Ultrastructural changes in myotendinous nerve endings induced by injection of botulinum toxin into the extraocular muscle

Background: The myotendinous nerve endings located in the extraocular muscles are considered as proprioceptors. The proprioception of extraocular muscles can be altered if botuminium toxin, which is widely used for the treatment of strabismus, damages the endings. The purpose of this study is to investigate the ultrastructural changes in myotendinous nerve endings after injection of botulinum toxin into the extraocular muscles. Methods: Under general anesthesia, 5 IU of botulinum toxin (0.1 ml) were injected into the superior and medial rectus muscles of one eye in each of 12 cats, and 0.1 ml of normal saline was injected into the muscles of the other eye. The myotendinous junction was harvested in four cats each at 1, 4, and 12 weeks after injection and examined using electron microscopy. The myotendinous junctions of four normal uninjected cats were also examined as a control group. Results: There were no morphological differences between the control group and saline injection group. In the botox injection group, separation of the myelin sheath and an increase in neurofilaments in axons of myelinated and unmyelinated nerve fibers were observed 1 week after injection and persisted until 12 weeks. Around the terminal nerve endings, incomplete Schwann cells with axonal exposure were observed, and fibroblast-like changes in Schwann cells were detected. These findings were not observed in the control group. Conclusions: Injection of botulinum toxin into the extraocular muscle induced ultrastructural changes in the myotendinous nerve endings. The possibility that those changes might diminish the proprioceptive abilities of the extraocular muscle should be considered when botulinum toxin is used for the treatment of strabismus.