The method of the exophthalmos value predicted calculation when planning the orbital decompression procedure in patients with endocrine ophthalmopathy

BACKGROUND: The most effective method of surgical treatment of lipogenic and mixed forms of edematous exophthalmos is currently the internal orbital decompression. During this surgical procedure, the excessive pathologically altered adipose tissue is removed from the external and the internal surgical spaces of the orbit. Many scientists are developing methods for calculating the volume of orbital fat, but the question on developing a method for predicted exophthalmos after internal orbital decompression, which could be used without attracting additional equipment and software, is easy to learn and does not require a long calculation time, remains actual. This method has to take into account the individual features of the patients orbital structure and be used for calculations in the bilateral proptosis correction. AIM: To develop and evaluate the effectiveness of a new method for calculating the eyeball position after orbital decompression. MATERIALS AND METHODS: 64 patients (126 orbits) with lipogenic and mixed forms of endocrine ophthalmopathy were examined. All patients underwent internal orbital decompression, during which the orbital fat was removed, the volume of which was calculated according to the developed original method. Patients underwent ophthalmological examination and MSCT before surgery and 6 months after it. . RESULTS: As a result of orbital decompression in the examined group, a decrease in proptosis was observed in all patients, and the exophthalmos calculated by the method corresponded to the eyeball position in patients in 6 months after surgery. The level of statistical significance of the planned postoperative eyeball position in relation to the actual postoperative exophthalmos calculated according to the Students t-test was 0.98 (p 0.05), that is, it can be argued that the groups do not differ, and no statistically significant differences were found. CONCLUSIONS: The developed method for calculating the estimated postoperative exophthalmos is effective without using additional software. This technique allows you to achieve a symmetrical eyeball position in the postoperative period and to reduce the risk of complications.

COMPUTED TOMOGRAPHY FOR DIAGNOSING GRAVES OPHTALMOPATHY

Graves ophtalmopathy (GO), thyroid eye disease (TED) and thyroid - associated orbitopathy (TAO) are terms referring to an autoimmune inflammatory process that affects the adipogenesis of orbital fat and periorbital tissue, associated with dysthyroidism. On imaging, such as computed tomography (CT) thyroid -associated orbitopathy (or thyroid -associated ophtalmopathy) is characterised by symmetrical and bilateral proptosis, secondary to extra-ocular muscle (EOM) enlargement and expansion of orbital fat. Imaging studies ca be useful in identifying patients risk to develop dysthyroid optic neuropathy and initiating early treatment of the condition, avoiding permanent visual loss. The purpose of this study was to reveal the prevalence of thyroid ophtalmopathy imaging considerations in Graves disease patients. A total of 19 patients were evaluated on computed tomography scanning the diameters and density of extra-ocular muscles, muscular index, proptosis, width of the optic nerve, width of superior ophthalmic vein and lacrimal gland position.

Diagnosis and Management of Orbital Fat Exposure During Endoscopic Sinus Surgery

Background: The orbital complication rate during endoscopic sinus surgery (ESS) is <1%. Orbital fat exposure during ESS can herald orbital complications including orbital hematoma, extraocular muscle trauma, optic nerve injury, or blindness. The objective of this study was to evaluate the current consensus regarding diagnosis and management of orbital fat exposure during ESS. Methods: A 24-point survey focused on orbital fat exposure during ESS was distributed to American Rhinologic Society members. Also, a retrospective review of 25 cases of orbital fat exposure drawn from the principal investigator’s 30-year experience was performed. Results: Over 10 000 surgical cases of the principal investigator were reviewed. Twenty-five patients had orbital fat exposure. Five developed minor complications while 2 were major (ie, temporary vision changes). Two hundred thirty-six surgeons responded to the survey; 93% had encountered orbital fat during ESS; 88% of surgeons identify orbital fat by either its appearance endoscopically or the “bulb press” test. Almost every responding surgeon will cautiously avoid further manipulation in the area of orbital fat exposure. Nearly half will immediately curtail the extent of surgery. Surgeons do not significantly change postoperative management. Considerations regarding observation in postanesthesia care unit, close follow-up, and strict nose blowing precautions are common. Conclusion: Orbital fat exposure during ESS is a rarely discussed, but clinically important. Orbital fat exposure can be a harbinger for major orbital complications that should be recognized by endoscopic appearance and confirmed with the bulb press test. Caution with “no further manipulation” of orbital fat is the guiding principle for intraoperative management, while postoperative management is generally expectant. Level 4 Evidence

PRL-1 overexpressed placenta-derived mesenchymal stem cells suppress adipogenesis in Graves’ ophthalmopathy through SREBP2/HMGCR pathway

Background Graves’ ophthalmopathy (GO) is a disorder, in which orbital connective tissues get in inflammation and increase in volume. Stimulants such as thyroid-stimulating hormone (TSH), insulin-like growth factor 1(IGF-1), IL-1, interferon γ, and platelet-derived growth factor cause differentiation into adipocytes of orbital fibroblasts (OFs) in the orbital fat and extraocular muscles. Human placental mesenchymal stem cells (hPMSCs) are known to have immune modulation effects on disease pathogenesis. Some reports suggest that hPMSCs can elicit therapeutic effects, but to date, research on this has been insufficient. In this study, we constructed PRL-1 overexpressed hPMSCs (hPMSCsPRL-1) in an attempt to enhance the suppressive function of adipogenesis in GO animal models. Methods In order to investigate the anti-adipogenic effects, primary OFs were incubated with differentiation medium for 10 days. After co-culturing with hPMSCsPRL-1, the characteristics of the OFs were analyzed using Nile red stain and quantitative real-time polymerase chain reaction. We then examined the in vivo regulatory effectiveness of hPMSCsPRL-1 in a GO mouse model that immunized by leg muscle electroporation of pTriEx1.1Neo-hTSHR A-subunit plasmid. Human PMSCsPRL-1 injection was performed in left orbit. We also analyzed the anti-adipogenic effects of hPMSCsPRL-1 in the GO model. Results We found that hPMSCsPRL-1 inhibited adipogenic activation factors, specifically PPARγ, C/EBPα, FABP4, SREBP2, and HMGCR, by 75.1%, 50%, 79.6%, 81.8%, and 87%, respectively, compared with naïve hPMSCs in adipogenesis-induced primary OFs from GO. Moreover, hPMSCsPRL-1 more effectively inhibited adipogenic factors ADIPONECTIN and HMGCR by 53.2% and 31.7%, respectively, than hPMSCs, compared with 15.8% and 29.8% using steroids in the orbital fat of the GO animal model. Conclusion Our findings suggest that hPMSCsPRL-1 would restore inflammation and adipogenesis of GO model and demonstrate that they could be applied as a novel treatment for GO patients.

Possible additional MRI markers for critical brain swelling with increased intracranial pressure in children?

A retrospective study was performed evaluating the volume and T2/T1 signal intensity of orbital fat in five children diagnosed with severe global brain swelling and confirmed cessation of cerebral perfusion. Imaging showed a volume increase (five of five) and a heterogeneous T2-hypointensity of orbital fat (four of five). This preliminary study suggests that swelling and T2-hypointensity of orbital fat may be a marker of global brain swelling and/or increased intracranial pressure.

Transcriptomic profiling of human orbital fat and differentiating orbital fibroblasts

Purpose: Orbital fat hyperplasia has a central role in the manifestations of thyroid-associated orbitopathy (TAO). To better understand the pathways involved in adipogenesis in TAO, we have used transcriptomic methods to analyze gene expression in control and TAO patients, as well as in differentiating orbital fibroblasts (OFs). Methods: We performed bulk RNA sequencing (RNA-Seq) on intraconal orbital fat to compare gene expression in control and TAO patients. We treated cultured OFs derived from TAO patients with media containing dexamethasone, insulin, rosiglitazone, and isobutylmethylxanthine (IBMX) to induce adipogenesis. We used single nuclear RNA-Seq (snRNA-Seq) profiling of treated OFs to compare gene expression over time in order to identify pathways that are involved in orbital adipogenesis in vitro and compared the dynamic patterns of gene expression identify differences in gene expression in control and TAO orbital fat. Results: Orbital fat from TAO and control patients segregate with principal component analysis (PCA). Numerous signaling pathways are enriched in orbital fat isolated from TAO patients. SnRNA-Seq of orbital fibroblasts undergoing adipogenesis reveals differential expression of adipocyte-specific genes over the developmental time course. Furthermore, genes that are enriched in TAO orbital fat are also upregulated in orbital adipocytes that differentiate in vitro, while genes that are enriched in control orbital fat are enriched in orbital fibroblasts prior to differentiation. Conclusions: Differentiating orbital fibroblasts serve as a model to study orbital fat hyperplasia seen in TAO. We demonstrate that the insulin-like growth factor-1 receptor (IGF-1R) and Wnt signaling pathways are differentially expressed early in orbital adipogenesis.