Treatment of Ptosis Using Brimonidine Tartrate for Anterior Laminectomy-Induced Horner Syndrome

Horner syndrome is characterized by the presence of a lesion at any location along the oculosympathetic pathway. It is clinically characterized by ipsilateral pupillarymiosis, facial anhidrosis, ipsilateral upper eyelid ptosis, and mild lower eyelid elevation.

Clinical Correspondence Treatment of Ptosis Using Brimonidine Tartrate for Anterior Laminectomy-Induced Horner Syndrome Ahmad Rehmani, DO, Isha Mehta, DO, Edward Smith, MD H orner syndrome is characterized by the presence of a lesion at any location along the oculosympathetic pathway. It is clinically characterized by ipsilateral pupillary miosis, facial anhidrosis, ipsilateral upper eyelid ptosis, and mild lower eyelid elevation. The course of sympathetic fibers destined for Muller's muscle in the upper eyelid is divided into first-, second-, and third-order segments. After leaving the area of the innominate artery on the right and the subclavian artery on the left just above the lung apex (around the level of the first and second thoracic spinal cord segments, T1/T2), postsynaptic second-order fibers pass through the inferior and middle cervical ganglia to terminate in the superior cervical ganglion at the level of the angle of the jaw (cervical spinal cord level C2) and carotid artery bifurcation. Postganglionic third-order fibers then ascend superiorly in the wall of the bifurcated carotid arteries, continue along the internal carotid artery (ICA) entering the cranium through the carotid canal into the cavernous sinus. Here, fibers leave the ICA to join the oculomotor nerve and course forward with the superior division of the oculomotor nerve as it passes through the orbital apex. The fibers then reach their final destination to innervate Muller's muscle. This muscle provides 1-3 mm of upper eyelid elevation (1). The use of selective alpha-2 agonists for improvement of Muller's muscle-related ptosis has been reported in the past with the use of apraclonidine (2,3). It is believed that, due to its mechanism of action, brimonidine cannot have this same effect as apraclonidine. However, here, we present a case of Horner syndrome- induced ptosis after anterior laminectomy; the signs improved with the instillation of brimonidine tartrate. CASE A 52-year-old woman with degenerative cervical spondylosis underwent anterior cervical discectomy and fusion. She presented 2 weeks later with right-sided ptosis. The patient stated that her right eyebrow was elevated, and that she noticed more wrinkles on the right side of her face. Other Department of Ophthalmology, Kingsbrook Jewish Medical Center, Brooklyn, New York. The authors report no conflicts of interest. Address correspondence to Ahmad Rehmani, DO, Department of Ophthalmology, Kingsbrook Jewish Medical Center, 327 Beach 19th Street, Far Rockaway, NY 11691; E-mail: [e-mail] Rehmani et al: J Neuro-Ophthalmol 2020; 40: 95-96 significant medical history included stage 0 breast cancer with lumpectomy and radiation 3 years earlier. The patient was taking no medications and had no ocular history. Visual acuities at presentation were 20/20 in both eyes. The pupillary examination revealed anisocoria, specifically miosis in the right eye that was more pronounced in dim illumination. No afferent pupillary defect was noted. Pupillary measurements in light conditions were 2.5 mm on the right and 3.5 mm on the left; in dark conditions, the pupils measured 2.5 mm on the right and 5.5 mm on the left. The external examination was significant for right ptosis with marginal reflex distances of 3 mm on the right and 5.5 mm on the left. The slit-lamp and fundus examinations were otherwise normal. Intraocular pressures were 10 mm Hg on the right and 12 mm Hg on the left; cup-to-disc ratios were 0.35. Right facial anhidrosis was noted. The patient was diagnosed with a right-sided Horner syndrome (Fig. 1). She was most bothered by the right upper eyelid ptosis but was advised that it would be observed for 6 months before considering surgical repair. In the interim, a trial of topical brimonidine tartrate 0.1% ophthalmic drops was started. The patient experienced immediate and dramatic improvement in the right ptosis (Fig. 2). She was given brimonidine tartrate 0.1% twice daily to treat the unilateral ptosis. On subsequent examination, the pupillary measurements were also remarkably more symmetric. Six weeks after her initial visit, while still using topical brimonidine tartrate, the patient's pupillary measurements in light conditions were 3 mm on the right and 4 mm on the left; in dark conditions were 4 mm on the right and 5 mm on the left. Marginal reflex distances were 5 mm on the right and 6 mm on the left. At a 3-month follow-up visit, the patient still experienced this improvement and also began to notice re-establishment of hidrosis on the right side of her face. The patient never experienced changes in vision, photophobia, glare, or halos while taking the brimonidine tartrate. DISCUSSION Classically, apraclonidine, an alpha-2 adrenergic agonist with weak alpha-1 adrenergic agonist activity is used in the diagnosis of Horner syndrome. Known as "relatively selective," its alpha-2 receptor activity predominates in a normal 95 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Clinical photograph at presentation illustrating right side upper eyelid ptosis and pupillary miosis associated with acute Horner syndrome. FIG. 2. Clinical photograph after instillation of topical brimonidine tartrate, demonstrating improvement in ptosis and miosis. physiologic state. In the Horner pupil, the alpha-1 agonist effect of apraclonidine predominates because of supersensitivity of alpha-1 receptors. This leads to pupillary mydriasis on instillation through contraction of the iris dilator muscles (1). In the same drug class, brimonidine tartrate is considered to be an even more highly selective alpha-2 agonist. It is 1,000-fold more selective for the alpha-2 agonist receptor (approximately 2 nM) than the alpha-1 agonist receptor (approximately 2000 nM) (4). This is why brimonidine tartrate is classically not believed to be effective for Horner syndrome-related ptosis. Immunohistopathologic examination of Muller's muscle by Skibell et al shows the presence of alpha-1D, alpha-2C, and beta-2 receptors, with a predominance of the alpha-1D receptors. Furthermore, the muscles examined exhibited different ratios of the 3 adrenergic receptors from specimen to specimen (3). This variability in concentrations of the adrenergic receptors could play a role in their response to apraclonidine vs brimonidine tartrate (2). Since alpha-2 receptor agonists inhibit the release of norepinephrine, they work in direct contrast to alpha-1 receptor activity located at the postsynaptic junction, which upregulate synaptic response resulting in eyelid elevation. In our patient, an immediate improvement in eyelid position was noted after instillation of 1 drop of brimonidine tartrate. Thus, it is likely that our patient not only had significant supersensi- tivity of alpha-1 receptors, but also likely had an increase in the ratio of alpha-1D to alpha-2C receptors. In terms of adverse effects, when compared with apraclonidine, brimonidine tartrate results in no mydriasis and no vasoconstriction in microvessels (4). Our patient had no visual complaints or side effects while taking brimonidine tartrate for her ptosis. Thus, we recommend consideration of brimonidine tartrate in patients with Horner syndrome who have of symptomatic ptosis. Brimonidine tartrate is not FDA-approved for correction of ptosis at this time; however, our report suggests that this agent may be helpful. 96 REFERENCES 1. Loewenfeld E. The Pupil: Anatomy, Physiology, and Clinical Applications. 2nd edition. New York, NY: ButterworthHeinemann, 1999. 2. Kirkpatrick CA, Shriver EM, Clark TJE, Kardon RH. Upper eyelid response to topical 0.5% apraclonidine. Ophthalmic Plast Reconstr Surg. 2018;34:13-19. 3. Skibell BC, Harvey JH, Oestreicher JH, Howarth D, Gibbs A, Wegrynowski T, Wing T, DeAngelis DD. Adrenergic receptors in the ptotic human eyelid: correlation with phenylephrine testing and surgical success in ptosis repair. Ophthalmic Plast Reconstr Surg. 2007;23:367-371. 4. Allergan. ALPHAGAN Brimonidine Tartrate Datasheet Version 4.0. Auckland, New Zealand: Allergan New Zealand Ltd, 2014. Available at: https://allergan-web-cdn-prod.azureedge.net/ allergan/allergannewzealand/media/allergannewzealand/ products/alphagan-nzds_dec14.pdf Rehmani et al: J Neuro-Ophthalmol 2020; 40: 95-96 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.