01OverviewDefinition, clinical context and the essential points that orientate the chapter.
Ptosis is a lowered upper eyelid, while anisocoria is a difference in pupil size. Either may occur alone, but their combination can localise disease along sympathetic or oculomotor pathways. Begin with onset and associated symptoms. A gradually progressive lid droop present in old photographs has a different risk profile from a change that developed with headache that morning. Ask specifically about double vision, eye or neck pain, trauma, visual loss, fatigability, swallowing and breathing. Establish whether unequal pupils are truly new rather than merely newly noticed.
The pupil constricts through parasympathetic fibres associated with the third cranial nerve and dilates through a sympathetic pathway running from the brain through the neck and back to the eye. Greater anisocoria in bright light suggests that the larger pupil cannot constrict normally. Greater anisocoria in darkness suggests that the smaller pupil cannot dilate normally. These observations guide localisation but do not independently establish the cause. Physiological anisocoria is usually modest and longstanding, with otherwise normal examination; a small difference should not be declared benign solely because it is below a chosen millimetre threshold.
Third-nerve dysfunction can produce marked ptosis, limited adduction, elevation and depression, and an eye resting down and out when the palsy is complete. Partial palsies may be subtler. A dilated poorly reactive pupil increases concern about compression, including a posterior communicating artery aneurysm, but the historical pupil-sparing rule is insufficient to exclude this. Modern UK neuro-ophthalmic practice supports imaging new isolated third-nerve palsies rather than assigning a microvascular cause from diabetes, pain or pupil appearance alone. Acute painful or pupil-involving presentations require immediate emergency assessment.
Horner syndrome results from interruption of sympathetic input and typically combines mild ptosis with a smaller pupil. Dilation lag may be visible after the lights are dimmed. Anhidrosis can help localisation but may be absent or difficult to establish, particularly with a postganglionic lesion. New painful Horner syndrome is a vascular emergency because internal carotid dissection may precede cerebral ischaemia. An apparently well patient with normal limb examination is not protected from that risk. Appropriate vascular imaging should not be postponed while arranging a confirmatory drop test.
Mechanical and muscular causes remain important. Aponeurotic ptosis commonly develops with age or after local factors affecting the levator attachment and often has preserved pupil reactions. Myasthenia causes variable, fatigable weakness and can mimic several ocular motor patterns; pupils are usually unaffected. Ask about diurnal variation and symptoms beyond the eyes. An ice-pack response may support ocular myasthenia in specialist assessment but does not replace neurological evaluation. Worsening swallowing or breathing difficulty requires emergency care rather than an outpatient antibody result.
A unilateral large pupil can follow contact with anticholinergic medication, eye drops, a transdermal patch or nebulised medication leaking towards the eye. Previous iris trauma or surgery can also alter pupil shape and reaction. A careful exposure history is useful, but a possible drug explanation should not override new ptosis, ophthalmoplegia or neurological symptoms. Check old photographs and prior eye records when available without delaying urgent action. A relative afferent pupillary defect is an asymmetric response during alternating illumination and usually reflects retinal or optic nerve dysfunction, not unequal resting pupil size itself.
In children, congenital ptosis requires assessment of visual development, refractive error and obstruction of the pupil. Recent onset, progression, anisocoria or associated neurological findings changes the urgency. Pharmacological testing needs specialist judgement. RCOphth advises against apraclonidine 1% for paediatric Horner testing, against 0.5% below six months, and extra caution below two years; paediatric use is off-label and contraindicated by the product information. A diagnostic drop test is therefore neither an innocuous screening step nor a prerequisite for referring a concerning child.
Key points
- Measure and compare pupils in bright and dim conditions before instilling diagnostic drops.
- Anisocoria greater in light points towards impaired constriction of the larger pupil.
- Anisocoria greater in darkness points towards impaired dilation of the smaller pupil.
- Third-nerve palsy affects lid elevation and eye movements; pupil sparing does not safely exclude compression.
- A painful acute Horner syndrome warrants emergency assessment for carotid dissection.
- Myasthenia can cause fluctuating ptosis and diplopia while sparing the pupils.
- Anisocoria and a relative afferent pupillary defect describe different abnormalities.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Neurological pathway lesions
Oculomotor or sympathetic interruption can combine a lid abnormality with pupil asymmetry. Vascular lesions, tumours, trauma and inflammatory disease may occur at different points along these pathways.
Muscular and aponeurotic causes
Neuromuscular junction dysfunction produces variable lid weakness, while aponeurotic change alters the levator's attachment. Congenital levator dysfunction can cause ptosis from early childhood.
Physiological or local pupil variation
Unequal pupils may be longstanding physiological variation or follow iris trauma, surgery or drug exposure. The pupil reaction and associated lid or movement findings help distinguish these from neurological patterns.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Impaired parasympathetic constriction
Disruption of fibres serving the iris sphincter reduces constriction and makes the affected pupil relatively larger in bright light. Associated third-nerve motor dysfunction can lower the lid and restrict eye movements.
- 2Loss of sympathetic dilation
Sympathetic interruption reduces dilation of the affected pupil and weakens the sympathetically supplied lid muscle. The resulting miosis and mild ptosis may occur without a complete facial sweating abnormality.
- 3Fatigable neuromuscular transmission
Impaired transmission at the neuromuscular junction produces fluctuating weakness of lid and extraocular muscles. Pupil smooth muscle is not affected in the same way, so pupil responses are generally preserved.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Look for a larger poorly reacting pupil, ptosis and deficits of adduction, elevation or depression. An incomplete ocular motor pattern remains significant, and a reactive pupil does not make a new third-nerve palsy safe to observe without assessment.
A small pupil with mild upper-lid droop and delayed dilation suggests Horner syndrome. Ask about new neck or orbital pain, neck injury, headache and symptoms along the sympathetic pathway; absence of facial sweating change does not exclude it.
Variable ptosis or diplopia that worsens with sustained use supports myasthenia, especially when pupil responses remain normal. Check speech, swallowing and respiratory symptoms rather than restricting the assessment to the eyelids.
A longstanding droop with stable pupils and ocular movements may reflect levator aponeurosis change or congenital dysfunction. Confirm duration and inspect for a mass or other local cause before considering corrective surgery.
Reduced vision, colour desaturation or an afferent pupil defect suggests optic nerve or retinal disease. These findings require their own evaluation and should not be conflated with the localisation of unequal resting pupil sizes.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Pupils in light and darknessFirst step - Why
- Identify which pupil behaves abnormally under different illumination conditions.
- Interpretation and limitations
- Record sizes, shape, direct and consensual responses and any dilation lag before drops. The pattern supports localisation but must be interpreted with motility, lid position and the clinical history.
- 02
Full ocular motility and neurological assessment - Why
- Detect a cranial-nerve pattern or additional signs requiring emergency investigation.
- Interpretation and limitations
- Test movements in each direction, alignment and visual function, then assess relevant cranial nerves and limbs. A partial palsy or isolated ocular presentation can still reflect a serious intracranial process.
- 03
Urgent neurovascular imaging when indicated - Why
- Identify aneurysm, dissection or another acute neurological cause.
- Interpretation and limitations
- Emergency clinicians and neuroradiology select CTA or MRA and accompanying brain or neck imaging according to the suspected lesion. A routine non-contrast head CT alone does not exclude every aneurysm or cervical arterial dissection.
- 04
Directed myasthenia evaluation - Why
- Investigate variable ocular weakness and assess systemic involvement.
- Interpretation and limitations
- Specialist testing may include acetylcholine-receptor antibodies, additional serology and neurophysiology. Negative antibodies do not exclude ocular myasthenia, and respiratory or bulbar deterioration must be assessed before laboratory confirmation.
- 05
Specialist pharmacological pupil testing - Why
- Clarify selected uncertain pupil abnormalities after urgency has been assessed.
- Interpretation and limitations
- Apraclonidine can support Horner diagnosis but may be falsely negative early, and use for diagnosis is off-label. Observe paediatric safety restrictions; do not use testing to postpone investigation of an acute painful presentation.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Aneurysmal third-nerve compression
An aneurysm may produce acute ocular motor weakness and ptosis with or without obvious pupil involvement. Pain and a dilated pupil increase concern but their absence does not establish a benign cause.
Horner syndrome
Sympathetic dysfunction usually produces a small pupil and mild ptosis, with anisocoria more evident in darkness. Causes range from longstanding injury to acute dissection or other lesions along the pathway.
Myasthenia or mechanical ptosis
Fluctuating weakness suggests myasthenia, whereas a stable droop may reflect congenital or aponeurotic dysfunction. Both can occur with normal pupils, so pupil symmetry alone does not distinguish them.
Pharmacological or iris abnormality
Local anticholinergic exposure, prior surgery or iris damage can produce a large or irregular pupil. An isolated pupil abnormality differs from combined ptosis and a patterned ocular motor deficit.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01Acute neurological concernTransfer for immediate assessmentFirst stepNew ptosis or anisocoria accompanies concerning pain, diplopia or neurological signs.+
- 1Document onset, pupils, motility and associated symptoms without creating avoidable delay.
- 2Arrange emergency assessment and explicitly communicate suspected aneurysm, dissection or acute neurological disease.
- 3Ensure appropriate specialist imaging is considered even when the pupil is spared in a new third-nerve palsy.
02Variable ocular weaknessAssess for myasthenia and severityPtosis or diplopia fluctuates with activity and pupil reactions remain preserved.+
- 1Ask directly about choking, nasal speech, weak cough and breathing difficulty.
- 2EscalationEscalate respiratory or significant bulbar deterioration through emergency medical services immediately.
- 3Arrange specialist evaluation and directed testing when the patient is stable, with advice about worsening weakness.
03Longstanding or incidental findingConfirm stability and functional effectThe finding appears established and no acute neurological warning features are present.+
- 1Compare previous photographs or records and examine pupils, motility and visual function carefully.
- 2Arrange appropriate eye review for uncertain anisocoria, symptomatic mechanical ptosis or paediatric visual-development risk.
- 3Explain which new pain, diplopia, pupil change or weakness should trigger urgent reassessment.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Neurological vascular injury
An underlying aneurysm or arterial dissection can be associated with haemorrhage or cerebral ischaemia. Ocular signs may precede more extensive neurological dysfunction and permanent disability.
Diplopia and field obstruction
Ocular misalignment can cause disabling binocular diplopia, while a lowered lid can obscure the superior visual field. Functional impact varies with gaze, fatigue and the degree of lid coverage.
Amblyopia in childhood
Persistent visual-axis obstruction or associated refractive asymmetry can impair visual development. Reduced vision may emerge even when the child does not describe blur or double vision.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- During acute evaluation, document evolving pupil size, eye movements, headache and neurological symptoms rather than relying on one initial examination.
- For a diagnosed microvascular palsy, follow the specialist recovery plan and reassess progression or failure to improve instead of allowing the label to become permanent without review.
- Monitor swallowing and breathing in suspected myasthenia whenever ocular weakness changes.
- In congenital ptosis, follow acuity, refraction, alignment and visual-axis coverage during childhood.
- After ptosis correction, assess eye closure and corneal protection as well as lid height.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Pupil sparing has limits
A normal pupil can coexist with a compressive lesion, particularly in an incomplete palsy. The relevant question is whether the patient has a new oculomotor deficit requiring imaging, not whether an older bedside rule appears reassuring.
Painful Horner can be isolated
Carotid dissection may first produce unilateral pain and sympathetic dysfunction before focal neurological deficits develop. Waiting for limb weakness or speech disturbance risks missing the opportunity for timely diagnosis.
A photograph is supporting evidence
Old images may establish longstanding asymmetry, but flash, gaze, head position and lighting alter apparent pupil and lid size. Use photographs alongside examination rather than as a stand-alone exclusion test.
Paediatric drops need supervision
If a specialist uses apraclonidine 0.5% in a child under two years despite its off-label and product-contraindicated status, RCOphth advises observation in the facility for two hours and clear information about delayed adverse effects.
A low lid can hide diplopia
A fully ptotic eyelid may prevent the patient noticing double vision. Carefully assess ocular movements rather than using the absence of reported diplopia to exclude a third-nerve palsy.
11Common pitfallsFrequent interpretation and management errors.
- 01
Reassuring a new third-nerve palsy because the patient has diabetes and a reactive pupil.
- 02
Waiting for pharmacological confirmation before imaging suspected acute carotid dissection.
- 03
Assuming that all anisocoria indicates an afferent pupillary defect.
- 04
Attributing a large pupil to medication before checking for accompanying ptosis or ophthalmoplegia.
- 05
Planning cosmetic ptosis treatment without considering neurological causes or childhood visual development.