CYCLOSPORINE PROTECTS THE EYELID SKIN FROM INJURY AFTER INJECTION OF DOXORUBICIN

Purpose. The myotoxic drug doxorubicin can treat blepharospasm and hem ifacial spasm permanently when injected directly into the eyelid of pa tients. One side effect of this treatment is the dose-related occurren ce of injury to the skin overlying the injection site. The purpose of this study was to determine if injection of the immunosuppressive agen t cyclosporin into rabbit eyelids before doxorubicin treatment could r educe the occurrence of injury to the overlying skin and to determine the effect of cyclosporin pretreatment on doxorubicin-induced muscle f iber loss. Methods. Anesthetized rabbits received injections of varyin g doses of cyclosporin 20 minutes before injection of either 0.5, 1, o r 2 mg doxorubicin. The rabbits were examined daily, and epithelial ch anges were recorded as to duration, time of onset, and healing. When t he skin was completely healed, the animals were killed and eyelid tiss ue was prepared for morphometric determination of muscle fiber number. Acute inflammation was quantitatively assessed using an Evans blue as say. Results. At specified doses, cyclosporin improved the doxorubicin chemomyectomy protocol in three ways. It delayed the onset of skin in jury at the higher doses of doxorubicin, and it markedly decreased the duration of skin injury. At some doses, cyclosporin completely preven ted the formation of epithelial defects. The combination, however, did not increase muscle loss compared to doxorubicin alone; in fact, it h ad a slightly myoprotective effect. A dose range for cyclosporin admin istration was determined that resulted in a quantitative and dose-depe ndent reduction in inflammation at the injection site. Conclusions. Th e injection of cyclosporin into the eyelids before doxorubicin treatme nt delayed the onset, reduced the duration, and limited the extent of development of eyelid skin injury. Perhaps by limiting cytokine releas e, cyclosporin decreased the inflammatory reaction com pared to that s een with doxorubicin alone. This combination has the potential to impr ove patient acceptance of doxorubicin chemomyectomy for the treatment of blepharospasm and hemifacial spasm.