Ocular Effects of the Sympathetic Nervous System

Topic 4: Confirmatory and Diagnostic Tests

Introduction and Objectives

After completing this unit, you will learn to:

  • Identify with 100% accuracy, the characteristics of pharmacological agents that can be used to determine the type of Horner’s syndrome that is present; and
  • Understand the appropriate use of these pharmacological agents in diagnostic tests, at the level of basic clinical fluency

Estimated time of completion: 7 minutes


Pharmacological Agents

Cocaine 10%

10% COCAINE DETERMINES WHETHER HORNER’S SYNDROME IS PRESENT OR NOT.

The following diagram represents a third-order sympathetic neuron ending on the iris dilator neuromuscular synaptic cleft.  Norepinephrine (NE) is released as the neurotransmitter that propagates the signal from the neuron to the muscle, causing pupillary dilation.

third-order neuromucular junction

Cocaine prevents the NE from being reuptaken from the synaptic cleft, causing a stronger dilation of the pupil.

In Horner’s syndrome, however, there is little NE in the synaptic cleft (since the sympathetic nervous supply to the dilator is interrupted), so the pupil will not dilate as much as in a normal pupil.

 

The steps for using 10% cocaine solution in the diagnosis of Horner’s syndrome are:

  1. Instill one drop of 10% cocaine solution in each eye
  2. Wait 30 minutes
  3. Determine the amount of pupillary dilation in each eye
    • If normal: both pupils should dilate an equal amount
    • If Horner’s: the affected pupil should dilate less than the unaffected pupil

Apraclonidine 0.5% (Iopidine)

IOPIDINE DETERMINES WHETHER HORNER’S SYNDROME IS PRESENT OR NOT.

  • Used as a substitute to cocaine (which can be hard to obtain)
  • Directly excites the sympathetic receptors on the iris dilator muscle, to cause pupillary dilation
  • Its very dilute concentration causes only mild pupillary dilation, normally
  • In Horner’s syndrome, the lack of NE in the synaptic cleft over long periods of time causes the muscle to react more robustly to stimulation
  • Affected pupil will dilate more quickly than normal pupil

Hydroxyamphetamine 1% (Paradrine)

1% HYDROXYAMPHETAMINE DETERMINES WHETHER HORNER’S SYNDROME IS 3rd-ORDER OR NOT.

Hydroxyamphetamine causes the release of stored NE from the third-order neuron into the synaptic cleft, causing pupillary dilation.

third-order neuromucular junction

If the third-order neuron is injured, it will not have NE stored in vesicles, however, and pupil dilation will not occur upon instillation of hydroxyamphetamine.

Hydroxyamphetamine is used to determine whether a previously-diagnosed Horner’s syndrome is caused by an injury to the third-order neuron.

 

The steps for using 1% hydroxyamphetamine in the diagnosis of Horner’s syndrome type are:

  1. Instill one drop of 1% hydroxyamphetamine solution in each eye
    • Must be done 72 hours after cocaine use, to allow cocaine to wear off
    • Wait 72 hours after apraclonidine use, too
  2. Determine the amount of pupillary dilation in each eye
    • If normal: both pupils should dilate an equal amount in both eyes
    • If 3rd-order Horner’s: the affected pupil should dilate less than the unaffected pupil
    • If 2nd- or 1st-order Horner’s: both pupils should dilate an equal amount in both eyes

Horner's Syndrome Pharmacology Summary
  Cocaine Apraclonidine (Iopidine) Hydroxyamphetamine (Paradrine)
Concentration 10% 1% 0.5%
Mechanism of Action Blocks NE reuptake Stimulate α-1 receptors Releases stored NE into synaptic cleft
Normal response Pupil dilation Pupil dilation (mild) Pupil dilation
Horner's syndrome response Reduced pupil dilation Pupil dilation (marked) If 3rd-order: Reduced pupil dilation
If 1st- or 2nd-order: Normal pupil dilation
Tests for Presence of Horner's syndrome Presence of Horner's syndrome Type of Horner's syndrome

Flowcharts (click for larger image)

Flowchart of First Step of Pharmacological Testing

Flowchart of Second Step of Pharmcological Testing


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