What are the causes of strabismus?

Causes of Strabismus

Strabismus arises from a diverse array of etiologies spanning congenital developmental abnormalities, acquired neurological and systemic diseases, sensory deprivation, aging-related changes, and iatrogenic complications—with the most recent comprehensive guidelines emphasizing that adult strabismus affects approximately 4% of the population and requires recognition of both peripheral neuromuscular causes and central nervous system dysfunction. 1

Congenital and Developmental Causes

Childhood-Onset Strabismus Persisting into Adulthood

• Recurrent, decompensated, or unresolved childhood strabismus represents a major category, where early-onset misalignment either persists or decompensates in adulthood 1
• Congenital cranial dysinnervation disorders (CCDDs) result from mutations in genes critical for brainstem ocular motoneuron development, including PHOX2A, SALL4, KIF21A, ROBO3, and HOXA1 2
• These disorders cause paralytic strabismus with limited eye movements due to deficits in cranial motor neuron differentiation or abnormal cranial nerve axon guidance 3

Genetic Syndromes

• Strabismus is a variable feature in over 255 genetic syndromes, most commonly those associated with intellectual disability 3
• The variable penetrance and association with neurological disorders underscores the likely neurological basis of strabismus pathophysiology 3
• Fourth nerve palsy is a notable congenital cause that may present in adulthood 1

Neurological Causes

Cranial Nerve Palsies

• Third nerve palsy causes strabismus through disruption of multiple extraocular muscles; pupil-involving presentations require urgent neuroimaging for aneurysmal compression 4
• Sixth nerve palsy results in esotropia from lateral rectus weakness 1
• Fourth nerve palsy causes vertical misalignment and torsional diplopia 1
• Skew deviation represents a supranuclear vertical misalignment from brainstem lesions 1

Central Nervous System Disorders

• Demyelinating plaques, tumors, hemorrhage, and infections involving the brainstem may cause strabismus through disruption of central oculomotor pathways 4
• Compressive lesions including aneurysms, meningiomas, schwannomas, and metastatic lesions must be ruled out when neurological signs are present 4
• Most comitant, non-restrictive, non-paralytic strabismus cases result from deficits in central neural pathways involved in visual perception and oculomotor control rather than peripheral muscle dysfunction 5, 6

Neuromuscular Disorders

• Myasthenia gravis causes variable strabismus from fluctuating neuromuscular transmission at the extraocular muscles 1

Sensory Causes

Vision Loss and Deprivation

• Sensory strabismus develops when significant vision loss in one eye disrupts binocular fusion mechanisms 1
• Asymmetric vision loss from macular degeneration, epiretinal membranes, myopic axial elongation, or diabetic retinopathy can trigger fixation switch diplopia 1
• Longstanding cataracts causing visual deprivation may result in acquired loss of central fusion 1

Fixation Switch Diplopia

• Occurs in patients with childhood strabismus history and suppression when cataract or refractive surgery improves vision in the previously suppressed eye, causing it to become dominant 1
• The previously suppressed eye now fixates, unmasking the underlying deviation 1

Age-Related and Anatomical Causes

Divergence Insufficiency and Sagging Eye Syndrome

• Divergence insufficiency esotropia presents with diplopia at distance, commonly in patients 60-80 years of age 1
• Sagging eye syndrome results from age-related lateral displacement of the lateral rectus pulley and medial displacement of the superior rectus, causing esotropia with distance diplopia and modest vertical misalignment 1
• Facial aging with blepharoptosis and deep superior lid sulci are commonly present 1
• More frequent in myopes and well-managed with prism or strabismus surgery 1

High Myopia

• Strabismus associated with high axial myopia, including strabismus fixus, results from progressive globe elongation and extraocular muscle displacement 1

Convergence Insufficiency

• Causes exotropia at near with difficulty maintaining fusion during reading and close work 1

Endocrine and Systemic Causes

Thyroid Eye Disease (Graves' Disease)

• Graves' disease causes restrictive strabismus from inflammatory infiltration and fibrosis of extraocular muscles 1
• Most commonly affects the inferior and medial rectus muscles 1
• Previously undiagnosed thyroid eye disease may be unmasked after cataract or other ocular surgery 1

Systemic Toxins

• Botulism causes abnormally reactive or fixed pupils in 24% of confirmed cases, which may be accompanied by extraocular muscle weakness 4

Traumatic Causes

Orbital Trauma

• Direct globe injury causes strabismus through mechanical disruption of extraocular muscles, orbital fractures with muscle entrapment, or nerve damage 1
• Orbital fractures may trap extraocular muscles, causing restrictive strabismus 1
• Adhesions and entrapment may extend deep into the orbit, complicating surgical management 1
• Globe laceration repair requiring temporary muscle disinsertion and reattachment may result in strabismus 1

Iatrogenic Causes

Anesthetic Myotoxicity

• Retrobulbar or peribulbar anesthesia for cataract extraction, keratoplasty, or other procedures causes myotoxicity in 0.23% of cases 1
• Initial presentation is transient paresis followed by deviation into the field of action of the involved muscle 1
• Superior and inferior rectus muscles are most commonly injured (70% inferior rectus), but any muscle including obliques may be involved 1
• Hypertropia or hypotropia results from restriction when damage is extensive, or overaction from focal contracture or hypertrophy 1

Cataract and Refractive Surgery

• Diplopia occurs in 0.18% of cataract surgeries overall 1
• Causes include anesthetic myotoxicity, bridle suture trauma causing muscle nicking with bleeding and scar formation, previously undiagnosed conditions, pre-existing/unmasked binocular disorders, and fixation switch diplopia 1
• Monovision choice may create fusional challenges 1
• Postoperative anisometropia, aniseikonia, and meridional aniseikonia may disrupt fusion 1

Glaucoma Surgery

• Trabeculectomy causes transient strabismus in 4% and persistent diplopia in 3% of patients 1
• Aqueous shunt surgery causes transient strabismus in 4-25% and persistent motility disorders in 2-77% depending on implant type and follow-up duration 1
• Binocular diplopia prevalence reaches 21% with plate reservoir surgery 1
• Mechanisms include mass effect from implant or bleb, scarring, fat adhesion, or incorporation of adjacent extraocular muscles 1
• Superotemporal implants cause hypertropia and exotropia; superonasal implants cause hypotropia 1
• Strabismus usually presents within 3 months, often within the first month 1

Scleral Buckling Surgery

• Persistent strabismus requiring intervention occurs in 3.8% of patients 1
• Causes are multifactorial: loss of fusion, poor vision, aniseikonia, direct muscle trauma, anesthetic myotoxicity, muscle malposition, scar formation, muscle slippage or disinsertion, superior oblique tendon entanglement, and mass effect 1, 7
• Approximately 50% have torsional component, usually excyclotropia 1, 7
• Encircling bands carry substantially higher risk than radial buckles 1
• Fusional disturbance and torsional diplopia may occur even without buckling 1

Pterygium Surgery

• Incidence under 3% (three cases in 920 procedures) 1
• Results from direct medial rectus injury or florid scarring with recurrence 1
• Consecutive exotropia from medial rectus damage or restrictive incomitant esotropia from scarring 1
• Retrobulbar anesthesia increases risk compared to topical anesthesia 1

Blepharoplasty and Eyelid Surgery

• Upper lid blepharoplasty may cause diplopia from trochlear damage 1
• Lower lid blepharoplasty may damage the inferior rectus 1
• Scarring, hemorrhage, and fat adherence are implicated mechanisms 1
• Excessive cautery, hemorrhage, and misdirected dissection are causative factors 1
• Ptosis repair may unmask previously existing strabismus, classically double elevator palsy with upgaze limitation 1

Critical Clinical Pitfalls

• Diplopia persisting beyond 6 months after ocular surgery is unlikely to resolve spontaneously and warrants referral to a strabismus specialist 1
• Unrecognized pre-existing strabismus should be checked by examining spectacles for prism correction and performing cycloplegic refraction 1
• The multifactorial and incomitant nature of post-surgical strabismus makes complete elimination of diplopia difficult or impossible in most cases 1
• Never assume pupil-sparing presentation when any degree of pupillary involvement exists—this requires full neuroimaging workup for potential aneurysm 4