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In this study, we investigated the performance of four deep learning frameworks of U-Net, U-NeXt, DeepLabV3+, and ConResNet in multi-class pixel-based segmentation of the extraocular muscles (EOMs) from coronal MRI. Performances of the four models were evaluated and compared with the standard F-measure-based metrics of intersection over union (IoU) and Dice, where the U-Net achieved the highest overall IoU and Dice scores of 0.77 and 0.85, respectively. Centroid distance offset between identified and ground truth EOM centroids was measured where U-Net and DeepLabV3+ achieved low offsets (p > 0.05) of 0.33 mm and 0.35 mm, respectively. Our results also demonstrated that segmentation accuracy varies in spatially different image planes. This study systematically compared factors that impact the variability of segmentation and morphometric accuracy of the deep learning models when applied to segmenting EOMs from MRI.

Lipids and lipoproteins have long been known to contribute to atherosclerosis and cardiovascular calcification. One theme of recent work is the study of lipoprotein (a) [Lp(a)], a lipoprotein particle similar to LDL-cholesterol that carries a long apoprotein tail and most of the circulating oxidized phospholipids.In-vitro studies show that Lp(a) stimulates osteoblastic differentiation and mineralization of vascular smooth muscle cells, while the association of Lp(a) with coronary artery calcification continues to have varying results, possibly because of the widely varying threshold levels of Lp(a) chosen for association analyses. Another emerging area in the field of cardiovascular calcification is pathological endothelial-to-mesenchymal transition (EndMT), the process whereby endothelial cell transition into multipotent mesenchymal cells, some of which differentiate into osteochondrogenic cells and mineralize. The effects of lipids and lipoproteins on EndMT suggest that they modulate cardiovascular calcification through multiple mechanisms. There are also emerging trends in imaging of calcific vasculopathy, including: intravascular optical coherence tomography for quantifying plaque characteristics, PET with a radiolabeled NaF tracer, with either CT or MRI to detect coronary plaque vulnerability.Recent work in this field includes studies of Lp(a), EndMT, and new imaging techniques.

The role of vitamin D in the cardiovascular system is complex because it regulates expression of genes involved in diverse metabolic processes. Although referred to as a vitamin, it is more accurately considered a steroid hormone, because it is produced endogenously in the presence of ultraviolet light. It occurs as a series of sequentially activated forms, here referred to as vitamin D-hormones. A little-known phenomenon, based on pre-clinical data, is that its biodistribution and potential effects on vascular disease likely depend on whether it is derived from diet or sunlight. Diet-derived vitamin D-hormones are carried in the blood, at least in part, in chylomicrons and lipoprotein particles, including low-density lipoprotein. Since low-density lipoprotein is known to accumulate in the artery wall and atherosclerotic plaque, diet-derived vitamin D-hormones may also collect there, and possibly promote the osteochondrogenic mineralization associated with plaque. Also, little known is the fact that the body stores vitamin D-hormones in adipose tissue with a half-life on the order of months, raising doubts about whether the use of the term "daily requirement" is appropriate. Cardiovascular effects of vitamin D-hormones are controversial, and risk appears to increase with both low and high blood levels. Since low serum vitamin D-hormone concentration is reportedly associated with increased cardiovascular and orthopedic risk, oral supplementation is widely used, often together with calcium supplements. However, meta-analyses show that oral vitamin D-hormone supplementation does not protect against cardiovascular events, findings that are also supported by a randomized controlled trial. These considerations suggest that prevalent recommendations for vitamin D-hormone supplementation for the purpose of cardiovascular protection should be carefully reconsidered.

Tractional tethering by the optic nerve (ON) on the eye as it rotates towards the midline in adduction is a significant ocular mechanical load and has been suggested as a cause of ON damage induced by repetitive eye movements. We designed an ocular finite element model (FEM) simulating 6° incremental adduction beyond the initial configuration of 26° adduction that is the observed threshold for ON tethering. This FEM permitted sensitivity analysis of ON tethering using observed material property variations in measured hyperelasticity of the anterior, equatorial, posterior, and peripapillary sclera; and the ON and its sheath. The FEM predicted that adduction beyond the initiation of ON tethering concentrates stress and strain on the temporal side of the optic disc and peripapillary sclera, the ON sheath junction with the sclera, and retrolaminar ON neural tissue. However, some unfavorable combinations of tissue properties within the published ranges imposed higher stresses in these regions. With the least favorable combinations of tissue properties, adduction tethering was predicted to stress the ON junction and peripapillary sclera more than extreme conditions of intraocular and intracranial pressure. These simulations support the concept that ON tethering in adduction could induce mechanical stresses that might contribute to ON damage.

Purpose of review Cardiovascular calcification, a common feature of atherosclerotic lesions, has long been known to associate with cardiovascular risk. The roles of lipoproteins in atherosclerosis are also established, and lipid-modifying therapies have shown capacity for plaque regression. However, the association of lipid-modifying therapies with calcification is more complex, and currently no medical therapies have been found to reverse or attenuate calcification in patients. In this review, we summarize recent developments in our understanding of the interplay between lipids and cardiovascular calcification, as well as new imaging modalities for assessing calcified atherosclerotic plaque vulnerability. Recent findings Recent clinical studies have highlighted the associations of lipoprotein subtypes, such as low-density and high-density lipoprotein particles, as well as lipoprotein (a) [Lp(a)], with coronary calcification and calcific aortic valve disease. Further, evidence continues to emerge for the utility of fused 18F-sodium fluoride positron-emission tomographic and computed tomographic (18F-NaF PET/CT) imaging in characterizing the microarchitecture and vulnerability of atherosclerotic plaque, in both humans and animal models. Summary The relationship between lipids and cardiovascular calcification is complex, and new imaging techniques, such as 18F-NaF PET/CT imaging, may allow for better identification of disease-modifying therapies and prediction of calcified plaque progression and stability to help guide clinical management.

Background: Coronary calcification associates closely with cardiovascular risk, but its progress is accelerated in response to some interventions widely used to reduce risk. This paradox suggests that qualitative, not just quantitative, changes in calcification may affect plaque stability. To determine if the microarchitecture of calcification varies with aging, Western diet, statin therapy, and high intensity, progressive exercise, we assessed changes in a priori selected computed tomography radiomic features (intensity, size, shape, and texture). Methods: Longitudinal computed tomography scans of mice ( Apoe −/− ) exposed to each of these conditions were autosegmented by deep learning segmentation, and radiomic features of the largest deposits were analyzed. Results: Over 20 weeks of aging, intensity and most size parameters increased, but surface-area-to-volume ratio (a measure of porosity) decreased, suggesting stabilization. However, texture features (coarseness, cluster tendency, and nonuniformity) increased, suggesting heterogeneity and likely destabilization. Shape parameters showed no significant changes, except sphericity, which showed a decrease. The Western diet had significant effects on radiomic features related to size and texture, but not intensity or shape. In mice undergoing either pravastatin treatment or exercise, the selected radiomic features of their computed tomography scans were not significantly different from those of their respective controls. Interestingly, the total number of calcific deposits increased significantly less in the 2 intervention groups compared with the respective controls, suggesting more coalescence and/or fewer de novo deposits. Conclusions: Thus, aging and standard interventions alter the microarchitectural features of vascular calcium deposits in ways that may alter plaque biomechanical stability.

The optic nerve (ON) is a recently recognized tractional load on the eye during larger horizontal eye rotations. In order to understand the mechanical behavior of the eye during adduction, it is necessary to characterize material properties of the sclera, ON, and in particular its sheath. We performed tensile loading of specimens taken from fresh postmortem human eyes to characterize the range of variation in their biomechanical properties and determine the effect of preconditioning. We fitted reduced polynomial hyperelastic models to represent the nonlinear tensile behavior of the anterior, equatorial, posterior, and peripapillary sclera, as well as the ON and its sheath. For comparison, we analyzed tangent moduli in low and high strain regions to represent stiffness. Scleral stiffness generally decreased from anterior to posterior ocular regions. The ON had the lowest tangent modulus, but was surrounded by a much stiffer sheath. The low-strain hyperelastic behaviors of adjacent anatomical regions of the ON, ON sheath, and posterior sclera were similar as appropriate to avoid discontinuities at their boundaries. Regional stiffnesses within individual eyes were moderately correlated, implying that mechanical properties in one region of an eye do not reliably reflect properties of another region of that eye, and that potentially pathological combinations could occur in an eye if regional properties are discrepant. Preconditioning modestly stiffened ocular tissues, except peripapillary sclera that softened. The nonlinear mechanical behavior of posterior ocular tissues permits their stresses to match closely at low strains, although progressively increasing strain causes particularly great stress in the peripapillary region.

Purpose Most reports of strabismus after glaucoma drainage device implantation study larger devices and rarely note the incidence of strabismus after Ahmed glaucoma valve (AGV) implantation. It is unknown if the pattern of strabismus is similar with smaller devices. We investigated characteristics of strabismus after AGV implantation. Design Retrospective review. Methods Institutional study of 732 patients at our institution undergoing AGV implantation between 2013 and 2018. Rate and characteristics of strabismus were the primary outcome; age, gender, and location of AGVs were also analyzed. Results We identified 29 patients who developed new-onset strabismus postoperatively after initial AGV implantation, for 4% incidence of strabismus. Twenty-one (72%) of these had diplopia. AGVs were implanted superotemporally in 21, superonasally in 5, inferotemporally in 1, and inferonasally in 2. Three patients were esotropic, 11 were exotropic, 4 had hypertropia, 2 had hypotropia, and 9 patients had combined horizontal/vertical strabismus (esotropia/hypotropia [n = 1] or exotropia/hypertropias [n = 8]). Exotropia was the most common type of strabismus in both the superotemporal and superonasal (60%) AGV groups. Superotemporal AGVs were more commonly associated with ipsilateral hypertropia (43%) than superonasal AGVs. Treatments included strabismus surgery (n = 14), prisms (n = 6), or an occlusive lens (n = 1). Discussion. In the largest single-center series of patients undergoing initial AGV implantation, the overall incidence of postoperative strabismus was 4%. This is comparable to strabismus incidence following implantation of other types of glaucoma drainage devices, even larger devices. The possibility of this complication should be discussed with patients prior to surgery.

Background: Endothelial-to-mesenchymal transition (EndMT), the process whereby endothelial cells (ECs) transition into multipotent stem cell-like cells, has been implicated in a variety of cardiovascular pathologies, including cardiovascular calcification. EndMT is a dynamic mechanical process that involves detachment of transitioning ECs from adjacent cells and active migration of these cells from the endothelium into the interstitium. While gene and protein expression profiles of ECs undergoing EndMT have been well characterized, less is known about the mechanical properties, or “mechanotype,” of ECs as they undergo EndMT. Methods/Results: Human aortic endothelial cells (HAEC) were treated with the inflammatory cytokine, tumor necrosis factor-α (TNF-α), to induce inflammatory EndMT. Real-time PCR analyses showed that TNF-α significantly reduced the expression of endothelial markers ( PECAM1, NOS3 ) by 24 hours and significantly increased the expression of mesenchymal markers ( COL1A1, COL3A1, FN1, CNN1 ) starting at 48 hours of treatment. Mechanotyping of EC was performed by evaluating cell deformability with the parallel microfiltration (PMF) technique. PMF is a novel method that determines relative deformability by filtering cells across a porous membrane. Results showed that TNF-α has a biphasic effect on EC deformability, increasing the deformability after 24 hours, while decreasing deformability after 48 hours of treatment. Deformability decreased further with 96 hours of TNF-α treatment. Transwell migration assays revealed that TNF-α increased migration of ECs through a porous membrane, whereas EC migration was not enhanced when assessed by a scratch wound assay. Conclusion: Our results demonstrate that ECs undergo dynamic changes in their mechanotype during inflammatory EndMT. A deeper understanding of the mechanisms governing these changes may help inform therapeutic targets for EndMT-associated disease processes.

Supplemental Digital Content is available in the text., Background: Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic differentiation of valvular interstitial cells are important contributory mechanisms. We aimed to establish whether inhibition of these pathways with denosumab or alendronic acid could reduce disease progression in aortic stenosis. Methods: In a single-center, parallel group, double-blind randomized controlled trial, patients >50 years of age with calcific aortic stenosis (peak aortic jet velocity >2.5 m/s) were randomized 2:1:2:1 to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly), or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and 18F-sodium fluoride positron emission tomography and computed tomography. The primary end point was the calculated 24-month change in aortic valve calcium score. Results: A total of 150 patients (mean age, 72±8 years; 21% women) with calcific aortic stenosis (peak aortic jet velocity, 3.36 m/s [2.93–3.82 m/s]; aortic valve calcium score, 1152 AU [655–2065 AU]) were randomized and received the allocated trial intervention: denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25; pooled for analysis). Serum C-terminal telopeptide, a measure of bone turnover, halved from baseline to 6 months with denosumab (0.23 [0.18–0.33 µg/L] to 0.11 µg/L [0.08–0.17 µg/L]) and alendronic acid (0.20 [0.14–0.28 µg/L] to 0.09 µg/L [0.08–0.13 µg/L]) but was unchanged with placebo (0.23 [0.17–0.30 µg/L] to 0.26 µg/L [0.16–0.31 µg/L]). There were no differences in 24-month change in aortic valve calcium score between denosumab and placebo (343 [198–804 AU] versus 354 AU [76–675 AU]; P=0.41) or alendronic acid and placebo (326 [138–813 AU] versus 354 AU [76–675 AU]; P=0.49). Similarly, there were no differences in change in peak aortic jet velocity or 18F-sodium fluoride aortic valve uptake. Conclusions: Neither denosumab nor alendronic acid affected progression of aortic valve calcification in patients with calcific aortic stenosis. Alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with this potentially fatal condition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

PURPOSE: We studied effects of age and horizontal duction on deformation of the optic nerve (ON) head and peripapillary retina 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 peripapillary retina were imaged by scanning laser ophthalmoscopy in central gaze, and 35° abd- 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±1.7μm (SEM) than the temporal half at 4.1±2.1μm (P

To assess interdevice agreement between the iCare IC200 rebound tonometer and Perkins applanation tonometry (gold standard) in a healthy pediatric population.A total of 42 eyes of 42 healthy children were assessed using both tonometers. Data was collected on subject's age, sex, best-corrected visual acuity, and central corneal thickness (CCT). Intraclass correlation coefficient (ICC) and Bland-Altman analyses were used to determine agreement between IC200 and Perkins applanation tonometers. Linear regression analyzed the effects of intraocular pressure (IOP) on device difference.The mean age and standard deviation of healthy pediatric subjects was 10.0 ± 3.3 years. The mean difference between IC200 and Perkins tonometers (IC200-Perkins) was 0.72 mm Hg, with a mean of 17.1 ± 3.0 mm Hg and 16.4 ± 2.5 mm Hg, respectively. The absolute agreement, or ICC, between tonometers was 0.63 (95% CI, 0.56-0.70). Bland-Altman analysis showed 95% limits of agreement ranging from -5.2 to +6.6 mm Hg. CCT was not correlated with IOP for either the IC200 (P = 0.35) or the Perkins tonometer (P = 0.052).Compared to applanation tonometry, IC200 overestimated IOP in healthy children, with a greater frequency of readings+2 mm Hg than-2 mm Hg compared to Perkins. There was moderate agreement between tonometers. CCT was not found to influence IOP measurement for either tonometer.

We evaluated patients with hypertropia compatible with a diagnosis of superior oblique (SO) palsy to ascertain whether the 3-step test (3ST) can distinguish SO atrophy characteristic of trochlear nerve pathology from masquerading conditions.Prospective cross-sectional study.In an academic practice, we performed quasi-coronal plane, surface coil magnetic resonance imaging in 83 patients clinically diagnosed with SO palsy. We evaluated alignment, SO cross-sectional area, SO contractility, and rectus muscle pulley positions.A total of 57 patients with mean age 39 years (SD = 21 years) had unilateral SO palsy manifested by SO atrophy (22 congenital and 35 acquired). There was normal SO size in 26 patients with an average age of 39 years (SD =16 years) considered masquerades (8 congenital and 18 acquired). Maximum palsied SO cross-section averaged 9.5 ± 3.8 mmThe 3ST pattern characteristic of unilateral SO palsy may be mimicked in all respects by masquerades.

Recent studies have found an association between high volumes of physical activity and increased levels of coronary artery calcification (CAC) among older male endurance athletes, yet the underlying mechanisms have remained largely elusive. Potential mechanisms include greater exposure to inflammatory cytokines, reactive oxygen species and oxidised low-density lipoproteins, as acute strenuous physical activity has been found to enhance their systemic release. Other possibilities include post-exercise elevations in circulating parathyroid hormone, which can modify the amount and morphology of calcific plaque, and long-term exposure to non-laminar blood flow within the coronary arteries during vigorous physical activity, particularly in individuals with pre-existing atherosclerosis. Further, although the association has only been identified in men, the role of testosterone in this process remains unclear. This brief review discusses the association between high-volume endurance exercise and CAC in older men, elaborates on the potential mechanisms underlying the increased calcification, and provides clinical implications and recommendations for those at risk.

PURPOSE: 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 neurogenic palsy. METHODS: 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 and down gazes. RESULTS: Muscle bellies in neurogenic palsy were markedly atrophic with maximal cross sections averaging 6.5±2.7 mm(2), in contrast with 13.5±3.0 mm(2) contralesionally (P 0.5) 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 = 0.001). The average difference in hypertropia between central gaze and infraversion was 9Δ in cases of tendon abnormalities, significantly greater than −4.1Δ in SO atrophy (P = 0.019). In contralesional version, average overelevation in adduction was 1.7 (scale of 0 – 4) in tendon abnormalities, and 2.6 in SO atrophy (p = 0.23), while average underdepression in adduction was −2.3 in cases of tendon abnormalities and −1.6 in SO atrophy (p = 0.82). Repair of the SO tendon in three cases was effective, while alternative procedures were performed when repair was infeasible. CONCLUSION: 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.

Ivanir and Trobe have claimed that hypertropia (HT) that is greater in upgaze than downgaze, or equal to it, is characteristic of decompensated congenital superior oblique (SO) palsy and never present in ischemic, traumatic, or tumorous SO palsy. The reliability of this claim was tested in patients with SO palsy confirmed by MRI demonstration of subnormal ipsilesional SO size.Quasi-coronal, surface coil MRI was performed in target-controlled central gaze to identify patients with a unilateral reduction in SO cross section indicative of palsy. Nine patients gave an unequivocal history or had markedly increased vertical fusional amplitudes indicative of congenital onset (mean age 38 ± 16 years, SD). Seven patients had unequivocal acquired onset (age 47 ± 14 years and symptom duration 5.4 ± 4.8 years), including 2 with demonstrated trochlear Schwannoma and 5 with onset after severe head trauma. Fifteen patients had gradually progressive onset unequivocally not congenital yet not associated with any identifiable precipitating event (age 52 ± 20 years and symptom duration 13 ± 14 years).Maximum SO cross section averaged 8.6 ± 3.9 mm2 in congenital palsy, not significantly different from 11.3 ± 3.5 mm2 in acquired palsy (P = 0.08) either unequivocally or progressively acquired, but significantly less than about 19 mm2 contralesionally in SO palsy (P10-4). Although mean central gaze HT was greater at 20.6 ± 8.0Δ in 9 cases of congenital than that in 22 acquired cases at 11.4 ± 6.8Δ (P = 0.002), HT was 8.4 ± 16.3Δ less in upgaze than downgaze in congenital SO palsy and 3.7 ± 11.2Δ less in acquired SO palsy. In congenital palsy, 33% of patients had HT greater in upgaze than downgaze while in 67% HT was greater in downgaze (by up to 42Δ). In acquired SO palsy, HT was greater in upgaze than downgaze or equal to it in 8 cases (36%, P = 0.87, X2). In acquired SO palsy, HT was greater in upgaze than downgaze in 37% and greater in downgaze than upgaze in 59% of cases. The HT was equal in upgaze and centralgaze in no congenital and 3 acquired cases of SO palsy. Trends were similar in unequivocal acquired and progressive acquired (noncongenital) SO palsy (P0.4).Hypertropia is not characteristically greater in upgaze than downgaze in congenital SO palsy proven by SO atrophy on MRI. In fact, average HT is greater in downgaze than upgaze in both acquired and congenital palsy, sometimes strikingly so in the latter. The finding of HT greater in upgaze than downgaze, or equal to it, does not reliably indicate that SO palsy is congenital, nor does maximum SO cross section.

Vascular calcification, once considered a degenerative, end-stage, and inevitable condition, is now recognized as a complex process regulated in a manner similar to skeletal bone at the molecular and cellular levels. Since the initial discovery of bone morphogenetic protein in calcified human atherosclerotic lesions, decades of research have now led to the recognition that the regulatory mechanisms and the biomolecules that control cardiovascular calcification overlap with those controlling skeletal mineralization. In this review, we focus on key biomolecules driving the ectopic calcification in the circulation and their regulation by metabolic, hormonal, and inflammatory stimuli. Although calcium deposits in the vessel wall introduce rupture stress at their edges facing applied tensile stress, they simultaneously reduce rupture stress at the orthogonal edges, leaving the net risk of plaque rupture and consequent cardiac events depending on local material strength. A clinically important consequence of the shared mechanisms between the vascular and bone tissues is that therapeutic agents designed to inhibit vascular calcification may adversely affect skeletal mineralization and vice versa. Thus, it is essential to consider both systems when developing therapeutic strategies.

BackgroundDespite the association of physical activity with improved cardiovascular outcomes and the association of high coronary artery calcification (CAC) scores with poor prognosis, elite endurance athletes have increased CAC. Yet, they nevertheless have better cardiovascular survival. We hypothesized that exercise may transform vascular calcium deposits to a more stable morphology.MethodsTo test this, hyperlipidemic mice (Apoe-/-) with baseline aortic calcification were separated into 2 groups (n = 9/group) with control mice allowed to move ad-lib while the exercise group underwent a progressive treadmill regimen for 9 weeks. All mice underwent blood collections and in vivo 18F-NaF μPET/μCT imaging both at the start and end of the exercise regimen. At euthanasia, aortic root specimens were obtained for histomorphometry.ResultsResults showed that, while aortic calcification progressed similarly in both groups based on µCT, the fold change in 18F-NaF density was significantly less in the exercise group. Histomorphometric analysis of the aortic root calcium deposits showed that the exercised mice had a lower mineral surface area index than the control group. The exercise regimen also raised serum PTH levels twofold.ConclusionThese findings suggest that weeks-long progressive exercise alters the microarchitecture of atherosclerotic calcium deposits by reducing mineral surface growth, potentially favoring plaque stability.

Although the three-step test (3ST) is typically used to diagnose superior oblique palsy (SOP), sagging eye syndrome (SES) has clinical similarities. We sought to determine if alignment measurements can distinguish unilateral SOP from hypertropia in SES.We studied hypertropic subjects who underwent surface-coil magnetic resonance imaging (MRI) demonstrating either SO cross-section reduction indicative of congenital or acquired palsy (SOP group) or lateral rectus muscle sag (SES group). Alignment was measured by Hess screen and prism-cover testing. Multiple supervised machine learning methods were employed to evaluate diagnostic accuracy. Rectus pulley coordinates were determined in SES cases fulfilling the 3ST.Twenty-three subjects had unilateral SOP manifested by SO atrophy. Eighteen others had normal SO size but MRI findings of SES. Maximum cross-section of the palsied SO was much smaller than contralaterally and in SES (P2 × 10-5). Inferior oblique cross-sections were similar in SOP and SES. In both SOP and SES, hypertropia increased in contralateral and decreased in ipsilateral gaze and was greater in ipsilateral than contralateral head tilt. In SES, nine subjects (50%) fulfilled the 3ST and had greater infraplacement of the lateral than medial rectus pulleys in the hypotropic orbit. Supervised machine learning of alignment data distinguished the diagnoses with areas under the receiver operating curves up to 0.93, representing excellent yet imperfect differential diagnosis.Because the 3ST is often positive in SES, clinical alignment patterns may confound SES with unilateral SOP, particularly acquired SOP. Machine learning substantially but imperfectly improves classification accuracy.

To characterize visual outcomes in children screened for retinopathy of prematurity (ROP).Retrospective, interventional case series.Patients who received ROP screening examinations at UCLA Medical Centers and were followed with outpatient eye examinations at Stein Eye Institute and/or Doheny Eye Institute (Los Angeles, California) were included. Data were collected on birth characteristics, worst type of ROP, and ROP treatment. Adverse visual outcomes included myopia, strabismus, amblyopia, macular dragging, and optic atrophy. Snellen visual acuity was reported for children 4 years and older.A total of 175 infants (350 eyes) were included for analysis (mean gestational age = 28.2 weeks and birth weight = 1059 g) from a screening population of 539 infants (1078 eyes, 32.4% follow-up) over a 9-year period. Fifteen eyes received primary anti-vascular endothelial growth factor (anti-VEGF) therapy, whereas 59 eyes received primary laser therapy. Primary anti-VEGF therapy, as compared with primary laser treatment, was associated with a decreased incidence of amblyopia (adjusted odds ratio [aOR] = 0.6-0.86, P.0001) after controlling for gestational age and birth weight. The rates of optic atrophy (P = .79), strabismus (P = .98), and myopia (P = .93) were not different between anti-VEGF and laser treatment groups. Infants receiving anti-VEGF therapy had more posterior disease than laser-treated infants (P = .041). Infants receiving laser therapy were more likely to have severe myopia (aOR = 1.02-1.3, P = .023), amblyopia (aOR = 1.12-1.61, P = .002), and optic atrophy (aOR = 1.01-1.32, P = .045) than infants not treated.These findings add to the advantages of anti-VEGF treatment compared with primary laser treatment, particularly in posterior ROP.

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 6mW/cm(2) irradiance for 30 minutes. 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

Purpose of review This review addresses recent developments in studies of lipid regulation of calcific disease of arteries and cardiac valves, including the role of nuclear receptors. The role of lipid-soluble signals and their receptors is timely given the recent evidence and concerns that lipid-lowering treatment may increase the rate of progression of coronary artery calcification, which has been long associated with increased cardiovascular risk. Understanding the mechanisms will be important for interpreting such clinical information. Recent findings New findings support regulation of calcific vascular and valvular disease by nuclear receptors, including the vitamin D receptor, glucocorticoid receptor, nutrient-sensing nuclear receptors (liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors), and sex hormone (estrogen and androgen) receptors. There were two major unexpected findings: first, vitamin D supplementation, which was previously believed to prevent or reduce vascular calcification, showed no cardiovascular benefit in large randomized, controlled trials. Second, both epidemiological studies and coronary intravascular ultrasound studies suggest that treatment with HMG-CoA reductase inhibitors increases progression of coronary artery calcification, raising a question of whether there are mechanically stable and unstable forms of coronary calcification. Summary For clinical practice and research, these new findings offer new fundamental mechanisms for vascular calcification and provide new cautionary insights for therapeutic avenues.

The soft-tissue composition of the eyelid varies from lateral to medial, in that the orbicularis area (in square millimeters) is greatest medially and least laterally, whereas the reverse is true for the preauricularis and postorbicularis fat. The purpose of this study was to describe the relative contribution of tissue types to the volume of the lower eyelid-midface junction. This is an observational cohort study of 11 subjects (20 eyes) without a history of orbital or periorbital surgery or abnormality. Quasi-sagittal surface coil magnetic resonance imaging scans in planes parallel to the long axis of each orbit were obtained during central gaze fixation. Measurements of the tissue area (in square millimeters) of the skin, preorbicularis fat, orbicularis, and postorbicularis fat were obtained in the center, medial, and lateral eyelid regions. Differences in tissue area across the eyelid were assessed. The segmental cross-sectional area and percentage of total segment represented by the orbicularis muscle increased from the lateral (9.4 mm; 21.8 percent) to the central (14.1 mm; 35.0 percent) and to the medial (18.5 mm; 47.0 percent) eyelid (p < 0.01). The inverse pattern was noted for both preorbicularis and postorbicularis fat, each occupying less area (in square millimeters) from lateral to medial (p < 0.01). Skin thickness did not vary significantly across the eyelid. The soft-tissue composition of the eyelid varies from lateral to medial in that the orbicularis increases in area, whereas the reverse is true for the preorbicularis and postorbicularis fat. This anatomical progression may help to explain the stereotypical location of blue discoloration in some patients after hyaluronic acid filler injection.

This review of disorders of the fourth cranial nerve includes discussion on anatomy, examination techniques, congenital and acquired etiologies, differential diagnosis, and management options. The findings of the superior oblique muscle on orbital MRI in patients with fourth nerve palsy have had a major impact on our understanding of this cranial neuropathy. In addition, briefly reviewed are rare disorders of the fourth nerve: superior oblique myokymia, Brown syndrome, and ocular neuromyotonia. It behooves the clinician to have a clear understanding of the role that the fourth cranial nerve plays in a variety of neuro-ophthalmic conditions.

Objective: Statins lower cardiovascular event risk, yet, they paradoxically increase coronary artery calcification, a marker consistently associated with increased cardiovascular risks. As calcium deposits influence rupture risk due to stress from compliance mismatch at their surfaces, we hypothesized that statins may lower cardiovascular risk by altering the microarchitecture of calcium deposits. Thus, using mice with preexisting vascular calcification, we tested whether pravastatin reduces the mineral surface area of calcium deposits. Approach and Results: Aged Apoe −/− mice were treated with pravastatin or vehicle for 20 weeks. Aortic calcification was assessed by in vivo micro-computed tomography/micro-positron emission tomography using fluorine-18-labeled sodium fluoride at weeks 0, 10, and 20 and by histomorphometry at euthanasia. Micro-computed tomography analysis showed that, in both groups, the amount of vascular calcification increased significantly over the 20-week period, but pravastatin treatment did not augment over the controls. In contrast, the micro-positron emission tomography analysis showed that, at week 10, the pravastatin group had less 18 F uptake, suggesting reduced surface area of actively mineralizing deposits, but this decrease was not sustained at week 20. However, a significant difference in the mineral deposit size was found by histomorphometry. The pravastatin group had significantly more aortic microcalcium deposits ( Conclusions: These results suggest that pravastatin treatment alters the microarchitecture of aortic calcium deposits with potential effects on plaque stability.

Purpose/aimThe optic nerve (ON) becomes taut during adduction beyond ~26° in healthy people and patients with primary open angle glaucoma (POAG), but only retracts the globe in POAG. We used magnetic resonance imaging (MRI) to investigate this difference.Materials and methodsMRI was obtained in 2-mm quasi-coronal planes in central gaze, and smaller (~23-25°) and larger (~30-31°) adduction and abduction in 21 controls and 12 POAG subjects whose intraocular pressure never exceeded 21mmHg. ON cross-sections were analyzed from the globe to 10 mm posteriorly. Area centroids were used to calculate ON path lengths and changes in cross-sections to calculate elongation assuming volume conservation.ResultsFor both groups, ON path was nearly straight (

PURPOSE: Magnetic resonance imaging (MRI) of extraocular muscle function was used to evaluate the role of newly-recognized mechanisms underlying compensation of large heterophoria by vertical fusional vergence (VFV). DESIGN: Prospective case series. METHODS: At one academic center, 8 adults with large hyperphoria and super-normal VFV underwent MRI during monocular and binocular fixation of a centered, near target. Contractility of the rectus and the superior oblique (SO) extraocular muscles in the hypertropic and hypotropic eyes was determined from changes in posterior partial volume (PPV). RESULTS: Five of 8 patients could sustain binocular fusion in the scanner; in these patients, VFV corrected about 5° misalignment, about five-fold greater than normal VFV. Vertical strabismus was mainly compensated by significant contractility of the lateral more than medial compartment of the inferior rectus (IR) in both eyes (P

Background Inferior rectus (IR) underaction may arise from various causes that are distinguishable through imaging. We investigated clinical and imaging characteristics of congenital and acquired causes of IR underaction. Methods Cases of IR underaction were selected from data prospectively collected in a study of orbital imaging in strabismic patients. Results Review identified 3 cases of congenital IR underaction (2 with bilateral IR aplasia and 1 with unilateral IR hypoplasia), 12 acquired cases, including 4 due to denervation (2 idiopathic, 1 after multiple strabismus surgeries, 1 after head trauma), and 8 cases of direct IR damage (5 with orbital trauma and 3 with previous surgery, including 2 sinus surgery and 1 laser blepharoplasty). Of the 23 cases, 11 adults had high-resolution magnetic resonance imaging, and 2 children had computed tomography. Imaging identified the anatomic diagnosis in congenital cases; in acquired cases, imaging helped to identify atrophy and exclude alternative orbital causes; and in direct mechanical damage, imaging clarified the mechanism of underaction, extent of IR damaged, and the degree of retained contractility. Patients with congenital IR absence or hypoplasia exhibited A pattern exotropia that was typically absent in isolated acquired denervation or direct IR damage. Conclusions Orbital imaging demonstrates a variety of abnormalities in patients with congenital or acquired IR hypofunction, helping to clarify the underlying mechanism and guide management.