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BACKROUD: Keratitis caused by Lasiodiplodia theobromae is rare and typically associated with a poor prognosis. Current literature lacks sufficient evidence on effective management of patients with this condition. CASE PRESENTATION: A 74-year-old former agricultural worker presented with a red right eye, discomfort, and decreased visual acuity, progressing over three days without treatment. Examination revealed type 2 diabetes and a non-perforating, spiculated corneal abscess with a hypopyon in the right eye. Initial treatment included a triple antibiotic therapy and supportive care. Direct mycological examination identified numerous septate mycelial filaments. Antifungal treatment with natamycin and voriconazole, both topically and orally, was initiated. Cultures confirmed Lasiodiplodia theobromae. The patient showed significant improvement. Treatment continued for eight weeks, with a final visual acuity of 20/50 due to a stromal scar. CONCLUSION: An extensive literature review conducted in November 2023, using databases such as PubMed and Google Scholar with the keywords "lasiodiplodia" and "keratitis" yielded no previous cases of this specific condition being managed solely with the combined use of natamycin and voriconazole. This antifungal combination is commonly included in most management protocols for fungal keratitis. Factors such as the use of corticosteroids and delayed diagnosis were noted to adversely affect the prognosis. This case and this systematic review underscores the potential for non-surgical management options in severe fungal keratitis.
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Antifúngicos , Ascomicetos , Infecciones Fúngicas del Ojo , Humanos , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/diagnóstico , Anciano , Antifúngicos/uso terapéutico , Ascomicetos/aislamiento & purificación , Masculino , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Queratitis/diagnóstico , Voriconazol/uso terapéutico , Agudeza Visual/fisiología , Natamicina/uso terapéutico , Quimioterapia CombinadaRESUMEN
Timely and effective diagnosis of fungal keratitis (FK) is necessary for suitable treatment and avoiding irreversible vision loss for patients. In vivo confocal microscopy (IVCM) has been widely adopted to guide the FK diagnosis. We present a deep learning framework for diagnosing fungal keratitis using IVCM images to assist ophthalmologists. Inspired by the real diagnostic process, our method employs a two-stage deep architecture for diagnostic predictions based on both image-level and sequence-level information. To the best of our knowledge, we collected the largest dataset with 96,632 IVCM images in total with expert labeling to train and evaluate our method. The specificity and sensitivity of our method in diagnosing FK on the unseen test set achieved 96.65% and 97.57%, comparable or better than experienced ophthalmologists. The network can provide image-level, sequence-level and patient-level diagnostic suggestions to physicians. The results show great promise for assisting ophthalmologists in FK diagnosis.
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Queratitis , Microscopía Confocal , Microscopía Confocal/métodos , Queratitis/microbiología , Queratitis/diagnóstico , Queratitis/diagnóstico por imagen , Humanos , Aprendizaje Profundo , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/diagnóstico por imagen , Infecciones Fúngicas del Ojo/patología , Redes Neurales de la Computación , Sensibilidad y EspecificidadRESUMEN
ABSTRACT: Keratomycosis is a serious corneal infection associated with high ocular morbidity that can lead to severe vision loss. It is estimated to affect more than 1 million patients annually, most commonly occurring in tropical climates, and represents a growing threat to patients worldwide. Despite aggressive medical management, fungal infections have a higher rate of perforation requiring surgical intervention compared with other infectious etiologies. Early diagnosis and appropriate treatment are keys to preserving vision and saving patients' eyes.Timely diagnosis of fungal keratitis helps minimize corneal damage and scarring and increases the likelihood of a favorable outcome. Studies have shown that correct identification of fungal infections is often delayed up to 2 to 3 weeks after initial presentation. This leads to incorrect or ineffective treatment for many patients. Diagnostic techniques explored in this study include corneal scrapings with staining and culture, visualization with in vivo confocal microscopy, molecular diagnostic techniques including polymerase chain reaction, and recently developed omics-based technologies.Treatment of fungal keratitis begins with topical antifungals. Medical management has been proven to be effective, but with limitations including poor drug penetration and low bioavailability. Cases that do not respond to topical therapy require more invasive and novel treatments to control the infection. We review the clinical trials that have shaped current practice patterns, with focus on the efficacy of topical natamycin as the primary therapy for filamentous fungal keratitis. We explore additional management strategies such as localized intrastromal and intracameral injections of antifungal medications, photodynamic therapy, and surgical intervention.
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Antifúngicos , Infecciones Fúngicas del Ojo , Queratitis , Humanos , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/terapia , Antifúngicos/uso terapéutico , Queratitis/diagnóstico , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Microscopía ConfocalRESUMEN
BACKGROUND: Mycotic keratitis (MK) represents a corneal infection, with Fusarium species identified as the leading cause. Fusarium is a genus of filamentous fungi commonly found in soil and plants. While many Fusarium species are harmless, some can cause serious infections in humans and animals, particularly Fusarium keratitis, that can lead to severe ocular infections, prevalent cause of monocular blindness in tropical and subtropical regions of the world. Due to its incidence and importance in ophthalmology, we conducted a systematic analysis of clinical cases to increase our understanding of Fusarium keratitis by gathering clinical and demographic data. METHODS: To conduct an analysis of Fusarium keratitis, we looked through the literature from the databases PubMed, Embase, Lilacs, and Google Scholar and found 99 papers that, between March 1969 and September 2023, corresponded to 163 cases of Fusarium keratitis. RESULTS: Our analysis revealed the Fusarium solani species complex as the predominant isolate, with females disproportionately affected by Fusarium keratitis. Notably, contact lens usage emerged as a significant risk factor, implicated in nearly half of cases. Diagnosis primarily relied on culture, while treatment predominantly involved topical natamycin, amphotericin B, and/or voriconazole. Surprisingly, our findings demonstrated a prevalence of cases originating from the United States, suggesting potential underreporting and underestimation of this mycosis in tropical regions. This shows the imperative for heightened vigilance, particularly in underdeveloped regions with substantial agricultural activity, where Fusarium infections may be more prevalent than currently reported. CONCLUSION: Our study sheds light on the clinical complexities of Fusarium keratitis and emphasizes the need for further research and surveillance to effectively tackle this vision-threatening condition. Furthermore, a timely identification and early initiation of antifungal treatment appear to be as important as the choice of initial treatment itself.
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Antifúngicos , Fusariosis , Fusarium , Queratitis , Humanos , Queratitis/microbiología , Queratitis/epidemiología , Queratitis/tratamiento farmacológico , Fusarium/aislamiento & purificación , Fusarium/clasificación , Fusarium/genética , Fusariosis/microbiología , Fusariosis/tratamiento farmacológico , Fusariosis/epidemiología , Fusariosis/diagnóstico , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/epidemiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Femenino , Voriconazol/uso terapéutico , Prevalencia , Factores de Riesgo , Masculino , Adulto , Persona de Mediana Edad , Lentes de Contacto/microbiología , Lentes de Contacto/efectos adversos , Anfotericina B/uso terapéutico , Natamicina/uso terapéutico , Anciano , Adulto Joven , AdolescenteRESUMEN
Purpose: to explore the anti-inflammatory effects of a nanobody (Nb) specific to ß-glucan on fungal keratitis (FK). Methods: in order to verify the therapeutic and anti-inflammatory efficacy of Nb in FK, the severity of inflammation was assessed with inflammatory scores, hematoxylin-eosin (HE) staining, and myeloperoxidase (MPO) assays. In corneas of mice of FK model and human corneal epithelial cells stimulated by fungal hyphae, real-time reverse transcriptase polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay were used to detect the expression levels of inflammatory cytokines and pattern recognition receptors (PRRs). In vivo, macrophages and neutrophils infiltration in the cornea stroma was detected by immunofluorescence (IFS) staining. Results: In murine models infected with Aspergillus fumigatus (A. fumigatus), Nb treatment could reduce the inflammatory scores. HE staining and MPO results showed Nb significantly alleviated corneal edema and reduced inflammatory cell infiltration 3 days post-infection. In addition, the expression levels of LOX-1 and Dectin-1 were significantly decreased in the Nb group in vivo. The expression of chemokines CCL2 and CXCL2 also decreased in the Nb group. Compared with the PBS group, the number of macrophages and neutrophils in the Nb group was significantly decreased, which was shown in IFS results. Moreover, Nb attenuated the expression of Dectin-1, LOX-1, and inflammatory mediators, including IL-6 and IL-8 in vitro. Conclusion: our study showed that Nb could alleviate FK by downregulating the expression of PRRs and inflammatory factors as well as reducing the infiltration of macrophages and neutrophils.
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Antiinflamatorios , Aspergillus fumigatus , Modelos Animales de Enfermedad , Queratitis , Anticuerpos de Dominio Único , beta-Glucanos , Animales , Queratitis/tratamiento farmacológico , Queratitis/microbiología , Ratones , beta-Glucanos/farmacología , Antiinflamatorios/farmacología , Humanos , Anticuerpos de Dominio Único/farmacología , Pared Celular/química , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Aspergilosis/inmunología , Córnea/efectos de los fármacos , Citocinas/metabolismo , Macrófagos/efectos de los fármacos , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunologíaRESUMEN
Fungal keratitis (FK) is a leading cause of preventable blindness and eye loss. The poor antifungal activity, increased drug resistance, limited corneal permeability, and unsatisfactory biosafety of conventional antifungal eye drops are among the majority of the challenges that need to be addressed for currently available antifungal drugs. Herein, this study proposes an effective strategy that employs chitosan-poly(ethylene glycol)-LK13 peptide conjugate (CPL) in the treatment of FK. Nanoassembly CPL can permeate the lipophilic corneal epithelium in the transcellular route, and its hydrophilicity surface is a feature to drive its permeability through hydrophilic stroma. When encountering fungal cell membrane, CPL dissembles and exposes the antimicrobial peptide (LK13) to destroy fungal cell membranes, the minimum inhibitory concentration values of CPL against Fusarium solani (F. solani) are always not to exceed 8 µg peptide/mL before and after drug resistance induction. In a rat model of Fusarium keratitis, CPL demonstrates superior therapeutic efficacy than commercially available natamycin ophthalmic suspension. This study provides more theoretical and experimental supports for the application of CPL in the treatment of FK.
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Antifúngicos , Quitosano , Córnea , Farmacorresistencia Fúngica , Fusarium , Queratitis , Pruebas de Sensibilidad Microbiana , Polietilenglicoles , Quitosano/química , Quitosano/farmacología , Queratitis/tratamiento farmacológico , Queratitis/microbiología , Antifúngicos/farmacología , Antifúngicos/química , Fusarium/efectos de los fármacos , Animales , Ratas , Farmacorresistencia Fúngica/efectos de los fármacos , Polietilenglicoles/química , Córnea/efectos de los fármacos , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Permeabilidad/efectos de los fármacos , Fusariosis/tratamiento farmacológico , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Natamicina/farmacología , Natamicina/administración & dosificación , Masculino , Modelos Animales de Enfermedad , Ratas Sprague-DawleyRESUMEN
INTRODUCTION: This research aims to describe clinical findings, epidemiology and treatment outcomes in patients with filamentous fungi keratitis of a tertiary centre in Germany over a 7-year period and to compare the efficacy of different antifungal treatments and the effect of additive topical steroids. METHODS: This retrospective study included 25 eyes of 23 patients from October 2013 to December 2020 with cultural isolates of filamentous fungi and corresponding keratitis. Best-corrected visual acuity (BCVA), clinical signs, symptoms, risk factors and outcome were extracted from medical records. RESULTS: Improvement of BVCA was noted in 68% of eyes. Mean BCVA of the study population increased from 0.75 logMAR [median 0.40, standard deviation (SD) 0.82, range 0-2.3] to 0.48 logMAR (median 0.10, SD 0.88, range - 0.1 to 3). The most commonly used antifungal topical treatment was a combination of natamycin 5% and voriconazole 2% (44% of eyes), followed by voriconazole 2% in 36% of cases. An antiinflammatory topical steroid was applied in 52%. In 16% of the eyes, penetrating keratoplasty (pKP) was performed. CONCLUSION: Diagnosis of filamentous fungi keratitis is often difficult or delayed. Outcomes can be poor even with intensive treatment because of high resistance to common antifungals. Access to natamycin 5% seems to lead to favourable outcomes in filamentous fungi keratitis.
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Antifúngicos , Infecciones Fúngicas del Ojo , Queratitis , Humanos , Estudios Retrospectivos , Femenino , Masculino , Antifúngicos/uso terapéutico , Persona de Mediana Edad , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Anciano , Adulto , Voriconazol/uso terapéutico , Anciano de 80 o más Años , Agudeza Visual , Resultado del Tratamiento , Natamicina/uso terapéutico , Queratoplastia PenetranteRESUMEN
BACKGROUND: Keratomycosis is a form of infectious keratitis, an infection of the cornea, which is caused by fungi. This disease is a leading cause of ocular morbidity globally with at least 60 % of the affected individuals becoming monocularly blind. OBJECTIVE: This bibliometric analysis aimed to comprehensively assess the existing body of literature, providing insights of the evolution of keratomycosis research by identifying key themes and research gaps. METHODS: This work used the modeling method Latent Dirichlet Allocation (LDA) to identify and interpret scientific information on topics concerning existing categories in a set of documents. The HJ-Biplot method was also used to determine the relationship between the analyzed topics, taking into consideration the years under study. RESULTS: This bibliometric analysis was performed on a total of 2,599 scientific articles published between 1992 and 2022. The five leading countries with more scientific production and citations on keratomycosis were The United States of America, followed by India, China, United Kingdom and Australia. The top five topics studied were Case Reports and Corneal Infections, which exhibited a decreasing trend; followed by Penetrating Keratoplasty and Corneal Surgery, Ocular Effects of Antifungal Drugs, Gene Expression and Inflammatory Response in the Cornea and Patient Data which have been increasing throughout the years. However Filamentous Fungi and Specific Pathogens, and Antifungal Therapies research has been decreasing in trend. CONCLUSION: Additional investigation into innovative antifungal drug therapies is crucial for proactively tackling the potential future resistance to antifungal agents in scientific writing.
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Bibliometría , Infecciones Fúngicas del Ojo , Queratitis , Humanos , Queratitis/microbiología , Infecciones Fúngicas del Ojo/microbiología , Antifúngicos/uso terapéutico , Salud Global , Hongos/clasificación , Hongos/aislamiento & purificación , Córnea/microbiologíaRESUMEN
A 40-year-old man presented with recurrent ocular surface masses in his left eye persisting for over a year. Despite undergoing resection of the conjunctival mass and receiving anti-inflammatory treatment at another hospital, the mass reappeared within a week post-surgery. Over the past 6 months, the mass gradually increased in size, accompanied by a decline in vision. Following conjunctival mass excision combined with amniotic membrane transplantation at Beijing Tongren Hospital, Capital Medical University, histopathological examination revealed a fungal infection of the conjunctiva, resulting in a diagnosis of fungal conjunctivitis and conjunctival granuloma in the left eye. The patient received systemic antifungal medications and local therapy, resulting in a stable condition with no recurrence of the mass.
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Infecciones Fúngicas del Ojo , Humanos , Masculino , Adulto , Infecciones Fúngicas del Ojo/diagnóstico , Conjuntiva/patología , Enfermedades de la Conjuntiva/diagnóstico , Enfermedades de la Conjuntiva/microbiología , Recurrencia , Conjuntivitis/diagnóstico , Conjuntivitis/microbiología , Granuloma/diagnóstico , Antifúngicos/uso terapéuticoRESUMEN
Fungal keratitis is a severe corneal infection characterized by suppurative and ulcerative lesions. Aspergillus fumigatus is a common cause of fungal keratitis. Antifungal drugs, such as natamycin, are currently the first-line treatment for fungal keratitis, but their ineffectiveness leads to blindness and perforation. Additionally, the development of fungal resistance makes treating fungal keratitis significantly more challenging. The present study used platelet-derived biomaterial (PDB) to manage A. fumigatus keratitis in the animal model. Freezing and thawing processes were used to prepare PDB, and then A. fumigatus keratitis was induced in the mice. Topical administration of PDB, natamycin, and plasma was performed; quantitative real-time PCR (qPCR) and histopathologic examination (HE) were used to assess the inhibitory effect of the mentioned compounds against fungal keratitis. The qPCR results showed that PDB significantly decreased the count of A. fumigatus compared to the control group (P-value ≤ 5). Natamycin also remarkably reduced the count of fungi in comparison to the untreated animal, but its inhibitory effect was not better than PDB (P-value > 5). The findings of HE also demonstrated that treatment with PDB and natamycin decreased the fungal loads in the corneal tissue. However, plasma did not show a significant inhibitory effect against A. fumigatus. PDB is intrinsically safe and free of any infections or allergic responses; additionally, this compound has a potential role in decreasing the burden of A. fumigatus and treating fungal keratitis. Therefore, scientists should consider PDB an applicable approach to managing fungal keratitis and an alternative to conventional antifungal agents.
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Antifúngicos , Aspergilosis , Aspergillus fumigatus , Queratitis , Aspergillus fumigatus/efectos de los fármacos , Animales , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Ratones , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Modelos Animales de Enfermedad , Materiales Biocompatibles , Plaquetas/efectos de los fármacos , Natamicina/farmacología , Natamicina/administración & dosificación , Natamicina/uso terapéutico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Córnea/microbiología , Córnea/patología , Córnea/efectos de los fármacosRESUMEN
This case report discusses a diagnosis of rhino-orbital-cerebral mucormycosis in a man aged 61 years who presented with vision loss, ophthalmoplegia, and ptosis.
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Infecciones Fúngicas del Ojo , Mucormicosis , Enfermedades Orbitales , Humanos , Mucormicosis/diagnóstico , Mucormicosis/microbiología , Mucormicosis/tratamiento farmacológico , Enfermedades Orbitales/microbiología , Enfermedades Orbitales/diagnóstico , Enfermedades Orbitales/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Masculino , Antifúngicos/uso terapéutico , Imagen por Resonancia Magnética , Enfermedades de los Senos Paranasales/microbiología , Enfermedades de los Senos Paranasales/diagnóstico , Enfermedades de los Senos Paranasales/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Enfermedades Nasales/microbiología , Enfermedades Nasales/diagnóstico , Enfermedades Nasales/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Anfotericina B/uso terapéuticoRESUMEN
BACKGROUND: Infectious keratitis, a significant contributor to blindness, with fungal keratitis accounting for nearly half of cases, poses a formidable diagnostic and therapeutic challenge due to its delayed clinical presentation, prolonged culture times, and the limited availability of effective antifungal medications. Furthermore, infections caused by rare fungal strains warrant equal attention in the management of this condition. CASE PRESENTATION: A case of fungal keratitis was presented, where corneal scraping material culture yielded pink colonies. Lactophenol cotton blue staining revealed distinctive spore formation consistent with the Fusarium species. Further analysis using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) identified the causative agent as Fusarium proliferatum. However, definitive diagnosis of Pseudonectria foliicola infection was confirmed through ITS sequencing. The patient's recovery was achieved with a combination therapy of voriconazole eye drops and itraconazole systemic treatment. CONCLUSION: Pseudonectria foliicola is a plant pathogenic bacterium that has never been reported in human infections before. Therefore, ophthalmologists should consider Pseudonectria foliicola as a possible cause of fungal keratitis, as early identification and timely treatment can help improve vision in most eyes.
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Antifúngicos , Infecciones Fúngicas del Ojo , Fusarium , Queratitis , Voriconazol , Humanos , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Queratitis/diagnóstico , Antifúngicos/uso terapéutico , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Voriconazol/uso terapéutico , Fusarium/aislamiento & purificación , Fusarium/efectos de los fármacos , Fusarium/patogenicidad , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Itraconazol/uso terapéutico , Fusariosis/tratamiento farmacológico , Fusariosis/microbiología , Fusariosis/diagnóstico , Masculino , Córnea/microbiología , Córnea/patología , Femenino , Persona de Mediana EdadRESUMEN
PURPOSE: To study the risk factors, clinical features, and treatment outcomes of patients with culture-negative keratitis (CNK). METHODS: A retrospective data review of 933 patients with CNK was performed from January 2018 to December 2020. The variables such as the history of injury, visual acuity, slit-lamp findings with measurements of size and depth of ulcer, microbiological evaluation, duct patency, blood glucose levels, and treatment were considered, and clinical outcome was analyzed. RESULTS: Of the 933 patients with CNK, 763 (81.8%) were medically managed, with a mean treatment duration of 2.08 ± 1.7 weeks. Among them, 622 (66.7%) were both smear and culture-negative, and 311 (33.3%) showed only smear positivity. Smear-positive patients showed a positive correlation with the history of injury. A higher incidence of fungal growth on repeat culture was observed. Surgical interventions were done only in 18.2% of the patients; the rest were treated with topical medications alone. CONCLUSION: High clinical suspicion, differentiation of causative organisms based on clinical findings, and initiating empirical therapy with broad-spectrum antibiotics and antifungals improve the ultimate prognosis in patients with CNK, even though a standard protocol for empirical medical treatment may differ among institutions and surgeons based on their clinical experience and geographical variations.
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Antibacterianos , Infecciones Bacterianas del Ojo , Infecciones Fúngicas del Ojo , Agudeza Visual , Humanos , Estudios Retrospectivos , Femenino , Masculino , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Persona de Mediana Edad , Agudeza Visual/fisiología , Adulto , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/terapia , Antibacterianos/uso terapéutico , Bacterias/aislamiento & purificación , Antifúngicos/uso terapéutico , Queratitis/microbiología , Queratitis/diagnóstico , Queratitis/tratamiento farmacológico , Factores de Riesgo , Estudios de Seguimiento , Hongos/aislamiento & purificación , Córnea/microbiología , Córnea/patología , AncianoRESUMEN
Introduction. Aspergillus flavus and Fusarium keratoplasticum are common causative pathogens of fungal keratitis (FK), a severe corneal disease associated with significant morbidity and vision loss. Escalating incidence of antifungal resistance to available antifungal drugs poses a major challenge to FK treatment. Cold atmospheric plasma (CAP) is a pioneering nonpharmacologic antimicrobial intervention that has demonstrated potential as a broad-spectrum antifungal treatment.Gap statement. Previous research highlights biofilm-associated resistance as a critical barrier to effective FK treatment. Although CAP has shown promise against various fungal infections, its efficacy against biofilm and conidial forms of FK pathogens remains inadequately explored.Aim. This study aims to investigate the antifungal efficacy of CAP against clinical fungal keratitis isolates of A. flavus and F. keratoplasticum in vitro.Methodology. Power parameters (22-27 kVpp, 300-400 Hz and 20-80 mA) of a dielectric barrier discharge CAP device were optimized for inactivation of A. flavus biofilms. Optimal applied voltage and total current were applied to F. keratoplasticum biofilms and conidial suspensions of A. flavus and F. keratoplasticum. The antifungal effect of CAP treatment was investigated by evaluating fungal viability through means of metabolic activity, c.f.u. enumeration (c.f.u. ml-1) and biofilm formation.Results. For both fungal species, CAP exhibited strong time-dependent inactivation, achieving greater than 80â% reduction in metabolic activity and c.f.u. ml-1 within 300 s or less, and complete inhibition after 600 s of treatment.Conclusion. Our findings indicate that CAP is a promising broad-spectrum antifungal intervention. CAP treatment effectively reduces fungal viability in both biofilm and conidial suspension cultures of A. flavus and F. keratoplasticum, suggesting its potential as an alternative treatment strategy for fungal keratitis.
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Antifúngicos , Aspergillus flavus , Biopelículas , Fusarium , Queratitis , Gases em Plasma , Esporas Fúngicas , Aspergillus flavus/efectos de los fármacos , Fusarium/efectos de los fármacos , Biopelículas/efectos de los fármacos , Gases em Plasma/farmacología , Esporas Fúngicas/efectos de los fármacos , Antifúngicos/farmacología , Queratitis/microbiología , Infecciones Fúngicas del Ojo/microbiología , Humanos , Fusariosis/microbiología , Viabilidad Microbiana/efectos de los fármacosRESUMEN
OBJECTIVES: To investigate the epidemiological characteristics and clinical outcomes of culture-proven bacterial and fungal keratitis at a single tertiary referral centre on Jeju Island, South Korea. DESIGN: A retrospective study design. SETTING: Data from a solitary referral centre on Jeju Island spanning January 2011 to December 2022. PARTICIPANTS: Among the 245 patients clinically diagnosed with infectious microbial keratitis, 110 individuals had culture-positive results. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the identification of causative microbial profiles and epidemiological characteristics, while the secondary outcome was the correlation of these factors with treatment outcomes. RESULTS: Of 245 patients, 110 (44.9%) had culture-positive infectious keratitis, showing 69 bacterial, 32 fungal, 4 superimposed bacterial and 5 cases with coinfection by bacteria and fungus. The most common pathogen was Pseudomonas species in 14.4% of the bacterial keratitis cases, followed by Staphylococcus epidermidis (9%), Staphylococcus aureus (8%) and Moraxella species (7%). The total treatment success rate for bacterial keratitis was 67.5%. The frequency of methicillin-resistant Staphylococcus on Jeju Island did increase during the study period. Fusarium species had the highest incidence at 22.2%, followed by Candida (16.7%) and Colletotrichum species (11.1%). 56.7% of fungal keratitis patients were successfully treated. An initial large corneal lesion (>3 mm) showed a statistically significant association with treatment failure. CONCLUSION: The incidence of Moraxella and Colletotrichum species in our study was higher than that reported in other districts with different climates and environments. The results reported here reflect the unique environmental features of Jeju Island, characterised by high humidity and temperatures.
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Infecciones Fúngicas del Ojo , Queratitis , Humanos , Estudios Retrospectivos , República de Corea/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Queratitis/epidemiología , Queratitis/microbiología , Adulto , Anciano , Infecciones Fúngicas del Ojo/epidemiología , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Bacterianas del Ojo/epidemiología , Infecciones Bacterianas del Ojo/microbiología , Antibacterianos/uso terapéutico , Incidencia , Centros de Atención Terciaria/estadística & datos numéricosRESUMEN
Purpose: The purpose of this study was to investigate the role and mechanism of microtubule-associated protein light chain-3 (LC3)-associated phagocytosis (LAP) in the immune response to Aspergillus fumigatus (A. fumigatus) keratitis. Methods: The formation of single-membrane phagosomes was visualized in the corneas of healthy or A. fumigatus-infected humans and C57BL/6 mice using transmission electron microscopy (TEM). Rubicon siRNA (si-Rubicon) was used to block Rubicon expression. RAW 264.7 cells or mice corneas were infected with A. fumigatus with or without pretreatment of si-Rubicon and scrambled siRNA. RAW 264.7 cells were pretreated with Dectin-1 antibody or Dectin-1 overexpressed plasmid and then stimulated with A. fumigatus. Flow cytometry was used to label macrophages in normal and infected corneas of mice. In mice with A. fumigatus keratitis, the severity of the disease was assessed using clinical scores. We used lentiviral technology to transfer GV348-Ubi-GFP-LC3-II-SV40-Puro Lentivirus into the mouse cornea. The GFP-LC3 fusion protein was visualized in corneal slices using a fluorescence microscope. We detected the mRNA and protein expressions of the inflammatory factors IL-6, IL-1ß, and IL-10 using real-time PCR (RT-PCR) and ELISA. We detected the expression of LAP-related proteins Rubicon, ATG-7, Beclin-1, and LC3-II using Western blot or immunofluorescence. Results: Accumulation of single-membrane phagosomes within macrophages was observed in the corneas of patients and mice with A. fumigatus keratitis using TEM. Flow cytometry (FCM) analysis results show that the number of macrophages in the cornea of mice significantly increases after infection with A. fumigatus. LAP-related proteins were significantly elevated in the corneas of mice and RAW 264.7 cells after infection with A. fumigatus. The si-Rubicon treatment elevated the clinical score of mice. In A. fumigatus keratitis mice, the si-Rubicon treated group showed significantly higher expression of IL-6 and IL-1ß and lower expression of IL-10 and LC3-II compared to the control group. In RAW 264.7 cells, treatment with the Dectin-1 overexpressed plasmid upregulated the expression of LAP-related proteins, a process that was significantly inhibited by the Dectin-1 antibody. Conclusions: LAP participates in the anti-inflammatory immune process of fungal keratitis (FK) and exerts an anti-inflammatory effect. LAP is regulated through the Dectin-1 signaling pathway in A. fumigatus keratitis.
Asunto(s)
Aspergilosis , Aspergillus fumigatus , Infecciones Fúngicas del Ojo , Queratitis , Ratones Endogámicos C57BL , Proteínas Asociadas a Microtúbulos , Fagocitosis , Animales , Femenino , Humanos , Ratones , Aspergilosis/microbiología , Aspergilosis/metabolismo , Aspergilosis/inmunología , Córnea/metabolismo , Córnea/microbiología , Córnea/patología , Modelos Animales de Enfermedad , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/metabolismo , Citometría de Flujo , Queratitis/microbiología , Queratitis/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Microscopía Electrónica de Transmisión , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genéticaRESUMEN
PURPOSE: Invasive fungal orbital infections (IFOI) may be difficult to differentiate from sinogenic bacterial orbital cellulitis (OC). This study investigates the features differentiating OC from IFOI on magnetic resonance imaging (MRI). METHODS: Retrospective study of adult patients with sinogenic OC and IFOI with pre-intervention MRI. Patients without post-septal involvement, non-sinogenic OC (e.g.: secondary to trauma) and poor-quality scans were excluded. Independent Sample's t test and Fisher's exact test were conducted with p < 0.05 deemed statistically significant. RESULTS: Eleven cases each of OC (Mean age: 41.6 ± 18.4 years-old, Male: 10) and IFOI (Mean age: 65.0 ± 16.6 years-old, Male: 9) between 2006 and 2023. IFOI patients were older, more likely immunocompromised and had a lower mean white-cell count (p value = 0.005, 0.035 and 0.017, respectively). The ethmoid and maxillary sinuses were most commonly involved in both entities. Pre-septal and lacrimal gland involvement were more common in OC (p = 0.001 and 0.008, respectively). Infiltrative OC orbital lesions were poorly demarcated, whilst those in IFOI were expansile/mass-like invading the orbit from the adjacent paranasal sinuses. Specific IFOI features included loss-of-contrast-enhancement (LoCE) of paranasal sinus tissues with orbital extension. Extra-orbital and -sinonasal extension indicative of IFOI included contiguous skull base or pterygopalatine fossa involvement, retro-antral and masticator space stranding and vasculitis. CONCLUSION: This study describes the key MRI features of IFOI including differentiating markers from OC. These specific features, such as LoCE of the paranasal and orbital soft tissues, the location and pattern of contiguous soft-tissue involvement, provide expedient identification of IFOI which necessitate early surgical intervention for microbiological confirmation of an invasive fungal pathology.
Asunto(s)
Infecciones Bacterianas del Ojo , Infecciones Fúngicas del Ojo , Imagen por Resonancia Magnética , Celulitis Orbitaria , Humanos , Masculino , Celulitis Orbitaria/microbiología , Celulitis Orbitaria/diagnóstico , Estudios Retrospectivos , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/microbiología , Adulto , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/microbiología , Anciano , Diagnóstico Diferencial , Femenino , Adulto Joven , Anciano de 80 o más Años , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/microbiología , Infecciones Fúngicas Invasoras/diagnóstico por imagenRESUMEN
A 32-year-old contact lens-wearing man with recent travel history to the Caribbean was referred for a corneal infiltrate in the left eye that worsened following 1-week of steroid-antibiotic therapy. Corneal cultures were obtained and sent to our facility's clinical microbiology laboratory for analysis. Same-day in vivo confocal microscopy revealed fungal elements. Nucleic acid sequencing performed on the isolated determined it to be a member of the entomopathogenic genus Metarhizium. Over the course of 3 months, the patient's corneal infiltrate ultimately resolved following topical natamycin 5 % therapy. This is the first reported case to have originated in the Caribbean and to utilize in vivo confocal microscopy to aid diagnosis. Our case also supports previous reports of success with natamycin therapy in treatment of Metarhizium sp. keratitis.
Asunto(s)
Antifúngicos , Queratitis , Metarhizium , Microscopía Confocal , Natamicina , Humanos , Natamicina/uso terapéutico , Natamicina/administración & dosificación , Masculino , Metarhizium/genética , Metarhizium/aislamiento & purificación , Adulto , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Queratitis/diagnóstico , Antifúngicos/uso terapéutico , Región del Caribe , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/diagnóstico , Resultado del Tratamiento , Administración Tópica , Córnea/microbiología , Córnea/patologíaRESUMEN
Purpose: Fungal keratitis (FK) is an invasive corneal infection associated with significant risk to vision. Although the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway has been recognized for its role in defending against viral infections, its involvement in FK still remains largely unclear. This study sought to elucidate the contribution of the cGAS/STING signaling pathway to the pathogenesis of FK. Methods: The expression of cGAS/STING signaling components was assessed in a murine model of Candida albicans keratitis through RNA sequencing, western blot analysis, immunofluorescence staining, and real-time PCR. Both genetic (utilizing Sting1gt/gt mice) and pharmacological (using C176) interventions were employed to inhibit STING activity, allowing for the evaluation of resultant pathogenic alterations in FK using slit-lamp examination, clinical scoring, hematoxylin and eosin (H&E) staining, fungal culture, and RNA sequencing. Subconjunctival administration of the NOD-like receptor protein 3 (NLRP3) inflammasome inhibitor MCC950 was performed to evaluate FK manifestations following STING activity blockade. Furthermore, the impact of the STING agonist diABZI on FK progression was investigated. Results: Compared to uninfected corneas, those infected with C. albicans exhibited increased expression of cGAS/STING signaling components, as well as its elevated activity. Inhibiting cGAS/STING signaling exacerbated the advancement of FK, as evidenced by elevated clinical scores, augmented fungal load, and heightened inflammatory response, including NLRP3 inflammasome activation and pyroptosis. Pharmacological inhibition of the NLRP3 inflammasome effectively mitigated the exacerbated FK by suppressing STING activity. Conversely, pre-activation of STING exacerbated FK progression compared to the PBS control, characterized by increased fungal burden and reinforced inflammatory infiltration. Conclusions: This study demonstrates the essential role of the cGAS/STING signaling pathway in FK pathogenesis and highlights the necessity of its proper activation for the host against FK.