Skip to main content

Advertisement

Log in

Pharmacologic strategies in the prevention and treatment of corneal transplant rejection

  • Original paper
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Corneal transplantation remains one of the most successful organ transplantation procedures in humans. The unique structure of the cornea, with its absence of blood vessels and corneal lymphatic, allows the survival of corneal allograft. Recent advances in sutures, storage media, microsurgical instrumentation, and new pharmacological strategies have greatly improved the success of corneal transplantation and the prevention of corneal allograft rejection. Our strategies in the management and prevention of corneal graft rejection can modify and improve the survival of corneal allografts. Preoperative evaluation, understanding the risk factors, and management of ocular surface disorders may greatly improve the survival of the corneal transplant. Early recognition of corneal allograft rejection and aggressive treatment may improve the survival of the corneal graft. Furthermore, patients who undergo corneal transplantation should be maintained under close ophthalmic surveillance and patients should be informed to report immediately whenever symptoms of corneal graft rejection occur. The mainstay of therapy is topical corticosteroids. In severe cases, periocular, intravenous, and oral corticosteroids therapy can be rendered. New therapeutic modalities such as cyclosporine, tacrolimus, daclizumab, mycophenolate mofetil, leflunomide, rapamycin, and others may prove to be of help in the prevention and treatment of corneal graft rejection. Early recognition of corneal graft rejection and prompt treatment are mandatory for the successful survival of the corneal allograft.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3 
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Beckingsale P, Mavrikakis I, Al-Yousuf N, Mavrikakis E, Daya SM (2006) Penetrating keratoplasty: outcomes from a corneal unit compared to national data. Br J Ophthalmol 90(6):728–731

    Article  PubMed  CAS  Google Scholar 

  2. Sangwan VS, Ramamurthy B, Shah U, Garg P, Sridhar MS, Rao GN (2005) Outcome of corneal transplant rejection: a 10 year study. Clin Exp Ophthalmol 33(6):623–627

    Article  Google Scholar 

  3. Afshari NA, Pittard AB, Siddiqui A, Klintworth GK (2006) Clinical study of Fuchs corneal endothelial dystrophy leading to penetrating keratoplasty: a 30-year experience. Arch Ophthalmol 124(6):777–780

    Article  PubMed  Google Scholar 

  4. Al-Hazzaa S, Tabbara KF (1988) Bacterial keratitis after penetrating keratoplasty. Ophthalmology 95(11):1504–1508

    PubMed  CAS  Google Scholar 

  5. Al-Faran MF, Tabbara KF (1991) Corneal dystrophies among patients undergoing penetrating keratoplasty. Cornea 10(1):13–16

    PubMed  CAS  Google Scholar 

  6. Al-Towerki A, Al-Rajhi AA, Wagoner MD (2004) Changing indications for keratoplasty at the King Khaled Eye Specialist Hospital (1983–2002). Cornea 23(6):584–588

    Article  PubMed  Google Scholar 

  7. Al-Swailem SA, Al-Rajhi AA, Wagoner MD (2005) Penetrating keratoplasty for macular corneal dystrophy. Ophthalmology 112(2):220–224

    Article  PubMed  Google Scholar 

  8. Randleman JB, Stulting RD (2006) Prevention and treatment of corneal graft rejection: current practice patterns (2004). Cornea 25(3):286–290

    Article  PubMed  Google Scholar 

  9. Williams KA, Esterman AJ, Bartlett C, Holland H, Hornsby NB, Coster DJ (2006) How effective is penetrating corneal transplantation? Factors influencing long-term outcome in multivariate analysis. Transplantation 81(6):896–901

    Article  PubMed  Google Scholar 

  10. Javadi MA, Motlagh BF, Jafarinasab MR, Rabbanikhah Z, Anissian A, Souri H, Yazdani S (2005) Outcomes of penetrating keratoplasty in keratoconus. Cornea 24(8):941–946

    Article  PubMed  Google Scholar 

  11. Dua HS, Azuara-Blanco A (1999) Corneal allograft rejection: risk factors, diagnosis, prevention and treatment [review]. Indian J Ophthalmol 47(1):3–9

    PubMed  CAS  Google Scholar 

  12. Niederkorn JY, Stevens C, Mellon J, Mayhew E (2006) CD4+ T-cell independent rejection of corneal allografts. Transplantation 81(8):1171–1178

    Article  PubMed  Google Scholar 

  13. Yamagami S, Hamrah P, Zhang Q, Liu Y, Huq S, Dana MR (2005) Early ocular chemokine gene expression and leukocyte infiltration after high-risk corneal transplantation. Mol Vis 11:632–640

    PubMed  CAS  Google Scholar 

  14. Nicholls SM, Banerjee S, Figueiredo FC, Crome S, Mistry S, Easty DL, Dick AD (2006) Differences in leukocyte phenotype and interferon-gamma expression in stroma and endothelium during corneal graft rejection. Exp Eye Res 83(2):339–347

    Article  PubMed  CAS  Google Scholar 

  15. Watson SL, Tuft SJ, Dart JK (2006) Patterns of rejection after deep lamellar keratoplasty. Ophthalmology 113(4):556–560

    Article  PubMed  Google Scholar 

  16. Niederkorn JY, Stevens C, Mellon J, Mayhew E (2006) Differential roles of CD8+ and CD8-T lymphocytes in corneal allograft rejection in “high-risk” hosts. Am J Transplant 6(4):705–713

    Article  PubMed  CAS  Google Scholar 

  17. Frost NA, Wu J, Lai TF, Coster DJ (2006) A review of randomized controlled trials of penetrating keratoplasty techniques. Ophthalmology 113(6):942–949

    Article  PubMed  Google Scholar 

  18. Collaborative Corneal Transplantation Studies Research Group (1992) Effectiveness of histocompatibility matching in high risk corneal transplantation. Arch Ophthalmol 110:1392–1403

    Google Scholar 

  19. Volker-Dieben HJ, Kok-van Alphen CC, Krut PJ (1979) Advances and disappointments, indications and restrictions regarding HLA matched corneal grafts in high risk cases. Doc Ophthalmol 46:219–226

    Article  PubMed  CAS  Google Scholar 

  20. Volker-Dieben HJ, Kok-van Alphen CC, Lansbergen Q, Persijn GG (1982) The effect of prospective HLA-A and -B matching on corneal graft survival. Acta Ophthalmol 60:203–212

    CAS  Google Scholar 

  21. Sanfilippo F, MacQueen JM, Vaughn WK, Foulks GN (1986) Reduced graft rejection with good HLA-A and HLA-B matching in high risk corneal transplantation. N Engl J Med 315:29–35

    Article  PubMed  CAS  Google Scholar 

  22. Price MO, Price FW Jr (2006) Efficacy of topical cyclosporine 0.05% for prevention of cornea transplant rejection episodes. Ophthalmology 113(10):1785–1790

    Article  PubMed  Google Scholar 

  23. Reed MH, Shapiro ME, Strom TB et al (1989) Prolongation of primate renal allograft survival by anti-Tac, an anti-human IL-2 receptor monoclonal antibody. Transplantation 47:55–59

    Article  PubMed  CAS  Google Scholar 

  24. Brown PS Jr, Parentean GL, Dirbas FM et al (1991) Anti-Tac-H, a humanized antibody to interleukin 2 receptor, prolongs primate cardiac allograft survival. Proc Natl Acad Sci USA 88:2663–2667

    Article  PubMed  CAS  Google Scholar 

  25. Wihelmus KR (2000) The treatment of herpes simplex virus epithelial keratitis. Trans Am Ophthalmol Soc 98:505–532

    Google Scholar 

  26. Hyndiuk R, Glasser D (1996) Herpes simplex keratitis. In: Tabbara KF, Hyndiuk R (eds) Infections of the eye, 2nd edn. Little, Brown, Boston, pp 361–386

    Google Scholar 

  27. O’Brien W (1996) Antiviral agents. In: Tabbara K, Hyndiuk R (eds) Infections of the eye, 2nd edn. Little, Brown, Boston, pp 269–280

    Google Scholar 

  28. Davies ME, Bondi JV, Grabowski L et al (1987) 2′-Nor-2′-deoxyguanosine is an effective therapeutic agent for treatment of experimental herpes keratitis. Antiviral Res 7(2):119–125

    Article  PubMed  CAS  Google Scholar 

  29. Gordon YJ, Capone A, Sheppard J et al (1987) 2′-nor-cGMP, a new cyclic derivative of 2′NDG, inhibits HSV-1 replication in vitro and the mouse keratitis model. Curr Eye Res 6(1):247–253

    Article  PubMed  CAS  Google Scholar 

  30. Shiota H, Naito T, Mimura Y (1987) Anti-herpes simplex virus (HSV) effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) in rabbit cornea. Curr Eye Res 6(1):241–245

    Article  PubMed  CAS  Google Scholar 

  31. Castela N, Vermerie N, Chast F et al (1994) Ganciclovir ophthalmic gel in herpes simplex virus rabbit keratitis: intraocular penetration and efficacy. J Ocul Pharmacol 10(2):439–451

    Article  PubMed  CAS  Google Scholar 

  32. Colin J, Hoh HB, Easty DL et al (1997) Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis. Cornea 16(4):393–399

    Article  PubMed  CAS  Google Scholar 

  33. Hoh HB, Hurley C, Claoue C et al (1996) Randomised trial of ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis: a multicentre study. Br J Ophthalmol 80(2):140–143

    Article  PubMed  CAS  Google Scholar 

  34. Tabbara KF (2005) Treatment of herpetic keratitis. Ophthalmology 112(9):1640

    Article  PubMed  Google Scholar 

  35. Pouliquen P, Elena PP, Malecaze F et al (1996) Assessment of the safety and local pharmacokinetics of a 0.15% gel of ganciclovir (Virgan®) in healthy volunteers. Invest Ophthalmol Vis Sci 37(3):S313

    Google Scholar 

  36. Shaw MM, Gurr WK, Watts PA et al (2001) Ganciclovir and penciclovir, but not acyclovir, induce apoptosis in herpes simplex virus thymidine kinase-transformed baby hamster kidney cells. Antivir Chem Chemother 12(3):175–186

    PubMed  CAS  Google Scholar 

  37. Epstein RJ, Seedor JA, Dreizen NG et al (1987) Penetrating keratoplasty for herpes simplex keratitis and keratoconus: allograft rejection and survival. Ophthalmology 94(8):935–944

    PubMed  CAS  Google Scholar 

  38. Ficker LA, Kirkness CM, Rice NS et al (1989) Changing management and improved prognosis for corneal grafting and herpes simplex keratitis. Ophthalmology 96(11):1587–1596

    PubMed  CAS  Google Scholar 

  39. Sonkin PL, Baratz KH, Frothingham R et al (1992) Acyclovir-resistant herpes simplex virus keratouveitis after penetrating keratoplasty. Ophthalmology 99(12):1805–1808

    PubMed  CAS  Google Scholar 

  40. Rapuano CJ, Cohen EJ, Brady SE et al (1990) Indications for and outcomes of repeat penetrating keratoplasty. Am J Ophthalmol 109(6):689–695

    PubMed  CAS  Google Scholar 

  41. De Kesel RJ, Koppen C, Leven M et al (2001) Primary graft failure caused by herpes simplex virus type I. Cornea 20(2):187–190

    Article  PubMed  Google Scholar 

  42. Akova YA, Onat M, Duman S (1999) Efficacy of low dose and long term oral acyclovir therapy after penetrating keratoplasty for herpes simplex keratitis. Ocul Immunol Inflamm 7(1):51–60

    Article  PubMed  CAS  Google Scholar 

  43. Lairson DR, Begley CE, Wilhelmus KR (2003) Prevention of herpes simplex virus eye disease. A cost-effectiveness analysis. Arch Ophthalmol 121(1):108–112

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Khalid F. Tabbara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tabbara, K.F. Pharmacologic strategies in the prevention and treatment of corneal transplant rejection. Int Ophthalmol 28, 223–232 (2008). https://doi.org/10.1007/s10792-007-9100-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-007-9100-7

Keywords

Navigation