Systemic cyclosporin A in high failure risk, repeated corneal transplantation. (Clinical Science).

Aim: To evaluate the efficacy of oral cyclosporin A in the prevention and treatment of immune graft rejection in heavily vascularised, repeated keratoplasties with high risk for failure.

Methods: 21 consecutive patients with 28 repeated corneal transplants and four quadrant vascularised recipient bed were treated with oral cyclosporin A for an average period of 1 2 months (range 1-41 months) and followed for an average period of 26.6 months (range 6-106 months). The average cyclosporin A blood level was 325 ng/ml (range 180-421 ng/ml). Within this group of 21 patients, another 12 regrafts were not treated with cyclosporin A and served as a control group.

Results: Nine of the 28 regrafts (32%) treated with cyclosporin A remained clear. The Kaplan-Meier curve showed a constant decline in survival of the treated grafts, although the survival proportion during the first year of treatment was statistically higher for the treated group compared with the untreated group. Once immune regraft rejection occurred, the regraft failed despite treatment with cyclosporin A and extensive topical and systemic corticosteroids. Nine regrafts (32%) had immune graft rejection and all ultimately failed compared with five in the untreated regrafts (42%, p = NS). Ten other regrafts (36%) in the treatment group failed due to causes other than immune regraft rejection.

Conclusions: Systemic cyclosporin A has a limited beneficial effect in preventing immune graft rejection in repeated corneal transplants in a highly vascularised corneal bed. When immune graft rejection occurs in such regrafts, the prognosis is poor despite aggressive medical treatment. Causes other than immune regraft rejection may also result in poor visual outcome in patients with clear regrafts.

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Cyclosporin A is a T cell mediated immunosuppressant drug that has been successfully used as a topical or systemic preparation for ocular surface disorders such as vernal and atopic conjunctivitis, (1 2) ocular pemphigoid, (2) ulcerative keratitis, (2) Mooren's ulcer, (2) dry eye, (3 4) keratoconjunctivitis sicca, (5) and uveitis. (6 7}

The effect of cyclosporin A on high rejection risk corneal transplants has not yet been fully established. Whereas cyclosporin A showed a substantial effect in prevention of immune graft rejection when given systemically in animal models, (8-10) it may have a limited effect when administered topically to animals and humans. (11 12) Several studies reported that topical cyclosporin A was effective in prevention of immune rejection of corneal graft in humans only when combined with topical corticosteroids. (13-15) Topical cyclosporin A treatment has been reported to be beneficial in corneal transplanted eyes with no or minimal corneal vascularisation. (16)

Since the topical effect of cyclosporin A is controversial, and the effect of systemic treatment has not been evaluated in extensive corneal bed vascularisation, we evaluated the effect of oral cyclosporin A on corneal transplants with high risk for immune graft rejection and subsequent failure. We selected heavily vascularised, repeated corneal grafts to evaluate whether systemic cyclosporin A decreases the risk of immune rejection since, to the best of our knowledge this was never evaluated before. We assessed whether this treatment, combined with topical and systemic corticosteroids, results in timely suppression of immune rejection and increases graft survival. As an internal control, we employed the regrafts of this four quadrant vascularised, repeated transplantation group that were untreated with cyclosporin A to compare the immune rejection rate between treatment and no prophylactic treatment. We compared the survival of the cyclosporin treated group with the entire regrafted group during the same pe riod.

METHODS

All patients who underwent repeated corneal transplantation between 1985 and 1998 and had four quadrant vascularisation of the corneal bed were included in the study. An informed consent specifying the potential benefit and adverse effects of oral cyclosporin A was obtained from all the patients before treatment.

Oral cyclosporin A (Sandimmun, Sandoz, Basle, Switzerland) was given daily starting immediately after …