Ординатура / Офтальмология / Английские материалы / Ocular Disease Mechanisms and Management_Levin, Albert_2010

Box 58.3  Amblyopic vision

•Reduced contrast sensitivity for small objects

•Positional uncertainty for all sized objects

nothing to do with the aforementioned threshold deficit. The first of these reasons involves spatial distortions that mainly affect central vision and high spatial frequencies. These distortions predominantly affect strabismic amblyopes.4 Their basis is not well understood but their presence has led to the suggestion that there may be a disruption to the retinotopic map provided by the amblyopic eye input (Box 58.3).25 Another suggestion is that spatial distortions are a result of anomalous interactions between cells with different orientation preferences subserved by the amblyopic eye.26 A possibly related finding is that strabismic amblyopes are more uncertain of the spatial position of objects when using their amblyopic eye.27 Nonstrabismic anisometropes do not have such a deficit.28 This has nothing to do with the poorer vision of the strabismic eye and it shows the unexpected property (i.e., compared with the contrast threshold deficit) of being spatial scale-invariant.29 What this means is that the positional uncertainly of large objects is just as pronounced as that for small objects. This is shown in Figure 58.3 (left panel) where spatial accuracy in a three-element alignment task for the fixing eye is compared to that of the fellow amblyopic eye for stimuli of a number of spatial scales (i.e., sizes). Sensitivity for both eyes varies with spatial scale, being better at finer spatial scales. Importantly, the deficit in amblyopia is similar for large and fine scales. Therefore a deficit in spatial accuracy does not provide a good explanation for spatial distortion since the former is spatial scale-invariant and the latter is not. Apart from an inaccuracy there is also, in most cases, a standing distortion (measured as a bias in alignment tasks) that may well relate to the perceived distortions.30–35 A number of attempts have been made to make this connection; both deficits could reflect different aspects of the fidelity of the retinotopic map. Animals with amblyopia secondary to a strabismus or lid suture experience exactly the same scale-invariant positional uncertainty as found in humans.29,36 The size (often an order of magnitude or more) and spatial scale invariance of this deficit are shown in Figure 58.3 (middle and right panel). The fact that such an anomaly occurs not only in cases of strabismus but also as a consequence of lid suture suggests that a basic, but hitherto unknown, aspect of visual development has been disrupted, rather than it simply being the consequence of an adaptation to the strabismus, such as anomalous retinal correspondence.37

So far we have only considered the detection or appearance of stimuli in local regions of the visual field, regions small enough that they could be potentially explained in terms of single cells in V1. There are also reported deficits in amblyopia involving the processing of stimuli across much larger regions of visual space. Such tasks are considered to be “global” if information in very different regions of space has to be interrelated in some way. Cells with sufficiently large receptive fields and the processing properties required to accomplish the combination of information across space are found in the ventral and dorsal streams of the extrastriate cortex. Although local motion sensitivity (i.e., V1) is thought

Models

Box 58.4  Amblyopic cortical deficit

•V1 (contrast sensitivity and positional uncertainty)

•Dorsal and ventral extrastriate cortex (global motion and form)

to be normal in amblyopia (but see Ho and Giaschi38), global motion sensitivity has been shown to be anomalous in both eyes of strabismic amblyopes. The form of the deficit suggests it is not due to the visibility problem (i.e., V1) but to the “global processing” of local motion thought to occur in the dorsal stream of the extrastriate cortex.39 Optic flow is also affected, suggesting a site beyond middle temporal area along the dorsal processing stream.40 A similar deficit occurs for global form processing, suggesting an extrastriate deficit along the ventral processing stream.41 There are two processes involved in the global processing of information, one involving integration and the other differentiation. The former involves the utilization of local signals distributed in different parts of the stimulus field, whereas the latter involves the segregation of signal from noise in the same parts of the field. Both operations must occur together in global signal/noise tasks (i.e., coherence measures) of the type that have revealed deficits in amblyopic processing. In similar tasks without noise where only signal integration is required, amblyopes perform normally on both a global form42 and global motion tasks.43 Since it is the introduction of noise to a global task that results in reduced performance for amblyopes, one is led to believe that signal/noise segregation is the main problem rather than signal integration per se.44 Until we know more about the physiological basis for this important operation in normal vision, it is premature to discuss its physiological basis in amblyopia. However, a starting point would be the suppressive surrounds that have been shown to be an important part of extrastriate receptive fields (e.g., MT) and thought to play a role in signal/noise segregation.45

There are also suggestions that the deficits in amblyopia extend to visual cognition (Box 58.4). It has been shown that numerosity judgments are deficient,46 that higher-order motion38 is defective, and that the perception of faces is impaired.47

Models

Models of visual loss in amblyopia are not well developed and tend to apply only to separate aspects of the dysfunction. They have tried to explain the contrast sensitivity deficit and the binocular vision deficit in terms of the function of single cells in area V1. None has been completely successful. For example, the loss of contrast sensitivity in amblyopia that affects mainly high spatial frequencies and central vision, at least for strabismics, is thought to be located in area V1 because some centrally located neurons display reduced contrast sensitivity and anomalous spatial properties.48 The fact that there is such variability from animal to animal and that the magnitude of the single-cell deficit is not enough to explain adequately the full extent of the behavioral deficit has led people to think that there is more to the story than is gleaned from the responses of single cells

Deprived cats

1000 LM01

Blob spread (80 mins)

1000 LM02

100

10

1

Strabismic cats

1000 S1

Blob spread (SDmin)

in V1.49 In strabismic animals with a mild to moderate amblyopia there do not appear to be fewer neurons subserving the amblyopic eye, but some of these neurons do show a reduced sensitivity.49 In strabismic animals where the amblyopia is severe, there is a suggestion that fewer neurons (i.e., as determined by the encounter rate) might subserve amblyopic function.50,51 What is generally agreed is that fewer neurons appear to have binocular connections in amblyopic animals.52

448

The binocular vision deficit in amblyopia has traditionally been thought to be the result of loss of binocular connections in area V1.52 However, a recent study53 has shown that binocular summation can be normal in strabismic amblyopes once the sensitivity difference between their eyes is taken into account, suggesting that substantial binocular connections may be intact. It remains a possibility that the connections at the single-cell level are in fact intact and that this can only be revealed by first equating the contrast of the

Figure 58.4  Two competing models to explain the spatial accuracy deficit in amblyopia. (A) A normal complement of cells with disordered connections. (B) Fewer cells with normal connections.

inputs to the two eyes, or observing the influence of one eye’s input on the other, rather than the response from each eye alone. Another important aspect of the physiology is that strabismic animals display interocular inhibitory interactions54 that may underlie the reduced binocular function in strabismic amblyopia and which may be amenable to treatment. There is good evidence that binocular function, including stereo, can be restored in strabismic and anisometropic amblyopes under suitable treatment regimes.9,10,12,13,55 The key issue for the future is to understand the nature of these suppressive interactions that prevent normal binocular and stereoscopic function in amblyopia.

The positional uncertainty deficit that is an important feature of the vision of strabismic amblyopes (Figure 58.3) has been explained in two related ways. Levi and Klein27 suggested that there were fewer cells driven by the amblyopic eye and as a consequence of the less than adequate sampling of space, positional accuracy is reduced (Figure 58.4B). The scale invariance of the deficit (Figure 58.3) would then imply that this undersampling occurs equally at all scales. The other proposal (Figure 58.4A) is that there is an uncalibrated neural disarray, implying not fewer cells, but rather a disarray in the retinotopic map. The idea is that at birth our visual systems are broadly accurate in their retinotopy but during visual experience this is refined or calibrated by functional Hebbian rules. A strabismus disrupts this calibration and results in a positionally uncalibrated cortex for the input from the deviated eye. While both proposals are able to explain the inaccuracy problem, the disarray hypothesis can account for the fixed spatial distortions reported by amblyopes.56,57 The physiology suggests that there are a number of explanations including a loss of cells, modified cellular properties, and aberrant nerve connections.

The global motion and global form deficits in amblyopia have been investigated more extensively psychophysically. It has been proposed that the deficits are not due to poor contrast sensitivity or indeed poor local motion or local orientation discrimination, as might occur in area V1, but rather are due to impaired segregation of signal and noise,58 a property of extrastriate cortex.

Brain imaging

The use of functional brain imaging in amblyopia is still at an early stage and the expectation that it will provide the

Critical periods

link between the behavioral picture of the dysfunction and the single-cell models has not yet been realized. What researchers have been able to show is that the cortical dysfunction extends well beyond V1, involving a substantial region of extrastriate cortex.59–61 This is shown in Figure 58.5, where functional activation is displayed on a flattened region of cortex, comparing the fixing and fellow amblyopic eye stimulation. The solid lines demark the boundaries of the different retinotopically distinct visual areas.

The deficit is extensive, involving a substantial region of extrastriate cortex. This is not surprising given the now welldocumented behavioral deficits for global form,62 global motion,39,40 higher-level motion and tracking,38,63 numerosity,46 positional uncertainty,28,57 and face perception.47 The single-cell models have concentrated on the V1 deficit in order to explain the contrast sensitivity deficit which is only a part, and possibly not that important a part, of the amblyopic syndrome. However, even the contrast sensitivity deficit may not be able to be adequately explained by considering V1 alone.48

An interesting result is that the retinotopic map supplied by the amblyopic eye is not as accurate as that from the fellow normal eye, at least in some strabismic amblyopes.64 This finding is not related to the reduction in acuity, or the magnitude of activation for that matter, but may play a role in the increased positional uncertainty and/or the spatial distortions known to be a property of the vision of strabismic amblyopes. It may reflect a human analog of the small adaptive shift in retinal coordinates found for cells in the lateral suprasylvian cortex of strabismic cats65 and postulated to be the neural basis of anomalous retinal correspondence.66

Critical periods

It has been known for a long time that there is a critical period for the creation of amblyopia. This comes out most clearly in studies of strabismus in humans, where the onset of strabismus after the age of 7−8 years does not cause amblyopia.66 The time course of the critical period for the production of ocular dominance shifts by monocular deprivation has been worked out for several species (Figure 58.6). It starts a short time after opening, peaks at a young age, and declines from then until puberty.

Experiments in both animals and humans have shown that there is not a single critical period, but several. Amblyopia can be reversed after the critical period for its creation is over; there are different critical periods for different visual functions; the duration of the critical period depends on the severity of its cause and the previous visual history of the animal; and in some circumstances a deficit can be created in the adult.67

The ability to reverse amblyopia after the end of the critical period emerges most clearly in studies of human anisometropia. A regime of full refractive correction, lenses, or prisms to improve alignment, 2−5 hours/day of occlusion, and active vision therapy over 10−20 weeks improves acuity by 75−100% in patients 8−49 years of age.68 The success appears to be due to the time and efforts of both eye care practitioners and patients. In addition, there are several cases showing recovery from strabismic amblyopia, in particular

Table 58.1  Major syndromes/conditions associated with strabismus

Genetic/developmental

Congenital fibrosis of the extraocular muscles

Down syndrome

Marfan syndrome

Albinism

Sotos syndrome

Duane retraction syndrome

Brown syndrome

Moebius syndrome

Prader−Willi syndrome

Chiari malformation

Craniofacial dysostoses

Mitochondrial myopathies

Charcot−Marie−Tooth disease/centronuclear myopathy

Acquired

Fetal alcohol syndrome

Fetal hydantoin syndrome

Premature birth/perinatal hypoxia

Hydrocephalus/Sylvian aqueduct syndrome

Cerebral palsy

Myasthenia gravis

Graves disease

Multiple sclerosis

Stroke

Figure 58.6  Critical period for ocular dominance shifts produced by monocular deprivation. The critical period starts shortly after eye opening, peaks a few weeks (rodents and higher mammals) or months (humans) after that, and declines until near puberty. At the peak, several days of monocular deprivation can produce a large ocular dominance shift.

the interesting case of stereo Sue, with recovery of stereoscopic vision in her 40s.55

The point that there are different critical periods for different visual functions emerges most clearly from experiments with animals.69 In macaques, the critical period for the magnocellular pathway, which deals with movement, occurs earlier than the critical period for the parvocellular

Pathophysiology

Table 58.2  Treatment options for strabismus/amblyopia

pathway, which deals with fine detail and acuity.70 In cats, the critical period for sensitivity to direction of movement ends earlier than the critical period for ocular dominance.71 In human strabismus, it is difficult to produce improvement in stereopsis after 2 years of age, notwithstanding the case of stereo Sue, whereas improvement in acuity can be obtained after operations up to 7−8 years of age.66 The production of amblyopia in adults has been found so far in mice with monocular deprivation and a light anesthetic72 − monocular deprivation being a more severe form of deprivation than strabismus, which in turn is more severe than anisometropia (Tables 58.1−58.4).

Pathophysiology

Experiments on animals have demonstrated some of the physiological mechanisms involved in amblyopia, mostly from models of deprivation amblyopia. Axons coming from the deprived eye retract, and axons from the nondeprived eye expand, with corresponding changes in the dendrites of the postsynaptic cells. In addition to these anatomical changes, there are physiological changes in the neural connections leading to the strengthening of active synapses and the weakening of inactive ones. The afferent signals activate receptors, second messengers, and various genes and proteins involved in these changes. Several of these substances are more abundant, or more active, during the critical period, accounting for the ability of the visual cortex to adapt to strabismus, anisometropia, and deprivation in infants and children.69 These are called plasticity factors.

The reduced ability of the adult visual cortex to make similar adaptations can be attributed partly to the lack of these plasticity factors. In addition, the neurons become less

Section 8  Pediatrics Chapter 58  Amblyopia

Deficiencies in optic radiations/tract/optic nerve (hypoplasia) or thalamus

Abnormal retinal circuitry/ retinoblastoma

Defects (refractive errors) in the optic apparatus (lens/ cornea): cataract/astigmatism

plastic for structural reasons. For example, they become myelinated, so that in mice mutant for the myelin NoGo receptor, plasticity is maintained beyond the end of the critical period.73 Moreover, there is a condensation of extracellular proteins into perineuronal nets, so that mutants that affect these processes also have increased plasticity beyond

Table 58.4  Animal models for strabismus and extraocular muscle (EOM) research

the end of the critical period.74 This is a very active area of research, but none of these findings is close to leading to a therapy in humans.

Summary

Amblyopia is not one condition but many. In each, a number of basic visual functions are disrupted, ranging from contrast sensitivity to positional uncertainty to higher cognitive functions such as numerosity. The deficit is mainly cortical and extends well beyond V1 to include large areas of processing in the dorsal and ventral streams of the extrastriate cortex. It is produced by imbalancing the visual input to the two eyes during the critical period of early visual development. Since there are different critical periods for different visual functions, the timing of this early visual disruption may be critical for the type of amblyopic produced and may account for the heterogeneity of the condition.

1.Hess RF, Pointer JS. Differences in the neural basis if human amblyopias: the distribution of the anomaly across

the visual field. Vis Res 1985;25:1577– 1594.

4.Hess RF, Campbell FW, Greenhalgh T. On the nature of the neural abnormality in human amblyopia; neural

aberrations and neural sensitivity loss. Pflugers Arch Eur J Physiol 1978;377: 201–207.

24.Hess RF, Bradley A. Contrast coding in amblyopia is only minimally impaired above threshold. Nature 1980;287:463– 464.

28.Hess RF, Holliday IE. The spatial localization deficit in amblyopia. Vis Res 1992;32:1319–1339.

29.Gingras G, Mitchell DE, Hess RF. The spatial localization deficit in visually deprived kittens. Vis Res 2005;45:975– 989.

30.Bedell HD, Flom MC. Monocular spatial distortion in strabismic amblyopia. Invest Ophthalmol Vis Sci 1981;20:263– 268.

39.Simmers AJ, Ledgeway T, Hess RF, et al. Deficits to global motion processing in human amblyopia. Vis Res 2003;43:729– 738.

48.Kiorpes L, Kiper DC, O’Keefe LP, et al. Neuronal correlates of amblyopia in the visual cortex of macaque monkeys with

experimental strabismus and anisometropia. J Neurosci 1998;18:6411– 6424.

53.Baker DH, Meese TS, Mansouri B, et al. Binocular summation of contrast remains intact in strabismic amblyopia. Invest Ophthalmol Vis Sci 2007;48:5332– 5338.

54.Sengpiel F, Jirmann K-U, Vorobyov V,

et al. Strabismic suppression is mediated by interactions in the primary visual

cortex. Cerebral Cortex 2006;16:1750– 1758.

59.Barnes GR, Hess RF, Dumoulin SO, et al. The cortical deficit in humans with strabismic amblyopia. J Physiol (Lond) 2001;533:281–297.

67.Daw NW. Critical periods and amblyopia. Arch Ophthalmol 1998; 116:502–505.

68.Wick B, Wingard M, Cotter S, et al. Anisometropic amblyopia: is the patient

Key references

ever too old to treat? Optom Vis Sci 1992;69:866–878.

73.McGee AW, Yang Y, Fischer QS, et al. Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor. Science 2005;309:2222– 2226.

74.Pizzorusso T, Medini P, Berardi N, et al. Reactivation of ocular dominance plasticity in the adult visual cortex. Science 2002;298:1248–1251.

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.1 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.

Clinical background

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.2 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).2 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

Strabismus

Christopher S von Bartheld, Scott A Croes, and L Alan Johnson

about 10 : 1.3 Many genetic and other syndromes are associated with strabismus (Table 59.1).

Historical development

Strabismus has a history in European, but not other cultures,4 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.4 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 reviewed4 and modern research and hypotheses about major causes of strabismus summarized.5

Epidemiology

The prevalence of strabismus among humans and other primates is approximately 4–6% with little geographic variation.3,6 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.3 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).

Genetics

There is a genetic predisposition to strabismus. With the exception of some specific strabismus syndromes, the inher-

Normal

Esotropia

Exotropia

Hypertropia

Figure 59.1  Deviation of the eyes in strabismic humans. The Hirschberg test (“corneal light reflex”) assesses eye alignment by the location of the light reflex. Note the light reflex centered in the straight, but not the deviated eyes. (Modified from Wright KW. Pediatric Ophthalmology and Strabismus. St. Louis: Mosby, 1995.)

itance pattern appears to be multifactorial. Approximately 20–30% of children born to strabismic parents will develop strabismus.3 Twin studies have shown a 70–80% concordance in monozygotic twins, but 30–40% in dizygotic twins.7 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.8

Diagnostic workup

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 strabismus9 (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-up10 (Figure 59.2). Sensory evaluation determines the presence of diplopia, suppression, anomalous retinal correspondence, and stereopsis.2,11,12 High-resolution orbital imaging (e.g., by dynamic magnetic resonance imaging) can reveal additional pathophysiological mechanisms relevant for treatment.13 These measures – and the patient’s history – contribute to determine the likely etiology and appropriate treatment (see below).

Clinical background

Table 59.1  Major syndromes/conditions associated with strabismus

Genetic/developmental

 Congenital fibrosis of the extraocular muscles

 Down syndrome

 Marfan syndrome

 Albinism

 Sotos syndrome

 Duane retraction syndrome

 Brown syndrome

 Moebius syndrome

 Prader–Willi syndrome

 Chiari malformation

 Craniofacial dysostoses

 Mitochondrial myopathies

 Charcot–Marie–Tooth disease/centronuclear myopathy

Acquired

 Fetal alcohol syndrome

 Fetal hydantoin syndrome

 Premature birth/perinatal hypoxia

 Hydrocephalus/sylvian aqueduct syndrome

 Cerebral palsy

 Myasthenia gravis

 Graves’ disease

 Multiple sclerosis

 Stroke

Differential diagnosis

Two conditions can be confused with true strabismus. In pseudostrabismus a wide, flat nasal bridge and epicanthal folds contribute to an esotropic appearance.9 Abnormalities of “angle kappa” reflect an increased disparity between the visual axis and the anatomic pupillary axis.9 In both conditions, cover testing will reveal the lack of actual strabismus.

Treatment

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,2 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.14,15 Botulinum toxin can be injected into overacting extraocular muscles to reduce their contractility.16–19 This approach is used in small-angle esotropia and in paretic strabismus where the toxin is injected into the overacting

C D

Figure 59.2  Cover and prism tests for the diagnosis of strabismus. In the normal individual (shown in Figure 59.1), the eyes remain straight when covered. (A) Esotropia: outward movement indicates that the right eye is esotropic. (B) Exotropia: inward movement indicates a right exotropia.

(C)Hypertropia: movement of the right eye indicates a right hypertropia.

(D)Measuring the angle of deviation with the Krimsky test: prisms of increasing power are placed before the strong (fixating) eye until the light reflex is centered in the weak (deviating) eye. Prisms of increasing power can also be placed before one eye until the shift of the eyes with alternating cover is neutralized (prism/alternate cover test). (Modified from Wright KW. Pediatric Ophthalmology and Strabismus. St. Louis: Mosby, 1995 and von Noorden GK. Atlas of Strabismus, 4th edn. St. Louis: Mosby, 1983.)

Box 59.1  Importance of early treatment

Early treatment – within months of recognition – is advised for optimal outcome in infantile strabismus

antagonist muscle to the paretic muscle.20 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).21,22

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.3,11,12,23,24

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

456

Table 59.2  Treatment options for strabismus/amblyopia

usually require eye muscle surgery25 or botulinum injections (Table 59.2).

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.9,26 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.27 Strabismus treatment should be considered restorative, rather than purely cosmetic.2,3 The most frequent complication of strabismus surgery or botulinum injection is an overor 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.17–20,33

Pathology

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.28,29 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