Citations

Purpose: Obesity is a major public health concern, and fat comprises a substantial portion of the orbital volume. We aimed to evaluate the relationship between body mass index (BMI) and orbital fat volume, and to assess whether BMI is associated with radiographic proptosis. Methods: We conducted a cross-sectional study of 99 orbits from patients who underwent orbital CT imaging between January 1 and December 31, 2018. Patients with systemic diseases affecting the orbits were excluded. When applicable, only the healthy orbit was analyzed. Subjects were evenly stratified into normal-weight, overweight, and obese groups by BMI. Using Visage Imaging Software, orbital structure volumes were measured. Orbital fat volume was calculated by subtracting extraocular muscle, globe, and optic nerve volumes from the total orbital volume. Multivariable linear regression, adjusted for age, gender, and race, assessed associations between BMI and orbital measurements. Results: Among individuals with BMI 17 to 25, total orbital volume increased by 1.20 cm 3 and orbital fat volume by 1.05 cm 3 per unit BMI. For BMI >25, both increased at a flatter slope. Obese patients had nearly double the orbital fat volume of normal-weight patients (10.7 vs. 5.4 cm 3 , p < 0.001). Radiographic proptosis trended higher in obese patients by 1.7 mm ( p = 0.114). Males had larger orbital structures and greater mean proptosis than females. Conclusions: Total orbital and fat volumes increased with BMI, particularly in the normal-to-overweight range. These findings support the need to update normative proptosis data and suggest weight loss may aid in managing mild symptomatic proptosis.

Background Sinonasal pathology, such as chronic inflammatory disease or neoplasm, can cause secondary nasolacrimal duct obstruction (sNLDO). There is a paucity of data on dacryocystorhinostomy (DCR) techniques and outcomes for NLDO secondary to known sinonasal pathologies. Objective To describe case characteristics, management, and surgical outcomes of sNLDO at a tertiary academic center. Methods Charts of DCR cases with at least 3 months follow-up done at a single institution over a 5-year period (2018-2022) were reviewed. Patient and surgical characteristics were recorded and compared between secondary and primary NLDO groups. The primary outcome was early functional success of DCR, assessed by improvement or resolution of epiphora at 3 months. Results A total of 236 cases were included. Of those, 79 (33.5%) were classified as secondary NLDO associated with sinonasal pathology. Reasons for sNLDO were sinonasal cancer (46.8%), chronic inflammatory disease (24.1%), trauma (16.5%), or prior head and neck radiation (31.6%). When comparing primary acquired NLDO to sNLDO cases, DCR for sNLDO was more likely to be performed endoscopically (68.4% vs 31.8%, P < .01), by a multidisciplinary team of rhinologist and oculoplastic surgeon (70.9% vs 8.3%, P < .01), and required bilateral surgery (36.7% vs 5.7%, P < .01). The overall functional success rate was 79.7% for sNLDO compared to 87.9% for primary acquired NLDO ( P < .01). Revision surgery for sNLDO, history of sinonasal malignancy, and radiation were associated with lower functional success rates (66.7%, 70.3%, and 68.0%, respectively). Canalicular pathology was more common in sNLDO cases (29.0% vs 8.3%, P < .01). Conclusions Secondary NLDO was more commonly managed with an endoscopic approach by a multidisciplinary team. Revisions for sNLDO, as well as cases with a history of sinonasal malignancy and radiation, had a markedly lower success rate, and sNLDO was frequently associated with canalicular obstruction. These findings may facilitate surgical planning and patient counseling.

Abstract Germline and osteoblast-directed deletion of G protein-gated inwardly rectifying K+ channel 3 (Girk3) was recently shown to increase bone mass after 18 wk of age in male mice. Here, we show that germline Girk3 deletion also increases trabecular and cortical bone mass and increases the mechanical strength of the femur in female mice after 18 wk of age. Unlike male mice, however, osteoblast-directed Girk3 deletion using 2.3 kb-Col1a1-Cre does not increase bone mass in adult female mice. To discover mechanisms underlying high bone mass in female Girk3−/− mice, bulk RNA-sequencing was performed on 2-d-old calvarial bone, revealing lower expression of proinflammatory cytokines such as IL-1β and IL-6 in Girk3−/− mice. Accordingly, cytokines and chemokines are largely suppressed in the circulation of adult Girk3−/− mice compared to WT littermates. The cytokines GM-CSF, IL-1β, IL-2, and IL-9 are reduced in the serum of both male and female Girk3−/− mice, while eotaxin, IFNγ, MIP-1α, and others are sexually dimorphic. Histomorphometry reveals that osteoclast activity is modestly reduced in Girk3−/− bone, which is supported by in vitro osteoclast resorption assays. However, deletion of Girk3 in myeloid-lineage cells with LysM-Cre is not sufficient to recapitulate high bone mass in either male or female mice. Moreover, female Girk3−/− mice are not protected from ovariectomy-induced bone loss. Finally, single-cell screening using cytometry by time-of-flight in the BM revealed no differences in immune cell abundances due to global Girk3 deletion. Taken together, while Girk3 regulates inflammatory cytokine expression in the bone and serum, deletion of Girk3 in myeloid-lineage cells does not affect bone mass.

OBJECTIVE In many individuals, type 2 diabetes (T2D) remains poorly controlled despite taking multiple glucose-lowering therapies. Several studies have demonstrated that endogenous hypercortisolism is prevalent among these individuals. We tested whether cortisol-directed therapy improves their glycemic control. RESEARCH DESIGN AND METHODS In this prospective, multicenter, double-blind study, 136 individuals with T2D (hemoglobin A1c [HbA1c] 7.5%–11.5% [58–102 mmol/mol] on multiple medications) and hypercortisolism (by dexamethasone suppression test) were randomized 2:1 to the glucocorticoid receptor antagonist mifepristone (300–900 mg once daily; n = 91) or placebo (n = 45) for 24 weeks, with stratification by presence/absence of an adrenal imaging abnormality. The primary end point was the change in HbA1c. Secondary end points included changes in glucose-lowering medications, weight, and waist circumference and safety. RESULTS Mean baseline HbA1c in the study cohort was 8.55% (69.9 mmol/mol). At 24 weeks, the least squares mean (LSM) difference from placebo in HbA1c was −1.32% (95% CI −1.81 to −0.83; P &lt; 0.001). Participants receiving mifepristone experienced reductions in body weight and waist circumference (placebo-adjusted LSM differences of −5.12 kg [95% CI −8.20 to −2.03] and −5.1 cm [−8.23 to −1.99], respectively). Of participants on mifepristone, 46% discontinued therapy, compared with 18% on placebo. Adverse events with mifepristone (&gt;10% of participants) included hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness, consistent with mifepristone’s known tolerability profile. Increases in blood pressure also occurred. CONCLUSIONS In individuals with inadequately controlled T2D and hypercortisolism, cortisol-directed medical therapy with mifepristone reduced HbA1c, with a manageable tolerability profile.

OBJECTIVE Despite the use of multiple glucose-lowering medications, glycemic targets are not met in a significant fraction of people with type 2 diabetes. In this prospective, observational study we assessed the prevalence of hypercortisolism, a potential contributing factor to inadequate glucose control. RESEARCH DESIGN AND METHODS Individuals with type 2 diabetes and HbA1c 7.5%–11.5% (58–102 mmol/mol) on two or more glucose-lowering medications with or without micro-/macrovascular complications or taking multiple blood pressure–lowering medications were screened with a 1-mg dexamethasone suppression test. Common causes of false-positive DSTs were excluded. The primary end point was the prevalence of hypercortisolism, defined as post-DST cortisol &gt;1.8 μg/dL (50 nmol/L). Characteristics associated with hypercortisolism were assessed with multiple logistic regression. The percentage and characteristics of participants with hypercortisolism and adrenal imaging abnormalities were also assessed. RESULTS Post-DST cortisol was unsuppressed in 252 of 1,057 participants (prevalence 23.8%; 95% CI 21.3, 26.5). Hypercortisolism prevalence was 33.3% among participants with cardiac disorders and 36.6% among those taking three or more blood pressure–lowering medications. Adrenal imaging abnormalities were reported in 34.7% of participants with hypercortisolism. Use of sodium–glucose cotransporter 2 inhibitors (odds ratio 1.558), maximum-dose glucagon-like peptide 1 receptor agonists (1.544), tirzepatide (1.981), or a higher number of blood pressure–lowering medications (1.390); older age (1.316); BMI &lt;30 kg/m2 (1.639); non-Latino/Hispanic ethnicity (3.718); and use of fibrates (2.676) or analgesics (1.457) were associated with higher prevalence (all P &lt; 0.03). CONCLUSIONS Hypercortisolism was associated with hyperglycemia in approximately one-quarter of individuals with inadequately controlled type 2 diabetes despite multiple medications.

Background Orbital decompression is an essential tool for reducing proptosis in thyroid eye disease (TED), yet the impact of surgical approach and preoperative factors on outcomes remains uncertain. Objective To compare proptosis reduction following different orbital decompression techniques, identify additional risk factors that may play a role in surgical orbital decompression outcomes, and develop clinical decision-making recommendations based on these results. Methods A retrospective analysis was performed on TED patients who underwent endoscopic medial wall, orbital floor, and/or open lateral wall decompression. We evaluated the influence of preoperative comorbidities, anatomic and laboratory values, and surgical approach on postdecompression Hertel exophthalmometry outcomes. Results Analysis encompassed 130 orbits from 80 patients, 83% female, 48 with preoperative diplopia, and mean age of 54.4 years. Preoperative Hertel measurement was predictive of extent of proptosis reduction ( P < .0001), indicating that higher initial Hertel measurement predicts greater absolute reduction following surgical intervention. Surgical technique correlated with outcome on univariate analysis ( P = .04), but not multivariate ( P = .13) analyses. When categorized into preoperative Hertel ranges, combined endoscopic medial and open lateral wall decompression resulted in mean proptosis reduction of 3.13 mm for range 20.01 to 24 mm and 3.85 mm for range 24.01 to 28 mm. Three-wall decompression resulted in mean proptosis reduction of 2.49 mm for and 3.84 mm for these ranges, respectively. Variables such as smoking, body mass index, orbital wall height, and TRAb level, did not affect outcomes. Nine patients had new onset diplopia. Conclusions Preoperative Hertel exophthalmometry is the strongest predictor of proptosis reduction following orbital decompression in TED. Surgical technique appears to be less impactful on outcome than expected. Surgical decision making should be individualized based on patient goals; these findings can be used to achieve proptosis reduction and limit the risk of new onset diplopia.

Purpose: To update the epidemiological patterns of facial nerve palsy (FNP) in Olmsted County, Minnesota. Methods: A retrospective chart review using the Rochester Epidemiology Project database was conducted. Patients aged ≥18 years receiving a diagnosis of FNP within the Rochester Epidemiology Project database from the years 2000 to 2010 were included in the study. Data collected included age, gender, cause of FNP, degree of paralysis, medical and/or surgical management, and outcomes. Overall incidence rates were determined using gender-specific population figures for Olmsted County. Incidence trends were compared with previous Rochester Epidemiology Project studies. Results: The most common cause for FNP was Bell palsy (70.3% of cases). The overall incidence rate for Bell palsy in Olmsted County from 2000 to 2010 was 39.9 (95% CI, 36.1–43.7) per 100,000 person-years. This is an absolute increase of 14.9 per 100,000 person-years and a 60% relative increase in Bell palsy compared with a previous study performed at Mayo Clinic using the Rochester Epidemiology Project database population data from 1968 to 1982. Patients were infrequently evaluated by an ophthalmologist (8.4% of cases), and surgical intervention to address ophthalmic sequelae was rare (1.7% of cases). Conclusions: The incidence of Bell palsy has increased dramatically over previous studies, which has occurred in the setting of declining herpes simplex virus type 1 seropositivity trends and increasing herpes zoster incidence in the United States. Few patients with FNP are referred to ophthalmologists, which may represent a gap in care for both acute and long-term ophthalmic sequelae.

Purpose: To review cases of lateral brow dermoid cysts and gain insight into the utility of preoperative imaging, incidence of intraorbital extension, and recurrence rate. Methods: This is a retrospective study of all patients who underwent excision of lateral brow dermoid cysts at the authors' academic center over a 37-year period. Results: A total of 136 patients were included. The median age at presentation was 5.6 months [interquartile range (IQR) 3–16.5], and the median age at removal was 1.5 years (IQR 0.9–3.4). Preoperative imaging was performed in 44 patients. Intraorbital communication was predicted in 4 patients who underwent imaging and confirmed in 6 patients (4.4%) intraoperatively. Superficial dermoids were the most common depth (n=79, 58.1%), followed by periosteal (n=37, 27.2%) and intraosseous (n=14, 10.3%). Two patients (1.4%) presented with postoperative hematoma that required surgical evacuation. Recurrence was seen in 2 patients (1.4%). Among those who completed a follow-up, the median follow-up time was 1 month (IQR 0.44–5.8 months). Conclusion: The authors' study revealed that the majority of lateral brow dermoid cysts are either superficial or involve the periosteum, with orbital involvement being rare. None of our patients demonstrated intracranial communication. Imaging did not seem to add clinical value in patients for whom there was no clinical suspicion for the involvement of the deeper tissues, so careful consideration of ordering preoperative imaging would help decrease health care costs and avoid radiation exposure, which is particularly concerning for pediatric patients. The recurrence rate of lateral brow dermoid cyst seems to be low but studies with longer follow-ups are needed.