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Neuroanatomical Structures in Extraocular Muscles and Their Potential Implication in the Management of Strabismus

Open AccessPublished:June 04, 2021DOI:https://doi.org/10.1016/j.yaoo.2021.04.004

      Keywords

      Key points

      • Human extraocular muscles contain neural structures important for the development and maintenance of binocular vision.
      • Strabismus and other oculomotor anomalies may be attributable to developmental delay or acquired dysfunctions associated with these structures.
      • Treatment options and their potential implications are discussed.

      Introduction

      Recent studies have promoted the concept that structures associated with extraocular muscles and the surrounding canopy of connective tissue play important roles in the control of eye movements, yet the neural substrate underlying their function is not fully resolved.
      Structural and functional changes occur in the human oculomotor system over the entire course of life. While structural rigor and muscular force gradually increase during postnatal development, the reverse effect occurs during the process of senescence. The oculomotor system must make long-term adjustments of the motor signal, in addition to all the short-term adjustments needed to compensate for functional fluctuations. The ability to perform constant fine-tuned corrections requires knowledge about the exact positions of the eyes. Extraocular muscles contain structures with unique sensory features, suggesting a potential capacity to monitor the position of the eyes in relation to the orbit, as well as the movement of associated fibrous structures. This type of extraretinal information enables the brain to compute the efferent signals required to retain ocular alignment during conjugate and disconjugate eye movements, as well as for holding the eyes stable in the new position of gaze. Broader neural functions are required if the gaze shift is facilitated by a contraction of muscles in the neck and torso. In such cases, somatic proprioception and vestibular information assimilates with visual and extraretinal information to create an optimal behavioral response. Dysfunctions in sensory integration may cause dyspraxia, loss of balance, and disruption of binocular alignment and strabismus. The latter anomaly is one of the most common eye conditions in children and represents a significant public health issue. The etiology and pathophysiology of this condition is not fully resolved, yet seemingly attributable to disturbance of ocular proprioception or proprioceptors. These factors should be taken into consideration in the management of strabismus and other binocular vision anomalies.
      Furthermore, several of the supranuclear structures receiving proprioception interact with pools of neurons involved in decision making, memory, and other cognitive functions. This indicates that ocular proprioception serves more neural functions than previously assumed. The notion that these functions can be augmented through noninvasive therapeutic regimens should not be dismissed.
      The current article seeks to review some of the unique neuroanatomical structures in human extraocular muscles and their neural circuits. Knowledge about the potential role of ocular proprioceptors might expand our understanding of the etiology of strabismus and other oculomotor anomalies. (The views promoted in this paper are founded on the author’s previous research and pertinent literature within the field of neuroscience.)

      Structure and function of human extraocular muscles

      Early differentiation and postnatal refinement of muscle fibers in the extraocular muscles is essential for normal development of binocular vision [
      • Danka Mohammed C.P.
      • Khalil R.
      Postnatal development of visual cortical function in the mammalian brain.
      ]. Muscle-fiber composition seems to be genetically predetermined, and the morphogenesis is almost complete at birth. The fibers are broadly classified based on the morphologic features that are critical to their function. Singly innervated fibers (SIFs) are most common and constitute more than 80% of the fiber population. Their efferent innervation consists of large diameter axons ensheathed by myelin, terminating on single neuromuscular junctions. Collectively, these coarse muscle fibers produce a forceful contraction, sufficient to counteract the opposing viscoelastic forces, and execute a saccadic eye movement.
      The multiply innervated fibers (MIFs) are less common and constitute the remaining 20% of the fiber population. Most efferent axons are small and lightly myelinated, forming numerous minute nerve terminals along the entire length of the muscle fiber (Fig. 1). MIFs do not propagate an action potential but produce instead slow-graded contractions. They are fatigue resistant and ideal for facilitating smooth-pursuit eye movements, gaze holding, and prolonged convergence [
      • Bruenech J.R.
      • Kjellevold Haugen I.B.
      The neuroanatomical basis for fine tuning of eye movements during close work.
      ]. The notion that these fine-tuned muscle fibers play a vital role in the development, and maintenance of binocular vision is strengthened by the presence of receptors, located at their distal tendon [
      • Bruenech J.R.
      • Ruskell G.L.
      Myotendinous nerve endings in human infant and adult extraocular muscles.
      ].
      Figure thumbnail gr1
      Fig. 1Transverse section of the medial rectus muscle showing the morphologic characteristics of SIF and MIF fibers. The singly innervated fibers have large diameters and abundance of sarcoplasmic reticulum. The multiply innervated fibers are smaller and more densely stained (represented by the small dark fiber in the center of the micrograph).

      Sensory receptors in human extraocular muscles

      Muscle spindles

      Spindles in human extraocular muscles have peculiar morphologic features and do not fully conform to the structural organization of their somatic counterparts. Peculiarities are present in both adult and infant muscle samples and hence not attributable to aging. The capacity of muscle spindles to provide effective proprioception, therefore, have been questioned [
      • Bruenech J.R.
      • Ruskell G.L.
      Muscle spindles in extraocular muscles of human infants.
      ]. In recent years, the attention has shifted to the tendon receptors, assumed to have a better proprioceptive capacity.

      Tendon receptors

      Human extraocular muscles lack the classic Golgi tendon organs found in somatic muscles and extraocular muscles of other species. Instead, they have myotendinous cylinders, also referred to as palisade endings. These structures are located in the distal end of MIFs. Nerve terminals arising from small myelinated axons are distributed between strands of contractile material in the junction between muscle and tendon. Cylindrical sheets of collagen encapsulate the neural elements to protect them from the mechanical force created by the adjacent muscle fibers (Fig. 2). This neuromuscular arrangement is consistent with that of other mechanoreceptors, indicative of a capacity to monitor active contraction as well as passive stretch [
      • Bruenech J.R.
      • Ruskell G.L.
      Myotendinous nerve endings in human infant and adult extraocular muscles.
      ,
      • Paduca A.
      • Bruenech J.R.
      Neuroanatomical structures in human extraocular muscles and their potential implication in the development of oculomotor disorders.
      ]. Myotendinous cylinders reside in all cross-sectional regions of both the global and orbital layer of extraocular muscles. They, therefore, are in a position to provide the brain with information about the force generated by fibers pulling on the scleral collagen, as well as from fibers pulling on the surrounding canopy of connective tissue.
      Figure thumbnail gr2
      Fig. 2Drawing to show the structural organization of the myotendinous cylinder. A recurrent small myelinated nerve fiber (thick black line) bifurcate and terminates in between strands of muscular material (illustrated in red). Sheets of cylindrical shaped collagen (black lines) encapsulate the structure.
      The orbital fiber layer (muscle fibers facing the orbit) envelopes the global layer in a “C”-shaped fashion. As the muscle fibers project toward the equator of the globe, they form sleeves of dense collagen [
      • Ruskell G.L.
      • Kjellevold Haugen I.B.
      • Bruenech J.R.
      • et al.
      Double insertions of extraocular rectus muscles in humans and the pulley theory.
      ]. The sleeves encircle the bulk of each muscle and function as pulleys. Demer [
      • Demer J.L.
      Compartmentalization of extraocular muscle function.
      ], who promoted the concept, elegantly demonstrated that these structures act as mechanical origins of extraocular muscles and influence each muscles direction of pull. He also demonstrated that the subunits of each muscle can be activated independently.
      This augments the complexity of oculomotor control and suggests that even horizontal rectus muscles may contribute in vertical excursion of the eye [
      • Demer J.L.
      Compartmentalization of extraocular muscle function.
      ]. The neural substrate underlying pulley activity and compartmental innervation awaits further research, yet it is reasonable to assume that disruption of ocular proprioception has an adverse effect on their function [
      • Bruenech J.R.
      • Kjellevold Haugen I.B.
      How does the structure of extraocular muscles and their nerves affect their function?.
      ].

      The role of proprioception in oculomotor control

      The eye is light in weight and the gravitational force remains relatively constant during eye movements. Furthermore, in contrast to many other somatic muscles, there is no external variable load acting on the extraocular muscles. These fundamental differences led to a long-standing controversy between 2 classic concepts. Helmholtz based his idea on the notion that the brain only needs a copy of the efferent signal in order to predict the position of the eye and to subsequently adjust the visual representation. In contrast, Sherrington advocated that the information about eye position is provided by muscle proprioceptors. Recent comparative and clinical studies have indicated that these concepts may not be mutually exclusive [
      • Paduca A.
      • Bruenech J.R.
      Neuroanatomical structures in human extraocular muscles and their potential implication in the development of oculomotor disorders.
      ]. The latter concept has gained more support in recent years through clinical experiments in which somatic proprioception is found to influence a subject`s registered eye position. The effect (also demonstrated in the Jendrassik Maneuver) is attributable to changes in sensory feedback from MIF non-twitch neurons [
      • Niechwiej-Szwedo E.
      • González E.
      • Bega S.
      • et al.
      Proprioceptive role for palisade endings in extraocular muscles: evidence from the Jendrassik Maneuver.
      ].

      The neural pathway for proprioception

      The ophthalmic division of the trigeminal nerve is assumed to be the primary neural pathway for ocular proprioception. Observations of a gradual decline in conjugacy, following disruption of this pathway in primates, indicates that proprioception plays a role in the long-term control of ocular alignment [
      • Lewis R.F.
      • Zee D.S.
      • Gaymard B.M.
      • et al.
      Extraocular muscle proprioception functions in the control of ocular alignment and eye movement conjugacy.
      ]. Clinical observations of oculomotor deficits in patients with pathologic conditions involving the ophthalmic nerve add credence to this view [
      • Campos E.C.
      • Bolzani R.
      • Schiavi C.
      • et al.
      Further evidence for the role of proprioception in space perception.
      ]. The primary afferent neurons reside in the trigeminal ganglion and electrophysiological evidence exists of proprioceptive projections to the superior colliculus, cerebellum, and cerebral cortex [
      • Schiavi C.
      Extraocular muscles tension, tonus, and proprioception in infantile strabismus: role of the oculomotor system in the pathogenesis of infantile strabismus-review of the literature.
      ].
      The cortical areas are interconnected by reciprocal pathways and have additional projections to the superior colliculus. Eye position information thus is available to all cortical areas involved in eye movement regulation, comprising the frontal eye field, the supplementary eye field, dorsolateral prefrontal cortex, parietal eye field, and the medial superior temporal area. Neurons in the latter area participate in motion perception and in the regulation of smooth-pursuit eye movements. The neuronal activity in this region varies depending on whether the movement is caused by an object movement or an eye movement. The ability to distinguish between the two is indicative of extraretinal input from MIFs [
      • Gulyás S.
      Supranuclear regulation of the eye movements and the significance of their disturbances.
      ].
      It is of interest that many of the cortical and subcortical structures involved in eye movement regulation, such as the dorsolateral prefrontal cortex and hippocampus, also are involved in cognitive functions. Recent studies within the field of neuropsychology suggest that the oculomotor system and hippocampal memory systems interact in a reciprocal manner, and that they not only influence one another, but are interdependent [
      • Ryan J.D.
      • Shen K.
      • Liu Z.X.
      The intersection between the oculomotor and hippocampal memory systems: empirical developments and clinical implications.
      ].

      The neural substrate for the control of eye movements

      Extraocular muscles act functionally as 3 antagonistic pairs, receiving reciprocal innervation. They also have motor correspondence with the synergistic muscles of the other eye to ensure synchronized horizontal eye movements (Hering’s law). The receptors associated with MIFs are in a unique position to monitor this type of activity, allowing the brain to compare the forces generated by the contraction of the 2 synergistic muscles with the opposing forces generated by the 2 antagonists. Detailed histologic studies, using high-resolution techniques, have revealed that MIFs have a more generous supply of unmyelinated nerve fibers than previously assumed (estimated motor unit of 1:1). This indicates that the oculomotor system can make muscle-force increments by activating one single muscle fiber at the time. This outranks all other somatic muscles in terms of motor control [
      • Bruenech J.R.
      • Kjellevold Haugen I.B.
      • Bak U.
      • et al.
      The oculomotor system's ability to adapt to structural changes caused by the process of senescence: a review.
      ].
      The motor neurons innervating the MIFs have modest cross-sectional diameters, reflecting the size of their axons (Fig. 3). They are located toward the periphery of the nuclei involved in ocular rotation (III, IV, and VI). The more prominent motor neurons, innervating the SIFs are accumulated in the core of the nuclei [
      • Hernández R.G.
      • Calvo P.M.
      • Blumer R.
      • et al.
      Functional diversity of motoneurons in the oculomotor system.
      ]. A third group of neurons resides in the oculomotor nuclear complex (Edinger-Westphal nucleus), giving rise to the parasympathetic innervation of the ciliary muscle. Histologic studies have revealed sensory nerve terminals residing in the latter muscle [
      • Flügel-Koch C.
      • Neuhuber W.L.
      • Kaufman P.L.
      • et al.
      Morphologic indication for proprioception in the human ciliary muscle.
      ]. Their morphologic features indicate that they have a potential capacity to convey information about the accommodation that occurs during disconjugate eye movements.
      Figure thumbnail gr3
      Fig. 3Transverse section of myelinated nerve fibers showing the spectrum of nerve fiber diameters.
      Electrical recordings from the motor neurons innervating extraocular muscles suggests that their activity is influenced by 2 distinct premotor circuits: 1 that encodes the velocity and duration of the movement; and 1 that provides the tonic discharge needed to hold the eye in the new position of gaze. Once the velocity signal has completed the saccadic movement, the signal is converted into a position signal (neural integration). If the position signal is insufficient or disrupted, eccentric eye position cannot be maintained. Hence, although MIFs are in the minority in human extraocular muscles, they seem to play a vital role in ocular alignment and fixation stability [
      • Shadmehr R.
      Distinct neural circuits for control of movement vs. holding still.
      ].
      The anatomic substrate of the neural integrator is not fully resolved, but a variety of supranuclear structures seem to participate in this process, including nucleus prepositus hypoglossi, interstitial nucleus of Cajal, and cerebellum [
      • Gulyás S.
      Supranuclear regulation of the eye movements and the significance of their disturbances.
      ]. The latter structure contains multisensory neurons with the ability to cross-reference and process information from the various sensory systems. The cerebro-cerebellum receives input from the cortical regions (including visual cortex), the spino-cerebellum receives input from proprioceptors in somatic and extraocular muscles, whereas the vestibulo-cerebellum receives input from the semicircular canals. This neural arrangement, which forms the basis for making adjustments to eye movements in relation to body movements and posture, have been elegantly demonstrated through various clinical studies [
      • Lennerstrand G.
      Strabismus and eye muscle function.
      ]. A growing body of evidence suggests that dysfunctions in neural integration are implicated in a broad spectrum of somatic motor anomalies as well as binocular vision anomalies.

      Binocular vision anomalies

      Strabismus is a common ocular anomaly with an estimated global prevalence of 3% to 5% [
      • Hashemi H.
      • Pakzad R.
      • Heydarian S.
      • et al.
      Global and regional prevalence of strabismus: a comprehensive systematic review and meta-analysis.
      ]. The condition is broadly classified in terms of the direction of the deviation, constancy, and comitance. Epidemiologic studies indicate that esotropia appears more often than exotropia; most cases are manifest and usually of concomitant origin [
      • Paduca A.
      • Arnaut O.
      • Cardaniuc C.
      • et al.
      Epidemiology of childhood manifest strabismus in the Republic of Moldova.
      ].
      The clinical characteristic of a concomitant strabismus is that the angle of deviation typically remains the same during all directions of gaze. Hence, the condition is seemingly not attributable to a specific muscle or cranial nerve. The misalignment is commonly diagnosed in patients with congenital or early-onset strabismus. The etiology is unresolved but dysfunctions of eye muscle proprioception during the sensitive period of development has been advocated. This view is supported through histologic studies where immature receptors were found in muscle samples obtained from subjects with congenital strabismus [
      • Park S.E.
      • Sa H.S.
      • Oh S.Y.
      Innervated myotendinous cylinders alterations in human extraocular muscles in patients with strabismus.
      ]. Structural anomalies of this kind were not observed in muscle samples obtained from normal subjects or from those with acquired incomitant strabismus.
      Proprioception also might play a role in the sequela of incomitant strabismus. The clinical characteristic typical of this type of strabismus is that the angle of deviation changes during different directions of gaze, usually caused by neurogenic, myogenic, or mechanical-restriction anomalies. However, long-standing incomitant deviations may become concomitant with the passage of time, arguably caused by a gradual resetting of synergistic muscles [
      • Lueder G.T.
      Orbital causes of incomitant strabismus.
      ]. This kind of neural tuning requires information about eye position, which suggests that proprioceptive information may arise even from paralytic muscles.

      Current concepts in the diagnosis and management of strabismus

      Many treatment options exist in the management of oculomotor anomalies. The choice of therapy by tradition is based on the clinician’s personal preferences and a careful examination of the patient. A recent study on the effect of shared decision making in adult strabismus care revealed that patients do not always understand what the different treatment options entail. Satisfaction, hence, was significantly higher among the patients who were actively included in the decision-making process [

      Paduca A, Arnaut O, Beschieru E, et al. Shared decision making and patients satisfaction with strabismus care—a pilot study. BMC Med Inform Decis Mak 21, 109 (2021).

      ]. Traditionally, the options fall into 2 distinct categories, nonsurgical and surgical treatment.

      Nonsurgical management of strabismus

      Optical corrections

      Accommodative esotropia is a common form of strabismus that is classically corrected with spectacles or contact lenses if the condition is fully accommodative. However, many of these patients develop partial accommodative esotropia over time and may need surgery to correct the residual angle of deviation. Clinical studies indicate that a spectacle correction promptly after onset of the condition gives the best prognosis [
      • Li B.
      • Sharan S.
      Post-operative analysis of pediatric esotropia associated with high hypermetropia.
      ]. The therapeutic effect of an early optical intervention is attributable to the binocular alignment that is usually established. A secondary effect is arguably the increased coherence between the proprioceptive signal arising from the smooth muscles of the ciliary body and the signal arising from extraocular muscles. A third therapeutic effect may be associated with the alleviation of the excessive force generated by both the intrinsic and extrinsic ocular muscles. Histologic studies have revealed that free nerve endings reside in the connective tissue strands bridging the oculomotor plant with the periorbita. These nerve endings resemble nociceptors with a potential capacity to create pain when subjected to mechanical stress. Their location and morphologic features have led to the opinion that they contribute to the discomfort and tension frequently reported by patients during prolonged convergence or when the eyes are forced into eccentric positions of gaze [

      Bruenech JR & Kjellevold Haugen IB. Neuromuscular principles in the visual system and their potential role in visual discomfort. In: Dainoff M.J. (eds.). Ergonomics and health aspects of work with computers. EHAWC 2007. Lecture Notes in Computer Science, vol. 4566. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73333-1_2

      ].
      The use of small reading adds and prisms to relieve various forms of ocular discomfort is well documented in the literature [
      • Yammouni R.
      • Evans B.J.
      An investigation of low power convex lenses (adds) for eyestrain in the digital age (CLEDA).
      ]. The notion that some of the therapeutic effect is attributable to a reduction in neuromuscular tension and reduced sympathetic activity cannot be dismissed. In cases of infantile esotropia, with no prominent refractive error, other methods of treatment usually are considered.

      Neuromuscular stimulation through exercise

      The beneficial effects of physical exercise, such as muscular hypertrophy and angiogenesis, is well documented in the literature. Accumulating evidence exists for increased neurogenesis [
      • Lin T.W.
      • Tsai S.F.
      • Kuo Y.M.
      Physical exercise enhances neuroplasticity and delays Alzheimer's disease.
      ]. The effect of training to correct eye movements and visual-motor deficiencies are not explored to the same extent, yet many of the benefits seem to be the same [
      • Fischetti F.
      • Cataldi S.
      • Giunto A.
      • et al.
      Effect of home-based oculomotor exercises on postural stability in healthy female adults.
      ]. However, achieving muscular hypertrophy may not be imperative in the treatment of oculomotor anomalies. Only small amounts of force are required to move the eyes, and many authorities promote the view that ocular misalignments are more attributable to neural abnormalities, rather than myogenic dysfunctions [
      • Schiavi C.
      Extraocular muscles tension, tonus, and proprioception in infantile strabismus: role of the oculomotor system in the pathogenesis of infantile strabismus-review of the literature.
      ]. This suggests that oculomotor therapy should target neural circuits, synaptic connections, and specific premotor regions in the brain. The cerebellum is renowned for its neuroplasticity and ability to learn and express procedural memories. Comparative studies of primates indicate that these abilities rely on long-term stimulation and input from sensory systems [
      • De Zeeuw C.I.
      • Ten Brinke M.M.
      Motor learning and the cerebellum.
      ]. The same seems to be the case in man. Patients with cerebellar dysfunctions respond well to conventional musculoskeletal therapy by improving gait, balance, and hand-eye coordination [
      • Rizzo J.R.
      • Fung J.K.
      • Hosseini M.
      • et al.
      Eye control deficits coupled to hand control deficits: eye-hand incoordination in chronic cerebral injury.
      ]. Input from ocular proprioceptors seem to contribute to the maintenance of these important functions. Studies in which body sway was found to increase after strabismus surgery in children, seem to support this view [
      • Matsuo T.
      • Narita A.
      • Senda M.
      • et al.
      Body sway increases immediately after strabismus surgery.
      ].
      Therapy aiming to enhance oculomotor functions and hand-eye coordination is arguably best achieved through stimulation of MIFs, because they have a direct impact on the cerebellum through their proprioceptive input. Visual tracking of moving targets and other methods of stimulating MIFs also may serve to attenuate neurodegeneration.
      Systematic and repetitive neuromuscular activity ensures a rapid release and reuptake of transmitter-substance, which has proved to be imperative for retaining synaptic structural stability. Histologic studies of human extraocular muscles have demonstrated that efferent nerve fibers tend to detach themselves from inactive muscle fibers. A further rearrangement of the efferent innervation will occur if the redundant axons find new targets (polyneural innervation) [
      • Bruenech J.R.
      • Kjellevold Haugen I.B.
      • Bak U.
      • et al.
      The oculomotor system's ability to adapt to structural changes caused by the process of senescence: a review.
      ]. Similar hypotrophic tendencies have been observed in pathologic conditions associated with mitochondrial dysfunction [
      • Gorman G.S.
      • Taylor R.W.
      Mitochondrial DNA abnormalities in ophthalmological disease.
      ]. Hence, consistent with neuromuscular systems elsewhere in the body, it seems imperative to keep the activity in the oculomotor system above a critical level, especially during the early stages of life. A postnatal delay occurs in the proliferation of myotendinous receptors. Their complement and morphologic features are seemingly not fully developed until the age of 5 [
      • Bruenech J.R.
      • Ruskell G.L.
      Myotendinous nerve endings in human infant and adult extraocular muscles.
      ]. These findings have recently been confirmed in extraocular muscles of various mammals [
      • Blumer R.
      • Streicher J.
      • Davis-López M.A.
      • et al.
      Palisade endings of extraocular muscles develop postnatally following different time courses.
      ]. Hence, the cerebellum and other supranuclear structures involved in the tuning of oculomotor activity are seemingly deprived of adequate information about eye position in the sensitive period of development. Consequently, the ability to monitor and adjust for neurogenic and myogenic changes is limited. A potential delay in the development of other sensory systems or ambiguity in the information they provide may augment the chances of developing strabismus.

      Surgical management of strabismus

      Strabismus surgery attempts to align the eyes by strengthening (resection), weakening (recession), or by changing the direction of pull of one or more of the extraocular muscles (Table 1). These surgical procedures have been applied and refined over many years. During a resection procedure, a bit of the distal part of the muscle is removed. The shortened muscle is then reinserted onto its original location on the sclera. This surgical intervention stands in contrast to the recession procedure in which the distal insertion is detached and reinserted more posteriorly, without altering muscle length. Although both procedures will change the muscle`s rotational effect on the eye, the functional and neurogenic implications are quite different. In terms of functional implications, the shortening of a muscle changes the length-tension relationship and increases the muscle`s pull on the scleral collagen.
      Table 1General principals behind strabismus surgery
      Type of procedureEffect on muscle
      RecessionWeakened
      Myotomy
      Myectomy
      Posterior fixation suture
      ResectionStrengthened
      Tucking
      Advancement
      Injection of botulinum toxinWeakened
      Injection of growth factors (experimental)Strengthened
      The neurogenic implications are associated with the number of receptors manipulated or removed, during the surgical procedure.
      However, these potential implications will vary depending on the morphologic features of the muscle that is operated. Preliminary results from histologic studies on muscle samples obtained during strabismus surgery indicate that larger esodeviations can be surgically corrected (resection) without disrupting the myotendinous region, compared with exodeviations. This is due to the nature of the tendon in the temporal rectus, which is significantly longer than its counterpart in the medial rectus [

      Paduca A, Bruenech JR, Lundmark P, et al. Can horizontal rectus muscle resection in strabismus surgery affect the proprioception? Black Sea Ophthalmological Society – BSOS Tbilisi International Ophthalmology Conference - TIOC, proceedings December 19 – 20, 2020 Tbilisi, Georgia.

      ]. This may be a contributing factor to the difference of surgical outcomes between manifest exotropia and esotropia [
      • Chen Y.W.
      • Lin S.A.
      • Lin P.W.
      • et al.
      The difference of surgical outcomes between manifest exotropia and esotropia.
      ]. Postoperative changes in spatial localization and other perceptual parameters may be primarily associated with those cases where the myotendinous receptors have been compromised [
      • Steinbach M.J.
      • Smith D.R.
      Spatial localization after strabismus surgery: evidence for inflow.
      ].

      Summary and discussion

      The degree to which disruption of ocular proprioception is attributed to strabismus and other oculomotor anomalies remains unclear, yet from this review, it seems legitimate to argue that ocular proprioceptors facilitate the following biological functions:
      • Development of visual functions
        • The myotendinous cylinders, located at the distal end of MIFs, seem to contribute to the development of stable bifoveal alignment. Receptors with similar morphologic features reside in the ciliary body, suggesting that proprioception also is involved in the modulation of the coarsely preprogrammed relationship between convergence and accommodation.
        • The developmental timeline for myotendinous cylinders seems to be significantly longer than for other receptors. Hence, information about the position of the eyes in relation to the orbit may be the weakest sensory signal in the early stages of the developmental period.
      • Tuning and adaptation
        • Morphologic alterations occur in the visual system with the passage of time, and the oculomotor system must make adaptations in response to all structural changes caused by growth and aging. This capability seems to rely on receptors in the extraocular muscles, as suggested in several histologic and clinical studies.
      • Visual processing and adjustments of the visual representation
        • Neurons in the extra striate visual areas are able to distinguish between displacements of a retinal image caused by an object movement versus an eye movement. This requires knowledge about the ocular rotation that has taken place. Accumulating evidence suggest that this information is provided by the receptors associated with the slow-contracting MIFs.
      • Balance and equilibrium
        • The cerebellum provides balance and equilibrium through input from vision, somatic proprioception, and the vestibular system. The neural contribution from the respective systems is elegantly demonstrated through the Romberg test or similar methods based on the same theoretic principal. The notion that ocular proprioceptors also contribute is indicated through various histologic and clinical studies.
      • Plasticity
        • Evidence, accumulated over the past decades indicates that the brain has a significant capacity to reorganize pathways, create new synaptic connections, and synthesize new neurons. This capacity seems to rely on sensory input. Information arising from ocular proprioceptors are conveyed to a broad spectrum of supranuclear structures and may contribute to the plasticity and the adaptation processes that occur in these regions of the brain. Some of these regions also are involved in executive functions. Cognitive skills are known to develop gradually over time, and the notion that ocular proprioception facilitates this development cannot be dismissed.
      • Double insertion of the distal tendon
        • Extraocular muscles pass through collagen structures near the equator of the globe, acting as muscle origins (pulleys). This concept challenges our conventional understanding of the muscle’s oculorotary actions, and the role they play in the pathophysiology of strabismus. The position of pulleys is critical to the rotational properties of the various muscles, yet the neural substrate for pulley activity is not fully resolved. Observations of receptors in the orbital fiber layer of extraocular muscles adds credence to the notion that proprioception may be involved in the dynamics of these collagen structures.
      • Innervation of muscle compartments
        • It has been demonstrated that the functional differentiation of extraocular muscles allows the oculomotor system to control individual compartments and subunits of each muscle with a high degree of independence. It is reasonable to argue that adjustments of their activity are monitored in the same manner as seen in somatic muscles.
      • Neural integration and gaze holding
        • The MIFs are fatigue resistant with the ability to make minute adjustments to eye position in response to changes detected through their sensory receptors. This type of neuromuscular arrangement represents a minute sensory-motor control loop, which facilitates gaze holding at the starting point and endpoint of eye movements. Muscle-fiber composition seems to vary considerably between individuals, and a low concentration of MIFs may thus have functional implications for both gaze holding and fixation stability.
      The current review supports the notion that our understanding of the external world relies on the brain’s ability to obtain and process information from different sensory systems. The summation of this information provides the basis for our perception, decision making, and subsequent behavior. From this standpoint, clinical evaluation of one single sense has a limited diagnostic value, unless it is put into context with the input from the other senses.
      Many treatment options exist in strabismus management, comprising optical corrections, occlusion, surgical procedures, Botox injections, or ocular exercises. Their therapeutic approach is very different in respect to their effect on proprioceptors and proprioception.
      Cumulative evidence supports the notion that stimulation of the various sensory systems can enhance a variety of biological functions, not limited to binocular vision and perception. This is the conceptual framework of many treatment regimens, comprising various avenues of orthoptic treatment, vision therapy, and multisensory therapy. However, not all patients may be suitable candidates for ocular eye exercises or visual stimulation.
      Strabismus surgery holds long traditions in the treatment of oculomotor anomalies. Previous studies on the outcome of strabismus surgery have indicated that various perceptual parameters may be affected, which may be attributable to disruption of proprioceptors or their neural pathways. However, more recent studies indicate that disruption of proprioception may occur to a lesser extent that previously assumed.

      Summary

      The main conclusion that can be drawn from this review is that proprioception plays an important role in development and maintaining binocular vision. It also is legitimate to argue that proprioception supports perceptual and cognitive functions. These views are founded on results from histologic research and comparative and experimental studies. Therefore, future research should be conducted in more realistic clinical settings so that the therapeutic effects and potential side effect of the various surgical as well as nonsurgical treatment regimens can be identified and documented. Such undertaking could prove beneficial to the clinical and scientific literature.

      Disclosure

      The author declares that there is no conflict of interest.

      Clinics care points

      • Disruption of proprioception from extraocular muscles may jeopardize the oculomotor system’s ability to adapt to structural changes caused by growth and senescence. Hence, clinical evaluation of ocular proprioception is warranted in the diagnosis and management of both developmental and acquired oculomotor anomalies.
      • Multiply innervated muscle fibers are fatigue resistant. Individuals with a genetically predetermined low composition of these fibers hence are predisposed to oculomotor anomalies associated with smooth-pursuit eye movements, gaze holding, and fixation stability.
      • Sensory input is known to increase neural plasticity and adaptation. Tracking slow-moving objects will stimulate multiply innervated muscle fibers and activate their associated receptors. This will initiate neural activity in a variety of supranuclear structures and may enhance their function.
      • The neuromuscular junctions in human extraocular muscles are labile and the metabolic activity must be kept above a critical level to avoid detachment of the efferent nerve terminal. Ocular exercise can serve to attenuate neuromuscular degeneration.
      • The cerebellum plays a vital role in retaining balance and hand-eye coordination. Rivalry between the sensory information it receives may cause neural integration disorders. The Romberg test, and other clinical tests based on the same theoretic principal, represent valuable diagnostic tools in the evaluation of somatic and oculomotor anomalies.
      • The distal tendon in the temporal rectus muscle is long, compared with its counterpart in the medial rectus muscle. Therefore, larger resections can be performed on the temporal rectus muscle, without disrupting sensory receptors, compared with resections on the medial rectus.

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