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Eyedrop testing in Horner Syndrome Eugene F. May, MD Neuro-ophthalmic Consultants Northwest Seattle Neuroscience Institute at Swedish Medical Center University.

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Presentation on theme: "Eyedrop testing in Horner Syndrome Eugene F. May, MD Neuro-ophthalmic Consultants Northwest Seattle Neuroscience Institute at Swedish Medical Center University."— Presentation transcript:

1 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

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

3 Anatomy

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8 Pharmacology

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10 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:

11 Miosis Ptosis –iris constrictor unopposed – mm miosis greatest in dim illumination dilation lag –pupil dilation is passive

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

13 Historical Background Dilute epinephrine test Cocaine test Hydroxyamphetamine test Apraclonidine test

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

15 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: 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:

16 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:

17 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:

18 Cocaine test Alternatives Why not cocaine? –difficult to obtain (?) –expensive (?) –short shelf life (?) –parents hesitant (?) –positive urine test (?)

19 Cocaine test Alternatives Apraclonidine 0.5%, 1% (Iopidine) –α 2 > α 1 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

20 Apraclonidine Studies show good sensitivity –1.00 (1%) and 0.88 (0.5%) –Morales J et al. Arch Ophthalmol. 2000;118: –Brown SM et al. Arch Ophthalmol. 2003;121: –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:

21 Apraclonidine must have high level of illumination sometimes normal pupil dilates

22 Apraclonidine Side effects –in children with glaucoma apnea, bradycardia, hypotension, somnolence, fatigue –in children with Horner syndrome conjunctival hyperemia sleepiness

23 Localization

24 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:

25 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.

26 Hydroxyamphetamine test Problems –range of variability exists even in normals –Cremer et al. Hydroxyamphetamine mydriasis in normal subjects. Am J Ophthalmol. 1990;110: 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

27 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 2 o neuron

28 Hydroxyamphetamine test Alternatives 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:

29 Hydroxyamphetamine test Alternatives 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.

30 Hydroxyamphetamine test Alternatives 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

31 Hydroxyamphetamine test Alternatives Not generally available in US: –Tyramine hydrochloride (5%) –Hydroxymethylamphetamine (Pholedrine)

32 Conclusions A combination of characteristic symptoms and signs allows a diagnosis of Horner syndrome

33 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

34 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

35 Thank you!


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