Short ReportsAdverse effects of apraclonidine used in thediagnosis of Horner syndrome in infantsPatrick Watts, FRCOphth,a Denise Satterfield, MD,b and May Kim Lim, MRCOphtha

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Apraclonidine, a selective �2-agonist, was developed to lotraocular pressure and minimize the systemic side effectsated with the use of its parent drug, clonidine.1 An investigthe site of action of apraclonidine incidentally uncovered aof anisocoria in patients with absent sympathetic innervatiopupil (Horner syndrome) due to its �1-effect on a pupil witvation supersensitivity.2 It has been used as a diagnosticHorner syndrome.3,4 We report adverse effects of topicclonidine when used in the diagnosis of Horner syndrome in

Case Reports

A 5-month-old infant girl was noted to have aria from the age of 4 weeks. On examinationdark, her pupils measured 5 mm in the righ

mm in the left eye. In light, the pupils were equal ain both eyes. One drop of 1% apraclonidine hydroc(Alcon Laboratories UK, Ltd.) was instilled in eaOn review 1 hour later, there was no reversalanisocoria; however, there was blanching of the perskin, and the parents reported that the infant wassively drowsy. Two hours after instillation of thethe infant was taken to the emergency department,she was found to be lethargic and difficult to rousbradycardia (84/min), shallow respiration (40/min)blood pressure of 115/85. Her oxygen saturation wbut improved rapidly to 100% with oxygen given vimask. Eight hours after instillation of drops, her costabilized and her vital signs returned to normal.

Following the experience with the above casmembers of the pediatric ophthalmology Internetsion group were asked for their experience in the fa questionnaire on side effects associated with the

Author affiliations: aDepartment of Ophthalmology, University Hospital of WCardiff, United Kingdom; and bDepartment of Ophthalmology, University ofCalifornia, Davis, California

Presented at the 32nd Annual Meeting of the American Association for PedOphthalmology and Strabismus, Keystone, Colorado, March 15-19, 2006.

Institution at which work was carried out: Department of Ophthalmology, UHospital of Wales, Cardiff CF14 4XW, UK.

The authors have no financial conflict of interest regarding the subject mattwork.

Submitted February 28, 2006.Revision accepted February 24, 2007.Reprint requests: Patrick Watts, Department of Ophthalmology, University

of Wales, Cardiff CF14 4XW, UK (email: patrickowatts@yahoo.co.uk).J AAPOS 2007;11:282-283.

Copyright © 2007 by the American Association for Pediatric OphthalmologStrabismus.

1091-8531/2007/$35.00 � 0doi:10.1016/j.jaapos.2007.02.015

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apraclonidine in the diagnosis of Horner syndroinfants.

Nine replies were received. In three cases, therno recognized side effects associated with theapraclonidine for the diagnosis of Horner synTwo cases were reports of adverse events witmonidine, a related �2-agonist, when used in thement of glaucoma.

Four infants were noted to have extreme droafter the instillation of apraclonidine for the diagnHorner syndrome. In three cases the patients wethan 6 months old, drowsiness was the only reporteffect, vital signs were not monitored, and nodetails could be recalled. The fourth case was a 10old infant girl who was given one drop of apraclo0.5% in each eye. One hour later, she became dunresponsive, and difficult to rouse. Her respiratowas 48 per minute; her heart rate was 158 per minuoxygen saturation was 100%. The unresponsivenesfor 10 hours.

In the two cases where details were recorded theno reversal of anisocoria, and urinary tests foecholamines were negative.

DiscussionThe index case and four additional cases of adverstions to apraclonidine used for the diagnosis of Hsyndrome in infants were identified through an Iinquiry. In three cases drowsiness was reported; twrequired emergency admission for unresponsivenescase was associated with bradycardia, hypertensiodecreased oxygen saturations.

Excessive sleepiness and lethargy has recently bported in 76% of children treated with brimonisimilar drug.5 In that report, a number of childrebeing treated with apraclonidine in addition tmonidine; hence, it is not clear what proportion oadverse effects could be attributed to apraclonidiadverse events have been reported with a single dapraclonidine when used in the diagnosis of Hsyndrome.

Cocaine eyedrops have been conventionally usedtablish a diagnosis of Horner syndrome, with hydrophetamine being used to differentiate between a ppostganglionic lesion.6,7 Cocaine is a controlled dris often difficult to acquire at short notice in busy prThe easy availability of apraclonidine, its mild �1-

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Volume 11 Number 3 / June 2007 Watts, Satterfield, and Lim 283

aged its use as a first-line drug in the diagnosis ofsympathetic paralysis.

The reported adverse effects included in thissuggest that apraclonidine should be used with caunot at all, in infants under the age of 6 months. Threduced concentration of apraclonidine (0.5%) is afective in the diagnosis of Horner syndrome,8 itimmaturity of the blood-brain barrier in young infanpermits central nervous system depression suggestipatients may still be at risk.9 If apraclonidine must bin infants younger than 6 months of age, the patientbe observed for a period of at least 2 hours after instof the drops, with admission to a pediatric ward proby lethargy, bradycardia, or a reduced respiratory

References1. Abrams DA, Robin AL, Pollack IP, deFaller JM, DeSantis L. T

and efficacy of topical 1% ALO 2145 ( p-aminoclonidine hydro

in normal volunteers. Arch Ophthalmol 1987;105:1205-7.

Journal of AAPOS

-

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tye)

2. Morales J, Brown SM, Abdul-Rahim AS, Crosson CE. Oculof apraclonidine in Horner syndrome. Arch Ophthalmol 2951-4.

3. Brown SM, Aouchiche R, Freedman KA. The utility of 0.5clonidine in the diagnosis of horner syndrome. Arch Op2003;121:1201-3.

4. Bacal DA, Levy SR. The use of apraclonidine in the diagHorner syndrome in pediatric patients. Arch Ophthalmol 2276-9.

5. Al-Shahwan S, Al-Torbak AA, Turkmani S, Al-Omran M, AI, Edward DP. Side-effect profile of brimonidine tartrate inOphthalmology 2005;112:2143.

6. Thompson HS, Mensher JH. Adrenergic mydriasis in Horndrome. Hydroxyamphetamine test for diagnosis of postgdefects. Am J Ophthalmol 1971;72:472-80.

7. Thompson HS. Pharmacologic localization in Horner’s syAm J Ophthalmol 1981;91:416-7.

8. Brown SM. The utility of 0.5% apraclonidine in the diagHorner syndrome. Arch Ophthalmol 2005;123:578; author r

9. Stewart PA, Hayakawa EM. Interendothelial junctional chaderlie the developmental ‘tightening’ of the blood-brain barri

Res 1987;429:271-81.

An Eye on the Arts – The Arts on the Eye

In his laboratory at St. Mary’s Hospital, Dr. Willcox mixed a bit of his alkaloid extractinto a solution and, with the help of an assistant, placed a couple of droplets into the cat’seye. Moments later the cat’s pupil expanded to many times its ordinary size. This was animportant clue, for it meant the substance he isolated was “mydriatic”, that is, it had thepower to dilate pupils.

He knew of only four alkaloidal poisons with that power: cocaine, atropine, and twoderivatives of henbane, hyocyamine and hyocine. He shined the bright light directly intothe cat’s eyes and found that the pupil held its new diameter. This allowed him to rule outcocaine, because its mydriatic powers were less pronounced. When exposed to a powerfullight, a pupil dilated with cocaine will still contract.

—Erik Larson (from Thunderstruck, Crown Publishers, 2006)