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B. A. Francis, E. L. Chang, J. D. Weiland, N. A. Sachs; Benzalkonium Chloride Induces Denervation of Orbicularis Oculi Muscle in Rabbits. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6325.
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To examine the potential for benzalkonium chloride (BAK) to cause denervation of the orbicularis oculi muscle in a rabbit model.
Pigmented rabbits were separated into 4 distinct groups. Group 1 consisted of 5 rabbits injected with 1 cc of BAK 0.5% in the orbicularis muscle of the upper eyelid. Group 2 consisted of 5 rabbits injected with 1 cc of BAK 0.25%. Group 3 consisted of 5 untreated rabbits. Group 4 was used to create the model for denervation testing and consisted of 20 rabbits with surgical severing of the facial nerve (to cause complete paralysis). A subcutaneous stimulating electrode was implanted in the upper eyelid, and biphasic controlled stimulation pulses were delivered. Strength-duration curves for lid twitch threshold were measured to determine the muscle activity and innervation status using methods described previously. Groups 1 and 3 were stimulated at 4 weeks post-injection and Group 2 rabbits at 1 week. Group 4 rabbits were stimulated at 1, 4, 8, and 16 weeks (n=5 each). The rabbits were sacrificed and the eyelids sent for histological analysis.
Group 4: The surgical paralysis model showed that at first total denervation occurs, but slowly reverses with regeneration of the facial nerve. Group 1: One rabbit developed an abscess at the injection site and was sacrificed at 1 week. The remaining four rabbits showed approximately 75% mean denervation of the orbicularis. Two showed complete denervation and two showed partial denervation with partial regeneration of muscle activity. Group 2: All five rabbits demonstrated almost complete denervation of the orbicularis oculi in the injected area. Group 3: All five rabbits showed normal orbicularis function. The histology of Groups 1, 2 and 4 (1, 4 weeks) demonstrated marked atrophy of the orbicularis oculi muscle when compared to controls.
Injection of BAK at moderate doses into the orbicularis muscle caused complete denervation and dysfunction of the muscle in our rabbit model. The amount of denervation was similar to those in which the facial nerve was surgically severed. There was partial recovery of nerve function at the longer (4 week) time point due to partial nerve regeneration. This is the first demonstration of denervation of skeletal muscle caused by this commonly used ophthalmic drug preservative. The clinical relevance of this finding may be the onset of lagophthalmos and eyelid retraction in patients with chronic BAK exposure.
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