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Effects of Repeated Eyelid Injections with Botulinum Toxin A on Innervation of Treated Muscles in Patients with Blepharospasm

ABSTRACT Purpose: To assess changes in innervation and muscle morphology after repeated botulinum toxin A injections in subjects with benign essential blepharospasm. Methods: Surgical waste specimens were processed for histologic examination of nerve fibers, neuromuscular junctions, fiber size, and central nucleation and compared to age matched controls and to two subjects with blepharospasm that had not received botulinum toxin A injections. Results: There was a significant increase in amount of nerve fibers and numbers of neuromuscular junctions in the orbicularis oculi muscles from subjects with blepharospasm treated repetitively with botulinum toxin A. In addition there was a significant decrease in mean muscle fiber cross-sectional area and an increase in central nucleation. The specimens from the subjects with only blepharospasm had the same density of nerves but had intermediate levels of neuromuscular junctions. Conclusions: These data suggest that repeated injections of botulinum toxin A has an effect on nerve and neuromuscular junction numbers, which are partly mirrored in orbicularis oculi muscle from subjects with blepharospasm only. These studies suggest the potential for modulating these changes in order to extend the duration of effectiveness of botulinum toxin.