Medicine – Pupils, Pupillary Light Reflex, Miosis, Horner Syndrome and Mydriasis

The pupil regulates the amount of light entering the eye. Its size is controlled by opposing parasympathetic pupilloconstrictor fibres and sympathetic pupillodilator fibres.

Abnormal pupil size or reactivity can therefore help localise lesions involving the optic nerve, midbrain, oculomotor nerve, sympathetic pathway, iris, or autonomic nervous system.

An asterisk (*) signifies a common cause.

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1. Parasympathetic Pupilloconstrictor Fibres

Parasympathetic fibres cause constriction of the pupil, or miosis.

The pathway begins in the Edinger–Westphal nucleus of the midbrain.

Preganglionic parasympathetic fibres then travel with the oculomotor nerve, CN III, to the ciliary ganglion in the orbit.

Postganglionic fibres travel through the short ciliary nerves to the:

Sphincter pupillae → constricts the pupil.

Ciliary muscle → allows accommodation for near vision.

Therefore:

Parasympathetic activation → miosis + accommodation.

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2. Sympathetic Pupillodilator Fibres

Sympathetic fibres cause dilatation of the pupil, or mydriasis.

The pathway begins in the hypothalamus and descends through the brainstem to the ciliospinal centre of Budge, approximately at spinal cord levels C8–T2.

Preganglionic fibres then leave the spinal cord, pass through the sympathetic chain, and ascend to the superior cervical ganglion.

Postganglionic fibres accompany the internal carotid artery into the skull and ultimately reach the eye.

They supply the:

Dilator pupillae → pupil dilatation.

They also contribute to eyelid elevation through Müller’s superior tarsal muscle and supply sympathetic fibres involved in facial sweating.

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3. Pupillary Light Reflex

The pupillary light reflex is the constriction of the pupils in response to light.

Shining light into one eye normally produces:

Direct response → constriction of the illuminated pupil.

Consensual response → constriction of the opposite pupil.

This occurs because the central pathway projects bilaterally to the Edinger–Westphal nuclei.

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4. Afferent Limb of the Light Reflex

The afferent limb detects the incoming light stimulus.

The pathway is:

Retina → optic nerve (CN II) → optic chiasm/optic tract → pretectal nuclei of the midbrain.

An important correction to the original note is that the lateral geniculate body is not the principal relay of the pupillary light reflex.

The lateral geniculate nucleus is primarily part of the pathway responsible for conscious vision.

For the pupillary reflex, fibres leave the optic tract and synapse in the pretectal area of the midbrain.

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5. Bilateral Midbrain Connection

Each pretectal nucleus sends fibres to both Edinger–Westphal nuclei.

This bilateral connection explains why shining light in one eye normally constricts both pupils.

Therefore:

One retina stimulated → both Edinger–Westphal nuclei activated → both pupils constrict.

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6. Efferent Limb of the Light Reflex

The efferent limb is parasympathetic.

The pathway is:

Edinger–Westphal nucleus → CN III → ciliary ganglion → short ciliary nerves → sphincter pupillae → pupillary constriction.

Therefore:

Afferent limb = CN II.

Efferent limb = CN III parasympathetic fibres.

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7. Pupillary Light Reflex – Note Form

Light enters eye → retina.

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Retina → optic nerve, CN II.

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Optic nerve fibres → optic chiasm and optic tract.

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Fibres leave visual pathway → pretectal nuclei in midbrain.

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Pretectal nuclei → bilateral Edinger–Westphal nuclei.

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Edinger–Westphal nucleus → CN III.

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CN III → ciliary ganglion.

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Short ciliary nerves → sphincter pupillae.

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Result → direct and consensual pupillary constriction.

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8. Causes of a Small Pupil – Miosis

Miosis means abnormal or marked constriction of the pupil.

Important causes include:

Age-related or senile miosis.

Horner syndrome.

Argyll Robertson pupil.

Certain autonomic disorders.

Opiates.

Pilocarpine and other miotic drugs.

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9. Senile Miosis

Pupils tend to become smaller with increasing age.

This physiological age-related reduction in pupil diameter is sometimes called senile miosis.

It is generally bilateral and does not itself indicate neurological disease.

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10. Horner Syndrome

Horner syndrome results from interruption of the sympathetic pathway supplying the eye and face.

The classic features are:

Ptosis.

Miosis.

Anhidrosis, depending on the level of the lesion.

A traditional fourth feature is enophthalmos, although the eye is usually not truly displaced backward.

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11. Miosis in Horner Syndrome

The sympathetic system normally activates the dilator pupillae muscle.

Loss of sympathetic input means the affected pupil cannot dilate normally.

Parasympathetic constrictor activity is therefore relatively unopposed.

The result is:

Ipsilateral miosis.

The difference in pupil size, or anisocoria, becomes more obvious in the dark because the abnormal pupil fails to dilate properly.

Therefore:

Horner anisocoria → greater in darkness.

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12. Ptosis in Horner Syndrome

The sympathetic fibres supply Müller’s superior tarsal muscle, which contributes a small amount to upper-eyelid elevation.

Loss of this sympathetic supply causes a mild ptosis.

This differs from third nerve palsy, where paralysis of the levator palpebrae superioris may cause much more severe ptosis.

Therefore:

Horner → mild ptosis.

CN III palsy → often marked ptosis.

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13. Anhidrosis

Anhidrosis means reduced or absent sweating.

Its distribution depends on where along the sympathetic pathway the lesion occurs.

Central or preganglionic lesions are more likely to cause significant facial anhidrosis.

Postganglionic lesions associated with the internal carotid artery may produce little or no facial anhidrosis because many sweat fibres have already travelled with the external carotid circulation.

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14. Enophthalmos

Traditional descriptions of Horner syndrome include enophthalmos, meaning that the eye appears sunken.

In humans this is usually apparent rather than true enophthalmos.

The combination of mild upper-lid ptosis and slight elevation of the lower eyelid makes the palpebral opening smaller, giving the impression that the eye lies deeper in the orbit.

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15. The Three-Neurone Sympathetic Pathway

The sympathetic pathway involved in Horner syndrome can be divided into:

First-order central neurone.

Second-order preganglionic neurone.

Third-order postganglionic neurone.

The site of interruption helps determine the possible underlying cause.

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16. First-Order or Central Horner Syndrome

First-order fibres descend from the hypothalamus through the brainstem and cervical spinal cord.

Important causes include:

*Brainstem stroke or other vascular lesion. **

Tumour.

Demyelination, including multiple sclerosis.

Spinal cord lesions.

Other neurological findings are often present because central lesions usually involve neighbouring structures.

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17. Vascular Causes*

A brainstem vascular lesion, particularly a lateral medullary stroke, can interrupt descending sympathetic fibres and cause Horner syndrome.

The patient may also have other brainstem signs, such as:

Vertigo.

Ataxia.

Dysphagia.

Sensory abnormalities.

Therefore, Horner syndrome accompanied by other acute neurological deficits should raise concern for a central vascular lesion.

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18. Preganglionic Horner Syndrome

Second-order sympathetic fibres leave the spinal cord and travel through the upper chest and neck before reaching the superior cervical ganglion.

Because this pathway passes close to the lung apex, lesions in the chest can produce Horner syndrome.

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19. Pancoast Tumour*

A Pancoast tumour, or superior sulcus lung tumour, is an important cause of preganglionic Horner syndrome.

The tumour occurs near the lung apex and may invade the sympathetic chain.

It may produce:

Horner syndrome.

Shoulder or arm pain.

Brachial plexus involvement.

Therefore:

Horner syndrome + shoulder/arm pain → consider an apical lung tumour.

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20. Other Chest Causes

Other lesions affecting the sympathetic chain in the thoracic inlet or mediastinum can also cause Horner syndrome.

These include:

Mediastinal masses.

Other apical thoracic lesions.

A cervical rib was traditionally listed as a possible cause through local compression, although it is much less important clinically than malignant or traumatic causes.

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21. Cervical Causes

The sympathetic chain passes through the neck, where it may be damaged by:

Cervical lymphadenopathy.

Neck trauma.

Thyroid or other cervical tumours.

Therefore, neck examination is important in unexplained Horner syndrome.

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22. Surgical and Iatrogenic Causes*

Horner syndrome can occur following procedures involving the neck.

Examples include:

Thyroid surgery.

Carotid surgery, including carotid endarterectomy.

Other cervical or thoracic operations.

Modern arterial catheter procedures can also occasionally damage the sympathetic pathway, although older references to carotid angiography as a common cause reflect historical practice.

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23. Postganglionic Horner Syndrome

Third-order sympathetic fibres leave the superior cervical ganglion and accompany the internal carotid artery toward the skull.

Important causes include:

Internal carotid artery dissection.

Cavernous sinus disease.

Other lesions along the internal carotid sympathetic plexus.

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24. Internal Carotid Artery Dissection

Internal carotid artery dissection is an especially important cause of acute painful Horner syndrome.

The sympathetic fibres run along the wall of the internal carotid artery and may be damaged when the artery dissects.

A classic presentation is:

Acute unilateral Horner syndrome + ipsilateral neck, facial, or head pain.

This requires urgent assessment because carotid dissection can cause cerebral ischaemia and stroke.

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25. Cavernous Sinus Lesion

Sympathetic fibres travel through the cavernous sinus alongside several cranial nerves.

A cavernous sinus lesion may therefore produce Horner syndrome together with:

Diplopia.

Ophthalmoplegia.

Trigeminal sensory abnormalities.

Other cranial nerve deficits.

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26. Horner Syndrome – Note Form

Sympathetic lesion → Horner syndrome.

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Miosis → loss of pupillary dilator activity.

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Ptosis → loss of sympathetic supply to Müller muscle.

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Anhidrosis → distribution depends on lesion level.

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Apparent enophthalmos → narrowing of palpebral fissure rather than true posterior displacement.

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Central causes: stroke, tumour, demyelination and spinal cord lesions.

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Preganglionic causes: Pancoast tumour, thoracic/mediastinal lesions, neck tumour or trauma, thyroid or carotid surgery.

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Postganglionic causes: internal carotid artery dissection and cavernous sinus lesions.

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27. Argyll Robertson Pupil

The Argyll Robertson pupil is classically a small, irregular pupil that accommodates but does not react normally to light.

This phenomenon is called:

Light-near dissociation.

In simple terms:

No or poor light response.

Near/accommodation response preserved.

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28. Association of Argyll Robertson Pupil

Argyll Robertson pupils are classically associated with neurosyphilis, particularly late syphilitic neurological disease.

The traditional memory phrase is:

“Accommodates but does not react.”

The finding is much less common in modern clinical practice than older textbooks suggest.

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29. Myotonic Dystrophy

Pupillary abnormalities can occur in myotonic dystrophy, including relatively small pupils and impaired pupillary responses.

However, miosis is not usually the key diagnostic feature.

More characteristic findings include:

Myotonia.

Distal muscle weakness.

Facial and temporal muscle wasting.

Early cataracts.

Cardiac conduction disease.

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30. Opiates

Opiates or opioids commonly cause bilateral marked pupillary constriction.

The classic description is:

Pinpoint pupils.

In opioid toxicity, this may occur with:

Reduced level of consciousness.

Respiratory depression.

Therefore:

Coma + respiratory depression + pinpoint pupils → strongly consider opioid toxicity, while remembering that other causes of coma can sometimes alter pupils as well.

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31. Pilocarpine

Pilocarpine is a muscarinic cholinergic agonist.

It stimulates the sphincter pupillae and causes:

Miosis.

It has ophthalmic uses, although its role in modern glaucoma treatment is more limited than historically.

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32. Causes of a Large Pupil – Mydriasis

Mydriasis means dilatation of the pupil.

It may result from:

Loss of parasympathetic constrictor activity.

or

Excess sympathetic activity/pharmacological stimulation.

Important causes include:

Adie tonic pupil.

Third nerve palsy.

Drugs.

Trauma.

Previous eye surgery.

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33. Adie Tonic Pupil

An Adie tonic pupil usually results from damage to parasympathetic fibres in or after the ciliary ganglion.

It typically produces a pupil that is:

Dilated.

Poorly reactive to light.

Slow or tonic in its response to near stimulation and redilatation.

The near response is often better preserved than the light response, producing another form of light-near dissociation.

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34. Holmes–Adie Syndrome

When the tonic pupil is associated with reduced or absent deep tendon reflexes, the condition is called Holmes–Adie syndrome.

Therefore:

Adie pupil + reduced tendon reflexes = Holmes–Adie syndrome.

It commonly affects otherwise healthy younger adults and is usually benign.

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35. Third Nerve Palsy

The third cranial nerve carries parasympathetic fibres responsible for pupil constriction.

Damage to these fibres may therefore result in:

Dilated pupil.

Poor or absent light reaction.

If a large pupil occurs together with:

Ptosis.

Down-and-out eye.

Diplopia.

a third nerve palsy should be suspected.

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36. Aneurysm and a Dilated Pupil

A particularly important emergency is:

Painful third nerve palsy + dilated pupil.

This raises concern for compression by a posterior communicating artery aneurysm.

Therefore, a new pupil-involving third nerve palsy requires urgent assessment.

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37. Drugs Causing Mydriasis

Many drugs can cause pupillary dilatation.

Important examples include:

Atropine.

Tropicamide.

Sympathomimetic/stimulant drugs such as amphetamines.

Some antidepressants and other medications with anticholinergic effects.

Atropine and tropicamide cause mydriasis mainly by blocking parasympathetic muscarinic activity at the iris sphincter.

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38. Tropicamide

Tropicamide is a short-acting antimuscarinic drug commonly used during ophthalmic examination to dilate the pupil.

It produces:

Mydriasis.

and some degree of:

Cycloplegia, or reduced accommodation.

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39. Atropine

Atropine blocks muscarinic receptors.

In the eye it causes:

Mydriasis.

Cycloplegia.

Its ocular effects last considerably longer than those of tropicamide.

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40. Trauma and Previous Eye Surgery

Direct trauma to the iris sphincter can leave the pupil abnormally dilated or irregular.

This is sometimes called traumatic mydriasis.

Previous ophthalmic surgery may also alter the shape, size or reactivity of the pupil.

Therefore, examination for:

Iris injury.

Surgical scars.

An irregular pupil.

may help identify a local ocular cause.

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41. Small Pupil – Note Form

Senile miosis: physiological pupil narrowing with age.

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Horner syndrome: miosis + mild ptosis ± anhidrosis.

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Argyll Robertson pupil: small irregular pupil with light-near dissociation; classically neurosyphilis.

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Opiates: bilateral pinpoint pupils, particularly important in opioid toxicity.

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Pilocarpine: pharmacological muscarinic stimulation causing miosis.

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42. Large Pupil – Note Form

Adie tonic pupil: large pupil with poor light response and tonic near response.

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Holmes–Adie syndrome: Adie pupil + reduced/absent tendon reflexes.

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Third nerve palsy: dilated pupil ± ptosis and down-and-out eye.

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Atropine/tropicamide: antimuscarinic pupillary dilatation.

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Amphetamines and other sympathomimetics: may cause mydriasis.

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Trauma/surgery: damage to iris sphincter may cause a persistently large or irregular pupil.

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43. Horner versus Third Nerve Palsy – Note Form

Horner syndrome → pupil SMALL.

Third nerve palsy → pupil may be LARGE.

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Horner ptosis → mild.

Third nerve ptosis → often marked.

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Horner eye movements → usually normal.

Third nerve palsy → eye movements markedly abnormal.

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Horner eye position → no classic down-and-out deviation.

Third nerve palsy → down-and-out eye.

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Horner anisocoria → greater in the DARK.

Parasympathetic pupil palsy → anisocoria usually greater in BRIGHT light because the large abnormal pupil cannot constrict.

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Key Clinical Pattern

The easiest way to organise pupillary abnormalities is to ask which autonomic pathway has failed.

Parasympathetic fibres constrict the pupil.

Sympathetic fibres dilate the pupil.

Therefore:

Sympathetic failure → small pupil → Horner syndrome.

Parasympathetic failure → large pupil → third nerve palsy, Adie pupil or antimuscarinic drug effect.

For the light reflex remember:

CN II IN → midbrain → bilateral Edinger–Westphal nuclei → CN III OUT.

And the most important emergency patterns are:

Painful Horner syndrome → consider internal carotid artery dissection.

Painful third nerve palsy with a dilated pupil → urgently exclude posterior communicating artery aneurysm.