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The teardrop sign: a rare dermatological reaction to brimonidine
  1. Department of Ophthalmology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
  1. Michael C Brodsky, MD, Arkansas Children's Hospital, 800 Marshall, Little Rock, AR, 72202, USA brodskymichaelc{at}

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Editor,—Brimonidine is a potent, highly selective α2 adrenergic agonist used for the treatment of open angle glaucoma and ocular hypertension. It lowers intraocular pressure by decreasing aqueous humour production and increasing uveoscleral outflow.1 2 The most common ocular and periocular side effects of brimonidine include ocular hyperaemia, itching, burning, or stinging; foreign body sensation, blurred vision, allergic, toxic, or follicular conjunctivitis, and lid hyperaemia.3 The following case describes a previously unreported periocular reaction to this medication.


A 23 year old white man with cerebral palsy, autism, and chronic open angle glaucoma had been treated with brimonidine 0.2% ophthalmic solution for 5 months when erythematous cheeks were first noted. The patient's grandmother questioned the schoolteachers about his sun exposure and requested that sunblock be applied each day before outdoor activities to prevent what she thought was a sunburn. Later, after bilateral application of brimonidine eyedrops, the patient's cheeks blanched in a streak pattern where runoff of the excess eyedrop occurred (Fig 1). His cheeks became red and his conjunctiva became hyperaemic. These effects lasted throughout the day. They recurred with subsequent brimonidine administration and later resolved upon discontinuation of the drug.

Figure 1

Linear skin blanching (arrows) after administration of brimonidine eyedrops.

To further investigate this unusual dermatological reaction, a brimonidine eyedrop was placed on the patient's cheek in a circular pattern. The contact area blanched almost immediately. The blanching intensified over a period of 30 minutes, and erythema developed in the surrounding skin. The blanching and erythema lasted approximately 20 hours before it began to fade. Complete resolution occurred by 22 hours. Another drop of brimonidine produced a similar regional blanching with surrounding erythema when placed on the patient's back.


Although brimonidine is almost 1000-fold more selective for the α2 than the α1 receptor subtype, its ability to cause vasoconstriction and reactive hyperaemia demonstrates that it has some α1 mediated effects.1Brimonidine is 23–32-fold more α2 selective than apraclonidine, and conjunctival blanching has been reported as an infrequent local effect of brimonidine, whereas it is seen in up to 85% of patients using apraclonidine.4 5

Our patient demonstrated a pronounced α1 mediated vascular reaction of the periocular skin. Brimonidine caused skin blanching and a surrounding hyperaemia that was not limited to the trail of the teardrop, but included the entire cheek. While the half life of intraocular pressure lowering effect of brimonidine is only 8–12 hours, the dermal vasoconstrictive effect of the drug persists for almost 24 hours.


Supported in part by a grant from Research to Prevent Blindness.