Isaamuddin Alvi

Key Points

• Typical patient: Young to middle-aged adult, more common in women
• Classic triad: Dilated pupil + light-near dissociation + slow tonic redilation (1)
• Hallmark exam finding: Sectoral sphincter palsy with vermiform pupil movements (use slit lamp)
• Benign course: Reassurance often sufficient; pupil may become smaller over years
• Red flags requiring urgent referral: Ptosis, diplopia, motility deficit, acute painful red eye

Introduction

A newly noticed dilated pupil can be unsettling for both patient and clinician because the differential includes compressive third nerve palsy, pharmacologic mydriasis, ocular trauma, and acute angle closure (2).

One of the common benign neuro-ophthalmic patterns is the tonic (Adie) pupil, caused by post-ganglionic parasympathetic dysfunction affecting the iris sphincter and often accommodation. Clinically, the pupil reacts poorly to light but constricts better to near, followed by a characteristically slow “tonic” re-dilation (1,3).

Tonic pupils typically present in young to middle-aged adults with a female predominance reported in most case series. While often unilateral at presentation, bilateral cases do occur in approximately 20% of patients, though usually not simultaneously (1,3).

When a tonic pupil is accompanied by reduced or absent deep tendon reflexes, the broader diagnosis is Holmes-Adie syndrome. In everyday practice, the pupil finding is Adie/tonic, while “Holmes-Adie” refers to the association with areflexia (1,3).

Clinical Assessment and Diagnosis

Presentation and Examination

Patients commonly present with anisocoria (often more obvious in bright light), photophobia, or near blur early on if accommodation is involved. On examination, a key feature is light-near dissociation: the pupil reacts poorly to light but constricts better to near effort and then redilates slowly once fixation returns to distance (1,2,3).

Slit-lamp examination is essential. Sectoral sphincter palsy and subtle “vermiform” (worm-like) movements of the pupillary margin are highly supportive of a tonic pupil pattern and can prevent unnecessary escalation when the history is unclear. These findings can be subtle and require magnification and patient observation during the examination (1,3,5).

Document the examination with pupil photography in light and dark conditions when possible. This provides invaluable comparison for follow-up and medicolegal documentation.

Excluding Dangerous Mimics

Because dangerous causes of anisocoria exist, a brief neuro-ophthalmic screen should be documented. Ptosis, diplopia, or ocular motility limitation warrant same-day neurology or neuro-ophthalmology referral for consideration of third nerve palsy rather than reliance on pharmacologic testing (2). Acute painful red eye with corneal haze requires immediate ophthalmology assessment for angle closure.

Systemic Assessment

If you are framing the case as Holmes-Adie syndrome, assess deep tendon reflexes (ankles and knees are classic). If there are prominent autonomic features such as abnormal sweating or heat intolerance, consider the autonomic spectrum and Ross syndrome (tonic pupils with areflexia and segmental anhidrosis/hypohidrosis) (8).

Pharmacologic Testing

When is pilocarpine testing needed? If the clinical examination clearly demonstrates light-near dissociation with sectoral palsy or vermiform movements in an otherwise healthy patient, pharmacologic confirmation is often unnecessary. Testing is most helpful in equivocal cases or when reassurance through objective testing is needed.

The classic bedside pharmacologic confirmation is the dilute pilocarpine test. A tonic pupil may show denervation hypersensitivity and constrict to dilute pilocarpine—commonly 0.125% (or 0.1% in some protocols)—with reassessment after 45-60 minutes. This test is supportive rather than perfectly specific, and results can be equivocal in very early presentations (1,4).

More recent evidence suggests that 0.0625% pilocarpine may outperform 0.125% for detecting denervation supersensitivity, particularly when quantified with pupillometry, and may be helpful in borderline cases (4).

Differential Diagnosis

A tonic pupil should be diagnosed confidently rather than by exclusion alone. High-stakes mimics—particularly third nerve palsy and anticholinergic pharmacologic mydriasis—are excluded by targeted history, motility and ptosis assessment, and an understanding of expected pharmacologic response patterns (2).

Condition	Exam pattern that helps	Pilocarpine clue (practical)
Holmes-Adie (tonic) pupil	Poor light response, better near response, slow redilation; sectoral palsy/vermiform movements may be seen.	Constricts to dilute pilocarpine due to hypersensitivity (commonly 0.1-0.125%; 0.0625% supported in some protocols).
Third nerve palsy	Ptosis and/or diplopia with ocular motility deficit; pupil may be involved or spared.	Pharmacologic testing is not the priority—management is driven by neuro exam and urgency of imaging. Same-day referral required.
Anticholinergic pharmacologic mydriasis	Very poor light and near response; exposure history (patches, plants, inhalers, drops).	Often does not constrict to stronger pilocarpine (classic teaching).
Traumatic or surgical mydriasis	Iris sphincter tears, irregular pupil, trauma or surgery history.	Variable; depends on mechanical sphincter integrity.
Acute angle closure	Painful red eye, headache or nausea, corneal haze, high IOP, mid-dilated sluggish pupil.	Treat as emergency; pilocarpine is therapeutic, not a diagnostic shortcut. Immediate ophthalmology referral required.

Table 1: Differentials of a dilated pupil with clinical and pharmacological test findings (1,2,4)

Management and Prognosis

Acute Management

Management is typically symptom-led. Many patients primarily need reassurance and clear documentation of the benign pattern. If near blur is troublesome, a temporary reading add is often sufficient. Photophobia can be managed with tinted lenses, and some clinicians use dilute pilocarpine for symptomatic relief while counseling about brow ache, ciliary spasm, induced myopia, and reduced night vision with miosis (1,3).

Natural History

Holmes-Adie syndrome is generally benign; the areflexia usually does not require treatment. Accommodation typically recovers over weeks to months, though recovery is often incomplete. Over years, the affected pupil often becomes progressively smaller and may eventually become the smaller of the two pupils (the “little old Adie”), which can complicate interpretation if the original presentation was not documented (1,3).

Atypical Presentations

If the presentation is atypical (for example, marked autonomic complaints, bilateral tonic pupils at onset, or cranial nerve deficits), broaden the work-up accordingly. Bilateral tonic pupils, particularly when presenting simultaneously, should prompt consideration of a more generalized neuropathic process (3,8,9). Case reports describe tonic pupil or Holmes-Adie-like presentations following infections, including COVID-19, and following vaccination, though these remain rare associations without established causality (6,7).

References

1. EyeWiki. Adie Pupil. EyeWiki [online]. 2026. [Accessed 5 January 2026]. Available from: https://eyewiki.org/Adie_Pupil
2. EyeWiki. Anisocoria. EyeWiki [online]. 2025. [Accessed 4 January 2026]. Available from: https://eyewiki.org/Anisocoria
3. Xu SY, Song MM, Li L, Li CX. Adie’s pupil: A diagnostic challenge for the physician. Medical science monitor: international medical journal of experimental and clinical research. 2022 Mar 8;28:e934657-1.
4. Yoo YJ, Hwang JM, Yang HK. Dilute pilocarpine test for diagnosis of Adie’s tonic pupil. Scientific Reports. 2021 May 12;11(1):10089.
5. Wakerley BR, Tan MH, Turner MR. Teaching Video Neuro Images: Acute Adie syndrome. Neurology. 2012 Sep 11;79(11):e97-.
6. Karaca G, Kabakçı AK. Holmes-Adie syndrome associated with BNT162b2 mRNA COVID-19 vaccine. Indian Journal of Ophthalmology-Case Reports. 2024 Jul 1;4(3):671-2.
7. Çakır GY, Paşaoğlu IB, Çakır İ, Solmaz B. Adie’s tonic pupil after COVID-19: a case report and literature review. Romanian Journal of Ophthalmology. 2024 Apr;68(2):89.
8. EyeWiki. Ross Syndrome. EyeWiki [online]. 2025. [Accessed 6 January 2026]. Available from: https://eyewiki.org/Ross_Syndrome
9. Bremner FD, Smith SE. Bilateral tonic pupils: Holmes Adie syndrome or generalised neuropathy? Br J Ophthalmol. 2007;91(12):1620-1623.