Abnormalities of the Pupil


Although pupil anomalies are commonly benign, they may be the first or only manifestation of a serious or even life-threatening disorder.

Physiological (‘simple’) anisocoria

  • Unequal pupil sizes in the absence of an underlying pathological cause
  • Idiopathic, stable and longstanding
  • Depending on the level of illumination, found in up to 20% of individuals
  • Increased prevalence with age

Tonic (Adie’s) pupil

  • Caused by parasympathetic denervation at the level of the ciliary ganglion
  • Most commonly seen in women (2.6:1) aged 20-40 years
  • Prevalence 2 per 1,000 of the general population
  • Usually idiopathic but case reports of associations with viral infections (e.g. varicella zoster) and a number of connective tissue diseases (e.g. Sjögren’s disease and rheumatoid arthritis). May also be seen in patients with generalised peripheral or autonomic neuropathies
  • When associated with absent or poor tendon reflexes known as Holmes-Adie syndrome

Horner’s syndrome

  • Congenital or acquired
  • Rare in adults, birth prevalence of 1 in 6250 for those with a congenital onset
  • Caused by interruption of the oculosympathetic innervation at any point along the neural pathway from the hypothalamus to the orbit
  • Usually benign or occurs after surgery, but could also indicate a carotid dissection or neoplasia

Argyll Robertson pupil

  • Associated with neurosyphilis
  • Thought to result from a lesion in the midbrain that disables the pathway for the pupillary light reflex but does not affect the more ventral pathway mediating the near reaction

Predisposing factors

Tonic pupil

  • Female gender

Horner’s syndrome

  • In children, birth trauma is the most common cause of Horner’s syndrome.

Argyll Robertson pupil

  • Observed in the tertiary and final stage of infection with syphilis.

Symptoms of pupil abnormalities

Generally asymptomatic, although pupil abnormalities may be associated with pain, photophobia or visual disturbance

Ipsilateral orbital, face, or neck pain has been reported in up to 58% of cases of Horner’s syndrome associated with internal carotid artery dissection

Signs of pupil abnormalities

Physiological (‘simple’) anisocoria

  • Anisocoria ≥0.5mm but typically <1mm
  • Degree of anisocoria remains relatively constant in light and dark conditions

Tonic (Adie’s) pupil

  • Affected pupil larger than normal, with decreased response to light but preserved or enhanced near response.
  • Pupil may be oval-shaped or shows segmental constriction
  • Unilateral in 80% of cases. The fellow pupil may become involved later
  • Affected pupil becomes smaller over time

Horner’s syndrome

  • Classic triad of ipsilateral ptosis, pupillary miosis, and facial anhydrosis (absence of sweating), but rarely all signs present
  • Mild ptosis, if present, of 1–2mm. This sign is reportedly absent in 12% of Horner’s syndrome
  • Ipsilateral miosis, with dilation lag
  • Anisocoria is more pronounced in the dark (particularly in the first 5 s of darkness)
  • Anhydrosis varies from the entire half face to a small patch on the forehead, depending on the location of the lesion
  • Horner syndrome that occurs very early in life can lead to iris heterochromia

Argyll Robertson pupil

  • Bilateral miosis with little or no constriction to direct light, but with apparently normal, pupil constriction to near targets.
ConditionPupillary signsAssociated
Unequal pupil sizes ≥0.5mm but <1mm. Asymmetry
similar in light and dark conditions
Tonic pupilAffected pupil larger.
Decreased response to light but normal near response
Rare, but could include varicella-zoster infection, giant cell arteritis and orbital trauma
Miosis of affected pupilMild ptosis and anhydrosis on affected side.
Heterochromia if congenital
Argyll-Robertson pupilBilateral miosis.
Minimal or no reaction to light but normal near response
Neurosyphilis (rare manifestation)

Differential diagnosis

Mechanical causes such as posterior synechiae, iris sphincter tears, or surgical injury

Management by optometrist

Practitioners should recognise their limitations and where necessary seek further advice or refer the patient elsewhere 

Non pharmacological 

For physiological anisocoria, old photographs can be diagnostically helpful
(GRADE*: Level of evidence=low, Strength of recommendation=strong)

Take thorough history including use of new medications that could affect the pupil, associated visual and/or neurological symptoms, previous or current malignancies and recent head or neck trauma. Initial slit lamp assessment to exclude mechanical causes such as posterior synechiae or iris sphincter tears
(GRADE*: Level of evidence=low, Strength of recommendation=strong)

Examination should include extraocular motility and whether or not ptosis is present
(GRADE*: Level of evidence=low, Strength of recommendation=strong)


Pharmacological testing is of limited value due to poor availability of the reagents and high false positive and false negative rates.
(GRADE*: Level of evidence=low, Strength of recommendation=strong)

Management category

A1: emergency (same day) referral without intervention if Horner’s syndrome is associated with neck pain. This should be considered a neurological emergency as it could indicate a carotid artery dissection

B2: alleviation/palliation; normally no referral

  • Physiological anisocoria
  • Tonic pupil

B1: Refer to ophthalmologist or neurologist.

  • Patients with suspected Horner’s syndrome may require MRI of the brain with contrast, as well as CT or MRI of the chest and neck
  • Suspected Argyll Robertson pupil requires serological tests for syphilis

Possible management by ophthalmologist

Often requires investigation and management by multi-disciplinary team

Evidence base

*GRADE: Grading of Recommendations Assessment, Development and Evaluation (see www.gradeworkinggroup.org)

Sources of evidence

Davagnanam I, Fraser CL, Miszkiel K, Daniel CS, Plant GT. Adult Horner's syndrome: a combined clinical, pharmacological, and imaging algorithm. Eye (Lond). 2013;27(3):291-8.

Gross JR, McClelland CM, Lee MS. An approach to anisocoria. Curr Opin Ophthalmol. 2016;27(6):486-492.

Lam BL, Thompson HS, Corbett JJ. The prevalence of simple anisocoria. Am J Ophthalmol. 1987;104(1):69-73.

Martin TJ. Horner's syndrome, Pseudo-Horner's syndrome, and simple anisocoria. Curr Neurol Neurosci Rep. 2007;7(5):397-406.

Moeller JJ, Maxner CE. The dilated pupil: an update. Curr Neurol Neurosci Rep. 2007;7(5):417-22.

Wilhelm H. Disorders of the pupil. Handb Clin Neurol. 2011;102:427-66.

Xu SY, Song MM, Li L, Li CX. Adie's Pupil: A Diagnostic Challenge for the Physician. Med Sci Monit. 2022;28:e934657.


What are Abnormalities of the Pupil?

The pupil (the circular black area in the middle of the coloured part of the eye) is usually the same size as the pupil on the other side, and the two pupils usually react together (for example to light). The pupils have muscles to constrict them (make them smaller) and muscles to dilate them (make them larger) and these are controlled by a network of nerves from the brain which works automatically. We all know that bright light makes the pupils smaller and dim light makes them larger. This makes a 20-times difference to the amount of light entering the eye. The pupils also constrict when we look at near objects (for example when we read), which makes focusing easier.

Normally this system works well, without our being aware of it, but there are many ways in which control can be lost. In a fifth of people, the pupils are usually slightly different in size (‘physiological anisocoria’). This is not a problem.

In 1 in 500 people, the nerves that control pupil constriction in one eye do not work properly (Tonic or Adie’s pupil). Usually a cause cannot be found, but rarely this can affect people following an infection or surgery to the eye socket.

In another condition, there is a small pupil on one side, a drooping of the upper lid, and no sweating on the same side of the face. This is known as Horner’s syndrome. It can occur in babies who are injured during birth, and in people with disease of the blood vessels, cancer or following some types of operation.

In Argyll Robertson pupil, both pupils are small and there is no reaction to light, but constriction for looking at near objects still happens. This condition is usually seen at a late stage of the sexually-transmitted infection syphilis and shows that the disease has affected the nervous system.

How is Abnormalities of the Pupil managed?

The optometrist who finds one of these conditions will either take no action, having explained the findings to the patient, or refer the patient to the ophthalmologist or neurologist if tests are needed.

Abnormalities of the pupil
Version 2
Date of search 24.08.22
Date of revision 05.09.22
Date of publication 19.12.22
Date for review 23.08.24

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