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Keywords = mycotic keratitis

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8 pages, 958 KiB  
Case Report
Efficacy of the Combined Intrastromal Injection of Voriconazole and Amphotericin B in Recalcitrant Fungal Keratitis
by Antonio Moramarco, Arianna Grendele, Danilo Iannetta, Simone Ottoboni, Giulia Gregori, Natalie di Geronimo, Margherita Ortalli, Tiziana Lazzarotto and Luigi Fontana
Microorganisms 2024, 12(5), 922; https://doi.org/10.3390/microorganisms12050922 - 30 Apr 2024
Cited by 2 | Viewed by 2005
Abstract
This study aims to report the efficacy of a combined intrastromal injection in optimizing the outcome of severe mycotic keratitis. Herein, we report a case series of 20 consecutive patients with positive fungal cultures not responding to topical antifungal treatment. Patients received cycles [...] Read more.
This study aims to report the efficacy of a combined intrastromal injection in optimizing the outcome of severe mycotic keratitis. Herein, we report a case series of 20 consecutive patients with positive fungal cultures not responding to topical antifungal treatment. Patients received cycles of intrastromal injections of voriconazole (50 µg/0.1 mL) and amphotericin B (2.5 µg/0.1 mL); all patients continued their topical antifungal therapy. The organisms isolated were Fusarium (n = 5), Aspergillus (n = 4), Candida (n = 4), Rhodotorula (n = 2), Penicillium (n = 2), Alternaria (n = 1), Bipolaris (n = 1), and Curvularia (n = 1). The size of the infiltrate varied from 6.5 to 1.5 mm. At presentation, the best corrected visual acuity (BCVA, namely, the best visual acuity achieved with glasses, if needed) was less than 20/400 in all patients, improving to better than 20/400 in eleven patients. Seven patients required surgical intervention; four of them underwent penetrating keratoplasty (PK) à chaud one month after the first intrastromal injection. Patients who underwent surgery achieved a BCVA of 20/40 or better. Combined intrastromal injections before therapeutic penetrating keratoplasty (TPK) effectively reduced ulcer size and graft diameter, preventing infection recurrence. Our results highlight the efficacy of combined intrastromal injections in optimizing outcomes for severe mycotic keratitis undergoing TPK. Full article
(This article belongs to the Special Issue Ocular Infections and Microbiota in Health and Disease 2.0)
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17 pages, 306 KiB  
Review
Recent Advances in Diagnosis and Treatment Approaches in Fungal Keratitis: A Narrative Review
by Laura Andreea Ghenciu, Alexandra Corina Faur, Sorin Lucian Bolintineanu, Madalina Casiana Salavat and Anca Laura Maghiari
Microorganisms 2024, 12(1), 161; https://doi.org/10.3390/microorganisms12010161 - 13 Jan 2024
Cited by 19 | Viewed by 5488
Abstract
Fungal keratitis represents a potentially sight-threatening infection associated with poor prognosis, as well as financial burden. Novel diagnostic methods include polymerase-chain-reaction (PCR)-based approaches, metagenomic deep sequences, in vivo confocal microscopy, and antifungal susceptibility testing. The ideal therapeutic approaches and outcomes have been widely [...] Read more.
Fungal keratitis represents a potentially sight-threatening infection associated with poor prognosis, as well as financial burden. Novel diagnostic methods include polymerase-chain-reaction (PCR)-based approaches, metagenomic deep sequences, in vivo confocal microscopy, and antifungal susceptibility testing. The ideal therapeutic approaches and outcomes have been widely discussed in recent times, with early therapy being of the utmost importance for the preservation of visual acuity, minimizing corneal damage and reducing the scar size. However, combination therapy can be more efficacious compared to monotherapy. Understanding the pathogenesis, early diagnosis, and prevention strategies can be of great importance. In this narrative, we discuss the recent progress that may aid our understanding of the diagnosis, treatment, and prevention of mycotic keratitis. Full article
(This article belongs to the Special Issue Infectious Eye Diseases and Prevention Control)
18 pages, 598 KiB  
Review
Candida Biofilm Eye Infection: Main Aspects and Advance in Novel Agents as Potential Source of Treatment
by Francesco Petrillo, Marica Sinoca, Antonio Maria Fea, Marilena Galdiero, Angela Maione, Emilia Galdiero, Marco Guida and Michele Reibaldi
Antibiotics 2023, 12(8), 1277; https://doi.org/10.3390/antibiotics12081277 - 2 Aug 2023
Cited by 9 | Viewed by 3420
Abstract
Fungi represent a very important cause of microbial eye infections, especially in tropical and developing countries, as they could cause sight-threating disease, such as keratitis and ocular candidiasis, resulting in irreversible vision loss. Candida species are among the most frequent microorganisms associated with [...] Read more.
Fungi represent a very important cause of microbial eye infections, especially in tropical and developing countries, as they could cause sight-threating disease, such as keratitis and ocular candidiasis, resulting in irreversible vision loss. Candida species are among the most frequent microorganisms associated with fungal infection. Although Candida albicans is still the most frequently detected organism among Candida subspecies, an important increase in non-albicans species has been reported. Mycotic infections often represent an important diagnostic-clinical problem due to the difficulties in performing the diagnosis and a therapeutic problem due to the limited availability of commercial drugs and the difficult penetration of antifungals into ocular tissues. The ability to form biofilms is another feature that makes Candida a dangerous pathogen. In this review, a summary of the state-of-the-art panorama about candida ocular pathology, diagnosis, and treatment has been conducted. Moreover, we also focused on new prospective natural compounds, including nanoparticles, micelles, and nanocarriers, as promising drug delivery systems to better cure ocular fungal and biofilm-related infections. The effect of the drug combination has also been examined from the perspective of increasing efficacy and improving the course of infections caused by Candida which are difficult to fight. Full article
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26 pages, 5357 KiB  
Article
Antifungal Combination Eye Drops for Fungal Keratitis Treatment
by Victoria Díaz-Tomé, Carlos Bendicho-Lavilla, Xurxo García-Otero, Rubén Varela-Fernández, Manuel Martín-Pastor, José Llovo-Taboada, Pilar Alonso-Alonso, Pablo Aguiar, Miguel González-Barcia, Anxo Fernández-Ferreiro and Francisco J. Otero-Espinar
Pharmaceutics 2023, 15(1), 35; https://doi.org/10.3390/pharmaceutics15010035 - 22 Dec 2022
Cited by 8 | Viewed by 3292
Abstract
Fungal keratitis (FK) is a corneal mycotic infection that can lead to vision loss. Furthermore, the severity of FK is aggravated by the emergence of resistant fungal species. There is currently only one FDA-approved formulation for FK treatment forcing hospital pharmacy departments to [...] Read more.
Fungal keratitis (FK) is a corneal mycotic infection that can lead to vision loss. Furthermore, the severity of FK is aggravated by the emergence of resistant fungal species. There is currently only one FDA-approved formulation for FK treatment forcing hospital pharmacy departments to reformulate intravenous drug preparations with unknown ocular bioavailability and toxicity. In the present study, natamycin/voriconazole formulations were developed and characterized to improve natamycin solubility, permanence, and safety. The solubility of natamycin was studied in the presence of two cyclodextrins: HPβCD and HPγCD. The HPβCD was chosen based on the solubility results. Natamycin/cyclodextrin (HPβCD) inclusion complexes characterization and a competition study between natamycin and voriconazole were conducted by NMR (Nuclear Magnetic Resonance). Based on these results, several eye drops with different polymer compositions were developed and subsequently characterized. Permeability studies suggested that the formulations improved the passage of natamycin through the cornea compared to the commercial formulation Natacyn®. The ocular safety of the formulations was determined by BCOP and HET-CAM. The antifungal activity assay demonstrated the ability of our formulations to inhibit the in vitro growth of different fungal species. All these results concluded that the formulations developed in the present study could significantly improve the treatment of FK. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 3rd Edition)
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7 pages, 2072 KiB  
Case Report
An Atypical Etiology of Fungal Keratitis Caused by Roussoella neopustulans
by Morgana F. Voidaleski, Flavio Queiroz-Telles, Hugo T. Itikawa, Guilherme G. Müller, Bruna J. F. S. Lima, Lucas E. Trevisoli, Regielly C. R. Cognialli, Roberta C. L. Crispim and Vania A. Vicente
J. Fungi 2022, 8(5), 507; https://doi.org/10.3390/jof8050507 - 15 May 2022
Cited by 4 | Viewed by 2261
Abstract
Fungal keratitis is caused by a wide spectrum of fungal genera, including molds and yeasts. We report a 42-year-old patient with mycotic keratitis after a direct trauma by a wood fragment. The fungal isolate was identified as Roussoella neopustulans by molecular methods. The [...] Read more.
Fungal keratitis is caused by a wide spectrum of fungal genera, including molds and yeasts. We report a 42-year-old patient with mycotic keratitis after a direct trauma by a wood fragment. The fungal isolate was identified as Roussoella neopustulans by molecular methods. The treatment with topic natamycin showed progressive improvement of the visual manifestations, and following three months of therapy, the patient regained sight. We report the first case of keratitis associated with R. neopustulans. Full article
(This article belongs to the Special Issue Fungal Infections of Implantation (Subcutaneous Mycoses))
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12 pages, 978 KiB  
Article
Diagnosing Fungal Keratitis and Simultaneously Identifying Fusarium and Aspergillus Keratitis with a Dot Hybridization Array
by Ming-Tse Kuo, Shiuh-Liang Hsu, Huey-Ling You, Shu-Fang Kuo, Po-Chiung Fang, Hun-Ju Yu, Alexander Chen, Chia-Yi Tseng, Yu-Hsuan Lai and Jiunn-Liang Chen
J. Fungi 2022, 8(1), 64; https://doi.org/10.3390/jof8010064 - 7 Jan 2022
Cited by 6 | Viewed by 2451
Abstract
Fungal keratitis (FK) is one of the most common microbial keratitis, which often leads to poor prognosis as a result of delayed diagnosis. Several studies implied that early differentiation of the two major FK, Fusarium and Aspergillus keratitis, could be helpful in selecting [...] Read more.
Fungal keratitis (FK) is one of the most common microbial keratitis, which often leads to poor prognosis as a result of delayed diagnosis. Several studies implied that early differentiation of the two major FK, Fusarium and Aspergillus keratitis, could be helpful in selecting effective anti-fungal regimens. Therefore, a novel dot hybridization array (DHA) was developed to diagnose FK and differentiate Fusarium and Aspergillus keratitis in this study. One hundred forty-six corneal scrapes obtained from one hundred forty-six subjects impressed with clinically suspected FK were used to evaluate the performance of the DHA. Among these patients, 107 (73.3%) patients had actual FK confirmed by culture and DNA sequencing. We found that the DHA had 93.5% sensitivity and 97.4% specificity in diagnosing FK. In addition, this array had 93.2% sensitivity and 93.8% specificity in diagnosing Fusarium keratitis, as well as 83.3% sensitivity and 100% specificity in diagnosing Aspergillus keratitis. Furthermore, it had 83.9% sensitivity and 100% specificity in identifying Fusarium solani keratitis. Thus, this newly developed DHA will be beneficial to earlier diagnosis, more precise treatment, and improve prognosis of FK, by minimizing medical refractory events and surgical needs. Full article
(This article belongs to the Special Issue Molecular Tissue Diagnosis of Fungal Infections)
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25 pages, 2220 KiB  
Review
Recent Perspectives in the Management of Fungal Keratitis
by Nimmy Raj, Murugesan Vanathi, Nishat Hussain Ahmed, Noopur Gupta, Neiwete Lomi and Radhika Tandon
J. Fungi 2021, 7(11), 907; https://doi.org/10.3390/jof7110907 - 26 Oct 2021
Cited by 52 | Viewed by 7853
Abstract
Mycotic keratitis is common in warm, humid regions with a varying profile of pathogenic fungi according to geographical origin, socioeconomic status, and climatic condition. Clinical diagnosis can be challenging in difficult cases and those refractory to treatment. Fungal hyphae on microscopic examination and [...] Read more.
Mycotic keratitis is common in warm, humid regions with a varying profile of pathogenic fungi according to geographical origin, socioeconomic status, and climatic condition. Clinical diagnosis can be challenging in difficult cases and those refractory to treatment. Fungal hyphae on microscopic examination and culture isolation have been the gold standard in the laboratory diagnosis of fungal keratitis. A culture isolate of the aetiological fungus is essential to perform antifungal susceptibility testing. As the culture isolation of fungi is time-consuming, causing delays in the initiation of treatment, newer investigative modalities such as in vivo confocal microscopy and molecular diagnostic methods have recently gained popularity. Molecular diagnostic techniques now help to obtain a rapid diagnosis of fungal keratitis. Genomic approaches are based on detecting amplicons of ribosomal RNA genes, with internal transcribed spacers being increasingly adopted. Metagenomic deep sequencing allows for rapid and accurate diagnosis without the need to wait for the fungus to grow. This is also helpful in identifying new emerging strains of fungi causing mycotic keratitis. A custom-tear proteomic approach will probably play an important diagnostic role in future in the management of mycotic keratitis. Positive repeat cultures are being suggested as an important gauge indicative of a poor prognosis. Positive repeat fungal cultures help to modify a treatment regimen by increasing its frequency, providing the addition of another topical and oral antifungal agent along with close follow-up for perforation and identifying need for early therapeutic keratoplasty. The role of collagen crosslinking in the treatment of fungal keratitis is not convincingly established. Rapid detection by multiplex PCR and antifungal susceptibility testing of the pathogenic fungi, adopted into a routine management protocol of fungal keratitis, will help to improve treatment outcome. Early therapy is essential in minimizing damage to the corneal tissue, thereby providing a better outcome. The role of conventional therapy with polyenes, systemic and targeted therapy of antifungal agents, newer azoles and echinocandins in fungal keratitis has been widely studied in recent times. Combination therapy can be more efficacious in comparison to monotherapy. Given the diversity of fungal aetiology, the emergence of new corneal pathogenic fungi with varying drug susceptibilities, increasing the drug resistance to antifungal agents in some genera and species, it is perhaps time to adopt recent molecular methods for precise identification and incorporate antifungal susceptibility testing as a routine. Full article
(This article belongs to the Special Issue Ocular Fungal Infections)
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36 pages, 9074 KiB  
Review
Mycotic Keratitis—A Global Threat from the Filamentous Fungi
by Jeremy J. Hoffman, Matthew J. Burton and Astrid Leck
J. Fungi 2021, 7(4), 273; https://doi.org/10.3390/jof7040273 - 3 Apr 2021
Cited by 89 | Viewed by 11357
Abstract
Mycotic or fungal keratitis (FK) is a sight-threatening disease, caused by infection of the cornea by filamentous fungi or yeasts. In tropical, low and middle-income countries, it accounts for the majority of cases of microbial keratitis (MK). Filamentous fungi, in particular Fusarium spp., [...] Read more.
Mycotic or fungal keratitis (FK) is a sight-threatening disease, caused by infection of the cornea by filamentous fungi or yeasts. In tropical, low and middle-income countries, it accounts for the majority of cases of microbial keratitis (MK). Filamentous fungi, in particular Fusarium spp., the aspergilli and dematiaceous fungi, are responsible for the greatest burden of disease. The predominant risk factor for filamentous fungal keratitis is trauma, typically with organic, plant-based material. In developed countries, contact lens wear and related products are frequently implicated as risk factors, and have been linked to global outbreaks of Fusarium keratitis in the recent past. In 2020, the incidence of FK was estimated to be over 1 million cases per year, and there is significant geographical variation; accounting for less than 1% of cases of MK in some European countries to over 80% in parts of south and south-east Asia. The proportion of MK cases is inversely correlated to distance from the equator and there is emerging evidence that the incidence of FK may be increasing. Diagnosing FK is challenging; accurate diagnosis relies on reliable microscopy and culture, aided by adjunctive tools such as in vivo confocal microscopy or PCR. Unfortunately, these facilities are infrequently available in areas most in need. Current topical antifungals are not very effective; infections can progress despite prompt treatment. Antifungal drops are often unavailable. When available, natamycin is usually first-line treatment. However, infections may progress to perforation in ~25% of cases. Future work needs to be directed at addressing these challenges and unmet needs. This review discusses the epidemiology, clinical features, diagnosis, management and aetiology of FK. Full article
(This article belongs to the Special Issue Emerging and Endemic Mycoses)
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11 pages, 241 KiB  
Article
Human Fungal Infections in Kuwait—Burden and Diagnostic Gaps
by Wadha Alfouzan, Faten Al-Wathiqi, Haya Altawalah, Mohammad Asadzadeh, Ziauddin Khan and David W. Denning
J. Fungi 2020, 6(4), 306; https://doi.org/10.3390/jof6040306 - 21 Nov 2020
Cited by 8 | Viewed by 3276
Abstract
Fungal infections are an increasingly important public health issue, yet accurate statistics on fungal burden worldwide and in Kuwait are scarce. Here we estimate the incidence and prevalence of fungal infections in Kuwait. Population statistics from 2018 collected by the Public Authority for [...] Read more.
Fungal infections are an increasingly important public health issue, yet accurate statistics on fungal burden worldwide and in Kuwait are scarce. Here we estimate the incidence and prevalence of fungal infections in Kuwait. Population statistics from 2018 collected by the Public Authority for Civil Information were used, as well as data from the Ministry of Health. A literature search for Kuwait data on mycotic diseases and population at risk (chronic obstructive pulmonary disease, HIV infection/AIDS, cancer, and transplant patients) was conducted. The population in 2018 was estimated at 4,226,920 million people: 1,303,246 million Kuwaitis and 2,923,674 million expatriates. We determined the annual burden of serious fungal infections number (per 100,000) from high to low based on earlier reported fungal rates for populations at risk: recurrent Candida vaginitis 54,842 (2595); severe asthma with fungal sensitisation 10,411 (246); allergic bronchopulmonary aspergillosis, 7887 (187); chronic pulmonary aspergillosis 995 (21.3); invasive aspergillosis 704 (16.7); fungal keratitis 654 (15.5); candidaemia 288 (6.8); Candida peritonitis 63 (3.5) and oesophageal candidiasis in HIV 33 (0.8). Besides identifying rising new risk groups and expanding reports on antifungal resistance, surveillance programs and further epidemiological studies are needed to achieve more precise assessments of fungal disease epidemiology and correlated morbidity and mortality. Full article
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