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OBJECTIVE: Microsporidial stromal keratitis (MSK) is an uncommon disease. Only several case series have been reported. We aimed to describe the clinical manifestations, histopathology and treatment outcomes of MSK. METHODS AND ANALYSIS: Retrospective data of MSK diagnosed between January 2009 and December 2020 at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand were retrieved. The diagnosis was made based on corneal scraping, corneal biopsy and corneal button histopathology findings. Detailed clinical characteristics, histopathological findings and treatment outcomes were reviewed and analysed. RESULTS: 21 patients with MSK with a mean age of 63.8 years (SD 12.2) had an indolent disease onset with a median of 9 months (IQR 2.2-12.0). Five patients (23.8%) experienced ocular traumas. Herpes stromal keratitis was the most common preliminary diagnosis (33.3%), followed by non-specific ulcers and fungal keratitis. The most common corneal finding was multifocal grey-white lesions with anterior to mid-stromal infiltration and fluffy borders (66.7%). Pathogens were identified by modified trichrome staining of corneal scrapings in 11 of 14 cases (78.6%). Histopathological examination showed positive Ziehl-Neelsen staining in 17 of 19 cases (89.5%). All patients received surgical treatment, with 18 receiving therapeutic penetrating keratoplasty (TPK), 2 undergoing deep anterior lamellar keratoplasty and 1 undergoing femtosecond laser-assisted anterior lamellar keratoplasty. The overall cure rate was 76.2% after the first surgery and 95.2% after the second surgery. CONCLUSION: MSK can be easily underdiagnosed. Clues to diagnosis included a history of chronic refractory stromal infiltration and typical corneal findings of deep stromal infiltration, without epithelial defects. TPK is the preferred treatment for MSK.
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Sustancia Propia , Infecciones Fúngicas del Ojo , Queratitis , Microscopía Confocal , Microsporidiosis , Humanos , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Femenino , Infecciones Fúngicas del Ojo/patología , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/terapia , Infecciones Fúngicas del Ojo/diagnóstico , Microsporidiosis/patología , Microsporidiosis/cirugía , Sustancia Propia/patología , Sustancia Propia/microbiología , Sustancia Propia/cirugía , Anciano , Queratitis/microbiología , Queratitis/patología , Queratitis/diagnóstico , Queratitis/terapia , Antifúngicos/uso terapéutico , Resultado del Tratamiento , Adulto , Trasplante de Córnea , Tailandia/epidemiología , BiopsiaRESUMEN
Fungal endophthalmitis is a chronic inflammatory condition of the eye's posterior segment that can lead to irreversible vision loss. While relatively rare in western countries, its incidence is notably higher in Asia, particularly India. The condition's prevalence is exacerbated by factors such as intravenous drug use, antibiotics, and ocular surgeries. Fungal endophthalmitis can be categorized as endogenous, arising from systemic infection, or exogenous, linked to external sources such as trauma or surgery. The fungal agents responsible vary by region, with Candida species common in the West and Aspergillus and Fusarium species more prevalent in India. Management typically involves vitrectomy and intravitreal antifungal drugs such as amphotericin B and voriconazole, though treatment is often complicated by multidrug resistance and culture-negative cases. Recent proteomic and transcriptomic analyses have highlighted the early and sustained activation of the host immune response during infection involving key inflammatory and oxidative stress-related proteins. Given the potential for excessive inflammation to cause retinal damage, targeted immunotherapies are crucial. Immunomodulation, which aims to balance the immune response, shows promise in preserving vision while effectively combating the infection. Key targets for immunomodulation include pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17), chemokines (CCL2, CXCL8), Toll-like receptors (TLR2, TLR4), and the complement system. Additionally, modulating the activity of macrophages, neutrophils, regulatory T cells, and Th17 cells, as well as targeting inflammasomes, can help control inflammation. Biologic agents and small molecule inhibitors offer further avenues for precise immune response modulation. This review underscores the importance of a comprehensive understanding of host-pathogen interactions in the development of effective therapies for fungal endophthalmitis.
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Antifúngicos , Endoftalmitis , Infecciones Fúngicas del Ojo , Endoftalmitis/microbiología , Endoftalmitis/tratamiento farmacológico , Humanos , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Citocinas/metabolismo , AnimalesRESUMEN
BACKGROUND: This study aims to evaluate the clinical outcomes and efficacy of a modified tectonic corneoscleral graft (TCG) in patients suffering from devastating corneoscleral infections. METHODS: Thirty-eight eyes from 38 patients who underwent the modified TCG were included in this study. The outcomes measured were recurrence rates, best-corrected visual acuity (BCVA), ocular surface stability, postoperative complications, and graft survival. RESULTS: Among the 38 patients, 23 had fungal infections, 9 had bacterial infections and 6 had Pythium insidiosum infections. At the final follow-up, with an average duration of 25.1 ± 8.6 months, the rate of monocular blindness decreased from 100 to 58%. Significant improvements in LogMAR BCVA were observed from preoperative to postoperative measurements (P < 0.001). Thirty-two eyes (84.2%) maintained a stable ocular surface. The survival rate of ocular surface stability was 84.2%±5.9% at one year and 57.7%±9.7% at three years post-surgery. Twenty eyes (52.6%) retained a clear graft, with a survival rate for graft clarity was 81.6%±6.3% at one year and 36.0%±10.8% at three years post-surgery. The incidence of immune rejection was 36.8%. Corneal epithelial defects were observed in ten patients, and choroidal detachment occurred in four patients. No cases of elevated intraocular pressure were detected. CONCLUSIONS: The modified TCG is effective in eradicating infections, preserving the eyeball, and maintaining useful vision in cases of devastating corneoscleral infections. Regular use of tacrolimus, timely administration of glucocorticoids, and good patient compliance can help mitigate postoperative challenges.
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Supervivencia de Injerto , Agudeza Visual , Humanos , Masculino , Femenino , Persona de Mediana Edad , Agudeza Visual/fisiología , Adulto , Anciano , Estudios Retrospectivos , Esclerótica/cirugía , Esclerótica/trasplante , Trasplante de Córnea/métodos , Adulto Joven , Enfermedades de la Córnea/cirugía , Adolescente , Enfermedades de la Esclerótica/cirugía , Estudios de Seguimiento , Infecciones Fúngicas del Ojo/cirugía , Infecciones del OjoRESUMEN
Candida species are common human pathogens that cause a wide range of diseases ranging from superficial to invasive candidiasis. However, basic studies focusing on the mechanisms underlying these diseases are limited. This article reviews our previous research on the mechanisms of superficial and invasive candidiasis, the virulence of Candida species, and Candida species fitness to hosts. Regarding invasive candidiasis, we focused on two types of infections: ocular candidiasis and endogenous candidiasis from the gastrointestinal tract. Using an established ocular candidiasis mouse model, along with retrospective epidemiological research, we found a strong association between Candida albicans and ocular candidiasis. Regarding endogenous candidiasis, research using Candida auris indicated that invasive strains had a higher capability for gastrointestinal tract colonization and showed greater dissemination compared with non-invasive strains. In terms of superficial candidiasis, we focused on the defense mechanism in vulvovaginal candidiasis. The results suggested that stimulated invariant natural killer T cells played a protective role against C. albicans vaginal infection and might be a therapeutic target for vulvovaginal candidiasis. Concerning Candida species fitness, we focused on environmental factors, particularly oxygen concentration, and evaluated biofilm formation under various oxygen concentrations, revealing that each Candida species favored different oxygen concentrations. In particular, Candida tropicalis showed greater biofilm formation under hypoxic conditions. Our research revealed several insights for understanding the exact mechanisms of candidiasis, which might lead to better control of Candida species infections and appropriate treatment.
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Biopelículas , Candida , Candidiasis , Modelos Animales de Enfermedad , Animales , Ratones , Candida/patogenicidad , Candidiasis/microbiología , Humanos , Biopelículas/crecimiento & desarrollo , Virulencia , Femenino , Candidiasis Vulvovaginal/microbiología , Infecciones Fúngicas del Ojo/microbiología , Candida albicans/patogenicidad , Candidiasis Invasiva/microbiologíaRESUMEN
BACKGROUND: Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro rose bengal photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates (Atalay HT et al., Curr Eye Res 43:1322-5, 2018, Arboleda A et al. Am J Ophthalmol 158:64-70, 2014). In one published series, RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthamoeba keratitis not responsive to medical therapy. METHODS: This international, randomized, sham and placebo controlled 2-arm clinical trial randomizes patients with smear positive fungal and acanthamoeba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) topical antimicrobial plus sham RB-PDT or 2) topical antimicrobial plus RB-PDT. DISCUSSION: We anticipate that RB-PDT will improve best spectacle-corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request. TRIAL REGISTRATION: NCT, NCT05110001 , Registered on November 5, 2021.
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Queratitis por Acanthamoeba , Infecciones Fúngicas del Ojo , Fotoquimioterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Rosa Bengala , Humanos , Rosa Bengala/uso terapéutico , Fotoquimioterapia/métodos , Queratitis por Acanthamoeba/tratamiento farmacológico , Queratitis por Acanthamoeba/diagnóstico , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Método Doble Ciego , Resultado del Tratamiento , Agudeza Visual , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Multicéntricos como Asunto , Luz VerdeRESUMEN
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
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
Infectious keratitis is a leading cause of corneal blindness worldwide with little information known about causative etiologies in Malawi, Africa. This area is resource-limited with ophthalmologist and microbiology services. The Department of Ophthalmology at the Kamuzu College of Health Sciences in Blantyre, Malawi, is a participating site of an international corneal ulcer consortium, capriCORN (Comprehensive Analysis of Pathogens, Resistomes, and Inflammatory-markers in the CORNea). In this study, 50 patients with corneal ulcers were swabbed for pathogen identification using RNA-sequencing. Corneal trauma was reported in 41% and 19% of the patients worked in agriculture. A pathogen was identified in 58% of the cases. Fungal pathogens predominated, followed by viruses and bacteria. Aspergillus, Fusarium, HSV-1, and Gardnerella were the most common pathogens detected. 50% of patients reported treatment with an antibiotic before presentation. Pathogens unusual for infectious keratitis, such as Subramaniula asteroids, Aureobasidium pullulans, and Gardnerella vaginalis, were also detected.
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Queratitis , Humanos , Malaui/epidemiología , Masculino , Adulto , Femenino , Queratitis/microbiología , Queratitis/epidemiología , Persona de Mediana Edad , Úlcera de la Córnea/microbiología , Úlcera de la Córnea/epidemiología , Adulto Joven , Adolescente , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/epidemiología , Anciano , Hongos/aislamiento & purificación , Hongos/clasificación , Bacterias/aislamiento & purificación , Bacterias/clasificación , Córnea/microbiología , Córnea/patologíaRESUMEN
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
OBJECTIVE: To describe a patient diagnosed with Exophiala jeanselmei keratitis. METHODS: We report a case of a patient who developed infectious keratitis following laser in situ keratomileusis and chronic topical steroid use for approximately six months in both eyes. An atypical infiltrate containing dark pigmentation was noted in the left eye on the initial presentation. During treatment, the infiltrates of the right eye began to exhibit a similar pigmentation. RESULTS: Early treatment with topical antifungals was initiated in the left eye and later in the right eye once culture results returned. Both eyes recovered with good vision after approximately one month. CONCLUSIONS: Patients treated with postoperative topical corticosteroids should be cautioned of potential adverse effects of chronic use and have close follow-up. If infectious keratitis develops, particularly after two weeks, then atypical organisms, such as fungi, should be considered. In addition, our case highlights the significance of recognizing and associating dark-pigmentation with fungal etiologies.
Asunto(s)
Antifúngicos , Exophiala , Infecciones Fúngicas del Ojo , Queratitis , Queratomileusis por Láser In Situ , Adulto , Humanos , Antifúngicos/uso terapéutico , Úlcera de la Córnea/microbiología , Úlcera de la Córnea/tratamiento farmacológico , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/etiología , Exophiala/aislamiento & purificación , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificación , Queratitis/microbiología , Queratitis/diagnóstico , Queratitis/tratamiento farmacológico , Queratitis/etiología , Queratomileusis por Láser In Situ/efectos adversos , Feohifomicosis/microbiología , Feohifomicosis/diagnóstico , Feohifomicosis/tratamiento farmacológicoRESUMEN
Keratitis is a corneal infection caused by various bacteria and fungi. Eye drop treatment of keratitis involves significant challenges due to difficulties in administration, inefficiencies in therapeutic dosage, and frequency of drug applications. All these are troublesome and result in unsuccessful treatment, high cost, time loss, development of drug resistance by microorganisms, and a massive burden on human health and the healthcare system. Most of the antibacterial and antifungal medications are non-water-soluble and/or include toxic drug formulations. Here, the aim was to develop drug-loaded contact lenses with therapeutic dosage formulations and extended drug release capability as an alternative to eye drops, by employing supercritical carbon dioxide (ScCO2) as a drug impregnation solvent to overcome inefficient ophthalmic drug use. ScCO2, known as a green solvent, has very low viscosity which provides high mass transfer power and could enhance drug penetration into contact lenses much better with respect to drug loading using other solvents. Here, moxifloxacin (MOX) antibiotic and amphotericin B (AMB) antifungal medicines were separately loaded into commercially available silicone hydrogel contact lenses through 1) drug adsorption from the aqueous solutions and 2) impregnation techniques via ScCO2 and their efficacies were compared. Drug impregnation parameters, i.e., 8-25 MPa pressure, 310-320 K temperature, 2-16-hour impregnation times, and the presence of ethanol as polar co-solvent were investigated for the optimization of the ScCO2 drug impregnation process. The highest drug loading and long-term release kinetic from the contact lenses were obtained at 25 MPa and 313 K with 2.5 h impregnation time by using 1 % ethanol (by volume). Furthermore, antibacterial/antifungal activities of the MOX- and AMB-impregnated contact lenses were effective against in vitro Pseudomonas aeruginosa (ATCC 10145) bacteria and Fusarium solani (ATCC 36031) fungus for up to one week. Consequently, the ScCO2 method can be effectively used to impregnate commercial contact lenses with drugs, and these can then be safely used for the treatment of keratitis. This offers a sustainable delivery system at effective dosage formulations with complete bacterial/fungal inhibition and termination, making it viable for real animal/human applications.
Asunto(s)
Anfotericina B , Antibacterianos , Antifúngicos , Dióxido de Carbono , Queratitis , Moxifloxacino , Dióxido de Carbono/química , Queratitis/tratamiento farmacológico , Queratitis/microbiología , Antibacterianos/química , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/administración & dosificación , Moxifloxacino/administración & dosificación , Moxifloxacino/química , Moxifloxacino/farmacología , Anfotericina B/administración & dosificación , Anfotericina B/química , Anfotericina B/farmacología , Liberación de Fármacos , Lentes de Contacto/microbiología , Fusarium/efectos de los fármacos , Humanos , Hidrogeles/química , Sistemas de Liberación de Medicamentos , Solventes/química , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiologíaRESUMEN
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.
Asunto(s)
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
Objective: The purpose of this study was to report a case of herpes simplex virus-1 (HSV-1) keratitis misdiagnosed as fungal keratitis due to its clinical presentation being similar to that of fungal keratitis, ultimately diagnosed by NGS. Patients and Methods: A 59-year-old male presented with reduced vision in the right eye, combined with a history of trauma with vegetative matter. The corneal ulcer was accompanied with feathery infiltration, satellite lesion, and endothelial plaques. In vivo confocal microscopy (IVCM) showed hyper-reflective linear, thin, and branching interlocking structures. Fungal keratitis was diagnosed. Voriconazole 100 mg orally daily, topical tobramycin and 1% voriconazole were initiated empirically right away. The condition was aggravated and penetrating keratoplasty was performed. Anterior segment optical coherence tomography (AS-OCT) demonstrated the presence of plaques with a clear boundary between plaques and endothelium, resembling the AS-OCT images observed in cases of viral keratitis. Next-generation sequencing (NGS) further detected HSV-1 deoxyribonucleic acid, and no fungal component was found. Antifungal agents were discontinued and antiviral treatments were added. Results: We successfully treated a patient with HSV-1 keratitis who was misdiagnosed due to clinical features and IVCM findings similar to fungal keratitis. The patient's infection was controlled. At 2 years after surgery, the cornea recovered well. Conclusions: HSV-1 keratitis with atypical clinical presentation can be easily misdiagnosed. This case report emphasizes the importance of NGS in diagnosing the pathogens of keratitis.
Asunto(s)
Errores Diagnósticos , Herpesvirus Humano 1 , Secuenciación de Nucleótidos de Alto Rendimiento , Queratitis Herpética , Humanos , Masculino , Persona de Mediana Edad , Herpesvirus Humano 1/aislamiento & purificación , Herpesvirus Humano 1/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Queratitis Herpética/diagnóstico , Queratitis Herpética/tratamiento farmacológico , Queratitis/diagnóstico , Queratitis/microbiología , Queratitis/virología , Queratitis/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Antifúngicos/uso terapéutico , Antivirales/uso terapéuticoRESUMEN
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.