Tachyphylaxis With Sustained Apraclonidine Use in the Treatment of Ptosis Associated With Horner Syndrome

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Tachyphylaxis With Sustained Apraclonidine Use in the Treatment of Ptosis Associated With Horner Syndrome Jessica A. Kraker, MD, MS, Deena A. Tajfirouz, MD, M. Tariq Bhatti, MD, John J. Chen, MD, PhD A 58-year-old man presented to the neuroophthalmology clinic with several years of right eyelid droop and asymmetric pupils. Examination showed right upper eyelid ptosis and miosis of the right pupil with anisocoria that was more prominent in dark conditions (Fig. 1A); 1% apraclonidine testing reversed the anisocoria and significantly improved ptosis, confirming the diagnosis of a Horner syndrome (Fig. 1B). MRI and angiogram of the head, neck, and chest were negative for a causative lesion. He was diagnosed with an idiopathic Horner syndrome. The patient was prescribed apraclonidine drops as needed for symptomatic relief of the ptosis until planned ptosis repair in 3 months. However, the patient was lost to follow up. He returned to clinic 1 year later with unchanged right eye ptosis and miosis, as well an allergic follicular conjunctivitis (Fig. 2). He had been using apraclonidine every 4 hours for the ptosis but reported he still had ptosis despite this frequent treatment. Repeat administration of apraclonidine in clinic revealed minimal improvement in the ptosis and no reversal of the anisocoria. Because he had developed allergic conjunctivitis and the apraclonidine was not improving the ptosis, he was FIG. 1. External photograph demonstrating right eye ptosis and anisocoria before 1% apraclonidine administration (top image) and reversal of anisocoria and improvement in ptosis after 1% apraclonidine administration (bottom image). Mayo Clinic Department of Ophthalmology (JAK, DAT, MTB, JJC), Rochester, Minnesota; and Mayo Clinic Department of Neurology (MTB, JJC), Rochester, Minnesota. The authors report no conflicts of interest. Address correspondence to John J. Chen, MD, PhD, 201 1st St SW, Rochester, MN 55905; E-mail: [e-mail] Kraker et al: J Neuro-Ophthalmol 2023; 43: e245-e246 instructed to stop the apraclonidine. At his 3-month return visit, the conjunctivitis had resolved and repeated apraclonidine challenge once again reversed the anisocoria and significantly improved the ptosis. He was referred to oculoplastics for definitive ptosis repair. e245 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. External photograph demonstrating right eye allergic conjunctivitis, upper eyelid ptosis, and miosis after several months of consistent 1% apraclonidine use. Both parasympathetic activation and sympathetic denervation cause miosis. Clues that aid in the diagnosis of a Horner syndrome include greater anisocoria in dark conditions, dilation lag, absence of a ciliospinal reflex, ipsilateral facial anhidrosis with compensatory contralateral facial flushing, and pharmacologic testing with sympathetic agonists, such as apraclonidine. Apraclonidine is an adrenergic agonist with stronger affinity for a2 receptors than a1 receptors. Following sympathetic denervation, a-receptors are upregulated, causing both mydriasis, via the effect of a1 stimulation of the dilator pupillae, and lid elevation, via the effect of a2 stimulation on Müller muscle (1). This mechanism underlies the false-negative testing of a Horner syndrome if apraclonidine is administered too soon after denervation because this process takes about a week to occur (2). However, it should be noted that rare false-negatives have been reported after this period (3) and true-positives have been reported before this period (4). In addition to being helpful in confirming Horner syndrome, apraclonidine can be used as a therapeutic agent for ptosis. In our patient, application both confirmed the diagnosis with reversal of anisocoria and prompted resolution of ptosis in order to provide symptomatic relief. We report that with prolonged use, supersensitivity denervation was lost but reappeared with a drug holiday, indicating a tachyphylactic phenomenon that occurred due to physiologic downregulation of a receptors. Tachyphylaxis of apraclonidine’s effectiveness in reducing intraocular pressure has been reported previously (5). However, this is the first known report of apraclonidine tachyphylaxis in the treatment of ptosis and miosis due to Horner syndrome. Therefore, the authors recommend apraclonidine as an infrequent, short-term option for the treatment of ptosis due to idiopathic Horner syndrome for patients who do not wish to undergo surgery or as a bridge to definitive surgical ptosis repair. Although allergic conjunctivitis is relatively common with topical apraclonidine, e246 systemic toxicities of alpha agonists such as apraclonidine are rare but include central nervous system depression, hypotension, bradycardia, bradypnea, and hypothermia (5). This is usually only clinically relevant in infants, and thus, apraclonidine should not be used in infants less than 1–2 years of age, but there have been rare instances of toxicity in adults in cases of excessive use (6). Due to tachyphylactic limitation in effectiveness as well as the potential for the development of an allergic reaction, it is not recommended as a long-term treatment for ptosis unless used very infrequently. Although the frequency and duration of apraclonidine administration that is needed to develop tachyphylaxis of its effect on ptosis is not known. STATEMENT OF AUTHORSHIP Conception and design: J. A. Kraker, D. A. Tajfirouz, M. T. Bhatti, J. J. Chen; acquisition of data: J. A. Kraker, D. A. Tajfirouz, J. J. Chen; analysis and interpretation of data: J. A. Kraker, J. J. Chen; drafting the manuscript: J. A. Kraker; revising the manuscript for intellectual content: J. A. Kraker, D. A. Tajfirouz, M. Tariq Bhatti, J. J. Chen; final approval of the completed manuscript: J. J. Chen. REFERENCES 1. Morales J, Brown SM, Abdul-Rahim AS, Crosson CE. Ocular effects of apraclonidine in Horner syndrome. Arch Ophthalmol. 2000;118:951–954. 2. Gao Z, Crompton JL. Horner syndrome: a practical approach to investigation and management. Asia Pac J Ophthalmol (Phila). 2012;1:175–179. 3. Dewan MA, Harrison AR, Lee MS. False-negative apraclonidine testing in acute Horner syndrome. 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