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PURPOSE: To report a case series of patients with uveitic glaucoma who were treated with micropulse transscleral cyclophotocoagulation (mpCPC). METHODS: This retrospective case series consists of patients from the University of Colorado Sue Anschutz-Rodgers Eye Center from 2015 to 2020 who were diagnosed with uveitic glaucoma. Information collected includes demographic data, type of uveitis, glaucoma severity, and prior glaucoma surgeries. Pre- and postoperative best corrected visual acuity, intraocular pressure (IOP), glaucoma medications, degree of inflammation, and uveitis therapies were included up to 36 months postoperatively. Surgical success was defined as an IOP reduction of 30% with achievement of IOP goal using the same number of glaucoma medications or less at 6 months or 1 year. Uveitis success was defined as the absence of persistent anterior uveitis at 3 months. RESULTS: Six patients and seven eyes with uveitic glaucoma underwent mpCPC. Types of uveitis included idiopathic anterior uveitis, HLA-B27-associated anterior uveitis, varicella zoster virus anterior uveitis, juvenile idiopathic arthritis-associated chronic anterior uveitis, lichen planus-associated intermediate uveitis, and sarcoidosis-associated panuveitis. Two of six eyes (33.3%) at 6 months and three of five eyes (60%) at 1 year achieved surgical success. Around 6 months postoperatively, two out of seven eyes (28.6%) required Ahmed glaucoma valve placement (n = 1) or repeat mpCPC (n = 1). One eye (14.3%) required phacoemulsification with goniotomy followed by an Ahmed glaucoma valve 18 months after mpCPC. There were no cases of persistent anterior uveitis, hypotony, or phthisis after mpCPC in this cohort. CONCLUSIONS: Micropulse transscleral cyclophotocoagulation may safely reduce intraocular pressure in some patients with uveitic glaucoma without exacerbation of intraocular inflammation. Multiple treatments may be required to achieve longer-term success.
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The advent of large-scale sequencing in both development and disease has identified large numbers of candidate genes that may be linked to important phenotypes. Validating the function of these candidates in vivo is challenging, due to low efficiency and low throughput of most model systems. We have developed a rapid, scalable system for assessing the role of candidate genes using zebrafish. We generated transgenic zebrafish in which Cas9 was knocked-in to the endogenous mitfa locus, a master transcription factor of the melanocyte lineage. We used this system to identify both cell-autonomous and non-cell autonomous regulators of normal melanocyte development. We then applied this to the melanoma setting to demonstrate that loss of genes required for melanocyte survival can paradoxically promote more aggressive phenotypes, highlighting that in vitro screens can mask in vivo phenotypes. Our high-efficiency genetic approach offers a versatile tool for exploring developmental processes and disease mechanisms that can readily be applied to other cell lineages.
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PURPOSE: To evaluate the diagnostic value of QuantiFERON Gold (QFT-G) testing for ocular inflammation in a low prevalence tuberculosis (TB) area. DESIGN: Diagnostic utility analysis. METHODS: A review was performed for all uveitis patients who underwent QFT-G testing at the University of Colorado Eye Center from 2009 to 2022. Records were reviewed to assess QFT-G positivity rate and to identify which patients were tested for diagnostic purposes, defined as meeting the Standardization of Uveitis Nomenclature (SUN) criteria for tubercular uveitis (TBU): anterior uveitis with iris nodules, serpiginous-like choroiditis, choroidal nodule resembling a tuberculoma, multifocal choroiditis, or occlusive retinal vasculitis. RESULTS: A total of 388 patients with uveitis underwent QFT-G testing, of which 17 (4.38%) were positive. Only one (5.88%) patient had true TBU with anterior uveitis with iris nodules. The remaining 16 (94.1%) patients did not meet SUN criteria for TBU and were incidentally found to be QFT-G positive during laboratory work-up prior to immunosuppression. The positive predictive value was 100% when QFT-G testing was performed in patients who met SUN criteria for TBU, whereas the positive predictive value was 0% for QFT-G testing performed in patients who did not meet SUN criteria for TBU. CONCLUSION: In low prevalence areas, the majority of QFT-G positive tests in uveitis patients are coincidental and unrelated to their uveitic disease process. The diagnostic value of a TB test is likely to be minimal unless the SUN clinical criteria for tubercular uveitis are met.
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Testes de Liberação de Interferon-gama , Tuberculose Ocular , Humanos , Tuberculose Ocular/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Uveíte/diagnóstico , Uveíte/microbiologia , Estudos Retrospectivos , Valor Preditivo dos Testes , Doenças Endêmicas , Idoso , Colorado/epidemiologia , Mycobacterium tuberculosis/isolamento & purificação , Mycobacterium tuberculosis/imunologia , Adulto JovemRESUMO
PURPOSE: This study investigates brain and globe abnormalities identified on magnetic resonance imaging (MRI) in children with congenital corneal opacities (CCO). DESIGN: Retrospective cohort study. METHODS: Clinical notes, radiology records, and genetic testing results were reviewed for patients diagnosed with corneal opacification within the first 6 months of life at a tertiary referral academic center between August 2008 and January 2018. Ocular findings, systemic anomalies, neuroimaging, and genetic testing results were summarized. RESULTS: A total of 135 patients presenting at age 1 day to 12 years (mean age, 1 year) were identified. Children with bilateral CCO were more likely to have systemic disease (P = 0.018). Of the entire cohort, 43 (31.8%) patients received MRI, of whom 27 (62.8%) had abnormal brain findings and 30 (69.7%) had abnormal orbital findings. The most common abnormal brain findings were ventriculomegaly (n = 16, 59.2%) and corpus callosum abnormalities (n = 10, 37.0%) followed by brainstem/pons anomalies (n = 5, 18.5%), and cerebellar anomalies (n = 2, 7.4%). Abnormal brain MRI findings were associated with the presence of neurologic (P = .003) and craniofacial (P = .034) disease. A total of 44 (32.1%) patients underwent genetic testing, of whom 29 (65.9%) had pathogenic results. CONCLUSIONS: More than 60% of the children with CCO who underwent MRI had abnormal brain and orbit findings that were correlated with significant neurologic disease. Furthermore, almost two-thirds of patients with CCO who underwent genetic testing had pathogenic results. These data demonstrate the value of systemic workup in children with CCO, and highlight the role of ophthalmologists in facilitating the diagnosis of systemic comorbidities associated with CCO.
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Opacidade da Córnea , Anormalidades do Olho , Criança , Humanos , Lactente , Estudos Retrospectivos , Opacidade da Córnea/diagnóstico , Opacidade da Córnea/genética , Opacidade da Córnea/congênito , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/genética , Testes GenéticosRESUMO
PURPOSE: To report outcomes of cataract surgery in type 1 diabetes mellitus (T1DM) compared with type 2 diabetes mellitus (T2DM) and patients without diabetes mellitus (DM). SETTING: Academic tertiary referral university hospital eye center, Aurora, Colorado. DESIGN: Retrospective chart review using the University of Colorado Cataract Outcomes Database for all cataract surgeries between 2014 and 2020. METHODS: Demographics, ocular history, and postoperative outcomes were compared across groups using general linear and logistic regression modeling with estimating equations to account for some patients having 2 eyes included. RESULTS: 8117 patients and 13 383 eyes were included. Compared with T2DM eyes undergoing cataract surgery (n = 3115), T1DM eyes (n = 233) were more likely to have a history of diabetic retinopathy (DR) (60.5% vs 23.6%, P < .0001), of which proliferative DR was the most common (63.1% vs 42.4%, P < .0001). T1DM eyes were also more likely to have a history of retinal detachment (RD) (9.0% vs 2.9%, P < .0001) and prior vitrectomy surgery (12.9% vs 4.0%, P < .0001). Despite having similar preoperative corrected distance visual acuity (CDVA) as T2DM eyes (logMAR 0.52 vs 0.44, P = .092), T1DM eyes had worse CDVA after cataract surgery (logMAR 0.27 vs 0.15, P = .0003). In a multivariate analysis, a history of proliferative DR and prior RD were significant predictors of worse postoperative CDVA ( P < .0001) but type of DM was not ( P = .894). CONCLUSIONS: T1DM eyes have worse visual outcomes after cataract surgery compared with T2DM eyes. Worse postoperative visual acuity was associated with worse preoperative DR and history of RD rather than type of DM.
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Extração de Catarata , Catarata , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Descolamento Retiniano , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/cirurgia , Estudos Retrospectivos , Catarata/complicações , Retinopatia Diabética/complicações , Descolamento Retiniano/cirurgiaRESUMO
PURPOSE: To test the antiseptic efficacy of povidone-iodine when mixed with topical lidocaine gel. SETTING: Emory School of Medicine, Atlanta, Georgia, USA. DESIGN: Experimental study. METHODS: Staphylococcus epidermidis, Staphylococcus aureus, viridans streptococci (Streptococcus sanguinis), Escherichia coli, and Pseudomonas aeruginosa were grown on blood agar plates with povidone-iodine and/or lidocaine gel. The efficacy of sterilization was quantified by surviving bacterial colony-forming units. RESULTS: Combination of povidone-iodine and lidocaine gel prevented bacterial growth to levels similar to povidone-iodine alone. Application of lidocaine gel to bacteria before povidone-iodine treatment allowed bacterial growth similar to controls not exposed to povidone-iodine. CONCLUSIONS: Povidone-iodine must be applied before lidocaine gel for effective antisepsis, but admixture of povidone-iodine with lidocaine gel was also effective and may reduce the risk of endophthalmitis associated with lidocaine gel use. This strategy offers a practice-changing alternative for preoperative prophylaxis in procedures requiring topical anesthesia.
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Anestesia , Anti-Infecciosos Locais , Humanos , Lidocaína , Povidona-Iodo , Staphylococcus epidermidisRESUMO
Laparoscopic colectomy is the preferred approach for surgical management of non-complicated diverticulitis, with lower complication rates, shorter length of stay, and decreased narcotic use compared with open surgery. Complicated diverticulitis, characterized by abscess, fistula or stricture, is more difficult to manage with minimally invasive surgery, with reports of higher conversion rates, prolonged operative time, longer length of stay, and increased complication rates. The robotic platform may provide an alternative safe and feasible option for managing complicated diverticulitis with minimally invasive surgery. A prospectively maintained database of robotic-assisted colorectal surgery performed at our university-affiliated community hospital was used to identify consecutive patients who underwent robotic-assisted surgery for complicated or non-complicated diverticulitis. Thirty-two patients with non-complicated diverticulitis and 36 patients with complicated diverticulitis had surgery between January, 1, 2014 and September 30, 2017. The database was used to compare the two groups of patients in regard to operative time, estimated blood loss, ureteral stent usage, conversions, ostomies, pelvic drains, post-operative complications, length of stay, return of bowel function, and post-operative narcotic use. Comparison of the two groups revealed significant differences in operative times (172 vs. 196 min, p = 0.01), conversions (3.1% vs. 22.2%, p = 0.03), ostomies (9.4% vs. 33.3%, p = 0.04), and pelvic drains (3.2% vs. 28.6%, p = 0.02). No significant differences were noted for estimated blood loss, complications, return of bowel function, narcotic use, length of stay, or readmissions. Four complicated diverticulitis patients had intra-operative ureteral stents, and there were no ureteral injuries in either group. Patients with complicated diverticulitis required longer operative time, and more often required conversion, an ostomy, and a pelvic drain. Robotic-assisted surgery is safe and feasible for both non-complicated and complicated diverticulitis.
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Procedimentos Cirúrgicos do Sistema Digestório , Diverticulite/cirurgia , Procedimentos Cirúrgicos Robóticos , Adulto , Idoso , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , StentsRESUMO
Glucagon-like peptide-1 (GLP-1) and its analogs act as appetite suppressants and have been proven to be clinically efficacious in reducing body weight in obese individuals. Central GLP-1 is expressed in a small population of brainstem cells located in the nucleus tractus solitarius (NTS), which project to a wide range of brain areas. However, it remains unclear how endogenous GLP-1 released in the brain contributes to appetite regulation. Using chemogenetic tools, we discovered that central GLP-1 acts on the midbrain ventral tegmental area (VTA) and suppresses high-fat food intake. We used integrated pathway tracing and synaptic physiology to further demonstrate that activation of GLP-1 receptors specifically reduces the excitatory synaptic strength of dopamine (DA) neurons within the VTA that project to the nucleus accumbens (NAc) medial shell. These data suggest that GLP-1 released from NTS neurons can reduce highly palatable food intake by suppressing mesolimbic DA signaling.
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Gorduras na Dieta , Neurônios Dopaminérgicos/metabolismo , Ingestão de Alimentos/fisiologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Sinapses/metabolismo , Área Tegmentar Ventral/metabolismo , Animais , Neurônios Dopaminérgicos/citologia , Camundongos , Camundongos Transgênicos , Núcleo Accumbens/citologia , Núcleo Accumbens/metabolismo , Transdução de Sinais/fisiologia , Área Tegmentar Ventral/citologiaRESUMO
Gain-of-toxic-function mutations in Seipin (Asparagine 88 to Serine (N88S) and Serine 90 to Leucine (S90L) mutations, both of which disrupt the N-glycosylation) cause autosomal dominant motor neuron diseases. However, the mechanism of how these missense mutations lead to motor neuropathy is unclear. Here, we analyze the impact of disruption of N-glycosylation of Seipin on synaptic transmission by over-expressing mutant Seipin in cultured cortical neurons via lentiviral infection. Immunostaining shows that over-expressed Seipin is partly colocalized with synaptic vesicle marker synaptophysin. Electrophysiological recordings reveal that the Seipin mutation significantly decreases the frequency, but not the amplitudes of miniature excitatory post-synaptic currents and miniature inhibitory post-synaptic currents. The amplitude of both evoked excitatory post-synaptic currents and inhibitory post-synaptic current is also compromised by mutant Seipin over-expression. The readily releasable pool and vesicular release probability of synaptic vesicles are both altered in neurons over-expressing Seipin-N88S, whereas neither γ-amino butyric acid (GABA) nor α-Amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) induced whole cell currents are affected. Moreover, electron microscopy analysis reveals decreased number of morphologically docked synaptic vesicles in Seipin-N88S-expressing neurons. These data demonstrate that Seipin-N88S mutation impairs synaptic neurotransmission, possibly by regulating the priming and docking of synaptic vesicles at the synapse.