PDF herunterladen
Klin Monbl Augenheilkd 2016; 233(02): 172-178
DOI: 10.1055/s-0041-109512
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Die Intraokularlinse als Arzneimittelträger: Stand der Forschung und Ausblick

Intraocular Lens as a Drug Delivery Device: State of the Art and Future Perspective
K. H. Eibl-Lindner
Augenklinik, Klinikum der Universität München
,
C. Wertheimer
Augenklinik, Klinikum der Universität München
,
A. Kampik
Augenklinik, Klinikum der Universität München
› Institutsangaben
Weitere Informationen

Publikationsverlauf

eingereicht 22. September 2015

akzeptiert 10. November 2015

Publikationsdatum:
15. Februar 2016 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Zusammenfassung

Die Intraokularlinse (IOL) als Medikamententräger stellt ein therapeutisches Konzept mit großem Entwicklungspotenzial dar. Häufige Folgen der Kataraktchirurgie, wie der Nachstar oder schwerwiegende Komplikationen wie ein starker intraokularer Reizzustand oder die Endophthalmitis, könnten durch die Implantation einer pharmakologisch modifizierten Kunstlinse im Idealfall mitbehandelt bzw. in ihrer Ausprägung geschwächt werden, ohne weitere therapeutische Maßnahmen einzuleiten. Eine pharmakologische IOL-Modifikation kann an der Oberfläche erfolgen („IOL-coating“) oder als direkte Beladung des optischen Materials mit einem Arzneimittel („IOL-soaking“). Eine weitere Möglichkeit besteht in der Befestigung eines Medikamententrägers an der Haptik („IOL-haptic-modification“). Bei dieser Variante würde das Material der IOL-Optik unbeeinflusst bleiben. Zahlreiche therapeutische Ziele und Einsatzmöglichkeiten einer pharmakologisch modifizierten IOL sind denkbar. Deshalb müssen unterschiedliche pharmakologische Wirkstoffklassen zunächst in vitro und in vivo auf ihre Sicherheit und Wirksamkeit untersucht werden. Welche Wirkstoffe tatsächlich für eine IOL-Modifikation geeignet und wirksam sind, ist Gegenstand präklinischer und klinischer Studien. In diesem Artikel geben wir eine Übersicht über die bisherigen wissenschaftlichen Entwicklungen und befassen uns mit zukünftigen Einsatzmöglichkeiten einer pharmakologisch modifizierten Intraokularlinse in der Kataraktchirurgie, wie z. B. mit einer mit Erufosin beladenen IOL zur pharmakologischen Nachstarprophylaxe, einer mit Heparin beladenen IOL zur Linderung des intraokularen Reizzustands nach Kataraktoperation oder mit einer mit Cefuroxim beladenen IOL zur Endophthalmitisprophylaxe.

Abstract

Development of an intraocular lens (IOL) as a drug delivery device has been pursued for many years and is a promising concept in modern cataract surgery. Common postoperative conditions such as posterior capsule opacification (PCO), intraocular inflammation or the rare but severe complications of cataract surgery like endophthalmitis are potential therapeutic targets for a drug-eluting IOL. There are three techniques of pharmacological IOL modification: Firstly, surface modification of the IOL (“coating”); secondly, IOL optic modification (“soaking”) and lastly, loading the IOL haptics with a slow release system. The last option does not interfere with the IOL optics at all. Therefore, a broad spectrum of pharmacological agents needs to be assessed in preclinical and clinical studies to determine which agent/IOL combination is safe and efficient. For pharmacological PCO prophylaxis, erufosine-loaded IOLs are of great clinical interest. Heparin-coated IOLs might become clinically relevant for attenuation of intraocular inflammation after cataract surgery and cefuroxime-loaded IOLs for endophthalmitis prophylaxis.

Schlüsselwörter

Katarakt - intraokulare Entzündungen - Pharmakologie - Intraokularlinse - Medikamententräger - Kataraktchirurgie - Nachstar - Reizzustand - Endophthalmitis

Key words

cataract - pharmacology - intraocular lens - drug delivery - cataract surgery - posterior capsule opacification - intraocular inflammation - endophthalmitis
 

  • Literatur

  • 1 Wenzel M, Auffarth G, Scharrer A et al. Ambulante und stationäre Intraokularchirurgie 2014: Ergebnisse der Umfrage von BDOC, BVA, DGII und DOG. Ophthalmo-Chirurgie 2015; 27: 155-166
    PubMedSuche in Google Scholar
  • 2 Apple DJ, Escobar-Gomez M, Zaugg B et al. Modern cataract surgery: unfinished business and unanswered questions. Surv Ophthalmol 2011; 56 (Suppl. 06) S3-S53
    CrossrefPubMedSuche in Google Scholar
  • 3 Dick HB, Tehrani M, Brauweiler P et al. [Complications of foldable intraocular lenses requiring explantation. Results of the 2000 and 2001 survey in Germany]. Ophthalmologe 2003; 100: 465-470
    PubMedSuche in Google Scholar
  • 4 Jones JJ, Jones YJ, Jin GJ. Indications and outcome of intraocular lens exchage during a recent 5-year period. Am J Ophthalmol 2014; 157: 154-162
    CrossrefPubMedSuche in Google Scholar
  • 5 Kaufmann HE, Katz JL. Pathology of the corneal endothelium. Invest Ophthalmol Vis Sci 1977; 16: 265-268
    PubMedSuche in Google Scholar
  • 6 Peyman GA, Zweig K. Dry coating of intraocular lenses with bovine submaxillary mucin. Am J Ophthalmol 1979; 87: 561-566
    CrossrefPubMedSuche in Google Scholar
  • 7 Olson RJ, Koloder H, Morgan KS et al. Polyvinyl alcohol as a protective coating on intraocular lenses. Arch Ophthalmol 1980; 98: 1840-1842
    CrossrefPubMedSuche in Google Scholar
  • 8 Bahn CF, Grosserode R, Musch DC et al. Effect of 1 % sodium hyaluronate (Healon) on a nonregenerating (feline) corneal endothelium. Invest Ophthalmol Vis Sci 1986; 27: 1485-1494
    PubMedSuche in Google Scholar
  • 9 Tehrani M, Dick HB, Wolters B et al. Material properties of various intraocular lenses in an experimental study. Ophthalmologica 2004; 218: 57-63
    CrossrefPubMedSuche in Google Scholar
  • 10 Apple DJ, Federman JL, Krolicki TJ et al. Irreversible silicone oil adhesion to silicone intraocular lenses. A clinicopathologic analysis. Ophthalmology 1996; 103: 1555-1561
    CrossrefPubMedSuche in Google Scholar
  • 11 Dick B, Schwenn O, Stoffelns B et al. [Adhesion of liquid perfluorocarbon to various intraocular lens materials. A light microscopy study]. Ophthalmologe 1998; 95: 301-306
    CrossrefPubMedSuche in Google Scholar
  • 12 Weston K, Nicholson R, Bunce C et al. An 8-year retrospective study of cataract surgery and postoperative endophthalmitis: injectable intraocular lenses may reduce the incidence of postoperative endophthalmitis. Br J Ophthalmol 2015; 99: 1377-1380
    CrossrefPubMedSuche in Google Scholar
  • 13 Cullin F, Busch T, Lundström M. Economic considerations related to choice of intraocular lens (IOL) and posterior capsule opacification frequency – a comparison of three different IOLs. Acta Ophthalmol 2014; 92: 179-183
    CrossrefPubMedSuche in Google Scholar
  • 14 Tomlins PJ, Sivaraj RR, Rauz S et al. Long-term biocompatibility and visual outcomes of a hydrophilic acrylic intraocular lens in patients with uveitis. J Cataract Refract Surg 2014; 40: 618-625
    CrossrefPubMedSuche in Google Scholar
  • 15 Findl O, Buehl W, Bauer P et al. Interventions for preventing posterior capsule opacification. Cochrane Database Syst Rev 2007; (3) CD003738
    PubMedSuche in Google Scholar
  • 16 Vock L, Crnej A, Findl O et al. Posterior capsule opacification in silicone and hydrophobis acrylic intraocular lenses with sharp-edge optics six years after surgery. Am J Ophthalmol 2009; 147: 683-690
    CrossrefPubMedSuche in Google Scholar
  • 17 Leydolt C, Schriefl S, Stifter E et al. Posterior capsule opaicification with the iMics 1NY-60 and AycrySof SN60WF1-piece hydrophobic acrylic intraocular lenses: 3-year results of a randomized trial. Am J Ophthalmol 2013; 156: 375-381
    CrossrefPubMedSuche in Google Scholar
  • 18 Leydolt C, Kriechbaum K, Schriefl S et al. Posterior capsule opaicification and neodymium : YAG rates with 2 single-piece hydrophobic acrylic intraokular lenses: three-year results. J Cataract Refract Surg 2013; 39: 1886-1892
    CrossrefPubMedSuche in Google Scholar
  • 19 Schriefl SM, Menapace R, Stifter E et al. Posterior capsule opacification and neodymium : YAG laser capsulotomy rates with 2 microincision intraocular lenses: four-year results. J Cataract Refract Surg 2015; 41: 956-963
    CrossrefPubMedSuche in Google Scholar
  • 20 Hirnschall N, Nishi Y, Crej A et al. Capsular bag stability and posterior capsule opacification of a plate-haptic design microincision cataract surgery intraocular lens: 3-year results of a randomised trial. Br J Ophthalmol 2013; 97: 1565-1568
    CrossrefPubMedSuche in Google Scholar
  • 21 Prinz A, Vecsel-Marlovits PV, Sonderhof D et al. Comparison of posterior capsule opacification between a 1-piece and a 3-piece microincision intraocular lens. Br J Ophthalmol 2013; 97: 18-22
    CrossrefPubMedSuche in Google Scholar
  • 22 Krall EM, Arlt EM, Jell G et al. Intraindividual aqueous flare comparison after implantation of hydrophobic intraocular lenses with or without a heparin-coated surface. J Cataract Refract Surg 2014; 40: 1363-1370
    CrossrefPubMedSuche in Google Scholar
  • 23 Eibl KH, Wertheimer C, Kernt M et al. Alkylphosphocholines for intraocular lens coating. J Cataract Refract Surg 2013; 39: 438-445
    CrossrefPubMedSuche in Google Scholar
  • 24 Wertheimer C, Brandlhuber U, Kook D et al. Erufosine, a phosphoinositide-3-kinase inhibitor, to mitigate posterior capsule opacification in the human capsular bag model. J Cataract Refract Surg 2015; 41: 1484-1489
    CrossrefPubMedSuche in Google Scholar
  • 25 Eperon S, Rodriguez-Aller M, Balaskas K et al. A new drug delivery system inhibits uveitis in an animal model after cataract surgery. Int J Pharm 2013; 443: 254-261
    CrossrefPubMedSuche in Google Scholar
  • 26 Garty S, Shirikawa R, Warsen A et al. Sustained antibiotic release from an intraocular lens-hydrogel assembly for cataract surgery. Invest Ophthalmol Vis Sci 2011; 52: 6109-6116
    CrossrefPubMedSuche in Google Scholar
  • 27 Duarte AR, Simplicio AL, Vega-Gonzalez A et al. Impregnation of an intraocular lens for ophthalmic drug delivery. Curr Drug Deliv 2008; 5: 102-107
    CrossrefPubMedSuche in Google Scholar
  • 28 Kugelberg M, Shafiei K, van der Ploeg I et al. Intraocular lens as adrug delivery system for dexamethasone. Acta Ophthalmol 2010; 88: 241-244
    CrossrefPubMedSuche in Google Scholar
  • 29 Nishi O, Nishi K, Morita T et al. Effect of intraocular sustained release of indomethacin on postoperative inflammation and posterior capsule opacification. J Cataract Refract Surg 1996; 22 (Suppl. 01) S806-S810
    CrossrefPubMedSuche in Google Scholar
  • 30 Shaw J, Smith EF, Desai RU et al. Can intraocular lense deliver antibiotics intracamerally?. J Ocul Pharmacol Ther 2010; 26: 587-589
    CrossrefPubMedSuche in Google Scholar
  • 31 Kleinmann G, Apple DJ, Chew J et al. Hydrophilic acrylic intraocular lens as a drug-delivery system: Pilot study. J Cataract Refract Surg 2006; 32: 652-654
    CrossrefPubMedSuche in Google Scholar
  • 32 Anderson EM, Noble ML, Garty S et al. Sustained release of antibiotics from poly(2-hydroxyethyl methacrylate) to prevent blinding infections after cataract surgery. Biomaterials 2009; 30: 5675-5681
    CrossrefPubMedSuche in Google Scholar
  • 33 Lipnitzki I, Ben Eliahu S, Marcovitz AL et al. Intraocular concentration of moxifloxacin after intracameral injection combined with presoaked intraocular lenses. J Cataract Refract Surg 2014; 40: 639-643
    CrossrefPubMedSuche in Google Scholar
  • 34 Sharma S, Sahu SK, Dhillon V et al. Reevaluating intracameral cerfuroxime as a prophylaxis against endophthalmitis after cataract surgery in India. J Cataract Refract Surg 2015; 41: 393-399
    CrossrefPubMedSuche in Google Scholar
  • 35 Tan CS, Wong HK, Yang FP. Epidemiology of postoperative endophthalmitis in an Asian population: 11-year incidence and effect of intracameral antibiotic agents. J Cataract Refract Surg 2012; 38: 425-430
    CrossrefPubMedSuche in Google Scholar
  • 36 Nentwich MM, Ta CN, Kreutzer C et al. Incidence of postoperative endophthalmitis from 1990 to 2009 using povidone-iodine but no intracameral antibiotics at a single academic institution. J Cataract Refract Surg 2015; 41: 58-66
    CrossrefPubMedSuche in Google Scholar
  • 37 Chang DF, Braga-Mele R, Henderson BA et al. Antibiotic prophylaxis of postoperative endophthalmitis after cataract surgery: Results oft he 2014 ASCRS member survey. J Cataract Refract Surg 2015; 41: 1300-1305
    CrossrefPubMedSuche in Google Scholar
  • 38 Röck T, Bramkamp M, Bartz-Schmidt KU et al. [Using intracameral cefuroxime reduces postoperative endophthalmitis rate: 5 years experience at the University Eye Hospital Tübingen]. Klin Monatsbl Augenheilkd 2014; 231: 1023-1028
    Thieme ConnectPubMedSuche in Google Scholar
  • 39 Dawes LJ, Illingworth CD, Wormstone IM. A fully human in vitro capsular bag model to permit intraocular lens evaluation. Invest Ophthalmol Vis Sci 2012; 53: 23-29
    CrossrefPubMedSuche in Google Scholar
  • 40 Wormstone IM, Eldred JA. Experimental models for posterior capsule opacification research. Exp Eye Res 2015; pii: S0014-4835(15)00142-6
    PubMedSuche in Google Scholar
  • 41 Bagley RG, Kurtzberg L, Rouleau C et al. Erufosine, an alkylphosphocholine, with differential toxicity to human cancer cells and bone marrow cells. Cancer Chemother Pharmacol 2011; 68: 1537-1546
    CrossrefPubMedSuche in Google Scholar
  • 42 Eibl KH, Liegl R, Kernt M et al. Alkylphosphocholines as a potential pharmacologic prophylaxis for posterior capsule opacification. J Cataract Refract Surg 2009; 35: 900-905
    CrossrefPubMedSuche in Google Scholar
  • 43 Wertheimer C, Brandlhuber U, Kook D et al. Erufosine, a phosphoinositide-3-kinase inhibitor, to mitigate posterior capsule opacification in the human capsular bag model. J Cataract Refract Surg 2015; 41: 1484-1489
    CrossrefPubMedSuche in Google Scholar
  • 44 Liegl R, Wertheimer C, Kernt M et al. Attenuation of human lens epithelial cell spreading, migration and contraction via downregulation of the PI3K/Akt pathway. Graefes Arch Clin Exp Ophthalmol 2014; 252: 285-292
    CrossrefPubMedSuche in Google Scholar
  • 45 Spalton DJ, Russel SL, Evans-Gowing R et al. Effect of total lens epithelial cell destruction on intraocular lens fixation in the human capsular bag. J Cataract Refract Surg 2014; 40: 306-312
    CrossrefPubMedSuche in Google Scholar
  • 46 Wertheimer C, Liegl R, Kernt M et al. EGF receptor inhibitor erlotinib as a potential pharmacological prophylaxis for posterior capsule opacification. Graefes Arch Clin Exp Ophthalmol 2013; 251: 1529-1540
    CrossrefPubMedSuche in Google Scholar
  • 47 Wertheimer C, Siedlecki J, Kook D et al. EGFR inhibitor Gefitinib attenuates posterior capsule opacification in vitro and in the ex vivo human capsular bag model. Graefes Arch Clin Exp Ophthalmol 2015; 253: 409-417
    CrossrefPubMedSuche in Google Scholar
  • 48 Gotoh N, Perdue NR, Matsushima H, Sage EH, Yan Q, Clark JI. An in vitro model of posterior capsular opacity: SPARC and TGF-beta2 minimize epithelial-to-mesenchymal transition in lens epithelium. Invest Ophthalmol Vis Sci 2007; 48: 4679-4687
    CrossrefPubMedSuche in Google Scholar