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PURPOSE: To report a novel optical coherence tomography (OCT) sign in the context of CRB1-related maculopathy, termed outer retinal columnar abnormalities (ORCA). METHODS: Retrospective, multicenter observational case series of 14 eyes of 8 patients with molecularly confirmed CRB1-related maculopathy and ORCA. Multimodal imaging scans and medical records patients with CRB1-related maculopathy were reviewed. Outcome measures included best-corrected visual acuity (BCVA), central subfield thickness on spectral-domain OCT (SD-OCT), presence of ORCAs and analysis of their change in appearance over time. RESULTS: At baseline, mean age was 18 +/- 10 years (range 9-36). All patients had an isolated macular dystrophy except for 1 case harboring a triallelic pathogenic variant. Variant c.498_506del was found in 9 cases (88%). At presentation, ORCA were visible on macular SD-OCT in all cases as multiform, vertical hyperreflective columnar alterations extending from the ellipsoid to the outer plexiform layer, with a variable degree of hyporeflective cystic spaces in the outer and inner nuclear layers. Over 6 +/- 4.7 follow-up years, the presence of ORCA varied greatly with a decrease in ORCA associated with sequential development of retinal atrophy. CONCLUSIONS: A high suspicion for CRB1-associated retinal dystrophy should arise in the presence of ORCA on SD-OCT, prompting genetic testing.
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BACKGROUND/AIMS: To evaluate the efficacy, safety and durability of intravitreal faricimab in patients with neovascular age-related macular degeneration (nAMD) with unsatisfactory response to traditional anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: Single-centre, prospective cohort study of all consecutive patients with nAMD who were switched to intravitreal faricimab from intravitreal ranibizumab or aflibercept, due to unsatisfactory treatment response (maximal fluid-free interval ≤ 8 weeks). Intravitreal faricimab was administered with a loading dose of four 4-weekly injections, followed by an 8-week extension. A treat and extend (T&E) regime was adopted thereafter. Primary outcome was the difference between the maximal fluid-free interval achieved with faricimab, and the one achieved before the switch. Morpho-functional outcomes were also assessed. Secondary outcome was accordance with clinical management when applying faricimab pivotal trial criteria versus our real-world T&E protocol, measured as a proportion. RESULTS: Twenty-six eyes of 26 patients with a median age of 82 years (range 77-85) were included. Patients were followed for 30.2 weeks (range 26.3-33.1). Maximal fluid-free interval after switch to faricimab (Mdn = 6.0 weeks; IQR = 4-8) was longer than the maximum interval before the switch (Mdn = 4.0 weeks; IQR = 4-4), p < 0.001. Comparing real-world T&E protocol with pivotal trial criteria, 8 (30.8%) eyes received the same clinical management while 18 (69.2%) eyes were kept at a shorter interval when following our T&E protocol. No serious adverse events were recorded. CONCLUSIONS: Faricimab appears to increase the fluid-free interval and allow extension of dosing interval in patients with nAMD poorly responsive to traditional anti-VEGF drugs.
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Anticuerpos Biespecíficos , Degeneración Macular , Degeneración Macular Húmeda , Humanos , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis , Estudios Prospectivos , Inyecciones Intravítreas , Agudeza Visual , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular , Degeneración Macular/tratamiento farmacológico , Proteínas Recombinantes de Fusión/uso terapéutico , Resultado del Tratamiento , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/tratamiento farmacológicoRESUMEN
PURPOSE: To describe the occurrence of bilateral outer retinal columnar abnormalities, non-vasogenic cystoid macular edema, and drusen in the context of dense deposit disease. METHODS: Case report. PATIENT: An 18-year-old female with dense deposit disease was referred to our specialist center for diagnosis and management with findings consistent with bilateral non-vasogenic cystoid macular edema and drusen. She was followed up in our clinic for forty months and treated with acetazolamide and ketorolac drops. RESULTS: Baseline examination revealed bilateral visual acuity (VA) reduction, and macular elevation with peripapillary drusen on fundus biomicroscopy. Optical coherence tomography revealed bilateral hyporeflective cystoid central macula changes, microcystoid changes with increased central subfield thickness (>450 microns), and outer retinal columnar abnormalities (ORCAs). Fluorescein angiography showed no evidence of macular leakage. Electrodiagnostic testing was within normal limits. Over the course of follow-up, she received treatment with acetazolamide 250mg BD PO and ketorolac 0.5% eye drops, with a partial reduction in her edema and improvement in VA. CONCLUSION: Dense deposit disease is a rare disease secondary to complement cascade dysregulation, associated with drusen. To the best of our knowledge, this is the first report of bilateral non-vasogenic cystoid macular edema and ORCA in a young female patient with dense deposit disease, confirmed with multimodal imaging.
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PURPOSE: To create an unsupervised cross-domain segmentation algorithm for segmenting intraretinal fluid and retinal layers on normal and pathologic macular OCT images from different manufacturers and camera devices. DESIGN: We sought to use generative adversarial networks (GANs) to generalize a segmentation model trained on one OCT device to segment B-scans obtained from a different OCT device manufacturer in a fully unsupervised approach without labeled data from the latter manufacturer. PARTICIPANTS: A total of 732 OCT B-scans from 4 different OCT devices (Heidelberg Spectralis, Topcon 1000, Maestro2, and Zeiss Plex Elite 9000). METHODS: We developed an unsupervised GAN model, GANSeg, to segment 7 retinal layers and intraretinal fluid in Topcon 1000 OCT images (domain B) that had access only to labeled data on Heidelberg Spectralis images (domain A). GANSeg was unsupervised because it had access only to 110 Heidelberg labeled OCTs and 556 raw and unlabeled Topcon 1000 OCTs. To validate GANSeg segmentations, 3 masked graders manually segmented 60 OCTs from an external Topcon 1000 test dataset independently. To test the limits of GANSeg, graders also manually segmented 3 OCTs from Zeiss Plex Elite 9000 and Topcon Maestro2. A U-Net was trained on the same labeled Heidelberg images as baseline. The GANSeg repository with labeled annotations is at https://github.com/uw-biomedical-ml/ganseg. MAIN OUTCOME MEASURES: Dice scores comparing segmentation results from GANSeg and the U-Net model with the manual segmented images. RESULTS: Although GANSeg and U-Net achieved comparable Dice scores performance as human experts on the labeled Heidelberg test dataset, only GANSeg achieved comparable Dice scores with the best performance for the ganglion cell layer plus inner plexiform layer (90%; 95% confidence interval [CI], 68%-96%) and the worst performance for intraretinal fluid (58%; 95% CI, 18%-89%), which was statistically similar to human graders (79%; 95% CI, 43%-94%). GANSeg significantly outperformed the U-Net model. Moreover, GANSeg generalized to both Zeiss and Topcon Maestro2 swept-source OCT domains, which it had never encountered before. CONCLUSIONS: GANSeg enables the transfer of supervised deep learning algorithms across OCT devices without labeled data, thereby greatly expanding the applicability of deep learning algorithms.
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Aprendizaje Profundo , Humanos , Tomografía de Coherencia Óptica/métodos , Retina/diagnóstico por imagen , AlgoritmosRESUMEN
BACKGROUND/AIMS: Microphthalmia and anophthalmia are rare conditions, which represent ocular maldevelopment; both may be associated with orbital cysts. Current literature recommends retention to stimulate orbital growth during socket rehabilitation but does not illustrate their potential to deform the periocular tissues. This study aims to illustrate the long-term outcomes when other elements, such as forniceal and lid development, are also considered when formulating bespoke treatment plans for patients. METHODS: Retrospective case series of 78 patients attending a single prosthetics clinic between 1988 and 2020. Clinical and surgical notes, radiological imaging, clinical photographs and patient/doctor satisfaction questionnaires were used to report patient outcomes and natural history data. RESULTS: 89 sockets of 78 patients (11 bilateral) were included; average age of presentation being 2.8 years (9 days to 29.5 years). Cysts were clinically detected (48%) or were incidental findings (52%). The mean follow-up time was 7.2 years (6 months to 28 years). Cysts in 46% of sockets underwent surgical excision while the remainder were retained. Satisfaction surveys were obtained for 75 patients, with cosmetic outcomes rated as 'excellent' or 'good' in 90% of cases by physicians and 97% of cases by patients or guardians. CONCLUSION: The favourable long-term outcomes in this study have resulted from bespoke plans which considered periocular tissue development, regional orbital growth and orbital volume replacement. The authors contemplate cyst excision if the prosthetic fitting or retention is impeded by the cyst as this often heralds the increased risk of long-term periocular distortion.
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Anoftalmos , Quistes , Microftalmía , Humanos , Preescolar , Anoftalmos/cirugía , Microftalmía/cirugía , Microftalmía/complicaciones , Estudios Retrospectivos , Ojo , Quistes/diagnóstico , Quistes/cirugía , Órbita/cirugíaRESUMEN
INTRODUCTION: Recent years have witnessed an upsurge of demand in eye care services in the UK. With a large proportion of patients referred to Hospital Eye Services (HES) for diagnostics and disease management, the referral process results in unnecessary referrals from erroneous diagnoses and delays in access to appropriate treatment. A potential solution is a teleophthalmology digital referral pathway linking community optometry and HES. METHODS AND ANALYSIS: The HERMES study (Teleophthalmology-enabled and artificial intelligence-ready referral pathway for community optometry referrals of retinal disease: a cluster randomised superiority trial with a linked diagnostic accuracy study) is a cluster randomised clinical trial for evaluating the effectiveness of a teleophthalmology referral pathway between community optometry and HES for retinal diseases. Nested within HERMES is a diagnostic accuracy study, which assesses the accuracy of an artificial intelligence (AI) decision support system (DSS) for automated diagnosis and referral recommendation. A postimplementation, observational substudy, a within-trial economic evaluation and discrete choice experiment will assess the feasibility of implementation of both digital technologies within a real-life setting. Patients with a suspicion of retinal disease, undergoing eye examination and optical coherence tomography (OCT) scans, will be recruited across 24 optometry practices in the UK. Optometry practices will be randomised to standard care or teleophthalmology. The primary outcome is the proportion of false-positive referrals (unnecessary HES visits) in the current referral pathway compared with the teleophthalmology referral pathway. OCT scans will be interpreted by the AI DSS, which provides a diagnosis and referral decision and the primary outcome for the AI diagnostic study is diagnostic accuracy of the referral decision made by the Moorfields-DeepMind AI system. Secondary outcomes relate to inappropriate referral rate, cost-effectiveness analyses and human-computer interaction (HCI) analyses. ETHICS AND DISSEMINATION: Ethical approval was obtained from the London-Bromley Research Ethics Committee (REC 20/LO/1299). Findings will be reported through academic journals in ophthalmology, health services research and HCI. TRIAL REGISTRATION NUMBER: ISRCTN18106677 (protocol V.1.1).
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Oftalmología , Optometría , Enfermedades de la Retina , Telemedicina , Inteligencia Artificial , Humanos , Oftalmología/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Derivación y Consulta , Enfermedades de la Retina/diagnóstico , Telemedicina/métodosRESUMEN
Macrophages are multifunctional cells essential to the immune system function, and the primary host cell in Leishmania braziliensis (Lb) infection. These cells are specialized in microorganism recognition and phagocytosis, but also activate other immune cells and present antigens, as well as promote inflammation and tissue repair. Here, we describe a protocol to obtain mononuclear cells from peripheral blood (PBMC) of healthy donors to separate monocytes that then differentiate into macrophages. These cells can then be infected in vitro at different Lb concentrations to evaluate the ability to control infection, as well as evaluate host cell immune response, which can be measured by several methods. PBMCs were first isolated by centrifuging with Ficoll-Hypaque gradient and then plated to allow monocytes to adhere to culture plates; non-adherent cells were removed by washing. Next, adherent cells were cultured with macrophage-colony stimulating factor (M-CSF) for 7 days to induce macrophage differentiation. We suggest plating 2 x 106 cells per well on 24-well plates in order to obtain 2 x 105 macrophages. Fully differentiated macrophages can then be infected with Lb for 4 or 24 hours. This protocol results in a significant percentage of infected cells, which can be assessed by optical or fluorescence microscopy. In addition to infection index, parasite load can be measured by counting the numbers of parasites inside each cell. Further molecular and functional assays can also be performed in culture supernatants or within the macrophages themselves, which allows this protocol to be applied in a variety of contexts and also adapted to other intracellular parasite species.
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Leishmania braziliensis , Células Cultivadas , Humanos , Inmunidad Innata , Leucocitos Mononucleares , Macrófagos , MonocitosRESUMEN
PURPOSE: To investigate the relation between the eighth edition of the American Joint Committee on Cancer staging system and histological risk classification for primary eyelid basal cell carcinoma. METHODS: Retrospective, observational case series of patients undergoing excisional biopsy for primary eyelid basal cell carcinoma in two tertiary centres between 2008 and 2018. Patients with <6 months of follow-up were excluded. Outcomes measured included histological subtype, American Joint Committee on Cancer 7 and 8 staging. RESULTS: A total of 222 cases were included over a 10-year period, with a mean (range) follow-up of 25.74 (6-120) months and a median (range) age of 70 (28-93) years. According to American Joint Committee on Cancer 8, the most common T category was T1a (64%), followed by T1b (18%) and T2a (8%). Of the 222 specimens, 183 (82.43%), 17 (7.66%), 19 (8.56%) and 3 (1.35%) were staged as IA, IB, IIA and IIB, respectively. The most common histological subtype was nodular in IA category and infiltrative in categories IB and IIA. Histologically, low-risk basal cell carcinomas were related to lower American Joint Committee on Cancer staging (IA), whereas high-risk basal cell carcinomas were related to American Joint Committee on Cancer stages IB and IIA (p < 0.001). No significant relation was found between T categorisation and risk stratification when adopting American Joint Committee on Cancer 7. CONCLUSION: American Joint Committee on Cancer 8 staging system is strongly related to primary eyelid basal cell carcinoma histological risk classification.
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Carcinoma Basocelular , Neoplasias Cutáneas , Párpados/patología , Humanos , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Estados UnidosRESUMEN
OBJECTIVES: To compare diabetic retinopathy (DR) grading and management plan between virtual review using widefield Clarus imaging and macular optical coherence tomography (OCT) versus slit lamp clinical examination and macular OCT. METHOD: New referrals over 3 months from the National Diabetic Eye Screening programme (DESP) were screened. Patients who had both Clarus widefield imaging and macular OCT were included. All patients underwent slit lamp examination in clinic. Data obtained from electronic patient records included referral reason, DR grading and management plan. Two graders retrospectively reviewed imaging and formulated a management plan blinded to results from patients' clinic visit. Results from virtual examination were compared with those from slit lamp examination. RESULTS: One-hundred and two eyes of 51 patients were assessed. 11 fundus photos from 7 patients and 15 fundus photos from 10 patients were deemed inadequate by grader G1 and G2, respectively. Eighteen (35%) patients and 11 (22%) patients from virtual assessment by G1 and G2, respectively were found to need a face a face appointment to aid diagnosis. Compared to slit lamp examination, 15% and 7.5% of patients from G1 and G2's virtual assessment respectively had different proposed management plan. Agreement of DR grading between both virtual graders and slit lamp examination was fair (Kappa's coefficient = 0.56). One case of slit lamp noted retinal neovascularization, which was graded as background retinopathy by DESP was also graded as such on virtual assessment. CONCLUSION: Widefield Clarus and OCT imaging allowed two-thirds of DESP referrals to be safely managed virtually.
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Diabetes Mellitus , Retinopatía Diabética , Retinopatía Diabética/diagnóstico por imagen , Humanos , Fotograbar , Derivación y Consulta , Estudios Retrospectivos , Lámpara de Hendidura , Microscopía con Lámpara de Hendidura , Medicina Estatal , Tomografía de Coherencia ÓpticaAsunto(s)
Cicatriz/diagnóstico , Infecciones Virales del Ojo/diagnóstico , Herpes Simple/diagnóstico , Herpesvirus Humano 1/aislamiento & purificación , Síndrome de Necrosis Retiniana Aguda/diagnóstico , Humor Acuoso/virología , Cicatriz/virología , Infecciones Virales del Ojo/virología , Femenino , Herpes Simple/virología , Herpesvirus Humano 1/genética , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Recurrencia , Síndrome de Necrosis Retiniana Aguda/virología , Tomografía de Coherencia Óptica , Cicatrización de HeridasRESUMEN
Direct halogenation of phenolic compounds present in the CH2Cl2 extract of the roots of Arrabidaea brachypoda was investigated to enhance chemodiversity. The approach is based on eco-friendly reactions using NaBr, NaI, and NaCl in aqueous media to generate multiple "unnatural" halogenated natural products from crude extracts. The halogenation reactions, monitored by UHPLC-PDA-ELSD-MS, were optimized to generate mono-, di-, or trihalogenated derivatives. To isolate these compounds, the reactions were scaled up and the halogenated analogues were isolated by semipreparative HPLC-UV and fully characterized by NMR and HR-MS data. All of the original 16 halogenated derivatives were evaluated for their antiparasitic activities against the parasites Leishmania amazonensis and Trypanosoma cruzi. Compounds presenting selective antiparasitic activities against one or both parasites with IC50 values comparable to the reference were identified.
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Antiparasitarios/química , Antiparasitarios/farmacología , Bignoniaceae/química , Extractos Vegetales/farmacología , Animales , Cromatografía Líquida de Alta Presión , Halogenación , Leishmania mexicana , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/parasitología , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Extractos Vegetales/química , Raíces de Plantas/química , Espectrofotometría Ultravioleta , Tripanocidas/química , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacosRESUMEN
BACKGROUND: The aim of this study was to analyze patients diagnosed, staged and treated for orbital and eyelid B-cell lymphoma (OEL). METHODS: One hundred and forty-one cases of OEL were included in this study. Primary endpoints were to analyze the histopathologic findings, the main risk factors and the type of treatment and to correlate them with recurrence of OEL. The secondary endpoint was to determine the progression-free survival (PFS) time. RESULTS: Extranodal marginal zone B-cell lymphoma was the most frequent subtype (66%), followed by small lymphocytic lymphoma (12.7%), diffuse large B-cell lymphoma (DLBCL) (9.2%), follicular lymphoma (6.6%), mantle cell lymphoma (4.3%) and Burkitt lymphoma (1.2%). The probability of relapse was influenced by the histopathologic subtype DLBCL (OR = 7.7, 95% CI 1.8-32.3) and treatment with chemotherapy (OR = 14.9, 95% CI 2.6-83.7). Multivariate analysis showed that the histopathologic subtype DLBCL and chemotherapy treatment retained statistical significance for a poorer PFS, with hazard ratios of 8.581 (p = 0.0112) and 9.239 (p = 0.0094), respectively. CONCLUSIONS: Five lymphoma subtypes were found in patients with OEL. The histopathologic subtype and the type of treatment were found to be the main factors influencing treatment outcome.
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PURPOSE: To report the different uncommon pathogenesis of three cases of severe vertical restrictive strabismus associated with progressive unilateral proptosis with similar clinical features. METHODS: Case series of three patients who presented to the Orbit Outpatient Service of Policlinico Gemelli with a history of left progressive unilateral proptosis, slowly worsening vertical strabismus and the left eye fixed in downward position. A thorough hematologic work up was performed. All patients underwent complete abdomen ultrasonography, orbital contrast enhanced magnetic resonance imaging, forced duction test under general anesthesia, and orbital biopsy. RESULTS: Patients were 30, 60, and 46 years old respectively. MRI showed left inferior rectus enlargement in two cases and superior rectus enlargement in one case, with contrast enhanced combined muscle belly and tendon enlargement in all cases. Patients underwent forced duction test, muscle weakening (in two cases), and muscle biopsy with histopathologic examination. The superior rectus appeared infiltrated by an undifferentiated high-grade pleomorphic sarcoma, whereas the two inferior recti were positive for idiopathic orbital inflammatory disease with fibrosis areas and neuromuscular choristoma, respectively. CONCLUSION: Although proptosis and acquired vertical restrictive strabismus are most commonly associated with thyroid associated orbitopathy (TAO), they can also be a manifestation of many other conditions and the differential diagnosis can be particularly challenging. The three reported cases presented indeed with similar clinical features but had three distinct underlying orbital etiologies, two of which were extremely uncommon.
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PURPOSE: Combined hamartoma of the retina and retinal pigment epithelium is a rare benign tumor characterized by a variable combination of glial, vascular, and pigmented components. The purpose of our study was to analyze the features of combined hamartoma of the retina and retinal pigment epithelium on optical coherence tomography angiography. METHODS: Small case series of two cases of combined hamartoma of the retina and retinal pigment epithelium with macular and optic nerve involvement, evaluated with multimodal imaging including optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography. RESULTS: On optical coherence tomography, combined hamartoma of the retina and retinal pigment epithelium is characterized by disruption of the inner neurosensory retina and a variable degree of involvement of the external retina. Optical coherence tomography angiography showed diffuse alterations of the retinal vessels of the superficial and deeper layers, extended to the peripapillary area. Vessel abnormalities included increased tortuosity and caliber of vessels, vascular traction, and vessel stretching within the lesion. CONCLUSION: Optical coherence tomography angiography allows in-depth multilayer analysis of tumor vascular network, highlighting the fine abnormalities of retinal vasculature characteristic of combined hamartoma of the retina and retinal pigment epithelium.
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Hamartoma/diagnóstico , Imagen Multimodal , Enfermedades de la Retina/diagnóstico , Epitelio Pigmentado de la Retina/patología , Adulto , Femenino , Angiografía con Fluoresceína , Humanos , Masculino , Nervio Óptico/patología , Vasos Retinianos/patología , Estudios Retrospectivos , Tomografía de Coherencia Óptica , TracciónRESUMEN
PURPOSE: To report a single-center experience with non-thyroid causes of extraocular muscle enlargement (EME), describing the association between clinical-radiological findings at presentation and the final histopathological diagnosis. METHODS: Retrospective consecutive case series of 59 patients with single or multiple EME on orbital imaging, in the absence of an etiological diagnosis at the time of presentation. All patients were submitted to orbital muscle biopsy in order to achieve a final etiological diagnosis. Patients with a confirmed diagnosis of thyroid-associated orbitopathy and vascular causes of EME which were angiographically and clinically diagnosed were excluded. Orbital ultrasound and radiologic evaluation (CT and/or MRI) were performed before surgery in all cases. Main outcomes measured included initial clinical-radiological findings and final histopathological features of EME. RESULTS: A diagnosis of lymphoma was confirmed in 13 cases (22%). Sixteen cases (27%) were diagnosed as orbital inflammatory disease including nonspecific idiopathic orbital inflammatory disease in 9 cases, IgG4-related disease in 4 cases, and sclerosing idiopathic orbital inflammatory disease in 3 cases. In 11 patients (18%), a diagnosis of metastatic tumor was made, whereas sarcoidosis, vascular malformations, Erdheim-Chester, and necrobiotic xanthogranuloma were diagnosed in 8 eyes (13.5%). Three patients (5%) with single muscle enlargement developed Graves disease 10 months later. Four patients (6.7%) were diagnosed with granulomatosis with polyangiitis. In 2 cases (3.3%), the diagnosis was unknown, with inconclusive biopsy results. Differential patterns for inflammatory/vascular, lymphomatous and metastatic EME were identified based on age and gender distribution and clinical-radiological characteristics at presentation. CONCLUSIONS: Initial clinical and radiological features may orientate the differential diagnosis of non-thyroid EME.
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Enfermedades Orbitales , Seudotumor Orbitario , Humanos , Músculos Oculomotores/diagnóstico por imagen , Enfermedades Orbitales/diagnóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Leishmaniasis are diseases caused by parasites belonging to Leishmania genus. The treatment with pentavalent antimonials present high toxicity. Secondary line drugs, such as amphotericin B and miltefosine also have a narrow therapeutic index. Therefore, there is an urgent need to develop new drugs to treat leishmaniasis. Here, we present the in vitro anti-leishmanial activity of unusual dimeric flavonoids purified from Arrabidaea brachypoda. Three compounds were tested against Leishmana sp. Compound 2 was the most active against promastigotes. Quantifying the in vitro infected macrophages revealed that compound 2 was also the most active against intracellular amastigotes of L. amazonensis, without displaying host cell toxicity. Drug combinations presented an additive effect, suggesting the absence of interaction between amphotericin B and compound 2. Amastigotes treated with compound 2 demonstrated alterations in the Golgi and accumulation of vesicles inside the flagellar pocket. Compound 2-treated amastigotes presented a high accumulation of cytoplasmic vesicles and a myelin-like structure. When administered in L. amazonensis-infected mice, neither the oral nor the topical treatments were effective against the parasite. Based on the high in vitro activity, dimeric flavonoids can be used as a lead structure for the development of new molecules that could be useful for structure-active studies against Leishmania.
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Antiprotozoarios/uso terapéutico , Bignoniaceae/química , Flavonoides/uso terapéutico , Leishmania/efectos de los fármacos , Anfotericina B/uso terapéutico , Animales , Flavonoides/química , Leishmania/patogenicidad , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Estructura MolecularRESUMEN
PURPOSE: To evaluate long-term outcomes of progressively enlarging cosmetic customized prostheses (CCP) early after birth followed by dermis fat graft (DFG), as a strategy of socket rehabilitation in children with clinical congenital anophthalmia (CCA). METHODS: Twenty patients with unilateral and two patients with bilateral CCA were enrolled. All patients were treated by inserting a CCP at the time of their first assessment which was then enlarged. Subsequently they underwent DFG. Differences in vertical palpebral aperture (VPA) and horizontal palpebral length (HPL), between affected and unaffected sides, were recorded at the first CCP fitting as well as before and after DFG. Satisfaction with cosmetic results, prosthetic retention, and complications rate were assessed. Magnetic resonance imaging of the orbit was performed in all patients before and after surgery. RESULTS: A significant decrease in the difference between the normal and the anophthalmic side of both PA and HPL was found over follow-up. Both VPA and HPL differences decreased by 47.6% (10.5 mm, range 1-28 mm) and by 7.1% (5.8 mm, range 0-18 mm), respectively. Satisfaction in terms of cosmetic outcomes proved to be very positive, being "very satisfied" for families and "satisfied" for physicians. Excellent retention of prostheses was observed in all cases. CONCLUSIONS: A rehabilitating strategy combining early CCP and further DFG proved to be a valuable approach in children with CCA, offering significant benefits in terms of socket expansion, prosthetic retention, psychological impact, and cosmetic outcomes.
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Tejido Adiposo/trasplante , Dermis/trasplante , Ojo Artificial , Anoftalmos/cirugía , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Órbita/cirugía , Diseño de Prótesis , Estudios RetrospectivosRESUMEN
PURPOSE: To report the case of a 13-year-old girl with torpedo maculopathy, evaluated with multimodal morpho-functional retinal imaging, including fundus photography, infra-red and blue fundus autofluorescence, swept-source optical coherence tomography (OCT), en face OCT, OCT angiography and microperimetry (MP). OBSERVATIONS: On fundus examination, a torpedo-like hypopigmented lesion was observed temporal to the fovea in the left eye. OCT showed disruption of outer retinal layers and the presence of a subretinal cleft. On OCTA, a diffuse attenuation of signal from choriocapillaris was observed along the lesion. Functional analysis with MP revealed a reduction of retinal sensitivity over the lesion. CONCLUSIONS: and importance: On OCTA, torpedo maculopathy is characterized by vascular alterations of the choriocapillaris along the lesion.