The Force Required to Inject a Column of Filler Through Facial Arteries.

BACKGROUND: Injectable fillers have become an integral part of facial rejuvenation, but vascular occlusion is a dreaded complication of such injections. OBJECTIVE: To determine the force required by the fingertip onto the plunger of the syringe to cause retrograde migration. METHODS: In this cadaver study, twelve 2-cm arterial segments and 4 fillers were tested. Injection pressure required to force a column of filler for 1 cm was measured. Five oculoplastics specialists were subsequently recruited and asked to inject the filler at a typical injection pressure. RESULTS: The nonhyaluronic acid filler required significantly more pressure to cause propagation of the material compared with all other fillers (p < .01). None of the other fillers differed significantly from each other. Typical injection pressures generated by experienced injectors were significantly lower than that required to cause propagation of filler at the desired velocity and significantly lower than mean arterial pressure. Measured pressure required to cause filler propagation was well within the normal range of the finger strength that can be generated by humans. CONCLUSION: Typical injection pressures from fingertip to plunger are lower than required to cause propagation of filler intravascularly.

Photochemical Collagen Cross-Linking Reverses Elastase-Induced Mechanical Degradation of Upper Eyelid Tarsus.

INTRODUCTION: The floppy eyelid syndrome describes an eyelid disorder characterized by floppy tarsal plates that may be caused by a loss of elastin. The authors attempted to create floppy eyelids by digesting elastin from cadaveric tarsus and then treated them with cross-linking using ultraviolet A and riboflavin. METHODS: Nine right and 9 left upper eyelids were excised from cadavers. Four vertical strips of central tarsus were removed from each eyelid. One strip of tarsus from each eyelid was treated with 10 units/ml of elastase for 2 hours. Another tarsal strip from each eyelid was immersed in normal saline for 2 hours (control). A third strip from the same eyelid was cross-linked using ultraviolet A at 6 mW/cm for 18 minutes. Finally, a fourth strip of tarsus was cross-linked in the same manner following treatment with elastase for 2 hours. A microtensile load cell was used to measure the Young modulus (stiffness) of each tissue. RESULTS: Mean (standard deviation) Young modulus for controls (18.9 ± 3.6 MPa) was significantly higher than samples treated with elastase alone (6.6 ± 3.8 MPa, p <0.01). Samples that were treated with cross-linking after elastase had a mean (standard deviation) Young modulus of 26 ± 2.3 MPa, while those treated with cross-linking alone had a mean (standard deviation) Young modulus of 34 ± 0.15 MPa. The differences in stiffness between all groups were significant (p <0.01). DISCUSSION: Treatment with elastase significantly reduces the stiffness of tarsal plates. This effect is reversed by cross-linking, raising the possibility of using this modality for the treatment of FES.

TITAN: inference of copy number architectures in clonal cell populations from tumor whole-genome sequence data.

The evolution of cancer genomes within a single tumor creates mixed cell populations with divergent somatic mutational landscapes. Inference of tumor subpopulations has been disproportionately focused on the assessment of somatic point mutations, whereas computational methods targeting evolutionary dynamics of copy number alterations (CNA) and loss of heterozygosity (LOH) in whole-genome sequencing data remain underdeveloped. We present a novel probabilistic model, TITAN, to infer CNA and LOH events while accounting for mixtures of cell populations, thereby estimating the proportion of cells harboring each event. We evaluate TITAN on idealized mixtures, simulating clonal populations from whole-genome sequences taken from genomically heterogeneous ovarian tumor sites collected from the same patient. In addition, we show in 23 whole genomes of breast tumors that the inference of CNA and LOH using TITAN critically informs population structure and the nature of the evolving cancer genome. Finally, we experimentally validated subclonal predictions using fluorescence in situ hybridization (FISH) and single-cell sequencing from an ovarian cancer patient sample, thereby recapitulating the key modeling assumptions of TITAN.

Rectus Extraocular Muscle Size and Pulley Location in Concomitant and Pattern Exotropia.

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.

Rectus Pulley Displacements without Abnormal Oblique Contractility Explain Strabismus in Superior Oblique Palsy.

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.

Scanning Laser Ophthalmoscopy Demonstrates Pediatric Optic Disc and Peripapillary Strain During Horizontal Eye Rotation.

Purpose: We employed automated analysis of scanning laser ophthalmoscopy (SLO) to determine if mechanical strains imposed on disc, and retinal and choroidal vessels during horizontal duction in children differ from those of adults.Methods: Thirty-one children aged 11.3 ± 2.7 (standard deviation) years underwent SLO in central gaze, and 35° ab- and adduction. Automated registration with deep learning-based optical flow analysis quantified vessel deformations as horizontal, vertical, shear, and equivalent strains. Choroidal vessel displacements in lightly pigmented fundi, and central disc vessel displacements, were also observed.Results: As in adults, strain in vessels during horizontal duction was greatest at the disc and decreased with distance from it. Strain in the pediatric disc was similar to published values in young adults,1 but in the peripapillary region was greater and propagated significantly more peripherally to at least three disc radii from it. During adduction in children, the nasal disc was compressed and disc vessels distorted, but the temporal half experienced tensile strain, while peripapillary tissues were compressed. The pattern was similar but strains were less in abduction (p < .001). Choroidal vessels were visualized in 24 of the 62 eyes and shifted directionally opposite overlying retinal vessels.Conclusions: Horizontal duction deforms the normal pediatric optic disc, central retinal vessels, peripapillary retina, and choroid, shearing the inner retina over the choroid. These mechanical effects occur at the sites of remodeling of the disc, sclera, and choroid associated with typical adult features that later emerge later, including optic cup enlargement, temporal disc tilting, and peripapillary atrophy.

Orbital Aging: A Computed Tomography-Based Study of 240 Orbits.

BACKGROUND: Previous studies have attempted to explain age-related changes to the orbit in isolation, often producing conflicting results. The authors used highly accurate imaging software to analyze computed tomographic scans to characterize changes related to age objectively. METHODS: In this case-control study, patients seen in an ear, nose, and throat clinic were screened for study entry. Male and female participants were divided into two age groups (20 to 30 years and 60 to 75 years). Primary outcomes included measurement of bony orbital dimensions, volume of soft tissues (muscle and fat volume), and anterior globe position. Three-dimensional reconstructions were created of each orbit allowing these measurements. The generalized estimating equation was used so that both orbits from each patient could be included without any bias. RESULTS: The final sample included 240 orbits from 120 patients. There were 30 patients in each age group. Among female participants, the bony orbital volume ( p < 0.05), fat volume ( p < 0.01), and central width ( p < 0.001) of the bony orbit increased with age. The anterior globe position was significantly greater in older female participants ( p < 0.01). For male participants, the fat volume ( p < 0.0001) and central height ( p < 0.03) increased with age; the lateral rim moved posteriorly with age ( p < 0.007). The anterior globe position was not different between the age groups in male participants ( p = 0.56). CONCLUSION: The female bony orbit expands with age and is associated with a more anterior position of the globe; the male bony orbital volume remains the same and the lateral rim moves posteriorly.

Special features of superior oblique hypofunction due to tendon abnormalities.

While most cases of superior oblique (SO) hypofunction represent contractile weakness due to denervation, sometimes the lesion is exclusively in the tendon. This study sought to distinguish the pattern of incomitant strabismus caused by deficiency of SO oculorotary force caused by tendon abnormalities versus that of neurogenic palsy. Clinical and magnetic resonance imaging (MRI) findings of 7 cases of unilateral SO tendon interruption or extirpation were compared with 11 cases of age matched unilateral SO palsy having intact tendons. We compared angles of misalignment with high-resolution MRI in central gaze and deorsumversion. Muscle bellies in neurogenic palsy were markedly atrophic with maximal cross sections averaging 6.5 ± 2.7 mm2, in contrast with 13.5 ± 3.0 mm2 contralesionally (P < .0001). In contrast, SO muscle bellies ipsilateral to tendon interruption had maximum cross sections averaging 15.1 ± 3.0 mm2 occurring more posterior than on the contralesional side whose maximum averaged 12.1 ± 2.4 mm2. While cross sections of SO bellies ipsilateral to tendon interruption exhibited normal contractile increase in infraduction (P < .0005), there was nevertheless strabismus with incomitance similar to that in SO atrophy. Binocular alignment was statistically similar (P > .5) in the two groups for all diagnostic positions, including head tilt, except in deorsumversion, where cases with SO tendon abnormalities averaged 20.5 ± 6.9Δ ipsilateral hypertropia, significantly more than 8.5 ± 6.6Δ in neurogenic SO atrophy (P = .001). The average difference in hypertropia Hypertropia averaged 9D greater in deorsumversion than central gaze in tendon abnormalities, but 4.1Δ less in SO atrophy (P< .019). In contralesional version, average overelevation in adduction was 1.7 (scale of 0-4) in tendon abnormalities, and 2.6 in SO atrophy (P = .23), while average underdepression in adduction was -2.3 in cases of tendon abnormalities and -1.6 in SO atrophy (P = .82). Repair of the SO tendon in three cases was effective, while alternative procedures were performed when repair was infeasible. While both denervation and tendon interruption impair SO oculorotary function, interruption causes greater hypertropia in infraversion. Surgical tightening of interrupted SO tendons may have particularly gratifying effects. Posterior SO thickening and large hypertropia in infraversion suggest SO tendon interruption that may guide a surgical strategy of tendon repair.

Bilaminar Structure of the Human Optic Nerve Sheath.

PURPOSE/AIM: We aimed to characterize the connective tissue microanatomy, elastin abundance, and fiber orientation in the human optic nerve sheath, also known as the optic nerve dura mater, for correlation with its biomechanical properties. MATERIALS AND METHODS: Seven whole human orbits aged 4-93 years, and five isolated human optic nerve sheaths aged 26-75 years were formalin fixed, paraffin embedded, coronally sectioned, stained by Masson trichrome and van Gieson's elastin methods, and analyzed quantitatively for elastin fiber abundance and orientation. Elastin area fraction was defined as area stained for elastin divided by total area. RESULTS: While unilaminar in children, the adult ON sheath exhibited distinct inner and outer layers. Collagen was denser and more compact in the inner layer. Elastin area fraction was significantly greater at 6.0 ± 0.4% (standard error of mean) in the inner than outer layer at 3.6 ± 0.4% (P < 10-5). Elastin fibers had three predominant orientations: longitudinal, diagonal, and circumferential. Of circumferential fibers, 63 ± 4.7% were in the inner and 37 ± 4.7% in the outer layer (P < 10-4). Longitudinal and diagonal fibers were uniformly distributed in both layers. Elastin density and sheath thickness increased significantly with age (P < .01). CONCLUSIONS: The adult human optic nerve sheath is bilaminar, with each layer containing elastin fibers oriented in multiple directions consistent with isotropic properties. Differences in laminar elastin density and orientation may reflect greater tensile loading in the inner than in the outer layer.

Differential Regional Stiffening of Sclera by Collagen Cross-linking.

Purpose: Corneal collagen cross-linking by ultraviolet light activation of riboflavin has been used clinically to enhance corneal stiffness. We sought to determine if cross-linking differentially affects scleral regions.Methods: Adjacent, parallel strips of sclera were cut from superolateral, superomedial, inferolateral, and inferomedial quadrants of posterior and equatorial sclera of 12 human cadaver eyes. One of each pair served as control while the other was cross-linked by immersion in 0.1% riboflavin and 365 nm exposure at 6 mW/cm2 irradiance for 30 min. Behavior of strips was characterized using a microtensile load cell. Preloaded strips were imaged using orthogonally mounted cameras and optical coherence tomography to determine specimen dimensions including cross-sectional area. Tension was measured during 0.1 mm/s constant rate elongation.Results: Young's modulus (YM), the slope of the relationship relating tensile stress to strain, was calculated at 8% strain, and increased significantly after cross-linking (P < .001). In posterior sclera, mean (± standard error of mean, SEM) YM is increased in the superolateral, superomedial, inferolateral, and inferomedial quadrants by 46 ± 15%, 32 ± 11%, 67 ± 20%, and 53 ± 11%, respectively. In equatorial sclera, YM is increased by 139 ± 43%, 68 ± 27%, 143 ± 92%, and 68 ± 14%, respectively. The YM of pooled equatorial quadrants increased significantly more than that of the pooled posterior quadrants.Conclusions: Scleral collagen cross-linking by ultraviolet activation of riboflavin differentially increases scleral YM more in the equatorial than posterior sclera, and most in the lateral, equatorial sclera. Cross-linking might be used to arrest progressive myopia or to prevent staphyloma formation.

Bilaminar Mechanics of the Human Optic Nerve Sheath.

PURPOSE/AIM: The adult human optic nerve (ON) sheath has recently been recognized to be bilaminar, consisting of inner layer (IL) and outer layer (OL). Since the ON and sheath exert tension on the globe in large angle adduction as these structures transmit reaction force of the medial rectus muscle to the globe, this study investigated the laminar biomechanics of the human ON sheath. MATERIALS AND METHODS: Biomechanical characterization was performed in ON sheath specimens from 12 pairs of fresh, post-mortem adult eyes. Some ON sheath specimens were tested completely, while others were separated into IL and OL. Uniaxial tensile loading under physiological temperature and humidity was used to characterize a linear approximation as Young's modulus, and hyperelastic non-linear behavior using the formulation of Ogden. Micro-indentation was performed by imposing small compressive deformations with small, hard spheres. Specimens of the same sheaths were paraffin embedded, sectioned at 10 micron thickness, and stained with van Gieson's stain for anatomical correlation. RESULTS: Mean (± standard error of the mean, SEM) tensile Young's modulus of the inner sheath at 19.8 ± 1.6 MPa significantly exceeded that for OL at 9.7 ± 1.2 MPa; the whole sheath showed intermediate modulus of 15.4 ± 1.1 MPa. Under compression, the inner sheath was stiffer (7.9 ± 0.5 vs 5.2 ± 0.5 kPa) and more viscous (150.8 ± 10.6 vs 75.6 ± 6 kPa s) than outer sheath. The inner sheath had denser elastin fibers than outer sheath, correlating with greater stiffness. CONCLUSIONS: We conclude that maximum tensile stiffness occurs in the elastin-rich ON sheath IL that inserts near the lamina cribrosa where tension in the sheath exerted during adduction tethering may be concentrated adjacent the ON head.

Age-dependent Deformation of the Optic Nerve Head and Peripapillary Retina by Horizontal Duction.

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.

Orbital Fat Volume After Treatment with Topical Prostaglandin Agonists.

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.

Biomechanical and Morphologic Effects of Collagen Cross-Linking in Human Tarsus.

PURPOSE: To investigate the feasibility of increasing the stiffness of human tarsal tissue following treatment with riboflavin and ultraviolet A (UVA) to induce cross-linking of collagen fibers. METHODS: In this case control study, 18 right and left upper eyelids were excised en bloc from 18 fresh-frozen cadavers. One side served as the control while the samples from the opposite side were cross-linked. Four 2 × 6-mm vertical strips of central tarsus were cut from the superior to inferior border of each tarsal plate. Sample tissue was irradiated with UVA at 6 mW/cm2 for 18 minutes. A microtensile load cell and an optical coherence tomography scanner allowed calculation of stiffness (Young's modulus). Six cross-linked samples and corresponding controls were stained with hematoxylin and eosin (H&E) and Masson trichrome stains. Four controls and four cross-linked samples were also reviewed with a transmission electron microscope. RESULTS: Mean Young's modulus in the linear region for controls was 28 ± 9 MPa and was much higher at 138 ± 8 MPa for cross-linked samples (P < 0.001), yielding a 493% mean stiffness increase. Staining with H&E and Masson did not reveal any histologic changes. Transmission electron microscopy showed a decrease in average diameter of 50 randomly selected collagen fibers from 47.2 ± 1.9 nm prior to cross-linking to 34.2 ± 1.1 nm post cross-linking (P < 0.001). Qualitatively, the collagen fibers appeared more closely packed following cross-linking. CONCLUSIONS: The findings of this study suggest that collagen cross-linking is a viable and effective modality for increasing the stiffness of human tarsal plates. TRANSLATIONAL RELEVANCE: This work provides proof that collagen cross-linking produces stiffening of the human tarsal plate and may be used in disorders that cause eyelid laxity.

Compression of the Choroid by Horizontal Duction.

Purpose: The optic nerve becomes tethered in adduction in most people, which deforms the disc. We investigated the effect of horizontal ocular duction and subject age on choroidal volume at the macular side of the optic disc. Methods: In 25 younger (18-33 years) and 15 older (50-73 years) normal subjects, the disc and the peripapillary choroid were imaged with optical coherence tomography (OCT) in central gaze and 35° adduction and abduction. The choroid temporal to the optic disc underlying the region between the Bruch's membrane opening and fovea was segmented into regions that were multiples of the disc radius for determination of local choroidal thickness. Regional volume changes from central gaze were determined in adduction and abduction. Results: In adduction, regional choroidal volume decreased by 42.4 ± 3.4 nanoliters (nL) (standard error of the mean) in younger (P < 0.0001) and 6.2 ± 2.6 nL in older (P < 0.02) subjects. Relative volume reduction in adduction was 7.5% ± 0.6% in younger (P < 0.001) and 1.3% ± 0.6% in older (P < 0.02) subjects. Volume reduction was greatest near the disc and significant up to three disc radii from it in younger and 1 radius in older subjects but was insignificant in abduction. Conclusions: Horizontal duction compresses the temporal peripapillary choroid, more in adduction than in abduction and more in younger than older subjects. This reflects duction-related peripapillary tissue deformation probably related, at least in part, to optic nerve tethering in adduction.

Rectus Extraocular Muscle Paths and Staphylomata in High Myopia.

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.

Antibody Conditioning Enables MHC-Mismatched Hematopoietic Stem Cell Transplants and Organ Graft Tolerance.

Hematopoietic cell transplantation can correct hematological and immunological disorders by replacing a diseased blood system with a healthy one, but this currently requires depleting a patient's existing hematopoietic system with toxic and non-specific chemotherapy, radiation, or both. Here we report an antibody-based conditioning protocol with reduced toxicity and enhanced specificity for robust hematopoietic stem cell (HSC) transplantation and engraftment in recipient mice. Host pre-treatment with six monoclonal antibodies targeting CD47, T cells, NK cells, and HSCs followed by donor HSC transplantation enabled stable hematopoietic system reconstitution in recipients with mismatches at half (haploidentical) or all major histocompatibility complex (MHC) genes. This approach allowed tolerance to heart tissue from HSC donor strains in haploidentical recipients, showing potential applications for solid organ transplantation without immune suppression. Fully mismatched chimeric mice developed antibody responses to nominal antigens, showing preserved functional immunity. These findings suggest approaches for transplanting immunologically mismatched HSCs and solid organs with limited toxicity.

Complete Genome Sequences of Mycobacterium smegmatis Phages NihilNomen and Carlyle, Isolated in Las Vegas, Nevada.

We present the complete genomes of the Mycobacterium smegmatis phages Carlyle and NihilNomen, isolated from soil in Las Vegas, Nevada. The phages were isolated and annotated by undergraduate students enrolled in the Phage Discovery course offered by the School of Life Sciences at the University of Nevada Las Vegas.

Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes.

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-2Rß 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.