Adie's Pupil (Tonic Pupil / Holmes-Adie Syndrome)

Right Adie pupil: large right pupil (A) with absent direct light reflex (B) - Kanski's Clinical Ophthalmology, p. 810

Pathophysiology

• Loss of the pupillary light reflex (sphincter pupillae denervated)
• Impaired accommodation (ciliary muscle denervated)

Epidemiology

• Predominantly affects young women (3rd-4th decade), more common in females than males
• Unilateral in ~80% at onset; the second eye often becomes involved over months to years
• May occasionally be inherited in an autosomal dominant pattern

Clinical Features

Holmes-Adie Syndrome

• Features of autonomic nerve dysfunction (excessive sweating = Ross syndrome)
• Orthostatic hypotension
• Occasionally bowel obstruction or urinary retention
• Impaired corneal sensation (trigeminal ophthalmic division fibers in ciliary ganglion)

Etiology

Diagnosis

Pharmacological Test (Key)

• Adie pupil: constricts (denervation hypersensitivity to cholinergic agent)
• Normal pupil: does not constrict

Note: Hypersensitivity may be absent in an acute Adie pupil - retest a few weeks later if index of suspicion is high.

Additional Workup

• Bilateral simultaneous Adie pupils: send syphilis serology, Sjögren antibodies, paraneoplastic panel, and screen for other causes listed above
• Unilateral Adie pupil: no further lab workup necessary in a typical young woman
• Infant (<1 year): refer to pediatric neurology to rule out familial dysautonomia (Riley-Day syndrome)

Differential Diagnosis

Treatment & Follow-up

• Pilocarpine 0.125% eye drops (b.i.d. to q.i.d.) for cosmesis and to aid accommodation
• No treatment reverses the underlying denervation
• If diagnosis is certain and unilateral: routine follow-up only
• Prognosis is generally benign; accommodation tends to recover but the light reflex does not

• Tonic (slow) near response with light-near dissociation
• One eye usually (80% unilateral)
• No light reflex (absent/sluggish)
• Iris vermiform (segmental palsy on slit lamp)
• Cholinergic hypersensitivity (pilocarpine 0.125% test)

Adie's Pupil - 10 Mark Essay (PG Exam Format)

Introduction (1 mark)

Etiology & Epidemiology (1 mark)

• Predominantly affects young women (20-40 years)
• Usually idiopathic
• Other causes: viral illness (VZV, HSV), orbital trauma/surgery, syphilis, Sjögren syndrome, paraneoplastic syndrome, GCA, Guillain-Barré syndrome
• Unilateral in 80% at onset; second eye may get involved later

Pathophysiology (2 marks) ⭐ High-yield

• Ciliary ganglion or short ciliary nerves are damaged
• Loss of postganglionic parasympathetic supply to:
  • Sphincter pupillae → absent light reflex, dilated pupil
  • Ciliary muscle → impaired accommodation

• Accommodative fibers outnumber pupillomotor fibers by 30:1
• During regeneration, accommodative fibers misdirect into the iris sphincter
• Result: near response is partially "restored" (not truly spared)
• Light reflex does NOT recover → light-near dissociation

Clinical Features (2 marks)

Symptoms

• Anisocoria (patient notices unequal pupils)
• Blurring of near vision (ciliary muscle paresis)
• Photophobia

Signs

Associations - Holmes-Adie Syndrome (1 mark)

• Absent/diminished knee jerk and ankle jerk
• Ross syndrome: + anhidrosis (segmental)
• Orthostatic hypotension
• Impaired corneal sensation

Diagnosis & Pharmacological Testing (2 marks) ⭐⭐ Most Important

Dilute Pilocarpine Test

• Instill 0.1% or 0.125% pilocarpine in both eyes
• Wait 10-15 minutes
• Adie pupil constricts → denervation hypersensitivity ✅
• Normal pupil: no response

⚠️ Hypersensitivity may be absent in acute Adie pupil - repeat test after a few weeks

When to investigate further?

Differential Diagnosis (1 mark)

Treatment (0.5 mark)

• Pilocarpine 0.125% drops b.i.d. to q.i.d. - for cosmesis and to aid accommodation
• No treatment reverses underlying denervation
• Reassurance - condition is benign
• Routine follow-up if diagnosis is certain

Prognosis (0.5 mark)

• Generally benign course
• Accommodation tends to recover over time
• Light reflex does NOT recover and may worsen
• Pupil progressively becomes miotic ("little old Adie") in chronic cases
• Tendency to involve the fellow eye over time

Quick Recall Box 🧠

Most commonly asked PG one-liners from this topic:

• "Denervation hypersensitivity is tested by?" → Pilocarpine 0.125%
• "Light-near dissociation in dilated pupil?" → Adie's pupil
• "Light-near dissociation in miotic pupil?" → Argyll Robertson pupil
• "Tonic pupil + areflexia?" → Holmes-Adie syndrome
• "Little old Adie?" → Long-standing Adie pupil becomes miotic