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Systemic ciclosporin A in high-risk keratoplasties

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Abstract

• Background: It was the purpose of this study to compile the results of all high-risk keratoplasties (kp) performed in our hospital under systemic ciclosporin A (Ci A) cover from 1987 through 1994. • Methods: One hundred and thirty-one keratoplasties were performed. Ci A was administered for an average period of 9.4 months. We aimed at trough levels of 100–150 ng/ml (monoclonal RIA/TDx). The 29 kp in group A were second or third repeat kp and/or the recipient cornea had severe deep vascularization in all quadrants and/or a transplant position at the limbus was inevitable (expected risk: only immune reactions). The 40 kp in group B were threatened by severe ocular surface disorders (without severe limbal stem cell insufficiency) and by immune reactions (atopic keratopathy, keratoconus with severe endogenous eczema or chronic blepharokeratoconjunctivitis). In the 45 kp of group C resurfacing problems from severe limbal stem cell insufficiency and immune reactions were anticipated (severe burns, pseudopemphigoid or Lyell syndrome). Group D comprised 17 kp with various diagnoses (e.g. kp in newborns, rheumatic andAcanthamoeba keratitis). • Results: In group A 91% of the grafts were clear 2 years postoperatively, in group B 76%, in group C 38% and in group D 18%. In 32 of 41 failed grafts (78%), resurfacing problems were the only reason for or participated in final graft failure. Immune reactions and other causes of graft failure were of minor importance. • Conclusions: (1) Systemic Ci A cover can efficiently suppress immune reactions. (2) With the suppression of immune reactions, resurfacing disorders become the most important single cause for functional graft failure. (3) For eyes with a considerable loss of limbal stem cells, limbal stem cell transplantation should be combined with systemic Ci A cover in order to improve the long-term prognosis for penetrating keratoplasty.

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References

  1. Baggesen K, Ehlers N, Lamm LU (1991) HLA-DR/RFLP compatible corneal grafts. Acta Ophthalmol 69:229–233

    CAS  Google Scholar 

  2. BenEzra D, Maftzir G, Courten C de, Timonen P (1990) Ocular penetration of cyclosporin A. III. The human eye. Brit J Ophthalmol 74:350–352

    CAS  Google Scholar 

  3. Boisjoly HM, Roy R, Bernard PM, Dubé I, Laughrea PA, Bazin R (1990) Association between corneal allograft reactions and HLA compatibility. Ophthalmology 97:1689–1698

    CAS  PubMed  Google Scholar 

  4. Chen YF, Gebhardt BM, Reidy JJ, Kaufman HE (1990) Cyclosporine-containing collagen shields suppress corneal allograft rejection. Am J Ophthalmol 109:132–137

    CAS  PubMed  Google Scholar 

  5. Chen JY, Tseng SCG (1990) Corneal epithelial wound healing in partial limbal deficiency. Invest Ophthalmol Vis Sci 31:1301–1314

    CAS  PubMed  Google Scholar 

  6. Collaborative Corneal Transplantation Studies CCTS (1992) Effectiveness of histocompatibility matching in highrisk corneal transplantation. Arch Ophthalmol 110:1392–1403

    Google Scholar 

  7. Coupland SE, Klebe S, Karow AC, Krause L, Bartlett RR, Hoffman F (1994) Leflunomide (HWA-486) in the allogenic rat penetrating keratoplasty model. Invest Ophthalmol Vis Sci 35:1878

    Google Scholar 

  8. Ehlers N, Andersen J (1987) Treatment of central corneal ulcers by à chaud transplantation of organ culture preserved donor tissue. Acta Ophthalmol 65:516–520

    CAS  Google Scholar 

  9. Ehlers N, Kissmeyer-Nielsen F (1979) Corneal transplantation and HLA histocompatibility. Acta Ophthalmol 57:738–741

    CAS  Google Scholar 

  10. Foulks GN, Sanfilippo FP, Locasio JA, MacQueen JM, Dawson D (1983) Histocompatibility testing for keratoplasty in high-risk patients. Ophthalmology 90:239–244

    CAS  PubMed  Google Scholar 

  11. Gnad HD, Skorpik C, Radda TM, Paroussis P, Menapace R, Klemen UM (1985) Immunsuppressive Therapie mit Cyclosporin A nach perforierender Keratoplastik. Klin Monatsbl Augenheilkd 187:398–399

    CAS  PubMed  Google Scholar 

  12. Heering P, Kutkuhn B, Kreuzpaitner G, Reinhard T, Sundmacher R, Grabensee B (1991) Untersuchungen zur Nierenfunktion nierengesunder Patienten unter Ciclosporin. Klin Wochenschr 69:880–886

    Article  CAS  PubMed  Google Scholar 

  13. Herbort CP, Matsubara M, Nishi M, Mochizuki M (1989) Penetrating keratoplasty in the rat: a model for the study of immunosuppressive treatment of graft rejection. Jpn J Ophthalmol 33:212–220

    CAS  PubMed  Google Scholar 

  14. Hill JC (1989) The use of cyclosporine in high-risk keratoplasty. Am J Ophthalmol 107:506–510

    CAS  PubMed  Google Scholar 

  15. Hill JC (1994) Systemic cyclosporine in high-risk keratoplasty. Short- versus long-term therapy. Ophthalmology 101:128–133

    CAS  PubMed  Google Scholar 

  16. Hoffmann F, Pahlitzsch T (1989) Predisposing factors in corneal graft rejection. Cornea 8:215–219

    CAS  PubMed  Google Scholar 

  17. Hoffmann F, Tregel M, Noske W, Bünte S (1994) HLA-A and -DR match reduces the allograft rejection after keratoplasty. Ger J Ophthalmol 3:100–104

    CAS  PubMed  Google Scholar 

  18. Holland EJ, Olsen TW, Ketcham JM, Florine C, Krachmer JH, Purcell JJ, Lam S, Tessler H, Sugar J (1993) Topical cyclosporin A in the treatment of anterior segment inflammatory disease. Cornea 12:413–419

    CAS  PubMed  Google Scholar 

  19. Hoppeler T, Balogh T, Kalman, Gloor B (1993) Autologe Limbustransplantation nach Verätzung. In: Gloor B, Hartmann C, Rochels R (eds) Kongreßband DGII. Springer, Berlin Heidelberg New York, pp 429–433

    Google Scholar 

  20. Huang AJW, Tseng SCG (1991) Corneal epithelial wound healing in the absence of limbal epithelium. Invest Ophthalmol Vis Sci 32:96–105

    CAS  PubMed  Google Scholar 

  21. Irschick EU, Siepe U, Pöttinger E, Daxer A, Ulmer H, Falk M, Göttinger W (1994) Eight years follow-up of high-risk corneal allograft recipients under a three months course of Cyclosporin A. Invest Ophthalmol Vis Sci 35 (4):1876

    Google Scholar 

  22. Kahan BD (1989) Cyclosporine. New Engl J Med 321:1725–1738

    CAS  PubMed  Google Scholar 

  23. Kenyon KR, Tseng SCG (1989) Limbal autograft transplantation for ocular surface disorders. Ophthalmology 96:709–723

    CAS  PubMed  Google Scholar 

  24. Kervick GN, Shepherd WF (1990) The pattern of corneal graft rejection. Cornea 9:234–237

    CAS  PubMed  Google Scholar 

  25. Kruse HA, Bechrakis NE, Heimann H, Diamantstein T, Hoffmann F (1991) Specific immunosuppressive therapy by monoclonal antibodies on rejection of orthoptic corneal allogenic grafts in the rat. Invest Ophthalmol Vis Sci 32:1119

    Google Scholar 

  26. Land W (1987) Optimal use of Sandimmun in organ transplantation. Springer, Berlin Heidelberg New York, pp 7–24

    Google Scholar 

  27. Maguire MG, Fink NE, Sugar A, Stark WJ, Stulting RD, CCTS (1993) Risk factors for corneal graft failure in high risk patients in the Collaborative Corneal Transplantation Studies. Invest Ophthalmol Vis Sci 34:1098

    Google Scholar 

  28. Milani JK, Pleyer U, Dukes A, Chou HJ, Lutz S, Rückert D, Schmidt K-H, Mondino BJ (1993) Prolongation of corneal allograft survival with liposome-encapsulated Cyclosporine in the rat eye. Ophthalmology 100:890–896

    CAS  PubMed  Google Scholar 

  29. Miller K, Kieselbach GF, Niederwieser D, Huber C, Margreiter R, Göttinger W (1985) Immunsuppression mit Cyclosporin A bei Risikokeratoplastiken. Klin Monatsbi Augenheilkd 187:394–397

    CAS  Google Scholar 

  30. Mytilineos J, Scherer S, Opeltz G (1990) Comparison of RFLP DR beta and serological HLA-DR typing in 1500 individuals. Transplantation 50:870–873

    CAS  PubMed  Google Scholar 

  31. Pels E, Gaag R van der (1984) HLA-A, B, C and HLA-DR antigens and dendritic cells in fresh and organ culture preserved corneas. Cornea 3:231–239

    PubMed  Google Scholar 

  32. Redbrake C, Tympnert J, Reim M (1993) Komplikationen nach Keratoplastik. Ophthalmologe 90 [Suppl 1]:47

    Google Scholar 

  33. Rehany U (1992) Suppression of allograft rejection in heavily vascularized human corneas. Second International Symposium on Ocular Inflammation, Jerusalem, 30 August–3 September 1992

  34. Riisom K, Ehlers N, Lamm L (1987) Post mortem HLA-DR typing of donor corneas using DNA hybridization technique. Acta Ophthalmol 65:430–432

    CAS  Google Scholar 

  35. Rossa V, Sundmacher R, Heering P (1990) Systemische Cyclosporin A Prophylaxe bei Risiko-Keratoplastiken. Klin Monatsbl Augenheilkd 197:466–469

    CAS  PubMed  Google Scholar 

  36. Stark WJ, Taylor HR, Blas WB, Maumenee AE (1978) Histocompatibility (HLA) antigens and keratoplasty. Am J Ophthalmol 86:595–604

    CAS  PubMed  Google Scholar 

  37. Sundmacher R (1977) Immunreaktionen nach Keratoplastik. Klin Monatsbl Augenheilkd 171:705–722

    CAS  PubMed  Google Scholar 

  38. Sundmacher R, Peter HH (1987) Cyclosporin A systemisch nach Keratoplastik wegen rheumatischer Hornhautperforation und essentieller Bindehautschrumpfung. Spektrum Augenheilkd 1:1–5

    Google Scholar 

  39. Sundmacher R, Reinhard T (1995) Central corneolimbal transplantation under systemic ciclosporin A cover for severe limbal stem cell deficiencies. Graefe's Arch Clin Exp Ophthalmol 234 (Suppl):S122-S125

    Google Scholar 

  40. Sundmacher R, Reinhard T, Heering P (1992) Six years' experience with systemic cyclosporin A prophylaxis in high-risk perforating keratoplasty patients. Ger J Ophthalmol 1:432–436

    CAS  PubMed  Google Scholar 

  41. Tan DTH, Ficker LA, Buckley RJ (1994) Limbal transplantation. Invest Ophthalmol Vis Sci 35:1913

    Google Scholar 

  42. Tuberville AW, Foster CS, Wood TO (1983) The effect of donor cornea epithelium removal on the incidence of allograft rejection reactions. Ophthalmology 90:1351–1356

    CAS  PubMed  Google Scholar 

  43. Vail A, Gore SM, Bradley BA, Easty DL, Rogers CA (1993) Corneal transplant follow-up study. Invest Ophthalmol Vis Sci 34:1366

    Google Scholar 

  44. Völcker-Dieben HJ, D'Amaro J (1988) Corneal transplantation: a single center experience 1976 to 1988. In: Terasaki P (ed) Clinical transplants 1988. UCLA Tissue Typing Laboratory, Los Angeles, Calif, pp 249–261

    Google Scholar 

  45. Völcker-Dieben HJ, Kok-van Alphen CC, Lansbergen Q, Persijn GG (1982) Different influences on corneal graft survival in 539 transplants. Acta Ophthalmol 60:190–202

    Google Scholar 

  46. Wiederholt M, Kossendrup D, Schulte W et al (1986) Pharmacokinetics of topical ciclosporin A in the rabbit eye. Invest Ophthalmol Vis Sci 27:519–524

    CAS  PubMed  Google Scholar 

  47. Wonigeit K (1988) Gegenwärtiger Stand der Immunsuppression bei der Organtransplantation. Chirurg 59:447–453

    CAS  PubMed  Google Scholar 

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Reinhard, T., Sundmacher, R. & Heering, P. Systemic ciclosporin A in high-risk keratoplasties. Graefe's Arch Clin Exp Ophthalmol 234 (Suppl 1), S115–S121 (1996). https://doi.org/10.1007/BF02343059

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  • DOI: https://doi.org/10.1007/BF02343059

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