Ocular Fungal Infections

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (1 April 2022) | Viewed by 29299

Special Issue Editors


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Guest Editor
1. School of Public Health and Administration, Universidad Peruana Cayetano Heredia, Lima, Peru
2. Faculty of Health Sciences, Universidad Tecnológica del Perú, Lima, Peru
Interests: public health; epidemiology; infectious diseases; medical mycology; sporotrichosis; Sporothrix; subcutaneous mycoses; implantation mycoses; white piedra
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Guest Editor
Departamento de Micología, Servicio de Dermatología. Hospital General de México "Dr. Eduardo Liceaga", Ciudad de México CP 06720, Mexico
Interests: cutaneous mycoses (superficial and deep); opportunistic mycoses and antifungal treatment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Fungal infections of the eye and ocular adnexa continue to be an important cause of ocular morbidity, particularly in the developing world. These infections have increased in recent decades due to spectrum antibiotic use, the growing number of patients undergoing procedures that lead to immunosuppression, postoperative infection, trauma, and prolonged corticosteroid use. Major pathogenic fungi include Aspergillus, Candida spp., Cryptococcus species, and Coccidioides spp., Fusarium, Penicillium, Pseudallescheria, dimorphic fungi Histoplasma capsulatum, Blastomyces dermatitidis, Sporothrix, and Coccidioides immitis. The diagnosis of ocular fungal infections can be difficult because of nonspecific clinical manifestations. Therefore, understanding ocular fungal infections will improve the clinical outcome of this condition.

For these reasons, this Special Issue is to collect novel findings, reviews, and expert opinions on the epidemiology, diagnosis, and treatment of ocular fungal infections, with a special focus on endophthalmitis, keratitis, orbital infections, systemic infections, and ocular adnexa. Studies covering the epidemiological aspects, clinical findings, laboratorial diagnosis, treatments, antifungal resistance, new etiological agents, as well as case reports will be welcome.

Dr. Max Carlos Ramírez-Soto
Dr. Alexandro Bonifaz
Guest Editors

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Keywords

  • Ocular mycoses
  • Ocular fungal infections
  • Fungal endophthalmitis
  • Fungal keratitis
  • Fungal infections of the ocular surface
  • Fungal infections of the ocular adnexa

Published Papers (8 papers)

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Editorial

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5 pages, 918 KiB  
Editorial
Ocular Fungal Infections
by Max Carlos Ramírez-Soto and Alexandro Bonifaz
J. Fungi 2022, 8(10), 1078; https://doi.org/10.3390/jof8101078 - 13 Oct 2022
Cited by 1 | Viewed by 2268
Abstract
Fungal infections of the eye continue to be an important cause of ocular morbidity and loss of vision, particularly in the developing world [...] Full article
(This article belongs to the Special Issue Ocular Fungal Infections)
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Research

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13 pages, 610 KiB  
Article
Risk Factors and Clinical Characteristics of Patients with Ocular Candidiasis
by Toru Sakamoto, Kenji Gotoh, Kenyu Hashimoto, Chiyoko Tanamachi and Hiroshi Watanabe
J. Fungi 2022, 8(5), 497; https://doi.org/10.3390/jof8050497 - 11 May 2022
Cited by 7 | Viewed by 2851
Abstract
Ocular candidiasis is a critical and challenging complication of candidemia. The purpose of this study was to investigate the appropriate timing for ophthalmologic examinations, risk factors for complications of ocular lesions, and their association with mortality. This retrospective cohort study applied, using multiple [...] Read more.
Ocular candidiasis is a critical and challenging complication of candidemia. The purpose of this study was to investigate the appropriate timing for ophthalmologic examinations, risk factors for complications of ocular lesions, and their association with mortality. This retrospective cohort study applied, using multiple logistic regression analysis and Cox regression models, to cases of candidemia (age ≥ 18 years) for patients who underwent ophthalmologic consultation. Of the 108 candidemia patients who underwent ophthalmologic examination, 27 (25%) contracted patients had ocular candidiasis, and 7 experienced the more severe condition of endophthalmitis, which included subjective ocular symptoms. In most cases, the initial ophthalmologic examination was performed within one week of the onset of candidiasis with a diagnosis of ocular candidiasis, but in three cases, the findings became apparent only after a second examination within 7–14 days after onset of candidiasis. The independent risk factor extracted for the development of ocular candidiasis was the isolation of C. albicans (OR, 4.85; 95% CI, 1.58–14.90), unremoved CVC (OR, 10.40; 95% CI, 1.74–62.16), and a high βDG value (>108.2 pg/mL) (HR, 2.83; 95% CI = 1.24–6.27). Continuous ophthalmologic examination is recommended in cases of candidemia with the above risk factors with an initial examination within 7 days of onset and a second examination 7–14 days after onset. Full article
(This article belongs to the Special Issue Ocular Fungal Infections)
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15 pages, 1752 KiB  
Article
Fusarium Keratitis in Taiwan: Molecular Identification, Antifungal Susceptibilities, and Clinical Features
by Tsung-En Huang, Jie-Hao Ou, Ning Hung, Lung-Kun Yeh, David Hui-Kang Ma, Hsin-Yuan Tan, Hung-Chi Chen, Kuo-Hsuan Hung, Yun-Chen Fan, Pei-Lun Sun and Ching-Hsi Hsiao
J. Fungi 2022, 8(5), 476; https://doi.org/10.3390/jof8050476 - 03 May 2022
Cited by 6 | Viewed by 2389
Abstract
We performed molecular identification and antifungal susceptibilities of pathogens and investigated clinical features of 43 culture-proven Fusarium keratitis cases from 2015–2020 in Taiwan. The pathogens were identified by sequencing of their internal transcribed spacer regions of ribosomal DNA and translation elongation factor 1α [...] Read more.
We performed molecular identification and antifungal susceptibilities of pathogens and investigated clinical features of 43 culture-proven Fusarium keratitis cases from 2015–2020 in Taiwan. The pathogens were identified by sequencing of their internal transcribed spacer regions of ribosomal DNA and translation elongation factor 1α gene; their antifungal susceptibilities (to seven agents) were determined by broth microdilution method. We also collected clinical data to compare the drug susceptibilities and clinical features of Fusarium solani species complex (FSSC) isolates with those of other Fusarium species complexes (non-FSSC). The FSSC accounted for 76.7% pathogens, among which F. falciforme (32.6%) and F. keratoplasticum (27.9%) were the most common species. Among clinically used antifungal agents, amphotericin B registered the lowest minimal inhibitory concentration (MIC), and the new azoles efinaconazole, lanoconazole and luliconazole, demonstrated even lower MICs against Fusarium species. The MICs of natamycin, voriconazole, chlorhexidine, lanoconazole, and luliconazole were higher for the FSSC than the non-FSSC, but no significant differences were noted in clinical outcomes, including corneal perforation and final visual acuity. In Taiwan, the FSSC was the most common complex in Fusarium keratitis; its MICs for five tested antifungal agents were higher than those of non-FSSC, but the clinical outcomes did not differ significantly. Full article
(This article belongs to the Special Issue Ocular Fungal Infections)
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11 pages, 7268 KiB  
Article
Multi-Scale Convolutional Neural Network for Accurate Corneal Segmentation in Early Detection of Fungal Keratitis
by Veena Mayya, Sowmya Kamath Shevgoor, Uma Kulkarni, Manali Hazarika, Prabal Datta Barua and U. Rajendra Acharya
J. Fungi 2021, 7(10), 850; https://doi.org/10.3390/jof7100850 - 11 Oct 2021
Cited by 18 | Viewed by 2980
Abstract
Microbial keratitis is an infection of the cornea of the eye that is commonly caused by prolonged contact lens wear, corneal trauma, pre-existing systemic disorders and other ocular surface disorders. It can result in severe visual impairment if improperly managed. According to the [...] Read more.
Microbial keratitis is an infection of the cornea of the eye that is commonly caused by prolonged contact lens wear, corneal trauma, pre-existing systemic disorders and other ocular surface disorders. It can result in severe visual impairment if improperly managed. According to the latest World Vision Report, at least 4.2 million people worldwide suffer from corneal opacities caused by infectious agents such as fungi, bacteria, protozoa and viruses. In patients with fungal keratitis (FK), often overt symptoms are not evident, until an advanced stage. Furthermore, it has been reported that clear discrimination between bacterial keratitis and FK is a challenging process even for trained corneal experts and is often misdiagnosed in more than 30% of the cases. However, if diagnosed early, vision impairment can be prevented through early cost-effective interventions. In this work, we propose a multi-scale convolutional neural network (MS-CNN) for accurate segmentation of the corneal region to enable early FK diagnosis. The proposed approach consists of a deep neural pipeline for corneal region segmentation followed by a ResNeXt model to differentiate between FK and non-FK classes. The model trained on the segmented images in the region of interest, achieved a diagnostic accuracy of 88.96%. The features learnt by the model emphasize that it can correctly identify dominant corneal lesions for detecting FK. Full article
(This article belongs to the Special Issue Ocular Fungal Infections)
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13 pages, 2852 KiB  
Article
Fungal Keratitis in Northern Thailand: Spectrum of Agents, Risk Factors and Putative Virulence Factors
by Siriporn Chongkae, Sirida Youngchim, Joshua D. Nosanchuk, Angkana Laliam, Chulaluck Tangmonkongvoragul and Kritsada Pruksaphon
J. Fungi 2021, 7(6), 475; https://doi.org/10.3390/jof7060475 - 11 Jun 2021
Cited by 7 | Viewed by 2408
Abstract
Fungal keratitis (FK) is a serious ocular infection that can result in various degrees of vision loss, including blindness. The aim of the study was to identify and retrospectively review all FK cases diagnosed between August 2012 and December 2020 at a tertiary [...] Read more.
Fungal keratitis (FK) is a serious ocular infection that can result in various degrees of vision loss, including blindness. The aim of the study was to identify and retrospectively review all FK cases diagnosed between August 2012 and December 2020 at a tertiary care hospital in northern Thailand with a specific focus on epidemiologic features, including season, patient sex and age, the spectrum of pathogens, and presence of certain putative virulence factors. Of 1237 patients with corneal ulcers, 294 (23.8%) were confirmed by direct microscopic examination and/or fungal culture. For the positive cases, direct examinations of Calcofluor white (CW) stains and KOH mounts were found in 97.3% (286/294) and 76.5% (225/294), respectively (p < 0.05). Of the cases diagnosed by microscopy and culture, fungi were isolated in 152 (51.7%), with Fusarium spp. being the most frequently identified (n = 69, 45.5%) followed by dematiaceous fungi (n = 45, 29.6%) and Aspergillus spp. (n = 18, 11.8%). The incidence of FK was higher in the rainy season of July to October. The mean age was 54.4 ± 14.4 (SD) years, with a range of 9–88 years. Males (75.8%) were affected significantly more than females (24.2%) (p < 0.05). Of 294 patients, 132 (44.9%) were middle-aged adults (41–60 years) and 107 (36.4%) were older than 60 years. Trauma to the eye by soil or vegetative matter were the most common preceding factors (188/294; 64.0%). We assessed two virulence factors. First, 142 of the 152 culture-positive FK cases were due to molds, indicating that hyphal morphogenesis is extremely important in disease. We also demonstrated that fungal melanization occurs in the molds during the course of FK by applying a melanin-specific monoclonal antibody (MAb) that labeled fungal elements in corneal samples of patients, and melanin particles derived from the hyphae were also recovered after treatment of the samples with proteolytic enzymes, denaturant and hot concentrated acid. In summary, we demonstrate that northern Thailand has a high rate of FK that is influenced by season and males engaged in outside activities are at highest risk for disease. Moulds are significantly more commonly responsible for FK, in part due to their capacity to form hyphae and melanins. Future studies will examine models of fungal corneal interactions and assess additional factors of virulence, such as secreted enzymes, to more deeply decipher the pathogenesis of FK. Full article
(This article belongs to the Special Issue Ocular Fungal Infections)
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Review

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20 pages, 7446 KiB  
Review
Fungal Endophthalmitis: A Comprehensive Review
by Abid A. Haseeb, Abdelrahman M. Elhusseiny, Mohammad Z. Siddiqui, Kinza T. Ahmad and Ahmed B. Sallam
J. Fungi 2021, 7(11), 996; https://doi.org/10.3390/jof7110996 - 22 Nov 2021
Cited by 36 | Viewed by 6590
Abstract
Endophthalmitis is a serious ophthalmologic condition involving purulent inflammation of the intraocular spaces. The underlying etiology of infectious endophthalmitis is typically bacterial or fungal. The mechanism of entry into the eye is either exogenous, involving seeding of an infectious source from outside the [...] Read more.
Endophthalmitis is a serious ophthalmologic condition involving purulent inflammation of the intraocular spaces. The underlying etiology of infectious endophthalmitis is typically bacterial or fungal. The mechanism of entry into the eye is either exogenous, involving seeding of an infectious source from outside the eye (e.g., trauma or surgical complications), or endogenous, involving transit of an infectious source to the eye via the bloodstream. The most common organism for fungal endophthalmitis is Candida albicans. The most common clinical manifestation of fungal endophthalmitis is vision loss, but other signs of inflammation and infection are frequently present. Fungal endophthalmitis is a clinical diagnosis, which can be supported by vitreous, aqueous, or blood cultures. Treatment involves systemic and intravitreal antifungal medications as well as possible pars plana vitrectomy. In this review, we examine these essential elements of understanding fungal endophthalmitis as a clinically relevant entity, which threatens patients’ vision. Full article
(This article belongs to the Special Issue Ocular Fungal Infections)
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20 pages, 2080 KiB  
Review
Ocular Sporotrichosis
by Max Carlos Ramírez-Soto, Andrés Tirado-Sánchez and Alexandro Bonifaz
J. Fungi 2021, 7(11), 951; https://doi.org/10.3390/jof7110951 - 10 Nov 2021
Cited by 10 | Viewed by 3330
Abstract
Sporotrichosis is a subacute or chronic mycosis predominant in tropical and subtropical regions. It is an infection of subcutaneous tissue caused by Sporothrix fungus species, but occasionally resulting in an extracutaneous condition, including osteoarticular, pulmonary, nervous central system, and ocular disease. Cases of [...] Read more.
Sporotrichosis is a subacute or chronic mycosis predominant in tropical and subtropical regions. It is an infection of subcutaneous tissue caused by Sporothrix fungus species, but occasionally resulting in an extracutaneous condition, including osteoarticular, pulmonary, nervous central system, and ocular disease. Cases of ocular sporotrichosis are rare, but reports have been increasing in recent decades. Ocular infections usually occur in hyperendemic areas of sporotrichosis. For its classification, anatomic criteria are used. The clinical presentation is the infection in the ocular adnexal and intraocular infection. Ocular adnexa infections include palpebral, conjunctivitis, and infections of the lacrimal sac. Intraocular infection includes exogenous or endogenous endophthalmitis. Most infections in the ocular adnexal have been reported in Brazil, China and Peru, and intraocular infections are limited to the USA and Brazil. Diagnosis is performed from Sporothrix isolation in the mycological examination from ocular or skin samples. Both sporotrichosis in the ocular adnexa and intraocular infection can mimic several infectious and non-infectious medical conditions. Ocular adnexa infections are treated with potassium iodide and itraconazole. The intraocular infection is treated with amphotericin B. This review describes the clinical findings and epidemiological, diagnosis, and treatment of ocular sporotrichosis. Full article
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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 29 | Viewed by 4419
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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