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Purpose: To elucidate a distinctive clinical feature in cases of microsporidial stromal keratitis (MSK)., Method: A retrospective observational study of cases with a histopathological and/or microbiological diagnosis of MSK on corneal biopsy or host corneal button between 2016 and 2022 was conducted., Results: Eighteen cases with a confirmed histopathological and/or microbiological diagnosis of MSK were detected. Careful review of slit-lamp photographs revealed the presence of pigmented keratic precipitates (KPs) beyond the area of stromal keratitis in five out of eighteen cases (27.7%)., Conclusion: The presence of pigmented KPs beyond the area of lesion can alert the clinician to keep microsporidia as a differential cause for stromal keratitis. Management can be tailored accordingly for a better outcome.

Competing Interests: Financial disclosures/conflicts of interest: None reported.

Purpose: The aim of this study was to evaluate the role of anterior segment optical coherence tomography during follow-up of infectious keratitis and to assess response to treatment., Methods: This was a prospective, consecutive, observational clinical series of cases. Twenty-three eyes of 23 patients with clinically proven fungal keratitis were included in the study. The patients received medical treatment according to clinical diagnosis, and follow-up was performed weekly. Slit-lamp examination and photography, and anterior segment optical coherence tomography were performed at initial and follow-up visits until corneal healing occurred. The main outcome measures included infiltrate depth, width, and density; central corneal thickness; minimal corneal thickness; corneal thickness at the site of the lesion; and stromal thickness at the center of the lesion., Results: Twenty-three eyes of 23 patients (17 men and 6 women), mean age 42.5 ± 19 (8-66) years, were clinically diagnosed with fungal keratitis. Localization was central in 14 cases and paracentral/peripheral in 9 cases. Healing time was 6 to 12 weeks. Minimal corneal thickness, corneal thickness at the site of lesion, and stromal thickness at the center of lesion, and also infiltrate width and depth changed significantly from the first visit to the healing stage at the last follow-up (0.009, 0.001, 0.007, 0.001, and <0.001, respectively)., Conclusions: In cases of fungal keratitis, anterior segment optical coherence tomography can provide the clinician with a quantitative assessment of a number of corneal parameters that can be used to determine effectiveness of therapy and confirm complete healing of the lesions that cannot be achieved by clinical evaluation., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To describe a patient diagnosed with Exophiala jeanselmei keratitis., Methods: We report a case of a patient who developed infectious keratitis following laser in situ keratomileusis and chronic topical steroid use for approximately six months in both eyes. An atypical infiltrate containing dark pigmentation was noted in the left eye on the initial presentation. During treatment, the infiltrates of the right eye began to exhibit a similar pigmentation., Results: Early treatment with topical antifungals was initiated in the left eye and later in the right eye once culture results returned. Both eyes recovered with good vision after approximately one month., Conclusions: Patients treated with postoperative topical corticosteroids should be cautioned of potential adverse effects of chronic use and have close follow-up. If infectious keratitis develops, particularly after two weeks, then atypical organisms, such as fungi, should be considered. In addition, our case highlights the significance of recognizing and associating dark-pigmentation with fungal etiologies., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Purpose: An increase in fungal and particularly filamentous keratitis has been observed in many geographic areas, mostly in contact lens wearers. This study seeks to characterize long-term trends in fungal keratitis in a continental climate area to provide guidance for diagnosis and treatment., Design: Retrospective multicentric case series., Methods: Cases of microbiology-confirmed fungal keratitis from 2003 to 2022 presenting to tertiary care centers across Canada were included. Charts were reviewed for patient demographics, risk factors, visual acuity, and treatments undertaken., Results: A total of 138 patients were identified: 75 had yeast keratitis while 63 had filamentous keratitis. Patients with yeast keratitis had more ocular surface disease (79% vs 28%) while patients with filamentous keratitis wore more refractive contact lenses (78% vs 19%). Candida species accounted for 96% of all yeast identified, while Aspergillus (32%) and Fusarium (26%) were the most common filamentous fungi species. The mean duration of treatment was 81 ± 96 days. Patients with yeast keratitis did not have significantly improved visual acuity with medical treatment (1.8 ± 1 LogMAR to 1.9 ± 1.5 LogMAR, P = .9980), in contrast to patients with filamentous keratitis (1.4 ± 1.2 LogMAR to 1.1 ± 1.3 LogMAR, P = .0093)., Conclusions: Fungal keratitis is increasing in incidence, with contact lenses emerging as one of the leading risk factors. Significant differences in the risk factors and visual outcomes exist between yeast keratitis and filamentous keratitis which may guide diagnosis and treatment., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background/aims: To determine the clinical features, predisposing factors, and management of infectious keratitis caused by Candida spp., Methods: Retrospective chart review., Results: The medical records of 52 patients (54 eyes) with Candida keratitis were available for statistical analysis. Thinning of the corneal stroma was identified in 34 eyes (63.0%), and corneal perforation occurred in 16 eyes (29.6%). Corneal thinning and perforation were more common in Candida albicans compared with non-albicans ( P-val  < .001, P  = .09, respectively). The most common predisposing factors for Candida keratitis were topical steroid use (21 patients, 40.4%), previous corneal transplantation (17 patients, 32.7%), and preexisting ocular surface disease (15 patients, 28.8%). Fourteen eyes (25.9%) required cyanoacrylate glue application and 10 eyes (18.5%) underwent therapeutic penetrating keratoplasty (TPK)., Conclusion: Local immunosuppression and ocular surface disease play an important role in Candida keratitis. C. albicans appears to be more invasive compared with non-albicans spp.

Purpose: To report the first case of Rhizopus sp keratitis in a 15-year-old male patient who had undergone a conventional Epi-off CXL procedure for progressive keratoconus., Methods: A 15-year-old male studying at school presented with defective vision in both eyes recently. He was diagnosed with progressive keratoconus in the right eye more than left eye. After the conventional CXL procedure, the patient developed corneal ulcer on third postoperative day., Results: The microbiological diagnosis of both BCL and ulcer revealed Rhizopus sp. The patient responded to topical antifungals, and the ulcer entirely healed with a large central scar., Conclusion: Rhizopus keratitis is rare in a healthy individual. Ours is the first case report of Rhizopus keratitis in patient undergone CXL., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To describe the first case of Pythium insidiosum keratitis masquerading as dematiaceous fungal keratitis in a seropositive male., Case Summary: A 44-year-old seropositive male previously treated for acute retinal necrosis presented with pain and defective vision in the right eye following a mud injury 5 days back. Presenting visual acuity was hand movements close to the face. Ocular examination revealed a 7 × 7 mm dense, greyish-white mid stromal infiltrate with pigmentation and few tentacles. The clinical diagnosis suggested fungal keratitis. Corneal scraping on 10% KOH and Gram stain revealed slender, aseptate hyaline hyphae. Before culture results, the patient was treated with topical 5% natamycin and 1% voriconazole, but the infiltrate progressed. Culture on 5% sheep blood agar revealed white fluffy, submerged, shiny, and appressed colonies, and Pythium insidiosum was confirmed by zoospore formation. The patient was further managed with topical linezolid 0.2% hourly, azithromycin 1% hourly, and adjuvant drugs., Conclusion: This is an uncommon presentation of Pythium keratitis masquerading as dematiaceous fungal keratitis in an immunocompromised male.

Purpose: Fungal keratitis (FK) is an invasive corneal infection associated with significant risk to vision. Although the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway has been recognized for its role in defending against viral infections, its involvement in FK still remains largely unclear. This study sought to elucidate the contribution of the cGAS/STING signaling pathway to the pathogenesis of FK., Methods: The expression of cGAS/STING signaling components was assessed in a murine model of Candida albicans keratitis through RNA sequencing, western blot analysis, immunofluorescence staining, and real-time PCR. Both genetic (utilizing Sting1gt/gt mice) and pharmacological (using C176) interventions were employed to inhibit STING activity, allowing for the evaluation of resultant pathogenic alterations in FK using slit-lamp examination, clinical scoring, hematoxylin and eosin (H&E) staining, fungal culture, and RNA sequencing. Subconjunctival administration of the NOD-like receptor protein 3 (NLRP3) inflammasome inhibitor MCC950 was performed to evaluate FK manifestations following STING activity blockade. Furthermore, the impact of the STING agonist diABZI on FK progression was investigated., Results: Compared to uninfected corneas, those infected with C. albicans exhibited increased expression of cGAS/STING signaling components, as well as its elevated activity. Inhibiting cGAS/STING signaling exacerbated the advancement of FK, as evidenced by elevated clinical scores, augmented fungal load, and heightened inflammatory response, including NLRP3 inflammasome activation and pyroptosis. Pharmacological inhibition of the NLRP3 inflammasome effectively mitigated the exacerbated FK by suppressing STING activity. Conversely, pre-activation of STING exacerbated FK progression compared to the PBS control, characterized by increased fungal burden and reinforced inflammatory infiltration., Conclusions: This study demonstrates the essential role of the cGAS/STING signaling pathway in FK pathogenesis and highlights the necessity of its proper activation for the host against FK.

Purpose: To evaluate and compare the results of the conjunctival flap (CF) and cryopreserved amniotic membrane graft (AMG) in the management of fungal corneal ulcers either with complications or non-responsive to medical treatment., Study Design: A retrospective observational study., Methods: Medical records of 30 patients with culture-positive fungal corneal ulcer treated with either CF or AMG (15 eyes in each group) in real world settings were retrieved for analysis. After the surgical procedure, patients were followed up on days 1, 7, 14, 21, 30, 60, 90, 120, and 180 to explore the outcomes of the operations along with complications., Results: Infecting fungi were of genus Fusarium (n = 11), Aspergillus (n = 10), Mucor (n = 4) and Penicillium (n = 10). The most common indication was resistant ulcer with perforation. After the procedure, epithelization was completed in 11(73.33%) patients in the CF, and 13 patients in the (86.67%) AMG group. Visual acuity improvement was significantly better in the latter group (CF: 1 [6.67%] vs. AMG: 7 [46.67%], p = 0.023). Flap failure occurred in 4 patients (26.67%) from the CF and 2 (13.33%) from the AMG group. No significant differences were found between the two groups regarding success rate (p = 0.651), epithelialization time (p = 0.691), healing of corneal ulcer (p = 0.651), and postoperative stability (p = 0.651) of the flaps., Conclusions: CF and AMG are both effective for the management of refractory fungal corneal ulcers. However, AMG appears to improve visual acuity better than CF., (© 2024. Japanese Ophthalmological Society.)

Fungal keratitis (FK) is an infectious eye disease that poses a significant risk of blindness. However, the effectiveness of conventional antifungal drugs is limited due to the intrinsic ocular barrier that impedes drug absorption. There is an urgent need to develop new therapeutic strategies to effectively combat FK. Herein, we synthesized an ultrasmall positively charged carbon dot using a simple stage-melting method. The carbon dot can penetrate the corneal barrier by opening the tight junctions, allowing them to reach the lesion site and effectively kill the fungi. The results both in vitro and in vivo demonstrated that it exhibited good biocompatibility and antifungal activity, significantly improving the therapeutic effect in a mouse model of FK. Therefore, this biophilic ultrasmall size and positive carbon dot, characterized by its ability to penetrate the corneal barrier and its antifungal properties, may offer valuable insights into the design of effective ocular nanomedicines.

Purpose: To compare the efficacy and rapidity of direct microscopic detection of fungal elements from corneal ulcers between 10% potassium hydroxide (KOH) and 1% Chicago Sky Blue 6B (CSB) in 10% KOH (CSB-KOH)., Methods: Thirty patients with clinically suspected fungal keratitis were recruited. Participants with impending corneal perforation were excluded. Two slides were smeared with corneal ulcer scrapings from the ulcer's edge and base for comparison of fungal staining solutions. One slide was infused with KOH, and the other slide was filled with CSB-KOH. Additional scraping was collected for inoculation on Sabouraud dextrose agar for fungal culture. The sensitivity, specificity and rapidity of both stainings were analyzed., Results: The sensitivity of fungal culture, KOH, and CSB-KOH were 43.75% (95% confidence interval [CI], 19.75%-70.12%), 62.50% (95% CI, 35.43%-84.80%), and 87.50% (95% CI, 61.65%-98.45%), respectively. The specificity were 100% (95% CI, 69.15%-100%) of both stainings and fungal culture which analyzed from 16 fungal keratitis cases by laboratory and clinical diagnosis. Mean CSB-KOH examination time was quicker than KOH with the mean time difference of 5.6 minutes (95% CI, 3.22-7.98 minutes) and p-value &lt; 0.001., Conclusions: CSB-KOH was more effective and faster than KOH in detecting fungal elements from corneal ulcers. Therefore, CSB-KOH may be beneficial in diagnosing fungal keratitis and preventing blindness. Moreover, to the best of our knowledge, this is the first use of CSB stain in fungal keratitis detection.

Purpose: The aim of this study was to validate the C-DU(KE) calculator as a predictor of treatment outcomes on a data set derived from patients with culture-positive ulcers., Methods: C-DU(KE) criteria were compiled from a data set consisting of 1063 cases of infectious keratitis from the Steroids for Corneal Ulcer Trial (SCUT) and Mycotic Ulcer Treatment Trial (MUTT) studies. These criteria include corticosteroid use after symptoms, visual acuity, ulcer area, fungal etiology, and elapsed time to organism-sensitive therapy. Univariate analysis was performed followed by multivariable logistic regressions on culture-exclusive and culture-inclusive models to assess for associations between the variables and outcome. The predictive probability of treatment failure, defined as the need for surgical intervention, was calculated for each study participant. Discrimination was assessed using the area under the curve for each model., Results: Overall, 17.9% of SCUT/MUTT participants required surgical intervention. Univariate analysis showed that decreased visual acuity, larger ulcer area, and fungal etiology had a significant association with failed medical management. The other 2 criteria did not. In the culture-exclusive model, 2 of 3 criteria, decreased vision [odds ratio (OR) = 3.13, P < 0.001] and increased ulcer area (OR = 1.03, P < 0.001), affected outcomes. In the culture-inclusive model, 3 of 5 criteria, decreased vision (OR = 4.9, P < 0.001), ulcer area (OR = 1.02, P < 0.001), and fungal etiology (OR = 9.8, P < 0.001), affected results. The area under the curves were 0.784 for the culture-exclusive model and 0.846 for the culture-inclusive model which were comparable to the original study., Conclusions: The C-DU(KE) calculator is generalizable to a study population from large international studies primarily taking place in India. These results support its use as a risk stratification tool assisting ophthalmologists in patient management., Competing Interests: V.L. Perez has financial relationships with Alcon, Dompe, EyeGate, Kala, Trefoil, Novartis, and Oculis. The remaining authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Fungal keratitis is a major cause of corneal blindness worldwide. Compared to other types of infectious keratitis, fungal keratitis has a relatively poor prognosis because of various factors such as delayed patient presentation and diagnosis. Although associated in earlier studies with poverty and low socioeconomic status, military personnel stationed in tropical and subtropical climates, in low-resource settings, are at risk. Here, we report a case of a 20-year-old active duty contact lens-wearing military service member stationed at Guantanamo Bay who developed a severe vision-threatening fungal keratitis in her left eye. Enhancing health and safety precautions in at-risk settings, maintaining vigilance, and leveraging new imaging modalities will be important to ensure early recognition and treatment., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The treatment of fungal keratitis (FK) is challenging due to the subacute indolent course, and initial misdiagnosis. In this retrospective case series, we highlight both the diagnostic and therapeutic roles of corneal biopsy together with amniotic membrane transplantation (AMT) in patients with refractory clinically presumed FK. Debulking biopsy and tectonic AMT were performed during the initial presentation. Biopsy specimens were sent for KOH smears and cultures. After KOH smears confirmed the presence of fungal elements, topical voriconazole 1% was prescribed for the first 72 h then tailored according to the clinical response and the culture results. The outcome measures were complete resolution of infection and restoration of corneal integrity. Cases associated with culture proven bacterial keratitis were excluded. Twelve cases were included in the study. KOH smears confirmed the presence of fungal growth in all specimens. Cultures grew Aspergillus in 6/12 cases, sensitive to voriconazole (5/6) and amphotericin (3/6); Fusarium (4/12), sensitive to both voriconazole and amphotericin; and no growth in 2/12 cases. Amphotericin 0.15% eye drops were added to the 7 cases with proven sensitivity and to the remaining 2 culture negative cases. Gradual resolution of infection was seen in all cases after 35.6 ± 7.8 days. In FK, a debulking biopsy simultaneously with AMT help decrease the microbial load, suppress the inflammatory process, support the corneal integrity, confirm the presence of fungal pathogen., (© 2024. The Author(s).)

Purpose: To analyze the influence of infiltrate size, depth, and organism on the outcome of microbial keratitis., Design: Retrospective comparative study., Methods: Medical records of patients with infective keratitis, who reported from January 2015 to December 2019 to a tertiary eye care center, were analyzed. Size and depth of ulcer at presentation were the factors used to group patients, and the influence on the outcome of the organism causing it was analyzed. Grouping was as follows: group A: ulcer size <6 mm/anterior to midstromal infiltrate, group B: ulcer < 6 mm/full-thickness infiltrate, group C: ulcer >6 mm/anterior to midstromal infiltrate, group D: ulcer > 6 mm/full-thickness infiltrate. Patients with viral keratitis or unidentified organism were excluded. Response to treatment and best-corrected visual acuity (BCVA) at the final follow-up were the outcome measures., Results: In the study, 1117/6276 patients were included, with 60.8% patients in group A. A significant improvement in visual acuity was noted in groups A/B compared to groups C/D. Group A had the best response to medical management, irrespective of the organism. Higher risk for surgery was noted in group C compared to group B, with group A as the reference. Overall resolution with medical treatment was noted in 70% miscellaneous keratitis, 64.8% bacterial keratitis, 64.3% mixed keratitis, 62.5% acanthamoeba keratitis, 52.6% fungal keratitis, and 12.1% Pythium keratitis. Bacteria and acanthamoeba responded better to medical management than fungal keratitis, whereas Pythium had the highest risk for surgery., Conclusion: An interplay between virulence of the organism along with depth and size of the infiltrate determines the outcome of microbial keratitis., (Copyright © 2023 Copyright: © 2023 Indian Journal of Ophthalmology.)

Purpose: To determine the demographic and microbiological profile involved in the causation of corneal ulcers in Eastern India during the COVID era., Method: Patients presenting with corneal ulcers fulfilling the inclusion and exclusion criteria were taken as the case. The study duration was from January 2021 to December 2021. Socio-demographic details and information about risk factors were noted. A detailed corneal examination followed by corneal scraping was performed for microbiological evaluation., Results: In 1 year, 99 infective corneal ulcer patients were evaluated. Farmers (24.2%) were found to be maximally affected by corneal ulcers. The peak in cases was recorded from October to December (38.4%). Ocular trauma was the commonest risk factor (42.4%). The majority (80.8%) of patients were already on some topical antimicrobials. 22.2% of samples showed fungal filaments on KOH mount; 54.5% of these cases turned out to be culture-positive. 17.56% of KOH-negative samples turned out to be culture-positive (fungal). Overall, the culture positivity rate was 28.28% out of which fungal isolates were 89.28% and bacterial isolates were 10.72%. Fusarium species were identified as the most common organism contributing 42.85%, followed by Aspergillus fumigatus (14.28%). 10.72% of cases were culture positive for Pseudomonas aeuroginosa., Conclusion: Trauma with the organic matter was the predominant cause of fungal keratitis. In this study, fungal keratitis was found to be more common. Fusarium was the most common isolate., Competing Interests: None

Purpose: To study epidemiological data, laboratory results, and risk factors associated with microbial keratitis., Methods: We conducted a retrospective study of corneal sample cultures from patients with microbial keratitis from January 2010 to December 2019. Results were analyzed according to the etiological diagnosis of bacterial, mycotic, or parasitic infection and were associated with related risk factors., Results: We analyzed 4810 corneal samples from 4047 patients (mean age 47.79 ± 20.68 years; male 53.27%). The prevalence of bacterial, fungal, and Acanthamoeba infections were 69.80%, 7.31%, and 3.51%, respectively. The most frequently isolated bacteria were coagulase-negative Staphylococcus (CoNS) (45.14%), S. aureus (10.02%), Pseudomonas spp. (8.80%), and Corynebacterium spp. (6.21%). Among CoNS, the main agent was S. epidermidis (n=665). For mycotic keratitis, Fusarium spp. (35.42%) and Candida parapsilosis (16.07%) were the most common agents among filamentous and yeasts isolates, respectively. Contact lens use was associated with a positive culture for Acanthamoeba spp. (OR = 19.04; p < 0.001) and Pseudomonas spp. (OR = 3.20; p < 0.001). Previous ocular trauma was associated with positive fungal cultures (OR = 1.80; p = 0.007), while older age was associated with positive bacterial culture (OR = 1.76; p = 0.001)., Conclusions: Our findings demonstrated a higher positivity of corneal sample cultures for bacteria. Among those, CoNS was the most frequently identified, with S. epidermidis as the main agent. In fungal keratitis, Fusarium spp. was the most commonly isolated. Contact lens wearers had higher risks of positive cultures for Acanthamoeba spp. and Pseudomonas spp. Ocular trauma increased the risk of fungal infection, while older age increased the risk of bacterial infection.

The epidemiology of corneal ulcers in Vietnam has not been well characterized. In this report, we reviewed retrospectively the microbiological data of patients with a clinical diagnosis of corneal ulcer at the microbiology laboratory of Vietnam National Eye Hospital from January 1, 2010 to March 31, 2023. We observed a seasonal pattern for fungal and microsporidial keratitis, with an annual peak in November, and an inverse relationship between fungal keratitis and inclement weather. The November peak coincided with one of the major harvesting seasons in Vietnam. We also observed increasing numbers of microsporidial and Acanthamoeba keratitis cases in recent years. Knowledge of these trends are helpful in guiding empirical treatment of corneal infections and preventing corneal blindness.

Purpose: To evaluate the efficacy and safety of hypochlorous acid (HOCI) eye drops in the treatment of fungal keratitis., Methods: 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., Results: 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 ( χ 2 = 14.332, p  = .001)., Conclusion: HOCI can accelerate the healing of fungal keratitis without obvious complications, indicating a promising future in the field of keratitis treatment.

Importance: Microbial keratitis (MK) is a common cause of unilateral visual impairment, blindness, and eye loss in low-income and middle-income countries. There is an urgent need to develop and implement rapid and simple point-of-care diagnostics for MK to increase the likelihood of good outcomes., Objective: To evaluate the diagnostic performance of the Aspergillus-specific lateral-flow device (AspLFD) to identify Aspergillus species causing MK in corneal scrape and corneal swab samples of patients presenting with microbial keratitis., Design, Setting, and Participants: This diagnostic study was conducted between May 2022 and January 2023 at the corneal clinic of Aravind Eye Hospital in Madurai, Tamil Nadu, India. All study participants were recruited during their first presentation to the clinic. Patients aged 15 years or older met the eligibility criteria if they were attending their first appointment, had a corneal ulcer that was suggestive of a bacterial or fungal infection, and were about to undergo diagnostic scrape and culture., Main Outcomes and Measures: Sensitivity and specificity of the AspLFD with corneal samples collected from patients with MK. During routine diagnostic scraping, a minimally invasive corneal swab and an additional corneal scrape were collected and transferred to aliquots of sample buffer and analyzed by lateral-flow device (LFD) if the patient met the inclusion criteria. Photographs of devices were taken with a smartphone and analyzed using a ratiometric approach, which was developed for this study. The AspLFD results were compared with culture reports., Results: The 198 participants who met the inclusion criteria had a mean (range) age of 51 (15-85) years and included 126 males (63.6%). Overall, 35 of 198 participants with corneal scrape (17.7%) and 17 of 40 participants with swab samples (42.5%) had positive culture results for Aspergillus species. Ratiometric analysis results for the scrape samples found that the AspLFD achieved high sensitivity (0.89; 95% CI, 0.74-0.95), high negative predictive value (0.97; 95% CI, 0.94-0.99), low negative likelihood ratio (0.12; 95% CI, 0.05-0.30), and an accuracy of 0.94 (95% CI, 0.90-0.97). Ratiometric analysis results for the swab samples showed that the AspLFD had high sensitivity (0.94; 95% CI, 0.73-1.00), high negative predictive value (0.95; 95% CI, 0.76-1.00), low negative likelihood ratio (0.07; 95% CI, 0.01-0.48), and an accuracy of 0.88 (95% CI, 0.73-0.96)., Conclusions and Relevance: Results of this diagnostic study suggest that AspLFD along with the ratiometric analysis of LFDs developed for this study has high diagnostic accuracy in identifying Aspergillus species from corneal scrapes and swabs. This technology is an important step toward the provision of point-of-care diagnostics for MK and could inform the clinical management strategy.

Background: To compare the performance of conventional, semi-nested and real-time panfungal ITS PCRs for diagnosing fungal keratitis (FK) and develop genus-specific real-time PCR for the most common aetiology of FK., Methods: This multicentric study includes 232 corneal samples from suspected FK patients from four centres across India between November 2019 through August 2021. A total of 87 corneal buttons were included for the comparison of conventional, semi-nested and real-time ITS PCRs, of which 68 were from confirmed FK patients. Of these 87 samples, 44 (microscopy and culture positive for Aspergillus sp. and/or Fusarium sp.) were used for the standardisation of genus-specific real-time primers/probes. Subsequently, the best method showing highest sensitivity and specificity was validated in 188 samples., Results: On Bayesian comparison, conventional ITS2 PCR showed best performance (sensitivity and specificity of 55.88% and 100%, respectively). Since, real-time ITS2 PCR was also considerably efficient (sensitivity and specificity of 51.47% and 84.21%, respectively) in comparison with the conventional PCR but faster, cost-effective, and less labor-intensive, ITS-2 real-time PCR is a suitable method that can be applied along with culture and microscopy. During validation, real-time PCR with genus-specific primers showed 61.76% and 91.18% sensitivity with specificity of 98.05% and 79.22%, respectively, for Aspergillus sp. and Fusarium sp. Aspergillus probe, Fusarium probe and duplex PCR showed sensitivity of 52.94%, 50% and 54.41% with specificity of 92.86%, 82.47% and 75%, respectively. No cross-reactivity of genus-specific PCRs was observed during standardisation., Conclusions: ITS-2 real-time PCR can be applied as an adjunct with conventional methods for the diagnosis of FK. The genus-specific duplex real-time PCRs are rapid which reduces the turnaround time (TAT) avoiding the need for sequencing., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Purpose: This pilot study assessed the safety and efficacy of low-temperature plasma (LTP) as an adjuvant treatment for mild to moderate fungal keratitis (FK)., Methods: Thirty FK patients were randomized into LTP (n = 15) and control (n = 15) groups. Patients were followed up for 3 months. The best-corrected visual acuity (BCVA), ulcer size, and hypopyon height were measured; healing time or complications were documented and compared., Results: More patients in the LTP group healed completely (11/15 in 48 days) compared with the control group (4/15 in 59.5 days), and those patients had a deeper initial ulcer depth and exhibited better BCVA improvements. Four patients failed after LTP treatment due to perforation, increased inflammatory infiltration, or hypopyon; those with more hypopyon were more likely to fail., Conclusions: LTP could be a promising adjuvant therapy to topical antifungal drugs for mild to moderate FK.

Microbial keratitis, a nonviral corneal infection caused by bacteria, fungi, and protozoa, is an urgent condition in ophthalmology requiring prompt treatment in order to prevent severe complications of corneal perforation and vision loss. It is difficult to distinguish between bacterial and fungal keratitis from image unimodal alone, as the characteristics of the sample images themselves are very close. Therefore, this study aims to develop a new deep learning model called knowledge-enhanced transform-based multimodal classifier that exploited the potential of slit-lamp images along with treatment texts to identify bacterial keratitis (BK) and fungal keratitis (FK). The model performance was evaluated in terms of the accuracy, specificity, sensitivity and the area under the curve (AUC). 704 images from 352 patients were divided into training, validation and testing set. In the testing set, our model reached the best accuracy was 93%, sensitivity was 0.97(95% CI [0.84,1]), specificity was 0.92(95% CI [0.76,0.98]) and AUC was 0.94(95% CI [0.92,0.96]), exceeding the benchmark accuracy of 0.86. The diagnostic average accuracies of BK ranged from 81 to 92%, respectively and those for FK were 89-97%. It is the first study to focus on the influence of disease changes and medication interventions on infectious keratitis and our model outperformed the benchmark models and reaching the state-of-the-art performance., (© 2023. The Author(s).)

Infectious keratitis refers to a group of corneal disorders in which corneal tissues suffer inflammation and damage caused by pathogenic infections. Among these disorders, fungal keratitis (FK) and acanthamoeba keratitis (AK) are particularly severe and can cause permanent blindness if not diagnosed early and accurately. In Vivo Confocal Microscopy (IVCM) allows for imaging of different corneal layers and provides an important tool for an early and accurate diagnosis. In this paper, we introduce the IVCM-Keratitis dataset, which comprises of a total of 4001 sample images of AK and FK, as well as non-specific keratitis (NSK) and healthy corneas classes. We use this dataset to develop multiple deep-learning models based on Convolutional Neural Networks (CNNs) to provide automated assistance in enhancing the diagnostic accuracy of confocal microscopy in infectious keratitis. Densenet161 had the best performance among these models, with an accuracy, precision, recall, and F1 score of 93.55%, 92.52%, 94.77%, and 96.93%, respectively. Our study highlights the potential of deep learning models to provide automated diagnostic assistance for infectious keratitis via confocal microscopy images, particularly in the early detection of AK and FK. The proposed model can provide valuable support to both experienced and inexperienced eye-care practitioners in confocal microscopy image analysis, by suggesting the most likely diagnosis. We further demonstrate that these models can highlight the areas of infection in the IVCM images and explain the reasons behind their diagnosis by utilizing saliency maps, a technique used in eXplainable Artificial Intelligence (XAI) to interpret these models., (© 2023. The Author(s).)

Purpose: 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., Conclusion: These outcomes suggest that CL is an effective and safe adjuvant method for controlling the progression of moderate and severe fungal keratitis., Trial Registration Number: ChiCTR2100050565., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate the efficacy of liposomal amphotericin B (L-AMB) for the treatment of fungal keratitis., Methods: Patients with fungal keratitis confirmed by potassium hydroxide (KOH) smear and/or confocal microscopy were administered topical L-AMB and randomized into three groups treated with three different formulations. The medication was administered two hourly till clinical improvement was achieved, followed by six hourly till complete resolution. The outcome measures were time to clinical improvement, resolution of epithelial defect, stromal infiltrate, hypopyon, extent and density of corneal opacity, neovascularization, and best corrected visual acuity (BCVA) at 3 months., Results: Mean age of the patients was 46.6 ± 14.8 years, and trauma with vegetative matter was the most common predisposing factor. Aspergillus flavus (36%) was the most common fungus cultured, followed by Fusarium (23%). Mean time to clinical improvement, time to resolution of epithelial defect, mean time to resolution of infiltrate, and time to resolution of hypopyon were 3.45 ± 1.38, 25.35 ± 8.46, 37.97 ± 9.94, and 13.33 ± 4.90 days, respectively, and they were comparable among the three groups. There was a significant difference between treatment failure and success cases in terms of days of presentation (P < 0.01), size of the epithelial defect (P-value 0.04), and infiltrate size at presentation (P-value 0.04). At 3 months follow-up, no statistically significant difference was noted in BCVA and mean scar size among groups., Conclusion: L-AMB in a gel form is an effective antifungal agent that promotes the healing of fungal ulcers with notably least vascularization and better tolerance., Trial Registration Number: CTRI/2020/04/024550., Competing Interests: None

Purpose: To evaluate the knowledge and skills of clinicians in differentiating cases of Pythium from fungal keratitis based on their clinical appearance., Methods: Thirty slit-lamp photographs from culture-proven cases of Pythium and fungal keratitis were selected for conducting a prospective online-based photographic survey. The participants were asked to identify the causative organism and enlist the specific clinical features which helped in reaching the diagnosis. Both cornea specialists and clinical fellows/trainees participated in the survey. Sensitivity, specificity, and predictive values were estimated, and the factors associated with these, including the identification rates of clinical signs, were evaluated using bivariate and multivariate linear regression analyses. The identification rates between the consultants and fellows were compared., Results: A total of 42 cornea specialists (28 consultants and 14 clinical fellows) participated in the survey. Clinicians were able to differentiate Pythium from fungal etiology in only 56% of cases. The differentiating ability between the consultants and fellows was statistically insignificant. Average sensitivity, specificity, and positive and negative predictive values for differentiating Pythium from fungus were 56%, 65%, 56%, and 66%, respectively. The specific clinical features enlisted by the participants to differentiate Pythium from fungus were the presence of tentacles, peripheral guttering, dot-like infiltrates, and elevated plaques., Conclusion: Clinical knowledge regarding the signs and symptoms and the microbiological identification of features for Pythium are still lacking among clinicians. As the treatment protocols are distinctly different for both, it is imperative to enhance the knowledge and diagnosing ability to tackle this emerging microorganism which causes high morbidity., Competing Interests: None

Introduction: This study was intended to investigate the clinical features and predisposing factors of fungal keratitis (FK), as well as molecular identification and antifungal susceptibility of causative agents in Tehran, Iran., Methods: This cross-sectional study was carried out from April 2019 to May 2021. All fungi isolates were identified using conventional methods and were confirmed by DNA-PCR-based molecular assays. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) was used to identify yeast species. Minimum inhibitory concentrations (MIC) of eight antifungal agents were assessed according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) microbroth dilution reference method., Results: Fungal etiology was confirmed in 86 (7.23%) of 1189 corneal ulcers. A significant predisposing factor for FK was ocular trauma caused by plant materials. Therapeutic penetrating keratoplasty (PKP) was required in 60.4% of cases. The predominant fungal species isolated was Fusarium spp. (39.5%) followed by Aspergillus spp. (32.5%) and Candida spp. (16.2%)., Discussion: The MIC results indicate that amphotericin B may be appropriate for treating FK caused by Fusarium species. FK caused by Candida spp. can be treated with flucytosine, voriconazole, posaconazole, miconazole, and caspofungin. In developing countries such as Iran, corneal infection due to filamentous fungi is a common cause of corneal damage. In this region, fungal keratitis is observed primarily within the context of agricultural activity and subsequent ocular trauma. Fungal keratitis can be managed better with understanding the "local" etiologies and antifungal susceptibility patterns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Soleimani, Izadi, Khodavaisy, Santos, Tehupeiory-Kooreman, Ghazvini, Hashemi, Mousavi, Aala, Abdorahimi, Aminizadeh, Abedinifar, Mahmoudi, Mohamadi, Rezaie and Verweij.)

Aim: To assess efficacy of intrastromal voriconazole (ISV) in the treatment of fungal keratitis non-responding to conventional antifungals. Methods: Eighteen patients with smear positive fungal keratitis, not responding to conventional topical/ systemic antifungal therapy up to 2 weeks, were included in the study. Afterwards, they were given ISV (50 µg in 0.1 ml) around the ulcer and continued to receive conventional antifungal therapy. Responses to treatment (decrease in size of the ulcer and infiltrates) were recorded daily for 3-days, at 1-week and every 2 weeks for 3-months, or until the ulcer had healed completely. Results: The mean age at presentation was 51 ± 17.83 years. The most common organism isolated was Fusarium (17/ 18), followed by Aspergillus (1/ 18). All the patients were successfully treated in terms of corneal healing, but one case did not improve in vision due to the existence of diabetic macular oedema. 6 patients improved after a single injection, 7 had to receive 2 and 5 improved after 3 injections. The mean number of injections in 17 treated patients was 1.94 ± 0.78. Moreover, the mean resolution time was 18.50 ± 6.25 days. The size of ulcer and height of hypopyon at presentation were noteworthy risk-factors linked to management outcomes. Deeper ulcers required a greater number of injections when compared to superficial ulcers. The mean best-corrected visual acuity improved from 0.94 to 0.25 at 3 months follow-up in all the patients. Conclusion: Intrastromal Voriconazole (50 µg/ 0.1 mL) appears to be an effective adjunct therapy in cases of recalcitrant deep fungal keratitis non-responding to conventional antifungals. Though, some may require repeated injections, timely ISV administration certainly reducing the need for tectonic/ therapeutic keratoplasty. Abbreviations: ISV = Intrastromal Voriconazole, AS-OCT = anterior-segment optical coherence topography, KOH = potassium hydroxide, BCVA = best-corrected visual acuity., (#x00A9; The Authors.Romanian Society of Ophthalmology.)

Aims: To evaluate the sensitivity and specificity of polymerase chain reaction (PCR), in vivo confocal microscopy (IVCM) and culture for microbial keratitis (MK) diagnosis., Methods: Retrospective review of PCR, IVCM and culture results for MK diagnosis at Moorfields Eye Hospital between August 2013 and December 2014., Results: PCR results were available for 259 MK patients with concurrent culture for 203/259 and IVCM for 149/259. Sensitivities and specificities with 95% confidence intervals [95% CI] were calculated for Acanthamoeba keratitis (AK) and fungal keratitis (FK), by comparison with culture, for both IVCM and PCR. For AK, FK and bacterial keratitis (BK) sensitivities were calculated, for each diagnostic method, by comparison with a composite reference standard (a positive result for one or more of culture, PCR or IVCM having a specificity of 100% by definition). For the latter, sensitivities with [95% CI] were: for AK, IVCM 77.1% [62.7-88.0%], PCR 63.3% [48.3-76.6%], culture 35.6 [21.9-51.2]; for FK, IVCM 81.8% [48.2-97.7%], PCR 30.8% [9.09-61.4%], culture 41.7% [15.2-72.3%]; for BK, PCR 25.0% [14.7-37.9%], culture 95.6% [87.6-99.1%]., Conclusion: IVCM was the most sensitive technique for AK and FK diagnosis but culture remains our gold standard for BK. These findings reflect results to be expected from service providers to UK ophthalmology units and demonstrates the need at our centre for ongoing diagnostic result audit leading to the potential to improve PCR diagnosis. Both FK and AK are now common in the UK; ophthalmology units need to have all these techniques available to optimise their MK management., (© 2021. The Author(s).)

Purpose: The purpose of this study was to determine whether astigmatism or corneal scarring is mediating the reduced visual acuity among patients with fungal keratitis randomized to corneal cross-linking (CXL)., Design: This was a prespecified exploratory outcome from an outcome-masked, 2 × 2 factorial design, randomized controlled clinical trial., Study Participants: Consecutive patients presented with moderate vision loss from a smear-positive fungal ulcer at Aravind Eye Hospital, Madurai, India., Intervention: Study eyes were randomized to one of 4 treatment combinations using an adaptive randomization protocol. The treatment arms included (1) topical natamycin 5% alone, (2) topical natamycin 5% plus CXL, (3) topical amphotericin B 0.15% alone, and (4) topical amphotericin 0.15% plus CXL. Best spectacle-corrected visual acuity (BSCVA), contact lens over-refraction, and scar size and depth as measured by a masked study ophthalmologist using a standardized protocol were recorded at 3 months. Pentacam Scheimpflug imaging was also obtained at 3 months., Main Outcome Measures: BSCVA and contact lens over-refraction, infiltrate and/or scar size and depth, total astigmatism of the front and back of the cornea, total lower-order and higher-order aberrations of the anterior and posterior cornea, and total densitometry of the anterior, central, and posterior stroma were recorded. We performed a mediation analysis looking at the proportion of the effect of CXL on BSCVA that was mediated through scar size, scar depth, astigmatism and density., Results: BSCVA at 3 months was available for 99 of 111 patients (89%) who had a mean of 0.82-LogMAR (SD 0.68). Three-month infiltrate and/or scar size ( P < 0.001), depth ( P < 0.001), and densitometry ( P = 0.001) were statistically significant predictors of 3-month BSCVA. Astigmatism seemed to mediate 23% of the effect of CXL on BSCVA, whereas scar size mediated 23%, scar depth 17%, and densitometry 7%., Conclusions: Corneal scarring and astigmatism are mediators of worse visual acuity after cross-linking in fungal keratitis. Corneal densitometry may be a helpful cornea-specific variable for clinicians and researchers in determining the effect of corneal scarring on visual acuity in specific patients and as an objective study outcome., Trial Registration: NCT02570321., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this study was to report the first case of keratitis caused by Cladorrhinum samala and review of the literature., Methods: This was a case report and literature review., Results: A 35-year-old immunocompetent man presented with pain, redness, and watering in the right eye 7 days after trauma with some foreign body. He was diagnosed with infectious keratitis, and a thorough microbiological workup was performed. Corneal scrapings were subjected to a potassium hydroxide (KOH) examination, Gram staining, bacterial (blood agar and Robertson cooked meat broth), and fungal culture (Sabouraud dextrose agar and brain-heart infusion agar). The KOH mount revealed septate fungal hyphae with irregular margins. Yellow-white nonsporulating mycelial growth was noted on the Sabouraud dextrose agar, which was identified as C. samala by sequencing. The patient responded to 5% natamycin and 1% voriconazole eye drops, and there was a formation of a corneal opacity in a period of 3 weeks., Conclusions: We report the first case of keratitis by C. samala, highlighting the emergence of a rare dematiaceous fungi causing keratitis and the role of molecular modalities in the diagnosis of nonsporulating fungi in suspected cases., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Purpose: To evaluate the therapeutic effect of incorporating continuous administration of voriconazole in the treatment of recalcitrant fungal keratitis., Methods: In this prospective case study, 5 consecutive patients (5 eyes) with fungal keratitis were treated with a standard protocol after the failing maximal conventional medical treatment. The protocol involved continuous lavage of the ulcer with 1% voriconazole through an irrigator for 2 h, twice a day, combined with local and systemic antifungals. Visual acuity, slit lamp findings of the ulcer, and fungal hyphae density by confocal microscope were documented, respectively., Results: In 4 patients, the clinical symptoms and slit lamp examination were significantly improved after only 3 days of treatment. The hyphae were shown to decrease in number and morphologically fragmented in corneal stroma by confocal microscopy. After the infection was controlled, 2 cases required further keratoplasty. In one case, the treatment was deemed ineffective and a conjunctival flap had to be created to help control the infection. In all 5 patients, the best spectacle-corrected visual acuity had improved after treatment. With more than 3 months of follow-up, no recurrence of infection was seen in any cases., Conclusion: Our treatment protocol demonstrated improvement in the treatment of clinically resistant fungal keratitis. Continuous lavage of voriconazole is easy to be implemented and well-tolerated by patients. Modification of the current protocol should be further explored to optimize the therapeutic effectiveness in future.

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., (© 2022 American College of Veterinary Ophthalmologists.)

Purpose: The purpose of this study was to report a case of fungal keratitis resistant to standard-of-care antimicrobial treatment and successful resolution, thanks to the repeated high-fluence accelerated photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL)., Methods: This was a case report., Results: A 79-year-old male patient with previous Descemet membrane endothelial keratoplasty presented with a corneal ulcer that was resistant to topical antimicrobial therapy and amniotic membrane placement. Fungal keratitis was diagnosed, and the cornea was on the verge of perforation. After over a month of topical and systemic therapy without marked improvement, the patient underwent 2 repeated high-fluence accelerated CXL procedures (7.2 J/cm2 using a UV irradiation of 30 mW/cm2 for 4 minutes) over an interval of 8 days (accumulated fluence of 14.4 J/cm2), which resulted in significant clinical improvement, with consolidation into a quiescent scar., Conclusions: PACK-CXL protocols delivering a total UV fluence of 5.4 J/cm2 (as per the original Dresden protocol for corneal ectasia cross-linking) can be an effective primary therapy for initial or superficial corneal infections because approximately half of the energy is absorbed in the first 100 μm of a riboflavin-soaked cornea. However, fungal keratitis may require higher fluences than 5.4 J/cm2 because, unlike ectatic corneas, corneal ulcers are not transparent, and the infection may involve deep stroma. This case illustrates how repeated high-fluence accelerated PACK-CXL can be used to successfully treat fungal keratitis resistant to conventional topical and systemic medications., Competing Interests: F. Hafezi is the chief scientific officer of EMAGine AG (Zug, Switzerland) and coinventor of the PCT applications CH2012/0000090 and PCT2014/CH000075 regarding CXL technology. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Fungal keratitis is a devastating and difficult-to-treat ocular infection with high morbidity. Understanding geographic microbiological and clinical trends helps to guide rapid and effective treatment. We therefore report the characteristics and outcomes of fungal keratitis in Toronto,ON Canada, over a 20-year period. An electronic search of microbiology records at University Health Network, Toronto, ON, Canada identified all patients with positive corneal fungal culture over a 20-year period seen at our tertiary referral cornea practice. Review of corresponding patient charts identified demographic and microbiological details, clinical course, treatment regimen, and final outcomes associated with each episode of culture-positive fungal keratitis. A total of 46 patients with 51 discrete fungal keratitis episodes were included. Five patients experienced recurrent fungal keratitis. Candida species accounted for 60.8% of positive fungal cultures, followed by Filamentous species at 35.3%. Preferred initial anti-fungal treatment was topical amphotericin at 36.7% followed by topical voriconazole at 32.6%. Surgical intervention was required in 48.9% with therapeutic penetrating keratoplasty being the most common procedure (22.4%). Final visual acuity (VA) of <20/200 was attributed to 58% of patients in this study. Risk factors for poor outcomes included poor VA, topical steroid use at presentation, Candida involvement, history of ocular surface disease, organic ocular trauma, or prior corneal transplantation. Candida is the most frequent keratomycotic pathogen in Toronto. Risk factors for poor visual outcome include prior corneal transplantation, ocular surface disease/trauma, or pre-existing topical steroid use. Early suspicion, diagnosis and treatment are paramount for best clinical outcomes., Lay Summary: Fungal keratitis can cause severe vision loss without effective treatment. In Toronto, Candida had been the most common species over a 20-year period. Poor clinical outcome was associated with low presenting visual acuity, previous corneal transplant, topical steroid use, trauma, and Candida involvement., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Purpose: To report the clinical outcome of Photodynamic Antimicrobial Therapy (PDAT) with Rose Bengal (RB) used as an early adjuvant therapy in patients with fungal keratitis and their microbiological and pathological correlation., Methods: Patients with microbiologically confirmed fungal keratitis underwent PDAT-RB along with topical natamycin 5% drops hourly and oral ketoconazole 200 mg twice a day. This was performed by applying rose bengal (0.1%) to the de-epithelialized cornea for 30 minutes, followed by irradiation with a 6 mW/cm 2 custom-made green LED source for 15 minutes (5.4 J/cm 2 ). The corresponding fungal isolates were tested in vitro using PDAT-RB and corneal buttons were evaluated for correlation., Results: Following informed consent, seven patients (male-5, female-2, mean age 47.7 years) with fungal keratitis were recruited. There were 3 cases each of Fusarium and Aspergillus flavus and 1 case of Acremonium sp. The average vertical and horizontal diameters of the corneal infiltrate were 4.12 ± 0.55 and 3.99 ± 1.19 mm, respectively. The average depth of corneal involvement was 283 ± 75.27µ as measured by anterior segment OCT. The clinical resolution was achieved in the cases with Fusarium keratitis with an average time of 39 days. Three cases of A. flavus and a single patient with Acremonium keratitis worsened and needed therapeutic keratoplasty (TPK) for resolution. Post-TPK, the corneal tissues grew A. flavus in one out of three cases and Acremonium sp. in one case. In vitro PDAT-RB experiment was performed on the corresponding fungal isolates grown from the corneal scraping. PDAT-RB produced clear inhibition of Fusarium and Acremonium sp. with no effect on the growth of A. flavus. Histopathologically, 2 out of 4 (50%) corneal buttons showed fungal filaments., Conclusions: While the in vitro and in vivo results of PDAT-RB matched for Fusarium sp. and Aspergillus flavus keratitis being favourable in the former and non-favourable in the latter, these results were discrepant in Acremonium sp.

Introduction: The aim of this study was to compare the efficacy of Photo-Activated Chromophore for Keratitis - Corneal Collagen Cross-linking (PACK-CXL) of three different total UVA fluence levels and topical voriconazole in treatment of fungal keratitis experimentally induced in rabbits., Methods: This is an interventional experimental study including both eyes of 16 rabbits (32 eyes). Fungal keratitis was induced by intrastromal injection of Fusarium Solani into the cornea. The rabbits were then divided into four groups (8 eyes for each) from which group A received Voriconazole eye drops and considered as control group. Group B, C, D received single PACK-CXL session with total fluence levels of 7.2, 10.0 and 15.0 J/cm2 for each respectively. Daily clinical examination was recorded and all corneas were removed for microbiology and histopathology on day ten., Results: The mean clinical signs score eyes treated with high fluence PACK-CXL showed evident clinical improvement from fourth to tenth day of treatment. This improvement was equivalent to that of Voriconazole treatment. The results showed better improvement with increasing the UVA total fluence levels but this difference was not statistically significant (P < 0.05). Similarly, the median CFU/ml declined on increasing UVA fluence but with no statistically significant values. Histopathological examination revealed better improvement of inflammatory signs on higher fluence levels compared to lower ones., Conclusions: High intensity PACK-CXL (30 mW/cm 2 ) was as effective as Voriconazole in the treatment of fungal keratitis in rabbits. Increasing the fluence of UVA was associated with slightly better clinical outcomes with no added risks. More clinical studies are needed to confirm these results.

Purpose: To report the successful treatment of 3 cases of recalcitrant fungal keratitis (FK) with high-dose oral posaconazole., Methods: This is a series of 3 patients from a single academic center with a culture-positive FK who were treated with oral posaconazole after failing to respond to conventional treatments., Results: All 3 patients had a history of contact lens wear. Two of the 3 cases were culture positive for Fusarium and the other for Paecilomyces . The infections of all 3 failed to respond to conventional antifungal therapies including varying combinations of topical, systemic, and intraocular antifungal therapies. All 3 cases rapidly responded to high-dose oral posaconazole ranging from 500 to 600 mg once daily. In 1 case, multiple courses of high-dose therapy were required to treat delayed recurrences of a latent infection. There were no significant adverse effects with the elevated dose, and treatment was administered with the guidance of an infectious disease specialist., Conclusions: In cases of recalcitrant FK failing to respond to conventional therapies, high-dose posaconazole, in the delayed-release tablet formulation, can be an effective treatment option., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To study the clinical presentation, mycological profile, and risk factors of fungal keratitis (FK) cases presenting at two tertiary-care centers, one each at North (Chandigarh) and Northeast (Assam) India, and to compare the spectrum of fungi recovered from the clinical and environmental samples at both locations., Methods: All patients with suspected FK were enrolled from both the centers between January 2018 and December 2019. Corneal samples were collected and processed as per standard laboratory protocols. Demographic details and clinical and mycological profiles were noted in all patients. Environmental sampling from the soil, air, and the vegetative matter was performed from both locations and neighboring districts., Results: Of the 475 suspected cases, 337 (71%) were diagnosed as FK (median age: 50 years; 77.2% males). The presence of diabetes, hypertension, blurred vision, and corneal discoloration was significantly higher in patients with FK compared to those without FK. Aspergillus sp. (52.1%) and Fusarium sp. (47.61%) were the predominant etiological agents isolated from cases in North and Northeast India, respectively. FK due to melanized fungi was associated with diabetes, trauma with animal tail, and corneal discoloration. A similar spectrum of fungi was seen in environmental and clinical samples in both the regions., Conclusion: The difference in etiological agents of FK and environmental fungal isolates in North and Northeast India highlights the need to identify the ecological niche of potential fungal pathogens. Prospective, multicenter studies, systematic environmental sampling, and the evaluation of the differences in causative agents and clinical presentation of FK from different parts of the country can substantially improve our understanding of its region-specific clinico-epidemiological profile., Competing Interests: None

Purpose: To report a new entity called "toxic non-inflammatory fungal keratitis.", Methods: Eyes manifesting infective keratitis with a history of prior administration of topical steroids were included in the study. The details pertaining to the type of injury, duration of injury, and primary treatment for corneal trauma were meticulously documented. The corneal tissues were scraped from the patients and were analyzed for fungal filaments by using a 10% KOH mount under a compound microscope. Moreover, these scraped materials were plated on blood agar and Sabouraud dextrose agar plates., Results: The corneal ulcers displayed a disproportionately reduced intensity of pain and improved visual acuity. Further, 10% KOH revealed profuse fungal filaments with few inflammatory cells in all the patients. The anterior chamber cells and flare were either reduced or entirely absent. There was no evidence of lid edema and surrounding corneal edema in any of the patients. The mean healing period was 28.8 days (standard deviation (SD): 10.05). The KOH mount revealed the presence of confluent fungal hyphae with a few inflammatory cell infiltrates. The Aspergillus species and Fusarium species were found in 47% and 40% of the cases, respectively., Conclusion: Toxic non-inflammatory fungal keratitis following steroid therapy needs to be considered in fungal ulcers with disproportionately less pain and good visual acuity. The fungal ulcers with altered clinical signs of classical inflammation need to be assessed for topical steroid misuse., Competing Interests: None

Purpose: To investigate if topical chlorhexidine 0.2%, which is low cost and easy to formulate, is noninferior to topical natamycin 5% for the treatment of filamentous fungal keratitis., Design: Randomized controlled, single-masked, noninferiority clinical trial., Participants: Adults attending a tertiary-level ophthalmic hospital in Nepal with filamentous fungal infection confirmed on smear or confocal microscopy., Methods: Participants were randomly allocated to receive topical chlorhexidine 0.2% or topical natamycin 5%. Primary analysis (intention-to-treat) was by linear regression, using baseline logarithm of the minimum angle of resolution (logMAR) best spectacle-corrected visual acuity (BSCVA) and treatment arm as prespecified covariates. Mixed fungal-bacterial infections were excluded from the primary analysis but included in secondary analyses and secondary safety-related outcomes. The noninferiority margin was 0.15 logMAR. This trial was registered with ISRCTN, number ISRCTN14332621., Main Outcome Measures: The primary outcome measure was BSCVA at 3 months. Secondary outcome measures included perforation or therapeutic penetrating keratoplasty by 90 days., Results: Between June 3, 2019, and November 9, 2020, 354 eligible participants were enrolled and randomly assigned: 178 to chlorhexidine and 176 to natamycin. Primary outcome data were available for 153 and 151 of the chlorhexidine and natamycin groups, respectively. Of these, mixed bacterial-fungal infections were found in 20 cases (12/153 chlorhexidine, 8/151 natamycin) and excluded from the primary analysis. Therefore, 284 patients were assessed for the primary outcome (141 chlorhexidine, 143 natamycin). We did not find evidence to suggest chlorhexidine was noninferior to natamycin and in fact found strong evidence to suggest that natamycin-treated participants had significantly better 3-month BSCVA than chlorhexidine-treated participants, after adjusting for baseline BSCVA (regression coefficient, -0.30; 95% confidence interval [CI], -0.42 to -0.18; P < 0.001). There were more perforations and emergency corneal grafts in the chlorhexidine arm (24/175, 13.7%) than in the natamycin arm (10/173, 5.8%; P = 0.018, mixed infections included), whereas natamycin-treated cases were less likely to perforate or require an emergency corneal graft, after adjusting for baseline ulcer depth (odds ratio, 0.34; 95% CI, 0.15-0.79; P = 0.013)., Conclusions: Treatment with natamycin is associated with significantly better visual acuity, with fewer adverse events, compared with treatment with chlorhexidine. Natamycin remains the preferred first-line monotherapy treatment for filamentous fungal keratitis., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Fungal keratitis, an infective disease of the cornea, represents a serious diagnostic and therapeutic problem that, if not recognized on time, could lead to irreversible eye damage. Herein we report a case of fungal keratitis due to Fusarium spp. infection. The 60-year-old man was admitted to our clinic due to an atraumatic acute onset of the disease, with a decrease in the visual acuity, photophobia, redness, and severe pain in the right eye. Clinical observation revealed an ulcer that affected 1/3 of the cornea and a hypopion in the anterior chamber. After the first results of microbiological analyzes, local and systemic antifungal therapy was applied. Due to the fact that the patient voluntarily left the treatment, there was a drastic worsening of the local findings as a full thickness total corneal infiltrate with more intense anterior chamber reaction. Finally, evisceration was performed. Given the fact that fungal keratitis is more prevalent in developing countries, official protocols and available effective antifungals are crucial for adequate treatment and a favorable outcome of this infection., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Marija Trenkic, Gordana Stankovic Babic, Marina Randelovic, Miljan Krstic, Marija Radenkovic, Suzana Tasic-Otasevic.)

Objectives: To present the demographic, etiological, clinical, and mycological characteristics and treatment results of fungal keratitis patients admitted to our clinic., Materials and Methods: The medical records of patients diagnosed with fungal keratitis between October 2012 and 2018 were reviewed. The diagnosis of fungal keratitis was confirmed mycologically and/or cytologically. Treatment response was defined as complete infiltrate resolution and re-epithelization with medical treatment and minor surgical interventions. Patients who underwent penetrating keratoplasty or evisceration due to clinical deterioration despite treatment were classified as treatment nonresponders and were compared with responders in terms of demographic, etiological, and clinical characteristics., Results: Seventy-two (12.8%) of 559 patients diagnosed with microbial keratitis in the 6-year period were fungal keratitis. Of these, 38 cases (38 eyes) without polymicrobial etiology were included in the study. The patients' mean age was 44.9±19.0 years (range: 2-80) and males predominated (14 females [36.8%], 24 males [63.2%]). Trauma (63.6%) was the most common predisposing factor in patients younger than 40 years old, whereas pathologies impairing ocular surface immunity were the leading risk factor (48.1%) in patients older than 40 years. Filamentous fungi were detected in 34 (89.5%) cases, while yeasts were found in 4 (10.5%) cases. Among 26 cases with positive cultures, Aspergillus species were the most common pathogens (42.3%). Infiltrate size before treatment was larger in nonresponders (14/38, 36.8%) compared to treatment responders (19/38, 50%) (p=0.049). In addition, rates of treatment response were higher in cases in which the infiltrate was located paracentrally compared to other cases (p=0.036)., Conclusion: Fungal keratitis is an important public health problem in our region. Ocular trauma is a leading etiology in men under the age of 40 years. In the 6-year period, we observed that the main causes of fungal keratitis were filamentous fungi, and most commonly Aspergillus species. In cases presenting with large and central lesions, aggressive treatment options should be considered and these patients should be followed up more closely., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2022 by Turkish Ophthalmological Association, Turkish Journal of Ophthalmology, published by Galenos Publishing House.)

Purpose: To compare the costs associated with medications and travel of patients with smear-proven bacterial keratitis and fungal keratitis in a tertiary care center in India., Methods: Retrospective analysis of case records of a cohort of patients who presented between April 2017 and March 2018 to a tertiary care center in India, with infectious keratitis who were smear-positive for bacteria or fungi, and whose costs of treatment and travel were supported by a philanthropic program., Results: In total, 672 case records of 177 smear-positive bacterial keratitis (BK) and 495 smear-positive fungal keratitis (FK) were included in the study. Further, 62% of BK and 75% of FK received more than one antimicrobial drug (P < 0.001). The mean total medication cost (INR) was significantly more in FK (959.1 ± 675.2) compared to BK (674.9 ± 463.7) (P < 0.0001). The mean medication cost (INR) per visit was also more for FK (201.1 ± 109.4) compared to BK (155.2 ± 84.1) (P < 0.0001). The mean total medication cost was significantly more for FK for both patients who healed with medical treatment (611.6 ± 395.6 for BK, 801.5 ± 599.9 for FK, P = 0.0005) and for patients who required TPK (953.7 ± 653.1 for BK, 1374.6 ± 701.5 for FK, P = 0.0023) compared to their respective counterparts in BK., Conclusion: Patients with fungal keratitis incurred significantly more on medications compared to patients with bacterial keratitis irrespective of whether they had healed with successful medical treatment or required therapeutic keratoplasty. Prolonged duration of treatment and the high costs of antifungal medications account for the significant economic burden of fungal keratitis., Competing Interests: None