aspergillus endophthalmitis

Doft B.H., Clarkson J.G., Rebell G., Forster R.K. Endogenous Aspergillus endophthalmitis in drug abusers. Kolomeyer A.M., Murphy K.M., Traband A., Frank I., Kim B.J. Endophthalmitis is a severe inflammation of the inside of the eye, usually due to bacterial or fungal infection. Smith T.C., Benefield R.J., Kim J.H. Real-time broad range PCR helps to rapidly identify the pathogenic fungus in comparison to the standard culturing method, which can speed up the treatment process [121]. analyzed outcomes of 66 patients where Aspergillus was the most common pathogen isolated. In invasive Aspergillus infection, successful treatment has also been achieved with the addition of triazoles or polyenes, although fluconazole is used in less severe cases [14,125]. Additionally, photophobia can occur in individuals without any ocular trauma or in those who use contact lenses [21]. Specifically, azole drugs interact with both CYP3A4 and 2C19, in which the P450 enzymes are responsible for metabolizing various drugs. This is due to a combination of its large molecular weight and the strong protein binding properties it possesses, with previous attempts of administering caspofungin intravenously failing to treat the eye [22,86,96,135,143]. Zhonghua Yan Ke Za Zhi. (A) An image of a 69-year-old womans infected eye 2 months post-cataract surgery. The guidelines of the Infectious Disease Society of America (IDSA) recommend estimating the levels of serum BDG for diagnosing invasive aspergillosis in high-risk patients such as those with hematologic malignancy and allogeneic HSC. Presumably contaminated intravenous infusion-induced Aspergillus terreus endogenous endophthalmitis presenting with posterior hypopyon. Endogenous Aspergillus endophthalmitis. Kupfahl C., Michalka A., Lass-Florl C., Fischer G., Haase G., Ruppert T., Geginat G., Hof H. Gliotoxin production by clinical and environmental Aspergillus fumigatus strains. While endogenous endophthalmitis is acquired hematogenously, the latter occurs due to ocular trauma or post-surgical complications [13]. sharing sensitive information, make sure youre on a federal In later stages of infection, the hematopoietic CARD9 signal amplifies the chemotactic signal and maintains lung neutrophil recruitment. Due to the relative scarcity of Aspergillus, the exploration of usable drug types has been limited to three classes of antimycotics as primary modes of treatment. In exogenous fungal endophthalmitis, Gao et al. After evaluation at the University of Southern California Roski Eye Institute, she was diagnosed with a likely fungal endogenous endophthalmitis based on ultrasound findings and underwent emergent vitrectomy. Typically, the initial examination is based upon the appearance of the eye, as well as any preexisting conditions or environmental factors which may aid in the subsequent diagnosis. About 34% of trauma cases were associated with A. flavus endophthalmitis [13]. On the other hand, studies of healthy and immunocompromised mice have also reported A. flavus to be more virulent, resulting in higher mortality [52,54,55]. Parazytol. Additionally, Aspergillus can directly invade the eye following injury or post-operative trauma resulting in endophthalmitis ( Figure 1 ), resulting in increased inflammation, fungal load, and retinal tissue damage, and reduced retinal function. Research in our laboratory is supported in part by National Institute of Health (NIH) Grants (R21AI135583, R01EY026964, and R01 EY027381 to A.K. For example, the condition may follow a procedure to treat cataracts or glaucoma. utilized 18S ribosomal ribonucleic acid (rRNA) primers to detect six Candida and five Aspergillus species from either aqueous humor or vitreous fluid specimens [119]. National Library of Medicine Endophthalmitis is a rare but severe disease of ocular inflammation involving vitreous or aqueous fluids and other intraocular tissues that can result in blindness. The dose-dependent toxicity of the retina was observed in rabbits who were given intravitreal injections of AmB-d by Axelrod et al. Zarrinfar H., Mirhendi H., Fata A., Khodadadi H., Kordbacheh P. Detection of Aspergillus flavus and A. fumigatus in Bronchoalveolar Lavage Specimens of Hematopoietic Stem Cell Transplants and Hematological Malignancies Patients by Real-Time Polymerase Chain Reaction, Nested PCR and Mycological Assays. BDG has been extensively studied and validated during the early surveillance and diagnosis of fungal infections, particularly in patients with hematologic malignancy, a critical illness, and solid organs, and allogeneic hematopoietic stem cell transplant (HSCT) populations [122]. Microbiol. Endophthalmitis, in general, is an inflammatory condition affecting the tissues and fluid of the eyeball. https://creativecommons.org/licenses/by/4.0/. Danielescu C., Cantemir A., Chiselita D. Successful treatment of fungal endophthalmitis using intravitreal caspofungin. IL-1 and IL-1 are also involved in this process [72,73]. Yoshida L.S., Abe S., Tsunawaki S. Fungal gliotoxin targets the onset of superoxide-generating NADPH oxidase of human neutrophils. and Paecilomyces spp. Both fungi up-regulated the expression of MMP-9 in the cultured microglia [106]. Panackal A.A., Bennett J.E., Williamson P.R. A clinical study showed a 23-year-old female presented with a history of taking steroids for the past year developing A. flavus endophthalmitis that led to sudden vision loss [57]. A case of aspergillus endophthalmitis in an immuncompetent woman: Intra-ocular penetration of oral voriconazole: A case report. Previous studies have shown that the inadequate penetration of echinocandins into various ocular compartments inhibits its ability to reach therapeutic levels, and direct administration is therefore advised [82]. Adam C.R., Sigler E.J. Patients with hyper IgE syndrome (i.e., Job syndrome; STAT3 deficiency) are susceptible to aspergillosis, usually at the age of 30 or 40 for those with bronchiectasis or emphysema [83]. Epithelial and endothelial host cells play crucial roles in internalizing the conidia through the Dectin-1-dependent pathway [44,45,46]. In cases of macular infection or vitritis from Aspergillus endophthalmitis, a combination of systemic and intravitreal antifungal agents should be used to ensure appropriate therapeutic levels within the posterior segment of the eye. Gupta N, Singh PK, Revankar SG, Chandrasekar PH, Kumar A. Microorganisms. 2018;116:296300. Patients with heart disease should be cautioned when azoles are used in combination with quinolones, as this can lead to prolongation of the QTc interval. The study further suggested the use of BDG testing to monitor the progression of the disease and response to therapy [122]. Taghizadeh-Armaki M., Hedayati M.T., Moqarabzadeh V., Ansari S., Mahdavi Omran S., Zarrinfar H., Saber S., Verweij P.E., Denning D.W., Seyedmousavi S. Effect of involved Aspergillus species on galactomannan in bronchoalveolar lavage of patients with invasive aspergillosis. is the main causative agent of fungal endophthalmitis [10]. with local and systemic antifungal therapy. However, in mice exposed to A. fumigatus conidia through the respiratory route, hematopoietic cells in the lung lacking CD18 are not associated with the inability to kill conidia via neutrophils [68]. Additionally, a study by Kernt et al. Of note, the popular agent fluconazole can be used against Candida, yet it is ineffective in the treatment of mold [76]. Aspergillus endophthalmitis is rare, representing less than 1% of ocular complications in heart and/or lung recipients ( Akerele and Lightman, 2007). Aspergillus endophthalmitis: Potential role for vitreous galactomannan testing? Before Puah S.H., Ng J., Ang B., Xu H., Agrawal R., Ho S.L. [18]. Wiad. Citation 27 Prakash et al described a case of endophthalmitis due to Aspergillus fumigatus in a 40-year-old man with angioimmunoblastic T-cell lymphoma, who finally . In contrast, in the fungal keratitis model, the transport of CD18-dependent neutrophils to the cornea is essential for the defense of the host [82]. Please enable it to take advantage of the complete set of features! Zanganeh E., Zarrinfar H., Rezaeetalab F., Fata A., Tohidi M., Najafzadeh M.J., Alizadeh M., Seyedmousavi S. Predominance of non-fumigatus Aspergillus species among patients suspected to pulmonary aspergillosis in a tropical and subtropical region of the Middle East. Nevertheless, deleterious effects should still be considered when choosing appropriate treatment options. Although smears taken from vitreous specimens may be examined immediately via direct microscopy, they have a success rate of 50% for fungal detection. Werner J.L., Metz A.E., Horn D., Schoeb T.R., Hewitt M.M., Schwiebert L.M., Faro-Trindade I., Brown G.D., Steele C. Requisite role for the dectin-1 beta-glucan receptor in pulmonary defense against Aspergillus fumigatus. The prevalence of Aspergillus endophthalmitis is reported as being around 7.1% among orthotopic liver transplant recipients [31], suggesting an increased susceptibility to Aspergillus in patients with organ transplants [31]. Underhill D.M., Pearlman E. Immune Interactions with Pathogenic and Commensal Fungi: A Two-Way Street. A major cell wall component of Aspergillus is the molecule galactomannan (GM), which is released at higher concentrations during Aspergillus infection [93]. (Ashok Kumar); writing (original draft preparation, review, editing), A.K. Gandhi J., Joseph J. It usually causes permanent loss of vision despite correct antibiotic treatment, and is associated with morbidity and mortality, especially if diagnosis and treatment is not early. Mice were injected with caspofungin at various concentrations and examined by both electroretinography (ERG) and histopathology. 2016;65:468475. (D) Three months later, showing clearance of the disease with restoration in the clarity of the anterior chamber and corneal graft. All authors have read and agreed to the published version of the manuscript. Drosophila melanogaster as a model organism for invasive aspergillosis. Principles and Practice of Pediatric Infectious Diseases. A study in a fly model of aspergillosis. Among the fungal pathogens, the Aspergillus species, Aspergillus fumigatus, continues to be more prevalent in fungal endophthalmitis patients. Liu C., Ji J., Wang Z., Chen H., Cao W., Sun X. Microbiological Isolates and Antibiotic Susceptibilities in Cases of Posttraumatic Endophthalmitis: A 15-Year Review. reported positive blood cultures of Aspergillus panophthalmitis in a 10-year retrospective review of endogenous endophthalmitis [118]. Rudramurthy S.M., Paul R.A., Chakrabarti A.A., Mouton J.W., Meis J.A. Post-operative and traumatic injuries are major contributing factors resulting in ocular fungal infections in healthy and, more importantly, immunocompromised individuals. Laboratory diagnosis of infectious endophthalmitis. eCollection 2019. To achieve this, repeated injections may be necessary, but they should only be performed after a thorough examination after the first injection [82]. Mice with neutropenia showed a higher disease severity with extended fungal burden and increased inflammatory mediators during exogenous A. fumigatus endophthalmitis [91]. Vinh D.C., Sugui J.A., Hsu A.P., Freeman A.F., Holland S.M. On the other hand, culturing is a common diagnostic method for fungi but has a relatively low sensitivity of 40%. Differential inflammatory response to Aspergillus flavus and Candida albicans infection in human retinal pigment epithelial cells: Role in treatment of endophthalmitis. Liu et al. Taylor P.R., Roy S., Meszaros E.C., Sun Y., Howell S.J., Malemud C.J., Pearlman E. JAK/STAT regulation of Aspergillus fumigatus corneal infections and IL-6/23-stimulated neutrophil, IL-17, elastase, and MMP9 activity. With an accuracy of approximately 70%, studies showed the successful diagnosis of Aspergillus in a specific immunocompromised patient cohort, suffering either from hematological malignancy or having undergone allogeneic HSCT [125,126,127]. Endogenous Aspergillus endophthalmitis is a rare complication of invasive aspergillosis and most often is seen in transplant patients receiving intense immunosuppressive agents. Common septate filamentous fungi are Aspergillus, Fusarium, Cephalosporium, Paecilomyces, and Penicillium species. Latg J.P., Chamilos G. Aspergillus fumigatus and Aspergillosis in 2019. Logan S., Rajan M., Graham E., Johnson E., Klein J. Unlike most forms of postoperative endophthalmitis, which occur when commensal colonizing ocular flora are inoculated into the eye, postsurgical P. aeruginosa endophthalmitis is more likely to result from exogenous . Additionally, Aspergillus can directly invade the eye following injury or post-operative trauma resulting in endophthalmitis (Figure 1), resulting in increased inflammation, fungal load, and retinal tissue damage, and reduced retinal function. They work by inhibiting the ability of Aspergillus to synthesize ergosterol via a blockade of 14-demethylase [125]. Keywords: Ruxolitinib, a small JAK/STAT inhibitor molecule, can reduce the death of human neutrophils stimulated by IL-6 and IL23 during Aspergillus infection [85]. In humans, Mendelian defects in CARD9 can cause spontaneous extrapulmonary aspergillosis, and the resulting fungal abscess in affected patients does not contain neutrophils [74]. (B) A cross-section image of the eye after enucleation. ), NIH Core Grant P30EY004068 (to Linda D. Hazlett), and an unrestricted grant from Research to Prevent Blindness Inc. (to Kresge Eye Institute, Wayne State University). (A) Eye 4 days after PKP. Hoenigl M., Krause R. Antifungal therapy of aspergillosis of the central nervous system and aspergillus endophthalmitis. Clinically, Aspergillus endophthalmitis presents with symptoms of ocular pain and blurry vision, which can be seen in both endogenous and exogenous forms [30]. HHS Vulnerability Disclosure, Help Shen Y.C., Liang C.Y., Wang C.Y., Lin K.H., Hsu M.Y., Yuen H.L., Wei L.C. Advanced diagnostic tools such as fluor angiography, fluorescence in situ hybridization (FISH), and retinochoroidal biopsy can potentially aid in complicated ocular infections [18]. In addition, a study reported the presence of sub-macular abscesses as well (Figure 2) [61]. There are a few major advantages in comparison to voriconazole when used in invasive aspergillosisit has a longer half-life, 56104 h, without reported renal or phototoxicity, no adverse central nervous system effect, and broader antifungal coverage outside of Aspergillus and Candida [32,141,142]. However, due to overlapping clinical symptoms with other endophthalmitis etiology, fungal endophthalmitis pose a challenge in its diagnosis and treatment. Another study by Mojumder et al. Chakrabarti A., Shivaprakash M.R., Singh R., Tarai B., George V.K., Fomda B.A., Gupta A. Fungal endophthalmitis: Fourteen years experience from a center in India. Riddell J.T., Comer G.M., Kauffman C.A. Endogenous Aspergillus endophthalmitis has been reported by Al Qahtani et al secondary to fungal endocarditis in an immunocompromised patient affected by Wegener' granulomatosis. Careers. It is pertinent to note that vitreous specimens are more reliable and sensitive than aqueous specimens in the process of fungal identification [111,112,113]. Fungal Endophthalmitis: A Comprehensive Review. Due to voriconazoles shorter half-life, there may be a need for repeated injections depending on the response to therapy after examination [82,134]. Regarding diagnosis, roughly 90% of cultured vitrectomy specimens are positive [122]. Heterogeneity Confounds Establishment of a Model Microbial Strain. Nevertheless, some cases involving Aspergillus endophthalmitis patients showed elevated levels of serum GM, and this thus might assist in the prognosis of Aspergillus infections [17,30]. Keller N.P. Ziaee A., Zia M., Goli M. Identification of saprophytic and allergenic fungi in indoor and outdoor environments. These patients are more susceptible to invasive aspergillosis due to recurrent bacterial infections, and the model of this anatomical lung defect reflects this. showed efficacy in the treatment of A. fumigatus endophthalmitis in C57BL/6J mice by isavuconazole. Haseeb A.A., Elhusseiny A.M., Siddiqui M.Z., Ahmad K.T., Sallam A.B. Pt 5. Before A drawback of caspofungin, amongst other echinocandins, is its inability to penetrate the eye when given systemically [22,86,96,135,143]. To diagnose fungal endophthalmitis, quantitative real-time PCR is one of the best readily available options. Bethesda, MD 20894, Web Policies These reports indicate retinal residential cells evoke an inflammatory response via TLRs during fungal endophthalmitis. However, many specific host molecular defense mechanisms are still poorly understood and require further research. -, Gniadek A., Macura A.B. Rabbit eyes injected with concentrations of 50 g/0.1 mL of caspofungin showed no sign of toxicity in their eye and no differences in either their a-wave or b-wave responses [133]. Additionally, a major issue concerning the use of GM as a diagnostic factor is the lack of a standard range of detection for immunocompromised patients. Another study involving A. flavus and C. albicans infections in microglial cells (CHME-3) demonstrated that cells challenged with A. flavus expressed higher levels of TLRs (TLR-1, -2, -5, -6, -7 and -9) as well as cytokines (IL-1, IL-6, IL-8, IL-10, and IL-17) in comparison to Candida. Antibodies to or genetic defects in the 2 integrin subunit of complement receptor 3 (i.e., CD18) inhibit the activation of NADPH oxidase in neutrophils during A. fumigatus infection [80]. Cytokine networking in lungs of immunocompetent mice in response to inhaled Aspergillus fumigatus. Hypopyons, found in 75% of symptomatic patients, are located posteriorly, and are commonly associated with creamy yellow exudates [60]. Purpose: The aim of this study was to describe the clinical presentations, management and factors determining outcomes of Aspergillus endophthalmitis. Unlike exogenous endophthalmitis, endogenous endophthalmitis can occur in both eyes, and its onset is typically subacute [25]. Sadiq M.A., Hassan M., Agarwal A., Sarwar S., Toufeeq S., Soliman M.K., Hanout M., Sepah Y.J., Do D.V., Nguyen Q.D. Invasive Aspergillosis by Aspergillus flavus: Epidemiology, Diagnosis, Antifungal Resistance, and Management. The pathobiology of Aspergillus fumigatus. Notably, the major drawbacks to PCR testing are its high cost and need for advanced equipment. PMC This may be related to the slow growth rate or the required specific growing conditions of Aspergillus. (B) After 6 days, the progression of the disease is quite apparent with white infiltrates and stromal melting (arrow). 2018;78:265270. Methods: The study included 91 eyes of 91 patients with culture-proven Aspergillus endophthalmitis. Weishaar P.D., Flynn H.W., Jr., Murray T.G., Davis J.L., Barr C.C., Gross J.G., Mein C.E., McLean W.C., Jr., Killian J.H. Dave T.V., Dave V.P., Sharma S., Karolia R., Joseph J., Pathengay A., Pappuru R.R., Das T. Infectious endophthalmitis leading to evisceration: Spectrum of bacterial and fungal pathogens and antibacterial susceptibility profile. The incidence of endogenous endophthalmitis ranges from 215%, including those caused by bacterial and fungal pathogens [25], where Aspergillus is the second most common cause of endogenous endophthalmitis, with the primary fungal pathogen being Candida albicans [26,27,28,29]. Wykoff C.C., Flynn H.W., Jr., Miller D., Scott I.U., Alfonso E.C. An important sign of Aspergillus endophthalmitis is the presence of inflammation in the affected eye interiors, including vitritis [9,63]. Polyenes are a versatile group of anti-mycotic drugs, one of the most widely used drugs in Aspergillus endophthalmitis treatment, and include amphotericin B (AmB) [11,17,21,61,65].

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