Beware of neurogenic keratoconjunctivitis sicca caused by otic medications

Neurogenic keratoconjunctivitis sicca (nKCS) is a rare form of dry eyes caused by the loss of efferent innervation to the lacrimal gland.¹ Due to the anatomic route of the facial nerve through the middle ear, otitis media is associated with the development of nKCS. Components of long-lasting otic medications have been shown to cause damage to the tympanic membrane or inner ear.²

A study published in the Journal of the American Veterinary Medical Association(JAVMA) indicates that nKCS in dogs is a potential adverse effect of otitis externa medications containing terbinafine and florfenicol.³ The study enrolled 29 client-owned dogs to characterize the clinical course and long-term prognosis of a suspected novel cause of nKCS secondary to florfenicol, terbinafine hydrochloride, mometasone furoate (Claro and Neptra) or florfenicol, terbinafine, betamethasone acetate (Osurnia). The study included dogs that had onset of clinical signs of nKCS within 1 day after application of otitis externa medications containing terbinafine and florfenicol and had documentation of low Schirmer tear test value (<15 mm/min) of affected eyes.

The study found that documented return of clinically normal tear production was identified in 24 of 29 dogs, with a median time from the application of ear medication to documented return of clinically normal tear production of 86 days (range, 19 to 482 days). The researchers diagnosed corneal ulcers in 20 out of 29 dogs (68%). Dogs that developed nKCS within 1 day after application of otitis externa medications containing terbinafine and florfenicol had a good prognosis for return of normal tear production within 1 year.

Nineteen of the dogs in this study received pilocarpine, the traditional choice for nKCS treatment. It stimulates the lacrimal gland to produce tears during the period when the nerve is not functioning. This alleviates the clinical signs of nKCS that result in discomfort and corneal damage but does not have any therapeutic benefit in improving nerve damage. Most dogs in this study regained normal tear function whether pilocarpine was prescribed, and there was no significant difference in time from ear medication administration to documentation of normal tear production.

Researchers strongly recommend that veterinarians comply with label recommendations and perform an evaluation of the tympanic membrane prior to application of otitis externa medications containing terbinafine and florfenicol, and to advise clients to monitor for signs of nKCS following administration. Clinical signs include blepharospasm, ocular discharge, third eyelid elevation, conjunctivitis, or a dry naris, often with dry, crusted debris partially occluding the ipsilateral nostril. If observed, the authors recommend immediate reexamination with STT and fluorescein staining, as rapid progression to sight-and globe-threatening ulceration is possible. Cleaning of the medication from the ear canal is recommended to prevent further absorption of the medication if clinical signs of nKCS are noted.

If a corneal ulcer is diagnosed, topical ophthalmic antimicrobials and systemic analgesics are recommended. Evaluation for concurrent neurologic abnormalities should be pursued and clients should be advised that those that develop deep corneal ulcers may have longer healing times. Referral to an ophthalmologist for surgical stabilization of the cornea is recommended if deep corneal ulcers are noted.

Callahan is a 2023 PharmD candidate at the University of Connecticut.

References

1. Webb AA, Cullen CL. Neuro-ophthalmology. In: Gelatt KN, Ben-Shlomo G, Gilger BC, Hendrix DVH, Kern TJ, Plummer CE, eds. Veterinary Ophthalmology. 6th ed. Vol 2. Wiley Blackwell; 2021:2285–2286.
2. Garosi LS, Lowrie ML, Swinbourne NF. Neurological manifestations of ear disease in dogs and cats. Vet Clin North Am Small Anim Pract. 2012;42(6):1143-1160. doi:10.1016/j.cvsm.2012.08.006
3. Bercovitz GR, Gaerig AM, Conway ED, et al. Long-lasting otic medications may be a rare cause of neurogenic keratoconjunctivitis sicca in dogs. J Am Vet Med Assoc. 2022;261(1):97-103. Published 2022 Nov 8. doi:10.2460/javma.22.07.0301