BASICS
DESCRIPTION
Round pupils that differ in size by 0.5 mm or more
EPIDEMIOLOGY
Prevalence
• 15–30% (physiologic)
• Other causes rare
RISK FACTORS
• Physiologic: None
• Trauma (including intraocular or brain surgery)
• Iritis
• Meningitis
• Topical contact with mydriatic or miotic (drop, ointment or plant)
• Paraspinal neuroblastoma
• Birth trauma
• Family history of anterior segment dysgenesis
Genetics
• Physiologic not genetic:
– Anterior segment dysgenesis may be due to a genetic disorder.
GENERAL PREVENTION
• Physiologic: None
• Genetic counseling for anterior segment dysgeneses
• Avoidance of contact with mydriatics and miotics
• Careful follow-up screening for patients at risk for iritis (e.g., juvenile idiopathic arthritis) to detect inflammation early
PATHOPHYSIOLOGY
• Maldevelopment or dysfunction of the pupillary dilator or sphincter muscle or
• Mechanical impairment of the pupil (e.g., posterior synechia) or
• Idiopathic (physiologic)
ETIOLOGY
• Physiologic/idiopathic (most common)
• Congenital Horner syndrome:
• Birth trauma including brachial plexus injury
• Neoplasm rare
• Acquired Horner syndrome
ALERT
Can represent metastatic neuroblastoma:
• Congenital third cranial nerve palsy
• Acquired third cranial nerve palsy:
– Trauma (most common) – surgical or nonsurgical
– Meningitis
– Tumor
– Aneurysm:
Unlikely under age 14
• Traumatic mydriasis (sphincter tears)
• Posterior synechiae due to iritis
• Adie’s tonic pupil:
– Much less common in children than in young women
– Usually idiopathic
• Pharmacologic mydriasis:
– Usually cycloplegic (pharmaceutical or environmental)
• Congenital miosis
• Aniridia and other anterior segment dysgenesis
COMMONLY ASSOCIATED CONDITIONS
• None in physiologic anisocoria
• Neoplasm in 23% of pediatric Horner syndrome (1)
ALERT
Note especially neuroblastoma metastatic to cervical sympathetic chain, which can be life threatening and requires urgent workup.
• Other neoplasms causing Horner syndrome in children include benign paraspinal neuroblastoma, rhabdomyosarcoma (2), Ewing sarcoma, and juvenile xanthogranuloma (1).
• Abnormalities of extraocular muscle function and strabismus in third cranial palsy
DIAGNOSIS
HISTORY
• Trauma:
– Nonocular:
– Birth trauma
– Surgical (neck or chest) or other postnatal trauma
– Ocular blunt trauma
– Intraocular surgery
• Age of onset:
– Review old photos
• Duration
• Ptosis:
– Horner syndrome (1–2 mm or less)
– Third cranial nerve palsy
• Anhidrosis/hypohidrosis:
– Seen in some but not all cases of Horner syndrome
• Contralateral facial flushing and ipsilateral hypohidrosis (Harlequin sign):
– Seen in some but not all cases of Horner syndrome in infants
• Longstanding iris heterochromia in congenital Horner and some anterior segment dysgenesis
PHYSICAL EXAM
• Acuity
• Normal in physiologic anisocoria
• May be decreased due to amblyopia in third nerve palsy and Adie’s
• Accommodative amplitudes/dynamic retinoscopy:
– May be decreased in third cranial nerve palsy and Adie’s tonic pupil)
• Pupils:
– Anisocoria greater in darkness (smaller pupil is abnormal):
– Physiologic anisocoria
– Horner syndrome
– Mechanical restriction
– Anisocoria greater in light (larger pupil is abnormal):
– Third cranial nerve palsy
– Adie’s pupil
– Traumatic mydriasis
– Pharmacologic mydriasis
– Dilation lag of smaller pupil:
– Horner syndrome
– Light-near dissociation:
– Adie’s tonic pupil
– Segmental constriction:
– Adie’s tonic pupil
– Relative difference in pupil size preserved in dim and bright illumination: Physiologic anisocoria
– Iris heterochromia (lighter iris ipsilateral to smaller pupil):
Congenital Horner syndrome
• Eyelids:
– 1–2 mm (but not more) of upper eyelid ptosis in Horner syndrome, ipsilateral to the smaller pupil
– More profound ptosis in third nerve palsy, ipsilateral to the larger pupil
– “Inverse ptosis” (slight elevation of the lower lid of the eye with the small pupil) with Horner syndrome)
• Motility:
– Normal with all causes of anisocoria except third nerve palsy
– Limitation of elevation, depression, and adduction in third nerve palsy:
The palsied eye is typically “down and out” (exotropic and hypotropic)
• Palpate abdomen and supraclavicular region looking for neuroblastoma or other neoplasm
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• If suspect Horner, with no clear evidence of birth injury: Spot urine for vanillylmandelic acid (VMA) and homovanillic acid (HVA)
• Note: Urine testing may not be as sensitive as imaging (1)[C] in diagnosing neuroblastoma
Imaging
• MRI (with and without gadolinium) of the brain, neck, chest, and upper abdomen if suspect Horner syndrome unless clear evidence of birth trauma (1)[C]:
– Some recent evidence (3)[C] questions the need for extensive evaluation of patients with Horner syndrome.
• MRI of brain with MRA if suspect third cranial palsy and no clear etiology
Diagnostic Procedures/Other
• Review old photographs to help determine whether anisocoria is congenital or acquired
• Pharmacologic testing for Horner syndrome:
– Cocaine 5% drops dilate the normal pupil but not the Horner pupil.
– Apraclonidine 0.5% produces reversal of anisocoria in 30–60 min in Horner syndrome.
– Effect easier to see in bright than in dim light (4)[C]
– Hydroxyamphetamine 1% dilates preganglionic but not postganglionic Horner pupil.
• Pharmacologic testing for Adie’s tonic pupil: Pilocarpine 0.125% constricts Adie’s pupil but not a normal pupil or a pharmacologically dilated pupil.
TREATMENT
MEDICATION
• For Adie’s tonic pupil: Pilocarpine 0.125% b.i.d.–q.i.d. can be used for cosmesis and to aid accommodation.
• For posterior synechiae due to iritis: Pharmacologic mydriasis (such as atropine 1% drops) to break the synechiae, in addition to topical steroid treatment (with systemic medication as indicated) for the iritis.
• Anisocoria due to other causes is not treated; instead, an underlying cause is identified and treatable.
ADDITIONAL TREATMENT
General Measures
• Amblyopia (most likely with third nerve palsy and Adie’s) is treated with refractive correction if needed, and patching or atropine penalization.
• Cosmetic contact lens is used if concerns about appearance in older children.
Issues for Referral
• Patients discovered to have evidence of a neoplasm should be referred without delay to appropriate specialists (oncology, neurosurgery).
• Patients below 12 months of age with Adie’s tonic pupil should be referred to pediatric neurology to rule out familial dysautonomia.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
• Physiologic: None needed
• Third nerve palsy and Adie’s: Follow-up to rule out amblyopia
• Possible Horner syndrome with equivocal clinical and/or pharmacologic findings: Re-examine in 3–6 months, consider repeat urine testing
• Follow-up for glaucoma in anterior segment dysgeneses
• Follow-up for other causes of anisocoria is determined by the underlying cause.
PATIENT EDUCATION
• Reassure parent that anisocoria itself does not affect acuity or visual development (except if accommodation impaired in Aides or third cranial palsy).
• If Horner syndrome is suspected but not proven, instruct the parent to watch for development of ptosis and anhidrosis.
PROGNOSIS
• Physiologic anisocoria: Excellent. No deficit is expected.
• Other causes: Prognosis depends on underlying cause.
REFERENCES
1. Mahoney NR, Liu GT, Menacker SJ, et al. Pediatric Horner syndrome: Etiologies and roles of imaging and urine studies to detect neuroblastoma and other responsible mass lesions. Am J Ophthalmol 2006;142(4):651–659.
2. Jeffery AR, Ellis FJ, Repka MX, et al. Pediatric Horner syndrome. J AAPOS 1998; 2(3):159–167.
3. Smith SJ, Diehl N, Leavitt JA, et al. Incidence of pediatric Horner syndrome and neuroblastoma threat. Arch Ophthalmol 2010;128(3):324–329.
4. Chen PL, Hsiao CH, Chen JT, et al. Efficacy of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients under low or high illumination. Am J Ophthalmol 2006;142(3):469–474.
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