Corticotropin releasing factor dramatically reduces inflammation at the site of local doxorubicin chemomyectomy

Purpose. The local injection of doxorubicin into the eyelid has proven to be an effective treatment for blepharospasm and hemifacial spasm. A major concern of patients continues to be the inflammation and soreness that develops over the injection site. Repeat injections also have an increased risk of skin injury. Local injection of corticotropin releasing factor (CRF) has been shown to substantially reduce acute inflammation by a variety of injuries. CRF appears to prevent the vascular leakage that occurs in tissues after injury. CRF was tested to determine if it would reduce the local inflammatory reaction caused by doxorubicin injection, and if it might help protect the eyelid skin from injury. Methods. CRF was injected into the eyelids of rabbits or monkeys 20 minutes prior to injections of 1 mg doxorubicin. Two doses of CRF were examined: 75 or 150 ug/eyelid. The animals were examined daily for skin changes. After one month, the animals were euthanized and the eyelids were examined for muscle loss. Results. CRF had a dramatic effect in reducing the inflammatory reaction in the treated eyelids. Normally, doxorubicin treated eyelids are sensitive to touch for several weeks. After CRF treatment, the eyelids could be touched with no reaction of discomfort. With doxorubicin only, all animals developed skin injury. Both doses of CRF pretreatment significantly reduced the total duration of skin injury, from one month for doxorubicin only, to about 2 weeks. CRF also caused a significant reduction in muscle loss compared to doxorubicin only in rabbits. In the monkey, CRF had no effect on muscle loss compared to doxorubicin alone. Conclusions. CRF pretreatment prior to doxorubicin injection resulted in the best treatment strategy developed thus far, as it improves muscle loss while protecting the adjacent skin. CRF pretreatment has the potential to improve patient acceptance of doxorubicin chemomyectomy for the treatment of blepharospasm and hemifacial spasm.