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Editor,—We read with great interest the recent article by Dua and Azuara-Blanco,1 describing the use of a new immunosuppressive agent FK-506 in patients receiving allo-limbal transplantation. The authors also describe a modified surgical approach. Although FK-506 appears to be a safe and effective treatment option in these patients, the follow up is longer than 1 year in only two of the six patients. These two patients experienced a limbal graft rejection episode in the postoperative period and we therefore feel that longer follow up is necessary before the efficacy of FK-506 can be properly established. It would also be interesting to compare FK-506 with cyclosporin A in future studies to assess the relative safety and efficacy of the two drugs.
The potential advantage of HLA matching was cited in the discussion by the authors. Although a recent study2 indicates that HLA matching may not totally obviate the need for immunosuppression, we believe that it will allow reduction of dosage and or duration of treatment with these potentially toxic drugs. In countries with a paucity of corneal donor tissue, where even hepatitis B positive donor tissue is sometimes used,3 live related donor tissue is a valuable source of stem cells. However, the modified surgical technique described by the authors1 would not be suitable for live related transplantation, as extent of tissue excision would prove detrimental to the donor eye.
We concur with the authors that adequate reconstitution of the ocular surface microenvironment is critical to the success of limbal transplantation procedures. We feel that the use of amniotic transplantation4 would have helped achieve this goal during surgery. We feel also that there are still many unanswered questions in limbal grafting for ocular surface reconstruction including the best surgical approach, the optimum amount of limbal stem cell transfer, the ideal microenvironment for survival of the transplanted limbal cells, the usefulness of HLA matching, and the role of newer immunosuppressive agents like FK-506. We suggest that before new information is available, the use of HLA matched live related limbal tissue, combined with amniotic membrane transplantation and long term immunosuppression of the recipient would be a viable option in the treatment of advanced ocular surface disease.
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Editor,—The authors have commented on the use of FK-506 as an immunosuppressive agent in patients with allo-limbal transplantation. Our experience with tacrolimus (FK-506, Prograf, Fujisawa Ltd, London) has been very good thus far. Since publication of the report, several of our patients have been followed for over 1 year now. Attempts to reduce FK-506 (with a view to stopping treatment) have resulted in rejection reactions in two patients (one more since publication of the paper), but resolved on increasing the dose. Younget al have expressed concern over the two patients who had developed rejection while on treatment with FK-506. They have interpreted this as implying poor efficacy of the drug. While we agree that the efficacy of this drug does need to be evaluated over a longer period of time, it needs to be emphasised that in one of these patients, where a rejection reaction was observed 4 months after transplantation, it corresponded with a very low trough level of the drug and responded to an increase in the drug dose. The second patient experienced rejection after stopping the drug, 13 months post-surgery and responded to reinstating FK-506 therapy. Thus, in both instances it was not the efficacy of the drug that was in question. A third patient (patient 3) had a similar experience on reducing drug dosage, 18 months post-surgery, emphasising the need for long term treatment with immunosuppressive agents.
We have also used this drug in the treatment of several “high risk” corneal transplants with excellent results (unpublished observations). Young et al have suggested a prospective comparison of FK-506 with cyclosporin. Our preliminary experience with the two drugs, in the treatment of endogenous posterior uveitis, showed some advantages of FK-506 over cyclosporin. In theory, however, both drugs should be effective and should perhaps be used in a complementary manner, if onset of side effects with one drug dictate cessation of therapy.
There is no doubt that the use of HLA matched material from living related donors will provide the advantages of “fresh tissue” and “matched tissue”. Unfortunately, however, not all patients have willing, living related donors. When cadaveric limbal allografts have to be used, the advantage of “freshness” is preferred over the potential benefit of a “close or near match” and the associated delay. Tsuboto et al have, however, shown that preserved (Optisol GS medium) tissue can be successfully used for limbal allografts.
Our technique (modification) is clearly designed for cadaveric material. There was never the suggestion that it should be employed for living related donors. Our belief is that, as for auto-limbal grafts, no more than 4 clock hours of limbal tissue should be harvested from any one eye of a living donor. This figure is admittedly empirical, and further experience with this technique is needed for more definite information.
Finally, in the last paragraph, Young et alcontradict themselves by, firstly, rightly pointing out the present limitations of limbal transplantation procedures and then making a very definitive statement in proposing use of HLA matched live related limbal tissue, combined with amniotic membrane transplantation and immunosuppression as a viable option. Amniotic membrane transplantation combined with limbal transplantation has been shown to give good results but there is no evidence to show that it is superior to any technique the does not employ the use of this membrane. Controlled randomised studies are also needed to sort out this issue.