Topical apraclonidine in the diagnosis of suspected Horner syndrome

Abstract

Topical cocaine is used to confirm the clinical diagnosis of ocular sympathetic denervation, or Horner Syndrome (HS). Cocaine blocks re-uptake of norepinephrine (NE) by sympathetic nerve terminals in the iris dilator muscle, transiently increasing its concentration in the synaptic junction. Norepinephrine activates alpha1 receptors in the iris dilator to cause pupil dilation. In HS, cocaine fails to dilate the affected pupil as much as the unaffected pupil, but its indirect action makes it a weak dilator, and the test can give equivocal results. Cocaine is also a controlled substance and therefore difficult to obtain. A practical and reliable alternative to cocaine is apraclonidine, an ocular hypotensive agent that has a weak direct action on alpha1 receptors and therefore minimal to no clinical effect on the pupils of normal eyes. Patients with HS have denervation supersensitivity of the alpha1 receptors in the iris stroma of the affected eye, making the pupil dilator responsive to apraclonidine. In patients with HS, reversal of anisocoria occurs after bilateral instillation of apraclonidine 1% or 0.5%. Two cases that demonstrate this effect are reported. Apraclonidine should be considered a candidate to replace cocaine in the pharmacologic diagnosis of HS if a gold-standard comparison study confirms these results.