Magnetic Resonance Imaging of Optic Nerve Traction During Adduction in Primary Open-Angle Glaucoma With Normal Intraocular Pressure.

PurposeWe used magnetic resonance imaging (MRI) to ascertain effects of optic nerve (ON) traction in adduction, a phenomenon proposed as neuropathic in primary open-angle glaucoma (POAG).MethodsSeventeen patients with POAG and maximal IOP ≤ 20 mm Hg, and 31 controls underwent MRI in central gaze and 20° to 30° abduction and adduction. Optic nerve and sheath area centroids permitted computation of midorbital lengths versus minimum paths.ResultsAverage mean deviation (±SEM) was -8.2 ± 1.2 dB in the 15 patients with POAG having interpretable perimetry. In central gaze, ON path length in POAG was significantly more redundant (104.5 ± 0.4% of geometric minimum) than in controls (102.9 ± 0.4%, P = 2.96 × 10-4). In both groups the ON became significantly straighter in adduction (28.6 ± 0.8° in POAG, 26.8 ± 1.1° in controls) than central gaze and abduction. In adduction, the ON in POAG straightened to 102.0% ± 0.2% of minimum path length versus 104.5% ± 0.4% in central gaze (P = 5.7 × 10-7), compared with controls who straightened to 101.6% ± 0.1% from 102.9% ± 0.3% in central gaze (P = 8.7 × 10-6); and globes retracted 0.73 ± 0.09 mm in POAG, but only 0.07 ± 0.08 mm in controls (P = 8.8 × 10-7). Both effects were confirmed in age-matched controls, and remained significant after correction for significant effects of age and axial globe length (P = 0.005).ConclusionsAlthough tethering and elongation of ON and sheath are normal in adduction, adduction is associated with abnormally great globe retraction in POAG without elevated IOP. Traction in adduction may cause mechanical overloading of the ON head and peripapillary sclera, thus contributing to or resulting from the optic neuropathy of glaucoma independent of IOP

Creep Behavior of Passive Bovine Extraocular Muscle

This paper characterized bovine extraocular muscles (EOMs) using creep, which represents long-term stretching induced by a constant force. After preliminary optimization of testing conditions, 20 fresh EOM samples were subjected to four different loading rates of 1.67, 3.33, 8.33, and 16.67%/s, after which creep was observed for 1,500 s. A published quasilinear viscoelastic (QLV) relaxation function was transformed to a creep function that was compared with data. Repeatable creep was observed for each loading rate and was similar among all six anatomical EOMs. The mean creep coefficient after 1,500 seconds for a wide range of initial loading rates was at 1.37 ± 0.03 (standard deviation, SD). The creep function derived from the relaxation-based QLV model agreed with observed creep to within 2.7% following 16.67%/s ramp loading. Measured creep agrees closely with a derived QLV model of EOM relaxation, validating a previous QLV model for characterization of EOM biomechanics

Evidence for Active Control of Rectus Extraocular Muscle Pulleys

PURPOSE. Connective tissue structures constrain paths of the rectus extraocular muscles (EOMs), acting as pulleys and serving as functional EOM origins. This study was conducted to investigate the relationship of orbital and global EOM layers to pulleys and kinematic implications of this anatomy. METHODS. High-resolution magnetic resonance imaging (MRI) was used to define the anterior paths of rectus EOMs, as influenced by gaze direction in living subjects. Pulley tissues were examined at cadaveric dissections and surgical exposures. Human and monkey orbits were step and serially sectioned for histologic staining to distinguish EOM fiber layers in relationship to pulleys. RESULTS. MRI consistently demonstrated gaze-related shifts in the anteroposterior locations of human EOM path inflections, as well as shifts in components of the pulleys themselves. Histologic studies of human and monkey orbits confirmed gross examinations and surgical exposures to indicate that the orbital layer of each rectus EOM inserts on its corresponding pulley, rather than on the globe. Only the global layer of the EOM inserts on the sclera. This dual insertion was visualized in vivo by MRI in human horizontal rectus EOMs. CONCLUSIONS. The authors propose the active-pulley hypothesis: By dual insertions the global layer of each rectus EOM rotates the globe while the orbital layer inserts on its pulley to position it linearly and thus influence the EOM's rotational axis. Pulley locations may also be altered in convergence. This overall arrangement is parsimoniously suited to account for numerous aspects of ocular dynamics and kinematics, including Listing's law. (Invest Ophthalmol Vis Sci. 2000;41: 1280 -1290 I nitial attempts to mathematically model binocular alignment showed the importance to extraocular muscle (EOM) action of EOM paths and the pivotal mechanical role of orbital connective tissues. The need for EOM path data motivated early radiographic studies in monkeys 1 and humans, 2 suggesting that paths of rectus EOMs are stabilized relative to the orbit. A decade ago, Miller 3 used relatively low-resolution MRI with three-dimensional (3-D) reconstruction to demonstrate stability of rectus EOM belly paths throughout the oculomotor range

Evidence for Active Control of Rectus Extraocular Muscle Pulleys

PURPOSE. Connective tissue structures constrain paths of the rectus extraocular muscles (EOMs), acting as pulleys and serving as functional EOM origins. This study was conducted to investigate the relationship of orbital and global EOM layers to pulleys and kinematic implications of this anatomy. METHODS. High-resolution magnetic resonance imaging (MRI) was used to define the anterior paths of rectus EOMs, as influenced by gaze direction in living subjects. Pulley tissues were examined at cadaveric dissections and surgical exposures. Human and monkey orbits were step and serially sectioned for histologic staining to distinguish EOM fiber layers in relationship to pulleys. RESULTS. MRI consistently demonstrated gaze-related shifts in the anteroposterior locations of human EOM path inflections, as well as shifts in components of the pulleys themselves. Histologic studies of human and monkey orbits confirmed gross examinations and surgical exposures to indicate that the orbital layer of each rectus EOM inserts on its corresponding pulley, rather than on the globe. Only the global layer of the EOM inserts on the sclera. This dual insertion was visualized in vivo by MRI in human horizontal rectus EOMs. CONCLUSIONS. The authors propose the active-pulley hypothesis: By dual insertions the global layer of each rectus EOM rotates the globe while the orbital layer inserts on its pulley to position it linearly and thus influence the EOM's rotational axis. Pulley locations may also be altered in convergence. This overall arrangement is parsimoniously suited to account for numerous aspects of ocular dynamics and kinematics, including Listing's law. (Invest Ophthalmol Vis Sci. 2000;41: 1280 -1290 I nitial attempts to mathematically model binocular alignment showed the importance to extraocular muscle (EOM) action of EOM paths and the pivotal mechanical role of orbital connective tissues. The need for EOM path data motivated early radiographic studies in monkeys 1 and humans, 2 suggesting that paths of rectus EOMs are stabilized relative to the orbit. A decade ago, Miller 3 used relatively low-resolution MRI with three-dimensional (3-D) reconstruction to demonstrate stability of rectus EOM belly paths throughout the oculomotor range

Absence of Relationship between Oblique Muscle Size and Bielschowsky Head Tilt Phenomenon in Clinically Diagnosed Superior Oblique Palsy

PURPOSE. To study whether the variation in maximum oblique muscle size accounts for individual variation in the Bielschowsky head tilt phenomenon (BHTP) in clinically diagnosed superior oblique (SO) palsy. METHODS. Seventeen subjects with clinically diagnosed earlyonset or idiopathic SO palsy and 14 normal subjects were enrolled in the study. Magnetic resonance imaging (MRI) in coronal and sagittal planes was used for quantitative morphometry of inferior oblique (IO) and SO muscles. Maximum crosssectional area of the SO and IO cross section at the mid-inferior rectus crossing were determined in central gaze and compared with paretic eye hypertropia on ipsilesional versus contralesional head tilt. RESULTS. Mean (ϮSD) maximum SO cross section was 18.1 Ϯ 3.2 mm 2 in normal subjects, 14.2 Ϯ 6.8 mm 2 ipsilesional to SO palsy, and 19.2 Ϯ 4.5 mm 2 contralesional to SO palsy. The ipsilesional SO cross section was significantly smaller than the contralesional (P ϭ 0.004) and normal (P ϭ 0.01) ones. The mean IO cross section was 18.3 Ϯ 3.5 mm 2 in normal subjects, 21.3 Ϯ 7.9 mm 2 ipsilesional to SO palsy (P ϭ 0.43), and 22.0 Ϯ 6.7 mm 2 contralesional to SO palsy (P ϭ 0.26). Hyperdeviation varied with head tilt by 20.1 Ϯ 5.5°in subjects with SO atrophy, and 10.3 Ϯ 5.6°in subjects without SO atrophy (P ϭ 0.003). Although oblique muscle cross sections did not correlate with BHTP, subjects with clinically diagnosed SO palsy segregated into groups exhibiting normal versus atrophic SO size. CONCLUSIONS. SO size does not account for the variation in BHTP in clinically diagnosed SO palsy, supporting the proposition that the BHTP is nonspecific for SO function. (Invest Ophthalmol Vis Sci. 2009;50:175-179) DOI:10.1167/iovs.08-2393 P atients with early onset or idiopathic superior oblique (SO) palsy are heterogeneous. Only when orbital imaging shows a large asymmetry in cross-sectional areas of the SO muscles is actual muscle weakness 1-4 likely. SO palsy may not necessarily be neuropathic, because abnormalities of the SO tendon, 5-8 or of orbital pulleys may cause incomitant vertical strabismus mimicking SO palsy. 9,10 For this reason, the gold standard for the diagnosis of SO palsy is ultimately radiographic. Nevertheless, much clinical literature on SO palsy is based on clinical, not radiographic, criteria. If clinical criteria are nonspecific for SO palsy, then some beliefs about SO palsy may benefit from reexamination. The Bielschowsky head tilt phenomenon (BHTP) consists of a greater hypertropia during head tilt to the ipsilesional than contralesional shoulder in patients seated upright and is used as a clinical lateralizing test for SO palsy. The biomechanical basis of the BHTP is not fully understood, but probably includes loss of downward and intorsional torque of the palsied SO in compensatory ocular counterrolling (OCR). 11 The BHTP is considered by many clinicians to be the defining clinical criterion for SO palsy. Oblique muscles have both vertical and torsional actions. Contractility of the SO can be radiographically determined by evaluating the change in SO cross-sectional area during gaze shift from supraduction to infraduction. In patients with SO palsy, SO contractility is well correlated with maximum SO cross-sectional area in central gaze. 12 Further, MRI evidence of SO muscle contractile change in vertical gaze shift resembles similar MRI findings during ocular counterrolling. 13 During static ocular counterrolling, 13 the posterior SO cross section was found to be greater during head tilt to the ipsilateral than the contralateral side, reflecting SO contraction to implement ocular torsion. 2 Because changes in SO cross section due to vertical duction resemble changes associated with OCR, we sought to analyze whether variation in SO size accounts for variation in BHTP in SO palsy. Recognizing that maximum SO cross-sectional size in the central gaze is highly correlated with SO contractility, 12 we supposed that the BHTP would also correlate with SO size if this diagnostic test directly reflects SO function. METHODS Subjects Subjects with clinically diagnosed congenital or idiopathic SO palsy, including presumably decompensated cases, were recruited from a prospective study of extraocular muscle function at Okayama University Hospital. The subjects agreed to participate and gave written informed consent according to a protocol conforming to the tenets of the Declaration of Helsinki. Diagnosis of SO palsy was based on clinical criteria including: ipsilesional hypertropia greater in the contralesional than the ipsilesional version, and greater during head tilt to the ipsilateral than the contralateral shoulder when seated upright (Bielschowsky head tilt test); a deficit in infraduction when the ipsilesional eye was adducted; and results of Hess screen testing performed by strabismologists confirming greater hypertropia in deorsumversion and V pattern. All participants underwent complete ophthalmic examinations, including measurement of heterophorias with prism and cover testing. The BHTP was defined quantitatively to be the difference From th

Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3).

PURPOSE. Three congenital fibrosis of the extraocular muscles phenotypes (CFEOM1-3) have been identified. Each represents a specific form of paralytic strabismus characterized by congenital restrictive ophthalmoplegia, often with accompanying ptosis. It has been demonstrated that CFEOM1 results from mutations in KIF21A and CFEOM2 from mutations in PHOX2A. This study was conducted to determine the incidence of KIF21A and PHOX2A mutations among individuals with the third CFEOM phenotype, CFEOM3. METHODS. All pedigrees and sporadic individuals with CFEOM3 in the authors' database were identified, whether the pedigrees were linked or consistent with linkage to the FEOM1, FEOM2, and/or FEOM3 loci was determined, and the appropriate pedigrees and the sporadic individuals were screened for mutations in KIF21A and PHOX2A. RESULTS. Twelve CFEOM3 pedigrees and 10 CFEOM3 sporadic individuals were identified in the database. The structures of eight of the pedigrees permitted the generation of meaningful linkage data. KIF21A was screened in 17 probands, and mutations were identified in two CFEOM3 pedigrees. One pedigree harbored a novel mutation (2841G-->A, M947I) and one harbored the most common and recurrent of the CFEOM1 mutations identified previously (2860C-->T, R954W). None of CFEOM3 pedigrees or sporadic individuals harbored mutations in PHOX2A. CONCLUSIONS. The results demonstrate that KIF21A mutations are a rare cause of CFEOM3 and that KIF21A mutations can be nonpenetrant. Although KIF21A is the first gene to be associated with CFEOM3, the results imply that mutations in the unidentified FEOM3 gene are the more common cause of this phenotype

Dynamic Visual Acuity of Normal Subjects During Vertical Optotype and Head Motion

Purpose. To characterize the effect of passive vertical head motion on dynamic visual acuity of young, normally sighted subjects wearing telescopic spectacles, and to relate this to the velocity of images on the retina. Methods. Static visual acuity was measured without motion. Dynamic visual acuity was measured during vertical, sinusoidal motion of either optotypes or of a servo-driven rotating chair in which subjects were seated. Dynamic visual acuity for head motion was measured unaided, as well as with 1.9X, 4X, and 6X telescopic spectacles. Vertical eye movements were recorded using magnetic search coils. Results. During optotype motion, acuity declined with increasing velocity to a minimum of 2 0 / 2 0 0 at 100°/sec. Pursuit gain (eye velocity/optotype velocity) for moving optotypes was low except for optotype velocities of 20°/sec of less. Dynamic visual acuity without telescopic spectacles was not sensitive to head motion. Static visual acuity improved with increasing telescopic spectacle power, but dynamic visual acuity became progressively impaired by head motion as telescopic spectacle power was increased. Compared with static visual acuity, head motion with peak velocity of 40°/sec reduced acuity two-fold for 1.9X telescopic spectacles, fourfold for 4X telescopic spectacles, and eightfold for 6X telescopic spectacles. Visual vestibulo-ocular rellex gain with telescopic spectacles increased to values markedly above 1.0, but was always less than telescopic spectacle magnification. There was visual tolerance of slip velocities of 2°/sec or less, above which acuity declined in proportion to the 0.6 power of retinal slip velocity. Above 2°/sec, retinal slip velocity accounted for 95% of the variance in dynamic visual acuity. Conclusions. These results confirm that acuity is sensitive to retinal image motion in the vertical direction, and extend this finding to indicate that sensitivity of acuity to vertical head motion during wearing of telescopic spectacles is attributable to retinal image slip velocity. Invest Ophthalmol Vis Sci 1993;34:1894-1906 .Dynamic visual acuity (DVA) is that acuity obtained during relative motion of either optotypes or observer

New Anatomic Concepts and Their Surgical Implications for the Treatment of Strabismus

Historically, much clinical thinking about strabismus hasbeen grounded in concepts of extraocular muscle (EOM) action that now appear incorrect in light of recent anatomical and physiological findings

Eye Movements, Strabismus, Amblyopia, and Neuro-Ophthalmology Independent Active Contraction of Extraocular Muscle Compartments

PURPOSE. Intramuscular innervation of horizontal rectus extraocular muscle (EOMs) is segregated into superior and inferior (transverse) compartments, whereas all EOMs are also divided into global (GL) and orbital (OL) layers with scleral and pulley insertions, respectively. Mechanical independence between both types of compartments has been demonstrated during passive tensile loading. We examined coupling between EOM compartments during active, ex vivo contraction. METHODS. Fresh bovine EOMs were removed, and one compartment of each was coated with hydrophobic petrolatum. Contraction of the uncoated compartment was induced by immersion in a solution of 50 mM CaCl 2 at 388C labeled with sodium fluorescein dye, whereas tensions in both compartments were monitored by strain gauges. Control experiments omitted petrolatum so that the entire EOM contracted. After physiological experiments, EOMs were sectioned transversely to demonstrate specificity of CaCl 2 permeation by yellow fluorescence dye excited by blue light. RESULTS. In control experiments without petrolatum, both transverse and GL and OL compartments contracted similarly. Selective compartmental omission of petrolatum caused markedly independent compartmental contraction whether measured at the GL or the OL insertions or for transverse compartments at the scleral insertion. Although some CaCl 2 spread occurred, mean (6SD) tension in the coated compartments averaged only 10.5 6 3.3% and 6.0 6 1.5% in GL/OL and transverse compartments, respectively relative to uncoated compartments. Fluorescein penetration confirmed selective CaCl 2 permeation. CONCLUSIONS. These data confirm passive tensile findings of mechanical independence of EOM compartments and extend results to active contraction. EOMs behave actively as if composed of mechanically independent parallel fiber bundles having different insertional targets, consistent with the active pulley and transverse compartmental hypotheses