01Approach to the Critical Patient/attcp45

Immediate priorities

›Dangerous mimics first

›Pupil-involving CN III palsy

›Ptosis or extraocular movement deficit with dilated pupil

›Posterior communicating artery aneurysm until excluded

›If any ptosis or ophthalmoplegia, emergent CTA or MRA head

›Subarachnoid hemorrhage

›Thunderclap headache with dilated pupil

›Depressed level of consciousness

›If worst headache of life, non-contrast CT head then LP

›Brainstem or toxicologic emergency

›Bilateral mydriasis with altered mental status

›Anticholinergic toxidrome features

›If unstable, ABC stabilization before workup

›Benign branch recognition

›Isolated tonic pupil pattern

›Dilated pupil with no ptosis

›Full extraocular movements

›Light-near dissociation

›Poor light reaction

›Slow tonic near constriction

›If classic and isolated, outpatient pathway appropriate

Key Concepts

›Core principle

›Isolated dilated pupil with no ptosis and full eye movements is Adie's until proven otherwise

›CN III palsy dilated pupil is virtually never isolated

›Ptosis or motility deficit redirects to vascular imaging

›Postganglionic parasympathetic denervation of iris sphincter

02History/hx83

Onset and presenting symptoms

›Discovery pattern

›Incidental finding

›Noticed in mirror

›Pointed out by others

›Acute or subacute onset

›One pupil suddenly larger

›Constant versus intermittent course

›Visual complaints

›Blurred near vision

›Accommodative difficulty

›Worse with sustained reading

›Photophobia

›Glare in bright light

›Improved with sunglasses

Key historical elements

›Precipitating context

›Recent viral or respiratory illness

›Postinfectious mechanism

›COVID-19 reported association

›Orbital trauma or surgery

›Ciliary ganglion injury

›Prior eye procedures

›Medication and exposure review

›Topical anticholinergic exposure

›Atropine, cyclopentolate, tropicamide

›Scopolamine patch transfer to eye

›Nebulized and systemic agents

03Physical Exam/exam52

Pupillary examination

›Pupil size and shape

›Affected pupil dilated

›Mydriatic in acute phase

›May appear irregular from segmental palsy

›Anisocoria characterization

›Greater in light early

›Affected pupil may become smaller over years

›Light and near responses

›Light reflex

›Absent or markedly diminished direct response

›Diminished consensual response from affected side

›Near response

›Tonic slow constriction to accommodation

›Slow redilation after near effort

›Light-near dissociation

›Near response better than light response

›Hallmark of tonic pupil

Slit lamp and ocular exam

›Slit lamp findings

›Segmental vermiform movements

›Worm-like iris sphincter contractions

›Pathognomonic for Adie's

›Iris sphincter inspection

›Sectoral palsy

›No sphincter tears unlike trauma

›Motility and lid assessment

›Extraocular movements

04Differential Diagnosis/ddx41

Dangerous diagnoses

›Life and vision threats

›Pupil-involving CN III palsy

›ICD-10 H49.0

›Always ptosis or motility deficit

›Emergent aneurysm exclusion

›Subarachnoid hemorrhage

›ICD-10 I60.9

›Thunderclap headache

›Brainstem lesion

›Altered consciousness

›Crossed neurologic signs

Benign and pharmacologic mimics

›Pupillary mimics

›Pharmacologic mydriasis

›Does not constrict to 1% pilocarpine

›Anticholinergic exposure history

›Physiologic anisocoria

›Less than or equal to 1 mm difference

›Both pupils react normally

›Present in about 20% of population

›Traumatic mydriasis

›Blunt ocular trauma history

›Sphincter tears on slit lamp

›Dissociation and small-pupil mimics

›Argyll-Robertson pupil

›Bilateral small irregular pupils

›Light-near dissociation with miosis

05Laboratory Tests/lt32

Targeted workup for atypical cases

›When labs are indicated

›Atypical or bilateral presentation

›Secondary cause concern

›Systemic symptoms

›Classic isolated case

›No routine labs needed

›Bedside pharmacologic test suffices

›Infectious screen

›Syphilis serology

›RPR or VDRL screening

›FTA-ABS confirmation

›Lyme serology

›Endemic exposure

›Two-tier testing

Systemic and autoimmune panels

›Metabolic and inflammatory

›Glycemic testing

›HbA1c

›Fasting glucose

›General panels

›CBC and CMP

›ESR and CRP

›Autoimmune and neuropathic

›Connective tissue screen

›ANA

›Anti-SSA and anti-SSB

›Anti-ganglioside antibodies

06Diagnostic Tests/dt53

Scoring Systems

›Pharmacologic diagnostic testing

›Dilute pilocarpine test

›Instill 0.0625% or 0.125% in both eyes

›Wait 30 to 40 minutes

›Adie's pupil constricts from denervation supersensitivity

›Normal pupil does not constrict significantly

›Diagnostic accuracy

›0.0625% pilocarpine AUC 0.954

›0.125% pilocarpine AUC 0.840

›Change in pupil diameter >= 0.5 mm gives 100% sensitivity

›Specificity 82.8% at that threshold

›1% pilocarpine test

›Distinguishes pharmacologic mydriasis

›Pharmacologic pupil does not constrict

›Adie's and CN III palsy both constrict

›Bedside clinical assessment

›Anisocoria in light versus dark

›Adie's anisocoria greater in light early

›Horner anisocoria greater in dark

›Light-near dissociation documentation

›Poor light response

›Tonic near response

MRI

›MRI brain indications

›Concern for compressive lesion

›Atypical or progressive features

›With contrast for infiltrative process

07Disposition/dispo24

Discharge pathway

›Safe discharge criteria

›Classic isolated Adie's pupil

›No ptosis and full extraocular movements

›No neurologic deficits

›Confirmatory testing

›Positive dilute pilocarpine response

›Pharmacologic mydriasis excluded

›Outpatient referral

›Ophthalmology or neurology follow-up

›Within 2 to 4 weeks

›Confirmation and counseling

›Return precaution counseling

›New ptosis or diplopia

›Worsening headache

Admission and urgent workup

›Mandatory escalation triggers

›Ptosis or extraocular movement limitation

›Emergent vascular imaging

›Neurosurgery consult if aneurysm

›Bilateral tonic pupils with neurologic signs

›Areflexia and ataxia

›Miller-Fisher or Guillain-Barre admission

›Systemic autonomic failure

›Symptomatic orthostasis

›Neurology evaluation

08Treatment/t40

Reassurance and symptomatic care

›Idiopathic Holmes-Adie management

›Reassurance

›Benign natural history

›No vision-threatening course

›Photophobia measures

›Sunglasses

›Tinted or photochromic lenses

›Accommodative support

›Reading glasses

›Near-add correction

Pharmacologic symptom control

›Topical pilocarpine therapy

›Dilute pilocarpine drops

›Pilocarpine 0.125% topical as needed

›For symptomatic blurred vision or photophobia

›Improves near function and cosmesis

›Administration counseling

›Brow ache possible initially

›Avoid in narrow-angle concern without specialist input

›No systemic medication routinely indicated

›Isolated Adie's needs no oral therapy

›Avoid unnecessary anticholinergics

Treatment of secondary causes

›Underlying etiology management

›Syphilis

›Penicillin G per stage-specific protocol

›Benzathine penicillin G 2.4 million units IM for early disease

09Special Populations/sp30

Pregnancy

›Pregnancy considerations

›Imaging approach

›MRI without gadolinium preferred when needed

›CTA reserved for true CN III palsy concern

›Medication safety

›Topical dilute pilocarpine minimal systemic absorption

›Avoid unnecessary systemic agents

›Secondary cause treatment

›Penicillin preferred for syphilis in pregnancy

›IVIG acceptable for Guillain-Barre variant

Geriatric

›Older adult features

›Broader differential

›Higher microvascular CN III palsy risk

›Diabetes and hypertension common

›Anisocoria interpretation

›Review old photographs

›Distinguish longstanding from new

›Medication review

›Nebulized ipratropium exposure

›Scopolamine patch use

Pediatrics

›Pediatric considerations

›Less common presentation

›Consider postinfectious cause

›Consider neuroblastoma-related when Horner

›Diagnostic approach

10Background/b39

Epidemiology

›Frequency and demographics

›Predominant in women

›Age 20 to 50 years

›Most cases idiopathic Holmes-Adie

›Laterality and progression

›Usually unilateral at onset

›Becomes bilateral about 4% per year

›Associated conditions

›Syphilis most common infectious link

›Autoimmune and paraneoplastic associations

Pathophysiology

›Mechanism of tonic pupil

›Postganglionic parasympathetic injury

›Ciliary ganglion lesion

›Short ciliary nerve damage

›Denervation and reinnervation

›Denervation supersensitivity to cholinergics

›Aberrant reinnervation from accommodative fibers

›Light-near dissociation results

›Holmes-Adie syndrome triad

›Tonic pupil

›Diminished deep tendon reflexes

›Segmental anhidrosis

Therapeutic Considerations

›Management principles

›Diagnosis before treatment

›Exclude CN III palsy

11Patient Discharge Instructions/pdi22

copy discharge instructions

›Your diagnosis

›You have a tonic (Adie's) pupil, a usually harmless condition

›One pupil is larger and reacts slowly to light

›It is not a sign of a stroke or emergency in your case

›Home care

›Use sunglasses for light sensitivity

›Use reading glasses if close-up vision is blurry

›Use prescribed dilute pilocarpine drops only as directed

›What to expect

›The larger pupil may slowly become smaller over months to years

›Light sensitivity and blurry near vision often improve with time

›The other eye may develop the same change later

›Return to the ER immediately if

›New drooping eyelid

›New double vision

›Sudden severe headache

›Weakness, numbness, or trouble walking

›Difficulty swallowing or speaking

›Follow up

›See ophthalmology or neurology within 2 to 4 weeks

›Bring old photos showing your eyes if available

›Keep any blood test or imaging appointments arranged

12References/r15

Guidelines and key sources

›Review and diagnostic sources

›Adie's pupil diagnostic challenge review (Medical Science Monitor 2022)

›Dilute pilocarpine test for Adie's tonic pupil (Scientific Reports 2021)

›Pupillary response to pilocarpine concentrations (American Journal of Ophthalmology 2002)

›Neuro-ophthalmology references

›Approach to anisocoria (Current Opinion in Ophthalmology 2016)

›The eye in neurological disease (Lancet 2004)

›Adult Strabismus Preferred Practice Pattern (Ophthalmology 2024)

›Syndromic associations

›Bilateral tonic pupils Holmes-Adie versus generalised neuropathy (BJO 2007)

›Tonic pupils with anti-GT1a and GQ1b antibodies (Internal Medicine 2022)

›Tonic pupils with acute ophthalmoplegic polyneuritis (Annals of Neurology 1977)

›Coding standards

›ICD-10 H57.05 tonic pupil

›SNOMED CT Adie syndrome concept

Evidence & Review

Evidence & Review