Abstract
We report a patient with peripheral rheumatoid corneal melting who developed a corneal perforation in one eye requiring tectonic keratoplasty. Nine consecutive corneal grafts were rapidly destroyed despite systemic immunosuppression with corticosteroid, cyclophosphamide, azathioprine and cyclosporin A. A rejection episode was observed in one graft before it melted and allograft rejection may have contributed to the destruction of other grafts. Corneal graft survival was ultimately achieved by systemic immunosuppression with the anti-lymphocyte monoclonal antibody, CAM-PATH-1H. A single episode of rejection developed in the early post-operative period which was easily reversed by topical corticosteroid. Corneal melting has not recurred and the graft has now remained intact and clear for 24 months. Anti-lymphocyte monoclonal antibodies may therefore provide effective immunosuppression in the treatment of refractory ocular disorders.
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Palay DA, Stulting RD, Waring GO, Wilson LA . Penetrating keratoplasty in patients with rheumatoid arthritis. Ophthalmology 1992;99:622–7.
Raizman MB, Sainz de la Maza M, Foster CS . Tectonic keratoplasty for peripheral ulcerative keratitis. Cornea 1991;10:312–6.
Jayson MIV, Easty DL . Ulceration of the cornea in rheumatoid arthritis. Ann Rheum Dis 1977;36:428–32.
Easty DL, Madden P, Jayson MIV, Carter C, Noble BA . Systemic immunosuppression in marginal keratolysis. Trans Ophthalmol Soc UK 1978;98:410–7.
Foster CS . Immunosuppressive therapy for external ocular inflammatory disease. Ophthalmology 1980;87:140–50.
Meyer PAR, Watson PG, Franks W, Dubord P . ‘Pulsed’ immunosuppressive therapy in the treatment of immunologically induced corneal and scleral disease. Eye 1987;1:487–95.
Hill JC . Systemic cyclosporine in high-risk keratoplasty. Short- versus long-term therapy. Ophthalmology 1994;101:128–33.
MacKay IR, Bignell JL, Smith PH, Crawford BA . Prevention of corneal-graft failure with the immunosuppressive drug azathioprine. Lancet 1967;2:479–82.
The Collaborative Corneal Transplantation Studies Research Group. The Collaborative Corneal Transplantation Studies (CCTS). Effectiveness of histocompatibility matching in high-risk corneal transplantation. Arch Ophthalmol 1992;110:1392–403.
Duguid IGM, Koulmanda M, Mandel TE . Prolongation of heterotopic human corneal graft survival in mice treated with an anti-CD4 monoclonal antibody. Transplant Proc 1990;22(5):2107–8.
He YG, Ross J, Niederkorn JY . Promotion of murine orthotopic corneal allograft survival by systemic administration of anti-CD4 monoclonal antibody. Invest Ophthalmol Vis Sci 1991;32:2723–8.
Ayliffe W, Alam Y, Bell EB, McLeod D, Hutchinson IV . Prolongation of rat corneal graft survival by treatment with anti-CD4 monoclonal antibody. Br J Ophthalmol 1992;76:602–6.
Duguid IGM, Koulmanda M, Mandel TE . Effect of monoclonal antibody on corneal graft survival across major and minor histocompatibility mismatches. Transplant Proc 1993;25(1 Pt 1):844.
Williams KA, Standfield SD, Wing SJ, Barras CW, Mills RA, Comacchio RM, Coster DJ . Patterns of corneal graft rejection in the rabbit and reversal of rejection with monoclonal antibodies. Transplantation 1992;54:38–43.
Jabs DA, Prendergast RA . Autoimmune ocular disease in MRL/Mp-lpr/lpr mice is suppressed by anti-CD4 antibody. Invest Ophthalmol Vis Sci 1991;32:2718–22.
Atalla L, Linker-Israeli M, Steinman L, Rao NA . Inhibition of autoimmune uveitis by anti-CD4 antibody. Invest Ophthalmol Vis Sci 1990;31:1264–70.
Ippoliti G, Fronterrè A . Use of locally injected anti-T monoclonal antibodies in the treatment of acute corneal graft rejection. Transplant Proc 1987;19(1 Pt 3):2579–80.
Ippoliti G, Fronterrè A . Usefulness of CD3 or CD6 anti-T monoclonal antibodies in the treatment of acute corneal graft rejection. Transplant Proc 1989;21(1 Pt 3):3133–4.
Hale G, Xia M-Q, Tighe HP, Dyer MJS, Waldmann H . The CAMPATH-1 antigen (CDw52). Tissue Antigens 1990;35:118–27.
Riechmann L, Clark M, Waldmann H, Winter G . Reshaping human antibodies for therapy. Nature 1988;332:323–7.
Isaacs JD, Watts RA, Hazleman BL, Hale G, Keogan MT, Cobbold SP, Waldmann H . Humanised monoclonal antibody therapy for rheumatoid arthritis. Lancet 1992;340:748–52.
Kyle V, Roddy J, Hale G, Hazleman BL, Waldmann H . Humanized monoclonal antibody treatment in rheumatoid arthritis. J Rheumatol 1991;18:1737–8.
Mathieson PW, Cobbold SP, Hale G, Clark MR, Oliveira DBG, Lockwood CM, Waldmann H . Monoclonal-antibody therapy in systemic vasculitis. N Engl J Med 1990;323:250–4.
Lockwood CM, Thiru S, Isaacs JD, Hale G, Waldmann H . Long-term remission of intractable systemic vasculitis with monoclonal antibody therapy. Lancet 1993;341:1620–2.
Friend PJ, Hale G, Waldmann H, Gore S, Thiru S, Joysey V, et al. Campath-1M - prophylactic use after kidney transplantation. A randomised controlled clinical trial. Transplantation 1989;48;248–53.
Friend PJ, Waldmann H, Hale G, Cobbold S, Rebello P, Thiru S, et al. Reversal of allograft rejection using the monoclonal antibody, CAMPATH-1G. Transplant Proc 1991;23(4):2253–4.
Pels E, Schuchard Y . Organ-culture preservation of human corneas. Doc Ophthalmol 1983;56:147–53.
Williams KA, Roder D, Esterman A, Muehlberg SM, Coster DJ . Factors predictive of corneal graft survival. Report from the Australian Corneal Graft Registry. Ophthalmology 1992;99:403–14.
Kenyon KR . Decision-making in the therapy of external eye disease. Noninfected corneal ulcers. Ophthalmology 1982;89:44–51.
Eiferman RA, Carothers DJ, Yankeelov JA . Peripheral rheumatoid ulceration and evidence for conjunctival collagenase production. Am J Ophthalmol 1979;87:703–9.
Michels ML, Cobo LM, Caldwell DS, Rice JR, Haynes BF . Rheumatoid arthritis and sterile corneal ulceration. Analysis of tissue immune effector cells and ocular epithelial antigens using monoclonal antibodies. Arthritis Rheum 1984;27:606–14.
Kervick GN, Pflugfelder SC, Haimovici R, Brown H, Tozman E, Yee R . Paracentral rheumatoid corneal ulceration. Clinical features and cyclosporin therapy. Ophthalmology 1992;99:80–8.
Khodadoust AA, Silverstein AM . Transplantation and rejection of individual cell layers of the cornea. Invest Ophthalmol 1969;8:180–95.
Khodadoust AA, Silverstein AM . Induction of corneal graft rejection by passive cell transfer. Invest Ophthalmol 1976;15:89–95.
Cobbold SP, Martin G, Waldmann H . The induction of skin graft tolerance in major histocompatibility complex-mismatched or primed recipients: primed cells can be tolerized in the periphery with anti-CD4 and anti-CD8 antibodies. Eur J Immunol 1990;20:2747–55.
Qin S, Cobbold SP, Pope H, Elliott J, Kioussis D, Davies J, Waldmann H . ‘Infectious’ transplantation tolerance. Science 1993;259:974–7.
Cobbold SP, Qin S, Leong LYW, Martin G, Waldmann H . Reprogramming the immune system for peripheral tolerance with CD4 and CD8 monoclonal antibodies. Immunol Rev 1992;129:165–201.
Thoft RA, Sugar J . Graft failure in keratoepithelioplasty. Cornea 1993;12:362–5.
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Newman, D., Isaacs, J., Watson, P. et al. Prevention of immune-mediated corneal graft destruction with the anti-lymphocyte monoclonal antibody, CAMPATH-1H. Eye 9, 564–569 (1995). https://doi.org/10.1038/eye.1995.140
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DOI: https://doi.org/10.1038/eye.1995.140
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