, Jeltes IG, Glasius E. Polygeline as a vitreous substitute: I. Observations in rabbits. Arch. Ophthalmol.76, 258–265 (1966).
   PubMedGoogle Scholar
• Suri S, Banerjee R. In vitro evaluation of in situ gels as short term vitreous substitutes. J. Biomed. Mater. Res.79A, 650–664 (2006).
   Web of Science ®Google Scholar
• Fernandez-Vigo J, Refojo MF, Verstraeten T. Evaluation of a viscoelastic solution of hydroxypropyl methylcellulose as a potential vitreous substitute. Retina10, 148–152 (1990).
   PubMed Web of Science ®Google Scholar
• Fernandez-Vigo J, Rey SAD, Concheiro A, Martinez R. Molecular weight dependence of the pharmacokinetic of hydroxypropyl methylcellulose in the vitreous. J. Ocul. Pharmacol.6(2), 137–142 (1990).
   PubMedGoogle Scholar
• DeJong C, Bali E, Libert J, Caspers-Velu L. Adcon-L hydrogel as a vitreous substitute: preliminary results. Bull. Soc. Belge Ophthalmol.278, 71–75 (2000).
   Google Scholar
• Davidorf FH, Chambers RB, Kwon OW, Doyle W, Gresak P, Frank SG. Ocular toxicity of vitreal pluronic polyol F-127. Retina10, 297–300 (1990).
   PubMed Web of Science ®Google Scholar
• Dalton PD, Chirila TV, Hong Y, Jefferson A. Oscillatory shear experiments as criteria for potential vitreous substitutes. Polym. Gels Netw.3, 429–444 (1995).
   Google Scholar
• Hong Y, Chirila TV, Vijayasekaran S, Shen W, Lou X, Dalton PD. Biodegradation in vitro and retention in the rabbit eye of crosslinked poly(1-vinyl-2-pyrrolidinone) hydrogel as a vitreous substitute. J. Biomed. Mater. Res.39, 650–659 (1998).
   PubMed Web of Science ®Google Scholar
• Hong Y, Chirila TV, Vijayasekaran S et al. Crosslinked poly(1-vinyl-2-pyrrolidininone) as a vitreous substitute. J. Biomed. Mater. Res.30, 441–448 (1996).
   PubMed Web of Science ®Google Scholar
• Vijayasekaran S, Chirila TV, Hong Y et al. Poly(1-vinyl-2-pyrrolidinone) hydrogels as vitreous substitutes: histopathological evaluation in the animal eye. J. Biomater. Sci. Polymer Edn.7(8), 695–696 (1996).
   Google Scholar
• Chirila TV, Hong Y. Poly(1-vinyl-2-pyrrolidinone) hydrogels as vitreous substitutes: a rheological study. Polym. Int.46, 183–195 (1998).
   Web of Science ®Google Scholar
• Refojo MF. Polymers in ophthalmic surgery. J. Biomed. Mater. Res.5, 113–119 (1971).
   PubMedGoogle Scholar
• Daniele S, Refojo MF, Schepens CL, Freeman HM. Glyceryl methacrylate hydrogel as a vitreous implant. An experimental study. Arch. Ophthalmol.80(1), 120–127 (1968).
   PubMedGoogle Scholar
• Hogen-Esch TE, Shah KR, Fitzgerald CR. Development of injectable poly(glyceryl methacrylate) hydrogels for vitreous prosthesis. J. Biomed. Mater. Res.10, 975–976 (1976).
   PubMed Web of Science ®Google Scholar
• Benlian W, Zhang J, Huibin W. The development of synthetic vitreous body and its experiment on rabbits. In: Polymers and Biomaterials. Feng H, Han Y, Huang L (Eds). Elsevier Science Publishers B.V., Amsterdam, The Netherlands 397–400 (1991).
   Google Scholar
• Yamauchi A. Synthetic vitreous body of PVA hydrogel. In: Polymer Gels. Fundamentals and Biomedical Applications. DeRossi D, Kajiwara K, Osada Y, Yamauchi A (Eds). Plenum Press, NY, USA 127–134 (1991).
   Google Scholar
• Maruoka S, Matsuura T, Kawasaki K et al. Biocompatibility of polyvinylalcohol gel as a vitreous substitute. Curr. Eye Res.31, 599–606 (2006).
   PubMed Web of Science ®Google Scholar
• Cavalieri F, Miano F, D’Antona P, Paradossi G. Study of gelling behavior of poly(vinyl alcohol)-methacrylate for potential utilizations in tissue replacement and drug delivery. Biomacromolecules5, 2439–2446 (2004).
   PubMed Web of Science ®Google Scholar
• Peyman GA, Conway MD, Karacorlu M et al. Evaluation of silicone gel as a long-term vitreous substitute in non-human primates. Ophthalmic Surg.23(12), 811–817 (1992).
   PubMedGoogle Scholar
• Hamilton PD, Aliyar HA, Ravi N. Biocompatibility of thiol-containing polyacrylamide polymers suitable for ophthalmic applications. Polym. Prepr.45, 495–496 (2004).
   Google Scholar
• Muller-Jensen K, Kohler H. An attempt to replace the vitreous body by polyacrylamide. Ber. Zusammenkunft. Dtsch Ophthalmol. Ges.68, 181–184 (1968).
   PubMedGoogle Scholar
• Refojo MF, Zauberman H. Optical properties of gels designed for vitreous implantation. Invest. Ophthalmol.12, 465–467 (1973).
   PubMedGoogle Scholar
• Aliyar HA, Foster WJ, Hamilton PD, Ravi N. Towards the development of an artificial human vitreous. Polym. Prepr.45, 469–470 (2004).
   Google Scholar
• Foster WJ, Aliyar HA, Hamilton P, Ravi N. Internal osmotic pressure as a mechanism of retinal attachment in a vitreous substitute. J. Bioactive Compatible Polymers21, 221–235 (2006).
   Web of Science ®Google Scholar
• Swindle KE, Hamilton PD, Ravi N. Advancements in the development of artificial vitreous humor utilizing polyacrylamide copolymers with disulfide crosslinkers. Polym. Prepr.47, 59–60 (2006).
   Google Scholar
• Swindle KE, Hamilton PD, Shui YB, Beebe DC, Ravi N. In situ formation of copolymeric hydrogels as vitreous substitutes. Presented at: Society for Biomaterials 2007 Annual Meeting Transactions. Chicago, IL, USA, April 17–21, 2007.
   Google Scholar
• Refojo MF. Polymers and devices in ophthalmology. Proceedings of the 1995 Fourteenth Southern Biomedical Engineering Conference. Shreveport, LA, USA, April 7–9, 1995.
   Google Scholar
• Peppas NA, Brannon-Peppas L. Hydrogels at critical conditions. Part 1. Thermodynamics and swelling behavior. J. Membr. Sci.48, 281–290 (1990).
   Web of Science ®Google Scholar