Systemic Corticosteroids

Corticosteroids are potent modulators of the immune system but have low specificity and serious side effects. Their well-known and serious side effects, including osteopaenia, weight gain, hyperglycaemia, hypercholesterolaemia, hypertension, and skin fragility, can occur with modest doses administered over relatively short periods. Despite this they are widely used in solid organ transplantation, where their combination with other immunosuppressive agents enables the use of lower doses of the individual agents with a corresponding reduction in the side effects. However, even when used in combination, the side effects from systemic administration of corticosteroids are considerable and they are generally avoided as maintenance therapy for patients receiving corneal transplants, even for high-risk patients.

They are used for graft rescue - to save corneal grafts that are undergoing allograft rejection - and for graft maintenance when the use of other agents is precluded by side effects, such as cyclosporin toxicity. The level of evidence for their efficacy is low. This is related to the long history of usage. Introduced into clinical practice in the 1960s they have assumed a place in the treatment of corneal graft rejection but have not been subjected to formal assessment as happens with new therapeutic agents today. Their role is so accepted that it would not be possible to arrange such a trial now. Furthermore there are theoretical grounds for using systemic corticosteroids to treat allograft rejection. Clonal expansion, the process that primes the immune system towards subsequent rejection, occurs in the facial and cervical lymph nodes beyond the reach of topical steroids [71]. In addition high levels of circulating corticosteroids are capable of redirecting the immune system [72]. The mechanisms are believed to be attributable to the removal of circulating T cells [73,74], the activated CD4-positive cells which are primed in the lymph nodes to trigger the next rejection episode being particularly susceptible [75], and pronounced suppression of inflammation.

There are data on the relative merits of oral and intravenous bolus steroids in the treatment of corneal allograft rejection, although the message is mixed. Some studies show a benefit from the use of intravenous methyl prednisolone [76-78], and others show no benefit at all [79]. Perhaps the appropriate approach is to continue to use oral prednisolone for the treatment of corneal allograft rejection because the balance of evidence suggests that there is no advantage from using intravenous therapy. Both routes of administration can result in complications, with the intravenous route having some additional and serious acute problems [58]. When using oral corticosteroids in this situation it is advisable to avoid prolonged therapy. In our practice we restrict the course of oral prednisolone to 3 weeks. If there has not been an improvement in the clinical picture in 3 weeks, it is assumed

4.lo Current Approaches to Immunomodulation for Corneal Transplantation

the rejection is steroid resistant and oral administration ceased.

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