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AimTo compare and evaluate the efficacy of topical 0.1% micafungin (MCFG) and topical 0.2% fluconazole (FCZ) in the treatment of Candida fungal keratitis.MethodsTwenty-nine eyes of 29 patients who were diagnosed as having Candida fungal keratitis, proven by corneal culture isolates, were investigated in this prospective study. Patients were divided into a MCFG treatment group (12 eyes) and an FCZ treatment group (17 eyes). Age, gender, initial status of ulcer (ulcer size and degree of injection), initial and final best-corrected visual acuity (BCVA), healing periods, final status of cornea and recurrences in each group were studied and compared.ResultsThere were no significant differences in relation to age, gender, ulcer size and degree of injection before treatment between the two groups. There were also no significant differences in the healing periods until complete epithelialisation (MCFG treatment group (41.3±38.0 days); FCZ treatment group (34.4±37.7 days)), change in BCVA, corneal clarity/opacification, perforation and recurrence status at the final examination between the two groups.ConclusionThe efficacy of 0.1% MCFG eye-drops appears to be comparable with that of 0.2% FCZ eye-drops in the treatment of Candida fungal keratitis.

Microbial keratitis caused by more than one microorganism is rare. It may occur as a coinfection or as a secondary infection superimposed with an existent microorganism. Both infectious and immune mechanisms are implicated in microbial keratitis. Herein, we report an unusual clinical case of viral and fungal mixed infection. Written informed consent was obtained from the patient.

Purpose. To analyze pathogens of keratomycosis resistant to antifungal therapy, the spectrum of sensitivity to antimicotic agents in series of fungal keratitis. Material and methods. There is a retrospective analysis of fungal keratitis in 12 patients (12 eyes) who underwent an inpatient treatment from August 2018 to January 2020 (18 months). Clinical data of patients was recorded in specially developed forms. Results.Keratomycosis was confirmed in 12 cases of keratitis with resistantce to the local antimicrobial and anti-inflammatory therapy during the study period. All patients used contact lenses from different manufacturers, had a history of outpatient treatment with antibacterial, non-steroidal anti-inflammatory eye drops, and keratoprotectors, topical glucocorticosteroids and antiherpetics for 2 weeks to 2 months. Identification of the pathogen was carried out by the direct microscopy method, followed cultural research in the mycological laboratory, as well as clinical manifestations. In 10 cases, Fusarium spp was detected, in 1 case – Penicillinum, in 1 case – Candida. According to the conclusion of the mycological study, 100% of fungal agents has resistance to fluconazole and amphotericin B. The sensitivity of agents to antimicotic agents was analyzed, and the equipment of antifungal drugs required for use on the basis of the study was revised. Conclusion. In a series of clinical cases of fungal keratitis, the dominant pathogen was Fuzarium. The found broad resistance to fluconazole and amphotericin B, high sensitivity to nystatin, terbinafine, and ketoconazole shows that each case of keratomycosis has an original clinical picture, must be considered in detail, and requires a careful diagnosis and individual treatment tactics.

PurposeTo provide recent data on patient demographics, clinical profile and outcomes of patients with microbial keratitis over a 5-year period at the Sydney Eye Hospital, and to identify seasonal variations of the main causative organisms.MethodA retrospective study of patients with a clinical diagnosis of microbial keratitis and corneal scrape performed between 1 January 2012 and 31 December 2016. Clinical information was gathered from medical records and pathology data.ResultsOne thousand fifty-two eyes from 979 patients with a mean age of 54.7 ± 21.5 years (range 18–100 years) were included. The majority of cases were bacterial (65%) followed by polymicrobial (2.4%), fungi (2.3%), and culture-negative (31%). Common risk factors for microbial keratitis were contact lens wear (63%) and previous topical steroid use (24%). Factors significantly associated with poor patient outcomes in the multivariate model were age, visual acuity, and epithelial defect size (p < 0.05). Patients with fungal or polymicrobial keratitis presented with worse clinical features at initial and final presentation (p < 0.05). There was a significant variation in the occurrence of Pseudomonas aeruginosa (p = 0.018) and fungal keratitis (predominately made up of Candida and Fusarium species) (p = 0.056) in the hottest seasons.ConclusionPoorer outcomes are more likely to be seen in older patients and those presenting with poor visual acuity and large epithelial defects at the initial presentation.

PurposeTo assess the effectiveness and safety of continuous lavage with 1% voriconazole (CL) for moderate and severe fungal keratitis.MethodsThirty-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.ResultsAt 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.ConclusionThese outcomes suggest that CL is an effective and safe adjuvant method for controlling the progression of moderate and severe fungal keratitis.Trial registration numberChiCTR2100050565.

Fungal keratitis (FK) is a serious pathogenic condition usually associated with significant ocular morbidity. Natamycin (NAT) is the first-line and only medication approved by the Food and Drug Administration for the treatment of FK. However, NAT suffers from poor corneal penetration, which limits its efficacy for treating deep keratitis. The objective of this work was to prepare NAT solid lipid nanoparticles (NAT-SLNs) to achieve sustained drug release and increased corneal penetration. NAT-SLNs were prepared using the emulsification-ultrasonication technique. Box- Behnken experimental design was applied to optimize the effects of independent processing variables (lipid concentration [X ], surfactant concentration [X ], and sonication frequency [X ]) on particle size (R ), zeta potential (ZP; R ), and drug entrapment efficiency (EE%) (R ) as responses. Drug release profile, ex vivo corneal permeation, antifungal susceptibility, and cytotoxicity of the optimized formula were evaluated. The optimized formula had a mean particle size of 42 r.nm (radius in nanometers), ZP of 26 mV, and EE% reached ~85%. NAT-SLNs showed an extended drug release profile of 10 hours, with enhanced corneal permeation in which the apparent permeability coefficient (P ) and steady-state flux (J ) reached 11.59×10 cm h and 3.94 mol h , respectively, in comparison with 7.28×10 cm h and 2.48 mol h for the unformulated drug, respectively. Antifungal activity was significantly improved, as indicated by increases in the inhibition zone of 8 and 6 mm against ATCC 1022 and a clinical isolate, respectively, and minimum inhibitory concentration values that were decreased 2.5-times against both of these pathogenic strains. NAT-SLNs were found to be non-irritating to corneal tissue. NAT-SLNs had a prolonged drug release rate that improved corneal penetration, and increased antifungal activity without cytotoxic effects on corneal tissues. Thus, NAT-SLNs represent a promising ocular delivery system for treatment of deep corneal keratitis.

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.

PurposeTo report clinical profile and compare management options for Pythium keratitis.MethodRetrospective interventional study of 46 patients diagnosed as Pythium keratitis by PCR DNA sequencing from January 2014 to July 2017. Interventions were categorised into medical management (MM) (topical azithromycin and linezolid with oral azithromycin at presentation), surgery (S) (therapeutic penetrating keratoplasty, TPK), surgical adjunct (SA) (cryotherapy±alcohol with TPK) and medical adjunct (MA) (MM after TPK).ResultsPrimary treatment included MM (1 eye), SA (3 eyes) and S (42 eyes). Recurrence occurred in 27/43 eyes (MM+S group). Second surgery (S) was required in 11 eyes (TPK-2), with additional procedures (SA) in 10 eyes and evisceration in five eyes. 8/43 eyes received MA after TPK-1. One eye required TPK-3. Recurrence occured in all eyes that received MA (100%) and in 28 of 54 TPKs (51.8%) (TPK 1+2+3) in 42 eyes. Recurrence was noted in 1/14 (7.1%) that underwent SA.ConclusionThe currently available and recommended treatment for Pythium keratitis is surgical by means of a TPK and in worse cases evisceration. In our study, MM/MA measures showed no benefit with recurrence or worsening of infection requiring resurgery. Almost 50% of TPKs had a recurrence requiring resurgery. However, adjunctive procedures during TPK appear to have additional benefit with low risk of recurrence and could be included as routine care.

Mycotic keratitis is a major cause of corneal blindness, especially in tropical and subtropical countries. The prognosis is markedly worse compared to bacterial keratitis. Delayed diagnosis and scarcity of effective antifungal agents are the major factors for poor outcome. Over the last decade, considerable progress has been made to rapidly diagnose cases with mycotic keratitis and increase the efficacy of treatment. This review article discusses the recent advances in diagnosis and management of mycotic keratitis with a brief discussion on rare and emerging organisms. A MEDLINE search was carried out for articles in English language, with the keywords, mycotic keratitis, fungal keratitis, emerging or atypical fungal pathogens in mycotic keratitis, investigations in mycotic keratitis, polymerase chain reaction in mycotic keratitis, confocal microscopy, treatment of mycotic keratitis, newer therapy for mycotic keratitis. All relevant articles were included in this review. Considering the limited studies available on newer diagnostic and therapeutic modalities in mycotic keratitis, case series as well as case reports were also included if felt important.

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.