PURPOSE: This study employed magnetic resonance imaging (MRI) to investigate possible size and contractility changes in the superior oblique (SO) muscle, and possible isometric hypertrophy in the inferior oblique (IO) muscle, resulting from abnormal mechanical loading in Brown syndrome (BrS). METHODS: High resolution orbital MRI was obtained in 4 congenital and 11 acquired cases of BrS, and compared with 44 normal subjects. Maximal cross-section areas and posterior partial volumes (PPVs) of the SO were analyzed in central gaze, supraduction, and infraduction [corrected] for the SO, and in central gaze only for the IO. RESULTS: In congenital BrS, mean maximum SO cross-sectional areas were 24% and 20% less than normal in affected and unaffected eyes, respectively (P = 0.0002). Mean PPV in congenital BrS was also significantly subnormal bilaterally (29% and 34% less in affected and unaffected eyes, respectively, P = 0.001). However, SO muscle size and volume were normal in acquired cases. The SO muscle did not relax in supraduction in BrS, although there was normal contractile thickening in infraduction. The IO muscle had normal size bilaterally in BrS. CONCLUSIONS: Congenital BrS may be associated with SO hypoplasia that could reflect hypoinnervation. However, unique isometric loading of oblique extraocular muscles due to restrictive hypotropia in adduction in BrS is generally not associated with changes in muscle bulk or in SO contractility. Unlike skeletal muscles, the bulk and contractility of extraocular muscles can therefore be regarded as independent of isometric exercise history. Restriction to elevation in BrS typically arises in the trochlea-tendon complex.

PURPOSE: Using high-resolution magnetic resonance imaging (MRI), we investigated whether rectus pulleys are significantly displaced in superior oblique (SO) palsy and whether displacements account for strabismus patterns. DESIGN: Prospective case-control study. PARTICIPANTS: Twenty-four patients diagnosed with SO palsy based on atrophy of the SO muscle on MRI and 19 age-matched orthotropic control subjects. METHODS: High-resolution, surface coil MRI scans were obtained in multiple, contiguous, quasicoronal planes during monocular central gaze fixation. Pulley locations in oculocentric coordinates in the following subgroups of patients with SO palsy were compared with normal results in subgroups of patients with SO palsy: unilateral versus bilateral, congenital versus acquired, and isotropic (round) versus anisotropic (elongated) SO atrophy. Expected effects of pulley displacements were modeled using Orbit 1.8 (Eidactics, San Francisco, CA) computational simulation. MAIN OUTCOME MEASURES: Rectus pulley positions and ocular torsion. RESULTS: Rectus pulleys typically were displaced in SO palsy. In unilateral SO palsy, on average the medial rectus (MR) pulley was displaced 1.1 mm superiorly, the superior rectus (SR) pulley was displaced 0.8 mm temporally, and the inferior rectus (IR) pulley was displaced 0.6 mm superiorly and 0.9 mm nasally from normal. Displacements were similar in bilateral SO palsy, with the SR pulley additionally displaced 0.9 mm superiorly. However, the lateral rectus pulley was not displaced in either unilateral or bilateral SO palsy. The SR and MR pulleys were displaced in congenital SO palsy, whereas the IR and MR pulleys were displaced in acquired palsy. Pulley positions did not differ between isotropic and anisotropic palsy or between patients with cyclotropia of less than 7° versus cyclotropia of 7° or more. Simulations predicted that the observed pulley displacements alone could cause patterns of incomitant strabismus typical of SO palsy, without requiring any abnormality of SO or inferior oblique strength. CONCLUSIONS: Rectus pulley displacements alone, without abnormal oblique muscle contractility, can create the clinical patterns of incomitant strabismus in SO palsy. This finding supports accumulating evidence that clinical binocular misalignment patterns are not reliable indicators of contractile function of the SO muscle. Ocular torsion does not correlate with and thus cannot account for pulley displacements in SO palsy.

PURPOSE: To investigate changes in volumes of extraocular muscle (EOM) compartments in unilateral superior oblique (SO) palsy using magnetic resonance imaging (MRI). METHODS: High-resolution, surface-coil MRI was obtained in 19 patients with unilateral SO palsy and 19 age-matched orthotropic control subjects. Rectus EOMs and the SO were divided into two anatomic compartments for volume analysis in patients with unilateral SO palsy, allowing comparison of total compartmental volumes versus controls. Medial and lateral compartmental volumes of the SO muscle were compared in patients with isotropic (round shape) versus anisotropic (elongated shape) SO atrophy. RESULTS: The medial and lateral compartments of the ipsilesional SO muscles were equally atrophic in isotropic SO palsy, whereas the lateral compartment was significantly smaller than the medial in anisotropic SO palsy (P = 0.01). In contrast to the SO, there were no differential compartmental volume changes in rectus EOMs; however, there was significant total muscle hypertrophy in the ipsilesional inferior rectus (IR) and lateral rectus (LR) muscles and contralesional superior rectus (SR) muscles. Medial rectus (MR) volume was normal both ipsi- and contralesionally. CONCLUSIONS: A subset of patients with SO palsy exhibit selective atrophy of the lateral, predominantly vertically acting SO compartment. Superior oblique atrophy is associated with whole-muscle volume changes in the ipsilesional IR, ipsilesional LR, and contralesional SR; however, SO muscle atrophy is not associated with compartmentally selective volume changes in the rectus EOMs. Selective compartmental SO pathology may provide an anatomic mechanism that explains some of the variability in clinical presentations of SO palsy.

PURPOSE: To determine whether rectus extraocular muscle (EOM) sizes and pulley locations contribute to exotropia, we used magnetic resonance imaging (MRI) to measure these factors in normal control participants and in patients with concomitant and pattern exotropia. DESIGN: Prospective case-control study. PARTICIPANTS: Nine patients with concomitant exotropia, 6 patients with pattern exotropia, and 21 orthotropic normal control participants. METHODS: High-resolution surface-coil MRI scans were obtained in contiguous, quasicoronal planes. Rectus pulley locations were determined in oculocentric coordinates for central gaze, supraduction, and infraduction. Cross sections in 4 contiguous image planes were summed and multiplied by the 2-mm slice thickness to obtain horizontal rectus posterior partial volumes (PPVs). MAIN OUTCOME MEASURES: Rectus pulley locations and horizontal rectus PPVs. RESULTS: Rectus pulleys were located differently in patients with A-pattern, versus V- and Y-pattern, exotropia. The lateral rectus (LR) pulleys were displaced significantly superiorly, the medial rectus (MR) pulleys were displaced inferiorly, and the inferior rectus pulleys were displaced laterally in A-pattern exotropia. However, the array of all rectus pulleys was excyclorotated in V- and Y-pattern exotropia. The PPV of the medial rectus muscle was statistically subnormal by approximately 29% in concomitant, but not pattern, exotropia (P < 0.05). The ratio of the PPV of the LR relative to the MR muscles in concomitant exotropia was significantly greater than in control participants and those with pattern exotropia (P < 0.05). CONCLUSIONS: Abnormalities of EOMs and pulleys contribute differently in pattern versus concomitant exotropia. Abnormal rectus pulley locations derange EOM pulling directions that contribute to pattern exotropia, but in concomitant exotropia, pulley locations are normal, and relatively small medial rectus size reduces relative adducting force.

PURPOSE: To investigate the relationship between displacement of extraocular muscles (EOMs) and staphyloma in high myopia using magnetic resonance imaging (MRI). DESIGN: Retrospective case-control study. METHODS: Setting: Institutional study. POPULATION: Twenty-nine highly myopic patients (46 eyes), 11 age-matched healthy control subjects (21 eyes), and 34 patients (66 eyes) with sagging eye syndrome. PROCEDURES: MRI was analyzed for aspect ratio (AR) of the ocular cross section, locations of staphylomata and EOMs, and status of superior rectus to lateral rectus (SR-LR) band ligament. MAIN OUTCOME MEASURES: Association between staphylomata with EOM paths and the LR-SR band. RESULTS: Several associations of staphylomata were statistically significant (P < .05). Most staphylomata were superotemporal. Myopic patients with staphyloma had larger ARs in quasi-coronal images than in myopic subjects without staphyloma or normal controls. Compared to patients with high myopia without staphyloma and normal controls, when staphyloma was present, there was more inferior LR displacement, larger LR-globe angle, and larger SR-LR displacement angle than in myopic subjects without staphyloma. Staphyloma in the superotemporal quadrant was associated with greater SR-LR angle than in other quadrants. There were significantly more ruptures of SR-LR band ligament in highly myopic patients with staphyloma than in those without staphyloma. CONCLUSIONS: Local staphylomata in high myopia reflect ocular asphericity and correlate with EOM paths. Myopic staphylomata are associated with inferior displacement of LR path and defect of the LR-SR band ligament.

PURPOSE: Intramuscular innervation of mammalian horizontal rectus extraocular muscles (EOMs) is compartmental. We sought evidence of similar compartmental innervation of the superior oblique (SO) muscle. METHODS: Three fresh bovine orbits and one human orbit were dissected to trace continuity of SO muscle and tendon fibers to the scleral insertions. Whole orbits were also obtained from four humans (two adults, a 17-month-old child, and a 33-week stillborn fetus), two rhesus monkeys, one rabbit, and one cow. Orbits were formalin fixed, embedded whole in paraffin, serially sectioned in the coronal plane at 10-μm thickness, and stained with Masson trichrome. Extraocular muscle fibers and branches of the trochlear nerve (CN4) were traced in serial sections and reconstructed in three dimensions. RESULTS: In the human, the lateral SO belly is in continuity with tendon fibers inserting more posteriorly on the sclera for infraducting mechanical advantage, while the medial belly is continuous with anteriorly inserting fibers having mechanical advantage for incycloduction. Fibers in the monkey superior SO insert more posteriorly on the sclera to favor infraduction, while the inferior portion inserts more anteriorly to favor incycloduction. In all species, CN4 bifurcates prior to penetrating the SO belly. Each branch innervates a nonoverlapping compartment of EOM fibers, consisting of medial and lateral compartments in humans and monkeys, and superior and inferior compartments in cows and rabbits. CONCLUSIONS: The SO muscle of humans and other mammals is compartmentally innervated in a manner that could permit separate CN4 branches to selectively influence vertical versus torsional action.

PURPOSE: To study effects of age and horizontal duction on deformation of the optic nerve head (ONH) and peripapillary retina (PPR), as reflected by displacement of vascular landmarks, to explore the influence of adduction tethering. DESIGN: Cross-sectional study. METHODS: Setting: University. STUDY POPULATION: Single eyes of 20 healthy young adults (average age 23.9 ± 3.9 [SD] years) were compared to 20 older subjects (average age 61.4 ± 9.3 years). Observational Procedure: The disc and PPR were imaged by scanning laser ophthalmoscopy in central gaze and at 35 degrees abduction and adduction. MAIN OUTCOME MEASURE: Deformations of the disc and adjacent PPR were measured by comparing positions of epipapillary and epiretinal blood vessels. RESULTS: Vessels within the ONH of younger subjects shifted temporally during adduction and nasally during abduction. Displacement of the nasal hemi-disc in adduction was greater at 38.5 ± 1.7 μm (standard error of mean) than the temporal half at 4.1 ± 2.1 μm (P < .001). PPR within 1 radius of the disc margin underwent 7.6 ± 1.6 μm average temporal displacement in adduction in young subjects. In abduction, the young temporal hemi-disc shifted 4.4 ± 0.6 μm nasally without significant displacement in the nasal half. Older subjects ONH showed less temporal shift and less displacement in the PPR within 1 disc radius (P < .0001) in adduction; the nasal hemi-disc shifted 24.5 ± 1.3 μm compared with 4.4 ± 2.1 μm in the temporal half. There were no significant deformations of the disc during abduction by older subjects. CONCLUSION: Large horizontal duction, particularly adduction, deforms the disc and peripapillary vasculature. This deformation, which is larger in younger than older subjects, may be due to optic nerve tethering in adduction.

Purpose

Topical prostaglandin analogs (PGAs) are common treatment for primary open-angle glaucoma (POAG) but reportedly may cause adnexal fat atrophy. We asked if patients with POAG treated with PGAs have abnormalities in orbital fat volume (OFV).

Methods

We studied 23 subjects with POAG who had never experienced intraocular pressure (IOP) exceeding 21 mm Hg and were treated long term with PGAs, in comparison with 21 age-matched controls. Orbital volume, non-fat orbital tissue volume, and OFV were measured using high-resolution magnetic resonance imaging.

Results

Subjects with POAG had been treated with PGAs for 39 ± 19 months (SD) and were all treated within the 4 months preceding study. In the region from trochlea to orbital apex, OFV in POAG was significantly less at 9.8 ± 1.9 mL than in the control subjects at 11.1 ± 1.3 mL (P = 0.019). However, between the globe-optic nerve junction (GONJ) and trochlea, OFV was similar in both groups. Width and cross sectional area of the bony orbit were significantly smaller in POAG than in controls (P < 0.0001). Posterior to the GONJ, the average orbital cross-sectional area was 68.2 mm2 smaller, and the orbital width averaged 1.5 mm smaller throughout the orbit, in patients with POAG than in controls.

Conclusions

Patients with POAG who have been treated with PGAs have lower overall OFV than controls, but OFV in the anterior orbit is similar in both groups. Lower overall OFV in POAG may be a primary association of this disorder with a horizontally narrower bony orbit, which may be a risk factor for POAG at nonelevated IOPs.

Interleukin-2 (IL-2) is a cytokine required for effector T cell expansion, survival, and function, especially for engineered T cells in adoptive cell immunotherapy, but its pleiotropy leads to simultaneous stimulation and suppression of immune responses as well as systemic toxicity, limiting its therapeutic use. We engineered IL-2 cytokine-receptor orthogonal (ortho) pairs that interact with one another, transmitting native IL-2 signals, but do not interact with their natural cytokine and receptor counterparts. Introduction of orthoIL-2Rβ into T cells enabled the selective cellular targeting of orthoIL-2 to engineered CD4⁺ and CD8⁺ T cells in vitro and in vivo, with limited off-target effects and negligible toxicity. OrthoIL-2 pairs were efficacious in a preclinical mouse cancer model of adoptive cell therapy and may therefore represent a synthetic approach to achieving selective potentiation of engineered cells.