Joel M. Miller

Heterotopic Muscle Pulleys or Oblique Muscle Dysfunction

INTRODUCTION The description of connective tissue sleeves that function as pulleys for the rectus extraocular muscles (EOMs) suggests that abnormalities of EOM pulley position might provide a mechanical basis for some forms of incomitant strabismus. Pulleys determine the paths and thus the pulling directions of EOMs. METHODS High-resolution magnetic resonance images spanning the orbits were obtained in primary position, upgaze, and downgaze for each subject. Paths of the EOMs were measured with reference to the orbital center and permitted inference of pulley locations. RESULTS Data from 18 orbits of orthotropic subjects defined means and SDs of normal EOM pulley coordinates. Eight patients, aged 17 to 60 years, had heterotopic EOM pulleys, defined as displaced at least 2 SDs from normal. We found one to eight heterotopic pulleys (considering both orbits) in each of four patients who had been diagnosed with marked superior oblique (SO) overaction and mild to marked inferior oblique (IO) underaction. Each patient had superior mislocation of at least one lateral rectus pulley by 1.8 to 4.9 mm. Three patients diagnosed with mild to moderate IO overaction and mild to moderate SO underaction in only one orbit had one to three heterotopic EOM pulleys. Each of those patients had at least one lateral rectus pulley inferiorly dislocated by 1.9 to 4.9 mm. The final patient, who was diagnosed with mild IO underaction and normal SO function bilaterally, had bilateral superior mislocation of the medial rectus pulleys by greater than 2 mm. Computer simulations using the Orbit program (Eidactics, San Francisco) incorporating individually measured pulley positions reproduced the clinical patterns of incomitant strabismus in all cases without postulating abnormalities of oblique muscle innervation or contractility. CONCLUSION Heterotopic EOM pulleys can cause patterns of incomitant strabismus that have been attributed to oblique muscle dysfunction. Even isolated mislocations of less than 2 mm, coupled with smaller mislocations of the other pulleys, can produce the clinical appearance of bilateral oblique dysfunction. Pulley heterotopy should be considered in the differential diagnosis of incomitant strabismus and oblique dysfunction.

Extraocular connective tissue architecture

Extraocular muscle pulleys, now well known to be kinematically significant extraocular structures, have been noted in passing and described in fragments several times over the past two centuries. They were late to be fully appreciated because biomechanical modeling of the orbit was not available to derive their kinematic consequences, and because pulleys are distributed condensations of collagen, elastin and smooth muscle (SM) that are not sharply delineated. Might other mechanically significant distributed extraocular structures still be awaiting description?An imaging approach is useful for describing distributed structures, but does not seem suitable for assessing mechanical properties. However, an image that distinguished types and densities of constituent tissues could give strong hints about mechanical properties. Thus, we have developed methods for producing three dimensional (3D) images of extraocular tissues based on thin histochemically processed slices, which distinguish collagen, elastin, striated muscle and SM. Overall tissue distortions caused by embedding for sectioning, and individual-slice distortions caused by thin sectioning and subsequent histologic processing were corrected by ordered image warping with intrinsic fiducials. We describe an extraocular structure, partly included in Lockwoods ligament, which contains dense elastin and SM bands, and which might refine horizontal eye alignment as a function of vertical gaze, and torsion in down-gaze. This active structure might therefore be a factor in strabismus and a target of therapeutic intervention.

Surgical implications of the rectus extraocular muscle pulleys

PURPOSE Magnetic resonance imaging (MRI) shows that the paths of rectus extraocular muscle bellies remain fixed in the orbit during large ocular rotations, and across large surgical transpositions of their insertions. This stability of muscle paths is due to their passage through pulleys which are coupled to the orbit and located in a coronal plane anterior to the muscle bellies near the equator of the globe. Autopsy studies have shown the pulleys to be fibroelastic sleeves consisting of dense bands of collagen and elastin, suspended from the orbit and adjacent extraocular muscle sleeves by bands of similar composition. Immunohistochemical studies have revealed substantial smooth muscle in the pulley suspensions and in posterior Tenons fascia. The pulleys function as mechanical origins of the rectus extraocular muscles in the sense of determining extraocular muscle pulling directusons. This study was conducted to determine the theoretical effects of the pulleys on the outcome of rectus transposition surgery. METHODS The functional and anatomical evidence for the existence of the rectus extraocular muscle pulleys was reviewed. In two patients, binocular alignment data were collected using the Hess screen test before and after vertical rectus transposition surgeries for lateral rectus paralysis. Paths of the rectus extraocular muscles were determined using high resolution MRI. The OrbitTM 1.5 extraocular biosimulation program was employed to compute theoretical binocular alignment and muscle paths, under alternative conditions including or omitting the pulleys. RESULTS Pulleys are required to account for observed paths of rectus extraocular muscles following transposition surgery. In the absence of pulleys, transposition of the superior and inferior rectus muscles to the lateral rectus insertion for abducens paralysis would result in bizarre ocular misalignments not observed clinically. CONCLUSIONS The human orbit contains specialized musculofibroelastic tissues in and just posterior to Tenons fascia, which serve as pulleys, determining actions of rectus extraocular muscles. These pulleys are located in a roughly coronal plane just posterior to the equator of the globe. Unimpaired pulley function is essential to effective muscle transposition surgery.

Quantitative Magnetic Resonance Morphometry of Extraocular Muscles: A New Diagnostic Tool in Paralytic Strabismus

Paralytic strabismus is often diagnostically ambiguous due to the similarity of patterns of misalignment produced by different mechanisms. To address this problem, we have developed a new technique employing high-resolution, surface coil magnetic resonance imaging to quantify extraocular muscle size and contractility. Adjacent coronal images are obtained spanning the anteroposterior extent of each orbit, and repeated in multiple directions of gaze. Contractility is evaluated from analysis of muscle cross-sectional areas. The quantitative size and contractile characteristics of normal rectus and superior oblique muscles are reviewed, along with the effects of superior oblique palsy. The morphometric features of lateral rectus palsy are illustrated by three clinical cases exhibiting deficient contractility and atrophy of the lateral rectus muscle. A case of superior oblique palsy is presented illustrating atrophy and lack of contractility of the involved superior oblique muscle. This imaging technique can be employed in any clinical center and permits insight into extraocular muscle function in complex strabismus cases.

Understanding and misunderstanding extraocular muscle pulleys

As evidence has mounted for the critical role of extraocular muscle (EOM) pulleys in normal ocular motility and disease, opposition to the notion has grown more strident. We review the stages through which pulley theory has developed, distinguishing passive, coordinated, weak differential, and strong differential pulley theories and focusing on points of controversy. There is overwhelming evidence that much of the eyes kinematics, once thought to require brainstem coordination of EOM innervations, is determined by orbital biomechanics. The main criticisms of pulley theory only apply to the strong differential theory, abandoned in 2002. Critiques of the notion of dual EOM insertions are shown to be mistaken. The role of smooth muscle and the issue of rotational noncommutativity are clarified. We discuss how pulley sleeves can be stabilized as required by the theory, noting that more work needs to be done in specifying the tissues involved.

Different motor systems use similar damped extraretinal eye position information

Extraretinal eye position information (EEPI) shifts the directional significance of retinal loci by an angle roughly equal to that of an associated saccade, with the shift reported to begin 0-250 ms before the saccade and to continue apace with the saccade, or sluggishly, over a period as much as an order of magnitude longer. These different estimates of remapping initiation and duration could be due to various factors, including different localizing responses, retinal loci of probe flashes, and saccade target predictability. We compared manual and gaze pointing to probe flashes at controlled retinal loci under identical stimulus conditions and in the same subjects, and found that EEPI was similar: both hand and gaze pointing EEPI shifted over about 140 ms, beginning about 50 ms before the saccade. For both pointing responses, remapping appeared to be initiated later for parafoveal loci than for loci 10 degrees to either side. We found no effect of saccade target predictability. We show that variability in EEPI and sensory processing only slightly (approximately 5%) inflates estimates of EEPI shift duration. Based on our results, and comparisons with recent studies, we argue that similar EEPI parameters apply to hand pointing, eye pointing and visual comparisons, and that remaining differences across studies can reasonably be attributed to differences in stimulus conditions.

Egocentric localization of a perisaccadic flash by manual pointing.

Reaching towards a visual object in the absence of visual referents relies on a chain of information, from the sensory signals encoding the objects image on the retina, to the motor signals driving the hand. One link in this chain is an extraretinal eye position signal (EEPS), which specifies the position of the eye in the head. EEPS must be updated in precise coordination with the eyes rapidly changing position, or perisaccadic visual targets will be mislocalized. There have been conflicting reports about the existence and nature of mislocalizations associated with saccades. We measured perisaccadic visual localization by presenting brief (250 microseconds), bright (6000 cd/m2), binocular, gaze-point (foveal) probe flashes in an otherwise dark field to normal human subjects instructed to point to them with an unseen hand. Saccade and fixation targets were auditory, making intravisual comparison impossible. Saccades, elicited randomly to left and right of straight ahead, had a mean magnitude of 8.9 deg. Control trials, employing only non-perisaccadic probes and providing feedback of pointing errors, were randomly interspersed, to monitor and control drift of hand-eye coordination. On average, localization began to shift for probes presented 2 msec after the eye began to move, reaching a stable post-saccadic value with time constant tau = 71 msec. A second experiment was similar, except that viewing was monocular, and probes were presented randomly, at gaze (on fovea), 6 deg left of gaze (right of fovea) and 6 deg right of gaze (left of fovea). The main analysis treated saccades larger than 8 deg: their mean magnitude was 12.9 deg. Flashes left of gaze were relocalized faster (tau = 65 msec) than flashes right of gaze (tau = 129 msec) around the time of leftward saccades. In contrast, flashes right of gaze were relocalized faster (tau = 62 msec) than flashes left of gaze (tau = 90 msec) around the time of rightward saccades. Time constant was independent of saccade size. Updating began for probes presented within 4 msec of the beginning of saccades, and was not a function of saccade or flash direction. Thus, there were no systematic mislocalizations of probes presented before eye movement, and large mislocalizations of probes presented during and after. Mislocalizations were, on average, always in the direction opposite the saccade, and were maximal (about half the magnitude of the completed saccade) near the end of the saccade. Stable post-saccadic localization was not achieved until about 100-300 msec after completion of a saccade; EEPS was updated slowly, compared to eye position itself. The visual field was not remapped uniformly: the side that would normally contain the target of a visually evoked saccade (and usually the target of a corrective saccade), was updated with a shorter time constant.

Eye Muscle Prosthesis

We inserted a silicone rubber elastic band along the course of a paralyzed lateral rectus and of a paralyzed superior oblique to restore alignment and to provide a spring against which the antagonist could pull. The lateral rectus band has been in place for 7 years. It provides alignment and a field of single binocular vision of 20 degrees. The superior oblique band has been in place for 17 months. It provides alignment and single vision over 30 degrees from the primary position except for a restriction in upgaze-adduction to 25 degrees (Brown syndrome) and in downgaze-adduction to 20 degrees. Such engineered elastic bands are a useful addition to current surgical techniques for management of cases of paralysis and restriction.

Motor nucleus activity fails to predict extraocular muscle forces in ocular convergence

For a given eye position, firing rates of abducens neurons (ABNs) generally (Mays et al. 1984), and lateral rectus (LR) motoneurons (MNs) in particular (Gamlin et al. 1989a), are higher in converged gaze than when convergence is relaxed, whereas LR and medial rectus (MR) muscle forces are slightly lower (Miller et al. 2002). Here, we confirm this finding for ABNs, report a similarly paradoxical finding for neurons in the MR subdivision of the oculomotor nucleus (MRNs), and, for the first time, simultaneously confirm the opposing sides of these paradoxes by recording physiological LR and MR forces. Four trained rhesus monkeys with binocular eye coils and custom muscle force transducers on the horizontal recti of one eye fixated near and far targets, making conjugate saccades and symmetric and asymmetric vergence movements of 16-27°. Consistent with earlier findings, we found in 44 ABNs that the slope of the rate-position relationship for symmetric vergence (k(V)) was lower than that for conjugate movement (k(C)) at distance, i.e., mean k(V)/k(C) = 0.50, which implies stronger LR innervation in convergence. We also found in 39 MRNs that mean k(V)/k(C) = 1.53, implying stronger MR innervation in convergence as well. Despite there being stronger innervation in convergence at a given eye position, we found both LR and MR muscle forces to be slightly lower in convergence, -0.40 and -0.20 g, respectively. We conclude that the relationship of ensemble MN activity to total oculorotary muscle force is different in converged gaze than when convergence is relaxed. We conjecture that LRMNs with k(V) < k(C) and MRMNs with k(V) > k(C) innervate muscle fibers that are weak, have mechanical coupling that attenuates their effective oculorotary force, or serve some nonoculorotary, regulatory function.

Bupivacaine injection of the lateral rectus muscle to treat esotropia

PURPOSE We report results of a pilot trial of bupivacaine injection into extraocular muscles as a method of enlarging and strengthening the muscles to treat strabismus. METHODS Bupivacaine, in volumes from 1.0 to 4.5 mL and concentrations from 0.75% to 3.0%, was injected into 1 lateral rectus muscle in each of 6 patients with comitant esotropia with the use of the electrical activity recorded from the needle tip to guide injection. Magnetic resonance imaging was performed before and at intervals after injection to estimate changes in muscle size. Clinical measures of alignment were made before and at intervals after injection. Two patients required a second injection for adequate effect. RESULTS Four patients showed improved eye alignment, averaging 12(Delta), measured an average of 367 days after the last injection (range, 244-540 days). Two patients were substantially unchanged. Alignment improvement for all 6 patients averaged 8(Delta) (range, 0-14(Delta)). Volumetric enlargement of the injected muscle, computed from magnetic resonance images, was 6.2% (range, -1.5% to 13.3%). There was a positive correlation between alignment change and muscle enlargement averaging 0.65. Injection caused a retrobulbar hemorrhage in an unchanged patient that cleared without affecting vision. CONCLUSIONS Bupivacaine injection improved eye alignment in 4 of 6 esotropic patients. There was a positive correlation between improved eye alignment and increased muscle size. Clinical and laboratory studies are underway to determine optimal dosages, effects in other strabismus conditions, and differential effects of bupivacaine on contractile and elastic muscle components.