ObjectiveExtreme obesity is a core phenotypic feature of Prader–Willi syndrome (PWS). Among numerous metabolic regulators, the endocannabinoid (eCB) system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB1R) blockade reverses obesity both in animals and humans. The first-in-class CB1R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects.MethodsWe studied eCB ‘tone’ in individuals with PWS and in the Magel2-null mouse model that recapitulates the major metabolic phenotypes of PWS and determined the efficacy of a peripherally restricted CB1R antagonist, JD5037 in treating obesity in these mice.ResultsIndividuals with PWS had elevated circulating levels of 2-arachidonoylglycerol and its endogenous precursor and breakdown ligand, arachidonic acid. Increased hypothalamic eCB ‘tone’, manifested by increased eCBs and upregulated CB1R, was associated with increased fat mass, reduced energy expenditure, and decreased voluntary activity in Magel2-null mice. Daily chronic treatment of obese Magel2-null mice and their littermate wild-type controls with JD5037 (3 mg/kg/d for 28 days) reduced body weight, reversed hyperphagia, and improved metabolic parameters related to their obese phenotype.ConclusionsDysregulation of the eCB/CB1R system may contribute to hyperphagia and obesity in Magel2-null mice and in individuals with PWS. Our results demonstrate that treatment with peripherally restricted CB1R antagonists may be an effective strategy for the management of severe obesity in PWS.

Severe insulin resistance and T2DM are the hallmarks of AS. However, patients with AS may present with multiple other endocrinopathies affecting growth and development.

We report the case of a healthy 59-year-old woman who presented with an acute abducens nerve palsy 2 days after receiving the Pfizer-BioNTech COVID-19 vaccine. In adults, such palsies are typically caused by microvascular disease or compressive tumors, although they have also been described after routine vaccinations. Given the temporal relationship between vaccination and the onset of symptoms, the lack of preexisting medical conditions, and unremarkable magnetic resonance imaging, the patient’s abducens nerve palsy was felt to be related to her vaccination. This case highlights the importance of recognizing the potential of a COVID-19 vaccine to have neurologic sequelae similar to those that as have been reported with the virus itself as well as with other vaccines.

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Alström Syndrome is a ciliopathy associated with obesity, insulin resistance/type 2 diabetes mellitus, cardiomyopathy, retinal degeneration, hearing loss, progressive liver and kidney disease, and normal cognitive function. ALMS1, the protein defective in this disorder, localizes to the cytoskeleton, microtubule organizing center, as well as the centrosomes and ciliary basal bodies and plays roles in formation and maintenance of cilia, cell cycle regulation, and endosomal trafficking. Kidney disease in this disorder has not been well characterized. We performed comprehensive multisystem evaluations on 38 patients. Kidney function decreased progressively; eGFR varied inversely with age (p = 0.002). Eighteen percent met the definition for chronic kidney disease (eGFR < 60 mL/min/1.73 m and proteinuria); all were adults with median age of 32.8 (20.6-37.9) years. After adjusting for age, there were no significant associations of kidney dysfunction with type 2 diabetes mellitus, dyslipidemia, hypertension, cardiomyopathy or portal hypertension suggesting that kidney disease in AS is a primary manifestation of the syndrome due to lack of ALMS1 protein. Approximately one-third of patients had hyperechogenicity of the renal parenchyma on imaging. While strict control of type 2 diabetes mellitus may decrease kidney-related morbidity and mortality in Alström syndrome, identification of novel targeted therapies is needed.

BACKGROUND AND OBJECTIVE: To report the incidence and clinical features of infectious endophthalmitis after intravitreal (IV) injection of anti-vascular endothelial growth factor inhibitors (VEGF) between 2018 and 2020 and to compare to prior rates. PATIENTS AND METHODS: Retrospective analysis of patients with endophthalmitis after anti-VEGF IV injections treated at Bascom Palmer Eye Institute between January 1, 2018, and December 31, 2020. RESULTS: Between 2018 and 2020, the rate of clinically diagnosed endophthalmitis was 0.014% (10/71,858) and of culture-positive was 0.008% (6/71,858). Clinically diagnosed endophthalmitis rates per injection were: aflibercept (0.022%); ranibizumab (0.019%); bevacizumab (0%); and brolucizumab (0%). Clinically diagnosed endophthalmitis rates were similar in the present study compared to those from 2005 to 2017 ( P = .84). Fifteen eyes were diagnosed with endophthalmitis (10 in-house, five external referrals). Of culture-positive eyes, the organisms were coagulase-negative Staphylococcus (8/11), Streptococcus species (2/11), and Abiotrophia defectiva (1/11). A universal face-masking policy in 2020 did not lower infection rates ( P = .73). CONCLUSION: Endophthalmitis rates after IV anti-VEGF remain low and are similar to prior reports. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:319–326.]

Purpose: A prior study revealed discrepancies in self-reported surgical numbers between male and female ophthalmology residents. This study further investigates the gender differences in self-reported procedural volume among vitreoretinal surgery fellows and examines the differences for surgical, medical, and total self-reported procedural volume between male and female vitreoretinal fellows.Methods: A retrospective review of case logs submitted to the American Society of Retina Specialists by first-year and second-year vitreoretinal fellows from July 1, 2018, to June 30, 2019, was performed. Fellows who reported fewer than 100 pars plana vitrectomies were excluded. A total of 133 fellows were included.Results: Overall, 37 of 57 (65%) first-year fellows and 59 of 76 (78%) second-year fellows were male. An average of 1,120 procedures were self-reported among all vitreoretinal fellows. In the group of second-year fellows at the completion of fellowship, men reported more total procedures (1,171 [864-1,600] vs. 1,005 [719-1,257]; P = 0.072). Women reported statistically significant fewer endolaser (P = 0.018), internal limiting membrane peel (P = 0.042), and cryoretinopexy (P = 0.002) procedures compared with men. When splitting the data by total surgical versus medical procedures, men reported more procedures than women both surgically (1,077 [799-1,490] vs. 925 [622-1,208]; P = 0.085) and medically (72 [41-116] vs. 56 [20-94]; P = 0.141), although these differences were not statistically significant.Conclusion: There is a trend for female vitreoretinal fellows to report fewer surgical procedures than their male counterparts, raising concerns for gender gaps in vitreoretinal surgical training. Further research is needed to verify this discrepancy and identify potential barriers that female vitreoretinal surgeons are facing in training.

A 51-year-old female underwent four upper zygomatic dental implants (ZI) and one upper and four lower conventional implants. Immediately postoperatively, the patient had pain and diplopia upon manual elevation of the edematous eyelid. Panoramic x-ray showed a malpositioned right upper ZI, requiring removal of the right upper ZI the following day. The patient had delayed referral to ophthalmology one month later for persistent diplopia. Computed tomography scan and magnetic resonance imaging demonstrated a right inferolateral fracture with fibrosis surrounding the inferior oblique muscle. Clinical exam showed right lower eyelid retraction, right hypotropia, and inability to elevate in adduction, consistent with a right inferior oblique paresis. Surgical exploration revealed incarceration of lid and orbital tissue into the fracture. After repositioning of the prolapsed tissue, a high-density porous polyethylene implant was placed for fracture repair. The inferior fornix was reconstructed with amniotic membrane and 5-fluorouracil was injected into the scar tissue. Six months later, the patient underwent strabismus surgery with resolution of symptoms.