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The correlation of phenylephrine 1% with hydroxyamphetamine 1% in Horner’s syndrome
  1. H V Danesh-Meyer1,2,
  2. P Savino2,
  3. R Sergott2
  1. 1Department of Ophthalmology, University of Auckland, Auckland, New Zealand
  2. 2Neuro-ophthalmic Services, Wills Eye Hospital, Thomas Jefferson Medical School, Philadelphia, PA, USA
  1. Correspondence to: Associate professor Helen V Danesh-Meyer Department of Ophthalmology, University of Auckland, Private Bag 92019, Auckland, New Zealand;

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Pharmacological testing in Horner’s syndrome involves the use of cocaine to confirm the diagnosis and hydroxyamphetamine to localise the lesion to the post-ganglionic (third order) or non-postganglionic neuron. However, hydroxyamphetamine bromide 1% (Paredrine) is not always readily available to the ophthalmologist. An alternative drug for localising the site of the lesion is phenylephrine 1% which can easily be prepared by dilution of stronger concentrations (2.5% or 10%) and which is almost universally available in most ophthalmologists’ offices. Because of the principle of denervation supersensitivity, a Horner’s syndrome produced by a lesion interrupting the postganglionic fibres should dilate the pupil when phenylephrine 1% is placed in the conjunctival sac. The pupil of a patient with central (first order) Horner’s syndrome should not dilate, while a pre-ganglionic (second order) pupil may dilate minimally1; a normal pupil may, at best, dilate minimally. The purpose of this study was to compare the pupillary response of patients with Horner’s syndrome to phenylephrine 1% and hydroxyamphetamine 1%.

Fourteen consecutive patients with Horner’s syndrome were prospectively tested with cocaine 10%, hydroxyamphetamine 1%, and phenylephrine 1% on separate days, at least 3 days apart. All pupils were measured in the same room lighting with a standard ruler 1 hour after instillation of two drops. Phenylephrine 1% was prepared on each examination day by diluting phenylephrine 10% hydrochloride (0.1 ml) with 0.9 ml of preservative free natural tear drops. The clinician interpreting each pharmacological test was masked to the results of the other pharmacological tests and the cause of Horner’s syndrome.

Nine of the 14 patients were men. The average age was 59 years (range 34–74 years). All patients underwent magnetic resonance imaging of head and neck, magnetic resonance angiography of the neck, and computed tomography of the chest. Horner’s syndrome was considered to be central in two patients and pre-ganglionic in one, based on neuroimaging. All 11 patients diagnosed with postganglionic Horner’s syndrome had normal neuroimaging, an isolated Horner’s syndrome, positive cocaine test and positive hydroxyamphetamine test. Table 1 shows the baseline pupil size and the change with each of the three pharmacological tests. After pharmacological testing with phenylephrine 1%, the mean increase in pupil size in patients with postganglionic Horner’s syndrome was 2.3 mm (SD 1.1 mm) and in the contralateral normal pupil was 0.2 mm (SD 0.2 mm) (paired t test: p<0.0001). The sensitivity of phenylephrine 1% was 81% and the specificity 100%. The mean increase in pupil diameter on the affected side in patients with postganglionic Horner’s syndrome after hydroxyamphetamine 1% was 0.27 mm (SD 0.3 mm) and was 2.65 mm (SD 0.3) in the contralateral normal pupil.

Table 1

Mean change in pupillary diameter in patients with Horner’s syndrome


The law of denervation supersensitivity states that an organ deprived of its normal innervation becomes more sensitive to the chemical transmitter normally released from those nerves. Thompson and Mensher documented supersensitivity of the iris dilator to phenylephrine 1% in one patient.1 They further tested 13 patients but used a 10% concentration, which dilates the normal pupil. They determined that the affected pupil of the three patients with post-ganglionic lesions dilated sooner and more vigorously than the unaffected pupil. Ramsay2 tested 14 patients with phenylephrine 1% and found in patients with Horner’s syndrome that 71% of pupils were supersensitive. However, the responses of the post-ganglionic and non-post-ganglionic Horner’s syndrome were not reported separately. Other studies have reported on the use of phenylephrine 10%1 and epinephrine 1%,3 and adrenaline (epinephrine) 0.1%1 in the pharmacological testing of Horner’s, but none has investigated the efficacy of phenylephrine 1% in identifying post-ganglionic Horner’s lesion. Our study shows that phenylephrine dilates the post-ganglionic Horner’s pupil, but not the non-post-ganglionic or normal pupil. We found the sensitivity of 81% and a specificity of 100%. Hydroxyamphetamine 1% has been shown to have a sensitivity of 93% and specificity of 83%.4 Only one out of 11 patients with Horner’s syndrome in our series had a lesion, which localised to the post-ganglionic neuron with hydroxyamphetamine 1%, but not with phenylephrine 1%.

Phenylephrine 1% has some limitations:

  1. It does not dilate the normal pupil. If neither pupil dilates with phenylephrine 1% it could be either because the lesion is non-post-ganglionic or the drops are ineffective.

  2. The degree of supersensitivity is determined by the extent of denervation. A partial post-ganglionic lesion may be difficult to distinguished from a preganglionic lesion; in both conditions the iris may dilate minimally. In our study there was only one patient with a preganglionic lesion.

  3. Tests for supersensitivity may also be subject to false positive errors owing to the variations in penetration of the drug. The drug should be placed strictly on intact corneas so that the same dose reaches each iris.

  4. Supersensitivity of the iris dilator increases with age. Phenylephrine sensitivity of the iris increases by 0.23 mm per decade after age 20.

In summary, we here report the first series of patients with Horner’s syndrome, which compared the pupillary response of phenylephrine 1% to hydroxyamphetamine 1%. Phenylephrine 1% correlates well with the results of hydroxyamphetamine 1% in localising the lesion to the post-ganglionic neuron and is a reliable alternative to hydroxyamphetamine 1% should pharmacological testing be desired and hydroxyamphetamine 1% not be available.