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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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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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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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Keratomycosis, caused by pathogenic fungi, is an intractable blinding eye disease. Corneal penetration is an essential requirement for conventional antifungal medications to address keratomycosis. Due to the distinctive anatomical and physiological structure of the cornea, the therapeutic efficacy is hampered by the inadequate penetration capacity. Despite the emergence of diverse antifungal drug delivery systems and advanced antifungal nanomaterials, it has remained challenging to achieve corneal penetration over the past decade. This study fabricates a penetrative ionic organic molecular cage-based nanozyme (OMCzyme) for treating keratomycosis. The synthesis of OMCzyme involved two steps. Initially, the ionic OMC is synthesized by a [2+3] cycloimination reaction of triformylphloroglucinol and 2,3-diaminopropionic acid. Subsequently, OMCzyme is fabricated by coordination of Fe2⁺ with carboxyl anions and phenolic hydroxyls in the organic cage, and further deposition of silver nanoparticles on the surface of OMC-Fe complex. The as-prepared OMCzyme demonstrates excellent water dispersion, peroxidase-like activity, in vitro and in vivo biocompatibility, and corneal penetration. Notably, the nanozyme displays targeted antifungal activity, effectively combating Fusarium solani with negligible cytotoxicity toward human corneal epithelial cells. The hybrid mimic is further demonstrated to be effective in treating keratomycosis in mice, indicating the potential of OMCzyme for curing fungal infectious diseases.

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Keratomycosis, also termed fungal keratitis (FK), is an invasive eye condition for which there is a lack of available effective treatment due to pharmacological shortages and vital ocular obstacles. This severe corneal infection typically suppurates and eventually ulcerates, ultimately causing blindness or decreased vision. According to epidemiological studies, FK is more common in warm, humid places with an agricultural economy. The use of nanoemulsion carriers for ocular fungal infection has been promoting better treatment and patient compliance. The persistent fungal infection like FK, affecting particularly the stroma heralds complications thereby posing difficulty in diagnosis and treatment. To help treat refractory cases and improve outcomes, recently targeted drug delivery techniques and novel antifungal drugs shall be explored. A delay in diagnosis may cause corneal fungal infections to have irreversible consequences, which cannot be avoided. However, infections can develop into ocular perforation even after receiving intense care. The commonly used chemotherapy for FK is based on topical (natamycin 5% is typically first-line therapy) and systemic administration of azole drugs. To address the problems related to better treatment, various nanoemulsion carriers were discussed. Novel drug delivery systems based on nanoemulsions are a viable therapeutic option for treating keratomycosis and may be a candidate method for overcoming obstacles in the treatment of many other ocular illnesses when combined with different hydrophobic medicines. With a brief explanation of the pathogenesis, this article seeks to give readers a thorough analysis of current trends, various treatment choices, and care strategies for fungal keratitis.

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Fungal keratitis is one of the major causes of microbial keratitis that may lead to corneal blindness. Many problems related to diagnosis and therapy are encountered in fungal keratitis, including difficulty in obtaining laboratory diagnoses and the availability and efficacy of antifungal medications. Intensive and prolonged use of antifungal topical preparations may not be enough. The use of antifungal medications is considered the main treatment for fungal keratitis. It is recommended to start antifungal therapy after confirmation of the clinical diagnosis with a smear or positive cultures. Topical application of antifungal medications is a mainstay for the treatment of fungal keratitis; however, systemic, intra-stromal, or intra-cameral routes may be used. Therapeutic keratoplasty is the main surgical procedure approved for the management of fungal keratitis with good success rate. Intrastromal corneal injection of antifungal medications may result in steady-state drug levels within the corneal tissue and prevent intervals of decreased antifungal drug concentration below its therapeutic level. In cases of severe fungal keratitis with deep stromal infiltration not responding to treatment, intracameral injection of antifungal agents may be effective. Collagen cross-linking has been proposed to be beneficial for cases of fungal keratitis as a stand-alone therapy or as an adjunct to antifungal medications. Although collagen cross-linking has been extensively studied in the past few years, its protocol still needs many modifications to optimize UV fluence levels, irradiation time, and concentration of riboflavin to achieve 100% microbial killing.

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This retrospective study evaluated tear film (TF) interferometry on horses examined in Northern Italy in 2019-2021. The objectives were to evaluate horses affected by keratitis, and to describe TF values in horses with no evidence of ocular disease. All horses received a complete ophthalmic examination and were examined with the Ocular Surface Analyser, Veterinary-setting, prior to eye manipulation, staining and sample collection. Eighteen horses with no evidence of ocular disease were included in the comparison group. Additionally, 46 horses displaying signs of keratitis (neovascularization, corneal opacities, ulceration, epithelial and subepithelial infiltrates) were evaluated. These horses were divided into presumed non-infectious and infectious or presumed infectious keratitis groups (one with proven bacterial origin, and the others with diagnosed or presumptive keratomycosis) with the former including immune-mediated keratitis. From the observations of TF interferometry in the comparison population the authors concluded that for non-invasive break-up time (NIBUT), the estimated preliminary reference interval was 10.4-31.2s, and for tear meniscus height (TMH), it was 0.215-0.457mm. Moreover, within the keratitis population, from an interferometric point of view punctate lesions of the ocular surface were present in all cases of active diagnosed or presumptive subepithelial keratomycosis but not in any of the non-infectious cases, either non-ulcerative or ulcerative. Limitations of the study include a relatively low number of horses examined and the fact that the diagnosis of infectious keratitis was presumptive and based on clinical improvement after treatment in some cases. To the authors' knowledge, this is the first report of TF interferometry performed in horses.

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Methods of treatment of fungal keratitis in the Russian Federation currently consist of non-standardized off-label methods due to the lack of licensed commercial antifungal solutions designed for use in ophthalmology. The article presents the results of successful treatment of fungal keratitis in experimental animals with a terbinafine solution, with effectiveness comparable to voriconazole lyophilizate diluted to 1%. PURPOSE: The study analyzed the effectiveness of terbinafine solution in the experimental treatment of fungal keratitis. MATERIAL AND METHODS: The study was conducted on Soviet chinchilla rabbits with signs of keratomycosis modeled during the experiment. Fifteen experimental animals were randomly divided into three comparison groups: group 1 received treatment with 1% voriconazole, group 2 - 0.1% terbinafine, group 3 did not receive treatment. RESULTS: Groups of rabbits treated with voriconazole and terbinafine showed comparable positive treatment results, but in the terbinafine group epithelization was completed earlier, and complete sanitation of the fungal microflora was achieved on day 3. CONCLUSION: One important advantage of 0.1% terbinafine suspension lies in availability of a local form designed for ophthalmological application. The advantage of local 0.1% terbinafine suspension is supported by the combination of signs and results, and the obtained data may be used for introducing it into practice after further clinical trials.

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Keratomycosis is common in Indian subcontinent. Diagnosis of the causal agent and successful management is a challenge for the clinician. Scedosporium is a rare fungus species, and it is relatively rare in causing keratomycosis. We report the case of a 29-year-old male who presented with complaints of redness, watering, and white lesion over his left eye. He sustained an injury in the left eye with vegetative matter. Corneal scraping was sent for potassium hydroxide staining and culture; fungal colony was seen in culture. Colony characters on Sabouraud dextrose agar and lactophenol cotton blue enabled a diagnosis of Scedosporium species. The patient was treated with topical Natamycin 5%, and complete resolution was seen at the end of 4 weeks. This case report highlights good response of keratitis caused by Scedosporium to topical Natamycin therapy.

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Fungi are ubiquitous in the environment and part of the commensal microflora on the conjunctiva of equine eyes. North Queensland, being tropical, presents an ideal environment for fungi growth. When the cornea is injured, fungi can invade the corneal stroma, resulting in keratomycosis. The objectives of this study were to determine the fungal species specific to the eyes of horses in the Townsville region; to investigate the potential risk factors associated with the presence of fungi; and to test their susceptibility to antifungals to create an empirical guide for treatment. The eyes of forty ophthalmologically normal horses from James Cook University were sampled throughout the summer months of December 2017, January 2018, and January and February 2020. Cultured fungi were identified morphologically, and their identity confirmed by comparing partial 18sRNA DNA sequences with the NCBI nucleotide database. Minimum inhibitory concentration testing of common antifungal medications was performed. Sixty-one out of eighty conjunctival samples grew fungi, and 21 different fungi genera were isolated. The most common genera were Aspergillus (18%, 26/141), Curvularia (14%,20/141), Rhodotorula (12%,17/141) and Penicillium (12%,17/141). No significant association was found between age or environmental factors and fungal culture status. Most fungi were highly susceptible to voriconazole and ketoconazole but resistant to fluconazole and amphotericin B. This adds to the body of evidence on which species of fungi are present as normal ocular microflora of horses living in tropical regions of Australia, and an avenue for treating them.

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BACKGROUND: Acrophialophora species is an infrequent human opportunistic pathogen. It is widely distributed in temperate as well as tropical regions. Here, we present a rare case of fungal keratitis caused by A. fusispora. CASE PRESENTATION: A 26-year male driver presented with pain, watering, redness, whitish discoloration, and blurring of vision in the left eye for the last 3-4 days. Upon examination, he had a dry-looking corneal ulcer with infiltration and satellite lesions. Corneal scrapings were positive for septate fungal hyphae by Gram staining and KOH mount. After five days, the growth observed was presumptively identified as genus Acrophialophora and finally identified as Acrophialophora fusispora by genetic sequencing. The patient failed to respond medically and was planned for therapeutic keratoplasty. DISCUSSION: To date, four cases of ocular involvement due to Acrophialophora have been described. Amongst which one case was associated with an immunocompromised state. Three of the cases were resolved medically, while one required therapeutic keratoplasty, indicating possible strong pathogenicity to the eye. CONCLUSION: As Acrophialophora seems to have a predilection for eye infections, an early diagnosis with timely appropriate treatment is the best way to restore the normal vision of a patient.

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PURPOSE: To investigate the dematiaceous fungal profile of patients with ocular mycoses attending a tertiary eye care hospital in Coimbatore, India METHODS: The identification of dematiaceous fungus based on their morphology, their genotypes, and the measurement of the minimum inhibitory concentrations (MICs) using microdilution method of routinely used antifungal drugs were all compared. RESULTS: A total of 148 dematiaceous fungi were isolated during a study period of 27 months. Isolates were confirmed as Curvularia spp. (n = 98), Exserohilum spp. (n = 32), Alternaria spp. (n = 14), Exophiala spp. (n = 2), Cladosporium sp. (n = 1) and Aureobasidium sp. (n = 1). Out of 50 well grown isolates characterized genotypically based on the amplification and sequencing of the ITS region of the ribosomal RNA gene cluster and subsequent BLAST analysis, Curvularia lunata (n = 24), C. aeria (n = 1), C. spicifera (n = 8), C. hawaiiensis (n = 1), C. maydis (n = 2), C. papendorfii (n = 2), C. geniculata (n = 3), C. tetramera (n = 2) and Exs. rostratum (n = 7) were identified. In vitro antifungal susceptibilities of the most tested dematiaceous isolates showed that voriconazole had a MIC50 of 0.25 µg ml-1, while amphotericin B had a MIC50 of 0.25 µg ml-1 for Curvularia spp. and Alternaria spp. CONCLUSION: Voriconazole proved to be the most effective drug against the pigmented filamentous fungi, followed by amphotericin B, itraconazole and econazole.

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This study aims to develop efficient topical therapy for keratomycosis using sertaconazolenitrate (STZN)-loaded leciplex (LP). The D-optimal design was used to optimize STZN-loaded LP by utilizing soy phosphatidylcholine (SPC) molar ratio (X1), cationic surfactant molar ratio (X2), and cationic surfactant type (X3) as the independent variables, whereas their impact was studied for entrapment efficiency percent (EE; Y1), particle size (PS; Y2), polydispersity index (PDI; Y3), zeta potential (ZP; Y4), and permeability coefficient (Kp; Y5). The optimized formula was evaluated regarding morphology, ex vivo permeation, mucoadhesion, stability, and in vivo studies. The optimized formula was spherical and showed EE of 84.87 ± 1.71%, PS of 39.70 ± 1.35 nm, PDI of 0.242 ± 0.006, ZP of +54.60 ± 0.24 mV, and Kp of 0.0577 ± 0.0001 cm/h. The ex vivo permeation study revealed that the optimized formula enhanced the Kp and corneal deposition by 2.78 and 12.49 folds, respectively, compared to the aqueous drug dispersion. Furthermore, the optimized formula was stable and revealed promising mucoadhesion properties. Finally, the in vivo studies showed that the optimized formula was superior to the drug dispersion in treating rats with induced keratomycosis. These results confirmed the capabilities of LP as a promising nanocarrier for treating ocular diseases topically.

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BACKGROUND: Fungal keratitis due to Fusarium species is known to be typical of developing countries; however, with the increasing use of contact lenses a rise of Fusarium keratitis has been observed in Germany. METHODS: In a monocentric retrospective study, we analyzed all patients who presented to our university eye hospital with infectious keratitis between January 2011 and December 2021 and had a proof of Fusarium species in either microscopy, culture or PCR. RESULTS: We could identify 13 patients with a proof of Fusarium species. A significant increase of cases in 2021 was observed. In 76.9% of our cases the patients were female and in 76.9% the patients had a history of prior contact lens use. In only 4 cases the initial corneal sample gave a positive result for Fusarium. On average the suspicion of fungal keratitis arose 13.1 days after onset of symptoms, correct diagnosis was achieved after 14.6 days. All isolated specimens showed resistance against at least one of the common fungicides. In 70% of our cases treatment with penetrating keratoplasty was necessary. The patients showed a 57.1% recurrence rate after penetrating keratoplasty. In 80% of our cases best documented visual acuity after Fusarium keratitis was ≤ 0.4. CONCLUSION: Due to difficult detection and a high resistance rate to common antifungals, Fusarium keratitis is prone to delayed diagnosis and limited treatment outcomes. Whenever risk factors are present and infectious keratitis does not respond to antibiotics, antimycotic treatment must be initiated. Early keratoplasty may be necessary.

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PURPOSE: To examine the relationship between Minimum Inhibitory Concentration (MICs) and response to therapy of 6 Fusarium spp. and 5 Aspergillus fumigatus isolated from equine ulcerative keratitis cases. PROCEDURE: Fungi were identified by morphology and Internal Transcribed Spacer (ITS) polymerase chain reaction (PCR) with sequencing and evaluated at the University of Texas Fungal Testing Laboratory for susceptibility to three azole antifungals (miconazole, voriconazole, posaconazole), natamycin, and two echinocandins (anidulafungin, caspofungin). A Mann-Whitney rank sum test was used for the comparison of time to heal between infections of different fungal genera and in vitro susceptibility to the drug administered. RESULTS: Fusarium spp. were resistant to azole antifungals in 6/6 cases (100%). Fusarium spp. were susceptible to echinocandins and natamycin in all cases. A. fumigatus was resistant to anidulafungin in 1/5 cases (20%) and posaconazole in 1/5 cases (20%) The remainder of A. fumigatus isolates were susceptible to all antifungal agents tested. Fusarium isolates were treated with antifungals to which they were not susceptible; however, all cases of A. fumigatus were treated with antifungals to which they were susceptible. All Fusarium cases and A. fumigatus cases experienced clinical resolution, regardless of surgical intervention. There was no statistical correlation between fungal genus and time to heal (p < .082). CONCLUSIONS: The in vitro susceptibility indicated that all cases of Fusarium spp. were resistant to azole antifungal drugs which were used as treatment. Clinical outcomes, however, showed that all cases healed despite resistance to antifungals.

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Purpose: This study aims to assess the testing methods used to detect fungal pathogens as well as the pathogenic profiles and drug susceptibility among fungal isolates from ocular sources collected in a tertiary eye hospital. Methods: The laboratory test records of patients with suspected ocular fungal infection from January 2010 to December 2019 at a tertiary eye care center in southern China were retrospectively evaluated. The isolated pathogens identified by smear examination and culture combined with microscopy were analyzed. For 2017-2019 fungal isolates, their antifungal susceptibilities to four antifungal agents were evaluated. Results: A total of 22,233 specimens (16,315 for culture and 5918 for direct smear examination) from 16,209 individuals were assessed, and 3317 specimens (2169 for culture and 1148 for smear examination) from 2395 patients had confirmed fungal infection. The mean age of patients was 50.6±14.2 years and 63.4% were male. The positive rate of smear examination was 19.4% and significantly higher than 13.3% of fungal culture (p< 0.001). Of 5812 patients who were simultaneously examined for culture and smear staining, 897 (15.43%) had positive findings for fungi. Among the 2420 positive findings, 2138 (88.3%) were from the cornea, and 133 (5.5%) were from intraocular samples. Fusarium spp. (40.5%) and Aspergillus spp. (22.0%) were the major fungal genera among the molds, whereas Candida spp. (4.6%) constituted the major yeast. Fusarium spp. had a lower antifungal susceptibility than Aspergillus spp. against voriconazole and amphotericin. And yeast spp. had the highest susceptibility to caspofungin. Conclusion: This study provided a 10-year assessment of fungi in ocular infections in southern China, giving support to epidemiological understanding and guiding empiric antimicrobial therapy.

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La córnea es la membrana transparente en forma de disco abombado, que constituye la parte anterior del globo ocular y se halla delante del iris. La infecciones de este tejido son muy comunes y pueden llegar a producir ulceras. Un tratamiento retardado o inadecuado puede dar lugar a complicaciones, una de estas puede ser la perforación corneal. (AU)

The cornea is the transparent membrane in the form of a bulging disc, which forms the front part of the eyeball and is located in front of the iris. Infections of this tissue are very common and can lead to ulcers. Delayed or inadequate treatment can lead to complications, one of which can be corneal perforation. (AU)

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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.

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BACKGROUND: Endophthalmitis is an uncommon yet devastating compilation of Fusarium keratitis. Cases of Fusarium keratitis are seen commonly in tropical regions of the world; however, they have been increasing in frequency in the United States. CASE REPORT: We present the case of a 36-year-old man who experienced an ocular lens expulsion secondary to Fusarium endophthalmitis. Why Should an Emergency Physician Be Aware of This?:Fusarium keratitis is becoming more common and can progress to endophthalmitis without proper management. This infection can be difficult to recognize and treat, so early action by the emergency physician could be the difference between vision loss and vision-sparing care.

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The expansion of polymicrobial keratomycosis (PMK) requires dynamic pharmacotherapy of antimycotics along with antibacterial agents such as fluconazole (FCZ) and ofloxacin (OFX). To effective clinical cure, different microbes require different dosage regimens. A responsive, selective, and fast method for estimation of FCZ and OFX in rabbit tears using high-performance liquid chromatography together with tandem mass spectrometry (LC-MS/MS) was established and validated using ketoconazole as an internal standard (IS). An isocratic separation was achieved using a C18 column with methanol and aqueous 0.2% formic acid (80:20, v/v) as a mobile phase with a total run time and flow rate of 4 min and 400 µL/ min, respectively. The FCZ and OFX were detected utilizing positive ion electrospray ionization (ESI) in multiple reactions monitoring mode. The tear sample extraction was carried out using simple deproteination using methanol. The systematic method validation was carried out according to USFDA regulatory guidelines for selectivity, linearity (r2>0.99), intra-day and inter-day precision and accuracy, matrix effect, dilution integrity, and stability. The validated bioanalytical method was successfully pertained to determine the pharmacokinetics profile of FCZ and OFX marketed formulation in preclinical rabbit tears.

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