Cyclosporin protects the eyelid skin from injury after injection of doxorubicin.
OBJECTIVE
The myotoxic drug doxorubicin can treat blepharospasm and hemifacial spasm permanently when injected directly into the eyelid of patients. One side effect of this treatment is the dose-related occurrence of injury to the skin overlying the injection site. The purpose of this study was to determine if injection of the immunosuppressive agent cyclosporin into rabbit eyelids before doxorubicin treatment could reduce the occurrence of injury to the overlying skin and to determine the effect of cyclosporin pretreatment on doxorubicin-induced muscle fiber loss.


METHODS
Anesthetized rabbits received injections of varying doses of cyclosporin 20 minutes before injection of either 0.5, 1, or 2 mg doxorubicin. The rabbits were examined daily, and epithelial changes were recorded as to duration, time of onset, and healing. When the skin was completely healed, the animals were killed and eyelid tissue was prepared for morphometric determination of muscle fiber number. Acute inflammation was quantitatively assessed using an Evans blue assay.


RESULTS
At specified doses, cyclosporin improved the doxorubicin chemomyectomy protocol in three ways. It delayed the onset of skin injury at the higher doses of doxorubicin, and it markedly decreased the duration of skin injury. At some doses, cyclosporin completely prevented the formation of epithelial defects. The combination, however, did not increase muscle loss compared to doxorubicin alone; in fact, it had a slightly myoprotective effect. A dose range for cyclosporin administration was determined that resulted in a quantitative and dose-dependent reduction in inflammation at the injection site.


CONCLUSIONS
The injection of cyclosporin into the eyelids before doxorubicin treatment delayed the onset, reduced the duration, and limited the extent of development of eyelid skin injury. Perhaps by limiting cytokine release, cyclosporin decreased the inflammatory reaction compared to that seen with doxorubicin alone. This combination has the potential to improve patient acceptance of doxorubicin chemomyectomy for the treatment of blepharospasm and hemifacial spasm.
McLoon
L K
LK
Department of Ophthalmology, University of Minnesota, Minneapolis 55455, USA.
Ozel
B
B
Wirtschafter
J
J
D000818:Animals; D001764:Blepharospasm / Q000188:drug therapy; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004317:Doxorubicin / Q000009:adverse effects* / Q000627:therapeutic use; D005141:Eyelid Diseases / Q000139:chemically induced / Q000517:prevention & control*; D005143:Eyelids / Q000187:drug effects; D005152:Facial Muscles / Q000187:drug effects; D007267:Injections; D009121:Muscle Denervation / Q000379:methods; D009801:Oculomotor Muscles / Q000187:drug effects; D011817:Rabbits; D012867:Skin / Q000187:drug effects; D012871:Skin Diseases / Q000139:chemically induced / Q000517:prevention & control*; D013035:Spasm / Q000188:drug therapy
D004317:Doxorubicin; D016572:Cyclosporine