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1.
Graefes Arch Clin Exp Ophthalmol ; 262(4): 1151-1159, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38047930

RESUMO

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.


Assuntos
Anticorpos Biespecíficos , Degeneração Macular , Degeneração Macular Exsudativa , Humanos , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese , Estudos Prospectivos , Injeções Intravítreas , Acuidade Visual , Ranibizumab , Receptores de Fatores de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular , Degeneração Macular/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Resultado do Tratamento , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico
2.
Ophthalmology ; 130(2): 213-222, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36154868

RESUMO

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.


Assuntos
Aprendizado Profundo , Humanos , Tomografia de Coerência Óptica/métodos , Retina/diagnóstico por imagem , Algoritmos
3.
J Nat Prod ; 83(9): 2631-2640, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32902988

RESUMO

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.


Assuntos
Antiparasitários/química , Antiparasitários/farmacologia , Bignoniaceae/química , Extratos Vegetais/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Halogenação , Leishmania mexicana , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Raízes de Plantas/química , Espectrofotometria Ultravioleta , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos
4.
Ophthalmic Plast Reconstr Surg ; 36(3): 284-291, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31789785

RESUMO

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.


Assuntos
Doenças Orbitárias , Pseudotumor Orbitário , Humanos , Músculos Oculomotores/diagnóstico por imagem , Doenças Orbitárias/diagnóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
5.
Retina ; 38(9): 1777-1785, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28699929

RESUMO

PURPOSE: To analyze the relationship between swelling of the arcuate nerve fiber layer (SANFL) and long-term decrease of retinal nerve fiber layer thickness after internal limiting membrane peeling for idiopathic epiretinal membrane, and to investigate if SANFL is related to a mechanical surgical damage. METHODS: Prospective, interventional consecutive case series of 46 eyes that underwent combined epiretinal membrane/internal limiting membrane peeling for idiopathic epiretinal membrane. Infrared, blue autofluorescence, color fundus imaging and measurement of retinal nerve fiber layer thickness in six peripapillary sectors by spectral-domain optical coherence tomography were performed preoperatively and at 2 weeks, 1, 3, 6, and 12 months after surgery. The presence of SANFL was checked postoperatively on infrared and blue autofluorescence fundus imaging, and the extent of each SANFL was measured on infrared fundus images. RESULTS: Areas of SANFL were identified in 39 eyes (84.8%) at 2-week follow-up. Retinal nerve fiber layer thickness significantly decreased in the temporal sectors at 1, 6, and 12 months (P < 0.0001). The linear extent of SANFL was significantly correlated with the percentage of reduction in retinal nerve fiber layer thickness in the temporal (R = 0.45; P < 0.0001) and infero-temporal (R = 0.23; P = 0.0008) sectors at 12 months of follow-up. Correspondence between sites of surgical grasping and the points of origin of SANFL was demonstrated on blue autofluorescence fundus images superimposed on intraoperative surgical frames. CONCLUSION: Early postoperative SANFL is correlated with late focal retinal nerve fiber layer thinning in the temporal sectors. Intraoperative surgical grasping seems to be a leading factor for the onset of SANFL.


Assuntos
Membrana Basal/cirurgia , Membrana Epirretiniana/cirurgia , Fibras Nervosas/patologia , Complicações Pós-Operatórias/patologia , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica/métodos , Cirurgia Vitreorretiniana/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Basal/patologia , Membrana Epirretiniana/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Acuidade Visual
6.
Molecules ; 24(1)2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30577423

RESUMO

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.


Assuntos
Antiprotozoários/uso terapêutico , Bignoniaceae/química , Flavonoides/uso terapêutico , Leishmania/efeitos dos fármacos , Anfotericina B/uso terapêutico , Animais , Flavonoides/química , Leishmania/patogenicidade , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , Estrutura Molecular
8.
Ophthalmologica ; 234(2): 101-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26183856

RESUMO

PURPOSE: To verify the efficacy of 25-gauge pars plana vitrectomy (PPV) for the management of posteriorly dislocated lens material after complicated cataract extraction and to determine in what patients this approach offers the optimal benefit in terms of efficacy and safety, considering the amount of retained nuclear material and the duration of surgery. METHODS: Forty eyes of 40 patients with retained lens fragments undergoing early (within 1 week) or late (within >1 week) 25-gauge PPV were retrospectively reviewed. The amount of dislocated nuclear material was graded by the surgeon intraoperatively, and the patients were divided into two groups according to the nuclear grading: group A (≤50% dropped nucleus) and group B (>50% dropped nucleus). The presence of brunescent nuclear pieces was considered. The outcomes measured included best-corrected visual acuity (BCVA) and postoperative complications such as retinal detachment, cystoid macular edema (CME) and postoperative ocular hypertension or hypotonia. RESULTS: The patients had a mean age of 78 years. The mean preoperative logarithm of the minimum angle of resolution (logMAR) BCVA was 0.57 ± 0.24 (20/80). A significant positive correlation was found between nuclear material grade and PPV duration (R2 = 0.81, p < 0.0001). None of the patients had dislocation of brunescent nuclear pieces. On postoperative day 1, the mean postoperative intraocular pressure was 16.75 ± 2.7 mm Hg, with no case of ocular hypotonia. At 6 months of follow-up, the mean logMAR BCVA improved to 0.23 ± 0.3 (20/32). Retinal detachment developed in 4 patients (10%), occurring only in patients of group B (p < 0.002). Four patients with late PPV developed postoperative CME, with no case of CME among patients with early vitrectomy (p = 0.014). CONCLUSION: Removal of dislocated lens fragments after complicated cataract surgery can be effectively managed with 25-gauge PPV, although it appears to be most efficient for cases with a limited amount of dislocated lens material. In consideration of the higher rate of retinal detachment observed in cases of prolonged PPV time, the expected duration of surgery should be taken into account when choosing the best surgical approach. Visual outcomes are not affected by the timing of PPV, whereas early vitrectomy seems to prevent the onset of inflammatory macular edema.


Assuntos
Subluxação do Cristalino/cirurgia , Microcirurgia/métodos , Facoemulsificação/efeitos adversos , Vitrectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pressão Intraocular/fisiologia , Subluxação do Cristalino/etiologia , Subluxação do Cristalino/fisiopatologia , Masculino , Fatores de Tempo , Acuidade Visual/fisiologia
10.
Br J Ophthalmol ; 107(6): 750-755, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35101939

RESUMO

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.


Assuntos
Anoftalmia , Cistos , Microftalmia , Humanos , Pré-Escolar , Anoftalmia/cirurgia , Microftalmia/cirurgia , Microftalmia/complicações , Estudos Retrospectivos , Olho , Cistos/diagnóstico , Cistos/cirurgia , Órbita/cirurgia
11.
Artigo em Inglês | MEDLINE | ID: mdl-37850973

RESUMO

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.

12.
BMJ Open ; 12(2): e055845, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35105593

RESUMO

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).


Assuntos
Oftalmologia , Optometria , Doenças Retinianas , Telemedicina , Inteligência Artificial , Humanos , Oftalmologia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Encaminhamento e Consulta , Doenças Retinianas/diagnóstico , Telemedicina/métodos
13.
Eye (Lond) ; 35(1): 299-306, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33082533

RESUMO

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.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Retinopatia Diabética/diagnóstico por imagem , Humanos , Fotografação , Encaminhamento e Consulta , Estudos Retrospectivos , Lâmpada de Fenda , Microscopia com Lâmpada de Fenda , Medicina Estatal , Tomografia de Coerência Óptica
14.
Eur J Ophthalmol ; 31(3): 1399-1404, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32418449

RESUMO

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.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Pálpebras/patologia , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Estados Unidos
15.
J Vis Exp ; (174)2021 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-34424241

RESUMO

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.


Assuntos
Leishmania braziliensis , Células Cultivadas , Humanos , Imunidade Inata , Leucócitos Mononucleares , Macrófagos , Monócitos
16.
Eur J Ophthalmol ; : 1120672120946929, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32720817

RESUMO

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.

17.
Eur J Ophthalmol ; 30(3): 595-599, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30764657

RESUMO

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.


Assuntos
Hamartoma/diagnóstico , Imagem Multimodal , Doenças Retinianas/diagnóstico , Epitélio Pigmentado da Retina/patologia , Adulto , Feminino , Angiofluoresceinografia , Humanos , Masculino , Nervo Óptico/patologia , Vasos Retinianos/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Tração
18.
Cancers (Basel) ; 12(9)2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32906630

RESUMO

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.

19.
Am J Ophthalmol Case Rep ; 10: 165-168, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29780930

RESUMO

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.

20.
Biomedicines ; 6(1)2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29414877

RESUMO

Although introduced for the treatment of maculopathies, photodynamic therapy (PDT) is now largely used in some eye cancers treatment. The selective tissue damage with PDT is achieved by sequestration of the photosensitizer in the target tissue and focal activation of the photosensitizer by low energy directed light. In this way, it is possible to achieve the destruction of the tumor tissue by safeguarding the surrounding healthy structures. Our study describes the clinical uses and efficacy of photodynamic therapy in ocular oncology.

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