Abnormalities of the Pupil

Aetiology

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

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.

Condition	Pupillary signs	Associated features
Physiological anisocoria	Unequal pupil sizes ≥0.5mm but <1mm. Asymmetry similar in light and dark conditions	None
Tonic pupil	Affected pupil larger. Decreased response to light but normal near response	Rare, but could include varicella-zoster infection, giant cell arteritis and orbital trauma
Horner’s syndrome	Miosis of affected pupil	Mild ptosis and anhydrosis on affected side. Heterochromia if congenital
Argyll-Robertson pupil	Bilateral miosis. Minimal or no reaction to light but normal near response	Neurosyphilis (rare manifestation)

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)

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

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.

Summary

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.

Clinical Management Guidelines

Clinical Management Guidelines

Abnormalities of the Pupil

Contents

Aetiology

Predisposing factors

Symptoms of pupil abnormalities

Signs of pupil abnormalities

Differential diagnosis

Management by optometrist

Non pharmacological

Pharmacological

Management category

Possible management by ophthalmologist

Evidence base

Summary

What are Abnormalities of the Pupil?

How is Abnormalities of the Pupil managed?

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