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Eyedrop testing in Horner Syndrome

Eyedrop testing in Horner Syndrome. Eugene F. May, MD Neuro-ophthalmic Consultants Northwest Seattle Neuroscience Institute at Swedish Medical Center University of Washington Seattle, WA. Horner JF. Über eine Form von Ptosis. Klinische Monatsblätter für Augenheilkunde. 1869;7:193-198.

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Eyedrop testing in Horner Syndrome

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  1. Eyedrop testing inHorner Syndrome Eugene F. May, MD Neuro-ophthalmic Consultants Northwest Seattle Neuroscience Institute at Swedish Medical Center University of Washington Seattle, WA

  2. Horner JF. Über eine Form von Ptosis. Klinische Monatsblätter für Augenheilkunde. 1869;7:193-198. • No references • Described by Claude Bernard (1850) • Described by Francois Pourfour de Petit (1727)

  3. Anatomy

  4. Pharmacology

  5. Findings • Ptosis • upper eyelid ptosis • inverse ptosis • narrowing of the palpebral fissure • facial anhidrosis • miosis • > 1.0 mm • dilatation lag • any combination of the above • van der Wiel HL The diagnosis of Horner’s syndrome. Clin Neurol Neurosurg. 1988;90:103-108.

  6. Miosis • Ptosis • iris constrictor unopposed • 1 - 1.5 mm miosis • greatest in dim illumination • dilation lag • pupil dilation is passive

  7. Is there a chance combination of the ptosis and miosis? • No anhidrosis • No associated neurologic symptoms or findings

  8. Historical Background • Dilute epinephrine test • Cocaine test • Hydroxyamphetamine test • Apraclonidine test

  9. Cocaine test • Cocaine hydrochloride, 10% • one or two drops in each eye • perhaps several minutes apart • measure pupil size before and 50-60 minutes later • maintain stable ambient lighting (what level?) • control near response • ?measure post-drop anisocoria • ?measure change in anisocoria pre- vs. post-drop

  10. Cocaine test • Normal eyes • post-cocaine anisocoria < 0.5 mm • pupils of Afro-americans react poorly to cocaine • Friedman JR et al. The cocaine test in normal patients. Am J Ophthalmol. 1984;98:808-810 • Horner syndrome • anisocoria of 1.0 mm or more is consistent • normal result does not exclude Horner’s • Van der Wiel HL, Van Gijn J. The diagnosis of Horner’s syndrome: use and limitations of the cocaine test. J Neurol Sci. 1986;74:311-316.

  11. Cocaine test • Chances of a Horner syndrome increase with anisocoria • anisocoria of 0.8 mm = odds ratio of 1050:1 • anisocoria of 1.0 mm = odds ratio of 6000:1 • but measured anisocoria of up to 0.9 mm in normals • anisocoria as little as 0.3 mm in Horner group Kardon RH et al. Critical evaluation of the cocaine test in the diagnosis of Horner’s syndrome. Arch Ophthalmol. 1990;108:384-387.

  12. Cocaine test • Absolute anisocoria more predictive than change in anisocoria • less overlap between groups • physiologic anisocoria • anisocoria actually decreased in most Kardon RH et al. Critical evaluation of the cocaine test in the diagnosis of Horner’s syndrome. Arch Ophthalmol. 1990;108:384-387.

  13. Cocaine testAlternatives • Why not cocaine? • difficult to obtain (?) • expensive (?) • short shelf life (?) • parents hesitant (?) • positive urine test (?)

  14. Cocaine testAlternatives • Apraclonidine 0.5%, 1% (Iopidine) • α2 > α1 adrenergic agonist • approved for treatment of IOP after trabeculoplasty • receptors upregulate after 5-8 days • reversal of anisocoria in several studies • 0.5% and 1.0% • denervation supersensitivity • actively dilates the abnormal pupil

  15. Apraclonidine • Studies show good sensitivity • 1.00 (1%) and 0.88 (0.5%) • Morales J et al. Arch Ophthalmol. 2000;118:951-954. • Brown SM et al. Arch Ophthalmol. 2003;121:1201-1203. • physiologic anisocoria: no reversal of anisocoria • Comparison studies • 0.5% vs 4% cocaine in children • equally sensitive • Chen P et al. J Ocular Pharm and Therapeutics. 2006;22:182-187.

  16. Apraclonidine • must have high level of illumination • sometimes normal pupil dilates

  17. Apraclonidine • Side effects • in children with glaucoma • apnea, bradycardia, hypotension, somnolence, fatigue • in children with Horner syndrome • conjunctival hyperemia • sleepiness

  18. Localization

  19. Hydroxyamphetamine test • Pivotal study • more reliable than dilute epinephrine testing • Thompson HS and Mensher JH. Adrenergic mydriasis in Horner’s syndrome. Hydroxyamphetamine test for diagnosis of postganglionic defects. Am J Ophthalmol 1971;72:472-480.

  20. Hydroxyamphetamine test • Post-drop anisocoria • difference in dilation • 1.0 mm: 85% chance of post-ganglionic lesion • 1.5 mm: 96% chance of post-ganglionic lesion Cremer SA, et al. Hydroxyamphetamine mydriasis in Horner’s syndrome. Am J Ophthalmol. 1990;110:66-70.

  21. Hydroxyamphetamine test • Problems • range of variability exists • even in normals • Cremer et al. Hydroxyamphetamine mydriasis in normal subjects. Am J Ophthalmol. 1990;110:66-70. • extent of deficit influences test results • false negative in acute Horner’s • one week before NE stores are exhausted • must wait two days after cocaine test

  22. Hydroxyamphetamine test • False positive • if second and third order neuron involved • extensive tumor • radiation • blood supply to the SCG arises lower in the neck • congenital • trans-synaptic degeneration of 2o neuron

  23. Hydroxyamphetamine testAlternatives • Hydroxyamphetamine not always available • Denervation supersensitivity • Dilute epinephrine • 55% false positives • 61% false negatives • Hydroxyamphetamine • 16% false positives • 4% false negatives • Maloney WF, et al. Am J Ophthalmol. 1980;90:394-402.

  24. Hydroxyamphetamine testAlternatives • Dilute (1%) phenylephrine • sensitivity 81%; specificity 100% • effects vary according to integrity of corneal epithelium • hydroxyamphetamine not dose-dependent • partial postganglionic lesion may not be distinguished from preganglionic lesion Danesh-Meyer HV et al. The correlation of phenylephrine 1% with hydroxyamphetamine 1% in Horner’s syndrome. Br J Ophthalmol. 2004;88:592-3.

  25. Hydroxyamphetamine testAlternatives • Problems with supersensitivity testing • dilution of eyedrop • degree of supersensitivity • preganglionic lesions cause relative supersensitivity • dilute solutions more dependent on corneal parameters • supersensitivity of the iris dilator increases with age

  26. Hydroxyamphetamine testAlternatives • Not generally available in US: • Tyramine hydrochloride (5%) • Hydroxymethylamphetamine (Pholedrine)

  27. Conclusions • A combination of characteristic symptoms and signs allows a diagnosis of Horner syndrome

  28. Conclusions • Cocaine testing is the eyedrop test of choice for diagnosing anisocoria due to Horner syndrome • 1.0 mm anisocoria after the eyedrops is a useful cutoff • apraclonidine testing is very helpful and the eyedrop is more readily available • bright light

  29. Conclusions • Hydroxyamphetamine testing helps localize the Horner syndrome to the third order neuron • 1.0 mm difference in dilation a useful cutoff • beware of false positives • dilute phenylephrine if hydroxyamphetamine not available

  30. Thank you!

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