Advertisement

Der Ophthalmologe

, Volume 100, Issue 12, pp 1109–1130 | Cite as

Wundheilung der Hornhaut

Teil II: Therapie von Wundheilungsstörungen
  • P. W. RieckEmail author
  • U. Pleyer
Weiterbildung – Zertifizierte Fortbildung

Zusammenfassung

Zur Therapie kornealer Wundheilungsstörungen steht eine Vielzahl medikamentöser und chirurgischer Maßnahmen zur Verfügung. Eine Indikation zur Applikation von Tränenersatzmitteln besteht beim Sicca-Syndrom und hiermit vergesellschafteten Epithelheilungsstörungen sowie nach refraktiver Chirurgie. Neuere Konzepte der pharmakologischen Stimulierung der epithelialen Wundheilung beinhalten die topische Anwendung von autologem Serum und Kollagenlinsen, deren Anwendung durch die BSE-Problematik zurzeit nicht möglich ist. Topisch applizierte Kortikosteroide weisen Wirkungen auf, die bei der Modulation der stromalen Wundheilung genutzt werden. Die pharmakologische Beeinflussung der Endothelheilung ist bisher noch limitiert. Bei nicht ausreichender Wirkung der pharmakologischen Therapie kommen operative Verfahren zum Einsatz. Die Transplantation von Amnionmembran hat einen festen Platz bei der Behandlung konservativ therapierefraktärer epithelialer und stromaler Defekte eingenommen. Die homologe bzw. autologe Limbusstammzelltransplantation wird in verschiedenen operationstechnischen Varianten durchgeführt. Die bisherigen Ergebnisse dieser Operation sind viel versprechend, eine weitere Optimierung der Methodik ist jedoch erforderlich.

Schlüsselwörter

Wundheilung Hornhaut Pharmakologie Transplantation Amnionmembran Limbusinsuffizienz 

Abstract

A multitude of medical and surgical measures are available to treat disorders of corneal wound healing. Artificial tear replacement is indicated for sicca syndrome and the associated disorders of epithelial wound healing as well as after refractive surgery. Newer pharmacological concepts to stimulate epithelial wound healing include topical application of autologous serum and collagen lenses, which presently cannot be employed because of the BSE problems. Topically applied corticosteroids exhibit properties that are used to modulate stromal wound healing. Transplantation of amniotic membrane has assumed a firm role in the treatment of epithelial and stromal defects refractory to conservative therapy. Homologous or autologous limbal stem cell transplantation is performed by various surgical techniques. The findings up to now for this operation are promising, but the method still requires optimization.

Keywords

Wound healing Cornea Pharmacology Transplantation Amniotic membrane Limbal insufficiency 

Literatur

  1. 1.
    Anderson DF, Ellies P, Pires RT, Tseng SC (2001) Amniotic membrane transplantation for partial limbal stem cell deficiency. Br J Ophthalmol 85:567–575CrossRefPubMedGoogle Scholar
  2. 2.
    Assouline M, Lamrani M, Abenhaim A et al. (1993) Prospective randomized trial of bFGF: epithelial wound healing after penetrating keratoplasty in human. Invest Ophthalmol Vis Sci [Suppl] 34:1374Google Scholar
  3. 3.
    Assouline M, Hutchinson C, Morton K et al. (1989) In vivo binding of topically applied human bFGF on rabbit corneal epithelial wound. Growth Factors 1:251–261PubMedGoogle Scholar
  4. 4.
    Azuara-Blanco A, Pillai CT, Dua HS (1999) Amniotic membrane transplantation for ocular surface reconstruction. Br J Ophthalmol 83:399–402PubMedGoogle Scholar
  5. 5.
    Caporossi A, Manetti C (1992) Epidermal growth factor in topical treatment following epikeratoplasty. Ophthalmologica 205:121–124PubMedGoogle Scholar
  6. 6.
    Chang JH, Kook MC, Lee IH et al. (1998) Effects of synthetic inhibitor of metalloproteinase and cyclosporin A on corneal haze after excimcr laser photorefractive keratectomy in rabbits. Exp Eye Res 66:389–396CrossRefPubMedGoogle Scholar
  7. 7.
    Corbett MC, O’Bart DP, Marshall J (1995) Do topical corticosteroids have al role following excimer laser photorefractive keratectomy (see comments). J Refract Surg 11:380–387PubMedGoogle Scholar
  8. 8.
    Cotsarelis G, Cheng SZ, Dong G et al. (1989) Existence of slow-cycling limbal epithelial cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells. Cell 57:201–209PubMedGoogle Scholar
  9. 9.
    Daniele S, Frati L, Fiore C, Santoni G (1979) The effect of the epidermal growth factor (EGF) on the corneal epithelium in humans. Albrecht Von Graefes Arch Klin Exp Ophthalmol 210:159–165PubMedGoogle Scholar
  10. 10.
    de Rötth A (1940) Plastic repair of conjunctival defects with fetal membrane. Arch Ophthalmol 23:522–525Google Scholar
  11. 11.
    Debbasch C, de Saint Jean M, Pisella P et al. (1999) Quaternary ammonium cytotoxicity in a human conjunctival cell line. J Fr Ophthalmol 22:950–958Google Scholar
  12. 12.
    Doughty MJ (1992) Effect of the use of artificial tears on the size of squamous cells of the rabbit corneal epithelium evaluated by scanning electron microscopy. Optom Vis Sci 69:451–457PubMedGoogle Scholar
  13. 13.
    Duchesne B, Tahi H, Galand A (2001) Use of human fibrin glue and amniotic membrane transplant in corneal perforation. Cornea 20:230–232CrossRefPubMedGoogle Scholar
  14. 14.
    Engelmann, K, Bednarz J, Böhnke M (1999) Endotheltransplantation und Wachstumsverhalten des humanen kornealen Endothels. Ophthalmologe 96:555–562CrossRefPubMedGoogle Scholar
  15. 15.
    Francesconi CM, Abad JC, Lim JE, Talamo JH (1998) Evaluation of pentoxifylline in the prevention of haze after photorefractive keratectomy in the rabbit. J Refract Surg 14:567–570PubMedGoogle Scholar
  16. 16.
    Frati L, Daniele S, Delogu A, Covelli I (1972) Selective binding of the epidermal growth factor and its specific effects on the epithelial cells of the cornea. Exp Eye Res 14:135–141PubMedGoogle Scholar
  17. 17.
    Fredj-Reygrobellet D, Plouet J, Delayre T et al. (1987) Effects of aFGF and bFGF on wound healing in rabbit corneas. Curr Eye Res 6:1205–1209PubMedGoogle Scholar
  18. 18.
    Friedberg ML, Pleyer U, Mondino BJ (1991) Device drug delivery to the eye. Collagen shields, iontophoresis, and pumps. Ophthalmology 98:722–732Google Scholar
  19. 19.
    Gan L, Fagerholm P, Kim H (1999) Effect of leukocytes on corneal cellular proliferation and wound healing. Invest Ophthalmol Vis Sci 40:575–581PubMedGoogle Scholar
  20. 20.
    Gartry DS, Kerr Muir MG, Marshall J (1991) Photorefrative keratectomy with an argon fluoride excimer laser: a clinical study. Refract Corneal Surg 7:420–435PubMedGoogle Scholar
  21. 21.
    Geerling G, Daniel JT, Dart JK et al. (2001) Toxicity of natural tear substitutes in a fully defined culture model of human corneal epithelial cells. Invest Ophthalmol Vis Sci 42:948–956PubMedGoogle Scholar
  22. 22.
    Geerling G, Hartwig D (2002) Autologe Serum-Augentropfen zur Therapie der Augenoberfläche. Ophthalmologe 99:949–959PubMedGoogle Scholar
  23. 23.
    Gillies MC, Garrett SK, Shina SM et al. (1996) Topical interferon alpha 2b for corneal haze after excimer laser photorefractive keratectomy. The Melbourne Excimer Laser Group. J Cataract Refract Surg 22:891–900PubMedGoogle Scholar
  24. 24.
    Gospodarowicz D, Mescher AL, Brown KD, Birdwell CR (1977) The role of fibroblast growth factor and epidermal growth factor in the proliferate response of the corneal and lens epithelium. Exp Eye Res 25:631–649PubMedGoogle Scholar
  25. 25.
    Grueterich M, Espana E, Tseng SCG (2002) Connexin 43 expression and proliferation of human limbal epithelium on intact and denuded amniotic membrane. Invest Ophthalmol Vis Sci 43:63–71PubMedGoogle Scholar
  26. 26.
    Hao Y, Ma DH, Hwang DG et al. (2000) Identification of antiangiogenic and antiinflammatory proteins in human amniotic membrane. Cornea 19:348–352CrossRefGoogle Scholar
  27. 27.
    Hoppenreijs VP, Pels E, Vrensen GF, Treffers WF (1994) Basic fibroblast growth factor stimulates corneal endothelial cell growth and endothelial wound healing of human corneas. Invest Ophthalmol Vis Sci 35:931–944Google Scholar
  28. 28.
    Hugues F, Le Jeunne C (1993) Systemic and local tolerability of ophthalmic drug formulations. An update. Drug Saf 8:365–380PubMedGoogle Scholar
  29. 29.
    Kandarakis AS, Page C, Kaufman HE (1984) The effect of epidermal growth factor on epithelial healing after penetrating keratoplasty in human eyes. Am J Ophthalmol 98:411–415PubMedGoogle Scholar
  30. 30.
    Kaszli FA, Krieglstein GK (1996) Tear film deficiencies pharmacology of eye drops and toxicity. Curr Opin Ophthalmol 7:12–16PubMedGoogle Scholar
  31. 31.
    Kenyon KR, Tseng SCG (1989) Limbal autograft transplantation for ocular surface disorders. Ophthalmology 96:709—723PubMedGoogle Scholar
  32. 32.
    Kim JC, Tseng SC (1995) Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas. Cornea 14:473–484PubMedGoogle Scholar
  33. 33.
    Kitazawa Y, Maekawa E, Sasaki S, Tokoro T, Mochizuki M, Ito S (1999) Cooling effect on excimer laser photorefractive keratectomy. J Cataract Refract Surg 25:1349–1355CrossRefPubMedGoogle Scholar
  34. 34.
    Kitazwa T, Kinoshita S, Fukita K et al. (1990) The mechanism of accelerated corneal epithelial healing by human epidermal growth factor. Invest Ophthalmol Vis Sci 31:1773–1778PubMedGoogle Scholar
  35. 35.
    Knorr M, Denk PO (1999) Inhibitory effect of Trapidil on the proliferation of bovine corneal fibroblasts in vitro. Grafes Arch Clin Exp Ophthalmol 237:72–77CrossRefGoogle Scholar
  36. 36.
    Koizumi NJ, Inatomi TJ, Sotozono CJ et al. (2000) Growth factor mRNA and protein in preserved human amniotic membrane. Curr Eye Res 20:173–177CrossRefPubMedGoogle Scholar
  37. 37.
    Kruse FE (1996) Die Stammzellen des Limbus und ihre Bedeutung für die Regeneration der Hornhautoberfläche. Ophthalmologe 93:633–643PubMedGoogle Scholar
  38. 38.
    Kruse FE, Rohrschneider K, Völcker HE (1999) Transplantation von Amnionmembran zur Rekonstruktion der Hornhautoberfläche. Ophthalmologe 96:673–678CrossRefPubMedGoogle Scholar
  39. 39.
    Lin CP, Boehnke M (2000) Effect of fortified antibiotic solutions on corneal epithelial wound healing. Cornea 19:204–206CrossRefPubMedGoogle Scholar
  40. 40.
    Lindberg K, Brown ME, Chaves HV et al. (1993) In vitro propagation of human ocular surface epithelial cells for transplantation. Invest Ophthalmol Vis Sci 34:2672–2679PubMedGoogle Scholar
  41. 41.
    Meller D, Pires RT, Mack RJ et al. (2000) Amniotic membrane transplantation for acute chemical or thermal burns. Ophthalmology 107:980–989CrossRefPubMedGoogle Scholar
  42. 42.
    Melles GRJ, Eggingk FAGJ, Lander F et al. (1998) A surgical technique for posterior lamellar keratoplasty. Cornea 17:618–626PubMedGoogle Scholar
  43. 43.
    Melles GRJ, Lander F, Rietveld FJ (2002) Transplantation of Descemet’s membrane carrying viable endothelium through a small scleral incision. Cornea 21:415–418CrossRefPubMedGoogle Scholar
  44. 44.
    Miyauchi S, Sugiyama T, Machida A et al. (1990) The effect of sodium Hyaloronate on the migration of rabbit corneal epithelium. I. An in vitro study. J Ocul Pharmacol 6:91–99PubMedGoogle Scholar
  45. 45.
    Na BK, Hwang JH, Shin EJ et al. (1999) Analysis of human amniotic membrane components as protease inhibitors for development of therapeutic agent for recalcitrant keratitis. Trophoblast Res 13:459–466Google Scholar
  46. 46.
    Nishida T, Nakamura M, Mishima H, Otori T (1991) Hyaluronan stimulates corneal epithelial migration. Exp Eye Res 53:753–758.PubMedGoogle Scholar
  47. 47.
    Nishida T, Tanaka T (1996) Extracellular matrix and growth factors in corneal wound healing. Curr Opin Ophthalmol 7:2–11Google Scholar
  48. 48.
    Pastor JC, Calonge M (1992) Epidermal growth factor and corneal wound healing. A multicenter study. Cornea 11:311–314PubMedGoogle Scholar
  49. 49.
    Pellegrini G, Traverso CE, Franzi AT et al. (1997) Long-term restoration of damaged corneal surface with autologous cultivated corneal epithelium. Lancet 349:990—993CrossRefPubMedGoogle Scholar
  50. 50.
    Pisella PJ, Fillacier K, Elena PP et al. (2000) Comparison of the effects of preserved ans unpreserved formulations of timolol on the ocular surface of albino rabbits. Ophthalmic Res 32:3–8Google Scholar
  51. 51.
    Pleyer U, Grammer J, Bachmann W, Thiel HJ (1995) Kollagenlinsen. Anwendungen und therapeutische Möglichkeiten. Akt Augenheilkd 20:173–183Google Scholar
  52. 52.
    Puangsricharern V, Tseng SCG (1995) Cytologic evidence of corneal diseases with limbal stem cell deficiency. Ophthalmology 102:1476–1485PubMedGoogle Scholar
  53. 53.
    Rieck P, Assouline M, Savoldelli M et al. (1992) Recombinant human basic fibroblast growth factor (Rh-bFGF) in three different wound models in rabbits: corneal wound healing effect an pharmacology. Exp Eye Res 54:987–988PubMedGoogle Scholar
  54. 54.
    Rieck P, Edelmann B, Schmidt S, Hartmann C (2001) Effekt von Prostaglandin F2α auf die Proliferation von Hornhautendothelzellen in vitro. Ophthalmologe 98:1157–1161CrossRefPubMedGoogle Scholar
  55. 55.
    Rieck P, Gigon M, Jaroszewski J et al. (2003) Increased endothelial survival of organ-cultured corneas stored in FGF-2-supplemented serum free medium. Invest Ophthalmol Vis Sci 44:3826–3832CrossRefPubMedGoogle Scholar
  56. 56.
    Ruffini JJ, Aquavella JV, LoCascio JA (1989) Effect of ollagen shields on corneal epithelization following penetrating keratoplasty. Ophthalmic Surg 20:21–25PubMedGoogle Scholar
  57. 57.
    Scardovi C, De Felice GP, Gazzaniga A (1993) Epidermal growth factor in the topical treatment of traumtic corneal ulcers. Ophthalmologica 206:119–124PubMedGoogle Scholar
  58. 58.
    Schermer A, Galvin S, Sun TT (1986) Differentiation-related expression of a major 64 K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells. J Cell Biol 103:49–62PubMedGoogle Scholar
  59. 59.
    Schipper I, Suppelt C, Gebbers JO (1997) Mitomycin C reduces scar formation after excimer laser photorefractive keratectomy in rabbits. Eye 11:649–655PubMedGoogle Scholar
  60. 60.
    Schultz G, Khaw PT, Oxford K et al. (1994) Growth factors and ocular wound healing. Eye 8:184–187PubMedGoogle Scholar
  61. 61.
    Schwartz DM, Fields HL, Duncan KG et al. (1998) Experimental study of tetrodotoxin, a long-acting topical anesthetic. Am J Ophthalmol 125:481–487CrossRefPubMedGoogle Scholar
  62. 62.
    Seitz B, Langenbucher A, Hafner A et al. (2002) Phtottherapeutische Keratektomie bei rezidivierender Erosio corneae (e-PTK). Ophthalmologe 99:703–708PubMedGoogle Scholar
  63. 63.
    Shimazaki J, Aiba M, Goto E et al. (2002) Transplantation of human limbal epithelium cultivated on amniotic membrane for the treatment of severe ocular surface disorders. Ophthalmology 109:1285–1290CrossRefPubMedGoogle Scholar
  64. 64.
    Shimmura S, Shimazaki J, Ohashi Y, Tsubota K (2001) Antiinflammatory effects of amniotic membrane transplantation in ocular surface disorders. Cornea 20:408–413CrossRefGoogle Scholar
  65. 65.
    Solomon A, Rosenblatt M, Monroy D et al. (2001) Suppression of interleukin 1 alpha and interleukin 1 beta in human limbal epithelial cells cultured on the amniotic membrane stromal matrix. Br J Ophthalmol 85:444–449CrossRefGoogle Scholar
  66. 66.
    Sun R, Hamilton RC, Gimbel HV (1999) Comparison of 4 topical anesthetic agents for effect and corneal toxicity in rabbits. J Cataract Refract Surg 25:1232–1236CrossRefPubMedGoogle Scholar
  67. 67.
    Talamo JH, Gollamudi S, Green WR et al. (1991) Modulation of corneal wound healing after excimer laser keratomileusis using topical mitomycin C and steroids. Arch Ophthalmol 109:1141–1146PubMedGoogle Scholar
  68. 68.
    Tan DTH, Ficker LA, Buckley RJ (1996) Limbal transplantation. Ophthalmology 103:29–36PubMedGoogle Scholar
  69. 69.
    Thom S, Myers J, Rapuano C et al. (1997) Effect of topical anti-transforming growth factor-beta on corneal stromal haze after photorefractive keratectomy in rabbits. J Cataract Refract Surg 23:1324–1330PubMedGoogle Scholar
  70. 70.
    Thompson P, Desbordes JM, Giraud J et al. (1982)The effect of an eye derived growth factor (EDGF) on corneal epithelial regeneration. Exp Eye Res 34:191–199PubMedGoogle Scholar
  71. 71.
    Tripathi BJ, Tripathi RC (1989) Cytotoxic effects of benzalkonium chloride and chlorobutanol on human corneal epithelial cells in vitro. Lens Eye Toxic Res 6:395–403PubMedGoogle Scholar
  72. 72.
    Tsai RJF, Tseng SCG (1994) Human allograft transplantation for corneal surface reconstruction. Cornea 15:389–400Google Scholar
  73. 73.
    Tsai RJF, Li LM, Chen JK (2000) Reconstruction of damaged comeas by transplantation of autologous limbal epithelial cells. N Eng J Med 343:86–93CrossRefGoogle Scholar
  74. 74.
    Tseng SCG, Kruse FE, Merritt J, Li DQ (1996) Comparison between serum-free and fibroblast-cocultured single-cell clonal culture systems: evidence showing that epithelial antiapoptotic activity is present in 3T3 fibroblast conditioned media. Curr Eye Res 15:973—984PubMedGoogle Scholar
  75. 75.
    Tsubota K, Satake Y, Ohyama M et al. (1996) Surgical reconstruction of the ocular surface in advanced ocular cicatrical pemphigoid and Stevens-Johnson syndrome. Am J Ophthalmol 122:38–52PubMedGoogle Scholar
  76. 76.
    Tsubota K, SatakeY, Kaido M et al. (1999) Treatment of severe ocular surface disorders with corneal epithelial stem-cell transplantation. N Eng J Med 340:1697–1703CrossRefGoogle Scholar
  77. 77.
    van Setten G (1997) Dry eye syndrome, tear film, pharmacology of eye drops, and toxicity. Curr Opin Ophthalmol 8:41–45Google Scholar
  78. 78.
    Wysenbeek YS, Loya N, Ben Sira I et al. (1988) The effect of sodium hyaluronate on the corneal epithelium. An ultrastructual study. Invest Ophthalmol Vis Sci 29:194–199PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Augenklinik Charité, Universitätsmedizin BerlinCampus Virchow KlinikumBerlin
  2. 2.Augenklinik Charité, Universitätsmedizin BerlinCampus Virchow KlinikumBerlin

Personalised recommendations