Hypoglobus, Exophthalmos, and Interpupillary Distance: Measuring Globe Dystopia in Thyroid Eye Disease.

PURPOSE: Thyroid eye disease (TED) is characterized by a variety of disfiguring periocular changes. Vertical globe changes affecting the relative position of the eyelids are not well understood in patients with TED. This study seeks to determine the effect of orbital decompression on vertical globe displacement in patients with TED, without TED, and with intraconal tumor (ICT). METHODS: For this cross-sectional study, a clinical database was used to identify patients with TED. Comparison groups were drawn from separate anonymized databases. Vertical position and interpupillary distance (IPD) were measured from photographs and exophthalmos was measured via Hertel's exophthalmometer. Primary outcomes were vertical globe position at baseline and postoperatively in patients with TED and ICT. Secondary outcomes included the relationship between vertical globe position, exophthalmos, and IPD. RESULTS: Among 269 participants meeting the inclusion criteria, mean vertical globe position was significantly lower in patients with TED following lateral decompression surgery compared to controls, after accounting for race, age, and sex. While patients with ICT had a significant difference in preoperative and postoperative IPD, patients with TED did not. Medial or inferior decompression did not significantly change globe position and lateral decompression did not cause lateral canthal dystopia in patients with TED. No association between postoperative changes in exophthalmometry, IPD, and globe position was found in patients with TED. CONCLUSIONS: Patients with TED experience hypoglobus that does not improve following decompression surgery. There was no correlation between change in vertical globe position and exophthalmos or IPD among patients with TED. Surgeons should discuss the possibility of hypoglobus as a persistent finding for patients with TED undergoing decompression surgery.

In vitro cytotoxicity and anti-cancer drug release behavior of methionine-coated magnetite nanoparticles as carriers.

A novel and specific drug delivery for in vitro cancer targeted are developed successfully by a simple one-step method. A CoFe2O4@Methionine core-shell nanoparticle was prepared by the reflux assay which amino acid in the surface makes ferrite biocompatible, enhances its chemical stability, and improves the drug-loading capacity. The synthesized nanoparticles were characterized using FTIR, TGA, XRD, SEM, TEM, and VSM which coating amino acid on the surface of CoFe2O4 was confirmed by XRD and TGA. The appearance of a new peak for C≡N confirms the formation of Letrozole-loaded carrier in the FTIR. The vibrating sample magnetometer of both bare CoFe2O4 and Methionine-coated CoFe2O4 nanoparticles exhibited room-temperature superparamagnetic behavior with a saturation value of 46 emu/g and 16.8 emu/g, respectively. The morphology and size of samples were characterized by SEM and TEM that the average size of the particle was around 28-29 nm. The loading of Letrozole and the effect of pH (5, 7.4) on the release behavior of the carrier was studied. The result of the drug release in pH is equal to 5 was about 88% which higher than pH is equal to 7.4. Also, the preparation had been evaluated for determining its cytotoxicity using MCF-7, MDA-MB-231, and MCF10A cells as an in vitro model, and the result vitro experiments showed that CoFe2O4@Methionine could significantly reduce cancer in cells model. These results demonstrate that core-shell nanoparticle was prepared is biocompatible and have potential use as drug delivery.

Synthesis and Characterization of Tetracycline Loaded Methionine-Coated NiFe2O4 Nanoparticles for Anticancer and Antibacterial Applications.

In the present study, nickel ferrite (NiFe2O4)-based smart magnetic nanoparticles were fabricated and coated with methionine. Physiochemical characterization of the obtained Met-NiFe2O4 nanoparticles revealed the presence of methionine coating over the nanoparticle surface. Drug release study indicated that Tet-Met-NiFe2O4 nanoparticles possess pH-responsive controlled drug release behavior for tetracycline (Tet). The drug loading content for Tet was found to be 0.27 mg/L of nanoparticles. In vitro cytotoxicity test showed that the Met-NiFe2O4 nanoparticles is biocompatible. Moreover, this magnetic nanostructured material shown strong anticancer property as these nanomaterials significantly reduced the viability of A375 cells when compared to free Tet solution. In addition, Tet-Met-NiFe2O4 nanoparticles also showed strong antibacterial activity against different bacterial pathogens.

Formulation and Characterization of Poly (Ethylene Glycol)-Coated Core-Shell Methionine Magnetic Nanoparticles as a Carrier for Naproxen Delivery: Growth Inhibition of Cancer Cells.

An efficient and selective drug delivery vehicle for cancer cells can remarkably improve therapeutic approaches. In this study, we focused on the synthesis and characterization of magnetic Ni1-xCoxFe2O4 nanoparticles (NPs) coated with two layers of methionine and polyethylene glycol to increase the loading capacity and lower toxicity to serve as an efficient drug carrier. Ni1-xCoxFe2O4@Methionine@PEG NPs were synthesized by a reflux method then characterized by FTIR, XRD, FESEM, TEM, and VSM. Naproxen was used as a model drug and its loading and release in the vehicles were evaluated. The results for loading efficiency showed 1 mg of Ni1-xCoxFe2O4@Methionine@PEG NPs could load 0.51 mg of the naproxen. Interestingly, Ni1-xCoxFe2O4@Methionine@PEG showed a gradual release of the drug, achieving a time-release up to 5 days, and demonstrated that a pH 5 release of the drug was about 20% higher than Ni1-xCoxFe2O4@Methionine NPs, which could enhance the intracellular drug release following endocytosis. At pH 7.4, the release of the drug was slower than Ni1-xCoxFe2O4@Methionine NPs; demonstrating the potential to minimize the adverse effects of anticancer drugs on normal tissues. Moreover, naproxen loaded onto the Ni1-xCoxFe2O4@Methionine@PEG NPs for breast cancer cell lines MDA-MB-231 and MCF-7 showed more significant cell death than the free drug, which was measured by an MTT assay. When comparing both cancer cells, we demonstrated that naproxen loaded onto the Ni1-xCoxFe2O4@Methionine@PEG NPs exhibited greater cell death effects on the MCF-7 cells compared with the MDA-MB-231 cells. The results of the hemolysis test also showed good hemocompatibility. The results indicated that the prepared magnetic nanocarrier could be suitable for controlled anticancer drug delivery.

Association between degenerative temporomandibular joint disorders, vertical facial growth, and airway dimension.

BACKGROUND: The goal of this study was to determine whether preexisting degenerative temporomandibular joint (TMJ) disorders are associated with hyperdivergent facial phenotype and decreased airway dimensions. METHODS: Cone-beam computed tomography scans of adult female and male individuals, 16 years of age and older, distributed in a case group defined as those with degenerative temporomandibular joint disorder (dTMJD; n = 31) or controls with normal TMJ findings (n = 242) were included. Odds ratios were calculated based on facial type and gender. Analysis of variance was used to compare the airway volume and cross section and mandibular measurements between the groups. RESULTS: Condylar, ramus, and mandibular heights were significantly smaller in the case group compared with the control group. The odds of having a long face subject was significantly higher (P < 0.00001) in the dTMJD group than in the control group with 81% of the dTMJD subjects versus 11% of the control group having long vertical facial dimensions. The smallest cross-sectional area of the airway of the dTMJD group was significantly narrower (P < 0.0361) compared with the controls. Within the control group, ramus height and mandibular alveolar housing for central incisors were significantly smaller (P < 0.0001; P < 0.007) in the long face subjects. CONCLUSIONS: The study shows that a long facial type is associated with findings of degenerative TMJ disorders and related condylar growth disturbances. These degenerative and growth changes may contribute to specific skeletal and dentofacial adaptations resulting in smaller condylar process, mandibular ramus, and body height; thinner alveolar housing at the lower incisor region; and smaller cross-sectional area of the airway.

The Relationship Between Eyebrow and Eyelid Position in Patients With Ptosis, Dermatochalasis and Controls.

PURPOSE: The purpose of this study is to explore mechanical and co-innervational factors involved in both voluntary and involuntary brow elevation among people affected by ptosis and dermatochalasis. METHODS: In this prospective cohort study of normal controls and eyelids with ptosis or dermatochalasis, marginal reflex distance (MRD1) and brow height were measured under the following conditions: neutral position, involuntary mechanical brow elevation, voluntary brow elevation, and maximal eyelid opening. The primary outcome measure was change in MRD1. Secondary outcome measures included brow height and coupling (mm brow height change per mm MRD1 change). Analysis of variance and t tests were performed for intra- and intercondition comparisons, respectively. RESULTS: Mechanical (involuntary) brow elevation significantly raised MRD1 in control eyelids and eyelids with dermatochalasis, but not in eyelids with ptosis. Voluntary brow elevation produced significantly greater brow height than maximal eyelid opening in controls and eyelids with dermatochalasis, but not in eyelids with ptosis. Maximal eyelid opening increased MRD1 greater than voluntary brow elevation significantly in control eyelids, but not in eyelids with dermatochalasis or ptosis. Coupling of the brow and eyelid margin during maximal eyelid opening was significantly greater in eyelids with ptosis relative to controls. CONCLUSIONS: In eyelids with ptosis, mechanical brow elevation does not change eyelid position; however, voluntary brow elevation raises eyelid position to a similar position as maximal eyelid opening. These results argue against the contention that the brow is elevated to mechanically lift the eyelid in ptosis and instead suggest that the brow elevation is driven by efforts to raise the eyelid, possibly via co-innervation.

The effect of eyebrow stenting on the measurement of levator excursion in normal and ptotic eyelids.

Introduction: Levator function is classically estimated by measuring upper eyelid excursion (ULE) with digital brow stenting. The purpose of this study is to compare ULE with and without brow stenting in normal and ptotic eyelids. Methods: In this prospective observational study, normal and ptotic eyelids were recruited. Subjects were photographed with and without digital brow stenting in primary position, downgaze, and upgaze. Measurements were conducted on digital photographs. The primary outcome measure was ULE (distance travelled by the eyelid margin between downgaze and upgaze). Normal and ptosis (MRD1 ≤ 2.5 mm or asymmetry ≥ 1 mm) subgroups were defined. Independent one-way ANOVA and independent samples t-tests were performed. This study was powered to detect a 1 mm difference in the primary outcome measure, assuming SD = 1 mm, with alpha = 0.05 and beta-error = 0.95. Results: Twenty-eight normal eyelids of 22 subjects and 28 ptotic eyes of 18 subjects were included. Stenting significantly (p < 0.01) increased ULE in the overall sample (+0.9 mm) and in controls (+1.2 mm), but not (p > 0.05) in ptotic eyelids (+0.5 mm). Post hoc analysis revealed a beta-error of 0.08 in the latter. Conclusion: ULE was significantly higher with brow stenting in normal eyelids (approximately +1.2 mm) but not in ptotic eyelids, possibly due to increased levator tone secondary to increased effort in the coupled frontalis.

Assessing the Accuracy of Eyelid Measurements Utilizing the Volk Eye Check System and Clinical Measurements.

PURPOSE: The purpose of this study was to validate the accuracy of marginal reflex distance 1 (MRD1) measurements obtained by the Volk Eye Check system, a modified smartphone that measures MRD1 automatically, relative to clinical and digital measurements. METHODS: In this prospective observational study of adults with normal eyelids and ptosis, MRD1 was measured clinically, digitally, and automatically with the Volk device. Eyes were divided into successful versus unsuccessful Volk trial groups; successful eyes were then subdivided into control and ptosis subgroups. The primary outcome measures were mean MRD1 obtained by the 3 modalities. Secondary outcome measures included the success rate of the device and the prevalence of ptosis within the successful and unsuccessful groups. RESULTS: In the overall sample of 88 eyes, clinical and digital MRD1 were not significantly different. Among eyes with successful Volk trials, significant differences in MRD1 measured by the 3 modalities were as follows: in the successful group, Volk MRD1 (3.05 mm) was significantly (p < 0.01) higher than digital MRD1 (2.68 mm); in the ptosis subgroup, Volk MRD1 (2.47 mm) was significantly higher than clinical (2.05 mm; p < 0.05) and digital MRD1 (1.91 mm; p < 0.01). Eyes in the successful group (66% of attempted collections) demonstrated significantly higher MRD1 (mean difference, 1.21 mm; p < 0.01) and were significantly less likely to demonstrate ptosis (2.7×; p < 0.05) than those in the unsuccessful group. CONCLUSIONS: The Volk device measures MRD1 well in normal patients but overestimates MRD1 in patients with ptosis. It may be most appropriate in assessing patients with normal or elevated eyelid position. Clinical and digital MRD1 measurements were not different than each other.

Vemurafenib (BRAF Inhibitor) Therapy for Orbital Erdheim-Chester Disease.

Erdheim-Chester disease is a rare xanthogranulomatous systemic disease, which involves the orbit in some cases. Through this case report, the authors review the treatment modalities used in orbital Erdheim-Chester disease and explore a newer modality of treatment. Cases of orbital Erdheim-Chester disease were identified in the literature utilizing a PubMed search and all the treatment modalities were reviewed. The response to treatment of orbital Erdheim-Chester disease has been poor with the various medical and surgical treatment modalities used in the past. The authors report the use of BRAF inhibitor with a remarkable response in our case.

Long-Term Evaluation of Eyebrow Soft Tissue Expansion in Thyroid Eye Disease.

PURPOSE: To evaluate the long-term transformation of lateral eyebrow soft tissue in a group of patients with known thyroid eye disease. METHODS: A retrospective review of all patients with a known diagnosis of thyroid eye disease with clinical photos available from both their initial diagnosis visit and at least 7 years following their initial visit was performed. Age at diagnosis, sex, disease activity, previous orbital, and eyelid surgery were noted, as was history of treatment with radioactive iodine, steroids, and external beam radiation. The area between the upper eyebrow and upper eyelid crease was evaluated in standardized photographs by a panel of 4 expert, independent, masked observers utilizing a previously published visual grading key. RESULTS: One hundred and four patients met inclusion criteria. Fifteen participants were male and 89 were female. The mean patient age was 50.6 years (±1.21 years), and the mean follow up duration was 10.0 years (±0.23 years). The mean initial photo grade (1.24) was significantly higher than the mean follow up photo grade (1.00; p < 0.01). In logistic regression analyses, only the initial photograph grade was significantly associated with improvement in eyebrow soft tissue appearance (p < 0.01). Medical and surgical treatments were not significantly associated with changes in eyebrow soft tissue appearance (all p > 0.05). CONCLUSIONS: Expansion of eyebrow soft tissue may improve over time in patients with thyroid eye disease. This change was not affected by age, sex, disease activity, surgery, or medical therapy.

Cardio-ventilatory coupling in young healthy resting subjects.

In this work, cardio-ventilatory coupling (CVC) refers to the statistical relationship between the onset of either inspiration (I) or expiration (E) and the timing of heartbeats (R-waves) before and after these respiratory events. CVC was assessed in healthy, young (<45 yr), resting, supine subjects (n = 19). Four intervals were analyzed: time from I-onset to both the prior R-wave (R-to-I) and the following R-wave (I-to-R), as well as time from E-onset to both the prior R-wave (R-to-E) and following R-wave (E-to-R). The degree of coupling was quantified in terms of transformed relative Shannon entropy (tRSE), and χ(2) tests based on histograms of interval times from 200 breaths. Subjects were studied twice, from 5 to 27 days apart, and the test-retest reliability of CVC measures was computed. Several factors pointed to the relative importance of the R-to-I interval compared with other intervals. Coupling was significantly stronger for the R-to-I interval, coupling reliability was largest for the R-to-I interval, and only tRSE for the R-to-I interval was correlated with height, weight, and body surface area. The high test-retest reliability for CVC in the R-to-I interval provides support for the hypothesis that CVC strength is a subject trait. Across subjects, a peak ~138 ms prior to I-onset was characteristic of CVC in the R-to-I interval, although individual subjects also had earlier peaks (longer R-to-I intervals). CVC for the R-to-I interval was unrelated to two separate measures of respiratory sinus arrhythmia (RSA), suggesting that these two forms of coupling (CVC and RSA) are independent.