Effects of repeated botulinum toxin injections on orbicularis oculi muscle

Histologic evaluation was conducted on 12 orbicularis oculi specimens from 11 patients with essential blepharospasm and Meige's disease who had received an average of 11.3 injections of botulinum A toxin over 3.5 years. Denervation was demonstrated by the spread of acetylcholinesterase staining on muscle fibers when specimens were evaluated within 11 weeks of the last injection. When specimens were taken after 12 weeks, spread of acetylcholinesterase was confined to the neuromuscular junctions, with little fiber size variability resembling normal muscle. Fibrosis seen in three specimens could be correlated to prior surgery. Repeated injections of botulinum toxin into human muscle do not appear to cause irreversible muscle atrophy or other degenerative changes. Denervation changes (fiber size variability, acetylcholinesterase spread) appear to correlate to the time interval since the last injection.