Ocular Candidiasis Research Articles

Basic Research on Candida Species.

Candida species are common human pathogens that cause a wide range of diseases ranging from superficial to invasive candidiasis. However, basic studies focusing on the mechanisms underlying these diseases are limited. This article reviews our previous research on the mechanisms of superficial and invasive candidiasis, the virulence of Candida species, and Candida species fitness to hosts. Regarding invasive candidiasis, we focused on two types of infections: ocular candidiasis and endogenous candidiasis from the gastrointestinal tract. Using an established ocular candidiasis mouse model, along with retrospective epidemiological research, we found a strong association between Candida albicans and ocular candidiasis. Regarding endogenous candidiasis, research using Candida auris indicated that invasive strains had a higher capability for gastrointestinal tract colonization and showed greater dissemination compared with non-invasive strains. In terms of superficial candidiasis, we focused on the defense mechanism in vulvovaginal candidiasis. The results suggested that stimulated invariant natural killer T cells played a protective role against C. albicans vaginal infection and might be a therapeutic target for vulvovaginal candidiasis. Concerning Candida species fitness, we focused on environmental factors, particularly oxygen concentration, and evaluated biofilm formation under various oxygen concentrations, revealing that each Candida species favored different oxygen concentrations. In particular, Candida tropicalis showed greater biofilm formation under hypoxic conditions. Our research revealed several insights for understanding the exact mechanisms of candidiasis, which might lead to better control of Candida species infections and appropriate treatment.

213. Do Patients with Candidemia Need an Ophthalmology Exam?

Abstract Background Candidemia can lead to hematogenous seeding of the eye resulting in chorioretinitis or endophthalmitis. IDSA recommends a screening dilated retinal examination for patients with candidemia, whilst American Academy of Ophthalmology (AAO) recently declared this a low value practice. Using an inter-disciplinary team, we evaluated ophthalmology examination for patients with candidemia. Methods We performed a retrospective study of patients with candidemia at an academic medical center and affiliated hospitals between January 2011 – June 2022. Electronic medical records were reviewed for demographics and baseline characteristics. The primary outcome was chorioretinitis and/or endophthalmitis. The study was adjudicated by independent review from infectious disease and ophthalmology providers. Results We included 308 patients with a blood culture positive for candida species. 149 patients (48%) received an ophthalmologic exam, of which 55% (82) were asymptomatic. Abnormal ocular findings concerning for presumed ocular candida complications were found in 12 patients (8%, 12/149), of which 4 had alternative diagnoses to candida choriorentinits or endophthalmitis. All of the remaining 8 patients (5%, 8/149) had presumed candida chorioretinitis with no cases of candida endophthalmitis and this led to a change in management in 88% (7/8) of patients (Table 1). Of the 8 patients, 3 patients were asymptomatic, making the number needed to screen 28 to detect presumed candida chorioretinitis amongst asymptomatic patients. We did not identify statistically significant risk factors for development of abnormal ocular findings (Table 2). Table 1 Clinical diagnosis and management of patients with candida chorioretinitis and/or endophthalmitis Table 2 Clinical features of patients with and without ocular candidiasis Conclusion IDSA and AAO recommend ophthalmologic examination in symptomatic and intubated patients with candidemia. We found a 5% incidence of presumed ocular candidiasis in patients with candidemia. Given the limitations of our study, we could not conclude for or against screening in asymptomatic patients as this did not lead to a significant change in patient outcomes. Inter-disciplinary decisions involving ophthalmology and infectious diseases can help inform best practices for screening in asymptomatic patients. Future studies should evaluate ocular photography and teleophthalmology as screening strategies. Disclosures All Authors: No reported disclosures

Candida Biofilm Eye Infection: Main Aspects and Advance in Novel Agents as Potential Source of Treatment.

Fungi represent a very important cause of microbial eye infections, especially in tropical and developing countries, as they could cause sight-threating disease, such as keratitis and ocular candidiasis, resulting in irreversible vision loss. Candida species are among the most frequent microorganisms associated with fungal infection. Although Candida albicans is still the most frequently detected organism among Candida subspecies, an important increase in non-albicans species has been reported. Mycotic infections often represent an important diagnostic-clinical problem due to the difficulties in performing the diagnosis and a therapeutic problem due to the limited availability of commercial drugs and the difficult penetration of antifungals into ocular tissues. The ability to form biofilms is another feature that makes Candida a dangerous pathogen. In this review, a summary of the state-of-the-art panorama about candida ocular pathology, diagnosis, and treatment has been conducted. Moreover, we also focused on new prospective natural compounds, including nanoparticles, micelles, and nanocarriers, as promising drug delivery systems to better cure ocular fungal and biofilm-related infections. The effect of the drug combination has also been examined from the perspective of increasing efficacy and improving the course of infections caused by Candida which are difficult to fight.

Corneal targeted Amorolfine HCl-mixed micelles for the management of ocular candidiasis: Preparation, in vitro characterization, ex vivo and in vivo assessments

Amorolfine Hydrochloride (AMO) is a broad-spectrum antifungal drug commonly used to treat onychomycosis. This work aims to introduce AMO as a new alternative for the management of oculomycosis, where its delivery to the corneal tissue is hindered by the poor aqueous solubility, besides further obstacles fronting the ophthalmic delivery such as brief residence time, and the prevailing anatomical barrier. This work presents the formulation of AMO-mixed micelles (AMO-MMs) incorporating Solutol HS15 and Pluronic F127 as surfactants and propylene glycol as a co-surfactant. The mixed micelles were prepared by the thin film hydration method and planned on the basis of a 32 21 factorial design. The optimal formulation F5 (Desirability = 0.788) was prepared with 5% SAA, Solutol HS15: Pluronic F127 1:1 ratio, and 0.5% PG. The particle size, the ZP value, and the drug loading percentage were 26.55 ± 1.68 nm, −2.90 ± 0.41mV, and 7.49 ± 0.01%, respectively. The solid-state characterization results confirmed the dispersion of the drug in the mixed micelles. The ex vivo permeation study was performed on cow cornea using labeled MMCs with a fluorescent dye to test corneal penetrability of the optimal formulation through confocal laser scanning microscopy. The minimum inhibitory concentration (MIC) of the optimal formulation was compared to the standard market product (Natamycin (5%) ophthalmic suspension against the Candida albicans strain using the microdilution method and was 3 folds less than that of the standard market product. Furthermore, the safety and efficacy profiles of the optimal formulation were studied and compared to the standard market product via an in vivo study on male Albino rabbits, which proved the biosafety and effectiveness of the optimal formulation. Inclusively, AMO-MMs could be an auspicious corneal delivery system for the management of fungal keratitis.

Ocular candidiasis in a tertiary hospital in Japan: A 10-year single-center retrospective study

Ocular candidiasis is a major complication of candidemia that is sometimes sight-threatening. Although prompt ophthalmologic consultation and antifungal medication have been emphasized, recent changes in the causative species and drug susceptibilities make the picture unclear. This study aimed to determine whether there are trends among patients with ocular candidiasis and included 80 patients with candidemia who underwent ophthalmological screening at our hospital between 2010 and 2020. Data on the clinical characteristics, comorbidities, biochemical test results, causative Candida species, treatment, outcomes, visual acuity, and antifungal susceptibility were collected and analyzed. Statistical analyses were performed by comparing two groups, namely, the ocular candidiasis (n = 29) and non-ocular candidiasis (n = 51) groups. In the ocular candidiasis group, there were significantly more cases of central venous catheter insertion (82.8%, p = 0.026) and Candida albicans candidemia (72.4%, p < 0.001). Regarding ocular involvement, the majority of patients were asymptomatic. Most cases improved with antifungal therapy, but one case underwent vitrectomy. Between 2016 and 2020, there was a diversification of species, with a decrease in Candida parapsilosis and the emergence of Candida glabrata and Candida tropicalis. Regarding drug susceptibility, the minimum inhibitory concentrations of echinocandin and 5-fluorocytosine against Candida albicans, Candida parapsilosis, and Candida glabrata were slightly increased. In conclusion, in addition to appropriately performing ophthalmologic examinations, it is beneficial to select antifungal agents according to the diversity of species and drug susceptibilities.

Prevalence of Ocular Candidiasis and Candida Endophthalmitis in Patients With Candidemia: A Systematic Review and Meta-Analysis.

Infectious diseases and ophthalmology professional societies have disagreed regarding ocular screening in patients with candidemia. We aimed to summarize the current evidence on the prevalence of ocular candidiasis (OC) and Candida endophthalmitis (CE) according to the standardized definitions. A literature search was conducted from the inception date through 16 October 2022 using PubMed, Embase, and SCOPUS. Pooled prevalence of ocular complications was derived from generalized linear mixed models (PROSPERO CRD42022326610). A total of 70 and 35 studies were included in the meta-analysis for OC and concordant CE (chorioretinitis with vitreous involvement), respectively. This study represented 8599 patients with candidemia who underwent ophthalmologic examination. Pooled prevalences (95% CI) of OC, overall CE, concordant CE, and discordant CE were 10.7% (8.4-13.5%), 3.1% (2.1-4.5%), 1.8% (1.3-2.6%), and 7.4% (4.5-12%) of patients screened, respectively. Studies from Asian countries had significantly higher concordant CE prevalence (95% CI) of patients screened (3.6%; 2.9-4.6%) compared with studies from European countries (1.4%; .4-5%) and American countries (1.4%; .9-2.2%) (P <.01). Presence of total parenteral nutrition and Candida albicans was associated with CE, with pooled odds ratios (95% CI) of 6.92 (3.58-13.36) and 3.02 (1.67-5.46), respectively. Prevalence of concordant CE overall and among Asian countries was 2 and 4 times higher than the prevalence previously reported by the American Academy of Ophthalmology (AAO) of <0.9%, respectively. There is an urgent need to study optimal screening protocols and to establish joint recommendations by the Infectious Diseases Society of America and AAO.

Diagnosis and management of ocular candidiasis with choroidal neovascularization using multimodal imaging

Diagnosis and management of ocular candidiasis with choroidal neovascularization using multimodal imaging

Pronounced capping effect of olaminosomes as nanostructured platforms in ocular candidiasis management

The aim of this study was to formulate and boost ocular targeting of Fenticonazole Nitrate (FTN)-loaded olaminosomes in order to improve drug corneal permeation and candidiasis treatment. Olaminosomes were formulated by ethanol injection technique applying a central composite design. The independent variables were: span 80 amount (mg) (A), oleylamine concentration (mg%) (B) and oleic acid: drug ratio (C). The dependent responses were: percent entrapment efficiency (EE %), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP) and in vitro drug release after 10 hours (Q10h). Numerical optimization by Design-Expert® software was adopted to select the optimum formula. This formula was chosen based on highest EE %, ZP (as absolute value) and Q10h and lowest PS and PDI. The optimum formula was subjected to further in vitro characterization via Differential scanning calorimetry, Transmission electron microscopy, Fourier transform infrared spectroscopy, pH determination, effect of storage, influence of terminal sterilization, detection of Minimal Inhibitory Concentration and ex vivo corneal penetration analysis. Safety and antifungal activity of the optimum formula were tested through various in vivo studies like ocular irritancy, corneal tolerance, corneal uptake and susceptibility test. The optimum formula with the maximum desirability value (0.972) revealed EE% (84.24%), PS (117.55 nm), ZP (−74.85 mV) and Q10h (91.26%) respectively. The optimum formula demonstrated ocular tolerance with enhanced corneal penetration behavior (428.66 µg/cm2) and boosted antifungal activity (56.13%) compared to FTN suspension (174.66 µg/cm2 and 30.83%). The previous results ensured the ability of olaminosomes to enhance the corneal penetration and antifungal efficacy of Fenticonazole Nitrate.

Corneal targeted fenticonazole nitrate-loaded novasomes for the management of ocular candidiasis: Preparation, in vitro characterization, ex vivo and in vivo assessments

The purpose of this manuscript was to develop and optimize Fenticonazole Nitrate (FTN)-loaded novasomes aiming to enhance drug corneal penetration and to improve its antifungal activity. Ethanol injection was used to formulate FTN-loaded novasomes adopting a central composite design. The researched factors were: stearic acid concentration (g%) (A), span 80: drug ratio (B) and cholesterol amount (mg) (C), and their effects on percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP), and in vitro drug release after 8 hours (Q8h) were studied. Numerical optimization by Design-Expert® software was employed to select the optimum formula in respect to highest EE%, ZP (as absolute value), and Q8h >80% and lowest PS and PDI. Additional evaluation of the optimum formula was accomplished by short term stability study, effect of gamma sterilization, determination of Minimal Inhibitory Concentration and ex vivo corneal permeation study. The in vivo evaluation of the optimum formula was done to ensure its safety via in vivo ocular irritancy and in vivo corneal tolerance studies. Also, the efficacy was confirmed through in vivo corneal uptake study and susceptibility test. The optimum formula with the highest desirability value (0.738) showed EE% (94.31%), PS (197.05 nm), ZP (-66.95 mV) and Q8h (85.33%). It revealed to be safe, with augmented corneal permeation (527.98 µg/cm2) that leads to higher antifungal activity. The above results confirmed the validity of novasomes to improve the corneal permeation and antifungal activity of Fenticonazole Nitrate.

Risk Factors and Clinical Characteristics of Patients with Ocular Candidiasis.

Ocular candidiasis is a critical and challenging complication of candidemia. The purpose of this study was to investigate the appropriate timing for ophthalmologic examinations, risk factors for complications of ocular lesions, and their association with mortality. This retrospective cohort study applied, using multiple logistic regression analysis and Cox regression models, to cases of candidemia (age ≥ 18 years) for patients who underwent ophthalmologic consultation. Of the 108 candidemia patients who underwent ophthalmologic examination, 27 (25%) contracted patients had ocular candidiasis, and 7 experienced the more severe condition of endophthalmitis, which included subjective ocular symptoms. In most cases, the initial ophthalmologic examination was performed within one week of the onset of candidiasis with a diagnosis of ocular candidiasis, but in three cases, the findings became apparent only after a second examination within 7–14 days after onset of candidiasis. The independent risk factor extracted for the development of ocular candidiasis was the isolation of C. albicans (OR, 4.85; 95% CI, 1.58–14.90), unremoved CVC (OR, 10.40; 95% CI, 1.74–62.16), and a high βDG value (>108.2 pg/mL) (HR, 2.83; 95% CI = 1.24–6.27). Continuous ophthalmologic examination is recommended in cases of candidemia with the above risk factors with an initial examination within 7 days of onset and a second examination 7–14 days after onset.

Miconazole Nitrate loaded Soluplus®-Pluronic® nano-micelles as promising Drug Delivery Systems for Ocular Fungal Infections: In vitro and In vivo Considerations

Miconazole nitrate (MN) is a broad-spectrum antifungal agent which suffers poor solubility and impermeability to the ocular tissue which limits its use in the treatment of ocular infections especially fungal keratitis, which is considered one of the most prevailing ocular infections. The current study aims to utilize polymeric mixed nano-micelles for the ocular delivery of MN using 33 full factorial design by varying the ratios of Pluronic® P123, Pluronic® F127, and Tetronic® T701 while the monitored responses were particle size, cloud point (CP), encapsulation efficiency (%EE) and %released at 6 hours (%Q6) at pH 7.4. The optimized formula was incorporated with Soluplus® (SP) to further enhance the (%EE) and the resultant formula was assessed in vitro as well as in vivo against C. albicans in treatment of induced ocular candidiasis using rabbits as a model animal. Results revealed that the optimized formula which comprised F127 and P123 in a ratio of (2:1) when incorporated with SP (SP-MPM) resulted in an increase in %EE from 35.12±3.18 to 99.19±7.03 with a particle size of 44.39±2.68nm with a sustained release profile and stability for 3 months at 4±2°C. In vivo results demonstrated the enhanced ability of SP-MPM for treatment of ocular candidiasis with enhanced % inhibition and susceptibility to C. albicans compared to 0.2% MN suspension confirmed with histopathological examination of rabbit’s eyes after 7 days of treatment with the absence of any degenerative effect to the ocular tissue. Thus, it can be concluded that SP-pluronic mixed nano-micelles offer a successful and stable ocular delivery platform for antifungal drug MN ensuring both its safety and efficacy.

Factors associated with the development of ocular candidiasis and ocular prognosis with echinocandin therapy for candidemia

PurposeTo evaluate the factors associated with the development of ocular candidiasis (OC) and ocular prognosis with echinocandin therapy for candidemia.MethodsThe medical records of 56 consecutive patients with a positive blood culture for Candida species between November 2016 and October 2019 were retrospectively reviewed. Information on patient characteristics, isolated Candida species, treatment details for candidemia, and ocular findings were extracted to identify factors associated with OC development.ResultsThe leading pathogen of candidemia was Candida albicans (C.albicans) (41.1%). Of 56 patients, 18 (32.1%) were diagnosed with chorioretinitis, categorized as either probable (8 patients) or possible OC (10 patients). There was no case of endophthalmitis with vitritis. The incidence of probable OC was not significantly different between the groups treated with echinocandins and other antifungal drugs (15.2% vs. 11.1%, p = 1.00). In all probable OC cases, systemic antifungal therapy was switched from echinocandins to azoles, and no case progressed to endophthalmitis. A multivariate logistic analysis revealed that female sex (adjusted odds ratio [aOR], 8.93; 95% confidence interval [CI], 1.09–72.9) and C. albicans (aOR, 23.6; 95% CI, 1.8–281) were independent factors associated with the development of probable OC.ConclusionOne-seventh of patients with candidemia developed probable OC. Given the evidence of female and C. albicans as the factors associated with OC development, careful ophthalmologic management is required with these factors, especially in candidemia. Although echinocandins had no correlation with OC development and did not lead to the deterioration of ocular prognosis, further investigation is required.

Incidence of chorioretinitis and endophthalmitis in hospitalized patients with fungemia.

Bloodstream candida infections can seed the eye via hematogenous spread and result in chorioretinitis or endophthalmitis. If undetected and untreated, this can result in permanent vision loss. Past studies evaluating incidence of ocular candidiasis among hospitalized patients with positive fungal blood cultures have demonstrated variable rates of occurrence, but recent studies have generally shown a lower incidence than was reported several decades ago. Given low rates of occurrence, the utility of screening patients with dilated fundus exams has been called into question. The primary aim of this investigation is to identify the rate of chorioretinitis and endophthalmitis based on dilated fundoscopy for patients with fungemia at a tertiary care hospital. This study was a retrospective chart review of adult patients admitted to the medical centre of the University of Arkansas for Medical Sciences (UAMS) between May 1, 2014 and December 31, 2017, who had positive fungal blood cultures during their hospitalization. There were 324 positive fungal cultures in 290 patients. Of this initial group, there were 161 eye exams. Ocular examination identified 7 of 161 patients (4.3%) with chorioretinitis or endophthalmitis. These outcomes along with previous studies support the current guidelines that screening with dilated fundus examination for these patients is appropriate and necessary.

1173. Ocular Candidiasis in Patients with Candidemia Diagnosed by Blood Culture Versus T2Candida® Assay

BackgroundOcular candidiasis (OC) is a serious complication of candidemia. Current guidelines recommend dilated fundoscopic exam (DFE) in all patients with candidemia. In this study, we examined characteristics and outcomes of patients at UAB Medical Center with candidemia diagnosed by blood culture (BC) or T2Candida® rapid diagnostic assay (T2C) who were found to have evidence of fungal disease on ophthalmologic exam.MethodsPatients from 2016-2019 with either 1) at least one positive BC for Candida species or 2) positive T2C assay and negative or no paired BC were identified and retrospectively reviewed. Patients with additional positive BC or T2C within 60 days were excluded from the analysis. Data collected included risk factors for candidemia, causative Candida species, and whether DFE was performed after diagnosis. Patients with evidence of OC by exam were compared by type of ocular involvement (chorioretinitis vs. vitritis), whether visual symptoms were present, and whether intravitreal injection was performed.ResultsA total of 360 episodes of candidemia diagnosed by BC and 288 by T2C alone were included. Of those who underwent DFE, 33 BC patients (12.9%) had findings concerning for OC compared to 18 (8.9%) T2C patients (p=0.177) (Table 2). T2C patients with OC were younger, were more likely to have a prolonged ICU stay and to be mechanically ventilated, and were less likely to be on TPN compared to the BC group. Identification of C. parapsilosis was significantly more common in T2C patients (Table 1). There were no significant differences in presence of visual symptoms, type of ocular involvement, need for intravitreal injection, or 30-day mortality (Table 3).Table 1. Demographics and risk factors Table 2. Episodes of candidemia and ocular candidiasis by year Table 3. Ocular findings and outcomes ConclusionThe frequency of ocular disease was similar between groups. Significantly more T2C patients had candidemia due to C. parapsilosis, and the groups differed in terms of risk factors for candidemia. There were no differences in frequency of intravitreal injection, severity of eye disease, or mortality. Despite recent concerns about the necessity of DFE in asymptomatic patients with candidemia, we believe these results emphasize the importance of performing DFE in candidemic patients and also support the practice of doing so in patients with positive T2C even in the absence of positive blood cultures.Disclosures Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Todd P. McCarty, MD, Amplyx (Scientific Research Study Investigator)Cidara (Scientific Research Study Investigator)

1688. Invasive Ocular Candidiasis: Who Is Really at Risk?

BackgroundThe Infectious Disease Society of America recommends that all patients with candidemia undergo a dilated retinal examination to exclude invasive ocular candidiasis. However, it remains unclear whether there are patients with candidemia who do not warrant routine surveillance because the risk of ocular infection is low.MethodsWe conducted a retrospective cohort study of all patients with candidemia diagnosed at three academic medical centers (Duke, University of North Carolina and University of Virginia) from 2012 to 2017. We collected risk factors for invasive ocular candidiasis based on previous literature and compared them between patients with and without invasive ocular candidiasis. We then built a multivariate logistic regression model to assess which risk factors were significant for developing invasive ocular candidiasis.ResultsOverall, 942 patients were diagnosed with candidemia over the study period. The mean age was 55.9 years, 56% were men, 25% were non-White. Among these patients, 120 (13%) were also diagnosed with invasive ocular candidiasis, 10% with chorioretinitis and 3% with vitreous involvement. In our logistic regression analysis, central venous catheter presence [OR 8.35 (3.53, 19.77)], intravenous drug use [OR 5.02 (2.63, 9.58)], immunosuppression [OR 2.40 (1.55, 3.70)], total parenteral nutrition [OR 2.28 (1.42, 3.66)], non-White race [OR 1.65 (1.07, 2.55)], older age [OR 1.02 (1.01, 1.03)],and female gender [OR 0.57 (0.37, 0.89)] were risk factors for developing invasive ocular candidiasis. In addition, we found that persons with candidemia due to C. albicans were more likely to have invasive ocular candidiasis [OR 1.86 (1.22, 2.85)].ConclusionThis cohort represents the largest study of patients with candidemia who developed invasive ocular candidiasis to date. Based on our findings, clinicians should develop targeted and cost-effective strategies for endophthalmitis screening. Disclosures All authors: No reported disclosures.

Candida Related Uveitis: Clinical Findings, Diagnosis, and Treatment

Candidiasis is a major cause of morbidity and mortality. Earlier identification and treatment of candidemia has led to a decline in the incidence of ocular candidiasis in recent years. Ocular candidiasis shows a progression from chorioretinitis to endophthalmitis and may cause significant vision loss. Therefore emphasis should be given to early detection and treatment of candidemia patients and appropriate screening programs for ocular involvement.

The incidence of endophthalmitis or macular involvement and the necessity of a routine ophthalmic examination in patients with candidemia.

BackgroundThe incidence of ocular candidiasis (OC) in patients with candidemia varies across different reports, and the issue of whether routine ophthalmoscopy improves outcomes has been raised. This study investigated the incidence of OC and evaluate whether the extent of OC impacts the clinical outcomes.MethodsThis retrospective study included non-neutropenic patients with candidemia who underwent treatment at one of 15 medical centers between 2010 and 2016. Chorioretinitis without other possible causes for the ocular lesions and endophthalmitis was classified as a probable OC. If signs of chorioretinitis were observed in patients with a systemic disease that causes similar ocular lesions, they were classified as a possible OC.ResultsIn total, 781 of 1089 patients with candidemia underwent an ophthalmic examination. The prevalence of OC was 19.5%. The time from the collection of a positive blood culture to the initial ophthalmic examination was 5.0 ± 3.9 days in patients with OC. The leading isolate was Candida albicans (77.9%). Possible OC was associated with unsuccessful treatments (resolution of ocular findings) (odds ratio: 0.354, 95% confidence interval: 0.141–0.887), indicating an overdiagnosis in patients with a possible OC. If these patients were excluded, the incidence fell to 12.8%. Endophthalmitis and/or macular involvement, both of which require aggressive therapy, were detected in 43.1% of patients; a significantly higher incidence of visual symptoms was observed in these patients.ConclusionEven when early routine ophthalmic examinations were performed, a high incidence of advanced ocular lesions was observed. These results suggest that routine ophthalmic examinations are still warranted in patients with candidemia.

Efficacy of T-2307, a novel arylamidine, against ocular complications of disseminated candidiasis in mice.

T-2307, a novel arylamidine, shows broad-spectrum activity against pathogenic fungi, including Candida albicans. Ocular candidiasis is one of the serious complications associated with Candida bloodstream infection and is known to be refractory to conventional antifungal agents. The aim of the present study was to clarify the effectiveness of T-2307 against ocular candidiasis using a mouse model. We evaluated ocular fungal burden in mice infected with C. albicans that received treatment with antifungal agents [T-2307, liposomal amphotericin B (LAMB) or fluconazole] for 3 consecutive days. We also assessed survival rates of mice after C. albicans infection followed by treatment for 7 consecutive days. In addition, ocular T-2307 concentrations and in vitro effectiveness against C. albicans biofilm formation were evaluated. The ocular fungal burdens were significantly reduced after T-2307 treatment compared with the control group (no treatment received) and were comparable with those observed following treatment with LAMB or fluconazole in both early- and late-phase treatment experiments. In addition, all of the mice treated with antifungal agents survived for 3 weeks after infection, whereas mice in the control group died within 3 days. The ocular T-2307 trough concentration was maintained above the MIC in the infected mice. An in vitro biofilm inhibition experiment showed that T-2307 suppressed C. albicans biofilm formation at the sub-MIC level, which was comparable with amphotericin B. Given these results in experimental disseminated candidiasis, T-2307 may be an effective treatment against the complication of ocular candidiasis.

Perioperative Ocular candidiasis in inflammatory bowel disease patients

Perioperative Ocular candidiasis in inflammatory bowel disease patients

Differences in Ocular Complications Between Candida albicans and Non-albicans Candida Infection Analyzed by Epidemiology and a Mouse Ocular Candidiasis Model.

Objectives: Candida species are a major cause of hospital infections, including ocular candidiasis, but few studies have examined the propensities of specific species to invade the eye or the unique immunological responses induced. This study examined the frequency and characteristics of species-specific Candida eye infections by epidemiology and experiments using a mouse ocular candidiasis model.Methods: We reviewed medical records of candidemia patients from January 2012 to March 2017. We also evaluated ocular fungal burden, inflammatory cytokine and chemokine profiles, and inflammatory cell profiles in mice infected with Candida albicans, Candida glabrata, or Candida parapsilosis.Results: During the study period, 20 ocular candidiasis cases were diagnosed among 99 candidemia patients examined by ophthalmologists. Although C. parapsilosis was the most frequent candidemia pathogen, only C. albicans infection was significantly associated with ocular candidiasis by multivariate analysis. In mice, ocular fungal burden and inflammatory mediators were significantly higher during C. albicans infection, and histopathological analysis revealed invading C. albicans surrounded by inflammatory cells. Ocular neutrophil and inflammatory monocyte numbers were significantly greater during C. albicans infection.Conclusion: Candida albicans is strongly associated with ocular candidiasis due to greater capacity for invasion, induction of inflammatory mediators, and recruitment of neutrophils and inflammatory monocytes.