Evolution has bestowed humans and other frontal-eyed foveate animals with considerable overlap of the visual fields from the right and left eye. This allows for binocular vision and stereopsis. The three-dimensional appearance of fused binocular objects and depth perception are major perceptual advances in evolution with adaptive value. Unfortunately, the advantages of binocular fusion and resulting correspondency of fused objects come with a price: they allow for the possibility of diplopia (double vision). Diplopia arises when the two eyes are misaligned – a condition called strabismus (Greek for squint). Strabismus has different consequences, depending on whether the misalignment occurs in a developing infant or in a mature adult. The successful formation of neural (and especially cortical) circuits for binocular vision is intricately linked to eye alignment and proper visual processing during development. This chapter provides an overview of strabismus with emphasis on the circular nature of interactions between the eye and the brain, and discusses current knowledge of pathophysiological mechanisms as well as treatment options.
Key symptoms and signs
Strabismus is a misalignment of the eyes which may occur in the horizontal or vertical direction ( Figure 59.1 ), or along a torsional axis. This misalignment may be constant, intermittent, or present only when normal binocular vision is interrupted. The term strabismus derives from the Greek strabizein, meaning to squint, to look obliquely or askance. Depending on age of onset, the individual may be asymptomatic, or may experience diplopia (double vision) or asthenopia (eyestrain). Diplopia is rarely a symptom in childhood strabismus, due to the development of suppression − the brain actively “turns off” one cortical image, usually that from the deviated (weaker) eye. Thus, strabismus in children can cause amblyopia (loss of visual acuity not directly attributable to a structural abnormality of the eye or visual pathways: see Chapter 58 ). In both children and adults, strabismus results in a partial or complete degradation of the quality of binocular vision. Infantile esotropia (inward turning of one or both eyes) is more common than exotropia (an outward deviation of the eye) by a ratio of about 10 : 1. Many genetic and other syndromes are associated with strabismus ( Table 59.1 ).
|Congenital fibrosis of the extraocular muscles|
|Duane retraction syndrome|
|Charcot–Marie–Tooth disease/centronuclear myopathy|
|Fetal alcohol syndrome|
|Fetal hydantoin syndrome|
|Premature birth/perinatal hypoxia|
|Hydrocephalus/sylvian aqueduct syndrome|
Strabismus has a history in European, but not other cultures, as the “evil eye” of mythology and primitive folklore, as exemplified by Flotsam and Jetsam, the creepy, cross-eyed servants of the sea witch, Ursula, in Disney’s animated feature film, The Little Mermaid . Hippocrates noticed that strabismus frequently affects parents and their children. Paulus of Aegina (Alexandria, 625–690) developed the use of a perforated mask to guide the squinting eye. Al-kindi (“Alkindius”) from Baghdad (813–873) advocated occlusion therapy and ocular exercises. A malposition of the lens or cornea was held responsible in the 18th century. In 1743, Buffon realized that the squinting eye had poorer vision and corrected refractive anomalies with glasses. Surgical treatment became common in the 19th century. Famous persons with squint include Michelangelo’s sculpture of David, and the 16th American president, Abraham Lincoln. The history of strabismus was comprehensively reviewed and modern research and hypotheses about major causes of strabismus summarized.
The prevalence of strabismus among humans and other primates is approximately 4–6% with little geographic variation. Thus, the number of people affected by strabismus worldwide in 2008 was about 330–350 million. Males and females are equally affected. The risk of infantile esotropia increases significantly in infants with prematurity, neonatal intraventricular hemorrhage, Down syndrome, or hydrocephalus. The importance of strabismus is reflected by the fact that four professional vision journals are devoted to strabismus: Journal of Pediatric Ophthalmology and Strabismus (since 1978); Strabismus (1993); Binocular Vision and Strabismus Quarterly (1996); and Journal of American Association for Pediatric Ophthalmology and Strabismus (1997).
There is a genetic predisposition to strabismus. With the exception of some specific strabismus syndromes, the inheritance pattern appears to be multifactorial. Approximately 20–30% of children born to strabismic parents will develop strabismus. Twin studies have shown a 70–80% concordance in monozygotic twins, but 30–40% in dizygotic twins. The cause of several congenital strabismus syndromes was localized to mutations in genes required for the development and connectivity of motoneurons that innervate extraocular muscles.
Both sensory and motor factors must be assessed. Ocular alignment can be grossly evaluated by the position of the corneal reflection of a light held in front of a patient’s eyes – in normally aligned eyes the light reflection is positioned symmetrically in each pupil ( Figure 59.1 ). In the cover test, movement of the eyes is examined first with vision in both eyes, and then the eyes are alternately blocked by an occluder as the patient maintains visual fixation on a target. Movement of the unoccluded eye indicates strabismus ( Figure 59.2 ). Variations of the cover and prism test more accurately assess and quantify the angle of deviation which is important for treatment and follow-up ( Figure 59.2 ). Sensory evaluation determines the presence of diplopia, suppression, anomalous retinal correspondence, and stereopsis. High-resolution orbital imaging (e.g., by dynamic magnetic resonance imaging) can reveal additional pathophysiological mechanisms relevant for treatment. These measures – and the patient’s history – contribute to determine the likely etiology and appropriate treatment (see below).
Two conditions can be confused with true strabismus. In pseudostrabismus a wide, flat nasal bridge and epicanthal folds contribute to an esotropic appearance. Abnormalities of “angle kappa” reflect an increased disparity between the visual axis and the anatomic pupillary axis. In both conditions, cover testing will reveal the lack of actual strabismus.
The treatment of strabismus varies with the type and cause. The correction of refractive errors with glasses is important. Appropriate hyperopic spectacle correction may be the only treatment needed for accommodative esotropia (overconvergence in response to a hyperopic refractive error). Types of strabismus that are due to weakness of the fusional reflexes can be treated with occlusion of one eye to reduce the suppression response and to increase the brain’s fusional response, or with exercises to strengthen the convergence reflex. Some optometrists advocate visual training more generally, but the effectiveness for other types of strabismus is controversial. Botulinum toxin can be injected into overacting extraocular muscles to reduce their contractility. This approach is used in small-angle esotropia and in paretic strabismus where the toxin is injected into the overacting antagonist muscle to the paretic muscle. The main techniques of strabismus surgery consist of recession to weaken an extraocular muscle (physically shortening it by moving its normal insertion), resection to strengthen a muscle (by removing a portion of the muscle), or transposition (by moving a muscle out of its original plane of action to assume the action of a paretic muscle).
Early treatment is advised in infantile esotropia to allow for the potential development of binocular vision and to decrease the risk of amblyopia and abnormal binocular vision as the visual system matures ( Box 59.1 ). A short interval between symptoms and alignment is a powerful predictor of treatment success. The eyes should be aligned within months upon recognition of the misalignment.
Early treatment – within months of recognition – is advised for optimal outcome in infantile strabismus
Sensory deficiencies such as a cataract, refractive error, or amblyopia have to be addressed, because sensory fusion is needed to maintain eye alignment and prevent postsurgical drift. In adults with acquired strabismus from trauma or cranial nerve palsy, a period of observation for spontaneous improvement is often indicated. In adults, small deviations may be managed with prism glasses, but larger deviations usually require eye muscle surgery or botulinum injections ( Table 59.2 ).
|Correction of refractive error||Sharpen retinal image to promote fusion|
|Relieve accommodative convergence|
|Extraocular muscle exercises||Strengthen convergence|
|Eye patch, penalization||Reduce suppression/treat amblyopia||,|
|Botulinum toxin||Weaken the overacting muscle||, , , ,|
|Trophic factors (experimental)||Strengthen the underacting muscle||, ,|
|Resection||Strengthen extraocular muscle||,|
|Recession||Weaken extraocular muscle||,|
|Transposition||Treatment of paralytic strabismus||,|
Prognosis and complications
Strabismus treatment reduces the likelihood of amblyopia and potentially restores binocular vision. The potential to relieve diplopia and improve binocularity (“fusional potential”) is present in both children and adults. Strabismus carries a stigma and psychosocial burden, i.e., strabismic patients may be regarded as less intelligent and can face discrimination in job hiring and promotion. Strabismus treatment should be considered restorative, rather than purely cosmetic. The most frequent complication of strabismus surgery or botulinum injection is an over- or undercorrection which may require further treatment. Success rates after single botulinum injections are lower (30–40%) than after initial surgery (90%), but final results after multiple botulinum injections can be comparable. Success rates differ between studies, based on the type of strabismus being treated.
Pathologies of strabismus vary greatly with the particular primary etiology (see below) and secondary adaptations that occur in response to the disturbance of binocular vision. At the level of the extraocular muscles, primary pathological conditions may involve inflammation, infiltration, fibrosis, scarring after trauma, as well as secondary adaptations due to altered usage of the muscle. Tissue from congenitally strabismic human eye muscles was examined for alterations in ultrastructure. Damaged myofibers were found, particularly at the scleral aspect, and damaged myofibers were lacking palisade endings (potential proprioceptive innervation). In general, lack of representative muscle samples from human surgery hampers progress. Primary pathologies may also be found at the level of the motor nerve, e.g., neuropathies or disorders of the neuromuscular junction. Within the brain, specific pathologies may reflect developmental (agenesis of motor nuclei) or acquired conditions (brain lesions due to stroke, trauma, or disease such as multiple sclerosis). The cortex may show alterations due to abnormal circuitry for binocular vision, making it difficult to distinguish between primary cause and secondary adaptation. In Graves’ disease (hyperthyroidism), shared epitopes between orbital fibroblasts, extraocular muscles, and the thyroid may lead to interstitial edema and enlarged extraocular muscles that are infiltrated with inflammatory cells (see Chapter 56 ). In Duane retraction syndrome, the abducens nucleus and nerve are absent or hypoplastic, and the lateral rectus muscle is innervated by a branch of the oculomotor nerve (see Chapter 57 ). In the autoimmune disease myasthenia gravis, circulating antibodies lead to a reduced number of acetylcholine receptors in neuromuscular junctions, reducing the safety factor and extraocular muscle function.