Aim: This study focuses on the development of a Caspofungin liposome for efficient ocular delivery by enhancing corneal penetration. Method: Quality by design (QbD) approach was adopted to identify critical factors that influence final liposomal formulation. The liposome developed using thin film hydration after optimization was subjected to characterization for physicochemical properties, irritation potential and corneal uptake. Results: The numerical optimization suggests an optimal formulation with a desirability value of 0.706, using CQAs as optimization goals with 95% prediction intervals. The optimized formulation showed no signs of irritation potential along with observation of significant corneal permeation. Conclusion: The liposomal formulation increased the permeability of Caspofungin, which could enhance the efficacy for the treatment of conditions, like fungal keratitis.
[Box: see text].

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.

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.
CONCLUSIONS: Additional investigation into innovative antifungal drug therapies is crucial for proactively tackling the potential future resistance to antifungal agents in scientific writing.

Fungal infections of cornea are important causes of blindness especially in developing nations with tropical climate. However, the challenges associated with current treatments are responsible for poor outcome. Natamycin is the only FDA-approved antifungal drug to treat fungal keratitis, but unfortunately due to its poor water solubility, it is available as suspension. The marketed suspension (5% Natamycin) has rapid precorneal clearance, poor corneal permeability, a higher frequency of administration, and corneal irritation due to undissolved suspended drug particles. In our study, we developed clear and stable natamycin-loaded nanomicelles (1% Natcel) to overcome the above challenges. We demonstrated that 1% Natcel could permeate the cornea better than 5% suspension. The developed 1% Natcel was able to provide sustained release for up to 24 h. Further, it was found to be biocompatible and also improved the mean residence time (MRT) than 5% suspension in tears. Therefore, the developed 1% Natcel could be a potential alternative treatment for fungal keratitis.

BACKGROUND: Antimicrobial resistance in microbial keratitis has not been previously explored in Alexandria. We aim to recommend effective therapies through identification of etiological agents, determination of antimicrobial susceptibilities, and comparing outcomes of empiric topical antimicrobials.
METHODS: In this 2022 prospective cohort conducted in Alexandria Main University Hospital cornea clinic, antimicrobial susceptibilities of isolated microorganisms from corneal scrapings were detected and antibiograms were developed. Bacterial (BK), fungal (FK), or mixed fungal/bacterial keratitis (MFBK) patients on empiric regimens were compared for ulcer healing, time-to-epithelialization, best-corrected visual acuity, interventions, and complications.
RESULTS: The prevalent microorganisms in 93 positive-cultures were coagulase-negative staphylococci (CoNS, 30.1%), Pseudomonas aeruginosa (14%), and Aspergillus spp. (12.9%). CoNS were susceptible to vancomycin (VAN, 100%) and moxifloxacin (MOX, 90.9%). Gram-negative bacteria showed more susceptibility to gatifloxacin (90.9%) than MOX (57.1%), and to gentamicin (GEN, 44.4%) than ceftazidime (CAZ, 11.8%). Methicillin-resistance reached 23.9% among Gram-positive bacteria. Fungi exhibited 10% resistance to voriconazole (VRC). Percentages of healed ulcers in 49 BK patients using GEN + VAN, CAZ + VAN and MOX were 85.7%, 44.4%, and 64.5%, respectively (p = 0.259). Their median time-to-epithelialization reached 21, 30, and 30 days, respectively (log-rank p = 0.020). In 51 FK patients, more ulcers (88.9%) healed with natamycin (NT) + VRC combination compared to VRC (39.1%) or NT (52.6%) (p = 0.036). Their median time-to-epithelialization was 65, 60, and 22 days, respectively (log-rank p < 0.001). The VRC group required more interventions (60.9%) than NT + VRC-treated group (11.1%) (p = 0.018). In 23 MFBK patients, none healed using NT + CAZ + VAN, while 50% healed using VRC + CAZ + VAN (p = 0.052). Regimens had comparable visual outcomes and complications.
CONCLUSIONS: Based on the higher detected susceptibility, we recommend empiric MOX in suspected Gram-positive BK, gatifloxacin in Gram-negative BK, and GEN + VAN in severe BK. Due to better outcomes, we recommend NT + VRC in severe FK.
BACKGROUND: ClinicalTrials.gov identifier, NCT05655689. Registered December 19, 2022- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05655689?cond=NCT05655689.&draw=2&rank=1.

Fungal keratitis (FK) is a fungal infection of the cornea, which is part of the eye and causes corneal ulcers and an increased risk of permanent blindness, which is often found in Candida albicans species. Amphotericin B (AMB), which is a group of polyenes as the first-line treatment of FK, is effective in annihilating C. albicans. However, AMB preparations such as eye drops and ointments have major drawbacks, for instance, requiring more frequent administrations, loss of the drug by the drainage process, and rapid elimination in the precornea, which result in low bioavailability of the drug. An ocular dissolving microneedle containing the solid dispersion amphotericin B (DMN-SD-AMB) had been developed using a mixture of poly(vinyl alcohol) (PVA) and poly(vinylpyrrolidone) (PVP) polymers, while the solid dispersion AMB (SD-AMB) was contained in the needle as a drug. This study aims to determine the most optimal and safest DMN-SD-AMB formula for the treatment of FK in the eye as well as a solution to overcome the low bioavailability of AMB eye drops and ointment preparations. SD-AMB had been successfully developed, which was characterized by increased antifungal activity and drug release in vitro compared to other treatments. Furthermore, DMN-SD-AMB studies had also been successfully performed with the best formulation, which exhibited the best ex vivo corneal permeation profile and antifungal activity as well as being safe from eye irritation. In addition, an in vivo antifungal activity using a rabbit infection model shows that the number of fungal colonies was 0.98 ± 0.11 log10 CFU/mL (F3), 5.76 ± 0.32 log10 CFU/mL (AMB eye drops), 4.01 ± 0.28 log10 CFU/mL (AMB ointments), and 9.09 ± 0.65 log10 CFU/mL (control), which differed significantly (p < 0.05). All of these results evidence that DMN-SD-AMB is a new approach to developing intraocular preparations for the treatment of FK.

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%.
The study analyzed the effectiveness of terbinafine solution in the experimental treatment of fungal keratitis.
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.
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.
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.
Способы лечения грибковых кератитов в Российской Федерации в настоящее время сводятся к нестандартизованным методам off-label по причине отсутствия лицензированных коммерческих противогрибковых растворов для применения в офтальмологии. В статье представлены результаты успешного лечения грибкового кератита у экспериментальных животных суспензией тербинафина, эффективность которого сопоставима с разведенным до 1% лиофилизатом вориконазола.
Изучение эффективности раствора тербинафина в экспериментальном лечении грибкового кератита.
Исследование проведено на кроликах породы советская шиншилла с признаками кератомикоза, смоделированного в ходе эксперимента. Пятнадцать экспериментальных животных были разделены рандомно на три группы сравнения: 1-я группа получала лечение 1,0% вориконазолом, 2-я группа — 0,1% тербинафином, 3-я группа лечения не получала.
В группах кроликов, получавших лечение кератомикоза вориконазолом и тербинафином, показаны сопоставимые положительные результаты лечения, однако в группе тербинафина эпителизация произошла раньше, а полная санация грибковой микрофлоры достигнута на 3-и сутки.
Важное конкурентное преимущество 0,1% суспензии тербинафина заключается в разработанной форме для местного применения в офтальмологии. Преимущество местного применения 0,1% суспензии тербинафина обосновано приведенной совокупностью признаков и результатов, однако полученные данные могут быть предложены для внедрения в практику после соответствующих клинических исследований.

To evaluate the efficacy and safety of hypochlorous acid (HOCI) eye drops in the treatment of fungal keratitis.
A total of 96 patients (96 eyes) with fungal keratitis were randomly divided into two groups: group Ι (conventional treatment + topical HOCI eye drops); The group II (conventional treatment). According to its severity, those patients were divided into grade Ι or grade II. Use of fungal scraping and culture to identify the type of fungal infection, slit lamp examination, and corneal fluorescein staining to observe regression, and confocal corneal microscopy to assess fungal mycelial changes. The main outcome measures were the success rate, healing time, visual recovery, and complications. The Kaplan-Meier curve method was used to analysis of the survival function of days to cure between the two groups.
There were no statistical differences between the two groups in terms of general condition, medical history, and grading. Corneal scraping results showed that all patients had filamentous fungi. For grade Ι patients, all patients were cured, and the patients in Group I showed faster healing speed than that in Group II (t = -3.665, p < .01). For grade II patients, the recovery time (t = -4.121, p < .01) and the disappearance of hypopyon (t = -4.291, p < .01) were significantly faster in the combination group. In grade Ι and II patients, the final visual acuity and the incidence of complications such as corneal neovascularization, cataract, and hyphema showed no differences in both groups. The survival curve showed that the healing rate of ulcers in the combination treatment group was faster than that in the conventional treatment group (χ2 = 14.332, p = .001).
HOCI can accelerate the healing of fungal keratitis without obvious complications, indicating a promising future in the field of keratitis treatment.

OBJECTIVE: To assess the effectiveness and safety of continuous lavage with 1% voriconazole (CL) for moderate and severe fungal keratitis.
METHODS: Thirty-one patients were randomized to receive topical eye drops either alone (T) or combined with continuous 1% voriconazole lavage (CL-T). The primary outcome was the cure rate at 3 months. The secondary outcomes were the 6-day efficacy, 3-day infiltration size and depth, hypopyon height, central corneal thickness (CCT), epithelial defect size, and subject feelings and clinical signs assessment scores.
RESULTS: At 3 months, the cure rate was comparable between the groups in patients with moderate fungal keratitis (66.7% vs. 62.5%, P = 0.60). However, among severe cases, 4 cases (44.4%) in the CL-T group healed successfully, while none in the T group; this difference was not significant (P = 0.08), although it was very close to 0.05. This may be related to the small sample size. After 6 days, the percentage of patients with \"worsened\" ulcers in the CL-T group was lower than that in the T group (0% vs. 31%, P = 0.043). The infiltration size, infiltration depth, and hypopyon height in the CL-T group were smaller than those in the T group after 3 days (all P < 0.05). There was no difference in CCT, epithelial defect size, subject feelings scores, or clinical signs scores between groups.
CONCLUSIONS: These outcomes suggest that CL is an effective and safe adjuvant method for controlling the progression of moderate and severe fungal keratitis.
BACKGROUND: ChiCTR2100050565.

UNASSIGNED: Fungal keratitis can be influenced by different genetic, environmental, and even iatrogenic factors that the impact of such factors can be very different in various populations. Thus, it should be attempted to provide a clear picture of the epidemiological situation of this disease in different areas. The aim of this study was to investigate the epidemiological aspects of fungal keratitis in a population sample from northern Iran.
UNASSIGNED: This cross-sectional study was conducted on all consecutive patients clinically suspected to fungal keratitis that were ultimately diagnosed by positive fungal culture that admitted to Amiralmomenin hospital in Rasht city, Iran, between 2011 and 2019. The sampling method was census. The required information was collected by reviewing the hospital\'s recorded files.
UNASSIGNED: Forty seven patients were examined in the study that 53.2% of the patients were men. Among the population of women, housewives-farmers with the prevalence rate of 45% and among the population of men, those with farm occupation with the prevalence rate of 52% formed the most common occupational subgroups. Most patients (89.3%) had no history of any ocular surgery or manipulation. Aspergillus was the most frequent pathogen (23.4%) followed by Penicillium (19.1%) and Fusarium (17.0%). History of chronic disorders was also revealed in 44.6%. The results of smear and culture obtained from the study were as follows: in 8.5% of patients as positive smear and positive culture, and in 91.5% as negative smear and positive culture. Only 2.1% used the lens.
UNASSIGNED: Fungal keratitis affects our male population slightly higher than females with the highest overall prevalence rate in the sixth and seventh decades of life. The most frequent fungal strains responsible for fungal keratitis include Aspergillus followed by Penicillium and Fusarium.