Antibiotic utilization in endoscopic dacryocystorhinostomy: a multi-institutional study and review of the literature.

PURPOSE: Utilization of antibiotics for endoscopic dacryocystorhinostomy (endo-DCR) is largely dependent on individual surgeon preference. This study aimed to investigate prescribing practices of pre-, peri-, and postoperative antibiotics and effects on postoperative infection rates in patients who underwent endo-DCR. METHODS: A retrospective chart review of institutional data at two academic centers of endo-DCR cases from 2015-2020 was performed. Postoperative infection rates for patients who received pre-, peri-, and postoperative antibiotics, individually or in combination, and those who did not, were compared via odds ratio and ANOVA linear regression. RESULTS: 331 endo-DCR cases were included; 22 cases (6.6%) had a postoperative infection. There was no significant difference in the infection rates between patients without an active preoperative dacryocystitis who received different permutations of peri- and postoperative antibiotics. Patients who received preoperative antibiotics within two weeks of surgery for preexisting acute dacryocystitis, but did not receive peri- or postoperative antibiotics, had a higher rate of postoperative infections (p = 008). CONCLUSIONS: Our data suggest antibiotics may be beneficial only when patients have a recent or active dacryocystitis prior to surgery. Otherwise, our data do not support the routine use of antibiotic prophylaxis in endo-DCR.

Diverse Research Teams and Underrepresented Groups in Clinical Studies.

Importance: Several ophthalmic diseases disproportionately affect racial and ethnic minority patients, yet most clinical trials struggle to enroll cohorts that are demographically representative of disease burden; some barriers to recruitment include time and transportation, language and cultural differences, and fear and mistrust of research due to historical abuses. Incorporating diversity within the research team has been proposed as a method to increase trust and improve engagement among potential study participants. Objective: To examine how demographic factors of potential research participants and personnel may be associated with patient consent rates to participate in prospective ophthalmic clinical studies. Design, Setting, and Participants: This retrospective cohort study included patients from an urban, academic hospital who were approached for consent to participate in prospective ophthalmic clinical studies conducted between January 2015 and December 2021. Main Outcomes and Measures: Multivariable logistic regression assessing associations between patient and research personnel demographics and rates of affirmative consent to participate was used. Results: In total, 1380 patients (mean [SD] age, 58.6 [14.9] years; 50.3% male) who were approached for consent to participate in 10 prospective ophthalmic clinical studies were included. Of prospective patients, 566 (43.5%) were Black; 327 (25.1%), Hispanic or Latino; 373 (28.6%), White; 36 (2.8%), other race and ethnicity; and 78 (5.8%) declined to answer. Black patients (odds ratio [OR], 0.32; 95% CI, 0.24-0.44; P < .001) and Hispanic or Latino patients (OR, 0.31; 95% CI, 0.20-0.47; P < .001) were less likely to consent compared with White patients. Patients with lower socioeconomic status were less likely to consent than patients with higher socioeconomic status (OR, 0.43; 95% CI, 0.33-0.53; P < .001). Concordance between patient and research staff race and ethnicity was associated with increased odds of affirmative consent (OR, 2.72; 95% CI, 1.99-3.73; P < .001). Conclusions and Relevance: In this cohort study, patients from underrepresented racial and ethnic groups and those with lower socioeconomic status were less likely to participate in ophthalmic clinical studies. Concordance of race and ethnicity between patients and research staff was associated with improved participant enrollment. These findings underscore the importance of increasing diversity in clinical research teams to improve racial and ethnic representation in clinical studies.

Thyroid Eye Disease.

Thyroid eye disease (TED), an autoimmune inflammatory disorder of the orbit, presents with a potential array of clinical sequelae. The pathophysiology behind TED has been partially characterized in the literature. There remain certain elusive mechanisms welcoming of research advances. Disease presentation can vary, but those that follow a characteristic course start mild and increase in severity before plateauing into an inactive phase. Diagnosis and evaluation include careful physical examination, targeted laboratory work up, appropriate imaging studies, and tailored treatment regimens. Special consideration may apply to certain populations, such as pediatric and pregnant patients.

Partial Stenosis and Complete Punctal Closure Following Topical Netarsudil Use for Glaucoma.

PURPOSE: To describe patients who developed partial or complete punctal closure after the use of topical netarsudil in the treatment of glaucoma, with documented reversal of symptoms on drug cessation. PATIENTS AND METHODS: This is a retrospective, single-center case series including patients treated with topical netarsudil who were documented to have developed punctal disease ipsilateral to the eye(s) being treated. A literature review was also performed to identify other similar reports. RESULTS: A total of 10 patients were included in the study. Six patients developed partial punctal stenosis and 4 patients developed complete closure of the puncta in 1 or both eye(s) ipsilateral to the use of the topical medication. None of the patients developed punctal disease on the non-netarsudil side. The time from initiation of netarsudil to the documentation of punctal disease ranged from 5-32.2 months (18.41±9.94). In the patients with complete punctal closure, discontinuation of the topical medication led to clinical reappearance of the punctal opening, ranging from 31-83 days after drug cessation (45.75±21.57). In 8 cases, discontinuation of netarsudil resulted in improved epiphora and degree of punctal stenosis on clinical examination. CONCLUSIONS: The use of topical netarsudil for glaucoma may lead to punctal stenosis and complete punctal closure. These side effects of netarsudil are relevant to therapeutic considerations for glaucoma patients.

Unilateral Familial Exudative Vitreoretinopathy: Clinical Profile and Pathology.

We report a case of a newborn with unilateral retinal detachment that could not be repaired. At examination under anesthesia, the retina was markedly abnormal and a presumptive diagnosis of retinal dysplasia was made. Several years later, the eye was enucleated because it was blind and painful. Final pathology was consistent with familial exudative vitreoretinopathy (FEVR). The literature describing unilateral retinal dysplasia is sparse. This case adds to the clinical spectrum of pathologic findings in FEVR.

Angiolymphoid Hyperplasia with Eosinophilia with Clinical Presentation Concerning for Juvenile Temporal Arteritis.

A 20-year-old boy presented with a mass superotemporal to the right eyebrow of 1 month's duration without a history of recent trauma. Complete examination and workup, including laboratory analysis, Doppler ultrasound imaging, and magnetic resonance imaging, suggested a diagnosis of juvenile temporal arteritis. Excisional biopsy and histopathology contradicted the preoperative workup and yielded the final diagnosis of angiolymphoid hyperplasia with eosinophilia, a rare eosinophilic dermatosis of unknown etiology. This case highlights the need for better characterization of temporal vascular tumors in the pediatric population.

Early discharge criteria in patients with acute bacterial skin and skin structure infections in a large tertiary-care teaching hospital in Florence, Italy.

The study is aimed at retrospectively estimating the percentage of inpatients with severe acute bacterial skin and skin structure infections (ABSSSI) who met the early discharged (ED) criteria adapted from Nathwani et al. (Int J Antimicrob Agents. 2016 Aug;48(2):127-36) and to calculate the number of hospitalization days that could be potentially saved. A retrospective study was conducted in a tertiary care hospital in Florence, Italy. We included all patients admitted for cellulitis and post-surgical infections from 2014 to 2017. Demographic and clinical data were obtained from electronic medical records. We a priori defined the following as a risk factor for non-adherence (RFNA): active or on methadone intravenous drug users, homeless, migrants without health care assistance, and patients who need a caregiver to take prescribed medications. One hundred sixty-two subjects were enrolled. Of them, 94 (58.0%) were male, and 113 (69.7%) had cellulitis/erysipelas. A microbiological isolate was obtained in 51 patients (31.4%); Staphylococcus aureus was the most frequent (47%). Eighty-four (51.8%) were ED suitable, with 258 (49.0%) patient days potentially saved. Among the 78 not ED suitable patients, the most common reason for prolonged length of stay (LOS) was having at least one RFNA (34.6%). Fourteen (18.0%) had one RFNA. Half of the patients admitted in our hospital met the ED criteria with a sparing close to 50% in terms of hospitalization days. Unstable social and personal factors were the most frequent causes for prolonged LOS. In this selected subset of patients, more recent and easier to administer treatments, including long-acting agents, could be proposed.

Acute Sterile Canaliculitis: A Case Report and Review of the Literature.

A 53-year-old male developed secondary canaliculitis after undergoing nasolacrimal intubation with a silicone stent. Negative cultures, symptoms refractory to antibiotics, and rapid resolution after stent removal suggest an immune reaction as the mechanism of canaliculitis. This case raises awareness of noninfectious hypersensitivity or hypersensitivity-like reactions as a potential acute or subacute complication of nasolacrimal stenting.

Non-Arteritic Anterior Ischemic Optic Neuropathy in Pilots.

BACKGROUND: Non-arteritic anterior ischemic optic neuropathy (NAION) is a common cause of optic neuropathy with the exact pathophysiology unknown. Risk factors include advanced age, small optic nerve head, hypertension, diabetes mellitus, and sleep apnea.6 High altitude is considered another risk factor, although only few cases have been reported. No cases of NAION have been reported to occur during flight.CASE REPORT: A 41-yr-old male pilot presented with vision change while performing high G-force maneuvers in an A10 fighter jet. He developed a paracentral visual field defect superiorly in the left eye. Contrasted MRI was within normal limits. The left optic nerve showed blurred margins while the right was sharp, but cupless. The left eye had similar episodes 16 mo before and 8 mo after, but not during flight.DISCUSSION: Our case may be the first reported NAION during flight in an airplane pilot. Our patient was an active U.S. Air Force pilot whose second episode of NAION occurred while performing maneuvers in a fighter jet. The patient is younger than expected for NAION and he did not have any of the commonly associated risk factors. His nonflight episodes suggest he was predisposed to NAION. G-force maneuvers, which restrict blood flow and force blood to the extremities away from the optic nerve head, were the precipitant of his second NAION. With a single case, whether high G maneuvers in general are a risk factor for NAION is unknown.Distefano AG, Lam BL. Non-arteritic anterior ischemic optic neuropathy in pilots. Aerosp Med Hum Perform. 2018; 89(11):1005-1007.

Necrotizing Orbital Cellulitis Secondary to Odontogenic Streptococcus constellatus.

A 69-year-old woman with orbital cellulitis secondary to odontogenic Streptococcus constellatus was transferred to the authors' institution for surgical management of infection refractory to intravenous antibiotics. She underwent debridement with preservation of the globe, recovering full motility. Visual recovery was limited by optic nerve ischemia. This case supports the importance of urgent surgical drainage in necrotizing orbital infections secondary to odontogenic Streptococcus constellatus.

Epithelial-Myoepithelial Carcinoma Presenting as a Pseudo Veno-Lymphatic Malformation.

A 41-year-old woman presented with several days of right eye pain and blurred vision. Examination and radiologic workup were consistent with a veno-lymphatic malformation, including demonstration of cystic fluid-fluid levels on imaging. Histopathology supported the presence of cystic spaces but revealed the final diagnosis of lacrimal epithelial-myoepithelial carcinoma, a rare neoplasm typically associated with the salivary gland. This represents the first reported case of lacrimal epithelial-myoepithelial carcinoma presenting with pain and evidence of intralesional cysts on radiographic and histopathologic evaluation. Better characterization will enable recognition, complete surgical excision, and potential adjuvant radiation therapy.

Regulation of hepatic energy metabolism and gluconeogenesis by BAD.

The homeostatic balance of hepatic glucose utilization, storage, and production is exquisitely controlled by hormonal signals and hepatic carbon metabolism during fed and fasted states. How the liver senses extracellular glucose to cue glucose utilization versus production is not fully understood. We show that the physiologic balance of hepatic glycolysis and gluconeogenesis is regulated by Bcl-2-associated agonist of cell death (BAD), a protein with roles in apoptosis and metabolism. BAD deficiency reprograms hepatic substrate and energy metabolism toward diminished glycolysis, excess fatty acid oxidation, and exaggerated glucose production that escapes suppression by insulin. Genetic and biochemical evidence suggests that BAD's suppression of gluconeogenesis is actuated by phosphorylation of its BCL-2 homology (BH)-3 domain and subsequent activation of glucokinase. The physiologic relevance of these findings is evident from the ability of a BAD phosphomimic variant to counteract unrestrained gluconeogenesis and improve glycemia in leptin-resistant and high-fat diet models of diabetes and insulin resistance.

Paradoxical effects of increased expression of PGC-1alpha on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism.

Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha has been shown to play critical roles in regulating mitochondria biogenesis, respiration, and muscle oxidative phenotype. Furthermore, reductions in the expression of PGC-1alpha in muscle have been implicated in the pathogenesis of type 2 diabetes. To determine the effect of increased muscle-specific PGC-1alpha expression on muscle mitochondrial function and glucose and lipid metabolism in vivo, we examined body composition, energy balance, and liver and muscle insulin sensitivity by hyperinsulinemic-euglycemic clamp studies and muscle energetics by using (31)P magnetic resonance spectroscopy in transgenic mice. Increased expression of PGC-1alpha in muscle resulted in a 2.4-fold increase in mitochondrial density, which was associated with an approximately 60% increase in the unidirectional rate of ATP synthesis. Surprisingly, there was no effect of increased muscle PGC-1alpha expression on whole-body energy expenditure, and PGC-1alpha transgenic mice were more prone to fat-induced insulin resistance because of decreased insulin-stimulated muscle glucose uptake. The reduced insulin-stimulated muscle glucose uptake could most likely be attributed to a relative increase in fatty acid delivery/triglyceride reesterfication, as reflected by increased expression of CD36, acyl-CoA:diacylglycerol acyltransferase1, and mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase, that may have exceeded mitochondrial fatty acid oxidation, resulting in increased intracellular lipid accumulation and an increase in the membrane to cytosol diacylglycerol content. This, in turn, caused activation of PKC, decreased insulin signaling at the level of insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, and skeletal muscle insulin resistance.

Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity.

Acetyl-CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation. To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total energy expenditure in Acc2(-/-) and WT control mice fed either regular or high-fat diets. To determine insulin action in vivo, we also measured whole-body insulin-stimulated liver and muscle glucose metabolism during a hyperinsulinemic-euglycemic clamp in Acc2(-/-) and WT control mice fed a high-fat diet. Contrary to previous studies that have suggested that increased fat oxidation might result in lower glucose oxidation, both fat and carbohydrate oxidation were simultaneously increased in Acc2(-/-) mice. This increase in both fat and carbohydrate oxidation resulted in an increase in total energy expenditure, reductions in fat and lean body mass and prevention from diet-induced obesity. Furthermore, Acc2(-/-) mice were protected from fat-induced peripheral and hepatic insulin resistance. These improvements in insulin-stimulated glucose metabolism were associated with reduced diacylglycerol content in muscle and liver, decreased PKC activity in muscle and PKCepsilon activity in liver, and increased insulin-stimulated Akt2 activity in these tissues. Taken together with previous work demonstrating that Acc2(-/-) mice have a normal lifespan, these data suggest that Acc2 inhibition is a viable therapeutic option for the treatment of obesity and type 2 diabetes.

Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance.

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and is strongly associated with obesity. Increased concentrations of intracellular fatty acid metabolites have been postulated to interfere with insulin signaling by activation of a serine kinase cascade involving PKCtheta in skeletal muscle. Uncoupling protein 3 (UCP3) has been postulated to dissipate the mitochondrial proton gradient and cause metabolic inefficiency. We therefore hypothesized that overexpression of UCP3 in skeletal muscle might protect against fat-induced insulin resistance in muscle by conversion of intramyocellular fat into thermal energy. Wild-type mice fed a high-fat diet were markedly insulin resistant, a result of defects in insulin-stimulated glucose uptake in skeletal muscle and hepatic insulin resistance. Insulin resistance in these tissues was associated with reduced insulin-stimulated insulin receptor substrate 1- (IRS-1-) and IRS-2-associated PI3K activity in muscle and liver, respectively. In contrast, UCP3-overexpressing mice were completely protected against fat-induced defects in insulin signaling and action in these tissues. Furthermore, these changes were associated with a lower membrane-to-cytosolic ratio of diacylglycerol and reduced PKCtheta activity in whole-body fat-matched UCP3 transgenic mice. These results suggest that increasing mitochondrial uncoupling in skeletal muscle may be an excellent therapeutic target for type 2 diabetes mellitus.