Strabismus, commonly known as crossed eyes or squint, is a visual disorder in which the eyes are misaligned and do not point in the same direction, preventing them from focusing simultaneously on the same point in space.[1] This misalignment can be constant or intermittent and may affect one or both eyes, leading to issues such as double vision, reduced depth perception, or amblyopia (lazy eye) if untreated.[2] It is estimated to affect 2% to 5% of the global population, with approximately 5 to 15 million cases in the United States alone.[1]The condition arises from disruptions in the coordination of the extraocular muscles, cranial nerves (particularly the third, fourth, and sixth), or central nervous system controls that govern eye alignment.[1] Common causes include congenital factors, such as genetic predispositions or developmental anomalies present at birth; refractive errors like hyperopia (farsightedness); neurological disorders including cerebral palsy, stroke, or cranial nerve palsies; and systemic conditions such as thyroid eye disease, diabetes, or retinopathy of prematurity.[3][4] In children, it often manifests before age 6, while adults may develop it due to trauma, injury, or underlying health issues.[2]Symptoms vary by type and severity but typically include noticeable eye deviation—inward (esotropia), outward (exotropia), upward (hypertropia), or downward (hypotropia)—along with head tilting to compensate for the misalignment, eye strain, or blurred vision.[1] In young children, the brain may suppress input from the deviated eye to avoid double vision, increasing the risk of amblyopia, which affects about one-third of untreated pediatric cases and can lead to permanent vision loss if not addressed by age 7 to 11.[3] Diagnosis involves comprehensive eye examinations, including visual acuity tests, cover-uncover tests to assess alignment, and sometimes neuroimaging for sudden-onset cases to rule out neurological causes.[2]Treatment focuses on restoring alignment and preventing vision complications, with early intervention being crucial for optimal outcomes.[1] Non-surgical options include corrective eyeglasses or contact lenses to address refractive errors, eye patching to strengthen the weaker eye, vision therapy or orthoptics to improve muscle coordination, and prism lenses to reduce double vision.[3] For persistent cases, surgical procedures adjust the extraocular muscles—such as recession (weakening) or resection (strengthening)—and are often more effective in children under 2 years old, though multiple surgeries may be needed.[5] Additional approaches like botulinum toxin injections can temporarily weaken overactive muscles.[2] With prompt management, the prognosis is generally excellent, minimizing long-term visual impairment, though lifelong monitoring may be required.[1]
Definition and Classification
Definition
Strabismus is a visual disorder characterized by the misalignment of the eyes, in which one or both eyes deviate from their normal parallel position, preventing them from focusing on the same point in space simultaneously.[1] This condition, commonly referred to as "crossed eyes" or "squint," disrupts binocular vision and can lead to symptoms such as double vision or suppressed vision in one eye.[6] Strabismus most frequently manifests in childhood but can also occur in adults due to various factors.[4]The misalignment in strabismus is distinguished as either manifest or latent. Tropia, or manifest strabismus (also known as heterotropia), refers to a constant deviation visible when both eyes are open and viewing an object, such as in esotropia or exotropia.[1] In contrast, phoria (or heterophoria) represents a latent misalignment that is typically controlled by the brain's fusional mechanisms during normal binocular viewing but becomes apparent when fusion is disrupted, for example, by covering one eye.[1]Normal eye alignment relies on the coordinated action of anatomical and neural structures. The extraocular muscles—six per eye, including the medial rectus, lateral rectus, superior rectus, inferior rectus, superior oblique, and inferior oblique—enable precise movements and maintain alignment within the bony orbits that house the eyes.[1] These muscles are innervated by cranial nerves III (oculomotor), IV (trochlear), and VI (abducens), with higher-level neural control from supranuclear pathways in the brainstem and cortex ensuring conjugate eye movements according to Sherrington's law of reciprocal innervation and Hering's law of equal innervation.[1]Historically, strabismus has been classified using terms derived from Greek roots to describe the direction of deviation; for instance, esotropia denotes an inward turn of the eye toward the nose ("eso" meaning inward and "trope" meaning turn), while exotropia indicates an outward deviation toward the temple ("exo" meaning outward).[7][8] These naming conventions form the basis for broader categorization of strabismus types.[7]
Types
Strabismus is classified by the direction of ocular misalignment, with esotropia referring to inward deviation of the eye toward the nose, exotropia indicating outward deviation away from the nose, hypertropia describing upward deviation, and hypotropia denoting downward deviation.[1] These directional categories form the primary basis for identifying the misalignment pattern observed during clinical examination.[9]Classification by onset distinguishes congenital or infantile strabismus, which manifests at or before 6 months of age, from acquired strabismus that develops later.[1] A prominent example is infantile esotropia, typically presenting as a large-angle constant inward deviation between 2 and 4 months of age, often exceeding 40 prism diopters.[9] In contrast, acquired forms may emerge after infancy due to various influences, though the specific timing aids in differentiating management approaches.[1]Strabismus is further categorized by laterality as unilateral, where the deviation consistently affects one eye, or alternating, in which either eye may deviate while the other fixes on the target.[1] Unilateral cases often lead to stronger fixation preference in one eye, whereas alternating forms maintain more balanced binocular potential.[9]Special types include paralytic strabismus, resulting from nerve or muscle palsy such as oculomotor nerve dysfunction causing limited eye movements, and restrictive strabismus, arising from mechanical restrictions like those in Brown syndrome where the superior oblique tendon limits elevation.[1] Additionally, strabismus is deemed incomitant if the deviation angle varies across different gaze directions, often linked to paralytic or restrictive etiologies, versus comitant, where the misalignment remains constant regardless of gaze position, commonly seen in congenital forms.[1] These distinctions guide precise diagnostic evaluation by highlighting whether the misalignment is uniform or gaze-dependent.[9]
Epidemiology and Risk Factors
Prevalence
Strabismus affects approximately 2% to 5% of children worldwide, with pooled estimates from systematic reviews indicating a global prevalence of 1.93% (95% CI: 1.64–2.21%) across all ages, though rates are higher in pediatric populations.[1][10][11] Exotropia is the more common form globally at 1.23% (95% CI: 1.00–1.46%), compared to esotropia at 0.77% (95% CI: 0.59–0.95%).[10]Prevalence peaks in infancy and early childhood, with about 2% of children affected by age 3 years and most cases manifesting before age 6.[12][1] Adult-onset strabismus is rarer, with an annual incidence of 54.1 cases per 100,000 adults (95% CI: 50.2–58.0) and a lifetime risk of approximately 4%.[13][14]Demographic variations influence occurrence, with higher rates observed in premature infants—up to 14.7% in the first year of life and 3% by age 5—compared to term infants.[15][16] A family history significantly elevates risk, with monozygotic twin concordance rates of 54%–82% for any strabismus.[17] Ethnically, exotropia predominates in African American, Asian, and Hispanic populations, while esotropia is more frequent among non-Hispanic White individuals; for example, exotropia accounts for over 50% of cases in some Asian cohorts versus under 30% in Caucasian groups.[18][19] Regional differences align with these patterns, showing higher exotropia prevalence in Asia (e.g., 4.84% in some Chinese preschoolers) and parts of Africa compared to esotropia-dominant rates in Europe and North America.[20][10]Over time, strabismus prevalence has remained stable at around 2%–4% in children, but detection has improved due to widespread vision screening programs in schools and pediatric care, leading to earlier identification in up to 5%–6% of screened populations in high-resource settings.[21][12] These programs, such as those recommended by the U.S. Preventive Services Task Force for ages 3–5, contribute to higher reported rates without altering underlying incidence.[22]
Risk Factors
Strabismus exhibits a significant genetic component, with family history serving as a major risk factor. Individuals with a first-degree relative affected by strabismus face a 3- to 5-fold increased relative risk, and odds ratios for familial occurrence range from 2.6 to 6.42, particularly in cases of accommodative esotropia where maternal family history elevates the odds to 6.42 (95% CI, 1.39-29.7). Twin studies further underscore heritability, showing concordance rates of 54%–82% in monozygotic twins compared to 14%–47% in dizygotic twins, indicating polygenic inheritance patterns without a single dominant gene. Up to 30.6% of strabismus patients report a close relative with the condition, supporting complex genetic influences that interact with environmental triggers.Prenatal and perinatal factors substantially heighten strabismus risk, particularly in vulnerable infants. Low birth weight (1000-1500 g) is associated with an odds ratio of 2.5 (95% CI, 1.02-8.94), while prematurity and related cicatricial retinopathy of prematurity confer an odds ratio of 5.89 (95% CI, 1.27-27.33). Maternal smoking during pregnancy independently increases the risk by 46%, with an overall odds ratio of 1.46 (95% CI, 1.32-1.60), escalating to 1.79 (95% CI, 1.39-2.31) for consumption of 10 or more cigarettes daily; this association holds across esotropia and exotropia subtypes. Difficult deliveries and other perinatal complications, including large head circumference and congenital abnormalities, further contribute to elevated risk through potential disruptions in early ocular development.Certain medical conditions are strongly linked to higher strabismus incidence, often due to underlying neurological or structural anomalies. Children with cerebral palsy face increased susceptibility, as do those with Down syndrome, where strabismus prevalence can exceed 50% in some cohorts. Hydrocephalus and brain tumors similarly elevate risk by affecting cranial nerve function and eye alignment, with affected individuals showing up to several-fold higher rates compared to the general population. Refractive errors, notably hyperopia exceeding +3.00 diopters (with odds ratios increasing to approximately 10–20 for +3.00 to +5.00 D compared to emmetropia), and significant anisometropia (e.g., OR 7.79 [95% CI: 4.46–8.43] when combined with hyperopia less than +3.00 D), predispose to accommodative esotropia.[23][24]Environmental exposures, including trauma, can precipitate strabismus by damaging ocular motor pathways. Head injuries from accidents, strokes, or other blunt force events are recognized risk factors, particularly in those with preexisting vulnerabilities, leading to acute or persistent misalignment through disruption of extraocular muscle control or cranial nerves. Prolonged screen time in children, while more firmly linked to myopia and convergence issues, has emerging associations with strabismic tendencies via sustained near-focus strain, though direct causation remains under investigation in pediatric populations.Early vision screening acts as a protective measure by facilitating timely detection and intervention, reducing the long-term impact of strabismus. Routine assessments from infancy through age 5, including red reflex tests and photoscreening, identify misalignment or amblyopia risks with high sensitivity, enabling treatments like glasses or patching that preserve binocular vision and prevent progression.
Causes and Pathophysiology
Etiology
Strabismus arises from a multifaceted etiology encompassing genetic, neurological, mechanical, sensory, and idiopathic factors, often interacting during critical periods of ocular development. These origins disrupt the precise coordination required for binocular alignment, leading to misalignment of the visual axes. While the precise triggers vary, they collectively impair the neuromuscular control or sensory input necessary for proper eye positioning.Genetic factors play a significant role in strabismus, particularly through mutations in genes regulating ocular morphogenesis and neural connectivity. For instance, mutations in the PAX6 gene, located on chromosome 11p13, are associated with a spectrum of ocular anomalies including strabismus, often as part of aniridia or isolated misalignment phenotypes.[25] These mutations can result in mild concomitant strabismus due to altered DNA transcription affecting eye development.[26] Other loci, such as STBMS1 at 7p22.1, contribute to non-syndromic forms with variable inheritance patterns.[27]Neurological etiologies involve dysfunction of the cranial nerves innervating the extraocular muscles, leading to paralytic strabismus. Palsies of the third (oculomotor), fourth (trochlear), or sixth (abducens) cranial nerves commonly cause acute or chronic misalignment, with sixth nerve palsy resulting in esotropia due to impaired lateral rectus function.[28] Fourth nerve palsy, the most frequent isolated cranial neuropathy, produces vertical tropia from superior oblique weakness.[29] Such palsies may stem from ischemic, traumatic, or compressive insults to the nerve pathways.Mechanical causes typically result from structural disruptions in the orbit or extraocular muscles, restricting or altering eye movement. Orbital fractures, often from blunt trauma, lead to restrictive strabismus by entrapping inferior rectus or connective tissues in the fracture site, commonly causing vertical or horizontal deviations.[30] This entrapment increases intraorbital pressure and impairs muscle excursion, as seen in blowout fractures of the orbital floor.[31]Sensory etiologies arise when visual input imbalances disrupt binocular fusion, prompting compensatory misalignment. Uncorrected refractive errors, such as high hyperopia, induce accommodative convergence excess, leading to esotropia as the eyes over-converge to focus.[32] This sensory deprivation inhibits normal fusional mechanisms, resulting in strabismus secondary to poor vision in one eye.[1]Idiopathic cases predominate in congenital esotropia, where no underlying genetic, neurological, or mechanical abnormality is identifiable despite thorough evaluation. Infantile esotropia, onset before six months, often manifests without a discernible cause, affecting approximately 1 in 300-500 infants and persisting as a primary developmental misalignment.[33]Developmental failures during infancy further contribute, particularly disruptions in foveal maturation or binocular fusion pathways. PAX6 mutations can impair foveal development, leading to hypoplasia and consequent strabismus by hindering central vision fixation.[34] Similarly, inadequate establishment of fusion mechanisms in early infancy prevents the brain from integrating binocular input, resulting in persistent tropia.[35] These etiologic factors ultimately influence downstream pathophysiological processes, such as adaptive changes in extraocular muscle innervation.
Mechanisms
Strabismus arises from an imbalance in the neural control of eye movements, involving disruptions in the oculomotor nuclei and supranuclear pathways that innervate the extraocular muscles. The oculomotor nuclei, including those for cranial nervesIII, IV, and VI, coordinate conjugate eye movements, but in strabismus, asymmetric signaling leads to misalignment by altering the balance between agonist and antagonist muscles. Supranuclear pathways, originating from cortical areas like the frontal eye fields and parietal lobe, integrate visual and vestibular inputs to maintain ocular alignment; lesions or developmental anomalies in these pathways can cause persistent deviation, as observed in infantile models where abnormal retinal projections to the dorsolateral geniculate nucleus disrupt normal oculomotor coordination.[36][37]Binocular vision disruption in strabismus primarily occurs through sensory adaptations that prevent diplopia, leading to suppression of the deviating eye's input and subsequent loss of stereopsis. Suppression involves cortical inhibition of conflicting images from misaligned eyes, particularly in the primary visual cortex, where monocular dominance columns favor the fixing eye and suppress the other to avoid double vision. This process often progresses to amblyopia, where neural connections in the visual pathway weaken for the non-dominant eye, resulting in diminished acuity and irreversible stereopsis loss if untreated during early development; studies in primate models confirm that such suppression emerges rapidly after misalignment, prioritizing single binocular vision over depth perception.[38][39][40]At the muscular level, strabismus involves dynamic imbalances in extraocular muscle function, characterized by overaction or underaction that exacerbates misalignment. In esotropia, for instance, overaction of the medial rectus muscle occurs due to unopposed contraction from weakened lateral rectus innervation, while underaction of the antagonist lateral rectus further promotes inward deviation; these patterns arise from Hering's law of equal innervation, where yoke muscles receive symmetric signals but orbital pulley systems alter force vectors. Secondary overactions, such as those in the inferior oblique, develop as compensatory responses to primary deviations, influenced by connective tissue pulleys in the orbit that guide muscle paths and modulate tension during gaze shifts.[41][42]Developmentally, strabismus manifests during critical periods in infancy when binocular fusion mechanisms are establishing, typically between birth and 6 months, where misalignment prevents the maturation of cortical fusional pathways. During this window, the visual system relies on correlated inputs from both eyes to wire binocular neurons in the visual cortex; persistent deviation disrupts this synaptogenesis, leading to a failure in establishing stereoscopic fusion and reinforcing monocular dominance. Longitudinal studies highlight that early-onset strabismus, if present before 3 months, significantly impairs the development of vergence and accommodation-convergence synergies, locking the system into non-fusional states.[43][44]Recent research as of 2025 underscores the role of cortical plasticity and genetic expression in strabismus pathogenesis, revealing how neurodevelopmental pathways contribute to misalignment. Genome-wide association studies have identified risk loci on chromosomes 2, 4, and 7 associated with esotropia and exotropia, influencing gene expression in cortical neurons that regulate oculomotor control. In induced pluripotent stem cell models, chromosome 4 duplications linked to strabismus alter expression of genes involved in synaptic plasticity and neuronal migration, reducing dendritic arborization in visual cortical layers and impairing binocular integration. These findings suggest that genetic variants modulate cortical plasticity during critical periods, providing a mechanistic link between heritability and persistent strabismic deviations.[45][46][47]
Signs and Symptoms
Ocular Signs
Strabismus manifests primarily through visible misalignment of the eyes, where one or both eyes deviate from the parallel position required for single binocular vision. In esotropia, the eye turns inward toward the nose, often appearing as crossed eyes, while in exotropia, the eye drifts outward away from the nose. Other forms include hypertropia, where the eye deviates upward, and hypotropia, downward. This deviation disrupts normal gaze and can be observed during fixation on a target.[48][49]Patients often adopt compensatory head postures, such as tilting or turning the head, to align the eyes and minimize misalignment or associated visual discomfort. These abnormal head positions improve visual acuity or avoid diplopia by optimizing the field of single vision. In cases of vertical misalignment, a head tilt may specifically counteract the deviation.[50][51]Associated ocular issues include diplopia, or double vision, resulting from the brain receiving conflicting images from misaligned eyes, which is more common in adults due to established binocular fusion. Reduced visual acuity may occur secondary to amblyopia, where the brain suppresses input from the deviating eye, leading to underdeveloped vision in that eye. Other common symptoms include eye strain (asthenopia), headaches, blurred vision, and squinting or closing one eye to achieve single vision.[52]Nystagmus, an involuntary oscillatory eye movement, can accompany strabismus, particularly in congenital cases, further impairing fixation.[49][53][54]The angle of deviation is measured in prism diopters (PD), a unit quantifying the prism power needed to neutralize the misalignment, depending on severity. The cover-uncover test detects strabismus by alternately covering each eye while observing for refixation movements, distinguishing manifest tropia from latent phoria.[55][56]Strabismus can present as constant, where misalignment persists in all gaze directions, or intermittent, occurring sporadically, often under fatigue or stress, as seen in basic exotropia. Intermittent forms may progress to constant over time if untreated.[57][52]Presentations differ by age: in children, it often manifests in early childhood, with congenital or infantile forms becoming evident by 6 months and other types, such as accommodative esotropia, developing up to age 7, while in adults, it typically arises acutely from neurological events like stroke or trauma, leading to sudden diplopia and deviation. Chronic adult cases may stem from unresolved childhood strabismus.[1][4]
Psychosocial Impacts
Strabismus significantly affects self-esteem in children, often leading to experiences of bullying and reduced confidence due to the visible misalignment of the eyes.[58] Children with strabismus report higher levels of emotional and social difficulties, including teasing from peers, which contributes to lower self-perception and avoidance of social situations.[59] These visible ocular signs exacerbate the emotional burden by drawing unwanted attention.[60]In children, strabismus can interfere with developmental processes, particularly the ability to read social cues effectively, leading to challenges in forming interpersonal relationships and interpreting nonverbal signals during interactions.[61] This disruption often results in heightened social anxiety and isolation, as affected children may struggle to engage confidently in group settings or peer activities.[62]Adults with strabismus frequently encounter social stigma, including avoidance of eye contact, which strains personal relationships and professional opportunities.[63] Perceptions of untrustworthiness or reduced attractiveness associated with eye misalignment can hinder employment prospects and social integration.[64] Strabismus in adults is linked to higher rates of anxiety and depression, with studies showing elevated scores on mental health assessments compared to the general population.[65] A meta-analysis confirms that individuals with strabismus experience increased risks of these conditions, often stemming from chronic psychosocial stress.[58]Treatment for strabismus has been associated with improved quality of life, including reductions in anxiety and depression symptoms, as well as enhanced social functioning.[66] Postoperative evaluations indicate significant gains in self-esteem and interpersonal confidence for both children and adults.[67]Cultural variations influence the perception of strabismus, with differing levels of stigma across societies; for instance, in some Asian contexts, though trustworthiness concerns persist.[68] These differences highlight how societal norms shape the psychosocial burden of the condition.[69]
Diagnosis
Clinical Assessment
The clinical assessment of strabismus begins with a detailed history taking to gather essential information about the condition's onset, progression, and potential contributing factors. Clinicians inquire about the age at which the ocular misalignment first appeared, as infantile onset before six months often indicates congenital forms, while later onset may suggest acquired causes.[70] Family history is routinely explored, given the genetic predisposition, as a positive family history of strabismus is common.[71] Associated symptoms, such as headaches, eye strain, or diplopia, are also documented, particularly in accommodative esotropia where uncorrected hyperopia can exacerbate these complaints.[32]Visual acuity testing follows to evaluate for amblyopia, a common complication of strabismus where suppressed vision in the deviating eye leads to reduced acuity. In cooperative patients, standardized charts like the Snellen chart are used to measure monocular and binocular acuity, aiming to detect differences greater than two lines between eyes that signal amblyogenic risk. For younger or non-verbal children, age-appropriate methods such as preferential looking or picture-based tests serve as equivalents to identify early visual deficits.[72]Ocular alignment is then assessed using objective tests to quantify the deviation. The Hirschberg test involves shining a penlight at the patient's eyes from approximately one-third meter and observing the corneal light reflex; asymmetry from the pupil center estimates the angle, with each millimeter displacement approximating 7 degrees or 15 prism diopters of misalignment.[73] In infants or uncooperative individuals, the Krimsky method modifies this by placing prisms over the fixing eye until the light reflex centers in the deviating eye's pupil, providing a more precise measurement for small deviations.[74]Motility evaluation examines extraocular muscle function through targeted assessments. Ductions test monocular movements in cardinal directions to detect restrictions, while versions evaluate binocular coordination using targets in nine gazes to identify underactions or overactions. Vergences assess fusional amplitudes, particularly convergence, by measuring the prism diopters required to break fusion at near and distance, helping differentiate comitant from incomitant strabismus.[75]Finally, refraction assessment is performed to uncover underlying refractive errors that may contribute to or mimic strabismus. Cycloplegic refraction, using agents like cyclopentolate to paralyze accommodation, is standard to accurately determine hyperopia or anisometropia, which can drive accommodative esotropia in up to 2% of children.[32] This step ensures that optical correction is prescribed appropriately before considering further interventions.[76]
Diagnostic Tests
The prism cover test serves as a primary quantitative method to measure the magnitude of ocular misalignment in strabismus, expressed in prism diopters (pd), by dissociating the eyes and neutralizing the deviation with prisms held before one eye while the patient fixates on a target.[77] This test quantifies both horizontal and vertical deviations, with the alternate prism cover test preferred for total deviation measurement and the simultaneous prism cover test used for smaller angles or latent components.[78]To characterize the direction and extent of strabismus, deviations are assessed in primary gaze (straight ahead) and eccentric gazes (up, down, left, right, and oblique positions), revealing patterns such as incomitance or A- or V-patterns where the deviation varies by gaze direction.[42] Measurements continue until reversal of the deviation occurs, ensuring accuracy in identifying primary versus secondary deviations, which is crucial for distinguishing constant from intermittent strabismus.[79]The synoptophore, an orthoptic instrument, evaluates binocular fusion by presenting separate images to each eye and measuring the angle of deviation while assessing the patient's ability to fuse them, often used in children to quantify strabismus and monitor treatment progress. Complementing this, stereopsis tests such as the Titmus fly (Randot) or TNO stereotests assess depth perception by detecting binocular disparity, with reduced stereoacuity indicating disrupted fusion in strabismic patients.[80] These tests help determine the sensory status, as poor stereopsis correlates with larger deviations and poorer prognosis for binocular vision recovery.[1]Imaging modalities are employed when strabismus suggests underlying neurological or orbital pathology, particularly in acute-onset or incomitant cases. Magnetic resonance imaging (MRI) is generally preferred for evaluating brainstem or cranial nerve involvement in incomitant strabismus due to its superior soft tissue resolution, while computed tomography (CT) is reserved for bony abnormalities or acute trauma.[81] Orbital ultrasound provides a non-invasive assessment of extraocular muscle enlargement or masses.[82]Electro-oculography (EOG), an electrophysiological test, records corneo-retinal potentials to quantify eye movements and detect subtle motility disorders in strabismus, such as harmonic kinetic disturbances or nystagmus suppression.[83] By placing electrodes around the orbits, EOG measures saccadic velocity, vergence, and fixation stability in primary and eccentric gazes, aiding diagnosis in cases where clinical tests are inconclusive, particularly in pediatric or non-cooperative patients.[84]Emerging diagnostic tools as of 2025 include artificial intelligence (AI)-powered systems using deep learning to detect and classify strabismus from facial images or wearable eye-tracking devices, achieving accuracies of 94-95% in preliminary studies, which may assist in early screening and triage.[85][86]
Differential Diagnosis
Strabismus must be differentiated from several conditions that present with apparent or true ocular misalignment, as misdiagnosis can delay appropriate management. Key mimics include pseudostrabismus, neurological disorders, restrictive myopathies, and systemic diseases, each distinguished by clinical history, examination findings, and targeted testing such as prism response or neuroimaging.[1]Pseudostrabismus is a common benign condition in infants mimicking esotropia due to a wide epicanthal fold or flat nasal bridge, creating an illusion of medial eye deviation without actual misalignment of the visual axes. It is differentiated from true strabismus by the absence of deviation on cover testing or Hirschberg light reflex, and it typically resolves spontaneously as facial features develop by age 1-2 years.[49][87]Neurological conditions such as cranial nerve palsies, particularly abducens (sixth) nerve palsy, can cause acute or incomitant strabismus with limited abduction and secondary esotropia, often accompanied by diplopia or head turn. These are distinguished from comitant strabismus by variable deviation in different gazes, poor response to prisms, and neuroimaging evidence of compressive lesions or ischemia; for instance, isolated sixth nerve palsy may indicate increased intracranial pressure.[1][49] Brain tumors, such as those in the posterior fossa or brainstem, may produce secondary strabismus through nerve compression or hydrocephalus, presenting with additional signs like headaches, vomiting, or papilledema, and are confirmed via MRI showing mass effect.[88][89]Thyroid eye disease (TED), also known as Graves' orbitopathy, leads to restrictive strabismus from extraocular muscle inflammation and fibrosis, typically causing vertical deviations or esotropia with proptosis and lid retraction. Differentiation relies on systemic hyperthyroidism history, elevated thyroid antibodies, orbital CT demonstrating muscle enlargement sparing the tendons, and forced duction testing revealing restriction, unlike the paretic pattern in non-restrictive strabismus.[90][91]Ocular congenital anomalies like Duane retraction syndrome mimic horizontal strabismus with limited abduction or adduction, globe retraction on attempted gaze, and eyelid fissure narrowing, but are distinguished by absent synkinesis in primary position and genetic associations (e.g., DURS1 locus mutations). Congenital fibrosis of the extraocular muscles (CFEOM) presents as restrictive, non-progressive ptosis and ophthalmoplegia from dysinnervation and fibrosis, differing from idiopathic strabismus by bilateral involvement, fixed eye positions, and genetic confirmation (e.g., KIF21A mutations). Nystagmus with a null point can simulate strabismus through compensatory head posture or apparent deviation to minimize oscillopsia, but is identified by the presence of involuntary eye movements on examination and best vision at the null position, without true misalignment on cover test.[92][93][94][54]Systemic diseases such as myasthenia gravis often manifest as variable, fatigable strabismus or ptosis mimicking cranial nerve palsies, with normal pupil function and improvement after rest or edrophonium testing. It is differentiated by electrophysiological studies (e.g., single-fiber EMG) or acetylcholine receptor antibodies, and lack of restriction on forced ductions, contrasting with fixed deviations in primary strabismus.[95][96]
Management
Optical Treatments
Optical treatments for strabismus primarily involve the use of corrective lenses to address underlying refractive errors, alleviate symptoms such as diplopia, and promote better eye alignment without invasive interventions. These methods are particularly effective in cases where strabismus is linked to accommodative or refractive issues, serving as a first-line approach for children and adults with mild deviations. By correcting hyperopia or other refractive errors, optical aids can reduce the accommodative demand that exacerbates esotropia, while prisms help fuse images to minimize double vision. Success varies by case, with studies reporting resolution or significant improvement in approximately 60-70% of refractive accommodative esotropia cases through glasses alone, though combined approaches may yield higher rates.[97][98]Prescription glasses are a cornerstone for managing strabismus associated with refractive errors, especially hyperopia, which can trigger accommodative esotropia by overworking the eyes' focusing mechanism. Full cycloplegic correction with glasses relaxes accommodation, thereby decreasing the convergence pull and improving alignment in up to 70% of children with high accommodative convergence to accommodation (AC/A) ratios. For instance, in hyperopic children, glasses have been shown to enhance stereoacuity and binocular vision, supporting retinal and visual cortex development. Indications include early-onset esotropia with significant hyperopia (>4 diopters), where glasses alone may resolve the deviation without further treatment.[99][100]Prism lenses, either ground-in or temporary Fresnel types, are employed to optically shift images and reduce diplopia in patients with small-angle strabismus, typically less than 15 prism diopters (PD). Ground-in prisms are permanently incorporated into spectacle lenses for long-term use, offering better optical quality, while Fresnel prisms—thin adhesive membranes—are used for trials or temporary relief, though they may slightly degrade acuity if exceeding 12 PD. These are indicated for adults with diplopia from residual post-surgical deviations or intermittent strabismus, as well as children with convergence insufficiency, where they improve fusion and control scores (e.g., from 3.6 to 3.3 on a 4-point scale after 8 weeks). One study reported 81% resolution of strabismus and diplopia over three years with prism glasses. Prisms are particularly beneficial in divergence insufficiency (2-18 PD), achieving 87-100% symptom relief, and vertical heterophorias, with 76-92% success in cases like superior oblique palsy.[101][102][99]Bifocals or progressive addition lenses (PALs) target convergence issues in accommodative esotropia, particularly nonrefractive types with high near-point deviations, by providing plus power for near tasks to lessen accommodative effort. These are indicated for children with residual near esotropia exceeding 8-10 PD despite full hyperopic correction, often improving binocular alignment and sensory fusion. Clinical trials show mixed efficacy, with one long-term study noting success in 25 of 44 patients over 17 years, and another reporting better logMAR visual acuity (0.69 ± 0.15) at six months compared to alternatives. PALs offer a seamless transition without visible lines but require adaptation; they are preferred for cosmetic reasons in older children.[103][104]Indications for optical treatments are broadest in refractive or mild strabismus cases, where they serve as non-invasive first-line options, potentially preventing amblyopia by promoting equal visual input. Monitoring involves regular follow-ups every 3-6 months in children to adjust prescriptions for growth-related refraction changes and assess deviation angles, visual acuity, and fusion using tools like Worth Dot tests. Compliance is key, with adjustments ensuring optimal fit and efficacy over time.[99][102][100]
Pharmacological and Non-Surgical Options
Pharmacological and non-surgical options for strabismus primarily target associated amblyopia or provide temporary muscle weakening to improve alignment, often serving as adjuncts to optical corrections or preoperative preparations, particularly in children under 8 years old.[105] These approaches include penalization therapies to strengthen the amblyopic eye and orthoptic exercises to enhance binocular function, with variable success rates depending on the deviation angle and patient compliance. Recent advancements as of 2025 also include digital binocular therapies, such as virtual reality-based training, recommended for improving fusion and stereopsis in convergence-related strabismus and amblyopia.[106][99]Occlusion therapy involves patching the preferred eye to force use of the amblyopic eye, treating the reduced vision often linked to strabismus.[105] Typically prescribed for 2-6 hours daily in children aged 3-7, it improves visual acuity by an average of 2-3 lines on eye charts, with effectiveness extending to adolescents if untreated earlier.[105] Atropine penalization offers an alternative by administering 1% eye drops to blur the preferred eye's near vision, administered daily or on weekends, achieving comparable acuity gains to patching without mechanical occlusion.[107] Both methods are indicated for moderate amblyopia (20/40 to 20/100) associated with strabismic deviations, with atropine showing higher compliance rates (78% vs. 49% for patching).[107] Limitations include variable long-term success, with reversal of amblyopia rare but possible, and side effects such as skin irritation from patches or light sensitivity from atropine.[105][107]Botulinum toxin type A injections temporarily paralyze overactive extraocular muscles by inhibiting acetylcholine release at the neuromuscular junction, with effects onset in 2-4 days and lasting 5-8 weeks.[108] Indicated for acute management of small-to-moderate deviations (<40 prism diopters) or paralytic strabismus, such as sixth nerve palsy, the procedure uses 2.5-5 units injected under topical anesthesia.[108] Success rates reach 76% for congenital esotropia under 35 prism diopters, often comparable to surgery but with shorter anesthesia times and potential for persistent alignment improvements via binocular adaptation.[108] In children, it serves as a preoperative adjunct to assess muscle balance, though multiple injections may be needed, and efficacy diminishes for large or restrictive cases.[108] Common limitations involve transient ptosis (12-25% incidence) and delayed full orthotropia.[108]Vision therapy, encompassing orthoptic exercises, aims to improve fusion, convergence, and eye coordination through targeted visual stimulation and binocular training.[99] These sessions, often office-based with home reinforcement, are suitable for mild strabismus in children under 8, particularly intermittent exotropia or esotropia, as an adjunct to other therapies.[99] A 2025 meta-analysis of 15 studies reported high efficacy for strabismus (effect size 0.9-1.1), enhancing alignment and stereopsis in select cases, though overall benefits vary by protocol adherence.[109] Recent reviews confirm improved orthophoria rates (e.g., <8 prism diopters in 70-80% of trained groups) and better simultaneous vision post-therapy.[99] Despite debated broad efficacy, 2025 analyses support its use for convergence-related deviations, with limitations including lack of standardized protocols and inconsistent long-term outcomes.[109][99]
Surgical Procedures
Surgical procedures for strabismus primarily involve adjusting the extraocular muscles to realign the eyes and improve binocular vision. These interventions target the six extraocular muscles responsible for eye movement, with the most common techniques being recession, which weakens an overacting muscle by reattaching it farther from its original insertion point, and resection, which strengthens an underacting muscle by shortening it through partial excision and reattachment closer to the origin.[110] For example, in esotropia, recession of the medial rectus muscle is frequently performed to reduce inward deviation.[111]The choice between unilateral and bilateral surgery depends on the deviation's magnitude and pattern; unilateral procedures address asymmetric or specific deficits, such as in sixth nerve palsy, while bilateral approaches are preferred for symmetric deviations to balance both eyes and minimize induced incomitance.[111] Surgical dosages are calculated based on the preoperative angle of deviation measured in prism diopters (PD), with guidelines indicating that 1 mm of medial rectus recession typically corrects approximately 3-4 PD of esotropia.[112] These dosages may be adjusted for factors like patient age, axial length, and prior surgeries to optimize outcomes.[111]Adjustable sutures enhance precision by allowing postoperative fine-tuning of muscle position under local or topical anesthesia, often within hours to a day after surgery.[113] This technique, commonly used in adults and select pediatric cases, employs methods like the bow-tie or sliding noose to reposition the muscle without reoperation, reducing under- or overcorrections in complex strabismus.[114] For congenital strabismus, surgery is ideally timed after 6-12 months of age to allow initial visual development while promoting binocularity, though earlier intervention before 10 months may benefit large-angle infantile esotropia.[115] Multiple surgeries are often required, with reoperation rates ranging from 10% to 20% depending on the strabismus type and initial correction.[116]Recent advances include minimally invasive strabismus surgery (MISS), which uses smaller incisions and endoscopic guidance to reduce tissue trauma and recovery time, showing promising alignment outcomes comparable to traditional methods as of 2025.[117] Emerging robotic assistance, such as with the da Vinci Xi system, has demonstrated feasibility in simulated procedures, offering enhanced precision and tremor reduction for delicate manipulations.[118] Pre-surgical optical treatments, like prism adaptation, may inform dosage planning but are not part of the operative phase.[111]
Prognosis and Complications
Treatment Outcomes
Treatment outcomes for strabismus are typically evaluated using metrics such as ocular alignment within 10 prism diopters (PD) of orthophoria and restoration of binocular vision, including stereopsis.[32][1]In accommodative esotropia, spectacle correction achieves resolution of misalignment in approximately 79% of cases over several years, with alignment maintained under full hyperopic correction in the majority of fully accommodative subtypes.[119] Surgical interventions for horizontal strabismus demonstrate initial success rates of 60-80%, defined as alignment within 10 PD, though recurrence occurs in 20-40% of patients within 1-3 years post-operation.[120][121]Outcomes are influenced by patient age at treatment, with early intervention before 2 years yielding superior binocular vision restoration compared to later ages, and by strabismus type, where comitant forms respond more favorably than paralytic cases due to preserved muscle function.[1][122]For associated amblyopia, patching therapy resolves the condition in about 70-80% of strabismic cases, though 20-25% experience persistence or recurrence requiring ongoing management.[123][124]Recent 2025 studies indicate that early surgical or non-surgical interventions enhance stereopsis recovery, with up to 74% of patients achieving measurable binocular depth perception improvements within one year.[125][126]
Long-Term Effects
If left untreated, particularly in children, strabismus can result in permanent amblyopia, where the brain suppresses input from the misaligned eye, leading to reduced visual acuity that becomes irreversible after approximately age 8 if not addressed.[1] This condition often accompanies loss of stereopsis, or depth perception, due to disrupted binocular vision development, which is especially pronounced in congenital cases not corrected between 6 months and 2 years of age.[127] Chronic diplopia, or persistent double vision, may also develop as a long-term consequence, exacerbating visual discomfort and potentially leading to avoidance of near tasks.[1]Following treatment, patients may experience overcorrection or undercorrection of the eye alignment, with approximately 20% of adults requiring additional surgery to achieve satisfactory outcomes.[128] In cases involving multiple surgeries, anterior segment ischemia—a rare vascular complication affecting the iris and ciliary body—can occur, with an incidence of about 1 in 13,000 procedures, and is more likely when operating on three or more rectus muscles in the same eye.[128][129]Strabismus and its management often necessitate lifelong monitoring to detect changes in alignment or vision, as recurrence can manifest in adulthood, with long-term follow-up studies reporting rates of 20-40% for esotropia and 22-59% for exotropia after initial correction.[121] Adult-onset recurrence or persistence of childhood strabismus may arise from factors such as altered near-work habits or underlying conditions, requiring periodic reassessment.[121]Surgical complications, though infrequent, include infections with an overall incidence of 0.14% and endophthalmitis in 1 per 18,500 to 350,000 cases, which can lead to scarring and permanent vision loss if severe.[128] Conjunctival scarring occurs in over 90% of surgeries but is typically mild; severe cases may cause restrictive strabismus.[128] Persistent diplopia post-surgery affects about 0.8% of adults, particularly those with poor suppression mechanisms.[128]Overall quality of life is reduced in individuals with strabismus due to visual limitations, but early intervention improves outcomes, with a 2025 study of 114 children showing significant post-surgical gains in eye-specific and psychosocial health-related quality of life scores, independent of age or strabismus type.[130] Longitudinal evidence links prompt treatment to better adult visual function, mitigating risks of enduring impairments.[1]
Strabismus in Animals
Occurrence in Animals
Strabismus manifests in various non-human species, primarily as a pathological condition rather than a normal variant, with higher incidence in domestic animals due to genetic predispositions and conformational traits. In dogs, it is commonly reported in brachycephalic breeds such as Boston Terriers, Pugs, and Shar-Peis, where the shortened skull leads to lateral strabismus (exotropia) as part of brachycephalic ocular syndrome, exacerbating exposure and potential discomfort.[131] This form is often congenital and hereditary, though exact prevalence rates in affected breeds remain underreported, with clinical observations suggesting it affects a notable proportion without precise population-level data.[132] Associated neurological disorders, such as vestibular dysfunction, can also induce positional ventral strabismus, particularly in older dogs.[133]In cats, congenital divergent strabismus is well-documented in Siamese and Himalayan breeds, resulting from genetic defects in the tyrosinase (TYR) gene that cause abnormal routing of optic nerve axons, akin to effects seen in albinism.[27] This inherited condition often co-occurs with nystagmus and is present from birth, contributing to reduced binocular vision.[134] Traumatic or acquired strabismus is less frequent but can arise from injuries or infections in both domestic and feral populations.Horses and livestock exhibit strabismus infrequently, typically as an acquired issue linked to trauma, such as proptosis or orbital fractures in equines, or convergent strabismus with exophthalmos in cattle breeds due to heritable defects.[135] In horses, it may accompany neurological conditions like vestibular syndrome, presenting unilaterally with head tilt.[136]Wild animals show rare occurrences, often in primates like macaques where natural strabismus affects about 4% of some populations, usually tied to developmental anomalies rather than adaptation.[137] While certain predators evolved divergent eye positions for enhanced monocular visual fields aiding hunting, true strabismus represents a misalignment deviation and is pathological in both wild and domestic contexts.[138]Veterinarians detect strabismus during routine ophthalmic exams by assessing eye alignment relative to the facial plane, noting deviations, compensatory head postures, or asymmetry in globe position, often using tools like ophthalmoscopy or Schirmer tear tests to rule out concurrent issues.[139] Early identification is crucial in breeds prone to congenital forms to monitor for associated visual or neurological impairments.
Veterinary Management
Veterinary management of strabismus in animals begins with diagnostic approaches adapted from human ophthalmology to account for species-specific behaviors and anatomy. In dogs and cats, initial evaluation includes a complete ophthalmic examination, such as assessment of pupillary light reflexes, menace response (an adaptation of the cover test to evaluate visual threat perception), and palpebral reflex testing to detect misalignment.[140]Neurological examination is essential to identify underlying causes like vestibular disease, with advanced imaging such as MRI or CT scans used for trauma-related cases to visualize orbital fractures or soft tissue abnormalities.[141] Blood tests may rule out systemic issues, while in horses, diagnosis often involves similar ophthalmic and neurological assessments, focusing on congenital or acquired deviations linked to vestibular disorders.[142]Treatment strategies prioritize addressing the underlying etiology, with non-invasive options preferred initially. In dogs, conservative management for congenital or inherited strabismus may involve environmental modifications to prevent injury, as many cases do not impair quality of life and require no intervention.[141] Surgical correction, involving extraocular muscle adjustment similar to human procedures, is reserved for acquired strabismus due to trauma or disease, with case reports indicating successful globe repositioning and resolution of deviation in selected patients, though overall success rates vary based on early intervention.[143] For birds, such as parrots or raptors, prism adaptations or corrective lenses are rarely feasible due to anatomical constraints, so management focuses on supportive care like habitat adjustments; surgery is uncommon and limited to severe cases. In horses, surgical intervention for congenital strabismus aims to realign the globe, while acquired forms may resolve with treatment of the primary neurologic condition.[142] Species-specific approaches include conservative husbandry corrections for reptiles and fish, where strabismus often stems from environmental factors like poor water quality or trauma; in arowana fish, for instance, 'drop eye' syndrome is managed by optimizing tank conditions without surgical options.[144]Prognosis for strabismus in animals is generally favorable in congenital cases treated early, particularly in dogs where surgical outcomes can restore alignment and prevent secondary complications like amblyopia analogs.[145] However, success is limited by animal cooperation during postoperative care and the underlying cause; acquired strabismus from trauma or infection carries a guarded outlook if not addressed promptly, with persistent deviation in up to 36% of canine proptosis cases post-treatment.[146]Ethical considerations in veterinary strabismus management emphasize animal welfare, prioritizing non-invasive diagnostics and treatments to minimize stress and pain.