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Arch Ophthalmol. 2003;121:1201-1203.

In 1999, Morales et al¹ reported that 1.0% apraclonidine hydrochloride (Iopidine; Alcon, Ft Worth, Tex) could be used to diagnose Horner syndrome. Apraclonidine caused reversal of anisocoria (the miotic pupil with Horner syndrome became larger than the normal pupil) in all patients in their study. Apraclonidine is primarily an ₂-receptor agonist, but it does have some weak ₁ affinity, as evidenced by conjunctival blanching. The authors postulated that the reversal of anisocoria was due to denervation hypersensitivity of ₁-receptors in the pupil dilator muscle. The purpose of our study is to determine whether 0.5% apraclonidine, which is less expensive and more readily available than the 1.0% formulation, might also be used to diagnose Horner syndrome in the same lighting conditions.

Report of Cases
Patients with known or newly diagnosed Horner syndrome in 2 of our practices (those of R.A. and K.A.F.) were invited to participate, and institutional review board approval was obtained. Cases were consecutive, and all were confirmed by pharmacologic testing. Demographic data collected included patient age, sex, etiology and duration of Horner syndrome (if known), lesion location (preganglionic or postganglionic, if known), and results of previous pharmacologic testing.

The baseline pupil diameter was recorded in both dark and light ambient illumination using a Rosenbaum pupil card and measuring to the nearest 0.5 mm. One drop of 0.5% apraclonidine was instilled into each eye. Pupil measurements were repeated 60 minutes later.

Patient demographic information and the results of previous pharmacologic testing are summarized in Table 1. The mean patient age was 51 years (range, 39-73 years). The difference in pupil diameter for each condition tested is illustrated in Figure 1 and Figure 2. The test sensitivity was 0.88.

View this table: [in this window] [in a new window] Patient Information

View larger version (28K): [in this window] [in a new window] Figure 1. Anisocoria in dark illumination at baseline (dark gray bars) and 60 minutes after the instillation of 0.5% apraclonidine (light gray bars). Negative values indicate that the pupil with Horner syndrome is smaller than the normal pupil. Positive values indicate that the pupil with Horner syndrome is larger than the normal pupil (reversal of anisocoria).

View larger version (29K): [in this window] [in a new window] Figure 2. Anisocoria in light illumination at baseline (dark gray bars) and 60 minutes after the instillation of 0.5% apraclonidine (light gray bars). Negative values indicate that the pupil with Horner syndrome is smaller than the normal pupil. Positive values indicate that the pupil with Horner syndrome is larger than the normal pupil (reversal of anisocoria).

Comment
In 1999, Morales et al¹ sought to investigate the intraocular pressure–lowering effect of 1.0% apraclonidine on preganglionic vs postganglionic ₂-receptors. They used a small cohort of patients with Horner syndrome in which those with preganglionic lesions showed a purely postganglionic pressure response; fellow eyes served as controls. Coincidentally, a remarkable reversal of anisocoria was found in all patients.

Compared with other ₂-agonists such as brimonidine tartrate, apraclonidine appears unique in having weak but clinically detectable ₁ activity. The authors postulated that the anisocoria reversal seen in patients with Horner syndrome demonstrated denervation hypersensitivity of postsynaptic ₁-receptors in the pupil dilator muscle. This effect may be indirectly amplified by the absence of presynaptic ₂-receptor activity, which normally down-regulates the release of norepinephrine into the synaptic junction and thus decelerates ₁-stimulated mydriasis. This theory was supported by evidence obtained through an extensive review of the clinical and pharmacologic literature pertaining to the action of apraclonidine,^2-5 and readers are referred to the original article¹ for that discussion. Our study was undertaken to determine whether 0.5% apraclonidine, currently the more readily available commercial product, might also cause reversal of anisocoria in patients with Horner syndrome.

Seven of 8 patients showed a reversal of anisocoria of at least 0.5 mm in both dark and light conditions. One patient did not show reversal. Although the small sample size precludes a detailed statistical analysis, an examination of the Figures shows that patients with a greater degree of anisocoria generally showed a greater degree of reverse anisocoria after apraclonidine instillation. This may reflect a greater or more long-standing degree of denervation and therefore of ₁-receptor hypersensitivity. It is not possible to correlate the degree of reversal with the location and duration of the lesion because both were unknown in several patients in this small series.

Clinically the anisocoria reversal, even when slight, was easily detected with the naked eye. Testing for Horner syndrome using 0.5% apraclonidine does not depend on highly accurate measurements of the pupil diameter and is unlikely to be confounded by physiologic variation in pupil size or mild differences in room illumination before and after apraclonidine administration. Topical cocaine hydrochloride and hydroxyamphetamine hydrobromide are increasingly difficult and costly to obtain and are rarely used for any purpose by ophthalmologists other than to diagnose Horner syndrome. Within our admittedly small cohort, we have demonstrated that 0.5% apraclonidine, which is readily available in a multidose preserved bottle, is an acceptably sensitive test for the detection of this infrequent condition. Even though the mechanism of action is different, we propose that 0.5% apraclonidine may be substituted for cocaine in the pharmacologic confirmation of Horner syndrome. For localization of the sympathetic lesion, hydroxyamphetamine is still required. If apraclonidine does not cause anisocoria reversal and there is an important therapeutic need to pharmacologically confirm the diagnosis, further assessment with the classic agents should be conducted.

AUTHOR INFORMATION
Drs Brown, Aouchiche, and Freedman have no relevant financial interest in this article.

Sandra M. Brown, MD
Lubbock, Tex

Rachid Aouchiche, MD
Ft Myers, Fla

Kenn A. Freedman, MD
Lubbock

Corresponding author: Sandra M. Brown, MD, 3601 Fourth St, Stop 7217, Lubbock, TX 79430 (e-mail: sandra.brown{at}ttuhsc.edu).

REFERENCES
1. Morales J, Brown SM, Abdul-Rahim AS, Crosson CE. Ocular effects of apraclonidine in Horner syndrome. Arch Ophthalmol. 2000;118:951-954. FREE FULL TEXT 2. Miller PE, Rhaesa SL. Effects of topical administration of 0.5% apraclonidine on intraocular pressure, pupil size, and heart rate in clinically normal cats. Am J Vet Res. 1996;57:83-86. PUBMED 3. Langham ME, Weinstein GW. Horner's syndrome: ocular supersensitivity to adrenergic amines. Arch Ophthalmol. 1967;78:462-469. ISI | PUBMED 4. Korczyn AD. Adrenergic denervation supersensitivity. Adv Neurol. 1975;9:113-120. PUBMED 5. Crosson CE, Heath AR, DeVries GW, Potter DE. Pharmacological evidence for heterogeneity of ocular alpha 2 adrenoceptors. Curr Eye Res. 1992;11:963-970. ISI | PUBMED

SECTION EDITOR: W. RICHARD GREEN, MD

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