Histology and Physiology of the Extraocular Muscles · Extraocular Muscles As described in Chapter 4, ... rectus muscles insert in a biﬁd fashion: ... line or thickening of the

C H A P T E R 6Histology andPhysiology of theExtraocular Muscles

As described in Chapter 4, the extraocularmuscles perform two functions: optostatic

and optokinetic. The optostatic function requiresthat the muscles maintain a state of postural tonic-ity; the optokinetic function requires that quick,tetanic contractions be performed. These two con-tradictory functions are served by two differentsets of muscles in the skeletal muscle system. Eyemuscles, however, are equipped to perform bothfunctions simultaneously. It is important to learnwhat mechanisms enable them to do so.

In principle the type of response by extraocularmuscles would be controlled either by the centralnervous system or by peripheral mechanisms re-siding in the extraocular muscles or by both. Wehave only sketchy information of the finer detailsof the central nervous system control of tonicand saccadic extraocular movements, but we havegained a little more insight into the structuraldifferentiation and physiologic and pharmacologicresponses of the extraocular muscles. The struc-ture of the extraocular muscles and its possiblerelation to their function will be discussed first.

In general, two types of striated muscles aredistinguished in the skeletal muscle system: (1)‘‘red’’ or dark muscles composed of fibers ofsmall diameter and rich in sarcoplasm and (2) paleor ‘‘white’’ muscles with fibers of greater diameterand scanty sarcoplasm. Red muscles contract moreslowly and are kept in a state of tonic contracture

101

by fewer impulses per second than are white mus-cles, which contract more quickly. Red musclesrelax more slowly than white muscles, and theirmetabolism increases much less during contrac-tion than that of white muscles. Consequently, redmuscles do not tire as easily as white muscles.Red muscles are more continuously active andserve the function of postural activity; white mus-cles are muscles of locomotion and quick activity.

Structure and Function of theExtraocular Muscles

General Histologic Characteristics

The histologic structure of eye muscles, whichperform the functions of both red and white mus-cles, differs in many respects from that of otherstriated muscles. Extraocular muscles contain fi-bers of varying diameters. In general they are thefinest fibers found in any striated muscles. Theyvary in diameter from 9 �m to 17 �m, with fibersas fine as 3 �m having been seen,72 but thesemuscles also contain coarse fibers up to 50 �m inwidth. One can appreciate the fineness of fibers ofextraocular muscles if their diameters are com-pared with those of fibers of the gluteus maximus(90 �m to 100 �m).

It was once believed that each muscle fiber

102 Physiology of the Sensorimotor Cooperation of the Eyes

runs through the entire length of the extraocularmuscle. If this were true, one would expect to findthe same number of fibers in sections taken fromthe central or peripheral part of the muscle. Thisview has not been shown to be valid. Fiber countsfrom the central portion of the muscle have beenconsistently higher (44% to 72%) than those takenfrom the proximal or distal portions.2, 57 Thesefindings indicate that many fibers must originateand terminate between the origin and the insertionof the muscle, suggesting that an interconnectionnetwork of muscle fibers must exist. Indeed, cho-linesterase-positive ‘‘myomyous’’ junctions havebeen described in eye muscles of various species,including humans.53

The extraocular muscles can be divided intotwo distinct portions. One portion is a peripheralorbital layer along the muscle surface and facesthe orbit, which contains thin fibers with manymitochondria. This layer encloses a second por-tion, the central or bulbar layer, close to the globe,which consists of thicker muscle fibers with vari-able mitochondrial content. Both zones are dis-tinctly separated from each other, sometimes byan internal perimysium, and their existence hasbeen confirmed by numerous investigators.20, 39,

42, 53 High-resolution magnetic resonance imaging(MRI) and orbital dissections have shown that therectus muscles insert in a bifid fashion: the globallayer terminates at the myotendinous scleral inser-tion, whereas the orbital layer branches off furtherposteriorly to insert at the pulley (see p. 41) ofeach muscle.26

Elastic tissue is unusually abundant in extraoc-ular muscles of adults, so much so that it has beendescribed as elastic bands.66 The elastic fibers arethick and are arranged parallel with the musclefibers. These longitudinal fibers are interconnectedby transverse elastic fibers that form a rather densenetwork around the muscle fibers. In neonates,elastic fibers are present only in the perimysium.Schiefferdecker66 therefore believed that the elas-tic fibers grow from the perimysium into the endo-mysium. He also thought that the abundance ofelastic tissue was a factor in fine regulation of eyemovements. Duke-Elder29 agreed with this view.However, Eisler33 believed it to be a secondary,mechanical phenomenon produced by frequentsmall pulls on the extraocular muscles.

Nerve Supply

In Chapter 4, it was mentioned that the nervesupply to extraocular muscles is extraordinarily

rich. The motor nerves are very thick, owing tothe large number of fibers they contain. The ratioof nerve fibers to muscle fibers is nearly 1:12 inextraocular muscles, whereas in skeletal musclesit may be as high as 1:125.57 The possibility thatthis rich nerve supply is partly responsible for fineregulation of eye movements cannot be over-looked.

The abundance of nerve fibers has led to theconclusion that the all-or-nothing law, or law ofisobolia, applies to eye muscles.45 According tothis general principle of neuromuscular physiol-ogy, individual muscle fibers always respond witha maximum contraction to every supraliminalstimulus. The amount of total contraction of amuscle depends on the number of fibers takingpart in a contraction.

Extraocular muscles also are provided with anumber of different types of nerve endings. Wool-lard76 recognized three types: (1) ordinary singlemotor end plates associated with coarser musclefibers; (2) multiple grapelike nerve endings, espe-cially around the tendons, which are believed tobe sensory in nature; and (3) very fine, nonmedul-lated fibers ending in the thinner muscle fibers.Newer studies of these different nerve endings arereported in the following discussion.

Physiologic and PharmacologicProperties

The physiologic and pharmacologic properties ofextraocular muscles correspond to the many un-usual histologic features of these muscles.Rehms60 stated that eye muscles require and re-ceive more oxygen than other skeletal muscles.Bjork8 showed by means of electromyography (seep. 109) that responses of extraocular muscles inhumans are considerably lower in amplitude (20to 150 �V), of much shorter duration (1 and 2ms), and much higher in frequency (up to 150cps) than those of peripheral skeletal muscles, inwhich the amplitude is 100 to 3000 �V; the dura-tion, 5 to 10 ms; and the frequency only up to 50cps. Bjork attributed these differences to the lownerve fiber-to-muscle fiber ratio of the motor unitsin extraocular muscles.

Extraocular muscles contract much morequickly than other voluntary muscles. Contractiontimes obtained from experiments on cats were:soleus muscle, 100 ms; gastrocnemius muscle, 40ms; and medial rectus muscle, 8 ms.23, 27 The greatspeed of contraction of extraocular muscles is in

Histology and Physiology of the Extraocular Muscles 103

keeping with the requirements of saccadic eyemovements and with what is known of the struc-ture and innervation of extraocular muscles. It isall the more striking when contrasted with anotherobservation.

Duke-Elder and Duke-Elder30 demonstratedthat the extrinsic muscles of eyes of cats contractunder the influence of acetylcholine. Acetylcho-line produces a strong contraction of smooth mus-cles in invertebrates and of some skeletal musclesin lower vertebrates, but has slight, if any, effecton skeletal muscles of mammals. Only denervatedmuscles of mammals or embryonic mammalianmuscles react strongly to acetylcholine. In thelower vertebrates the differences in reaction toacetylcholine are indicative of the nature of mus-cles. The more quickly a muscle acts, the less itis apt to respond to acetylcholine; the more itsaction is one of postural tonicity, the more stronglyit will respond to acetylcholine.

Since the discovery that a dual motor system ofslow and fast fibers exists in extraocular muscles,experiments have shown that acetylcholine, cho-line, and nicotine cause slow and tonic contractionof slow fibers, whereas fast fibers respond with afast twitch. The response of extraocular musclesto neuromuscular blocking agents is of clinicalinterest, since these drugs are often used duringgeneral anesthesia.

Slow and Fast Twitch Fibers

Customarily, one thinks of voluntary striated mus-cles as being characterized by fibers that respondto a single stimulus applied to their nerve with anungraded fast twitch, followed by speedy relax-ation, and accompanied by propagated electricalactivity. Repetitive stimuli of relatively high fre-quency are required to maintain a tetanic contrac-tion of these fibers. In contrast, smooth and otherslowly contractile muscle systems do not react toa single stimulus applied to their nerve, but theydo respond with a slow, maintained graded con-traction to a few repetitive stimuli, unaccompaniedby electrical activity. There are also pharmaco-logic differences between these two systems,which, in general, are present in spatially unre-lated muscle groups.

Sommerkamp,69 in his pharmacologic studieswith acetylcholine, intimated the existence of aslow contractile system in striated muscles of am-phibians, which produced a rapid twitch of thesartorius muscle of the frog but a slow maintained

contraction of the rectus abdominis muscle.Within iliofibularis muscle of the frog, Sommer-kamp was able to separate a group of fibers thatresponded to acetylcholine by a twitch and a sec-ond group of fibers (the ‘‘tonus bundle’’) in whichacetylcholine produced a slow, tonic contraction.

Anatomical studies by Kruger43 and his schooluncovered the structural basis for fast and slowfiber systems in striated muscles. He stated thatthe system giving twitch responses had a Fibril-lenstruktur, and the system responsible for theslow contractions had a Felderstruktur. In thecourse of time, the two systems have been demon-strated in skeletal muscles of amphibians, reptiles,and birds, but not of mammals. Although Krugerbelieved that he had found the two systems alsoin mammalian muscles, most workers agree withHess37 that these two systems occur in mammalsonly in extraocular muscles, where they have beenfound in the rabbit,42 guinea pig,36 cat,18, 38 mon-key,19, 57 and human.10, 28

The Fibrillenstruktur type of the fast fiber sys-tem is characterized anatomically by small, well-defined myofibrils, each surrounded by abundantsarcoplasm and having an even, punctate appear-ance as seen with the light microscope (Fig. 6–1A). Light microscopic and electron microscopicexaminations show a well-developed sarcoplasmicreticulum, a regular tubular (T) system in eachsarcomere, a straight Z line, and a well-marked Mline or thickening of the filaments in the middleof the A band. The nuclei of the fibers are usuallylocated peripherally and are only infrequently cen-trally located (Figs. 6–2 and 6–3A).

In contrast, slow fibrils of the Felderstrukturtype are clumped together in a more or less afi-brillar-appearing mass of myofilaments with large,partially fused fibrils in scant sarcoplasm (Fig.6–1B). The sarcoplasmic reticulum is poorly de-veloped; the T system is absent or consists ofaberrant elements; the Z line follows a zigzagcourse; and the M line is absent. Mayr53 considersthe presence or absence of the M band as a distin-guishing sign between the two fiber types unrelia-ble. The nuclei are located centrally or slightlyeccentrically (Fig. 6–3B). The Felderstruktur sys-tems stain more deeply than the Fibrillenstruktursystems. Peachey59 subdivided fiber types ac-cording to their electron microscopic characteris-tics into five groups, and similar classificationshave been suggested by others.2, 53 Miller54 drewattention to the microstructural changes that extra-ocular muscles undergo with advancing age.


FIGURE 6–1. Transverse sectionof human inferior oblique muscle.Electron micrographs. A, Fibrillen-struktur fiber. Numerous ele-ments of sarcoplasmic reticulum(arrows) (X36,000). B, Felder-struktur fiber. Scattered mito-chondria and elements of sarco-plasmic reticulum (arrows) lie inthe indistinct mass of myofila-ments (X18,00). (From Brandt DE,Leeson CR: Structural differencesof fast and slow fibers in humanextraocular muscle. Am J Oph-thalmol 62:478, 1996.)

Fibrillenstruktur fibers are innervated by thick,heavily myelinated nerves joining the muscle fiberwith single, typical motor and so-called en plaqueend plates (Fig. 6–4), showing junctional foldsand numerous synaptic vesicles in the terminalaxon. Unlike typical skeletal muscle, Felder-struktur fibers are innervated by multiple grapelikenerve terminals, so-called en grappe endings, de-rived from efferent nerves of small diameter ar-ranged linearly or in loose collections and scat-tered throughout the muscle from origin toinsertion (see Fig. 6–4). According to Cheng andBreinin,18 the synaptic membrane of these termi-nals has only a few rudimentary invaginations andthe terminal axon contains granular as well asagranular synaptic vesicles.

With the exception of extraocular muscles, sin-gle fibers are innervated by multiple endplates inonly two other muscles, the tensor tympani andthe stapedius.34 The presence of multiple endplatesindicates that the fiber is innervated by eithermultiple branches from the same nerve or by inputfrom more than one nerve fiber. Although poly-neuronal innervation occurs in several types ofvertebrate muscles, Bach-y-Rita and Lennerstrand7

were not able to demonstrate this function in theextraocular muscles of cats. Lennerstrand46 distin-guished further between multiple innervated fibersthat conduct and those that do not conduct actionpotentials, but his hypothesis has not been univer-sally accepted.15, 53

The percentage of multiple innervated muscle


FIGURE 6–2. Transverse section of human inferioroblique muscle showing Fibrillenstruktur (arrows) andFelderstruktur fibers. (Light micrograph; X400.) Note thatthe Felderstruktur fibers take a much deeper stain. (FromBrandt DE, Leeson CR: Structural differences of fast andslow fibers in human extraocular muscle. Am J Ophthal-mol 62:478, 1996.)

fibers is higher in the orbital region than in thecentral zone of extraocular muscles and varieswith the species.53 However, the fact that bothtypes of fibers are present in the two zones isof considerable importance when attempting to

FIGURE 6–3. Longitudinal sections through superior oblique muscle of cat. Electron micrographs. A,Fast twitch fiber. Separation of fibrils by sarcoplasmic reticulum; straight M and Z lines; regularlyoccurring T system (arrows) (X16,000). B, Slow twitch fiber. Poor separation of fibrils; sparsesarcoplasmic reticulum; M and Z lines wavy; absent tubular system (X16,000). (From Hess A: Thestructure of vertebrate slow and fast twitch muscle fibers. Invest Ophthalmol 6:217, 1967.)

correlate the structure of the extraocular muscleswith their function.

The electron microscopic differences betweenthe fibrillar and field type of fibers emphasize thedifferences in their functions: the fibrillar type isfast fibers and the field type is slow fibers. Thepresence of the T system and the abundance ofsarcoplasmic reticulum may serve to transmit ex-citatory impulses with greater rapidity; the largeconcentration of mitochondria between the fibrilsmay be related to the considerable oxidative re-quirements associated with twitch contractions.The virtual absence of the T system and the sparsesarcoplasmic reticulum and mitochondrial concen-tration may be evidence for the slow, tonic con-traction of the field type of fiber structures andtheir lesser demand for oxidative metabolism. Theexperimental work of Asmussen and Kiessling4

has shown that fast twitch fibers respond to dener-vation with atrophy and slow twitch fibers withhypertrophy.

Pharmacologic studies of the behavior of extra-ocular muscles are of particular interest. Kern42

showed that the superior rectus muscle of therabbit consists of two layers, an upper thin layermade up of Felderstruktur fibers, and a lowerlayer, the bulk of the muscle, composed of Fibril-lenstruktur fibers. Kern was able to separate thetwo muscle strips. When those of the Felder-struktur type were exposed to a low dose of ace-tylcholine (0.5 �g/mL), a tonic contraction ofabout 80 mg lasting for more than 6 minutesdeveloped. In contrast, one fifth of the Fibrillen-


FIGURE 6–4. Simple en plaque endings common in muscle fibers (F) of Fibrillenstruktur type, 9 to11. Rare finding of two en plaque endings on one muscle fiber, 12. En grappe nerve endingscommonly found on Felderstruktur fibers, 13, 14. (From Dietert SE: The demonstration of differenttypes of muscle fibers in human extraocular muscle by electron microscopy and cholinesterasestaining. Invest Ophthalmol 4:51, 1965.)

struktur strips did not respond at all to acetylcho-line, and only a small response rise in tension wasnoted in the remaining preparations (Fig. 6–5).This minimal response may be explained by some

FIGURE 6–5. Response of rabbit’s superior rectus mus-cle to acetylcholine (A). a, response of muscle strip com-prising only Felderstruktur fibers; b, response of Fibrillen-struktur fibers. Calibration 20 mg/min. (From Kern R: Acomparative pharmacologic histologic study of slow- andfast-twitch fibers in the superior rectus muscle of therabbit. Invest Ophthalmol 4:901, 1965.)

admixture of slow fibers to the preparation. In-creased concentrations of acetylcholine (0.1 to 1.0�g/mL) induced faster and higher rises in bothtypes of preparations. The responses of the Fibril-lenstruktur strips were proportionately lower thanthose of the Felderstruktur strips and returnedrapidly to the baseline level, whereas tensions ofthe latter strips remained elevated for longer than10 minutes and returned to the baseline level afterthe drug was washed out.

The presence of two different fiber systems, aslow and a fast system, was confirmed by Katzand Eakins40 in experiments with succinylcholineand other depolarizing agents. These authorsfound that the initial effect of succinylcholine onthe superior rectus muscle of cats was to increasethe baseline tension without an effect on the twitchresponse. The greater the dose of succinylcholine,the greater the rise of the baseline tension. Eventu-ally the twitch response became depressed, andwith a dosage of 128 �g/kg of succinylcholine itwas abolished (Fig. 6–6). The anterior tibial mus-cle did not respond with a rise in baseline tension,but its twitch response was abolished with muchlower doses of the drug than in the superior rec-tus muscle.

Katz and Eakins believed that responses ofextraocular muscles to succinylcholine and other


FIGURE 6–6. Response of thesuperior rectus muscle (SR) andthe anterior tibial muscle (TA) ofthe cat to succinylcholine. (FromKatz RL, Eakins KE: Pharmacolog-ical studies of extraocular mus-cles. Invest Ophthalmol 6:261,1967.)

depolarizing agents found in their experiment areexplained by the presence of two neuromuscularsystems: the increase in baseline tension is attrib-utable to the tonic (slow) system, and the decreasein twitch response is attributable to the twitch(fast) system.40

Although there is abundant ultrastructural andpharmacologic evidence to support the notion oftwo principal fiber types (slow and fast twitch) inthe human extraocular muscle, several authorshave proposed classifications that are based onas many as five to six fiber types.2, 3, 53 Theseclassifications take into account a much widerrange of structural and contractile features foreach fiber type than the older studies cited above.

Some reservations may be in order to distin-guish muscle fibers exclusively on the basis oftheir electron microscopic characteristics, since ithas been shown that fibers may change back andforth from Felderstruktur to Fibrillenstrukturalong their length.25, 58 Brooke and Kaiser14 intro-duced a histochemical classification based on the

TABLE 6–1. Comparison of Skeletal and ExtraocularMuscle

Ocular Skeletal

Fiber diameter 9–17 �m 90–100 �m(gluteus maximus)

Ratio of nerve to 1:1–17 Up to 1:300muscle fiber

Contraction time Fast SlowAcetylcholine High Low or absent

sensitivity

presence of slightly different isoforms of myosinin various types of slow and fast twitch fibers andmore recent research has distinguished fiber typeson the basis of immunohistochemical studies, us-ing various antimyosin antibodies.62, 65, 75

The main features distinguishing skeletal fromextraocular muscle are summarized in Table 6–1and the various characteristics of slow and fastfiber types are shown in Table 6–2. The reader isreferred to several recent reviews for more de-tailed information.3, 13, 46, 61

Structural and FunctionalCorrelations

Inferring a correlation between fast fibers and fasteye movements (saccades) and slow fibers and

TABLE 6–2. Characteristics of Slow and Fast TwitchFibers in Extraocular Muscles

Slow Twitch Fast Twitch

Thin motor nerve fibers Thick motor nerve fibersMultiply innervated (en Singly innervated (en

grappe) plaque)Large, poorly delineated Small, well-delineated

muscle fibrils muscle fibrils(Felderstruktur) (Fibrillenstruktur)

No conduction of action Conduction of actionpotential potential

Slow, sustained Fast contraction (phasic)contraction (tonic)

Predominantly in orbital Predominantly in centrallayer (bulbar) layer


slow eye movements (vergences) is tempting. Ifthis were so, then two separate neural pathwayswould exist, one for the saccadic and the other forthe tonic function, each with its own separatesupranuclear component and subnuclei in the ocu-lomotor complex.

Miller56 found the outer part of extraocularmuscles of rhesus monkeys to consist of fiberswith small cells having the histochemical and elec-tromyographic characteristics of red muscles. Thecentral part of these muscles consisted of fiberswith large cells having the characteristics of whitemuscles. An intermediate area between the outerand central zones was made up of a mixture oflarge and small cells. Miller attributed slow eyemovements to the outer red part of the fibers andfaster eye movements to the central white part.56

However, these notions were dispelled by thefindings of Keller and Robinson,41 which are in-compatible with the existence of two muscularsystems, one for saccadic and one for tonic func-tion. These authors induced saccadic, pursuit, andvergence movements in alert, unanesthetized mon-keys while simultaneously recording the electricresponses from cells of the abducens nucleus bymeans of microelectrodes. All investigated cellsresponded to all movements; no cells respondedselectively. Keller and Robinson concluded thatthere was a single common pathway for saccadic,pursuit, and vergence movements.41 The undeni-able differences in muscle fiber types then wouldhave to be correlated with some other functionaldifferences in the oculomotor system. For exam-ple, Keller and Robinson found fibers with a dis-charge frequency of 150 spikes per second withthe eye in primary position, that is, during theentire time the animal was awake. As Bjork8 hadalready determined from electromyographic stud-ies, this amounts to an intensity and duration farin excess of that required from other muscle sys-tems. On the other hand, units in which the thresh-old lies lateral to the primary position are recruitedinto activity for only brief periods of lateral gazeor during lateral saccades. Their role of intermit-tent activity is not unlike that of other skeletalmuscles. Keller and Robinson conclude that itwould be remarkable if such large differences insynaptic transmission and muscle metabolismwere not reflected in morphologic differences.This observation by Keller and Robinson mightwell explain the presence of twitch fibers withdifferent physiologic responses,41 but one fails to

see how it could account for the difference be-tween fast and slow fibers.

Scott and Collins67 and Collins21 recorded fromslow and fast fibers in the orbital and centrallayers of human extraocular muscles to analyzetheir contribution to various types of eye move-ments. During fixation in different eye positions,the fast fibers are inactive outside the field ofaction of the muscle. As the muscle approachesits maximal field of action, their activity begins toincrease. Conversely, slow fibers are active evenin extreme positions of gaze outside the field ofaction of the muscle. Their activity increases non-linearly as the eye begins to fixate more and morein the field of action of the muscle. This innerva-tional pattern is similar during slow followingmovements; however, during fast saccades, bothslow and fast fibers are activated maximally dur-ing the first phase of the saccades, then begin todecay logarithmically to their new equilibriumwith a time constant of about half the duration ofthe saccade. The work of these investigatorsleaves little doubt that both slow and fast fiberscontribute to tonic and phasic activity but notnecessarily simultaneously in the case of tonicactivity. Scott and Collins suggested that variousmuscle fiber types are functionally differentiatedby the amount of work they do rather than by thetype of eye movement to which they contribute.67

One may hope that future work will permitapplication of laboratory findings in extraocularmuscles to the clinical study of strabismus. Extra-ocular muscles contain different types of musclefibrils with intricate ultramicroscopic structuresand fibers with highly differentiated nerve end-ings. They are surely there to subserve specificfunctional needs. This seems more probable whenone considers that even such anatomically andembryologically closely related muscles as the le-vator of the upper lid in humans28 and the retractorbulbi in the rabbit42 do not share the peculiaritiesof extraocular muscles.

There is justification in comparing the actionof extraocular muscles with the action of flexormuscles of amphibians. Flexor muscles of frogscontain tonic bundles required for the amplexus.Kuffler and Vaughan Williams44 established thatslow and fast fibers in these muscles are syner-gistic, that the state of tension of slow fibers isdirectly related to stimulus frequency, and thatany amount of slow fiber tension could collapseinstantly by superimposition of a single twitch


contraction. A comparable phenomenon may takeplace in extraocular muscles.

Regardless of what future studies may uncover,the uniqueness of the structure and function ofextraocular muscles remains unquestionable.28

These muscles have many structural and thereforefunctional features that are present in some skele-tal muscle systems and absent in others whichenable them to carry out their complex and highlyspecialized tasks.

The effect of the autonomous nervous systemon extraocular muscles is uncertain because mor-phologic, pharmacologic, and electrophysiologicstudies have produced contradictory results.1, 11, 12,

28, 30, 31, 44, 62, 75, 76 There is no convincing evidencefor sympathetic innervation of extraocular mus-cles.

Muscle Spindles and PalisadeEndings in the ExtraocularMuscles

Groups of fine cross-striated fibers with centrallylocated nuclei surrounded by a thin, torpedo-shaped capsule are found in all skeletal muscles.These so-called muscle spindles are propriocep-tive sensory organs. Since publication of the stud-ies by Daniel,24 Cooper and Daniel,22 and others,there is no doubt that human extraocular musclesalso contain muscle spindles. The density of thesespindles is about the same as in skeletal muscle51

and their presence is not, as had originally beenassumed, age-related.9 Whether extraocular mus-cle spindles are capable of providing propriocep-tive information is a subject of debate. In view ofdistinct histologic differences from spindles foundin skeletal muscles.51, 63, 64 Ruskell doubts this ca-pacity.64 On the other hand, passive stretching ofan extraocular muscle causes changes in ocularalignment and lack of pointing accuracy35 andvisual illusions can be elicted by muscle vibra-tion.73, 74 Lennerstrand and coworkers49 reportedthat vibration-induced eye movements differed innormal and exotropic subjects. Most current re-search seems to indicate that there may indeed besensory feedback from muscle spindles eventhough the role of this inflow under casual condi-tions of seeing is by no means clear (see alsop. 30).

Another possible source of proprioceptive inputis the palisade endings, which have been describedin the tendinous insertion of human extraocular

muscle.61, 68 Lewis and Zee50 believe that the ten-don organs rather than the muscle spindles areproviding feedback as to the position of the eye,52

a view that is also shared by Steinbach and Smith71

and by Richmond and coworkers.61

The peripheral and central pathways of extraoc-ular muscle proprioception have been defined byManni and Bortolami,52 who showed, on the basisof histologic and electrophysiologic studies, thatthe perikarya of first-order neurons are located inthe semilunar ganglion. Whereas the peripheralnerve process innervates the muscle spindle, thecentral nerve processes terminate in the ipsilateralportion of the spinal trigeminal nucleus and inthe main sensory trigeminal nucleus. Second-orderneurons have been identified in these nuclei andproject on the cerebellum and the mesodiencepha-lic areas. These data refer to animal studies andthere is no information yet on the route of centrip-etal information from the extraocular muscles inhumans.

The functional significance of the muscle spin-dles, palisade endings, and other proprioceptivesensors is discussed in Chapter 2. For additionalreviews of current theories, see Bach-y-Rita,5, 6

Lennerstrand,47, 48 and Steinbach.70

Electromyography

Electrical responses have been recorded from ex-traocular muscles of animal eyes for many years.Following Bjork’s study8 of electromyography ofhuman eyes in 1952 and subsequent elaborationby a number of researchers, important contribu-tions have been made toward understanding of thefunction of extraocular muscles in normal andpathologic states. Basically, electromyographyconsists of oscilloscopic recording of suitably am-plified electrical activities of a muscle. Monopolaror bipolar electrodes are inserted into the muscleto record the current. The electrodes are placedextracellularly. This basic technique may be highlyrefined by use of various electronic componentsfor integration, analysis, and storage of responses.

Extraocular muscles are especially interestingto those engaged in electromyographic studies be-cause of their low nerve fiber-to-muscle fiber ratio.The anatomical motor unit consists of the neuroncell body, its axon, and the muscle fibers inner-vated by that axon. All these fibers dischargesynchronously when the axon is stimulated. Theintegrated voltage of this discharge constitutes the


electric motor unit. Since only a few fibers of anextraocular muscle are innervated by one axon,electromyography comes close to recording theelectrical activity of a single anatomical motorneuron in such a muscle.

Electromyography has proved to be of value inassessing paretic and pseudoparetic conditions ofextraocular muscles, in myopathies, and in eluci-dating the pathophysiology of the retraction syn-drome (see Chapter 21). No specific abnormalitiesare revealed in patients with comitant strabismus.8

Great difficulties are encountered in quantifyingelectromyograms.12 The smallest movement distin-guishable by means of ocular electromyography isabout 5�. All this puts limitations on the use ofelectromyography in studying the physiology ofthe motor functions of the eyes. It should be benoted that the applicability of electromyographyis, for technical reasons, limited. The introductionof electrodes into the muscles is easy only forrectus muscles, although some discomfort is al-ways part of this procedure. The insertion of elec-trodes into the oblique muscle is far more difficult.Generally, no more than two muscles in eacheye can be studied simultaneously. Multichannelrecordings have recently been obtained after inser-tion of electrodes into the muscles during surgicalprocedures. The recordings were performed daysafter surgery and without discomfort to the patient,after which the electrodes simply pulled out of themuscle.17 This approach may hopefully providebetter information on electrical activity of the ex-traocular muscles.

FIGURE 6–7. Simultaneous electromyograms of the four rectus muscles. Note the graded increasein electrical activity in the right medial (RMR) and left lacteral rectus (LLR) muscles with correspondingdecrease in activity all the way to zero in the right lateral (RLR) and left medial rectus (LMR) musclesas the eyes perform a levoversion movement. With return to the primary position the RLR and LMRresume their activity and increase it in the ensuing dextroversion while the activity in the RMR andLLR decreases. (Courtesy of Prof. Alfred Huber, Zurich.)

Despite these limitations electromyography hasresulted in important contributions to the kinesiol-ogy of extraocular muscles. In essence, electro-myographic studies have given incontrovertibleproof for certain basic facts that were known, orassumed to be known, from physiologic or clinicalexperience. The contributions of electromyogra-phy to the anomalies of ocular movements arediscussed in the appropriate place in various chap-ters dealing with these anomalies.

Electromyographically, there is no ‘‘rest’’ ofthe extraocular muscles (and no ‘‘position of rest’’of the eyes). In primary position and with theeyes grossly fixed, extraocular muscles are neverelectrically silent but manifest a tonic activity.Complete inactivity of electrical discharge in ex-traocular muscles is encountered only in deepsleep or deep anesthesia.

When a muscle rotates an eye into its field ofaction, there is an increment of electrical activityaccompanied by graded inhibition of the activityof the direct antagonist (Sherrington’s law of re-ciprocal innervation). Similarly, in extreme gazeto the right, the left medial rectus fires maximallywhile the left lateral rectus is electrically silent.The opposite is true in extreme gaze to the left(Fig. 6–7). Figure 6–7 also shows that in a wakingperson a muscle may be electrically silent onlywhen in extreme positions out of its field of action.Whenever an eye diverges, an increment in theelectrical activity occurs in the lateral rectus mus-cle. For the electromyographic behavior of extra-


FIGURE 6–8. Electromyogram of saccadicmovement showing saccadic burst in the ago-nistic medial rectus muscle. (Courtesy of Dr.James E. Miller, St. Louis.)

ocular muscles in vergences and a discussion sur-rounding it, see Chapter 4.

Saccadic movements differ from vergencemovements in their innervational pattern. Miller55

found that they are initiated by a sudden burst ofmotor unit activity of the agonist with correspond-ing inhibition in the antagonist (Fig. 6–8). Theduration of the initial burst is proportional to theextent of the movement (30 ms for a 2.5� move-ment to 150 ms for a 40� movement).

This initial burst is followed immediately byan orderly series of uniformly firing motor units.The firing rate of the motor unit depends on theangular displacement from primary position.Large movements (15� to 20�) cause a second orthird saccadic burst representing efforts to over-come a lag in fixation. These findings are in ac-cord with those made by optical and electro-oculo-graphic recordings of eye movements.

Sources of Tonus of theExtraocular Muscles

The presence of fast and slow fibers in extraocularmuscles and their electrophysiologic characteris-tics and pharmacologic properties provide evi-dence for some of the peripheral mechanisms thatcontribute to the tonus of these muscles. Thisexciting new knowledge must not obscure the factthat the tonus of extraocular muscles is basicallyregulated by neural influences.

Neurophysiologists have established that thereare differences in the frequency of firing of motorneurons innervating slow and fast muscles in thehind limbs of cats and other experimental animals.Buller and coworkers16 stated that the shorter

afterpolarization of motor neurons supplying fastmuscles32 permits fast frequency of firing and isappropriately related to the contraction time ofmuscles. As a consequence, motor neurons withlarger afterhyperpolarization have frequencies ofdischarge appropriate to the slow muscles theyinnervate. Buller and coworkers also made theobservation in cross-union experiments that whena nerve from a fast motor neuron is made toinnervate a slow muscle, the muscle is trans-formed into a fast muscle; slow or tonic motorneurons, similarly transferred, convert fast mus-cles into slow.16 No corresponding observationsexist for extraocular muscles or other musclesinnervated by cranial nerves.

Irrespective of peripheral mechanisms, themost important source of tonus of extraocularmuscles is reflex in origin. A certain tonus withinthe central nervous system is kept up by stimulifrom sensory sources. Light itself is a powerfulsource of tonus. In adult humans, reflex tonusfrom neck muscles appears to be of minor impor-tance. All the more important are reflexes resultingfrom vestibular stimulations. These stimulationsto a large degree control the position of the eyesin space. They are active when the head is erect,and they also regulate the position of the eyeswith every movement of the head.

In humans, with their highly developed binocu-lar vision, however, the most powerful tonic im-pulses flow from the process of vision. Psycho-optical reflexes have superseded in importancesuch unconditioned reflexes as those that arisefrom proprioception and the vestibular system.In uniocular and binocular vision, these impulsesproduce the fixation reflex. In binocular vision,disparate stimulation elicits fusional movements


and maintains the proper relative position of theeyes.

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