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Sample records for virus epithelial keratitis

  1. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis

    Science.gov (United States)

    Wilhelmus, Kirk R

    2015-01-01

    Background Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis which, though usually self-limiting, may persist or progress without treatment. Objectives To compare the relative effectiveness of antiviral agents, interferon, and corneal debridement in the treatment of HSV epithelial keratitis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 12), PubMed (January 1946 to 31 December 2014), EMBASE (January 1980 to 31 December 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to 31 December 2014), System for Information on Grey Literature in Europe (OpenGrey) (January 1995 to 31 December 2014), BIOSIS (January 1926 to 5 May 2014), Scopus (January 1966 to 31 December 2014), Japan Science and Technology Institute (J-Global) (January 1975 to 31 December 2014), China National Knowledge Infrastructure (CNKI) (January 1979 to 31 December 2014), British Library’s Electronic Table of Contents (Zetoc) (January 1993 to 7 May 2014). We looked for trials listed on the the metaRegister of Controlled Trials (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en), Chinese Clinical Trial Registry, the U.S. Food and Drug Administration (FDA) (www.fda.gov/), National Institute for Health and Clinical Excellence (NICE) (www.evidence.nhs.uk) and the European Medicines Agency (EMA) (www.ema.europa.eu/ema/) as of 31 December 2014. There were no language or date restrictions in the search for trials. We also culled literature digests and conference proceedings as of 15 April 2014. There were no language or date restrictions in the search for trials. Selection criteria Randomised and quasi-randomised trials of HSV dendritic or geographic epithelial keratitis were included that reported the proportion of

  2. Recurrent herpes simplex virus keratitis in a young Nigerian male ...

    African Journals Online (AJOL)

    Herpes Simplex Virus Keratitis is the infection of cornea by double stranded DNA Viruses.This condition has a tendency to reoccur after a certain period of time. A 25 year old male presented to the clinic with reduced visual acuity, itching, redness, pain and photophobia in the left eye. Onset of symptoms was 10 days prior to ...

  3. Cytoarchitecture of epithelial inflammatory infiltration indicates the aetiology of infectious keratitis.

    Science.gov (United States)

    Smedowski, Adrian; Tarnawska, Dorota; Orski, Michal; Wroblewska-Czajka, Ewa; Kaarniranta, Kai; Aragona, Pasquale; Wylegala, Edward

    2017-06-01

    To analyse cytological features of corneal epithelium in infectious keratitis. One hundred and eighteen patients (53 males and 65 females) diagnosed with acute stage of infectious keratitis (45 viral, 40 bacterial, 23 fungal, 10 Acanthamoeba keratitis) were included in study. We performed retrospective analysis of bright and blue-light slit-lamp photographs and in vivo corneal confocal microscopy scans of the corneal epithelium from five corneal regions (superior, inferior, temporal, nasal and central). Density, morphology of inflammatory cells and their relation to epithelial structures, as well as density of nerve fibres, were evaluated in relation to the keratitis aetiology. We characterized five morphological types of inflammatory cells forming infiltration. Cell and nerve fibre densities showed significant differences between groups, and the most intense inflammatory infiltration was associated with fungal then bacterial, viral and Acanthamoeba keratitis. Additionally, differences in aetiology-specific ratio of round/non-round inflammatory cells were observed. Confocal microscopy analysis in infectious keratitis of various aetiologies revealed quantitative and qualitative differences in inflammatory cell infiltration expressed in different ratio of round/non-round inflammatory cells. In vivo microscopic analysis of both the corneal epithelial layer cytopathology and the cytology of inflammatory infiltration provides a fast and specific differentiation of keratitis aetiology that may increase the accuracy in the selection of the initial treatment. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  4. Acanthamoeba keratitis in a non-contact lens wearer with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, Birgitte Rønde; Kronborg, Gitte

    2003-01-01

    Acanthamoeba keratitis is potentially blinding and often associated with contact lens wearing. A human immunodeficiency virus (HIV)-positive patient, a non-contact lens wearer, presented with keratitis. She experienced a protracted course of disease, characterized by exacerbations and remissions...... keratitis the diagnosis is delayed, pathognomonic features are often not seen and visual outcome is usually poor. There is no known relation between HIV infection and Acanthamoeba keratitis....

  5. Necrotizing Keratitis Caused by Acyclovir-Resistant Herpes Simplex Virus

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    Koji Toriyama

    2014-10-01

    Full Text Available Background: We report a case of necrotizing keratitis caused by acyclovir (ACV-resistant herpes simplex virus (HSV with a clinical appearance similar to a previous fungal keratitis infection. Methods: Observational case report. Results: Penetrating keratoplasty was performed in the left eye with a history of herpetic keratitis that resolved with periodic treatment with ACV ointment and a topical steroid. The left eye was painful and red with an abscess and corneal erosion in the peripheral donor cornea. Examination of the scraped corneal epithelium by light microscopy and culturing identified Candida albicans; polymerase chain reaction (PCR was negative for human herpes viruses. After antifungal treatment, the ocular pain gradually decreased and the lesions slowly improved but recurred with a similar clinical appearance. A second light microscopy examination and cultures were negative for pathogens including C. albicans. PCR was positive for HSV-1 DNA; treatment with 3% topical ACV ointment was unsuccessful. A third examination showed only HSV-1 DNA. Despite antiviral ACV ointment, no clinical improvement occurred based on the HSV DNA copy numbers, which were the same before and after treatment, indicating a possible ACV-resistant strain. When topical trifluorothymidine was substituted for ACV, clinical improvement occurred and the HSV DNA copy numbers decreased. Conclusion: Necrotizing keratitis induced by ACV-resistant HSV occurred independently after fungal keratitis, with a similar clinical appearance in this case, making diagnosis and treatment difficult. Monitoring the HSV DNA load by real-time PCR could be useful for refractory cases even with atypical clinical appearances.

  6. In-vivo immunofluorescence confocal microscopy of herpes simplex virus type 1 keratitis

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    Kaufman, Stephen C.; Laird, Jeffery A.; Beuerman, Roger W.

    1996-05-01

    The white-light confocal microscope offers an in vivo, cellular-level resolution view of the cornea. This instrument has proven to be a valuable research and diagnostic tool for the study of infectious keratitis. In this study, we investigate the direct visualization of herpes simplex virus type 1 (HSV-1)-infected corneal epithelium, with in vivo confocal microscopy, using HSV-1 immunofluorescent antibodies. New Zealand white rabbits were infected with McKrae strain of HSV-1 in one eye; the other eye of each rabbit was used as an uninfected control. Four days later, the rabbits were anesthetized and a cellulose sponge was applied to each cornea, and a drop of direct HSV fluorescein-tagged antibody was placed on each sponge every 3 to 5 minutes for 1 hour. Fluorescence confocal microscopy was then performed. The HSV-infected corneas showed broad regions of hyperfluorescent epithelial cells. The uninfected corneas revealed no background fluorescence. Thus, using the confocal microscope with a fluorescent cube, we were able to visualize HSV-infected corneal epithelial cells tagged with a direct fluorescent antibody. This process may prove to be a useful clinical tool for the in vivo diagnosis of HSV keratitis.

  7. Corneal herpes simplex virus type 1 superinfection in patients with recrudescent herpetic keratitis

    NARCIS (Netherlands)

    L. Remeijer (Lies); J. Maertzdorf (Jeroen); J. Buitenwerf (Johannes); A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George)

    2002-01-01

    textabstractPURPOSE: Herpetic keratitis is a common sequel of a corneal infection with herpes simplex virus (HSV)-1. Recrudescent herpetic keratitis (RHK) may result in irreversible damage to the cornea. Recurrences may be caused by reactivation of endogenous HSV-1 or reinfection with exogenous

  8. Corneal herpes simplex virus type 1 superinfection in patients with recrudescent herpetic keratitis.

    NARCIS (Netherlands)

    L. Remeijer (Lies); J. Maertzdorf (Jeroen); J. Buitenwerf (Johannes); A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George)

    2002-01-01

    textabstractPURPOSE: Herpetic keratitis is a common sequel of a corneal infection with herpes simplex virus (HSV)-1. Recrudescent herpetic keratitis (RHK) may result in irreversible damage to the cornea. Recurrences may be caused by reactivation of endogenous HSV-1 or reinfection with exogenous

  9. [Role of Herpes simplex virus in the immune stromal keratitis].

    Science.gov (United States)

    Vinagre, C; Martínez, M J; Vogel, M; Traipe, L; Stoppel, J; Squella, O; Srur, M; Charlín, R

    2001-03-01

    Herpes simplex virus (HSV) infection of the cornea is a leading cause of blindness in occidental countries and a common recurrent manifestation of it is the immune stromal keratitis (ISK). However, it is not known whether active viral replication occurs during the acute phase of the disease, because isolation of the virus by conventional culture techniques has not been accomplished. To establish the presence of HSV in patients with ISK. Fourteen corneal swabbing samples, from active diseased eyes of patients with clinical diagnosis of ISK, were submitted to Herpchek and PCR for the identification of HSV antigens and genome. All ISK samples were negative by both techniques. It was not possible to identify HSV antigens nor their genome by the methodology used. It is likely that, they can't be detected in corneal superficial layers or probably there is no viral replication at this stage of the disease, so antiviral therapy should be reconsidered.

  10. Human herpes simplex virus keratitis: the pathogenesis revisted

    NARCIS (Netherlands)

    L. Remeijer (Lies)

    2002-01-01

    textabstractThe aim of this thesis is to elucidate pathogenic mechanisms of different forms of human HSV keratitis. HSV infection of the corneal epithelium causes a classical dendritic shaped lesion. Many studies could explain the development and growth in dendritic keratitis, but none of these

  11. Coexistence of herpes simplex virus infection in microsporidial stromal keratitis associated with granulomatous inflammation.

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    Mittal, Ruchi; Balne, Praveen K; Sahu, Srikant; Das, Sujata; Sharma, Savitri

    2017-04-01

    Microsporidial stromal keratitis poses several diagnostic challenges. Patients may present with corneal ulceration, marked stromal thinning, or even as a quite corneal scar. The presentation of microsporidial stromal keratitis commonly mimics viral keratitis. Microbiology scrapings are usually helpful; however, scraping and culture-negative cases pose a significant diagnostic dilemma. Histopathological examination is diagnostic but shows varying degree of inflammation, predominantly composed of polymorphonuclear leukocytes. Granulomatous inflammation, in microsporidial stromal keratitis, is never well described, and the authors in this article aim to describe the presence of granulomatous inflammation in microsporidial stromal keratitis, in patients with associated herpes simplex virus (HSV) keratitis. This was a retrospective and observational study conducted at a tertiary eye care center. Of 263 patients who underwent therapeutic penetrating keratoplasty for infectious keratitis, during 2011-2013, seven patients were diagnosed as microsporidial stromal keratitis. Microsporidial spores could be demonstrated on microbiological scrapings in 5/7 (71%) of cases, but identified on histopathological examination and also confirmed on polymerase chain reaction (PCR) for microsporidium in 100% of cases. There was evidence of diffuse stromal necrosis with markedly severe degree of polymorphonuclear leukocytic infiltrates, with granulomatous inflammation in 42% of cases. Interestingly, these were positive for HSV-1 DNA on PCR. Review of medical records revealed much severe clinical presentations in patients with granulomatous inflammation, in comparison to cases without granulomatous inflammation. The authors hereby recommend that severe clinical presentation in patients with microsporidial stromal keratitis, markedly dense polymorphonuclear leukocytic infiltrates or the presence of granulomatous inflammation on the histopathological examination, should be investigated

  12. [Herpetic keratitis: clinical-virological correlation].

    Science.gov (United States)

    Martínez, M J; Vogel, M; Stoppel, J; Charlin, R; Squella, O; Srur, M; Traipe, L; Verdaguer, J; Suárez, M

    1997-06-01

    Herpetic keratitis is the main infectious cause of corneal opacity. The existence of effective antiviral agents underscores the need of an early diagnosis. To correlate clinical features of herpetic keratitis with virological studies. Forty one patients with a clinical diagnosis of herpetic keratitis were studied. Viral isolation, polymerase chain reaction (PCR) and typification were done in a sample taken by swabbing the ocular lesion. Twenty six patients (31% female) had epithelial keratitis, that was mild or moderate in 88% of cases and acute in 77% of them. In 20 patients (77%), viral isolation and PCR were positive (HSV-2 in one case). Fifteen patients (67% female) had stromal keratitis, 93% of cases were moderate or severe and 53% were acute. Viral isolation was negative in all cases and in 20% PCR was positive. Viral isolation and PCR were equally sensitive in epithelial keratitis, but in stromal keratitis only PCR could detect the virus. Moderate acute dendrite was the predominant clinical manifestation. The higher proportion of women with stromal keratitis supports its possibly autoimmune etiology. HSV-2 is seldomly isolated and possibly associated to vertical transmission.

  13. Herpes Simplex epithelial keratitis associated with daily disposable contact lens wear.

    Science.gov (United States)

    Hamroush, Ahmed; Welch, James

    2014-06-01

    To report a case of epithelial Herpes Simplex keratitis in a patient wearing daily disposable contact lenses. Case report. A 30-year-old female contact lens wearer presented to the emergency clinic with a painful, red left eye associated with an acute reduction of vision over 48 h. On examination, confluent dendritic ulcers were present on the cornea. Neither pertinent ocular nor medical history was obtained to explain such a dramatic clinical presentation. Contact lens wear was the only risk factor identified, perhaps resulting in deviation of the immune response at the ocular surface, with consequent extensive dendritic ulceration. Copyright © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  14. Acanthamoeba keratitis in a non-contact lens wearer with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, Birgitte Rønde; Kronborg, Gitte

    2003-01-01

    Acanthamoeba keratitis is potentially blinding and often associated with contact lens wearing. A human immunodeficiency virus (HIV)-positive patient, a non-contact lens wearer, presented with keratitis. She experienced a protracted course of disease, characterized by exacerbations and remissions......, and was treated with various topical antibiotics and steroids. 13 months after symptom onset the eye was removed owing to serious scarring of cornea and unbearable pain. Microbiological and histopathological examination of the cornea showed Acanthamoeba. In non-contact lens wearers suffering from Acanthamoeba...

  15. Topical ganciclovir in the treatment of acute herpetic keratitis.

    Science.gov (United States)

    Tabbara, Khalid F; Al Balushi, Noorjehan

    2010-08-19

    Herpetic keratitis is caused by herpes simplex virus (HSV) and is a common cause of corneal blindness. Following a primary ocular herpetic infection, latency of the virus occurs, followed by subsequent recurrences of herpetic keratitis. Such recurrences may lead to structural damage of the cornea. Recurrent herpetic keratitis is a common indication for corneal transplantation. Recurrences of herpetic keratitis in the corneal graft may lead to corneal graft rejection. Several antiviral agents for HSV are available, including the thymidine analogs. Prolonged use of thymidine analogs may lead to toxicity of the ocular surface, including epithelial keratitis, corneal ulcers, follicular conjunctivitis, and punctal occlusions. Availability of topical antiviral agents that are safe and effective in the treatment and prophylaxis of herpetic keratitis is highly desirable. Ganciclovir is a potent inhibitor of members of the herpes virus family. The drug has been used systemically for the treatment of cytomegalovirus (CMV) retinitis. Its hematologic toxicity secondary to systemic administration led to its limited use in herpetic infections. On the other hand, topical ganciclovir has been shown to be as safe and effective as acyclovir in the treatment of herpetic epithelial keratitis. Furthermore, topical ganciclovir can reach therapeutic levels in the cornea and aqueous humor following topical application. Several clinical trials have shown that topical ganciclovir 0.15% ophthalmic gel is safe and effective in the treatment and prophylaxis of herpetic epithelial disease. Long-term use of ganciclovir ophthalmic gel in patients with penetrating keratoplasty following herpetic keratitis has prevented recurrences of the disease. Topical ganciclovir ophthalmic gel is well tolerated, does not cause toxic effects on the ocular surface, and does not cause hematologic abnormalities. Clinical studies have underscored the potential role of ganciclovir ophthalmic gel in the treatment and

  16. Varicella-Zoster Virus Keratitis with Asymptomatic Conjunctival Viral Shedding in the Contralateral Eye

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    Akio Miyakoshi

    2012-10-01

    Full Text Available Purpose: To report a case of varicella-zoster virus (VZV keratitis with detection of VZV DNA in the tear fluid of not only the symptomatic eye but also the contralateral asymptomatic eye by polymerase chain reaction (PCR. Methods: This is a case report. A 63-year-old otherwise healthy woman presented with circular corneal ulcer and stromal opacity with infiltration accompanied by mild conjunctival and ciliary injections in the left eye. Bacterial cultures of the corneal scrapings and virus PCR analyses of tear fluid from both eyes were performed. Results: No pathogen was found by bacterial cultures. PCR was negative for Acanthamoeba, herpes simplex virus and cytomegalovirus, but positive for VZV. VZV DNA was also detected in the unaffected eye. Based on the diagnosis of VZV keratitis, oral valacyclovir and acyclovir eye ointment were administered to the corneal infected eye. The infected eye was healed and VZV DNA turned negative in the tear fluid of the treated eye after 6 months of treatment; however, VZV DNA was still positive in the tear fluid of the contralateral eye. Conclusions: To our knowledge, this is the first case report of the detection of VZV DNA in the tear fluid of both affected and unaffected eyes in a patient with VZV keratitis. Asymptomatic conjunctival shedding of VZV may continue in the healthy unaffected eye in VZV keratitis patients.

  17. Incidence of Herpes Simplex Virus Keratitis in HIV/AIDS patients compared with the general population.

    Science.gov (United States)

    Burcea, M; Gheorghe, A; Pop, M

    2015-01-01

    Acquired immune deficiency syndrome (AIDS) is associated with a wide spectrum of systemic and ocular infectious diseases. Little information is known about Herpes Simplex Virus type 1 (HSV-1) keratoconjunctivitis in association with AIDS. Because HSV-1 is becoming, day by day, a common eye disease (nearly 100% patients of over 60 years old harbor HSV in their trigeminal ganglia at autopsy), this article discussing a worldwide public health problem. The purpose of this paper is to compare the incidence and clinical aspects of HSV-1 Keratitis in HIV/ AIDS patients compared with the general population who develops HSV- 1 Keratitis. The study is retrospective and comparative. Each patient was examined thoroughly at the biomicroscope ocular slit after corneal staining with fluorescein or rose bengal. Visual acuity, intraocular pressure and corneal sensitivity were also examined. From 170 patients with HIV and ocular anterior segment disorders, 47 patients had viral etiology. 58 patients had keratitis; 14 of them were HSV-1 keratitis. Doctors should be aware of the existence of the ocular damage in HIV/ AIDS and emphasize the importance of regular ophthalmologic examination of patients with HIV/ AIDS as HSV infection is common nowadays among the general population.

  18. [Keratitis - Infectious or Autoimmune?].

    Science.gov (United States)

    Messmer, E M

    2016-07-01

    Histopathological evaluation of ocular tissues is important in differentiating between infectious and autoimmune disease. Inflammation, necrosis and keratolysis are common to most forms of keratitis. Histopathology can be of great help in identifying the causative organism, establishing a final diagnosis and/or managing the patient with herpes simplex virus keratitis, mycotic keratitis, acanthamoeba keratitis or microsporidia keratoconjunctivitis. Important pathogenetic knowledge with therapeutic relevance has been gained from histopathological studies in nummular keratitis after epidemic keratoconjunctivitis and atopic keratoconjunctivitis. Georg Thieme Verlag KG Stuttgart · New York.

  19. Recurrence rates of herpes simplex virus keratitis in contact lens and non-contact lens wearers.

    Science.gov (United States)

    Mucci, Joti Juneja; Utz, Virginia M; Galor, Anat; Feuer, William; Jeng, Bennie H

    2009-07-01

    To evaluate the recurrence rates of herpes simplex virus (HSV) keratitis in contact lens wearers compared with non-contact lens wearers. Retrospective cohort study. Charts of patients diagnosed with HSV keratitis seen at the Cleveland Clinic between January 2001 and December 2004 were reviewed. One hundred seventeen patients were included in this study: 21 contact lens wearers and 96 non-contact lens wearers. Contact lens wearers were found to have a higher median recurrence rate (0.4 episodes/year) compared with non-contact lens wearers (0.2 episodes/year) (P=0.02). A multivariate regression evaluating factors predictive of the number of recurrences found that contact lens use remained a significant predictive variable (P=0.02) when accounting for patient demographic and disease factors and variable follow-up time. Patients with a history of HSV keratitis should be counseled about the potential increased risk of recurrence that may be associated with contact lens wear.

  20. Fungal Keratitis

    Science.gov (United States)

    ... Español Eye Health / Eye Health A-Z Fungal Keratitis Sections What is Fungal Keratitis? Fungal Keratitis Causes ... Keratitis Symptoms Fungal Keratitis Treatment What is Fungal Keratitis? Leer en Español: ¿Qué Es la Queratitis Fúngica? ...

  1. Herpes Keratitis

    Science.gov (United States)

    ... Stories Español Eye Health / Eye Health A-Z Herpes Keratitis Sections What is Herpes Keratitis? Herpes Keratitis ... Herpes Keratitis Symptoms Herpes Keratitis Treatment What is Herpes Keratitis? Leer en Español: ¿Qué es la queratitis ...

  2. Topical ganciclovir in the treatment of acute herpetic keratitis

    Directory of Open Access Journals (Sweden)

    Khalid F Tabbara

    2010-08-01

    Full Text Available Khalid F Tabbara1,2,3, Noorjehan Al Balushi11The Eye Center and The Eye Foundation for Research in Ophthalmology, Riyadh, 2Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; 3The Wilmer Ophthalmological Institute of The Johns Hopkins University School of Medicine, Baltimore, Maryland, USAAbstract: Herpetic keratitis is caused by herpes simplex virus (HSV and is a common cause of corneal blindness. Following a primary ocular herpetic infection, latency of the virus occurs, followed by subsequent recurrences of herpetic keratitis. Such recurrences may lead to structural damage of the cornea. Recurrent herpetic keratitis is a common indication for corneal transplantation. Recurrences of herpetic keratitis in the corneal graft may lead to corneal graft rejection. Several antiviral agents for HSV are available, including the thymidine analogs. Prolonged use of thymidine analogs may lead to toxicity of the ocular surface, including epithelial keratitis, corneal ulcers, follicular conjunctivitis, and punctal occlusions. Availability of topical antiviral agents that are safe and effective in the treatment and prophylaxis of herpetic keratitis is highly desirable. Ganciclovir is a potent inhibitor of members of the herpes virus family. The drug has been used systemically for the treatment of cytomegalovirus (CMV retinitis. Its hematologic toxicity secondary to systemic administration led to its limited use in herpetic infections. On the other hand, topical ganciclovir has been shown to be as safe and effective as acyclovir in the treatment of herpetic epithelial keratitis. Furthermore, topical ganciclovir can reach therapeutic levels in the cornea and aqueous humor following topical application. Several clinical trials have shown that topical ganciclovir 0.15% ophthalmic gel is safe and effective in the treatment and prophylaxis of herpetic epithelial disease. Long-term use of ganciclovir ophthalmic

  3. Clinical efficacy of oral and topical acyclovir in herpes simplex virus stromal necrotizing keratitis

    Directory of Open Access Journals (Sweden)

    Surabhi Dutt

    2016-01-01

    Full Text Available Purpose: To evaluate the efficacy of systemic and topical antiviral therapy in the treatment of active herpes simplex virus (HSV necrotizing stromal keratitis (NSK. Design: Prospective interventional case series. Methodology: Patients with a diagnosis of HSV NSK based on history and clinical findings were enrolled in the study. A standard protocol was used for microbiologic investigations. Ten weeks regime of systemic acyclovir and 2 weeks of topical acyclovir was given. Complete ophthalmic examination was performed at every visit. Outcome measures were a reduction in the area of infiltration and improvement in visual acuity. Results: Fifteen patients were enrolled in the study. The mean age of presentation was 51.53 years. The duration of symptoms at presentation ranged from 2 to 8 weeks. HSV1 DNA polymerase chain reaction was positive in 70% cases of those tested. Area of infiltration at trial entry and at the end of 2 weeks of antiviral treatment reduced significantly (P = 0.007. All patients showed a complete resolution of keratitis at the end of study. Conclusion: Topical and systemic acyclovir for treatment of NSK facilitates healing of ulceration. Topical steroids after initial antiviral therapy are safe and decreases inflammation and improve visual recovery. Early initiation of therapy has better outcomes as compared to late presentations.

  4. Bacterial Keratitis

    Science.gov (United States)

    ... Español Eye Health / Eye Health A-Z Bacterial Keratitis Sections What Is Bacterial Keratitis? Bacterial Keratitis Symptoms ... Lens Care Bacterial Keratitis Treatment What Is Bacterial Keratitis? Leer en Español: ¿Qué Es la Queratitis Bacteriana? ...

  5. Conjunctival Flap Covering Combined with Antiviral and Steroid Therapy for Severe Herpes Simplex Virus Necrotizing Stromal Keratitis

    Directory of Open Access Journals (Sweden)

    Hua Gao

    2015-01-01

    Full Text Available Herpes simplex virus (HSV necrotizing stromal keratitis is a common type of herpetic stromal keratitis (HSK. Antiviral medication alone cannot control the disease, and corticosteroid eye drops may aggravate the ulcer and result in corneal perforation. Amniotic membrane transplantation effectively treats superficial corneal ulcer resulting from necrotizing stromal HSK. However, the efficacy of this approach seems to be limited for more serious cases. This study presented the clinical treatment of severe HSV necrotizing stromal keratitis (ulcer depth greater than half of the corneal stroma by conjunctival flap covering surgery in 25 patients (25 eyes combined with antivirus and corticosteroid treatment at Shandong Eye Hospital from January 2007 to December 2013. Clinical results showed that the mean best spectacle-corrected visual acuity improved from preoperative 20/333 to postoperative 20/40 (P<0.05. All patients recovered ocular surface stabilization. There was recurrence in two eyes, which was cured with antiviral medication. Conjunctival flap covering combined with antivirus and corticosteroid treatment is effective in treating severe HSV necrotizing stromal keratitis.

  6. Acanthamoeba keratitis and contact lens wear.

    Science.gov (United States)

    Lindsay, Richard G; Watters, Grant; Johnson, Richard; Ormonde, Susan E; Snibson, Grant R

    2007-09-01

    Acanthamoeba keratitis is a rare but serious complication of contact lens wear that may cause severe visual loss. The clinical picture is usually characterised by severe pain, sometimes disproportionate to the signs, with an early superficial keratitis that is often misdiagnosed as herpes simplex virus (HSV) keratitis. Advanced stages of the infection are usually characterised by central corneal epithelial loss and marked stromal opacification with subsequent loss of vision. In this paper, six cases of contact lens-related Acanthamoeba keratitis that occurred in Australia and New Zealand over a three-year period are described. Three of the patients were disposable soft lens wearers, two were hybrid lens wearers and one was a rigid gas permeable lens wearer. For all six cases, the risk factors for Acanthamoeba keratitis were contact lens wear with inappropriate or ineffective lens maintenance and exposure of the contact lenses to tap or other sources of water. All six patients responded well to medical therapy that involved topical use of appropriate therapeutic agents, most commonly polyhexamethylene biguanide and propamidine isethionate, although two of the patients also subsequently underwent deep lamellar keratoplasty due to residual corneal surface irregularity and stromal scarring. Despite the significant advances that have been made in the medical therapy of Acanthamoeba keratitis over the past 10 years, prevention remains the best treatment and patients who wear contact lenses must be thoroughly educated about the proper use and care of the lenses. In particular, exposure of the contact lenses to tap water or other sources of water should be avoided.

  7. Bilateral disciform keratitis in Reiter's syndrome.

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    Suresh, Palanisamy S

    2016-09-01

    Reiter's syndrome is commonly associated with conjunctivitis and rarely with uveitis. Bilateral disciform keratitis at presentation is a very rare manifestation in Reiter's syndrome. A 13-year-old boy developed bilateral disciform keratitis with oligoarthritis following an episode of conjunctivitis. In addition he had suspected bacterial keratitis with hypopyon in the left eye as a possible secondary infection of an epithelial defect that is a feature of Reiter's keratitis. Empirical treatment with intensive topical antibiotics as a therapeutic trial completely resolved the hypopyon and the disciform keratitis settled with topical steroid treatment. The patient achieved a best corrected vision of 20/20 in both the eyes 6 weeks after the treatment. Bilateral disciform keratitis can occur as a complication of Reiter's syndrome. Also the possibility of secondary infection of the epithelial defect needs to be borne in mind.

  8. Pathogenesis of microbial keratitis.

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    Lakhundi, Sahreena; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2017-03-01

    Microbial keratitis is a sight-threatening ocular infection caused by bacteria, fungi, and protist pathogens. Epithelial defects and injuries are key predisposing factors making the eye susceptible to corneal pathogens. Among bacterial pathogens, the most common agents responsible for keratitis include Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia and Serratia species. Fungal agents of corneal infections include both filamentous as well as yeast, including Fusarium, Aspergillus, Phaeohyphomycetes, Curvularia, Paecilomyces, Scedosporium and Candida species, while in protists, Acanthamoeba spp. are responsible for causing ocular disease. Clinical features include redness, pain, tearing, blur vision and inflammation but symptoms vary depending on the causative agent. The underlying molecular mechanisms associated with microbial pathogenesis include virulence factors as well as the host factors that aid in the progression of keratitis, resulting in damage to the ocular tissue. The treatment therefore should focus not only on the elimination of the culprit but also on the neutralization of virulence factors to minimize the damage, in addition to repairing the damaged tissue. A complete understanding of the pathogenesis of microbial keratitis will lead to the rational development of therapeutic interventions. This is a timely review of our current understanding of the advances made in this field in a comprehensible manner. Coupled with the recently available genome sequence information and high throughput genomics technology, and the availability of innovative approaches, this will stimulate interest in this field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Fungal keratitis

    National Research Council Canada - National Science Library

    Tuli, Sonal S

    2011-01-01

    What is the most appropriate management of fungal keratitis? Traditionally, topical Natamycin is the most commonly used medication for filamentous fungi while Amphotericin B is most commonly used for yeast...

  10. Ganciclovir ophthalmic gel in herpes simplex virus rabbit keratitis: intraocular penetration and efficacy.

    Science.gov (United States)

    Castela, N; Vermerie, N; Chast, F; Sauvageon-Martre, H; Denis, J; Godard, V; Goldschmidt, P; Pouliquen, Y

    1994-01-01

    A chronic administration of three ganciclovir gels (0.2%, 0.05%, 0.0125%) was compared with a placebo gel and a 3% acyclovir ophthalmic ointment in the treatment of HSV-1 rabbit keratitis. All the ganciclovir gels showed a clinical efficacy: a significant reduction of the corneal ulcer area, clouding and vascularization (p efficacy was slower than using acyclovir ointment. No significant difference could be shown between the 0.2% and 0.05% ganciclovir gels or the 0.05% ganciclovir gel and the acyclovir treatment on viral isolation, when it was performed on pooled samples. The distribution of ganciclovir and acyclovir into the rabbit eyes (HPLC methods), were similar but markedly higher in solid tissues than ocular fluids. It might explain the recovery from tissue damages. The mean corneal ganciclovir concentrations were largely higher than ED 50 of ganciclovir for HSV-1. No toxicity was expected, due to very limited systemic availability. This study suggests a comparable activity on HSV-1 superficial keratitis between 0.05%, 0.2% ganciclovir gels and 3% acyclovir ointment. Higher concentration of ganciclovir gels are probably necessary in order to treat the HSV-1 kerato-uveitis.

  11. Detection of herpes simplex-1 and -2 and varicella zoster virus by quantitative real-time polymerase chain reaction in corneas from patients with bacterial keratitis.

    Science.gov (United States)

    Nascimento, Heloisa; Watanabe, Aripuanã; Vieira, Ana Carolina Cabreira; Pelegrini, Andrea; Yu, Maria Cecília; Bispo, Paulo José Martins; Granato, Celso Francisco Hernandes; Höfling-Lima, Ana Luisa

    2017-01-01

    Bacterial keratitis occurs worldwide, and despite recent developments, it remains a potentially blinding condition. This study assesses the presence of herpes simplex virus (HSV-1 and -2) and varicella zoster virus (VZV) by quantitative real-time polymerase chain reaction (qPCR) in corneal scrapings from patients with bacterial keratitis. A total of 65 patients with clinical diagnoses of infectious corneal ulcers prospectively underwent clinical eye examinations. Corneal scrapings were investigated by Gram staining, Giemsa staining, culture, and qPCR (the study group). Risk factors and epidemiological data were recorded. The control group comprising 25 eyes with typical herpes dendritic keratitis was also analyzed by qPCR. From the study group (n=65), nine patients (13.8%) had negative smears, cultures, and qPCR findings. Fifty-six (86.2%) patients had positive cultures: 51 for bacteria, 4 for fungi, and 1 for amoebae. Of the patients who had positive bacterial cultures, qPCR identified 10 patients who were also positive for virus: one for VZV and nine for HSV-1. Of the 25 patients in the control group, 21 tested positive for HSV-1 by qPCR analysis. Herpes may be present in patients with bacterial corneal ulcers, and qPCR may be useful in its detection.

  12. Human papilloma virus--its association with epithelial proliferative lesions.

    Science.gov (United States)

    Costa, L J; Silveira, F R; Batista, J M; Birman, E G

    1994-01-01

    The Papillomaviruses are DNA viruses which belong to the Papova family, having a great affinity for epithelial tissue. They can produce proliferative lesions either in the skin or mucosa, in man and other animals. Various kinds of lesions, mainly benign, are caused by numerous types of HPV involving the well-known verruca vulgaris, oral papilloma, condiloma acuminatum and the focal epithelial hyperplasia, as well as a possible association with other alterations and lesions.

  13. Distinguishing infective versus noninfective keratitis

    Directory of Open Access Journals (Sweden)

    Srinivasan M

    2008-01-01

    Full Text Available For the purpose of this symposium, the term "keratitis" implies suppurative nonviral and viral keratitis. Corneal ulcers have been described in ancient literature. But even today, despite the availability of a wide range of newer antimicrobials and new diagnostic techniques, infective keratitis continues to pose a diagnostic and therapeutic challenge. This article focuses on the key diagnostic clinical features of the most common organisms causing infective keratitis - bacteria, fungi, viruses, nocardia and acanthamoeba - in India. While the clinical features in some cases are fairly straightforward, most cases challenge the clinician. We describe the salient clinical features which can help arrive at a diagnosis to begin appropriate treatment immediately, prior to the laboratory report.

  14. Fungal keratitis

    Directory of Open Access Journals (Sweden)

    Sonal S Tuli

    2011-02-01

    Full Text Available Sonal S TuliUniversity of Florida, Gainesville, FL, USA  Clinical question: What is the most appropriate management of fungal keratitis?Results: Traditionally, topical Natamycin is the most commonly used medication for filamentous fungi while Amphotericin B is most commonly used for yeast. Voriconazole is rapidly becoming the drug of choice for all fungal keratitis because of its wide spectrum of coverage and increased penetration into the cornea.Implementation: Repeated debridement of the ulcer is recommended for the penetration of topical medications. While small, peripheral ulcers may be treated in the community, larger or central ulcers, especially if associated with signs suggestive of anterior chamber penetration should be referred to a tertiary center. Prolonged therapy for approximately four weeks is usually necessary.Keywords: fungal keratitis, keratomycosis, antifungal medications, debridement

  15. Acanthamoeba Keratitis FAQs

    Science.gov (United States)

    ... Submit What's this? Submit Button Parasites Home Acanthamoeba Keratitis FAQs Recommend on Facebook Tweet Share Compartir Frequently Asked Questions What is Acanthamoeba keratitis? Acanthamoeba keratitis is a rare but serious infection ...

  16. Ganciclovir ophthalmic gel 0.15% for the treatment of acute herpetic keratitis: background, effectiveness, tolerability, safety, and future applications

    Science.gov (United States)

    Chou, Timothy Y; Hong, Bennett Y

    2014-01-01

    Eye disease due to herpes simplex virus (HSV) is a leading cause of ocular morbidity and the number one infectious cause of unilateral corneal blindness in the developed parts of the globe. Recurrent keratitis can result in progressive corneal scarring, thinning, and vascularization. Antiviral agents employed against HSV have primarily been nucleoside analogs. Early generation drugs included idoxuridine, iododesoxycytidine, vidarabine, and trifluridine. While effective, they tended to have low bioavailability and measurable local cellular toxicity due to their nonselective mode of action. Acyclovir 0.3% ointment is a more selective agent, and had become a first-line topical drug for acute HSV keratitis in Europe and other places outside of the US. Ganciclovir 0.15% gel is the most recently approved topical treatment for herpes keratitis. Compared to acyclovir 0.3% ointment, ganciclovir 0.15% gel has been shown to be better tolerated and no less effective in several Phase II and III trials. Additionally, topical ganciclovir does not cause adverse systemic side effects and is therapeutic at lower concentrations. Based on safety, efficacy, and tolerability, ganciclovir 0.15% gel should now be considered a front-line topical drug in the treatment of dendritic herpes simplex epithelial keratitis. Topics of future investigation regarding other potential uses for ganciclovir gel may include the prophylaxis of recurrent HSV epithelial keratitis, treatment of other forms of ocular disease caused by herpesviruses and adenovirus, and ganciclovir gel as an adjunct to antitumor therapy. PMID:25187721

  17. Prevention of herpes simplex virus induced stromal keratitis by a glycoprotein B-specific monoclonal antibody.

    Directory of Open Access Journals (Sweden)

    Adalbert Krawczyk

    Full Text Available The increasing incidence of acyclovir (ACV and multidrug-resistant strains in patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis (HSK is a major health problem in industrialized countries and often results in blindness. To overcome this obstacle, we have previously developed an HSV-gB-specific monoclonal antibody (mAb 2c that proved to be highly protective in immunodeficient NOD/SCID-mice towards genital infections. In the present study, we examined the effectivity of mAb 2c in preventing the immunopathological disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis or 24, 40, and 56 hours after infection (post-exposure immunotherapy. Topical treatment was performed by periodical inoculations (5 times per day of antibody-containing eye drops as control, starting at 24 h post infection. Systemic antibody treatment markedly reduced viral loads at the site of infection and completely protected mice from developing HSK. The administration of the antiviral antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart (mAb hu2c was equally effective in protecting mice from HSV-induced HSK when compared to the parental mouse antibody. These results warrant the future development of this antibody as a novel approach for the treatment of corneal HSV-infections in humans.

  18. The role of Epstein–Barr virus in epithelial malignancies

    Science.gov (United States)

    Tsao, Sai-Wah; Tsang, Chi Man; To, Ka-Fai; Lo, Kwok-Wai

    2015-01-01

    The close association of Epstein–Barr virus (EBV) infection with non-keratinizing nasopharyngeal carcinomas and a subset of gastric carcinomas suggests that EBV infection is a crucial event in these cancers. The difficulties encountered in infecting and transforming primary epithelial cells in experimental systems suggest that the role of EBV in epithelial malignancies is complex and multifactorial in nature. Genetic alterations in the premalignant epithelium may support the establishment of latent EBV infection, which is believed to be an initiation event. Oncogenic properties have been reported in multiple EBV latent genes. The BamH1 A rightwards transcripts (BARTs) and the BART-encoded microRNAs (miR-BARTs) are highly expressed in EBV-associated epithelial malignancies and may induce malignant transformation. However, enhanced proliferation may not be the crucial function of EBV infection in epithelial malignancies, at least in the early stages of cancer development. EBV-encoded gene products may confer anti-apoptotic properties and promote the survival of infected premalignant epithelial cells harbouring genetic alterations. Multiple EBV-encoded microRNAs have been reported to have immune evasion functions. Genetic alterations in host cells, as well as inflammatory stroma, could modulate the expression of EBV genes and alter the growth properties of infected premalignant epithelial cells, encouraging their selection during carcinogenesis. PMID:25251730

  19. Alternaria Keratitis after Deep Anterior Lamellar Keratoplasty

    OpenAIRE

    Mekhla Naik; Mohd. Shahbaaz,; Jay Sheth; Sunderamoorthy, S. K.

    2014-01-01

    To describe a case of Alternaria keratitis in a 30-year-old male patient who presented with bilateral vascularised central corneal opacity and underwent deep anterior lamellar keratoplasty (DALK) in the left eye. Patient was treated for recurrent epithelial defect with a bandage contact lens in the follow-up visits after DALK. Subsequently, patient presented with pigmented fungal keratitis, which on culture examination of the corneal scrapping demonstrated Alternaria species. Patient had to u...

  20. Incidence of Herpes Simplex Virus Keratitis in HIV/AIDS patients compared with the general population

    OpenAIRE

    Burcea, M; Gheorghe, A.; Pop, M

    2015-01-01

    Acquired immune deficiency syndrome (AIDS) is associated with a wide spectrum of systemic and ocular infectious diseases. Little information is known about Herpes Simplex Virus type 1 (HSV-1) keratoconjunctivitis in association with AIDS. Because HSV-1 is becoming, day by day, a common eye disease (nearly 100% patients of over 60 years old harbor HSV in their trigeminal ganglia at autopsy), this article discussing a worldwide public health problem. Aim. The purpose of this paper is to compare...

  1. Alternaria keratitis after deep anterior lamellar keratoplasty.

    Science.gov (United States)

    Naik, Mekhla; Mohd Shahbaaz; Sheth, Jay; Sunderamoorthy, S K

    2014-01-01

    To describe a case of Alternaria keratitis in a 30-year-old male patient who presented with bilateral vascularised central corneal opacity and underwent deep anterior lamellar keratoplasty (DALK) in the left eye. Patient was treated for recurrent epithelial defect with a bandage contact lens in the follow-up visits after DALK. Subsequently, patient presented with pigmented fungal keratitis, which on culture examination of the corneal scrapping demonstrated Alternaria species. Patient had to undergo a repeat DALK as the keratitis did not resolve with medical therapy alone. Patient did not have a recurrence for 11 months following the regraft. This case report highlights the importance of considering the Alternaria species as a possibile cause of non-resolving fungal keratitis after DALK.

  2. A prospective study of the clinical characteristics of patients with herpes simplex and varicella zoster keratitis, presenting to a New Zealand emergency eye clinic.

    Science.gov (United States)

    McDonald, Elissa M; Patel, Dipika V; McGhee, Charles N J

    2015-03-01

    To identify the demographic and clinical associations of patients presenting with herpetic keratitis in New Zealand compared with presentations of presumed microbial keratitis. A prospective, 6-month, observational case series of presumed microbial keratitis (including marginal keratitis), specifically identifying all cases of herpes simplex and varicella zoster keratitis attending an emergency eye clinic was conducted. Main outcome measures included demographics, presenting signs and symptoms, and medical, ocular, and drug history. A total of 140 cases of herpetic keratitis were identified, which comprised 125 cases of herpes simplex virus (89%) and 15 cases of varicella zoster virus (11%). Herpes simplex keratitis was associated with a history of keratitis (n = 58, phi = 0.24, P herpes simplex keratitis and ocular surface disease (n = 8, phi = -0.16, P herpes simplex as a possible cause of keratitis. Clinicians prescribing inhaled corticosteroids or topical corticosteroid creams should be aware of possible association with herpes simplex keratitis.

  3. Immunoregulation by airway epithelial cells (AECs against respiratory virus infection

    Directory of Open Access Journals (Sweden)

    Yan YAN

    2017-11-01

    Full Text Available The respiratory tract is primary contact site of the body and environment, and it is ventilated by 10-20 thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbes, which contain the disease-causing pathogens. Airway epithelial cells (AECs are known to have innate sensor functions, which are similar to the "professional" immune cells, such as alveolar macrophage and sub- or intra-epithelial dendritic cells (DCs. Thus AECs are able to detect invading microbial danger including different types of respiratory viruses, and mount a potent host response, for example, activating type Ⅰ interferon signaling pathway genes. To avoid chronic inflammation and maintain the immunological homeostasis, the pulmonary system has developed intrinsic mechanisms to control local immune responses. Most recently, the role of AECs in control of local immunity has gained much attention, as 1 AECs express the pattern recognition receptors (PRRs, such as Toll-like receptors, retinoic acid inducible gene Ⅰ (RIG-I-like receptor, and so on, thus AECs are equipped to participate in innate detection of microbial encounter; 2 To keep immunological homeostasis in the respiratory tract, AECs behave not only as innate immune sensors but also as immune modulators in parallel, through modulating the sensitivity of innate immune sensing of both AECs per se and sub- or intra-epithelial immune cells; 3 Loss of modularity capacity of AECs might be involved in the development of chronic airway diseases. In present review, how the AECs act will be intensively discussed in response to respiratory viruses and modulate the local immunity through cis- and trans-factors (direct and indirect factors, as well as the consequence of impairment of this control of local immunity, in the development and exacerbation of airway diseases, such as acute and chronic rhinosinusitis. DOI: 10.11855/j.issn.0577-7402.2017.10.02

  4. Epstein–Barr virus (EBV-associated epithelial and non-epithelial lesions of the oral cavity

    Directory of Open Access Journals (Sweden)

    Kentaro Kikuchi

    2017-08-01

    Full Text Available Epstein–Barr virus (EBV is known to be associated with the development of malignant lymphoma and lymphoproliferative disorders (LPDs in immunocompromised patients. EBV, a B-lymphotropic gamma-herpesvirus, causes infectious mononucleosis and oral hairy leukoplakia, as well as various pathological types of lymphoid malignancy. Furthermore, EBV is associated with epithelial malignancies such as nasopharyngeal carcinoma (NPC, salivary gland tumor, gastric carcinoma and breast carcinoma. In terms of oral disease, there have been several reports of EBV-related oral squamous cell carcinoma (OSCC worldwide. However, the role of EBV in tumorigenesis of human oral epithelial or lymphoid tissue is unclear. This review summarizes EBV-related epithelial and non-epithelial tumors or tumor-like lesions of the oral cavity. In addition, we describe EBV latent genes and their expression in normal epithelium, inflamed gingiva, epithelial dysplasia and SCC, as well as considering LPDs (MTX- and age-related and DLBCLs of the oral cavity.

  5. Ganciclovir ophthalmic gel 0.15%: in acute herpetic keratitis (dendritic ulcers).

    Science.gov (United States)

    Croxtall, Jamie D

    2011-03-26

    Dendritic epithelial keratitis is most commonly caused by infections of herpes simplex virus (HSV) type 1 (HSV-1), and less frequently by HSV type 2 (HSV-2). Ganciclovir, a guanosine nucleoside analogue, is a well established broad-spectrum antiviral agent that inhibits replication of viral DNA and is active against both HSV-1 and -2 and several other viruses. Ganciclovir ophthalmic gel 0.15% is a five-times-daily topical preparation that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers). A randomized, open-label, phase III trial in immunocompetent patients with acute herpetic keratitis showed that ganciclovir ophthalmic gel 0.15% applied five times daily provided effective clinical resolution of dendritic ulcers following 7 days of treatment (primary endpoint). Moreover, a retrospective analysis of noninferiority showed that ganciclovir ophthalmic gel 0.15% was no less effective than aciclovir (acyclovir) ointment 3%. A pooled analysis of three randomized, single-masked, phase II multinational trials also showed high rates of dendritic ulcer healing at day 7 for eyes treated with ganciclovir ophthalmic gel 0.15% and aciclovir ointment 3%. Furthermore, in the individual phase II trials, most patients showed evidence of healed dendritic and geographic ulcers at day 14 in either treatment arm. Median healing times with either treatment ranged from 6 to 10 days. Ganciclovir ophthalmic gel 0.15% was generally well tolerated and was associated with a significantly lower incidence of visual disturbances than aciclovir ointment 3% in the phase III trial.

  6. Acute Herpetic Keratitis: What is the Role for Ganciclovir Ophthalmic Gel?

    Directory of Open Access Journals (Sweden)

    Afsun Sahin

    2012-01-01

    Full Text Available Herpes simplex keratitis (HSK is a major cause of corneal blindness in the world. Following the primary infection, the virus enters into a latent phase. Recurrent infectious or immune keratitis cause structural damage to the cornea, scarring, and may lead to blindness. Several commercially available topical and oral antiviral drugs for HSK are currently available. However, toxicity and low patient compliance hamper their use in HSK. Further, oral antiviral drugs alone are not always effective in HSK. Thus, there had been a need for safe and effective topical antiviral agents against HSK. Systemic ganciclovir has been in use for the treatment of cytomegalovirus infections. Recently, topical ganciclovir has become available for use in patients with HSK. Ganciclovir 0.15% ophthalmic gel has been shown to be both safe and effective against viruses of the herpes family. Topical ganciclovir ophthalmic gel is well tolerated and does not cause significant toxic effects on the ocular surface. Several multicenter studies have revealed the potential role of ganciclovir ophthalmic gel in the treatment and prophylaxis of epithelial HSK. In this paper, we have reviewed the pharmacology, efficacy, side effects, and the role of ganciclovir ophthalmic gel 0.15% in the treatment of acute herpetic keratitis.

  7. A Case of Peripheral Ulcerative Keratitis Associated with Autoimmune Hepatitis

    Directory of Open Access Journals (Sweden)

    Hamoon Eshraghi

    2017-01-01

    Full Text Available Purpose. To describe a case of peripheral ulcerative keratitis in the setting of autoimmune hepatitis and possible overlap syndrome with primary sclerosing cholangitis. Case Report. A 48-year-old African American female with autoimmune hepatitis with possible overlap syndrome with primary sclerosing cholangitis presented with tearing, irritation, and injection of the left eye that was determined to be peripheral ulcerative keratitis. The patient was treated with topical and systemic steroids, immunosuppressant drugs (azathioprine and mycophenolate mofetil, a biologic (rituximab, and surgery (conjunctival resection, and the peripheral ulcerative keratitis epithelialized but ultimately led to corneal perforation. Conclusion. In this unique case, a patient with peripheral ulcerative keratitis who underwent treatment ultimately had a corneal perforation. This case may suggest a possible relationship between autoimmune hepatitis and peripheral ulcerative keratitis.

  8. Achromobacter xylosoxidans keratitis after contact lens usage.

    Science.gov (United States)

    Park, Jung Hyun; Song, Nang Hee; Koh, Jae Woong

    2012-02-01

    To report on Achromobacter xylosoxidans keratitis in two healthy patients who had worn contact lenses foran extended period of time. A 36-year-old female and a 21-year-old female visited our hospital with ocular pain and blurred vision. Both patients had a history of wearing soft contact lenses for over fve years with occasional overnight wear. At the initial presentation, a slit lamp examination revealed corneal stromal infiltrations and epithelial defects with peripheral neovascularization in both patients. Microbiological examinations were performed from samples of corneal scrapings, contact lenses, contact lens cases, and solution. The culture resulting from the samples taken from the contact lenses, contact lens cases, and solution were all positive for Achromobacter xylosoxidans. Confrming that the direct cause of the keratitis was the contact lenses, the frst patient was prescribed ceftazidime and amikacin drops sensitive to Achromobacter xylosoxidans. The second patient was treated with 0.3% gatifoxacin and fortifed tobramycin drops. After treatment, the corneal epithelial defects were completely healed, and subepithelial corneal opacity was observed. Two cases of Achromobacter xylosoxidans keratitis were reported in healthy young females who wore soft contact lenses. Achromobacter xylosoxidans should be considered a rare but potentially harmful pathogen for lens-induced keratitis in healthy hosts.

  9. Resting B cells as a transfer vehicle for Epstein-Barr virus infection of epithelial cells.

    Science.gov (United States)

    Shannon-Lowe, C D; Neuhierl, B; Baldwin, G; Rickinson, A B; Delecluse, H-J

    2006-05-02

    Epstein-Barr virus (EBV), an orally transmitted herpesvirus, efficiently targets B lymphocytes through binding of the viral envelope glycoprotein gp350 to the complement receptor CD21. How the virus accesses epithelial cells is less well understood, because such cells are largely resistant to infection with cell-free virus in vitro. Here, we show that, after binding to primary B cells, most Epstein-Barr virions are not internalized but remain on the B cell surface and from there can transfer efficiently to CD21-negative epithelial cells, increasing epithelial infection by 10(3)- to 10(4)-fold compared with cell-free virus. Transfer infection is associated with the formation of B cell-epithelial conjugates with gp350/CD21 complexes focused at the intercellular synapse; transfer involves the gp85 and gp110 viral glycoproteins but is independent of gp42, the HLA class II ligand that is essential for B cell entry. Therefore, through efficient binding to the B cell surface, EBV has developed a means of simultaneously accessing both lymphoid and epithelial compartments; in particular, infection of pharyngeal epithelium by orally transmitted virus becomes independent of initial virus replication in the B cell system.

  10. Achromobacter xylosoxidans Keratitis after Contact Lens Usage

    OpenAIRE

    Park, Jung Hyun; Song, Nang Hee; Koh, Jae Woong

    2012-01-01

    To report on Achromobacter xylosoxidans keratitis in two healthy patients who had worn contact lenses foran extended period of time. A 36-year-old female and a 21-year-old female visited our hospital with ocular pain and blurred vision. Both patients had a history of wearing soft contact lenses for over fve years with occasional overnight wear. At the initial presentation, a slit lamp examination revealed corneal stromal infiltrations and epithelial defects with peripheral neovascularization ...

  11. Microbial keratitis after Boston type I keratoprosthesis implantation: incidence, organisms, risk factors, and outcomes.

    Science.gov (United States)

    Kim, Michelle J; Yu, Fei; Aldave, Anthony J

    2013-11-01

    To identify the incidence of and risk factors for microbial keratitis after implantation of the Boston type I keratoprosthesis (Massachusetts Eye and Ear Infirmary, Boston, MA). Retrospective, single-surgeon consecutive case series. A total of 105 patients (125 keratoprosthesis procedures in 110 eyes) who underwent Boston type I keratoprosthesis implantation at the Jules Stein Eye Institute between May 1, 2004, and April 1, 2012. Data regarding ocular history, relevant intraoperative data, postoperative management, and outcomes were collected for each procedure. Risk factor analyses were performed using the Fisher exact test, log-rank test, and hazard ratio (HR). Incidence of microbial keratitis, organisms responsible, risk factors, and outcomes. During the period under review, 20 presumed infectious infiltrates were diagnosed in 15 eyes (13.6%) of 15 patients (14.3%), for a rate of 0.073 infections per eye-year. The rate of culture-positive bacterial keratitis was 0.022 infections per eye-year, and the rate of culture-positive fungal keratitis was 0.015 infections per eye-year. Topical vancomycin use, topical steroid use, and contact lens wear did not increase the incidence of infectious keratitis, but prolonged vancomycin use was associated with an increased risk for fungal keratitis and infectious keratitis overall. Persistent corneal epithelial defect formation also was associated with an increased incidence of fungal keratitis and infectious keratitis overall. There were no cases of endophthalmitis resulting from infectious keratitis. Infectious keratitis develops in 13.6% of eyes after keratoprosthesis implantation, with a similar rate of culture-positive bacterial and fungal keratitis. The observed rate of microbial keratitis suggests the need for additional topical antimicrobial prophylaxis after keratoprosthesis implantation in eyes at higher risk, such as those with persistent corneal epithelial defect formation or prolonged vancomycin use. Copyright

  12. The prognostic significance of virus-associated changes in grade 1 cervical intra-epithelial neoplasia

    DEFF Research Database (Denmark)

    Bagi, P; Worning, A M; Nordsten, M

    1987-01-01

    Virus-associated changes of the cervix uteri were assessed in patients treated for grade 1 cervical intra-epithelial neoplasia (CIN). Of 106 patients evaluated, 67 (63%) had virus-associated changes. The patients were treated without regard to the presence/absence of virus-associated changes. In 26...... patients the treatment was unsuccessful (persistence, recurrence, or progression of the neoplasia). The frequency of treatment failure was 33% in patients with, and 10% in patients without virus-associated changes (p less than 0.025). It is recommended that patients with CIN 1 and virus-associated changes...

  13. Infectious keratitis after keratoplasty.

    Science.gov (United States)

    Davila, Jose R; Mian, Shahzad I

    2016-07-01

    Infectious keratitis is an uncommon but serious complication after corneal transplantation that threatens the visual potential of corneal grafts. Several large retrospective studies from sites worldwide have documented the experiences of corneal surgeons with this sight-threatening complication. The present review synthesizes and compares incidence rates, risk factors, common microorganisms, treatments, and visual prognoses of patients with postkeratoplasty infectious keratitis. In 2012, endothelial keratoplasty replaced penetrating keratoplasty as the most commonly performed corneal transplantation procedure in the United States. Although reported rates of infectious keratitis after endothelial keratoplasty appear to be less than after penetrating keratoplasty, there are still too few publications documenting infectious keratitis after endothelial keratoplasty or anterior lamellar keratoplasty to adequately assess outcomes. Infectious keratitis continues to be a serious complication among all types of keratoplasty, threatening the viability of the grafted tissues and visual outcomes of patients. Reports from various sites worldwide indicate differences in incidence rates and common infecting microorganisms between high- and middle-income countries. Most reports agree that suture-related problems and factors contributing to a suboptimal ocular surface are the primary risk factors for developing infectious keratitis. In general, patients with infectious keratitis following keratoplasty have a poor visual prognosis because of the difficulty of successful treatment without residual scarring.

  14. Replication of influenza A virus in swine umbilical cord epithelial stem-like cells.

    Science.gov (United States)

    Khatri, Mahesh; Chattha, Kuldeep S

    2015-01-01

    In this study, we describe the isolation and characterization of epithelial stem-like cells from the swine umbilical cord and their susceptibility to influenza virus infection. Swine umbilical cord epithelial stem cells (SUCECs) expressed stem cell and pluripotency associated markers such as SSEA-1, SSEA-4, TRA 1-60 and TRA 1-81 and Oct4. Morphologically, cells displayed polygonal morphology and were found to express epithelial markers; pancytokeratin, cytokeratin-18 and occludin; mesenchymal cell markers CD44, CD90 and haematopoietic cell marker CD45 were not detected on these cells. The cells had extensive proliferation and self- renewal properties. The cells also possessed immunomodulatory activity and inhibited the proliferation of T cells. Also, higher levels of anti-inflammatory cytokine IL-10 were detected in SUCEC-T cell co-cultures. The cells were multipotent and differentiated into lung epithelial cells when cultured in epithelial differentiation media. We also examined if SUCECs are susceptible to infection with influenza virus. SUCECs expressed sialic acid receptors, used by influenza virus for binding to cells. The 2009 pandemic influenza virus and swine influenza virus replicated in these cells. SUCECs due to their differentiation and immunoregulatory properties will be useful as cellular therapy in a pig model for human diseases. Additionally, our data indicate that influenza virus can infect SUCECs and may transmit influenza virus from mother to fetus through umbilical cord and transplantation of influenza virus-infected stem cells may transmit infection to recipients. Therefore, we propose that umbilical cord cells, in addition to other agents, should also be tested for influenza virus before cryopreservation for future use as a cell therapy for disease conditions.

  15. Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses.

    Science.gov (United States)

    VanLeuven, James T; Ridenhour, Benjamin J; Gonzalez, Andres J; Miller, Craig R; Miura, Tanya A

    2017-01-01

    The severity of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to viruses from different families while controlling other experimental parameters. Murine models are commonly used to study the pathogenesis of respiratory viral infections, and in vitro studies using murine cells provide mechanistic insight into the pathogenesis observed in vivo. We used microarray analysis to compare changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to distinguish shared and virus-specific mechanisms of pathogenesis in the respiratory tract.

  16. Peripheral Ulcerative Keratitis

    Science.gov (United States)

    ... Abbreviations Weights & Measures ENGLISH View Professional English Deutsch Japanese Espaniol Find information on medical topics, symptoms, drugs, ... oval in shape. Diagnosis A doctor's evaluation Sometimes culture The diagnosis of peripheral ulcerative keratitis is suspected ...

  17. Diagnosis and management of neurotrophic keratitis

    Directory of Open Access Journals (Sweden)

    Sacchetti M

    2014-03-01

    Full Text Available Marta Sacchetti,1 Alessandro Lambiase2 1Cornea and Ocular Surface Unit, Ospedale San Raffaele di Milano-IRCCS, Milan, 2Ophthalmology, University La Sapienza of Rome, Italy Abstract: Neurotrophic keratitis (NK is a degenerative disease characterized by corneal sensitivity reduction, spontaneous epithelium breakdown, and impairment of corneal healing. Several causes of NK, including herpetic keratitis, diabetes, and ophthalmic and neurosurgical procedures, share the common mechanism of trigeminal damage. Diagnosis of NK requires accurate investigation of clinical ocular and systemic history, complete eye examination, and assessment of corneal sensitivity. All diagnostic procedures to achieve correct diagnosis and classification of NK, including additional examinations such as in vivo confocal microscopy, are reviewed. NK can be classified according to severity of corneal damage, ie, epithelial alterations (stage 1, persistent epithelial defect (stage 2, and corneal ulcer (stage 3. Management of NK should be based on clinical severity, and aimed at promoting corneal healing and preventing progression of the disease to stromal melting and perforation. Concomitant ocular diseases, such as exposure keratitis, dry eye, and limbal stem cell deficiency, negatively influence the outcome of NK and should be treated. Currently, no specific medical treatment exists, and surgical approaches, such as amniotic membrane transplantation and conjunctival flap, are effective in preserving eye integrity, without ameliorating corneal sensitivity or visual function. This review describes experimental and clinical reports showing several novel and potential therapies for NK, including growth factors and metalloprotease inhibitors, as well as three ongoing Phase II clinical trials. Keywords: neurotrophic keratitis, cornea sensitivity, cornea innervation, persistent epithelial defect

  18. DIESEL EXHAUST ENHANCES INFLUENZA VIRUS INFECTIONS IN RESPIRATORY EPITHELIAL CELLS

    Science.gov (United States)

    Several factors, such as age and nutritional status can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects ...

  19. Painful Acute Corneal Ulceration and Anterior Stromal Keratitis in an Adolescent With Reactive Arthritis.

    Science.gov (United States)

    Lyons, Christopher J; AlQahtani, Elham; Tsang, Hughie; Moloney, Gregory T; Gardiner, Jane

    2016-12-08

    Reactive arthritis is occasionally associated with conjunctivitis and uveitis, but rarely keratitis. The authors describe a patient with paracentral anterior stromal keratitis with overlying epithelial erosion and multiple satellite subepithelial infiltrates. The initial appearance and the severe pain were suggestive of an infectious process. Recovery was rapid following introduction of topical steroid, with features suggesting an immune process in the recovery phase. The authors suggest that a history of arthritis and/or recent enteritis should be sought in the work-up of an atypical keratitis with or without epithelial defect. [J Pediatr Ophthalmol Strabismus. 2016;53:e61-e63.]. Copyright 2016, SLACK Incorporated.

  20. Contact lens-related acanthamoeba keratitis.

    Science.gov (United States)

    Stapleton, Fiona; Ozkan, Jerome; Jalbert, Isabelle; Holden, Brien A; Petsoglou, Con; McClellan, Kathy

    2009-10-01

    Acanthamoeba keratitis is a rare but severe disease, with more than 95% of cases occurring in contact lens wearers. With a worldwide resurgence of contact lens-related disease, this report illustrates the clinical characteristics and treatment challenges representative of this disease. This report describes Acanthamoeba keratitis in a 47-year-old female using extended wear silicone hydrogel contact lenses, with a history of swimming in a home pool and failure to subsequently disinfect the contact lenses. The diagnosis was based on clinical signs, disease course, and confocal microscopy results despite a negative result for corneal smear and culture. The corneal signs included an epithelial defect, epithelial irregularities, anterior stromal infiltrates, perineural infiltrates, an anterior stromal ring infiltrate, and hypopyon. The case was diagnosed as an infective keratitis and treated promptly using intensive topical administration of fortified gentamicin and cephalothin. The high likelihood Acanthamoeba prompted immediate use of polyhexamethylbiguanide and chlorhexidine, with propamide and adjunct treatment using atropine and oral diclofenac. Steroids were added on day 3, and the frequency of administration of antibacterial treatment was gradually reduced and ceased by day 10. The analgesia was stopped at 3 months. The frequency of administration of antiamoeba therapy and steroid treatment was slowly reduced and all treatment was ceased after 18 months. Despite considerable morbidity in terms of the treatment duration, hospitalization, outpatient appointments, and associated disease costs, the final visual outcome (6/6) was excellent.

  1. Bat airway epithelial cells: a novel tool for the study of zoonotic viruses.

    Directory of Open Access Journals (Sweden)

    Isabella Eckerle

    Full Text Available Bats have been increasingly recognized as reservoir of important zoonotic viruses. However, until now many attempts to isolate bat-borne viruses in cell culture have been unsuccessful. Further, experimental studies on reservoir host species have been limited by the difficulty of rearing these species. The epithelium of the respiratory tract plays a central role during airborne transmission, as it is the first tissue encountered by viral particles. Although several cell lines from bats were established recently, no well-characterized, selectively cultured airway epithelial cells were available so far. Here, primary cells and immortalized cell lines from bats of the two important suborders Yangochiroptera and Yinpterochiroptera, Carollia perspicillata (Seba's short-tailed bat and Eidolon helvum (Straw-colored fruit bat, were successfully cultured under standardized conditions from both fresh and frozen organ specimens by cell outgrowth of organ explants and by the use of serum-free primary cell culture medium. Cells were immortalized to generate permanent cell lines. Cells were characterized for their epithelial properties such as expression of cytokeratin and tight junctions proteins and permissiveness for viral infection with Rift-Valley fever virus and vesicular stomatitis virus Indiana. These cells can serve as suitable models for the study of bat-borne viruses and complement cell culture models for virus infection in human airway epithelial cells.

  2. Bat airway epithelial cells: a novel tool for the study of zoonotic viruses.

    Science.gov (United States)

    Eckerle, Isabella; Ehlen, Lukas; Kallies, René; Wollny, Robert; Corman, Victor M; Cottontail, Veronika M; Tschapka, Marco; Oppong, Samuel; Drosten, Christian; Müller, Marcel A

    2014-01-01

    Bats have been increasingly recognized as reservoir of important zoonotic viruses. However, until now many attempts to isolate bat-borne viruses in cell culture have been unsuccessful. Further, experimental studies on reservoir host species have been limited by the difficulty of rearing these species. The epithelium of the respiratory tract plays a central role during airborne transmission, as it is the first tissue encountered by viral particles. Although several cell lines from bats were established recently, no well-characterized, selectively cultured airway epithelial cells were available so far. Here, primary cells and immortalized cell lines from bats of the two important suborders Yangochiroptera and Yinpterochiroptera, Carollia perspicillata (Seba's short-tailed bat) and Eidolon helvum (Straw-colored fruit bat), were successfully cultured under standardized conditions from both fresh and frozen organ specimens by cell outgrowth of organ explants and by the use of serum-free primary cell culture medium. Cells were immortalized to generate permanent cell lines. Cells were characterized for their epithelial properties such as expression of cytokeratin and tight junctions proteins and permissiveness for viral infection with Rift-Valley fever virus and vesicular stomatitis virus Indiana. These cells can serve as suitable models for the study of bat-borne viruses and complement cell culture models for virus infection in human airway epithelial cells.

  3. Unilateral Punctate Keratitis Secondary to Wallenberg Syndrome

    Science.gov (United States)

    Boto, Ana; Del Hierro, Almudena; Capote, Maria; Noval, Susana; Garcia, Amanda; Santiago, Susana

    2014-01-01

    We studied three patients who developed left unilateral punctate keratitis after suffering left-sided Wallenberg Syndrome. A complex evolution occurred in two of them. In all cases, neurophysiological studies showed damage in the trigeminal sensory component at the bulbar level. Corneal involvement secondary to Wallenberg syndrome is a rare cause of unilateral superficial punctate keratitis. The loss of corneal sensitivity caused by trigeminal neuropathy leads to epithelial erosions that are frequently unobserved by the patient, resulting in a high risk of corneal-ulcer development with the possibility of superinfection. Neurophysiological studies can help to locate the anatomical level of damage at the ophthalmic branch of the trigeminal nerve, confirming the suspected etiology of stroke, and demonstrating that prior vascular involvement coincides with the location of trigeminal nerve damage. In some of these patients, oculofacial pain is a distinctive feature. PMID:24882965

  4. Oct4+ stem/progenitor swine lung epithelial cells are targets for influenza virus replication.

    Science.gov (United States)

    Khatri, Mahesh; Goyal, Sagar M; Saif, Yehia M

    2012-06-01

    We isolated stem/progenitor epithelial cells from the lungs of 4- to 6-week-old pigs. The epithelial progenitor colony cells were surrounded by mesenchymal stromal cells. The progenitor epithelial colony cells expressed stem cell markers such as octamer binding transcription factor 4 (Oct4) and stage-specific embryonic antigen 1 (SSEA-1), as well as the epithelial markers pancytokeratin, cytokeratin-18, and occludin, but not mesenchymal (CD44, CD29, and CD90) and hematopoietic (CD45) markers. The colony cells had extensive self-renewal potential and had the capacity to undergo differentiation to alveolar type I- and type II-like pneumocytes. Additionally, these cells expressed sialic acid receptors and supported the active replication of influenza virus, which was accompanied by cell lysis. The lysis of progenitor epithelial cells by influenza virus may cause a marked reduction in the potential of progenitor cells for self renewal and for their ability to differentiate into specialized cells of the lung. These observations suggest the possible involvement of lung stem/progenitor cells in influenza virus infection.

  5. Targeting Herpetic Keratitis by Gene Therapy

    Directory of Open Access Journals (Sweden)

    Hossein Mostafa Elbadawy

    2012-01-01

    Full Text Available Ocular gene therapy is rapidly becoming a reality. By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents. Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1 can cause serious complications that may lead to blindness. Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution. This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies. Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping. Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets. Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization. Successful gene therapy can provide innovative physiological and pharmaceutical solutions against herpetic keratitis.

  6. Keratitis in association with herpes zoster and varicella vaccines.

    Science.gov (United States)

    Grillo, A P; Fraunfelder, F W

    2017-07-01

    The objective of this review was to collect reports of keratitis in association with herpes zoster virus (HZV) or varicella zoster virus (VZV) vaccines. HZV vaccination is intended for at-risk adult populations and VZV vaccination is intended for all pediatric patients. We reviewed the literature and reports of keratitis in association with herpes zoster or varicella vaccine from the National Registry of Drug-Induced Ocular Side Effects and the World Health Organization. Twenty-four cases of unilateral keratitis in association with VZV vaccines were collected from the adverse reaction databases and literature. In most cases, the onset of keratitis occurred within days of vaccination and resolved with topical steroid eye drops and oral acyclovir. Data suggest that keratitis in association with herpes zoster or varicella vaccine is rare, is usually self-limited or resolves with treatment. The mechanism may be the persistence of viral antigens in the cornea after VZV vaccination or herpes zoster ophthalmicus. This reaction is probable, given the plausible biological mechanism, the temporal relationship between vaccination and keratitis, and overall patterns of presentation after vaccination. Copyright 2017 Clarivate Analytics.

  7. Enhanced adherence of Strontococcus pneumoniae to human epithelial cells infected with respiratory syncytial virus

    NARCIS (Netherlands)

    Hament, JM; Aerts, PC; Fleer, A; Van Dijk, H; Kimpen, JLL; Wolfs, TFW

    In the present study, we analyzed the effect of a preceding respiratory syncytial virus (RSV) infection of human respiratory epithelial cells on the adherence of Streptococcus pneumoniae tested by means of a cytometric fluorescence assay. Adherence of clinically relevant pneumococcal serotypes 3, 9,

  8. Patterned entry and egress by Epstein-Barr virus in polarized CR2-positive epithelial cells.

    Science.gov (United States)

    Chodosh, J; Gan, Y j; Holder, V P; Sixbey, J W

    2000-01-20

    In polarized epithelium direction of viral entry and release correlates with proclivity of a virus to establish local versus systemic infection. The Epstein-Barr virus (EBV), whose principal tissue reservoir is B lymphocytes, also has disease manifestations in epithelium, suggesting intertissue spread potentially influenced by epithelial cell polarity. We stably transfected the B lymphocyte EBV receptor (CR2/CD21) into Madin-Darby canine kidney (MDCK) epithelial cells used extensively to study effects of cell polarity on infection by both DNA and RNA viruses. CR2/CD21 was detected on both apical and basolateral surfaces of polarized MDCK cells, with predominant expression basolaterally. However, infectivity was up to four-fold greater apically, suggesting that endogenous cell surface molecules, sorted asymmetrically onto polarized plasma membranes, may be involved in EBV entry into MDCK cells. EBV gp350/220, a replicative cycle glycoprotein added to the virus envelope on egress through the cell membrane, was immunolocalized by confocal microscopy to basolateral cell surfaces only. Apical entry of EBV with subsequent basolateral release of newly replicated virus favors systemic infection by viral dissemination to underlying lymphocytic aggregations. Under conditions of long-term culture, latent EBV was not stably maintained in these cells, suggesting that the epithelial phase of acute EBV infection may be transient. Copyright 2000 Academic Press.

  9. Multidrug resistant Fusarium keratitis.

    Science.gov (United States)

    Antequera, P; Garcia-Conca, V; Martín-González, C; Ortiz-de-la-Tabla, V

    2015-08-01

    We report a case of keratitis in a female contact lens wearer, who developed a deep corneal abscess. The culture of a corneal biopsy scraping was positive for multiresistant Fusarium solani. The patient has a complicated clinical course and failed to respond to local and systemic antifungal treatment, requiring eye enucleation. Fusarium keratitis may progress to severe endophthalmitis. Clinical suspicion is paramount in order to start antifungal therapy without delay. Therapy is complex due to the high resistance of this organism to usual antifungal drugs. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  10. Diversity of Microbial Species Implicated in Keratitis: A Review

    Science.gov (United States)

    Karsten, Elisabeth; Watson, Stephanie Lousie; Foster, Leslie John Ray

    2012-01-01

    Background: Microbial keratitis is an infectious disease of the cornea characterised by inflammation and is considered an ophthalmic emergency requiring immediate attention. While a variety of pathogenic microbes associated with microbial keratitis have been identified, a comprehensive review identifying the diversity of species has not been completed. Methods: A search of peer-reviewed publications including case reports and research articles reporting microorganims implicated in keratitis was conducted. Search engines including PubMed, Scopus and Web of Science with years ranging from 1950-2012 were used. Results: 232 different species from 142 genera, representing 80 families were found to be implicated in microbial keratitis. Fungi exhibited the largest diversity with 144 species from 92 genera. In comparison, 77 species of bacteria from 42 genera, 12 species of protozoa from 4 genera and 4 types of virus were identified as the infectious agents. A comparison of their aetiologies shows reports of similarities between genera. Conclusions: The diversity of microbial species implicated in keratitis has not previously been reported and is considerably greater than suggested by incidence studies. Effective treatment is heavily reliant upon correct identification of the responsible microorganisms. Species identification, the risk factors associated with, and pathogenesis of microbial keratitis will allow the development of improved therapies. This review provides a resource for clinicians and researchers to assist in identification and readily source treatment information. PMID:23248737

  11. Calotropis procera -induced keratitis

    Directory of Open Access Journals (Sweden)

    Pandey Nidhi

    2009-01-01

    Full Text Available Calotropis procera produces copious amounts of latex, which has been shown to possess several pharmacological properities. Its local application produces intense inflammatory response. In the 10 cases of Calotropis procera -induced keratitis reported here, the clinical picture showed corneal edema with striate keratopathy without any evidence of intraocular inflammation. The inflammation was reversed by the local application of steroid drops.

  12. Calotropis procera -induced keratitis.

    Science.gov (United States)

    Pandey, Nidhi; Chandrakar, A K; Garg, M L; Patel, Santosh Singh

    2009-01-01

    Calotropis procera produces copious amounts of latex, which has been shown to possess several pharmacological properities. Its local application produces intense inflammatory response. In the 10 cases of Calotropis procera -induced keratitis reported here, the clinical picture showed corneal edema with striate keratopathy without any evidence of intraocular inflammation. The inflammation was reversed by the local application of steroid drops.

  13. Cryotherapy in Dendritic Keratitis.

    African Journals Online (AJOL)

    This study evaluates the effectiveness of cryotherapy in the treatment of dendritic Keratitis where antiviral agents are not available. The results show some improvement in visual acuity while one patient has a drop in vision. The extent of corneal scarring appears to depend on the duration of the disease and extent of stroma.

  14. associated with keratitis.

    African Journals Online (AJOL)

    2004-02-23

    Feb 23, 2004 ... Gent = Gentamicin. Ery = Erythromycin. Cip = Ciprofloxacin. F = FEMALE. Clox = Cloxacin. Norf = Norfloxacin. Tetr = Tetracycline. Gent Clox An Ery. P. N ... blood adsorption. In conclusion, the involvement of Escherichia coli in bacterial keratitis requires further investigation. Also, considering the sensitivity ...

  15. Candida albicans keratitis modified by steroid application

    Directory of Open Access Journals (Sweden)

    Kaoru Araki-Sasaki

    2009-02-01

    Full Text Available Kaoru Araki-Sasaki1, Hiroko Sonoyama1, Tsutomu Kawasaki1, Nariyasu Kazama1, Hidenao Ideta1, Yoshitsugu Inoue21Ideta Eye Hospital, Kumamoto City, Kumamoto, Japan; 2Department of Ophthalmology, Tottori University, Koyama-Minami, Tottori, Japan Abstract: The paper reports on Candida albicans ocular infection modified by steroid eye drops. A 74-year-old male complained of conjunctival injection and pain in his right eye three months after pterygium and cataract surgery. After treatment with antibiotics and steroid eye drops for three days, he was referred to our hospital. Clear localized corneal endothelial plaque with injection of ciliary body was observed. No erosion of the corneal epithelium, or infiltration of stromal edema was observed, suggesting that the pathological organism derived from the intracameral region. Because ocular infection was suspected, steroid eye drops were stopped, which led immediately to typical infectious keratitis in the pathological region, with epithelial erosion, fluffy abscess, stromal infiltration, and edema. For diagnostic purposes, the plaque was surgically removed with forceps and the anterior chamber was irrigated with antibiotics. The smear and culture examination from the plaque revealed C. albicans surrounded by neutrophils. However, aqueous fluid and fibrous tissue after gonio procedure contained no mycotic organisms. Topical fluconazole, micafungin, and pimaricin with oral itraconazole (150 mg/day were effective. Special attention is needed when prescribing steroid eye drops to treat corneal disease especially postoperatively. Diagnosing infectious keratitis is sometimes difficult because of modification by some factors, such as postoperative conditions, scarring, and drug-induced masking. Here, we report on mycotic keratitis modified by postoperative steroid administration. Keywords: Candida albicans, cataract surgery, steroid, mycotic keratitis

  16. Clinical Efficacy of Oral Ganciclovir for Prophylaxis and Treatment of Recurrent Herpes Simplex Keratitis

    National Research Council Canada - National Science Library

    Xin Wang Linnong Wang Nianlang Wu Xinjun Ma Jianjiang Xu

    2015-01-01

    Background:Herpes simplex keratitis (HSK) caused by herpes simplex virus 1 (HSV-1),which has high recurrent rate and incidence of severe vision loss,is the leading cause of infectious blindness...

  17. Animal Models of Bacterial Keratitis

    Science.gov (United States)

    Marquart, Mary E.

    2011-01-01

    Bacterial keratitis is a disease of the cornea characterized by pain, redness, inflammation, and opacity. Common causes of this disease are Pseudomonas aeruginosa and Staphylococcus aureus. Animal models of keratitis have been used to elucidate both the bacterial factors and the host inflammatory response involved in the disease. Reviewed herein are animal models of bacterial keratitis and some of the key findings in the last several decades. PMID:21274270

  18. Animal Models of Bacterial Keratitis

    Directory of Open Access Journals (Sweden)

    Mary E. Marquart

    2011-01-01

    Full Text Available Bacterial keratitis is a disease of the cornea characterized by pain, redness, inflammation, and opacity. Common causes of this disease are Pseudomonas aeruginosa and Staphylococcus aureus. Animal models of keratitis have been used to elucidate both the bacterial factors and the host inflammatory response involved in the disease. Reviewed herein are animal models of bacterial keratitis and some of the key findings in the last several decades.

  19. Ring Keratitis Associated With Topical Abuse of a Dilute Anesthetic After Refractive Surgery

    Directory of Open Access Journals (Sweden)

    Yu-Chih Hou

    2009-12-01

    Full Text Available Anesthetic toxic keratitis is rare and presents as a ring keratitis, which is often misdiagnosed as Acanthamoeba keratitis. Here, we report an unusual case of toxic keratitis caused by topical abuse of a dilute anesthetic. A 26-year-old woman presented with bilateral corneal edema, ring infiltrates, pigmented keratic precipitate, Descemet's membrane folding, and strong anterior chamber reactions 2 weeks after laser subepithelial keratomileusis surgery. Tracing back her medical history, topical dilute 0.1% proparacaine was prescribed and frequently used for 1 month. Toxic keratitis was suspected. After discontinuation of the topical anesthetic and initiation of treatment with topical 20% autologous serum, complete corneal epithelialization was achieved within 1 week. Corneal infiltrates and anterior chamber reaction gradually subsided. Vision improved from finger counting to 20/20 in the right eye and 20/25 in the left eye, but confocal microscopy showed decreased corneal endothelial cells. Topical abuse of a dilute topical anesthetic can cause severe toxic keratitis and endothelial cell loss. The physician must be aware of the signs of topical anesthetic abuse and should not prescribe even a dilute anesthetic for long-term use. Autologous serum can help in the recovery of toxic keratitis.

  20. [The entry of Epstein-Barr virus into B lymphocytes and epithelial cells during infection].

    Science.gov (United States)

    Zuo, Lie-Lian; Zhu, Mei-Juan; Du, Shu-Juan; Lu, Jian-Hong; Li, Gui-Yuan

    2014-07-01

    Epstein-Barr virus (EBV) is a human herpesvirus associated with important human diseases, including infectious mononucleosis syndrome, malignant lymphoma, and nasopharyngeal carcinoma. The mechanism of EBV entry into host cells remains a subject of intensive research. After decades of study, researchers have identified several key proteins and different patterns of EBV intrusion into host cells. The viral surface glycoproteins, gp350/220, gp42, gB, gH, and gL, are involved in interactions with the CR2 receptor on the surface of B lymphocytes during viral entry. However, the majority of epithelial cells lack CR2 receptor expression, which makes viral invasion much more complex than in B lymphocytes. Three different models have been proposed to explain how EBV enters epithelial cells: (1) "transfer of infection", mediated by B lymphocytes or Langerhans cells; (2) EBV utilizes its own proteins during the process of fusion with the cell membrane; and (3) progeny virions arising from EBV-infected epithelial cells cross lateral membranes into adjacent epithelial cells. This review will discuss the relevant mechanism of viral entry into B lymphocytes and epithelial cells during EBV infection.

  1. Adjunctive Therapies for Bacterial Keratitis.

    Science.gov (United States)

    Dakhil, Turki Abdulaziz Bin; Stone, Donald U; Gritz, David C

    2017-01-01

    Bacterial keratitis is the most common type among all types of infectious keratitis. Currently, antibiotics are the main-stay of treatment. The objective of this systematic review is to review published clinical studies which discuss the adjunctive treatment of bacterial keratitis to guide clinical decision-making. We reviewed the role of a variety of medications and surgeries which can help in managing bacterial keratitis complications, which include as thinning, perforation, and impaired wound healing. We have included appropriate animal and laboratory studies, case reports and case series, and randomized clinical trials regarding each therapy.

  2. Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Dhananjay M Nawandar

    2015-10-01

    Full Text Available Epstein-Barr virus (EBV is a human herpesvirus associated with B-cell and epithelial cell malignancies. EBV lytically infects normal differentiated oral epithelial cells, where it causes a tongue lesion known as oral hairy leukoplakia (OHL in immunosuppressed patients. However, the cellular mechanism(s that enable EBV to establish exclusively lytic infection in normal differentiated oral epithelial cells are not currently understood. Here we show that a cellular transcription factor known to promote epithelial cell differentiation, KLF4, induces differentiation-dependent lytic EBV infection by binding to and activating the two EBV immediate-early gene (BZLF1 and BRLF1 promoters. We demonstrate that latently EBV-infected, telomerase-immortalized normal oral keratinocyte (NOKs cells undergo lytic viral reactivation confined to the more differentiated cell layers in organotypic raft culture. Furthermore, we show that endogenous KLF4 expression is required for efficient lytic viral reactivation in response to phorbol ester and sodium butyrate treatment in several different EBV-infected epithelial cell lines, and that the combination of KLF4 and another differentiation-dependent cellular transcription factor, BLIMP1, is highly synergistic for inducing lytic EBV infection. We confirm that both KLF4 and BLIMP1 are expressed in differentiated, but not undifferentiated, epithelial cells in normal tongue tissue, and show that KLF4 and BLIMP1 are both expressed in a patient-derived OHL lesion. In contrast, KLF4 protein is not detectably expressed in B cells, where EBV normally enters latent infection, although KLF4 over-expression is sufficient to induce lytic EBV reactivation in Burkitt lymphoma cells. Thus, KLF4, together with BLIMP1, plays a critical role in mediating lytic EBV reactivation in epithelial cells.

  3. A Case of Retained Graphite Anterior Chamber Foreign Body Masquerading as Stromal Keratitis

    OpenAIRE

    Han, Eun Ryung; Wee, Won Ryang; Lee, Jin Hak; Hyon, Joon Young

    2011-01-01

    We report a case of a retained graphite anterior chamber foreign body that was masquerading as stromal keratitis. A 28-year-old male visited with complaints of visual disturbance and hyperemia in his right eye for four weeks. On initial examination, he presented with a stromal edema involving the inferior half of the cornea, epithelial microcysts, and moderate chamber inflammation. Suspecting herpetic stromal keratitis, he was treated with anti-viral and anti-inflammatory agents. One month af...

  4. Antibodies to gp350/220 Enhance the Ability of Epstein-Barr Virus To Infect Epithelial Cells

    OpenAIRE

    Turk, Susan M.; Jiang, Ru; Chesnokova, Liudmila S.; Hutt-Fletcher, Lindsey M.

    2006-01-01

    Epstein-Barr virus (EBV) is a persistent, orally transmitted herpesvirus that replicates in B cells and epithelial cells and is associated with lymphoid and epithelial malignancies. The virus binds to CD21 on B cells via glycoprotein gp350/220 and infects efficiently. Infection of cultured epithelial cells has not typically been efficient but can occur in the absence of gp350/220 and CD21 and in vivo is thought to be important to the development of nasopharyngeal carcinoma. We report here tha...

  5. Clinical pattern of recurrent herpes simplex keratitis

    Directory of Open Access Journals (Sweden)

    Saini Jagjit

    1999-01-01

    Full Text Available Purpose: To document the clinical pattern in recurrent herpes simplex disease. Methods: Eyes with clinically documented pattern of corneal manifestation on more than one occasion were analysed. For each eye recruited, the clinical pattern of the disease at each recurrence of herpes simplex corneal disease, age, disease-free intervals, triggering factors, laterality and steroid abuse were noted and evaluated. Results: For an average follow up of 6.9 years, a recurrence rate of 0.6 episodes per year was observed. Disease-free intervals of 75.7 months for epithelial herpes simplex disease was considerably longer than the 21.3 months observed for stromal disease. Clinical pattern of recurrence was of the same type following first episode of disciform keratitis, epithelial keratitis and endothelitis in 84%, 72.7%, and 75% of the eyes respectively. Conclusion: Herpes simplex disease often recurs in the same manifest clinical pattern as the first episode. This clinical evidence provides additional support for the potential role of herpes simplex biotypes in determining manifestation of clinical disease pattern.

  6. [Keratitis due to Acanthamoeba].

    Science.gov (United States)

    Pérez-Irezábal, Julio; Martínez, Inés; Isasa, Patricia; Barrón, Jorge

    2006-10-01

    Free-living amebae appertaining to the genus Acanthamoeba, Naegleria and Balamuthia are the most prevalent protozoa found in the environment. These amebae have a cosmopolitan distribution in soil, air and water, providing multiple opportunities for contacts with humans and animals, although they only occasionally cause disease. Acanthamoeba spp. are the causative agent of granulomatous amebic encephalitis, a rare and often fatal disease of the central nervous system, and amebic keratitis, a painful disease of the eyes. Keratitis usually follows a chronic course due to the delay in diagnosis and subsequent treatment. The clear increase in Acanthamoeba keratitis in the last 20 years is related to the use and deficient maintenance of contact lenses, and to swimming while wearing them. The expected incidence is one case per 30,000 contact lens wearers per year, with 88% of cases occurring in persons wearing hydrogel lenses. This review presents information on the morphology, life-cycle and epidemiology of Acanthamoeba, as well as on diagnostic procedures (culture), appropriate antimicrobial therapy, and prevention measures.

  7. Infection of differentiated airway epithelial cells from caprine lungs by viruses of the bovine respiratory disease complex.

    Science.gov (United States)

    Kirchhoff, Jana; Uhlenbruck, Sabine; Keil, Günther M; Schwegmann-Wessels, Christel; Ganter, Martin; Herrler, Georg

    2014-05-14

    Bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus type 3 (BPIV3) and bovine herpesvirus type 1 (BHV-1) are important pathogens associated with the bovine respiratory disease complex (BRDC). Non-bovine ruminants such as goats may also be infected and serve as a virus reservoir to be considered in the development of control strategies. To evaluate the susceptibility of caprine airway epithelial cells to infection by viruses of BRDC, we established a culture system for differentiated caprine epithelial cells. For this purpose, we generated precision-cut lung slices (PCLS), in which cells are retained in their original structural configuration and remain viable for more than a week. The three bovine viruses were found to preferentially infect different cell types. Ciliated epithelial cells were the major target cells of BPIV3, whereas BHV-1 preferred basal cells. Cells infected by BRSV were detected in submucosal cell layers. This spectrum of susceptible cells is the same as that reported recently for infected bovine PCLS. While infection of caprine cells by BRSV and BPIV3 was as efficient as that reported for bovine cells, infection of caprine cells by BHV-1 required a tenfold higher dose of infectious virus as compared to infection of bovine airway cells. These results support the notion that non-bovine ruminants may serve as a reservoir for viruses of BRDC and introduce a culture system to analyze virus infection of differentiated airway epithelial cells from the caprine lung. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Differential Mucin Expression by Respiratory Syncytial Virus and Human Metapneumovirus Infection in Human Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Ma. Del Rocío Baños-Lara

    2015-01-01

    Full Text Available Mucins (MUC constitute an important component of the inflammatory and innate immune response. However, the expression of these molecules by respiratory viral infections is still largely unknown. Respiratory syncytial virus (RSV and human metapneumovirus (hMPV are two close-related paramyxoviruses that can cause severe low respiratory tract disease in infants and young children worldwide. Currently, there is not vaccine available for neither virus. In this work, we explored the differential expression of MUC by RSV and hMPV in human epithelial cells. Our data indicate that the MUC expression by RSV and hMPV differs significantly, as we observed a stronger induction of MUC8, MUC15, MUC20, MUC21, and MUC22 by RSV infection while the expression of MUC1, MUC2, and MUC5B was dominated by the infection with hMPV. These results may contribute to the different immune response induced by these two respiratory viruses.

  9. Human ocular-derived virus-specific CD4+ T cells control Varicella zoster virus replication in human retinal pigment epithelial cells

    NARCIS (Netherlands)

    J.C. Milikan (Johannes); G.S. Baarsma (Seerp); R.W.A.M. Kuijpers (Robert); A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George)

    2009-01-01

    textabstractPURPOSE. Varicella zoster virus (VZV)-induced retinitis is characterized by the presence of virus-infected cells in the retinal layer and the ocular infiltration of VZV-specific T cells. Herein, the susceptibility of human retinal pigment epithelial (RPE) cells to VZV infection and the

  10. BENIGN EPITHELIAL NEOPLASIA ASSOCIATED WITH BETA-HUMAN PAPILLOMA VIRUS

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    V. A. Molochkov

    2014-01-01

    Full Text Available Aim: To study an association between acrochordon and human papilloma virus (HPV using quantitative analysis of viral desoxyribonucleic acid (DNA; to detect different phenotypes of beta-HPV. Materials and methods: We examined 52  patients (22 immuno-suppressed patients and 30 immunocompetent subjects in the Dermatovenereology and Dermato-Oncology Department and Chronic Dialysis and Kidney Transplantation Department of the Moscow Regional Research and Clinical Institute (MONIKI. Control group included 49 healthy donors. Burr biopsy samples (micro-samples of acrochordon and intact skin (apper arm were collected in sterile conditions. After sample procession and DNA isolation using DNK-sorb-C kit (Central Research Institute for Epidemiology – CRIE, polymerase chain reaction for HPV was performed with real-time fluorescent hybridization detection. For DNA amplification and detection we used RotorGene 3000 analyzer (Corbett Research, Australia. In the beta-HPV assay, recombinant plasmids were used as positive controls and control human beta-globin gene fragments (CRIE. 4 oligo-nucleotide systems (group-specific primers and probes were used for the detection of beta-HPV DNA. Results: Preliminary data indicated that acrochordons of open and covered skin regions were common in renal transplant recipients. Beta-HPV DNA was more frequent in acrochordons and intact skin (64% and 54% of renal transplant recipients compared to healthy donors (47%. 57% of renal transplant recipients demonstrated mixed infection in acrochordons. Conclusion: HPV DNA was frequently detected in acrochordons and intact skin of renal transplant recipients. In immunocompetent patients prevalence of HPV DNA in acrochordons was significantly higher compared to intact skin.

  11. Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

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    Yuen Kit M

    2009-10-01

    Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

  12. Roles of Epstein-Barr virus glycoproteins gp350 and gp25 in the infection of human epithelial cells.

    Science.gov (United States)

    Maruo, S; Yang, L; Takada, K

    2001-10-01

    Epstein-Barr virus (EBV) is associated with various epithelial malignancies such as nasopharyngeal carcinoma and gastric carcinoma, and causes oral hairy leukoplakia, a productive EBV infection of the differentiated epithelium of the tongue. However, it is not clear by what mechanism EBV infects epithelial cells. We generated a recombinant EBV that expresses enhanced green fluorescent protein in order to monitor EBV entrance into epithelial cells quickly and quantitatively. Using this monitoring system, we examined the roles of gp350 and gp25 in EBV infection of epithelial cells by utilizing soluble forms of the gp350 and gp25 proteins. EBV infection of three of four examined epithelial cell lines, 293, NU-GC-3 and Lovo, was almost completely blocked by pretreatment of cells with a soluble form of gp350 (designated gp350Ig), and this blockage was dependent on the CD21-binding region of gp350. On the other hand, infection of the other epithelial cell line, AGS, was not inhibited at all by pretreatment with gp350Ig. Moreover, we found that a soluble form of gp25 (designated gp25Ig) preferentially bound to epithelial cells rather than B cells, and pretreatment of cells with gp25Ig substantially blocked EBV infection of some epithelial cells. These results indicate the existence of two distinct pathways in EBV infection of epithelial cells, a gp350-dependent pathway and a gp350-independent pathway, and that gp25 can play a role in the infection of some epithelial cells.

  13. Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells

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    Coyle Peter V

    2011-01-01

    Full Text Available Abstract Background Human respiratory syncytial virus (RSV causes severe respiratory disease in infants. Airway epithelial cells are the principle targets of RSV infection. However, the mechanisms by which it causes disease are poorly understood. Most RSV pathogenesis data are derived using laboratory-adapted prototypic strains. We hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (PBECs. Methods To address this hypothesis, we isolated three RSV strains from infants hospitalized with bronchiolitis and compared them with the prototypic RSV A2 in terms of cytopathology, virus growth kinetics and chemokine secretion in infected PBEC monolayers. Results RSV A2 rapidly obliterated the PBECs, whereas the clinical isolates caused much less cytopathology. Concomitantly, RSV A2 also grew faster and to higher titers in PBECs. Furthermore, dramatically increased secretion of IP-10 and RANTES was evident following A2 infection compared with the clinical isolates. Conclusions The prototypic RSV strain A2 is poorly representative of recent clinical isolates in terms of cytopathogenicity, viral growth kinetics and pro-inflammatory responses induced following infection of PBEC monolayers. Thus, the choice of RSV strain may have important implications for future RSV pathogenesis studies.

  14. Ferret airway epithelial cell cultures support efficient replication of influenza B virus but not mumps virus.

    Science.gov (United States)

    Elderfield, Ruth A; Parker, Lauren; Stilwell, Peter; Roberts, Kim L; Schepelmann, Silke; Barclay, Wendy S

    2015-08-01

    Ferrets have become the model animal of choice for influenza pathology and transmission experiments as they are permissive and susceptible to human influenza A viruses. However, inoculation of ferrets with mumps virus (MuV) did not lead to successful infections. We evaluated the use of highly differentiated ferret tracheal epithelium cell cultures, FTE, for predicting the potential of ferrets to support respiratory viral infections. FTE cultures supported productive replication of human influenza A and B viruses but not of MuV, whereas analogous cells generated from human airways supported replication of all three viruses. We propose that in vitro strategies using these cultures might serve as a method of triaging viruses and potentially reducing the use of ferrets in viral studies.

  15. Clinical Characteristics of Alternaria Keratitis

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    Ching-Hsi Hsiao

    2014-01-01

    Full Text Available Purpose. Alternaria spp. are an uncommon cause of mycotic keratitis. Previous studies on Alternaria keratitis have generally been limited to case reports. We examined the clinical characteristics of Alternaria keratitis in this study. Methods. The characteristics and outcomes of 7 patients with culture-proven Alternaria keratitis treated in our hospital were compared with 25 previously reported cases. Results. The risk factors for Alternaria keratitis were trauma in 5 patients and soft contact lenses in 1 patient. Six patients with early diagnosis (<2 weeks were cured with medical antimicrobial treatment; a patch graft was required in 1 patient with perforation. When incorporated with previous reports on Alternaria keratitis (n=32, 14 (44% infections followed trauma, 10 (31% were associated with preexisting corneal disease or previous ocular surgery, and 5 (16% occurred in soft contact lens wearers. Successful medical treatment was achieved in 23 (72% patients, including 10 out of 21 eyes (48% treated with natamycin and/or amphotericin B. Therapeutic penetrating keratoplasty was performed in 9 (28% cases. Conclusions. Alternaria keratitis is generally associated with specific risk factors and responds to medical treatment when early diagnosis is performed and prompt antifungal treatment is initiated.

  16. Clinical and corneal microbial profile of infectious keratitis in a high HIV prevalence setting in rural South Africa.

    Science.gov (United States)

    Schaftenaar, E; Peters, R P H; Baarsma, G S; Meenken, C; Khosa, N S; Getu, S; McIntyre, J A; Osterhaus, A D M E; Verjans, G M G M

    2016-09-01

    The purpose of this investigation was to determine the clinical and corneal microbial profile of infectious keratitis in a high human immunodeficiency virus (HIV) prevalence setting in rural South Africa. Data in this cross-sectional study were collected from patients presenting with symptoms of infectious keratitis (n = 46) at the ophthalmology outpatient department of three hospitals in rural South Africa. Corneal swabs were tested for herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV) and adenovirus DNA by real-time polymerase chain reaction (PCR) and for bacteria and fungi by culture. Based on clinical history, disease characteristics and laboratory results, 29 (63 %) patients were diagnosed as viral keratitis, including 14 (48 %) viral keratitis cases complicated by bacterial superinfection, and 17 (37 %) as bacterial keratitis. VZV and HSV-1 DNA was detected in 11 (24 %) and 5 (11 %) corneal swabs, respectively. Among clinically defined viral keratitis cases, a negative viral swab was predominantly (93 %) observed in cases with subepithelial inflammation and was significantly associated with an increased duration of symptoms (p = 0.003). The majority of bacteria cultured were Gram-positive (24/35), including Staphylococcus epidermidis and S. aureus. Viral aetiology was significantly associated with a history of herpes zoster ophthalmicus (p data implicate a high prevalence of herpetic keratitis, in part complicated by bacterial superinfection and/or uveitis, in HIV-infected individuals presenting with infectious keratitis in rural South Africa.

  17. Microbial keratitis secondary to unintended poor compliance with scleral gas-permeable contact lenses.

    Science.gov (United States)

    Zimmerman, Aaron B; Marks, Amanda

    2014-01-01

    To report a case of neurotrophic keratitis in which scleral contact lenses improved vision from 20/100 to 20/20, however, due to poor lens care, an incident of microbial keratitis developed. A 64-year-old man with an ocular history of neurotrophic keratitis secondary to herpes simplex in each eye was successfully fit with scleral lenses. He subsequently developed microbial keratitis due to a number of risk factors. The lesion was culture negative, yet was very responsive to treatment with moxifloxacin. The lesion fully healed, and the patient did not suffer additional vision loss. This case demonstrates the ability of scleral lenses to correct visual impairments secondary to poor epithelial integrity and illustrates the importance of the practitioner providing detailed lens care instruction.

  18. Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells.

    Science.gov (United States)

    Ko, Seongyeol; Gu, Min Jeong; Kim, Cheol Gyun; Kye, Yoon Chul; Lim, Younggap; Lee, Ji Eun; Park, Byung-Chul; Chu, Hyuk; Han, Seung Hyun; Yun, Cheol-Heui

    2017-10-01

    Porcine epidemic diarrhea virus (PEDV) invades porcine intestinal epithelial cells (IECs) and causes diarrhea and dehydration in pigs. In the present study, we showed a suppression of PEDV infection in porcine jejunum intestinal epithelial cells (IPEC-J2) by an increase in autophagy. Autophagy was activated by rapamycin at a dose that does not affect cell viability and tight junction permeability. The induction of autophagy was examined by LC3I/LC3II conversion. To confirm the autophagic-flux (entire autophagy pathway), autophagolysosomes were examined by an immunofluorescence assay. Pre-treatment with rapamycin significantly restricted not only a 1 h infection but also a longer infection (24 h) with PEDV, while this effect disappeared when autophagy was blocked. Co-localization of PEDV and autophagosomes suggests that PEDV could be a target of autophagy. Moreover, alleviation of PEDV-induced cell death in IPEC-J2 cells pretreated with rapamycin demonstrates a protective effect of rapamycin against PEDV-induced epithelial cell death. Collectively, the present study suggests an early prevention against PEDV infection in IPEC-J2 cells via autophagy that might be an effective strategy for the restriction of PEDV, and opens up the possibility of the use of rapamycin in vivo as an effective prophylactic and prevention treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements

    Energy Technology Data Exchange (ETDEWEB)

    Band, V.; Zajchowski, D.; Kulesa, V.; Sager, R. (Dana-Farber Cancer Institute, Boston, MA (USA))

    1990-01-01

    Human papilloma virus (HPV) types 16 and 18 are most commonly associated with cervical carcinoma in patients and induce immortalization of human keratinocytes in culture. HPV has not been associated with breast cancer. This report describes the immortalization of normal human mammary epithelial cells (76N) by plasmid pHPV18 or pHPV16, each containing the linearized viral genome. Transfectants were grown continuously for more than 60 passages, whereas 76N cells senesce after 18-20 passages. The transfectants also differ from 76N cells in cloning in a completely defined medium called D2 and growing a minimally supplemented defined medium (D3) containing epidermal growth factor. All transfectant tested contain integrated HPV DNA, express HPV RNA, and produce HPV E7 protein. HPV transfectants do not form tumors in a nude mouse assay. It is concluded that products of the HPV genome induce immortalization of human breast epithelial cells and reduce their growth factor requirements. This result raises the possibility that HPV might be involved in breast cancer. Furthermore, other tissue-specific primary epithelial cells that are presently difficult to grown and investigate may also be immortalized by HPV.

  20. Detecção do vírus herpes simples por reação em cadeia da polimerase em pacientes com ceratite herpética típica ou atípica Molecular detection of herpes simplex virus by polymerase chain reaction in patients with typical and atypical herpetic keratitis

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    Afonso Kamimura

    2008-12-01

    Full Text Available OBJETIVO: Avaliação dos pacientes com o quadro clínico de ceratite herpética (CH típicas e atípicas, pela reação em cadeia da polimerase (PCR correlacionando com o diagnóstico clínico. MÉTODOS: Foi realizada a PCR em 28 pacientes com ceratite herpética típica e atípica. RESULTADOS: A PCR foi positiva em 57,14% (n=16 do total (n=28. Nos casos de CH típica a positividade foi de 60,00% (n=12 em 20 casos. Para CH epitelial a positividade foi de 69,23% (n=9, sendo 77,78% (n=7 apenas para as lesões epiteliais dendríticas. Os casos de CH atípica apresentaram positividade de 50% (n=4 em oito casos. CONCLUSÃO: Quadro clínico típico de CH teve boa correlação com o resultado positivo observado na PCR. Entretanto, metade dos pacientes com o quadro de CH atípica apresentou PCR positivo, portanto, o exame do PCR é teste importante para o auxílio e diagnóstico da CH. No caso de CH estromal, foi demonstrado que a técnica da PCR conseguiu identificar o vírus HSV.PURPOSE: To evaluate patients with clinically typical and atypical herpetic keratitis (HK by means of polymerase chain reaction (PCR as compared with the clinical diagnosis. METHODS: PCR in 28 patients with clinical symptoms of typical and atypical HK was performed. RESULTS: PCR was positive in 57.14% (n=16 of the total cases (n=28. The test was positive in 60.0% (n=12 of the 20 typical HK cases. For epithelial HK, the test was positive in 69.23% (n=9, and 77.78% (n=7 only for dendritic injuries. Atypical HK presented a positive test in 50% (n=4 of eight cases. CONCLUSION: Clinical typical picture of HK had a good correlation with the positive result of PCR, mainly for epithelial injury of the dendritic type. However, 50% of the patients with atypical HK presented positive PCR. This result showed that PCR test can provide an effective HK diagnosis. In the stromal case of HK, PCR was a useful technique to identify HSV virus.

  1. Hendra and Nipah Virus Infection in Cultured Human Olfactory Epithelial Cells.

    Science.gov (United States)

    Borisevich, Viktoriya; Ozdener, Mehmet Hakan; Malik, Bilal; Rockx, Barry

    2017-01-01

    Henipaviruses are emerging zoonotic viruses and causative agents of encephalitis in humans. However, the mechanisms of entry into the central nervous system (CNS) in humans are not known. Here, we evaluated the possible role of olfactory epithelium in virus entry into the CNS. We characterized Hendra virus (HeV) and Nipah virus (NiV) infection of primary human olfactory epithelial cultures. We show that henipaviruses can infect mature olfactory sensory neurons. Henipaviruses replicated efficiently, resulting in cytopathic effect and limited induction of host responses. These results show that human olfactory epithelium is susceptible to infection with henipaviruses, suggesting that this could be a pathway for neuroinvasion in humans. IMPORTANCE Henipaviruses are emerging zoonotic pathogens that can cause acute and severe respiratory and neurological disease in humans. The pathways by which henipaviruses enter the central nervous system (CNS) in humans are still unknown. The observation that human olfactory neurons are highly susceptible to infection with henipaviruses demonstrates that the olfactory epithelium can serve as a site of Henipavirus entry into the CNS.

  2. Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation

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    Hai Hu

    2016-07-01

    Full Text Available Whether the human tumor virus, Epstein–Barr Virus (EBV, promotes breast cancer remains controversial and a potential mechanism has remained elusive. Here we show that EBV can infect primary mammary epithelial cells (MECs that express the receptor CD21. EBV infection leads to the expansion of early MEC progenitor cells with a stem cell phenotype, activates MET signaling and enforces a differentiation block. When MECs were implanted as xenografts, EBV infection cooperated with activated Ras and accelerated the formation of breast cancer. Infection in EBV-related tumors was of a latency type II pattern, similar to nasopharyngeal carcinoma (NPC. A human gene expression signature for MECs infected with EBV, termed EBVness, was associated with high grade, estrogen-receptor-negative status, p53 mutation and poor survival. In 11/33 EBVness-positive tumors, EBV-DNA was detected by fluorescent in situ hybridization for the viral LMP1 and BXLF2 genes. In an analysis of the TCGA breast cancer data EBVness correlated with the presence of the APOBEC mutational signature. We conclude that a contribution of EBV to breast cancer etiology is plausible, through a mechanism in which EBV infection predisposes mammary epithelial cells to malignant transformation, but is no longer required once malignant transformation has occurred.

  3. Comparison of Mycotic Keratitis with Nonmycotic Keratitis: An Epidemiological Study

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    Mohammad M. Khater

    2014-01-01

    Full Text Available Purpose. This work aims to study the problems encountered with and the different epidemiological features of patients with fungal keratitis. Patients and Methods. All cases with keratitis attending the Outpatient Clinic of Ophthalmology Department at Tanta University Hospital during three years from the first of January 2011 to the end of December 2013 were selected and carefully examined and cases with mycotic keratitis were further examined and investigated. Results. From 66303 attendants during this period with different complaints, there were 361 cases (0.54% with mycotic keratitis and 473 cases (0.71% of nonmycotic origin. Mycotic keratitis is common between 40 and 60 years, more in farmers (64%, families with large number and large crowding index, rural than urban residence, and patients with outdoor water sources and insanitary sewage disposal. Positive fungal cultures were obtained in 84.5% and were negative in 15.5% of cases in spite of their typical clinical findings for diagnosis and their improvement with antifungal therapy. Conclusion. Mycotic keratitis is more frequent in farmers, rural areas, outdoor water supply, insanitary sewage disposal, and patients preceded with organic trauma. Atypical clinical findings were found in some cases and not all cases improved with specific antifungal therapy.

  4. Comparison of mycotic keratitis with nonmycotic keratitis: an epidemiological study.

    Science.gov (United States)

    Khater, Mohammad M; Shehab, Nehal S; El-Badry, Anwar S

    2014-01-01

    Purpose. This work aims to study the problems encountered with and the different epidemiological features of patients with fungal keratitis. Patients and Methods. All cases with keratitis attending the Outpatient Clinic of Ophthalmology Department at Tanta University Hospital during three years from the first of January 2011 to the end of December 2013 were selected and carefully examined and cases with mycotic keratitis were further examined and investigated. Results. From 66303 attendants during this period with different complaints, there were 361 cases (0.54%) with mycotic keratitis and 473 cases (0.71%) of nonmycotic origin. Mycotic keratitis is common between 40 and 60 years, more in farmers (64%), families with large number and large crowding index, rural than urban residence, and patients with outdoor water sources and insanitary sewage disposal. Positive fungal cultures were obtained in 84.5% and were negative in 15.5% of cases in spite of their typical clinical findings for diagnosis and their improvement with antifungal therapy. Conclusion. Mycotic keratitis is more frequent in farmers, rural areas, outdoor water supply, insanitary sewage disposal, and patients preceded with organic trauma. Atypical clinical findings were found in some cases and not all cases improved with specific antifungal therapy.

  5. In vivo confocal microscopy for the detection of canine fungal keratitis and monitoring of therapeutic response.

    Science.gov (United States)

    Ledbetter, Eric C; Norman, Mary L; Starr, Jennifer K

    2016-05-01

    To describe in vivo corneal confocal microscopy of dogs during the clinical course of fungal keratitis and correlate findings with clinical evaluations and an ex vivo experimental canine fungal keratitis model. Seven dogs with naturally acquired fungal keratitis and ex vivo canine corneas experimentally infected with clinical fungal isolates. Dogs with naturally acquired fungal keratitis were examined by in vivo laser scanning confocal microscopy. Initial confocal microscopic examinations were performed to assist in establishing the diagnosis of fungal keratitis. Serial confocal microscopic examinations were performed to guide antifungal chemotherapy. Confocal microscopy images of canine corneal fungal isolates were obtained by examination of experimentally infected ex vivo canine corneas to corroborate in vivo findings. Fungi cultured and detected by PCR from canine corneal samples included Candida albicans, Fusarium incarnatum-equiseti, Malassezia pachydermatis, and a Rhodotorula sp. Linear, branching, interlocking, hyperreflective structures were detected by confocal microscopy in dogs with filamentous fungal keratitis and round to oval hyperreflective structures were detected in dogs with yeast fungal keratitis. Antifungal chemotherapy was associated with a progressive reduction in the distribution and density of corneal fungal elements, alterations to fungal morphology, decreased leukocyte numbers, restoration of epithelial layers, and an increased number of visible keratocyte nuclei. No dogs had a recurrence of fungal keratitis following medication discontinuation. Confocal microscopic fungal morphologies were similar between in vivo and ex vivo examinations. In vivo corneal confocal microscopy is a rapid method of diagnosing fungal keratitis in dogs and provides a noninvasive mechanism for monitoring therapeutic response. © 2015 American College of Veterinary Ophthalmologists.

  6. Medical interventions for fungal keratitis.

    OpenAIRE

    FlorCruz, NV; Evans, JR

    2015-01-01

    Fungal keratitis is a fungal infection of the cornea. It is common in lower income countries, particularly in agricultural areas but relatively uncommon in higher income countries. Although there are medications available, their effectiveness is unclear. To assess the effects of different antifungal drugs in the management of fungal keratitis. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Othe...

  7. [Syphilitic parenchymatous keratitis].

    Science.gov (United States)

    Ignat, F; Davidescu, L

    1997-01-01

    It shows a clinical observation about luetic bilateral keratitis at a young man 17 years old. The high-positive VDRL, the presence of the AT antigen, the bilateral low hearing perception and the left low hearing transmission associated with minimal dental malformations suggest the luetic congenital etiology of the disease. The AT positive-test at the patient's mother (which VDRL is negative) shows a tardive luetic infection during the pregnancy, that has determined the apparition at the fetus of congenital lately lues. The specific antiluetic treatment with Benzylpenicillinum kalicum and Prednisonums the evolution of the disease is spectacularly good. Six weeks after the beginning of the treatment V.A. is 1 at the both eyes and the neoformation vessels are completely obturated. The paper insists on the medical and social implications of the ignored complications of late lues.

  8. Antibodies to gp350/220 enhance the ability of Epstein-Barr virus to infect epithelial cells.

    Science.gov (United States)

    Turk, Susan M; Jiang, Ru; Chesnokova, Liudmila S; Hutt-Fletcher, Lindsey M

    2006-10-01

    Epstein-Barr virus (EBV) is a persistent, orally transmitted herpesvirus that replicates in B cells and epithelial cells and is associated with lymphoid and epithelial malignancies. The virus binds to CD21 on B cells via glycoprotein gp350/220 and infects efficiently. Infection of cultured epithelial cells has not typically been efficient but can occur in the absence of gp350/220 and CD21 and in vivo is thought to be important to the development of nasopharyngeal carcinoma. We report here that antibodies to gp350/220, which inhibit EBV infection of B cells, enhance infection of epithelial cells. The effect is not mediated by Fc receptor binding but is further enhanced by antibody cross-linking, which may patch gp350/220 in the virus envelope. Saliva from EBV-seropositive individuals has similar effects that can be reversed by depletion of antibody. The results are consistent with a model in which gp350/220 interferes with the access of other important players to the epithelial cell surface. The results may have implications for the development of nasopharyngeal carcinoma in high-risk populations in which elevated titers of antibody to EBV lytic cycle proteins are prognostic.

  9. INHIBITION OF RESPIRATORY SYNCYTIAL VIRUS (RSV)-INDUCED INFLAMMATION BY 3-NITROTYROSINE IN HUMAN BRONCHIAL EPITHELIAL CELLS

    Science.gov (United States)

    Inhibition of Respiratory Syncytial Virus (RSV)-Induced Inflammation by 3-Nitrotyrosine in Human Bronchial Epithelial Cells. J. M. Soukup, MPH 1, ZW. Li, MD 2 and YC. T. Huang, MD 1. 1 NHEERL, US Environmental Protection Agency, RTP, NC and 2 CEMALB, University of North Carolina,...

  10. Analysis of antiviral response in human epithelial cells infected with hepatitis E virus.

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    Pradip B Devhare

    Full Text Available Hepatitis E virus (HEV is a major cause of enterically transmitted acute hepatitis in developing nations and occurs in sporadic and epidemic forms. The disease may become severe with high mortality (20% among pregnant women. Due to lack of efficient cell culture system and small animal model, early molecular events of HEV infection are not yet known. In the present study, human lung epithelial cells, A549, were infected with HEV to monitor expression levels of genes/proteins in antiviral pathways. Both live and UV inactivated virus elicited robust induction of inflammatory cytokines/chemokines such as IL-6, IL-8, TNF-α, and RANTES within 12 h of infection. Cells exposed to soluble capsid protein showed no induction suggesting the capsid structure and not the protein being detected as the pathogen pattern by cells. A delayed up-regulation of type I interferon genes only by the live virus at 48 h post HEV infection indicated the need of virus replication. However, absence of secreted interferons till 96 h suggested possible involvement of post-transcriptional regulation of type I IFN expression. HEV infected cells showed activation of both NF-κB and IRF3 transcription factors when seen at protein levels; however, reporter gene assays showed predominant expression via NF-κB promoter as compared to IRF3 promoter. Knockdown experiments done using siRNAs showed involvement of MyD88 and TRIF adaptors in generating antiviral response thus indicating role of TLR2, TLR4 and TLR3 in sensing viral molecules. MAVS knockdown surprisingly enhanced only proinflammatory cytokines and not type I IFNs. This suggested that HEV not only down-regulates RIG-I helicase like receptor mediated IFN induction but also employs MAVS in curtailing host inflammatory response. Our findings uncover an early cellular response in HEV infection and associated molecular mechanisms suggesting the potential role of inflammatory response triggered by HEV infection in host immune

  11. Topical ganciclovir in the treatment of acute herpetic keratitis

    OpenAIRE

    Tabbara, Khalid

    2010-01-01

    Khalid F Tabbara1,2,3, Noorjehan Al Balushi11The Eye Center and The Eye Foundation for Research in Ophthalmology, Riyadh, 2Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; 3The Wilmer Ophthalmological Institute of The Johns Hopkins University School of Medicine, Baltimore, Maryland, USAAbstract: Herpetic keratitis is caused by herpes simplex virus (HSV) and is a common cause of corneal blindness. Following a primary ocular herpetic infec...

  12. New Treatments for Bacterial Keratitis

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    Raymond L. M. Wong

    2012-01-01

    Full Text Available Purpose. To review the newer treatments for bacterial keratitis. Data Sources. PubMed literature search up to April 2012. Study Selection. Key words used for literature search: “infectious keratitis”, “microbial keratitis”, “infective keratitis”, “new treatments for infectious keratitis”, “fourth generation fluoroquinolones”, “moxifloxacin”, “gatifloxacin”, “collagen cross-linking”, and “photodynamic therapy”. Data Extraction. Over 2400 articles were retrieved. Large scale studies or publications at more recent dates were selected. Data Synthesis. Broad spectrum antibiotics have been the main stay of treatment for bacterial keratitis but with the emergence of bacterial resistance; there is a need for newer antimicrobial agents and treatment methods. Fourth-generation fluoroquinolones and corneal collagen cross-linking are amongst the new treatments. In vitro studies and prospective clinical trials have shown that fourth-generation fluoroquinolones are better than the older generation fluoroquinolones and are as potent as combined fortified antibiotics against common pathogens that cause bacterial keratitis. Collagen cross-linking was shown to improve healing of infectious corneal ulcer in treatment-resistant cases or as an adjunct to antibiotics treatment. Conclusion. Fourth-generation fluoroquinolones are good alternatives to standard treatment of bacterial keratitis using combined fortified topical antibiotics. Collagen cross-linking may be considered in treatment-resistant infectious keratitis or as an adjunct to antibiotics therapy.

  13. Lysosome-associated membrane glycoprotein 3 is involved in influenza A virus replication in human lung epithelial (A549 cells

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    Wang Jianwei

    2011-08-01

    Full Text Available Abstract Background Influenza A virus mutates rapidly, rendering antiviral therapies and vaccines directed against virus-encoded targets ineffective. Knowledge of the host factors and molecular pathways exploited by influenza virus will provide further targets for novel antiviral strategies. However, the critical host factors involved in influenza virus infection have not been fully defined. Results We demonstrated that LAMP3, a member of lysosome-associated membrane glycoprotein (LAMP family, was significantly induced in human lung epithelial (A549 cells upon influenza A virus infection. Knockdown of LAMP3 expression by RNA interference attenuated production of viral nucleoprotein (NP as well as virus titers. Confocal microscopy results demonstrated that viral NP is colocalized within LAMP3 positive vesicles at early stages of virus infection. Furthermore, knockdown of LAMP3 expression led to a reduction in nuclear accumulation of viral NP and impeded virus replication. Conclusions LAMP3 is an influenza A virus inducible gene, and plays an important role in viral post-entry steps. Our observations may provide insights into the mechanism of influenza virus replication and potential targets for novel anti-influenza therapeutics.

  14. Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro.

    Directory of Open Access Journals (Sweden)

    Ussama M Abdel-Motal

    Full Text Available Although cervico-vaginal epithelial cells of the female lower genital tract provide the initial defense system against HIV-1 infection, the protection is sometimes incomplete. Thus, enhancing anti-HIV-1 humoral immunity at the mucosal cell surface by local expression of anti-HIV-1 broadly neutralizing antibodies (BnAb that block HIV-1 entry would provide an important new intervention that could slow the spread of HIV/AIDS.This study tested the hypothesis that adeno-associated virus (AAV-BnAb gene transfer to cervico-vaginal epithelial cells will lead to protection against HIV-1. Accordingly, a recombinant AAV vector that encodes human b12 anti-HIV gp120 BnAb as a single-chain variable fragment Fc fusion (scFvFc, or "minibody" was constructed. The secreted b12 minibody was shown to be biologically functional in binding to virus envelope protein, neutralizing HIV-1 and importantly, blocking transfer and infectivity of HIV-1(bal in an organotypic human vaginal epithelial cell (VEC model. Furthermore, cervico-vaginal epithelial stem cells were found to be efficiently transduced by the optimal AAV serotype mediated expression of GFP.This study provides the foundation for a novel microbicide strategy to protect against sexual transmission of HIV-1 by AAV transfer of broadly neutralizing antibody genes to cervico-vaginal epithelial stem cells that could replenish b12 BnAb secreting cells through multiple menstrual cycles.

  15. A Cross-Study Biomarker Signature of Human Bronchial Epithelial Cells Infected with Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Luiz Gustavo Gardinassi

    2016-01-01

    Full Text Available Respiratory syncytial virus (RSV is a major cause of lower respiratory tract infections in children, elderly, and immunocompromised individuals. Despite of advances in diagnosis and treatment, biomarkers of RSV infection are still unclear. To understand the host response and propose signatures of RSV infection, previous studies evaluated the transcriptional profile of the human bronchial epithelial cell line—BEAS-2B—infected with different strains of this virus. However, the evolution of statistical methods and functional analysis together with the large amount of expression data provide opportunities to uncover novel biomarkers of inflammation and infections. In view of those facts publicly available microarray datasets from RSV-infected BEAS-2B cells were analyzed with linear model-based statistics and the platform for functional analysis InnateDB. The results from those analyses argue for the reevaluation of previously reported transcription patterns and biological pathways in BEAS-2B cell lines infected with RSV. Importantly, this study revealed a biosignature constituted by genes such as ABCC4, ARMC8, BCLAF1, EZH1, FAM118A, FAM208B, FUS, HSPH1, KAZN, MAP3K2, N6AMT1, PRMT2, S100PBP, SERPINA1, TLK2, ZNF322, and ZNF337 which should be considered in the development of new molecular diagnosis tools.

  16. Initial treatment of microbial keratitis.

    Science.gov (United States)

    Blanton, C L; Rapuano, C J; Cohen, E J; Laibson, P R

    1996-04-01

    The common occurrence of failed medical treatment in microbial keratitis led us to investigate this phenomenon. We retrospectively reviewed all ulcers that presented to our department for 24 consecutive months. We classified each ulcer as either a therapeutic success or failure based on a precise definition of the response to initial antibiotic selection. We then analyzed multiple factors including: antibiotic selection, ophthalmic disease, ulcer characteristics, and management, to determine their significance in the success or failure in treating microbial keratitis. Complications were also examined. Important factors in failure were non-fortified antibiotics (P ulcers (P = 0.051) were of borderline significance. Sensitivity results reflect high sensitivity among successfully treated patients when appropriate antibiotics are chosen. This report provides insight into current practice patterns and potential means to improve success in managing microbial keratitis.

  17. Tropism and Infectivity of Influenza Virus, Including Highly Pathogenic Avian H5N1 Virus, in Ferret Tracheal Differentiated Primary Epithelial Cell Cultures

    Science.gov (United States)

    Zeng, Hui; Goldsmith, Cynthia S.; Maines, Taronna R.; Belser, Jessica A.; Gustin, Kortney M.; Pekosz, Andrew; Zaki, Sherif R.; Katz, Jacqueline M.

    2013-01-01

    Tropism and adaptation of influenza viruses to new hosts is partly dependent on the distribution of the sialic acid (SA) receptors to which the viral hemagglutinin (HA) binds. Ferrets have been established as a valuable in vivo model of influenza virus pathogenesis and transmission because of similarities to humans in the distribution of HA receptors and in clinical signs of infection. In this study, we developed a ferret tracheal differentiated primary epithelial cell culture model that consisted of a layered epithelium structure with ciliated and nonciliated cells on its apical surface. We found that human-like (α2,6-linked) receptors predominated on ciliated cells, whereas avian-like (α2,3-linked) receptors, which were less abundant, were presented on nonciliated cells. When we compared the tropism and infectivity of three human (H1 and H3) and two avian (H1 and H5) influenza viruses, we observed that the human influenza viruses primarily infected ciliated cells and replicated efficiently, whereas a highly pathogenic avian H5N1 virus (A/Vietnam/1203/2004) replicated efficiently within nonciliated cells despite a low initial infection rate. Furthermore, compared to other influenza viruses tested, VN/1203 virus replicated more efficiently in cells isolated from the lower trachea and at a higher temperature (37°C) compared to a lower temperature (33°C). VN/1203 virus infection also induced higher levels of immune mediator genes and cell death, and virus was recovered from the basolateral side of the cell monolayer. This ferret tracheal differentiated primary epithelial cell culture system provides a valuable in vitro model for studying cellular tropism, infectivity, and the pathogenesis of influenza viruses. PMID:23255802

  18. Herpetic optic neuritis associated with herpetic keratitis.

    Science.gov (United States)

    Sáenz-Francés, F; Calvo-González, C; Jiménez-Santos, M; Méndez-Hernández, C; Fernandez-Vidal, A M; Martínez-de-la-Casa, J M; García-Sánchez, J; García-Feijoó, J

    2007-01-01

    To report a case of herpetic optic neuritis associated with herpetic keratitis. A 65 year old woman presented with oedema in the nasal sector of his right papilla. Blood biochemistry, a haemogram, erythrocyte sedimentation rate and C-reactive protein were all normal. The patient was diagnosed as having a non-arteritic anterior ischaemic optic neuropathy. One week later slit lamp examination showed diffuse stromal corneal oedema and a dendritic lesion in the nasal zone of the corneal epithelium. Serology for varicela-zoster virus was positive. Treatment was started with valacyclovir given orally and topical acyclovir ointment. A week later, the optic disc swelling and corneal lesions had resolved. The precise mechanism through which the papilla and cornea were successively affected in our patient is unclear but the sensitive innervation of both these structures is provided by the nasal branch of the nasociliary nerve and the spread of herpes via this nerve could affect both sites.

  19. Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis.

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    Furusawa, Takaaki; Iwano, Hidetomo; Hiyashimizu, Yutaro; Matsubara, Kazuki; Higuchi, Hidetoshi; Nagahata, Hajime; Niwa, Hidekazu; Katayama, Yoshinari; Kinoshita, Yuta; Hagiwara, Katsuro; Iwasaki, Tomohito; Tanji, Yasunori; Yokota, Hiroshi; Tamura, Yutaka

    2016-09-01

    Bacterial keratitis of the horse is mainly caused by staphylococci, streptococci, and pseudomonads. Of these bacteria, Pseudomonas aeruginosa sometimes causes rapid corneal corruption and, in some cases, blindness. Antimicrobial resistance can make treatment very difficult. Therefore, new strategies to control bacterial infection are required. A bacteriophage (phage) is a virus that specifically infects and kills bacteria. Since phage often can lyse antibiotic-resistant bacteria because the killing mechanism is different, we examined the use of phage to treat horse bacterial keratitis. We isolated Myoviridae or Podoviridae phages, which together have a broad host range. They adsorb efficiently to host bacteria; more than 80% of the ΦR18 phage were adsorbed to host cells after 30 s. In our keratitis mouse model, the administration of phage within 3 h also could kill bacteria and suppress keratitis. A phage multiplicity of infection of 100 times the host bacterial number could kill host bacteria effectively. A cocktail of two phages suppressed bacteria in the keratitis model mouse. These data demonstrated that the phages in this study could completely prevent the keratitis caused by P. aeruginosa in a keratitis mouse model. Furthermore, these results suggest that phage may be a more effective prophylaxis for horse keratitis than the current preventive use of antibiotics. Such treatment may reduce the use of antibiotics and therefore antibiotic resistance. Further studies are required to assess phage therapy as a candidate for treatment of horse keratitis. Antibiotic-resistant bacteria are emerging all over the world. Bacteriophages have great potential for resolution of this problem. A bacteriophage, or phage, is a virus that infects bacteria specifically. As a novel therapeutic strategy against racehorse keratitis caused by Pseudomonas aeruginosa, we propose the application of phages for treatment. Phages isolated in this work had in vitro effectiveness for a broad

  20. Acanthamoeba keratitis cluster: an increase in Acanthamoeba keratitis in Australia.

    Science.gov (United States)

    Ku, Jae Yee; Chan, Fiona M; Beckingsale, Peter

    2009-03-01

    This study was undertaken in response to an increase in the number of patients treated for Acanthamoeba keratitis at a tertiary referral hospital in Brisbane, Australia. Incidence and patient characteristics were investigated over a 4-year period. A retrospective consecutive case series study was performed on patients with Acanthamoeba keratitis presenting to the Princess Alexandra Hospital between January 2003 and March 2007. Nine cases of Acanthamoeba keratitis were identified over 12 months from March 2006 to March 2007 compared with four cases over the previous 37 months from January 2003 to February 2006. This was an increase from 0.07 cases per 1000 outpatient visits to 0.42 per 1000 (P = 0.003). Of the 13 cases, 11 patients used soft contact lenses of which two used monthly extended overnight wear silicone hydrogel lenses. Of the five patients who specified the type of contact lens solution they had used, three reported using AMO Complete Moistureplus Multipurpose solution, one reported using the AMO Complete Comfortplus Multipurpose solution and one was unsure which type of AMO Complete solution they were using. There has been a significant increase in incidence of cases of Acanthamoeba keratitis presenting to our institution. The type of contact lens solution and the use of silicon hydrogel lenses combined with extended overnight wear may play a role; however, the significance is unclear given the small numbers for analysis. Further study of incidence and patient characteristics is warranted to identify risk factors and causes for the rising incidence.

  1. Respiratory syncytial virus can infect basal cells and alter human airway epithelial differentiation.

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    B David Persson

    Full Text Available Respiratory syncytial virus (RSV is a major cause of morbidity and mortality worldwide, causing severe respiratory illness in infants and immune compromised patients. The ciliated cells of the human airway epithelium have been considered to be the exclusive target of RSV, although recent data have suggested that basal cells, the progenitors for the conducting airway epithelium, may also become infected in vivo. Using either mechanical or chemical injury models, we have demonstrated a robust RSV infection of p63+ basal cells in air-liquid interface (ALI cultures of human bronchial epithelial cells. In addition, proliferating basal cells in 2D culture were also susceptible to RSV infection. We therefore tested the hypothesis that RSV infection of this progenitor cell would influence the differentiation status of the airway epithelium. RSV infection of basal cells on the day of seeding (MOI≤0.0001, resulted in the formation of an epithelium that showed a profound loss of ciliated cells and gain of secretory cells as assessed by acetylated α-tubulin and MUC5AC/MUC5B immunostaining, respectively. The mechanism driving the switch in epithelial phenotype is in part driven by the induced type I and type III interferon response that we demonstrate is triggered early following RSV infection. Neutralization of this response attenuates the RSV-induced loss of ciliated cells. Together, these data show that through infection of proliferating airway basal cells, RSV has the potential to influence the cellular composition of the airway epithelium. The resulting phenotype might be expected to contribute towards both the severity of acute infection, as well as to the longer-term consequences of viral exacerbations in patients with pre-existing respiratory diseases.

  2. Persistent Transmissible Gastroenteritis Virus Infection Enhances Enterotoxigenic Escherichia coli K88 Adhesion by Promoting Epithelial-Mesenchymal Transition in Intestinal Epithelial Cells.

    Science.gov (United States)

    Xia, Lu; Dai, Lei; Yu, Qinghua; Yang, Qian

    2017-11-01

    Transmissible gastroenteritis virus (TGEV) is a coronavirus characterized by diarrhea and high morbidity rates, and the mortality rate is 100% in piglets less than 2 weeks old. Pigs infected with TGEV often suffer secondary infection by other pathogens, which aggravates the severity of diarrhea, but the mechanisms remain unknown. Here, we hypothesized that persistent TGEV infection stimulates the epithelial-mesenchymal transition (EMT), and thus enterotoxigenic Escherichia coli (ETEC) can more easily adhere to generating cells. Intestinal epithelial cells are the primary targets of TGEV and ETEC infections. We found that TGEV can persistently infect porcine intestinal columnar epithelial cells (IPEC-J2) and cause EMT, consistent with multiple changes in key cell characteristics. Infected cells display fibroblast-like shapes; exhibit increases in levels of mesenchymal markers with a corresponding loss of epithelial markers; have enhanced expression levels of interleukin-1β (IL-1β), IL-6, IL-8, transforming growth factor β (TGF-β), and tumor necrosis factor alpha (TNF-α) mRNAs; and demonstrate increases in migratory and invasive behaviors. Additional experiments showed that the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling pathways via TGF-β is critical for the TGEV-mediated EMT process. Cellular uptake is also modified in cells that have undergone EMT. TGEV-infected cells have higher levels of integrin α5 and fibronectin and exhibit enhanced ETEC K88 adhesion. Reversal of EMT reduces ETEC K88 adhesion and inhibits the expression of integrin α5 and fibronectin. Overall, these results suggest that TGEV infection induces EMT in IPEC-J2 cells, increasing the adhesion of ETEC K88 in the intestine and facilitating dual infection. IMPORTANCE Transmissible gastroenteritis virus (TGEV) causes pig diarrhea and is often followed by secondary infection by other pathogens. In this study, we showed

  3. Rapid and sensitive diagnosis of fungal keratitis with direct PCR without template DNA extraction.

    Science.gov (United States)

    Zhao, G; Zhai, H; Yuan, Q; Sun, S; Liu, T; Xie, L

    2014-10-01

    This study was aimed at developing a direct PCR assay without template DNA extraction for the rapid and sensitive diagnosis of infectious keratitis. Eighty corneal scrapings from 67 consecutive patients with clinically suspected infectious keratitis were analysed prospectively. Direct PCR was performed with all scrapings, with specific primers for fungi, bacteria, herpes simplex virus-1 (HSV-1) and Acanthamoeba simultaneously. The results were compared with those obtained from culture, smear, and confocal microscopy. Discrepant results were resolved according to the therapeutic effects of the corresponding antimicrobial drugs. The lowest detection limit of direct PCR was ten copies of each pathogen. Sixty-six scrapings yielded positive results with direct PCR, giving a total positive detection rate of 82.5% (66/80). For 34 patients with high suspicion of fungal keratitis, the positive detection rate of direct PCR was 84.8% (39/46). This rate increased to 91.2% (31/34) when repeated scrapings were excluded, and was significantly higher than the rates obtained with culture (35.3%, 12/34) and smear (64.7%, 22/34) (p keratitis with direct PCR and culture were 98.0% and 47.1% (p keratitis, and it is expected to have an impact on the diagnosis and treatment of infectious keratitis in the future. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  4. Detection Of Hepatitis B Virus DNA In Moroccan Patients With Epithelial Ovarian Carcinoma EOC By Polymerase Chain Reaction

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    Mustapha Benhessou

    2015-08-01

    Full Text Available Abstract Epithelial ovarian cancer EOC is the most common type of ovarian cancer representing 90 of all ovarian cancers. The viruses are known as human malignancies agents. We tried to analyze the presence of Hepatitis B Virus infection in women with epithelial ovarian carcinoma. PCR-based detection of HBV infections was carried out on 50 tissue samples from patients with histologically proven EOC using consensus primers. The samples analyzed showed 8 450 positivity for HBV-DNA in cancerous ovarian tissues. All of the positive patients had serous adenocarcinoma and advanced stage disease. The results of this study suggest that hepatitis B could play a major role in the etiology of ovarian cancer.

  5. Calotropis procera-induced keratitis

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    Pandey, Nidhi; Chandrakar, A K; M.L. Garg; Patel, Santosh Singh

    2009-01-01

    Calotropis procera produces copious amounts of latex, which has been shown to possess several pharmacological properities. Its local application produces intense inflammatory response. In the 10 cases of Calotropis procera-induced keratitis reported here, the clinical picture showed corneal edema with striate keratopathy without any evidence of intraocular inflammation. The inflammation was reversed by the local application of steroid drops.

  6. Keratitis due to Shigella flexneri.

    NARCIS (Netherlands)

    Muytjens, H.L.; Eggink, C.A.; Dijkman, F.C.A.P.; Bakkers, J.M.J.E.; Melchers, W.J.G.

    2006-01-01

    Multiresistant Shigella flexneri isolates were cultured from the cornea and stool of a girl. Genetic analysis showed the isolates were identical. Shigella spp. are rare causes of ulcerative keratitis; there have only been 14 published cases since 1943. Although prognosis after local treatment is

  7. A novel rat contact lens model for Fusarium keratitis.

    Science.gov (United States)

    Abou Shousha, Mohamed; Santos, Andrea Rachelle C; Oechsler, Rafael A; Iovieno, Alfonso; Maestre-Mesa, Jorge; Ruggeri, Marco; Echegaray, Jose J; Dubovy, Sander R; Perez, Victor L; Miller, Darlene; Alfonso, Eduardo C; Bajenaru, M Livia

    2013-01-01

    The aim of this study was to develop and characterize a new contact lens-associated fungal keratitis rat model and to assess the ability of non-invasive spectral-domain optical coherence tomography (SD-OCT) to detect pathological changes in vivo in fungal keratitis. We used SD-OCT to image and measure the cornea of Sprague Dawley rats. Fusarium infection was initiated in the rat eye by fitting Fusarium solani-soaked contact lenses on the experimental eye, while the control animals received contact lenses soaked in sterile saline. The fungal infection was monitored with periodic slit-lamp examination and in vivo SD-OCT imaging of the rat eye, and confirmed by histology, counting of viable fungi in the infected rat cornea, and PCR with specific primers for Fusarium sp. We imaged and measured the rat cornea with SD-OCT. Custom-made contact lenses were developed based on the OCT measurements. Incubation of contact lenses in a F. solani suspension resulted in biofilm formation. We induced contact lens-associated Fusarium keratitis by fitting the rat eyes for 4 h with the Fusarium-contaminated contact lenses. The SD-OCT images of the cornea correlated well with the slit-lamp and histopathological results and clearly defined clinical signs of infection, namely, increased corneal thickening, loss of epithelial continuity, hyper-reflective areas representing infiltrates, and endothelial plaques characteristic of fungal infection. Moreover, in three cases, SD-OCT detected the infection without any clear findings on slit-lamp examination. Infection was confirmed with histological fungal staining, PCR, and microbiological culture positivity. We developed a highly reproducible rat contact lens model and successfully induced contact lens-associated Fusarium keratitis in this model. The clinical presentation of contact lens-associated Fusarium keratitis in the rat model is similar to the human condition. SD-OCT is a valuable tool that non-invasively revealed characteristic signs

  8. A novel rat contact lens model for Fusarium keratitis

    Science.gov (United States)

    Abou Shousha, Mohamed; Santos, Andrea Rachelle C.; Oechsler, Rafael A.; Iovieno, Alfonso; Maestre-Mesa, Jorge; Ruggeri, Marco; Echegaray, Jose J.; Dubovy, Sander R.; Perez, Victor L.; Miller, Darlene; Alfonso, Eduardo C.

    2013-01-01

    Purpose The aim of this study was to develop and characterize a new contact lens–associated fungal keratitis rat model and to assess the ability of non-invasive spectral-domain optical coherence tomography (SD-OCT) to detect pathological changes in vivo in fungal keratitis. Methods We used SD-OCT to image and measure the cornea of Sprague Dawley rats. Fusarium infection was initiated in the rat eye by fitting Fusarium solani–soaked contact lenses on the experimental eye, while the control animals received contact lenses soaked in sterile saline. The fungal infection was monitored with periodic slit-lamp examination and in vivo SD-OCT imaging of the rat eye, and confirmed by histology, counting of viable fungi in the infected rat cornea, and PCR with specific primers for Fusarium sp. Results We imaged and measured the rat cornea with SD-OCT. Custom-made contact lenses were developed based on the OCT measurements. Incubation of contact lenses in a F. solani suspension resulted in biofilm formation. We induced contact lens–associated Fusarium keratitis by fitting the rat eyes for 4 h with the Fusarium-contaminated contact lenses. The SD-OCT images of the cornea correlated well with the slit-lamp and histopathological results and clearly defined clinical signs of infection, namely, increased corneal thickening, loss of epithelial continuity, hyper-reflective areas representing infiltrates, and endothelial plaques characteristic of fungal infection. Moreover, in three cases, SD-OCT detected the infection without any clear findings on slit-lamp examination. Infection was confirmed with histological fungal staining, PCR, and microbiological culture positivity. Conclusions We developed a highly reproducible rat contact lens model and successfully induced contact lens–associated Fusarium keratitis in this model. The clinical presentation of contact lens–associated Fusarium keratitis in the rat model is similar to the human condition. SD-OCT is a valuable tool that

  9. Differential replication of avian influenza H9N2 viruses in human alveolar epithelial A549 cells

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    Peiris Malik

    2010-03-01

    Full Text Available Abstract Avian influenza virus H9N2 isolates cause a mild influenza-like illness in humans. However, the pathogenesis of the H9N2 subtypes in human remains to be investigated. Using a human alveolar epithelial cell line A549 as host, we found that A/Quail/Hong Kong/G1/97 (H9N2/G1, which shares 6 viral "internal genes" with the lethal A/Hong Kong/156/97 (H5N1/97 virus, replicates efficiently whereas other H9N2 viruses, A/Duck/Hong Kong/Y280/97 (H9N2/Y280 and A/Chicken/Hong Kong/G9/97 (H9N2/G9, replicate poorly. Interestingly, we found that there is a difference in the translation of viral protein but not in the infectivity or transcription of viral genes of these H9N2 viruses in the infected cells. This difference may possibly be explained by H9N2/G1 being more efficient on viral protein production in specific cell types. These findings suggest that the H9N2/G1 virus like its counterpart H5N1/97 may be better adapted to the human host and replicates efficiently in human alveolar epithelial cells.

  10. Epstein-Barr virus (EBV) in infectious mononucleosis: detection of the virus in tonsillar B lymphocytes but not in desquamated oropharyngeal epithelial cells

    Science.gov (United States)

    Niedobitek, G; Agathanggelou, A; Steven, N; Young, L S

    2000-01-01

    Aims—Despite its well established tropism for B cells, the nature of the cellular compartment(s) mediating primary and persistent Epstein-Barr virus (EBV) infection is still a matter of controversy. In view of the association of EBV with several lymphoid and epithelial malignancies, resolution of this issue is important. Methods—Desquamated oropharyngeal epithelial cells from 10 patients with acute infectious mononucleosis and from seven chronic virus carriers were studied for evidence of EBV infection using in situ hybridisation for the detection of the small EBV encoded RNAs (EBERs) and of the viral genome. In addition, immunocytochemistry was used to detect the BZLF1 transactivator protein of EBV. Results—There was no evidence of latent or replicative EBV infection in oropharyngeal epithelial cells in any of the samples. In contrast, EBV infected B cells were readily identified in a tonsil from a patient with infectious mononucleosis. Conclusions—The results suggest that oropharyngeal epithelial cells are not a major site of EBV infection and provide further support for the notion that B cells mediate primary and persistent EBV infection. PMID:10884920

  11. Shifting trends in microbial keratitis following penetrating keratoplasty in Taiwan.

    Science.gov (United States)

    Chen, Hung-Chi; Lee, Chia-Yi; Lin, Hung-Yu; Ma, David Hui-Kang; Chen, Phil Yeong-Fong; Hsiao, Ching-Hsi; Lin, Hsin-Chiung; Yeh, Lung-Kun; Tan, Hsin-Yuan

    2017-02-01

    To investigate the clinical and microbiological profiles from microbial keratitis following penetrating keratoplasty (PKP) in a tertiary referral center in Taiwan, the medical records of 648 consecutive patients (648 eyes) undergoing PKP between January 2003 and December 2007 were retrospectively reviewed. Patients who subsequently sustained microbial keratitis were enrolled and analyzed for potential risk factors, clinical manifestations, microbiological profiles, complications, graft survival, and final visual outcome. A total number of 42 corneal graft infections (6.5%) were recruited. Mean interval between corneal transplantation and graft infection was 12 ± 9.5 months. Potential risk factors included suture-related problems (31.0%), lid abnormalities (23.8%), persistent epithelial defect (23.8%), contact lens use (14.3%), dry eye (11.9%), and prior rejection episodes (4.8%). Lesions were discovered mostly at the donor-recipient junction ([DRJ] 45.2%). Positive cultures were identified in all of the morbid eyes, of which Pseudomonas aeruginosa was the most common pathogen (38.1%). Despite mandatory hospitalization and topical fortified antibiotics management, complications ensued such as graft failure (71.4%), hypopyon (21.4%), corneal perforation (14.3%), wound dehiscence (11.9%), and endophthalmitis (4.8%). The visual outcome was dismal that graft clarity was achieved in only 12 eyes (28.6%), and that final visual acuity deteriorated to less than 20/200 in 28 eyes (66.7%). In conclusion, microbial keratitis following PKP is a devastating event that severely impairs graft survival rate and postoperative visual outcome which usually occur within the first postoperative year. The incidence of post-PKP microbial keratitis has generally decreased in recent years whilst P. aeroginosa prevails as the leading cause of graft infection in our hospital. Close follow-up by ophthalmologists and elevated self-awareness of patients for at least one year are always

  12. Epstein-Barr virus gH is essential for penetration of B cells but also plays a role in attachment of virus to epithelial cells.

    Science.gov (United States)

    Molesworth, S J; Lake, C M; Borza, C M; Turk, S M; Hutt-Fletcher, L M

    2000-07-01

    Entry of Epstein-Barr virus (EBV) into B cells is initiated by attachment of glycoprotein gp350 to the complement receptor type 2 (CR2). A complex of three glycoproteins, gH, gL, and gp42, is subsequently required for penetration. Gp42 binds to HLA class II, which functions as an entry mediator or coreceptor and, by analogy with other herpesviruses, gH is then thought to be involved virus-cell fusion. However, entry of virus into epithelial cells is thought to be different. It can be initiated by attachment by an unknown glycoprotein in the absence of CR2. There is no interaction between gp42 and HLA class II and instead a distinct complex of only the two glycoproteins gH and gL interacts with a novel entry mediator. Again, by analogy with other viruses gH is thought to be critical to fusion. To investigate further the different roles of gH in infection of the two cell types and to examine its influence on the assembly of the gH-gL-gp42 complex, we constructed two viruses, one in which the gH open reading frame was interrupted by a cassette expressing a neomycin resistance gene and the gene for green fluorescent protein and one as a control in which the neighboring nonessential thymidine kinase gene was interrupted with the same cassette. Virus lacking gH exited from cells normally, although loss of gH resulted in rapid turnover of gL and gp42 as well. The virus bound normally to B lymphocytes but could not infect them unless cells and bound virus were treated with polyethylene glycol to induce fusion. In contrast, virus that lacked the gH complex was impaired in attachment to epithelial cells and the effects of monoclonal antibodies to gH implied that this resulted from loss of gH rather than other members of the complex. These results suggest a role for gH in both attachment and penetration into epithelial cells.

  13. Evaluation of accelerated collagen cross-linking for the treatment of melting keratitis in ten cats.

    Science.gov (United States)

    Famose, Frank

    2015-03-01

    Melting keratitis is a serious condition presenting a high risk of permanent blindness and is caused by infectious or noninfectious factors. In humans, the clinical efficacy of collagen cross-linking (CXL) has been described in the treatment of refractory infectious keratitis by arresting keratomalacia. The aim of this study was to evaluate the efficacy of accelerated CXL for the treatment of melting keratitis in cats. Ten cats were treated for unilateral melting keratitis by accelerated CXL. Corneas were irradiated by UVA (370 nm) at 30 mW/cm² irradiance for 3 min after soaking with 0.1% riboflavin in 20% dextran for 30 min (D1). Follow-up was conducted 3, 7, 14, and 30 days after treatment. Pain improvement was noted for all cases at D4 examination. Epithelial healing was observed at D8 for 9 of 10 cases and at D15 for 1 of 10 cases. Resolution of cellular infiltration was observed for all cases at D8 examination. The corneal vascularization was reduced for 9 of 10 cats by D31. At D31, all cases presented a variable degree of corneal fibrosis, but all eyes had visual function. No recurrent infection was observed. Accelerated CXL appears to be a valuable option for the treatment of melting keratitis in cats. All the cases have reached a satisfactory outcome despite the individual differences in the conditions prior to the CXL treatment and the variable presence of infectious agents. © 2013 American College of Veterinary Ophthalmologists.

  14. Microbial Keratitis After Penetrating Keratoplasty.

    Science.gov (United States)

    Sun, Jen-Pin; Chen, Wei-Li; Huang, Jehn-Yu; Hou, Yu-Chih; Wang, I-Jong; Hu, Fung-Rong

    2017-06-01

    To report the incidence, microbiological profile, graft survival, and determining factors of microbial keratitis after penetrating keratoplasty (PK). Observational case series. The study involved 51 patients (52 eyes) who were treated at a single tertiary referral center during a 10-year period. Retrospective chart review included medical records of all patients diagnosed with microbial keratitis after penetrating keratoplasty at the National Taiwan University Hospital between January 2000 and December 2009. The main outcome measures were incidence of graft infection, microbial profile, and graft survival status. There were 871 PKs performed and 67 episodes in 52 eyes of culture-positive microbial keratitis during the study period. There were 32 infectious episodes (47.8%) in the first year post-PK and 35 episodes (52.2%) after the first year post-PK. Forty-four gram-positive bacterial isolates (57.9%), 17 gram-negative bacterial isolates (22.4%), and 15 fungal isolates (19.7%) were found. Twenty-three (34.3%) grafts remained clear after the infection episode with a mean follow-up of 1127 days (range, 25-3962 days). There was no difference in graft survival rate regarding the original indication of PK or offending pathogen. Suture-related infection was associated with decreased risk of graft failure (P = .02), while the factor associated with increased risk of graft failure was usage of antiglaucoma agents (P = .01). Infectious keratitis after penetrating keratoplasty leads to a high graft failure rate. Such complications can occur before or after the first year post-PK. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Influenza A virus infection of intestinal epithelial cells enhances the adhesion ability of Crohn's disease associated Escherichia coli strains.

    Science.gov (United States)

    Aleandri, Marta; Conte, Maria Pia; Simonetti, Giovanna; Panella, Simona; Celestino, Ignacio; Checconi, Paola; Marazzato, Massimiliano; Longhi, Catia; Goldoni, Paola; Nicoletti, Mauro; Barnich, Nicolas; Palamara, Anna Teresa; Schippa, Serena; Nencioni, Lucia

    2015-01-01

    Modifications of intestinal glycoreceptors expression, in particular CEACAM6, typically found in ileal Crohn's disease (CD), favor, among the commensal species of microbiota, the enrichment in Escherichia coli. Removal of protein glycosidic residues by neuraminidase, a sialidase typical of influenza virus, increases adhesion ability of Escherichia coli to Caco-2 intestinal cells. In this study we investigated whether influenza virus infection of human intestinal epithelial cells could influence the adhesiveness of different Escherichia coli strains isolated from CD patients by altering surface glycoreceptors. Influenza virus infection of intestinal cells increased exposure of galactose and mannose residues on the cell surface. In particular, glycoreceptors Thomsen-Friedenreich and CEACAM6 were over-expressed in influenza virus infected cells. In the same experimental conditions, a significant increase in bacterial adhesiveness was observed, independently of their own adhesive ability. The increase was reverted by treatment with anti-TF and anti-CEACAM6 antibodies. Interestingly, influenza virus was able to efficiently replicate in human primary intestinal cells leading to TF exposure. Finally, intestinal infected cells produced high levels of pro-inflammatory cytokines compared to control. Overall these data suggest that influenza virus infection, could constitute an additional risk factor in CD patients.

  16. Clinical treatment on patients with infectious keratitis by chestnut thorn

    Directory of Open Access Journals (Sweden)

    Ai-Chao Zhang

    2013-09-01

    Full Text Available AIM:To investigate the clinical treatment on patients with infectious keratitis by chestnut thorn. METHODS: Retrospective analysis of 28 cases(28 eyeswith infectious keratitis due to chestnut thorn from June 2009 to October 2012. All patients had the clinical manifestations such as local infiltration, edema and ulcer formation. Chestnut thorn located deeply into corneal stroma, but did not penetrate into the anterior chamber. All patients underwent emergency surgery to remove chestnut thorn, of which 14 patients underwent corneal debridement joint multilayer amniotic membrane transplantation as the treatment group, and the other 14 patients refused amniotic membrane transplantation and had the chestnut thorn removed only as the control group. The corneal epithelial healing time, the degree of improvement of visual acuity and the incidence of complications were compared between the two groups after 3 months.RESULTS: The corneal epithelial average healing time of the treatment group was significantly shortened compared with the control group(t=13.6, PCONCLUSION: For the patients with corneal ulcer due to deep chestnut thorn, emergency surgery of corneal debridement joint multilayer amniotic membrane transplantation can promote the repair of the cornea and prevent the occurrence of complications after injury.

  17. Update on peripheral ulcerative keratitis

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    Yagci A

    2012-05-01

    Full Text Available Ayse YagciEge University, School of Medicine, Department of Ophthalmology, Izmir, TurkeyAbstract: Ulcerative inflammation of the cornea occurs in the perilimbal cornea, and is associated with autoimmune collagen vascular and arthritic diseases. Rheumatoid arthritis is the most frequent underlying disease. The tendency for peripheral location is due to the distinct morphologic and immunologic characteristics of the limbal conjunctiva, which provides access for circulating immune complexes to the peripheral cornea via the capillary network. Deposition of immune complexes in the terminal ends of limbal vessels initiates immune-mediated vasculitis, and causes inflammatory cell and protein leakage due to vessel wall damage. Development of peripheral ulcerative keratitis associated with systemic disease may represent worsening of a potentially life-threatening disease. Accompanying scleritis, particularly the necrotizing form, is usually observed in severe cases, which may result in corneal perforation and loss of vision. Although first-line treatment with systemic corticosteroids is indicated for acute phases, immunosuppressive and cytotoxic agents are required for treatment of peripheral ulcerative keratitis associated with multisystem disorders. Recently, infliximab, a chimeric antibody against proinflammatory cytokine tumor necrosis factor-alpha, was reported to be effective in cases refractory to conventional immunomodulatory therapy. The potential side effects of these therapies require close follow-up and regular laboratory surveillance.Keywords: autoimmune disease, peripheral ulcerative keratitis, treatment, tumor necrosis factor-alpha

  18. Amniotic membrane transplantation for persistent corneal ulcers and perforations in acute fungal keratitis.

    Science.gov (United States)

    Chen, Hung-Chi; Tan, Hsin-Yuan; Hsiao, Ching-Hsi; Huang, Samuel Chao-Ming; Lin, Ken-Kuo; Ma, David Hui-Kang

    2006-06-01

    To report the therapeutic effect and complications of amniotic membrane transplantation (AMT) in acute fungal keratitis. Diagnosis of fungal keratitis was confirmed by cultures in 23 eyes of 23 patients. The indications to perform AMT were to promote reepithelialization in non-healing ulcers or to prevent corneal perforation. Antifungal agents were administered throughout the whole course of hospitalization. Repeated cultures were performed immediately before AMT. The main outcome measurements were epithelial healing rate, necessity of therapeutic penetrating keratoplasty (TPK), and persistence of infection. During a mean follow-up time of 20.6 months +/- 23.22 (6-65 months) AMT was performed during the active phase of the keratitis (fungal culture was still positive) in 16 patients (69.6%), and during the inactive phase (fungal culture negative) in 7 patients (30.4%). Single-layer AMT was performed in 17 patients, and double-layer AMT was performed in 6 patients with corneal perforation and anterior chamber collapse. Complete epithelialization was observed in 12 patients (75%) in the active group and in 7 patients (100%) in the inactive group. Treatment failure requiring TPK was experienced in 4 patients (25%) in the active group. Persistent fungal keratitis was noted in 2 patients (8.7%) in that group. The final visual acuity improved in 17 cases, worsened in 2 cases, and remained unchanged in 4 cases. Twelve of the 23 eyes (52.2%) in this study preserved useful vision (20/400 and better) with or without subsequent surgeries. AMT is effective in promoting epithelialization and preventing corneal perforations in acute fungal keratitis, and there is no risk of rejection. However, the risk of persistent or recurrent infection necessitates continued antifungal treatment and patient monitoring.

  19. Keratitis with Elizabethkingia meningoseptica occurring after contact lens wear: a case report.

    Science.gov (United States)

    Yang, Young Seong; Chun, Ji Woong; Koh, Jae Woong

    2013-04-01

    To report keratitis with Elizabethkingia meningoseptica, which occurred in a healthy patient after wearing contact lenses for 6 months. A 24-year-old male patient visited our hospital with ocular pain. This patient had a history of wearing soft contact lenses for 6 months, about 10 hours per day. At initial presentation, slit lamp examination showed corneal stromal infiltrations and small epithelial defect. Microbiological examinations were performed from corneal scrapings, contact lenses, and the contact lens case and solution. The culture results from contact lenses, contact lens case and solution were all positive for Elizabethkingia meningoseptica. Thus, we could confirm that the direct cause of keratitis was contamination of the contact lenses. The patient was treated with 0.3% gatifloxacin. After treatment, the corneal epithelial defect was completely healed, and a slight residual subepithelial corneal opacity was observed. We diagnosed keratitis with Elizabethkingia meningoseptica in a healthy young male wearing soft contact lenses. We conclude that Elizabethkingia meningoseptica should be considered as a rare but potential pathogen for lens-related keratitis in a healthy host.

  20. Keratitis with Elizabethkingia meningoseptica Occurring after Contact Lens Wear: A Case Report

    OpenAIRE

    Yang, Young Seong; Chun, Ji Woong; Koh, Jae Woong

    2013-01-01

    To report keratitis with Elizabethkingia meningoseptica, which occurred in a healthy patient after wearing contact lenses for 6 months. A 24-year-old male patient visited our hospital with ocular pain. This patient had a history of wearing soft contact lenses for 6 months, about 10 hours per day. At initial presentation, slit lamp examination showed corneal stromal infiltrations and small epithelial defect. Microbiological examinations were performed from corneal scrapings, contact lenses, an...

  1. Influenza Virus Infects Epithelial Stem/Progenitor Cells of the Distal Lung: Impact on Fgfr2b-Driven Epithelial Repair.

    Directory of Open Access Journals (Sweden)

    Jennifer Quantius

    2016-06-01

    Full Text Available Influenza Virus (IV pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6high. This cell fraction expressed the stem cell antigen-1, highly enriched lung stem/progenitor cells previously characterized by the signature integrin(β4+CD200+, and upregulated the p63/krt5 regeneration program after IV-induced injury. Using 3-dimensional organoid cultures derived from these epithelial stem/progenitor cells (EpiSPC, and in vivo infection models including transgenic mice, we reveal that their expansion, barrier renewal and outcome after IV-induced injury critically depended on Fgfr2b signaling. Importantly, IV infected EpiSPC exhibited severely impaired renewal capacity due to IV-induced blockade of β-catenin-dependent Fgfr2b signaling, evidenced by loss of alveolar tissue repair capacity after intrapulmonary EpiSPC transplantation in vivo. Intratracheal application of exogenous Fgf10, however, resulted in increased engagement of non-infected EpiSPC for tissue regeneration, demonstrated by improved proliferative potential, restoration of alveolar barrier function and increased survival following IV pneumonia. Together, these data suggest that tropism of IV to distal lung stem cell niches represents an important factor of pathogenicity and highlight impaired Fgfr2b signaling as underlying mechanism. Furthermore, increase of

  2. Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells.

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    Karen L Oslund

    Full Text Available Airway epithelial cells are the first line of defense against viral infections and are instrumental in coordinating the inflammatory response. In this study, we demonstrate the synergistic stimulation of CXCL10 mRNA and protein, a key chemokine responsible for the early immune response to viral infection, following treatment of airway epithelial cells with IFN γ and influenza virus. The synergism also occurred when the cells were treated with IFN γ and a viral replication mimicker (dsRNA both in vitro and in vivo. Despite the requirement of type I interferon (IFNAR signaling in dsRNA-induced CXCL10, the synergism was independent of the IFNAR pathway since it wasn't affected by the addition of a neutralizing IFNAR antibody or the complete lack of IFNAR expression. Furthermore, the same synergistic effect was also observed when a CXCL10 promoter reporter was examined. Although the responsive promoter region contains both ISRE and NFκB sites, western blot analysis indicated that the combined treatment of IFN γ and dsRNA significantly augmented NFκB but not STAT1 activation as compared to the single treatment. Therefore, we conclude that IFN γ and dsRNA act in concert to potentiate CXCL10 expression in airway epithelial cells via an NFκB-dependent but IFNAR-STAT independent pathway and it is at least partly regulated at the transcriptional level.

  3. Peste des Petits Ruminants Virus Enters Caprine Endometrial Epithelial Cells via the Caveolae-Mediated Endocytosis Pathway

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    Bo Yang

    2018-02-01

    Full Text Available Peste des petits ruminants virus (PPRV causes an acute and highly contagious disease of sheep and goats and has spread with alarming speed around the world. The pathology of Peste des petits ruminants is linked to retrogressive changes and necrotic lesions in lymphoid tissues and epithelial cells. However, the process of PPRV entry into host epithelial cells remains largely unknown. Here, we performed a comprehensive study of the entry mechanism of PPRV into caprine endometrial epithelial cells (EECs. We clearly demonstrated that PPRV internalization was inhibited by chloroquine and ammonium chloride, which elevate the pH of various organelles. However, PPRV entry was not affected by chlorpromazine and knockdown of the clathrin heavy chain in EECs. In addition, we found that the internalization of PPRV was dependent on dynamin and membrane cholesterol and was suppressed by silencing of caveolin-1. Macropinocytosis did not play a role, but phosphatidylinositol 3-kinase (PI3K was required for PPRV internalization. Cell type and receptor-dependent differences indicated that PPRV entry into caprine fetal fibroblast cells (FFCs occurred via a different route. Taken together, our findings demonstrate that PPRV enters EECs through a cholesterol-dependent caveolae-mediated uptake mechanism that is pH-dependent and requires dynamin and PI3K but is independent of clathrin. This potentially provides insight into the entry mechanisms of other morbilliviruses.

  4. Effect of respiratory syncytial virus (RSV) infection on the adherence of pathogenic bacteria to human epithelial cells

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    Faden, H.; Hong, J.J.; Ogra, P.L.

    1986-03-01

    The effect of RSV infection on the adherence of Streptococcus pneumoniae (SP), Haemophilus influenzae (HI) and Staphylococcus aureus (SA) to human epithelial cells was determined. RSV-infected Hep-2 cell cultures at different stages of expression of surface viral antigens and bacteria labeled with /sup 3/H-thymidine were employed to examine the kinetics of bacterial adherence to virus-infected cells. RSV infection did not alter the magnitude of adherence of HI or SA to HEp-2 cells. However, adherence of SP to HEp-2 cells was significantly (P < 0.01) enhanced by prior RSV infection. The degree of adherence was directly related to the amount of viral antigen expressed on the cell surface. The adherence was temperature dependent, with maximal adherence observed at 37/sup 0/C. Heat-inactivation of SP did not alter adherence characteristics. These data suggest that RSV infection increases adherence of SP to the surface of epithelial cells in vitro. Since attachment of bacteria to mucosal surfaces is the first step in many infections, it is suggested that viral infections of epithelial cells render them more susceptible to bacterial adherence. Thus, RSV infection in vivo may predispose children to SP infections, such as in otitis media, by increasing colonization with SP.

  5. Epstein-Barr virus infection of polarized epithelial cells via the basolateral surface by memory B cell-mediated transfer infection.

    Science.gov (United States)

    Shannon-Lowe, Claire; Rowe, Martin

    2011-05-01

    Epstein Barr virus (EBV) exhibits a distinct tropism for both B cells and epithelial cells. The virus persists as a latent infection of memory B cells in healthy individuals, but a role for infection of normal epithelial is also likely. Infection of B cells is initiated by the interaction of the major EBV glycoprotein gp350 with CD21 on the B cell surface. Fusion is triggered by the interaction of the EBV glycoprotein, gp42 with HLA class II, and is thereafter mediated by the core fusion complex, gH/gL/gp42. In contrast, direct infection of CD21-negative epithelial cells is inefficient, but efficient infection can be achieved by a process called transfer infection. In this study, we characterise the molecular interactions involved in the three stages of transfer infection of epithelial cells: (i) CD21-mediated co-capping of EBV and integrins on B cells, and activation of the adhesion molecules, (ii) conjugate formation between EBV-loaded B cells and epithelial cells via the capped adhesion molecules, and (iii) interaction of EBV glycoproteins with epithelial cells, with subsequent fusion and uptake of virions. Infection of epithelial cells required the EBV gH and gL glycoproteins, but not gp42. Using an in vitro model of normal polarized epithelia, we demonstrated that polarization of the EBV receptor(s) and adhesion molecules restricted transfer infection to the basolateral surface. Furthermore, the adhesions between EBV-loaded B cells and the basolateral surface of epithelial cells included CD11b on the B cell interacting with heparan sulphate moieties of CD44v3 and LEEP-CAM on epithelial cells. Consequently, transfer infection was efficiently mediated via CD11b-positive memory B cells but not by CD11b-negative naïve B cells. Together, these findings have important implications for understanding the mechanisms of EBV infection of normal and pre-malignant epithelial cells in vivo.

  6. Cross-linking for microbial keratitis.

    Science.gov (United States)

    Chan, Tommy C Y; Agarwal, Tushar; Vajpayee, Rasik B; Jhanji, Vishal

    2016-07-01

    Microbial keratitis is one of the leading causes of ocular morbidity. The standard treatment consists of antibiotics, which is intensive and is fraught with risks of antibiotic resistance. Corneal collagen cross-linking (CXL) has recently been advocated as an adjunctive therapy for management of microbial keratitis. The addition of CXL to ongoing antimicrobial treatment can have a potential effect on overall duration of the disease, need for corneal transplantation, final visual outcome, and long-term impact on drug resistance pattern. CXL has been used in cases with bacterial, fungal as well as amoebic keratitis. However, so far the reported results have been variable and the evidence is largely anecdotal. The debate over the safety and efficacy of this modality continues especially with regards to its utilization in early phases of the disease when the corneal involvement is limited to the anterior stroma. CXL appears to be a promising adjunctive treatment in selective cases of mild to moderate bacterial keratitis. Its efficacy in fungal and amoebic keratitis is questionable. Treatment protocols in microbial keratitis need to be individualized. Long-term, prospective, randomized trials are needed to determine its usefulness in microbial keratitis.

  7. Allovahlkampfia spelaea Causing Keratitis in Humans.

    Science.gov (United States)

    Tolba, Mohammed Essa Marghany; Huseein, Enas Abdelhameed Mahmoud; Farrag, Haiam Mohamed Mahmoud; Mohamed, Hanan El Deek; Kobayashi, Seiki; Suzuki, Jun; Ali, Tarek Ahmed Mohamed; Sugano, Sumio

    2016-07-01

    Free-living amoebae are present worldwide. They can survive in different environment causing human diseases in some instances. Acanthamoeba sp. is known for causing sight-threatening keratitis in humans. Free-living amoeba keratitis is more common in developing countries. Amoebae of family Vahlkampfiidae are rarely reported to cause such affections. A new genus, Allovahlkampfia spelaea was recently identified from caves with no data about pathogenicity in humans. We tried to identify the causative free-living amoeba in a case of keratitis in an Egyptian patient using morphological and molecular techniques. Pathogenic amoebae were culture using monoxenic culture system. Identification through morphological features and 18S ribosomal RNA subunit DNA amplification and sequencing was done. Pathogenicity to laboratory rabbits and ability to produce keratitis were assessed experimentally. Allovahlkampfia spelaea was identified as a cause of human keratitis. Whole sequence of 18S ribosomal subunit DNA was sequenced and assembled. The Egyptian strain was closely related to SK1 strain isolated in Slovenia. The ability to induce keratitis was confirmed using animal model. This the first time to report Allovahlkampfia spelaea as a human pathogen. Combining both molecular and morphological identification is critical to correctly diagnose amoebae causing keratitis in humans. Use of different pairs of primers and sequencing amplified DNA is needed to prevent misdiagnosis.

  8. High degree of overlap between responses to a virus and to the house dust mite allergen in airway epithelial cells.

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    Korneliusz Golebski

    Full Text Available BACKGROUND: Airway epithelium is widely considered to play an active role in immune responses through its ability to detect changes in the environment and to generate a microenvironment for immune competent cells. Therefore, besides its role as a physical barrier, epithelium affects the outcome of the immune response by the production of various pro-inflammatory mediators. METHODS: We stimulated airway epithelial cells with viral double stranded RNA analogue poly(I:C or with house dust mite in a time course of 24 hours. In order to determine cytokines production by stimulated cells, we performed multiplex enzyme linked immunosorbant assay (ELISA. RESULTS: We demonstrate that the temporal pattern of the genes that respond to virus exposure in airway epithelium resembles to a significant degree their pattern of response to HDM. The gene expression pattern of EGR1, DUSP1, FOSL1, JUN, MYC, and IL6 is rather similar after viral (poly(I:C and HDM exposure. However, both triggers also induce a specific response (e.g. ATF3, FOS, and NFKB1. We confirmed these data by showing that epithelial cells produce a variety of similar mediators in response to both poly(I:C and HDM challenge (IL1-RA, IL-17, IFN-α and MIP1-α, sometimes with a quantitative difference in response (IL2-R, IL-6, IL-8, MCP-1, MIG, and HGF. Interestingly, only four mediators (IL-12, IP-10, RANTES and VEGF where up-regulated specifically by poly(I:C and not by HDM. Additionally, we report that pre-exposure to HDM deregulates production of cytokines and mediators in response to poly(I:C. CONCLUSIONS: Epithelial cells responses to the HDM-allergen and a virus strongly resemble both in gene expression and in protein level explaining why these two responses may affect each other.

  9. Leukocyte-derived IFN-α/β and epithelial IFN-λ constitute a compartmentalized mucosal defense system that restricts enteric virus infections.

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    Tanel Mahlakõiv

    2015-04-01

    Full Text Available Epithelial cells are a major port of entry for many viruses, but the molecular networks which protect barrier surfaces against viral infections are incompletely understood. Viral infections induce simultaneous production of type I (IFN-α/β and type III (IFN-λ interferons. All nucleated cells are believed to respond to IFN-α/β, whereas IFN-λ responses are largely confined to epithelial cells. We observed that intestinal epithelial cells, unlike hematopoietic cells of this organ, express only very low levels of functional IFN-α/β receptors. Accordingly, after oral infection of IFN-α/β receptor-deficient mice, human reovirus type 3 specifically infected cells in the lamina propria but, strikingly, did not productively replicate in gut epithelial cells. By contrast, reovirus replicated almost exclusively in gut epithelial cells of IFN-λ receptor-deficient mice, suggesting that the gut mucosa is equipped with a compartmentalized IFN system in which epithelial cells mainly respond to IFN-λ that they produce after viral infection, whereas other cells of the gut mostly rely on IFN-α/β for antiviral defense. In suckling mice with IFN-λ receptor deficiency, reovirus replicated in the gut epithelium and additionally infected epithelial cells lining the bile ducts, indicating that infants may use IFN-λ for the control of virus infections in various epithelia-rich tissues. Thus, IFN-λ should be regarded as an autonomous virus defense system of the gut mucosa and other epithelial barriers that may have evolved to avoid unnecessarily frequent triggering of the IFN-α/β system which would induce exacerbated inflammation.

  10. Leukocyte-derived IFN-α/β and epithelial IFN-λ constitute a compartmentalized mucosal defense system that restricts enteric virus infections.

    Science.gov (United States)

    Mahlakõiv, Tanel; Hernandez, Pedro; Gronke, Konrad; Diefenbach, Andreas; Staeheli, Peter

    2015-04-01

    Epithelial cells are a major port of entry for many viruses, but the molecular networks which protect barrier surfaces against viral infections are incompletely understood. Viral infections induce simultaneous production of type I (IFN-α/β) and type III (IFN-λ) interferons. All nucleated cells are believed to respond to IFN-α/β, whereas IFN-λ responses are largely confined to epithelial cells. We observed that intestinal epithelial cells, unlike hematopoietic cells of this organ, express only very low levels of functional IFN-α/β receptors. Accordingly, after oral infection of IFN-α/β receptor-deficient mice, human reovirus type 3 specifically infected cells in the lamina propria but, strikingly, did not productively replicate in gut epithelial cells. By contrast, reovirus replicated almost exclusively in gut epithelial cells of IFN-λ receptor-deficient mice, suggesting that the gut mucosa is equipped with a compartmentalized IFN system in which epithelial cells mainly respond to IFN-λ that they produce after viral infection, whereas other cells of the gut mostly rely on IFN-α/β for antiviral defense. In suckling mice with IFN-λ receptor deficiency, reovirus replicated in the gut epithelium and additionally infected epithelial cells lining the bile ducts, indicating that infants may use IFN-λ for the control of virus infections in various epithelia-rich tissues. Thus, IFN-λ should be regarded as an autonomous virus defense system of the gut mucosa and other epithelial barriers that may have evolved to avoid unnecessarily frequent triggering of the IFN-α/β system which would induce exacerbated inflammation.

  11. Conjunctival geographic ulcer: an overlooked sign of herpes simplex virus infection.

    Science.gov (United States)

    Hung, Jia-Horung; Chu, Chang-Yao; Lee, Chaw-Ning; Hsu, Chao-Kai; Lee, Julia Yu-Yun; Wang, Jen-Ren; Chang, Kung-Chao; Huang, Fu-Chin

    2015-03-01

    Herpes simplex virus (HSV) ocular infection causes significant visual burden worldwide. Despite the fact that dendritic or geographic corneal ulcers are typical findings in HSV epithelial keratitis, conjunctival ulcer as a sign of HSV infection has rarely been reported. Although easily overlooked, this important sign could be enhanced by fluorescein staining. We report two cases of conjunctival geographic ulcers proven to be HSV infection by viral isolation and polymerase chain reaction (PCR). One patient had bilateral disease and blepharitis, and the other had unilateral involvement without skin lesions. With timely diagnosis and proper management, excellent visual outcome can be expected. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Ganciclovir ophthalmic gel 0.15%: safety and efficacy of a new treatment for herpes simplex keratitis.

    Science.gov (United States)

    Kaufman, Herbert E; Haw, Weldon H

    2012-07-01

    Until the availability of ganciclovir ophthalmic gel in 2009, the only option for treating herpes simplex (HSV) keratitis in the USA has been trifluridine (TFT), a compound with tolerability issues related to its nonselective inhibition of DNA replication in both normal cells and virus-infected cells. Ganciclovir has selective pharmacologic activity on viral thymidine kinase and a lower potential for toxicity to healthy human cells. Our objective was to evaluate safety and efficacy findings reported with the use of ganciclovir ophthalmic gel, both for HSV keratitis and other potential clinical indications. Clinical and preclinical data with ganciclovir were identified through a comprehensive electronic search of PubMed and Medline, using the search terms ganciclovir, ganciclovir 0.15% ophthalmic gel, acyclovir, acyclovir ointment 3%, herpes simplex keratitis, treatment of herpes simplex keratitis, and adenoviral keratoconjunctivitis. The authors were also granted access to previously unpublished ganciclovir surveillance safety data from Bausch & Lomb, Inc. No clinical data comparing ganciclovir ophthalmic gel to 1% trifluorothymidine (TFT) for HSV keratitis could be identified. Four international, randomized, multicenter clinical trials have demonstrated that ganciclovir gel is at least as effective as acyclovir ointment for the treatment of HSV keratitis. Ganciclovir gel was better tolerated, with lower rates of blurred vision, eye irritation, and punctate keratitis. Recent data also indicate it may hold promise as a treatment for adenoviral keratoconjunctivitis. Worldwide safety surveillance data collected over the past 10-15 years in over 30 countries suggests an extremely low rate of spontaneously reported adverse events with ganciclovir ophthalmic gel. Current data suggest that ganciclovir ophthalmic gel has similar efficacy as acyclovir ointment for the treatment of HSV keratitis and is better tolerated. Clinical head-to-head studies comparing ganciclovir and

  13. Nocardia transvalensis keratitis: an emerging pathology among travelers returning from Asia

    Science.gov (United States)

    2011-01-01

    Background The incidence rate of Nocardia keratitis is increasing, with new species identified thanks to molecular methods. We herein report a case of Nocardia transvalensis keratitis, illustrating this emerging pathology among travellers returning from Asia. Case presentation A 23-year-old man presented with a 10-week history of ocular pain, redness, and blurred vision in his right eye following a projectile foreign body impacting the cornea while motor biking in Thaïland. At presentation, a central epithelial defect with a central whitish stromal infiltrate associated with pinhead satellite infiltrates was observed. Identification with 16S rRNA PCR sequencing and microbiological culture of corneal scraping and revealed N. transvalensis as the causative organism. Treatment was initiated with intensive topical amikacin, oral ketoconazole and oral doxycycline. After a four-week treatment period, the corneal infiltrate decreased so that only a faint subepithelial opacity remained. Conclusion Nocardia organisms should be suspected as the causative agent of any case of keratitis in travelers returning from Asia. With appropriate therapy, Nocardia keratitis resolves, resulting in good visual outcome. PMID:22040176

  14. Fungal keratitis - improving diagnostics by confocal microscopy

    DEFF Research Database (Denmark)

    Nielsen, Esben; Heegaard, S; Prause, J U

    2013-01-01

    Purpose: Introducing a simple image grading system to support the interpretation of in vivo confocal microscopy (IVCM) images in filamentous fungal keratitis. Setting: Clinical and confocal studies took place at the Department of Ophthalmology, Aarhus University Hospital, Denmark. Histopathological...... analysis was performed at the Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark. Methods: A recent series of consecutive patients with filamentous fungal keratitis is presented to demonstrate the results from in-house IVCM. Based upon our experience...... with IVCM and previously published images, we composed a grading system for interpreting IVCM images of filamentous fungal keratitis. Results: A recent case series of filamentous fungal keratitis from 2011 to 2012 was examined. There were 3 male and 3 female patients. Mean age was 44.5 years (range 12...

  15. Microbial keratitis in West and East Malaysia

    OpenAIRE

    Vanitha Ratnalingam; Thiageswari Umapathy; Kala Sumugam; Hanida Hanafi; Shamala Retnasabapathy

    2017-01-01

    AIM: To evaluate the epidemiological and etiological factors of microbial keratitis seen in tertiary hospitals in West and East Malaysia.METHODS: A total of 207 patients were enrolled. Patients referred for microbial keratitis to Sungai Buloh Hospital and Kuala Lumpur Hospital in West Malaysia and Queen Elizabeth Hospital and Kuching General Hospital in East Malaysia were recruited. Risk factors were documented. Corneal scrapings for microscopy and culture were performed.RESULTS: The most com...

  16. Hendra and Nipah virus infection in cultured human olfactory epithelial cells

    NARCIS (Netherlands)

    Borisevich, V. (Viktoriya); Ozdener, M.H. (Mehmet Hakan); Malik, B. (Bilal); B. Rockx (Barry)

    2017-01-01

    textabstractHenipaviruses are emerging zoonotic viruses and causative agents of encephalitis in humans. However, the mechanisms of entry into the central nervous system (CNS) in humans are not known. Here, we evaluated the possible role of olfactory epithelium in virus entry into the CNS. We

  17. Fungal keratitis - improving diagnostics by confocal microscopy.

    Science.gov (United States)

    Nielsen, E; Heegaard, S; Prause, J U; Ivarsen, A; Mortensen, K L; Hjortdal, J

    2013-09-01

    Introducing a simple image grading system to support the interpretation of in vivo confocal microscopy (IVCM) images in filamentous fungal keratitis. Clinical and confocal studies took place at the Department of Ophthalmology, Aarhus University Hospital, Denmark. Histopathological analysis was performed at the Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark. A recent series of consecutive patients with filamentous fungal keratitis is presented to demonstrate the results from in-house IVCM. Based upon our experience with IVCM and previously published images, we composed a grading system for interpreting IVCM images of filamentous fungal keratitis. A recent case series of filamentous fungal keratitis from 2011 to 2012 was examined. There were 3 male and 3 female patients. Mean age was 44.5 years (range 12-69), 6 out of 17 (35%) cultures were positive and a total of 6/7 (86%) IVCM scans were positive. Three different categories of IVCM results for the grading of diagnostic certainty were formed. IVCM is a valuable tool for diagnosing filamentous fungal keratitis. In order to improve the reliability of IVCM, we suggest implementing a simple and clinically applicable grading system for aiding the interpretation of IVCM images of filamentous fungal keratitis.

  18. Fungal Keratitis - Improving Diagnostics by Confocal Microscopy

    Directory of Open Access Journals (Sweden)

    Esben Nielsen

    2013-12-01

    Full Text Available Purpose: Introducing a simple image grading system to support the interpretation of in vivo confocal microscopy (IVCM images in filamentous fungal keratitis. Setting: Clinical and confocal studies took place at the Department of Ophthalmology, Aarhus University Hospital, Denmark. Histopathological analysis was performed at the Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark. Methods: A recent series of consecutive patients with filamentous fungal keratitis is presented to demonstrate the results from in-house IVCM. Based upon our experience with IVCM and previously published images, we composed a grading system for interpreting IVCM images of filamentous fungal keratitis. Results: A recent case series of filamentous fungal keratitis from 2011 to 2012 was examined. There were 3 male and 3 female patients. Mean age was 44.5 years (range 12-69, 6 out of 17 (35% cultures were positive and a total of 6/7 (86% IVCM scans were positive. Three different categories of IVCM results for the grading of diagnostic certainty were formed. Conclusion: IVCM is a valuable tool for diagnosing filamentous fungal keratitis. In order to improve the reliability of IVCM, we suggest implementing a simple and clinically applicable grading system for aiding the interpretation of IVCM images of filamentous fungal keratitis.

  19. Clinical experience in managing Fusarium solani keratitis.

    Science.gov (United States)

    Lin, H-C; Chu, P-H; Kuo, Y-H; Shen, S-C

    2005-05-01

    Fusarium solani keratitis is a rare ocular infectious disease. The clinical characteristics and treatment methods of 18 patients with culture proven F. solani keratitis between July 1997 and December 2003 and with a follow-up period of more than 4 months were analysed retrospectively. The patients were divided into two groups based on the severity of keratitis. Group A (n = 13) displayed non-severe keratitis and were treated with debridement, lamellar keratectomy and antifungal medication. Group B (n = 5) displayed severe keratomycosis and were treated with lamellar keratectomy combined with amniotic membrane transplantation (AMT) and antifungal medication. In group A, wound healing did not interfere with the integrity of the anterior chamber. The mean re-epithelialisation time was 12.67 days (range: 5-21 days). All patients were free of major immediate postoperative complications. In group B, AMT preserved the anterior chamber integrity in two cases, but failed to do so in the other three cases. Therapeutic patch grafts were required in these three cases. Non-severe F. solani keratitis is best treated with superficial keratectomy. Timely AMT combined with lamellar keratectomy appears to be an adjuvant therapy for severe keratomycosis and avoiding emergent therapeutic penetrating keratoplasty. However, AMT was effective in cases involving non-suppurative Fusarium keratitis.

  20. Proteomics in the Study of Bacterial Keratitis

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    Rachida Bouhenni

    2015-12-01

    Full Text Available Bacterial keratitis is a serious ocular infection that can cause severe visual loss if treatment is not initiated at an early stage. It is most commonly caused by Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, or Serratia species. Depending on the invading organism, bacterial keratitis can progress rapidly, leading to corneal destruction and potential blindness. Common risk factors for bacterial keratitis include contact lens wear, ocular trauma, ocular surface disease, ocular surgery, lid deformity, chronic use of topical steroids, contaminated ocular medications or solutions, and systemic immunosuppression. The pathogenesis of bacterial keratitis, which depends on the bacterium-host interaction and the virulence of the invading bacterium, is complicated and not completely understood. This review highlights some of the proteomic technologies that have been used to identify virulence factors and the host response to infections of bacterial keratitis in order to understand the disease process and develop improved methods of diagnosis and treatment. Although work in this field is not abundant, proteomic technologies have provided valuable information toward our current knowledge of bacterial keratitis. More studies using global proteomic approaches are warranted because it is an important tool to identify novel targets for intervention and prevention of corneal damage caused by these virulent microorganisms.

  1. Proteomic analysis of mitochondria in respiratory epithelial cells infected with human respiratory syncytial virus and functional implications for virus and cell biology.

    Science.gov (United States)

    Munday, Diane C; Howell, Gareth; Barr, John N; Hiscox, Julian A

    2015-03-01

    The aim of this study was to quantitatively characterise the mitochondrial proteome of airway epithelial cells infected with human respiratory syncytial virus (HRSV), a major cause of paediatric illness. Quantitative proteomics, underpinned by stable isotope labelling with amino acids in cell culture, coupled to LC-MS/MS, was applied to mitochondrial fractions prepared from HRSV-infected and mock-infected cells 12 and 24 h post-infection. Datasets were analysed using ingenuity pathway analysis, and the results were validated and characterised using bioimaging, targeted inhibition and gene depletion. The data quantitatively indicated that antiviral signalling proteins converged on mitochondria during HRSV infection. The mitochondrial receptor protein Tom70 was found to act in an antiviral manner, while its chaperone, Hsp90, was confirmed to be a positive viral factor. Proteins associated with different organelles were also co-enriched in the mitochondrial fractions from HRSV-infected cells, suggesting that alterations in organelle dynamics and membrane associations occur during virus infection. Protein and pathway-specific alterations occur to the mitochondrial proteome in a spatial and temporal manner during HRSV infection, suggesting that this organelle may have altered functions. These could be targeted as part of potential therapeutic strategies to disrupt virus biology. © 2014 Royal Pharmaceutical Society.

  2. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment

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    Yan Cao

    2017-01-01

    Full Text Available Peripheral ulcerative keratitis (PUK is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, Wegener granulomatosis (WG, relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis.

  3. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment

    Science.gov (United States)

    Cao, Yan; Zhang, Wensong; Wu, Jie; Zhang, Hong

    2017-01-01

    Peripheral ulcerative keratitis (PUK) is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Wegener granulomatosis (WG), relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis. PMID:28785483

  4. Results with the Boston Type I keratoprosthesis after Acanthamoeba keratitis.

    Science.gov (United States)

    Santos, Albert; Silva, Luzia Diegues; de Sousa, Luciene Barbosa; de Freitas, Denise; de Oliveira, Lauro Augusto

    2017-06-01

    To report the outcomes of implantation of the Boston Type I keratoprosthesis in three patients with Acanthamoeba keratitis (AK), a severe infection that can lead to significant visual loss. Case series reporting three patients with difficult cases of AK that needed multiple corneal transplantations and glaucoma surgeries. All patients were implanted with the Boston Type I keratoprosthesis device. The main outcomes measure were the visual function and anatomical retention after implantation of the Boston Type I keratoprosthesis. All patients retained the device over the long-term and had good visual function. In one patient a retroprosthetic membrane developed and in another patient an epithelial lip developed over the anterior surface of the keratoprosthesis. The visual acuities range from 20/25 to 20/80 in the implanted eyes. The Boston Type I keratoprosthesis resulted in good anatomic and functional results after multiple graft failures after AK.

  5. [Contact lens-related keratitis].

    Science.gov (United States)

    Steiber, Zita; Berta, András; Módis, László

    2013-11-10

    Nowadays, keratitis, corneal infection due to wearing contact lens means an increasingly serious problem. Neglected cases may lead to corneal damage that can cause blindness in cases of otherwise healthy eyes. Early diagnosis based on the clinical picture and the typical patient history is an important way of prevention. Prophylaxis is substantial to avoid bacterial and viral infection that is highly essential in this group of diseases. Teaching contact lens wearers the proper contact lens care, storage, sterility, and hygiene regulations is of great importance. In case of corneal inflammation early accurate diagnosis supported by microbiological culture from contact lenses, storage boxes or cornea is very useful. Thereafter, targeted drug therapy or in therapy-resistant cases surgical treatment may even be necessary in order to sustain suitable visual acuity.

  6. Keratoneuritis is not pathognomonic of Acanthamoeba keratitis: a case report of Pseudomonas keratitis.

    Science.gov (United States)

    Roels, Dimitri; De Craene, Sophie; Kestelyn, Philippe

    2017-02-01

    The presence of keratoneuritis in a radial pattern is considered to be a virtually pathognomonic sign of Acanthamoeba keratitis. We report a case of a massive keratoneuritis as a presenting sign in Pseudomonas keratitis in a contact lens wearer, thereby further challenging this concept.

  7. Curative effect assessment of bandage contact lens in neurogenic keratitis

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    Yu-Zhao Sun

    2014-12-01

    Full Text Available AIM:To observe the curative effect of bandage contact lens in neurogenic keratitis.METHODS:Twenty cases of neurogenic keratitis were studied attheDepartment of Ophthalmology, the first Affiliated Hospital of China Medical University, between October 2012 and June 2013. These included 13 males and 7 females, aged from 35 to 88y. Patients were voluntarily divided into an experimental group (lens wearing group, n=10 and control group (drug therapy, n=10. In experimental group patients wore silicone hydrogel bandage soft contact lens. Both groups used the following eyedrops:0.5% levofloxacin TID; 0.5% Sodium carboxymethyl cellulose QID; fibroblast growth factor BID; ganciclovir BID [cases complicated with herpes simplex virus (HSV]; compound tropicamide BID (cases concurrent hypopyon. The healing time of corneal ulcer and complication rates were observed in the two groups.RESULTS: The healing time of corneal ulcer in the experimental group was 10.80±4.44d versus 46.70±13.88d in the control group (P<0.05. No complications occurred in the experimental group, except for the lens falling off twice in one case, the patient recovered eight days after rewearing the lens. While in the control group, all cases vascularized, 2 cases were complicated with descemetocele that recovered with amniotic membrane transplantation and 1 case was complicated with corneal perforation that recovered by autologous conjunctival flap covering.CONCLUSION: Bandage contact lens is a safe and effective method of treating neurogenic keratitis and significantly shortened the healing time of corneal ulcer.

  8. Examination of epithelial tissue cytokine response to natural peste des petits ruminants virus (PPRV) infection in sheep and goats by immunohistochemistry.

    Science.gov (United States)

    Atmaca, H T; Kul, O

    2012-01-01

    In this study, we aimed to evaluate expression of IL-4, IL-10, TNF-α, IFN-γ and iNOS in lingual, buccal mucosa and lung epithelial tissue using immunoperoxidase technique and to compare with the tissues of control animals. The tissues used in the study were collected from 17 PPRV-affected and 5 healthy sheep and goats. In PPRV positive animals, the lungs, lingual and buccal mucosa had significantly higher iNOS, IFN-γ and TNF-α expressions compared to control group animals. There was no significant difference between PPRV positive and control groups for IL-4 and IL-10 expressions of epithelial tissues. In conclusion, the epithelial tissues infected by PPRV showed significant iNOS, IFN-γ and TNF-α expressions and they might play an important role in the initiation and regulation of cytokine response, as they take place in the first host barrier to be in contact with PPRV. It is suggested that the more epithelial damage produced by PPRV the more cytokine response may result in the infected epithelial cells. The first demonstration of iNOS expression and epithelial cytokine response to PPRV in natural cases is important because it may contribute to an early initiation of systemic immunity against PPRV infection, in addition to direct elimination of the virus during the initial epithelial phase of the infection.

  9. Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.

    Directory of Open Access Journals (Sweden)

    Katrin Högner

    2013-02-01

    Full Text Available Influenza viruses (IV cause pneumonia in humans with progression to lung failure and fatal outcome. Dysregulated release of cytokines including type I interferons (IFNs has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection. Using ex vivo and in vivo IV infection models, we demonstrate that alveolar macrophage (AM-expressed IFN-β significantly contributes to IV-induced alveolar epithelial cell (AEC injury by autocrine induction of the pro-apoptotic factor TNF-related apoptosis-inducing ligand (TRAIL. Of note, TRAIL was highly upregulated in and released from AM of patients with pandemic H1N1 IV-induced acute lung injury. Elucidating the cell-specific underlying signalling pathways revealed that IV infection induced IFN-β release in AM in a protein kinase R- (PKR- and NF-κB-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-β and TRAIL displayed reduced alveolar epithelial cell apoptosis and attenuated lung injury during severe IV pneumonia. Together, we demonstrate that macrophage-released type I IFNs, apart from their well-known anti-viral properties, contribute to IV-induced AEC damage and lung injury by autocrine induction of the pro-apoptotic factor TRAIL. Our data suggest that therapeutic targeting of the macrophage IFN-β-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury.

  10. Practice patterns for herpes simplex keratitis: A survey of ophthalmologists in Gulf Coast countries.

    Science.gov (United States)

    Alkhayyal, Mashael A; Stone, Donald U

    2017-01-01

    Herpes simplex is a common cause of visual disability, and there are published evidence-based guidelines for therapy. This survey aims to determine the preferred practice patterns of ophthalmologists in Gulf Coast Countries regarding herpetic eye disease, as well as identify areas of controversy or barriers to acceptance of evidence-based protocols. Anonymous web-based survey of ophthalmologists in Saudi Arabia, Bahrain, the United Arab Emirates, and Oman. There were 48 responses to the survey. For a first episode of epithelial dendritic keratitis, 28.2% reported "observation" rather than specific therapy. The majority of respondents utilize oral or topical antiviral for epithelial keratitis, with oral antiviral being the most popular (43.6%). The majority also included a corticosteroid with antiviral for stromal keratitis (83.9%) or iritis (70.3%). Over 90% prescribe a prophylactic antiviral after keratoplasty for herpetic eye disease, although the length of therapy ranged widely from disease was ranked as the most important factor when considering antiviral prophylaxis, followed by risk of adverse effects. Topical cyclosporine was utilized "never or almost never" by 76.9% of respondents. Most respondents report following evidence-based guidelines. There was less consensus in areas where there are remaining knowledge gaps, such as the length of antiviral prophylaxis after keratoplasty and the potential role for topical cyclosporine.

  11. Influenza A virus protein PB1-F2 exacerbates IFN-beta expression of human respiratory epithelial cells.

    Science.gov (United States)

    Le Goffic, Ronan; Bouguyon, Edwige; Chevalier, Christophe; Vidic, Jasmina; Da Costa, Bruno; Leymarie, Olivier; Bourdieu, Christiane; Decamps, Laure; Dhorne-Pollet, Sophie; Delmas, Bernard

    2010-10-15

    The PB1-F2 protein of the influenza A virus (IAV) contributes to viral pathogenesis by a mechanism that is not well understood. PB1-F2 was shown to modulate apoptosis and to be targeted by the CD8(+) T cell response. In this study, we examined the downstream effects of PB1-F2 protein during IAV infection by measuring expression of the cellular genes in response to infection with wild-type WSN/33 and PB1-F2 knockout viruses in human lung epithelial cells. Wild-type virus infection resulted in a significant induction of genes involved in innate immunity. Knocking out the PB1-F2 gene strongly decreased the magnitude of expression of cellular genes implicated in antiviral response and MHC class I Ag presentation, suggesting that PB1-F2 exacerbates innate immune response. Biological network analysis revealed the IFN pathway as a link between PB1-F2 and deregulated genes. Using quantitative RT-PCR and IFN-β gene reporter assay, we determined that PB1-F2 mediates an upregulation of IFN-β expression that is dependent on NF-κB but not on AP-1 and IFN regulatory factor-3 transcription factors. Recombinant viruses knocked out for the PB1-F2 and/or the nonstructural viral protein 1 (the viral antagonist of the IFN response) genes provide further evidence that PB1-F2 increases IFN-β expression and that nonstructural viral protein 1 strongly antagonizes the effect of PB1-F2 on the innate response. Finally, we compared the effect of PB1-F2 variants taken from several IAV strains on IFN-β expression and found that PB1-F2-mediated IFN-β induction is significantly influenced by its amino acid sequence, demonstrating its importance in the host cell response triggered by IAV infection.

  12. Human immunodeficiency virus receptor and coreceptor expression on human uterine epithelial cells: regulation of expression during the menstrual cycle and implications for human immunodeficiency virus infection.

    Science.gov (United States)

    Yeaman, Grant R; Howell, Alexandra L; Weldon, Sally; Demian, Douglas J; Collins, Jane E; O'Connell, Denise M; Asin, Susana N; Wira, Charles R; Fanger, Michael W

    2003-05-01

    Human immunodeficiency virus-1 (HIV-1) is primarily a sexually transmitted disease. Identification of cell populations within the female reproductive tract that are initially infected, and the events involved in transmission of infection to other cells, remain to be established. In this report, we evaluated expression of HIV receptors and coreceptors on epithelial cells in the uterus and found they express several receptors critical for HIV infection including CD4, CXCR4, CCR5 and galactosylceramide (GalC). Moreover, expression of these receptors varied during the menstrual cycle. Expression of CD4 and CCR5 on uterine epithelial cells is high throughout the proliferative phase of the menstrual cycle when blood levels of oestradiol are high. In contrast, CXCR4 expression increased gradually throughout the proliferative phase. During the secretory phase of the cycle when both oestradiol and progesterone are elevated, CD4 and CCR5 expression decreased whereas CXCR4 expression remained elevated. Expression of GalC on endometrial glands is higher during the secretory phase than during the proliferative phase of the menstrual cycle. Because epithelial cells line the female reproductive tract and express HIV receptors and coreceptors, it is likely that they are one of the first cell types to become infected. The hormonal regulation of HIV receptor expression may affect a woman's susceptibility to HIV infection during her menstrual cycle. Moreover, selective coreceptor expression could account for the preferential transmission of R5-HIV-1 strains to women. In addition, these studies provide evidence that the uterus, and potentially the entire upper reproductive tract, are important sites for the initial events involved in HIV infection.

  13. Corneal Collagen Cross-Linking for Infectious Keratitis: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Papaioannou, Lamprini; Miligkos, Michael; Papathanassiou, Miltiadis

    2016-01-01

    To assess the efficacy of corneal collagen cross-linking (CXL) in the management of infectious keratitis. Comprehensive literature search was performed in MEDLINE/PubMed and Cochrane Central Register of Controlled Trials using combinations of the following search terms: "corneal collagen cross linking" or "photoactivated riboflavin" or "UVA light and riboflavin" and "infectious keratitis" or "corneal ulcer." Last search was on March 19, 2015. Extracted data from individual studies were summarized and summary proportions of eyes healed and complications for different subgroups were estimated. Twenty-five studies were included (2 randomized controlled trials, 13 case series, and 10 case reports) with a total of 210 eyes of 209 patients, of which 175 eyes underwent CXL. Causative microorganisms were bacteria, fungi, acanthamoeba, and Herpes simplex virus in 96, 32, 11, and 2 cases, respectively. Coinfections were present in 13 and cause was inconclusive in 21 cases. Sixteen of 175 eyes received no additional antibiotics, whereas 159 underwent CXL as an adjunct to antimicrobial treatment. Proportion of eyes healed with CXL was 87.2% (95% confidence interval (CI), 81.9%, 91.8%). For bacterial keratitis, the proportion of eyes healed was 85.7% (95% CI, 78.5%, 91.7%), whereas 10/11 and 25/32 eyes with acanthamoeba and fungal keratitis, respectively, were healed (available data not sufficient to provide a valid proportion analysis). Treatment resulted in corneal melting and tectonic keratoplasty in both Herpes simplex virus cases. CXL seems promising in the management of infectious keratitis, excluding viral infections. However, more randomized controlled trials are required to assess its efficacy.

  14. Contact lens induced Pseudomonas keratitis following descemet stripping automated endothelial keratoplasty.

    Science.gov (United States)

    Dhiman, Rebika; Singh, Archita; Tandon, Radhika; Vanathi, M

    2015-10-01

    To report a case of bandage contact lens induced infectious keratitis caused by Pseudomonas aeruginosa following DSAEK. A 56-year-old female who underwent DSAEK at our institute for pseudophakic bullous keratopathy, developed contact lens induced keratitis in the fifth post operative week. Best corrected visual acuity (BCVA) reduced to perception of light in the left eye. Slit lamp examination revealed an epithelial ulcer measuring 4.7mm×6mm with surrounding infiltrates in the anterior stroma with hypopyon. The interface was clear. The corneoscleral rim culture of the donor tissue showed no growth on bacterial and fungal culture ruling out the possibility of donor-to-host transmission of infection. Microbiological evaluation identified the causative agent to be Pseudomonas aeruginosa. Based on culture and sensitivity report patient was started on hourly instillation of topical polymyxin B 20,000IU and fortified ceftazidime 5%. A response to treatment was noted and there was a complete resolution of keratitis with residual scarring. There have been case reports suggesting a host to donor transmission of infection which manifests during the postoperative period. To the best of our knowledge there are no reports of bandage contact lens associated Pseudomonas keratitis in a case that has undergone DSAEK. The prolonged use of bandage contact lens, lens contamination, stagnation of tear film behind the lens, compromised ocular surface and post operative use of topical steroids can contribute to infectious keratitis in DSAEK cases. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  15. Evaluation of accelerated collagen cross-linking for the treatment of melting keratitis in eight dogs.

    Science.gov (United States)

    Famose, Frank

    2014-09-01

    Melting keratitis is serious condition presenting a high risk of permanent blindness and is caused by infectious or noninfectious factors. In humans, the clinical efficacy of collagen cross-linking (CXL) has been described in the treatment of refractory infectious keratitis by arresting keratomalacia. The aim of this study was to evaluate the efficacy of accelerated CXL for the treatment of melting keratitis in dogs. Eight dogs were treated for unilateral melting keratitis by accelerated CXL. Corneas were irradiated by UVA (370 nm) at 30 mW/cm² irradiance for 3 min after soaking by 0.1% riboflavin in 20% dextran for 30 min. Follow-up was conducted 3, 7, 14, and 30 days after treatment. Pain improvement was observed for all cases within 3 days after treatment. Epithelial healing was observed within 15 days for all cases. Disappearance of cellular infiltration was observed for all cases at day 7. The corneal vascularization disappeared for 4 of 8 dogs and was reduced for 4 of 8 dogs within 1 month. At 1 month, all cases presented a variable degree of corneal scarring, but all eyes had visual function. No recurrent infection was observed. The main observation of this study is that all the cases have presented with the same clinical result regardless of the presence and the sensitivity of the infectious agents and regardless of the duration of the condition prior to CXL treatment. Accelerated CXL appears to be a valuable option for the treatment of melting keratitis. © 2013 American College of Veterinary Ophthalmologists.

  16. Coinfection with Acanthamoeba and Pseudomonas in contact lens-associated keratitis.

    Science.gov (United States)

    Sharma, Reetika; Jhanji, Vishal; Satpathy, Gita; Sharma, Namrata; Khokhar, Sudarshan; Agarwal, Tushar

    2013-02-01

    To report coinfection with Acanthamoeba and Pseudomonas aeruginosa in a case with contact lens-associated keratitis. A 20-year-old woman presented to the emergency department of our hospital with a 4-day history of progressively increasing pain, redness, photophobia, mucopurulent discharge, and diminution of vision in her right eye. She was being treated for contact lens-related Pseudomonas keratitis in another hospital before presentation. Gram stain of corneal scrapings revealed gram-negative bacilli. Both Gram stain and 10% KOH wet mount showed the presence of Acanthamoeba cysts. Microbiological cultures obtained from contact lenses and contact lens storage case showed the presence of Pseudomonas aeruginosa and Acanthamoeba. Topical therapy was started in the form of hourly gentamycin 1.3%, cefazolin 5%, chlorhexidine 0.02%, propamidine 0.1%, polymyxin B 30,000 IU eye drops, and neosporin (neomycin, bacitracin, polymyxin) eye ointment four times a day. Symptomatic improvement was observed within 48 hours, along with a decrease in the density of infiltrates and a reduction in the anterior chamber reaction. Repeat corneal scrapings on day 10 showed Acanthamoeba but no bacilli. Progressive resolution of the infiltrate was noted during the next few days. Epithelialization was complete by day 24, following which the amoebicidal therapy was tapered during the next 4 weeks. Complete resolution of keratitis was achieved after 7 weeks of treatment. Both P. aeruginosa and Acanthamoeba are potentially devastating causes of microbial keratitis. Our case highlights the importance of considering the possibility of a concurrent infection in cases with contact lens-related keratitis.

  17. Clinical and corneal microbial profile of infectious keratitis in a high HIV prevalence setting in rural South Africa

    NARCIS (Netherlands)

    W. Schaftenaar (Willem); R.P.H. Peters (Remco); G.S. Baarsma (Seerp); C. Meenken (Christina); N.S. Khosa; S. Getu (Sarah); J.A. McIntyre (James); A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George)

    2016-01-01

    textabstractThe purpose of this investigation was to determine the clinical and corneal microbial profile of infectious keratitis in a high human immunodeficiency virus (HIV) prevalence setting in rural South Africa. Data in this cross-sectional study were collected from patients presenting with

  18. Recent advances in diagnosis and management of Mycotic Keratitis.

    Science.gov (United States)

    Maharana, Prafulla K; Sharma, Namrata; Nagpal, Ritu; Jhanji, Vishal; Das, Sujata; Vajpayee, Rasik B

    2016-05-01

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

  19. Introduction of plasmid DNA and oligonucleotides into lung epithelial cells by the hemagglutinating virus of Japan (HVJ)-liposome method.

    Science.gov (United States)

    Yoshida, M; Hayashi, S; Sakuma-Mochizuki, J; Abe, K; Arai, T; Mori, M; Goya, S; Matsuoka, H; Kaneda, Y; Kishimoto, T

    1999-01-01

    The hemagglutinating virus of Japan (HVJ) fused with liposomes provides a unique transfection vehicle with characteristics of both virus vector and liposome. Here we investigate the efficiency and safety of the HVJ-liposome technique in delivering foreign genes and oligonucleotides into the lung of the Wistar rat. A plasmid vector containing the Escherichia coli beta-galactosidase (beta-gal) gene and the chicken beta-actin promoter was transfected via the trachea using the HVJ-liposome method. Cytochemical staining showed expression of exogenous beta-gal activity in airway epithelial cells, alveolar macrophages, and alveolar type II cells. This activity persisted at least 28 days after administration of the genes. FITC-labeled oligonucleotides also were introduced into the same types of lung cells as those expressing beta-gal. After instillation of HVJ-liposome, anti-HVJ antibodies were detected in the sera of the rats, but even after repeated administration of HVJ-liposome, no marked histopathologic change was observed while exogenous beta-gal expression was detected in pulmonary cells.

  20. Exophiala phaeomuriformis Fungal Keratitis: Case Report and In Vivo Confocal Microscopy Findings.

    Science.gov (United States)

    Aggarwal, Shruti; Yamaguchi, Takefumi; Dana, Reza; Hamrah, Pedram

    2017-03-01

    Corneal infections, particularly fungal keratitis due to rare fungal species, pose a diagnostic and therapeutic challenge because of difficulty in identification and varying susceptibility profiles. In this study, we report the first case of fungal keratitis because of Exophiala phaeomuriformis. We report the clinical findings and microbial identification techniques of a case of fungal keratitis due to E. phaeomuriformis. An 84-year-old woman presented with redness, pain, and itching in the left eye for 2 weeks. Slit-lamp biomicroscopy revealed one broken suture from previous penetrating keratoplasty (PKP), black infiltrates at the 4-o'clock position, without an overlying epithelial defect and hypopyon. Microbial identification was based cultures on Sabouraud dextrose agar and DNA sequencing and correlations to laser in vivo confocal microscopy (IVCM; Heidelberg Retinal Tomograph 3/Rostock Cornea Module, Heidelberg Engineering) and multiphoton microscopy (Ultima Microscope; Prairie Technologies) images. Slit-lamp biomicroscopy revealed one broken suture from previous PKP, black infiltrates at the 4-o'clock position, without an overlying epithelial defect and hypopyon. Based on a clinical suspicion of fungal keratitis, antifungals and fortified antibiotics were started. However, the patient did not respond to therapy and required urgent PKP. After surgery, the patient was maintained on topical and systemic voriconazole and also topical 2% cyclosporine for 5 months because of possibility of scleral involvement noticed during surgery. At the end of the treatment period, her vision improved from hand motion to 20/40, with no recurrence observed in a follow-up period of 1 year. Results of diagnostic tests were supported by fungal elements in stroma on IVCM. Culture from the infiltrate grew black yeast. DNA sequencing led to the diagnosis of E. phaeomuriformis keratitis. Antifungal susceptibility testing revealed sensitivity to voriconazole. This is, to our knowledge

  1. [Multilayer amniotic membrane transplantation for treatment of necrotizing herpes simplex stromal keratitis].

    Science.gov (United States)

    Shi, Wei-yun; Chen, Min; Wang, Fu-hua; Zhao, Jing; Ma, Lin; Xie, Li-xin

    2005-12-01

    To evaluate the efficacy of multilayer amniotic membrane transplantation (AMT) combined with antivirus and corticosteroid drug to treat necrotizing herpes simplex stromal keratitis. Thirteen patients (13 eyes) of necrotizing stromal keratitis were referred to Shandong Eye Institute and Qingdao Eye Hospital between January 2003 and April 2004. The course of disease was 3 - 22 months (mean 15 months). Corneal inflammation persisted and corneal ulcer progressed despite topical and systemic antiviral treatment for over 1 weeks. Multilayer amniotic membrane transplantation was performed after excluding of bacterial and fungal infection by microbiologic studies including smears and cultures of necrotic corneal tissue and confocal microscope. Topical and systemic antiviral medications were given with adjuvant corticosteroid eyedrops postoperatively. We investigated the healing of corneal ulcer and improvement of stromal edema with slit lamp biomicroscope, the integrity of corneal defect with fluorescein staining, the migration of healthy corneal epithelial cells and transformation of amniotic membrane with confocal microscopy. All patients were followed up for 3 - 13 months (mean 10 months). Corneal ulcer healed within 1 - 3 weeks postoperatively with negative fluorescein staining. Corneal stromal edema faded away within 1 month. Superficial amniotic membrane patches dissolved or shed on postoperative day 7 - 10, while the deeper grafts were adhered into the ulcer and fused with the surrounding fibroblasts. One of these grafts remained in situ more than 3 months. Confocal microscope examination indicated flat epithelial progenitor cells on the surface of residual amniotic membrane. Corneal transparence was achieved in 7 eyes, macula in 4 eyes and leucoma in 2 eyes 3 months after the operation. No recurrence of necrotizing stromal keratitis was occurred in 13 patients during the follow-up period. Multilayer AMT combined with antivirus and corticosteroid treatment is an

  2. Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Qun Wu

    Full Text Available The use of electronic cigarettes (e-cigarettes is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV infection.We examined the effects of e-cigarette liquid (e-liquid on pro-inflammatory cytokine (e.g., IL-6 production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1 in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

  3. Cleavage of the SARS coronavirus spike glycoprotein by airway proteases enhances virus entry into human bronchial epithelial cells in vitro.

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    Yiu-Wing Kam

    Full Text Available BACKGROUND: Entry of enveloped viruses into host cells requires the activation of viral envelope glycoproteins through cleavage by either intracellular or extracellular proteases. In order to gain insight into the molecular basis of protease cleavage and its impact on the efficiency of viral entry, we investigated the susceptibility of a recombinant native full-length S-protein trimer (triSpike of the severe acute respiratory syndrome coronavirus (SARS-CoV to cleavage by various airway proteases. METHODOLOGY/PRINCIPAL FINDINGS: PURIFIED TRISPIKE PROTEINS WERE READILY CLEAVED IN VITRO BY THREE DIFFERENT AIRWAY PROTEASES: trypsin, plasmin and TMPRSS11a. High Performance Liquid Chromatography (HPLC and amino acid sequencing analyses identified two arginine residues (R667 and R797 as potential protease cleavage site(s. The effect of protease-dependent enhancement of SARS-CoV infection was demonstrated with ACE2 expressing human bronchial epithelial cells 16HBE. Airway proteases regulate the infectivity of SARS-CoV in a fashion dependent on previous receptor binding. The role of arginine residues was further shown with mutant constructs (R667A, R797A or R797AR667A. Mutation of R667 or R797 did not affect the expression of S-protein but resulted in a differential efficacy of pseudotyping into SARS-CoVpp. The R667A SARS-CoVpp mutant exhibited a lack of virus entry enhancement following protease treatment. CONCLUSIONS/SIGNIFICANCE: These results suggest that SARS S-protein is susceptible to airway protease cleavage and, furthermore, that protease mediated enhancement of virus entry depends on specific conformation of SARS S-protein upon ACE2 binding. These data have direct implications for the cell entry mechanism of SARS-CoV along the respiratory system and, furthermore expand the possibility of identifying potential therapeutic agents against SARS-CoV.

  4. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

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    Jumat, Muhammad Raihan [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Yan, Yan [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Ravi, Laxmi Iyer [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Wong, Puisan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Huong, Tra Nguyen [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Li, Chunwei [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Tan, Boon Huan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Wang, De Yun [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Sugrue, Richard J., E-mail: rjsugrue@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore)

    2015-10-15

    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function.

  5. Early host responses of seasonal and pandemic influenza A viruses in primary well-differentiated human lung epithelial cells.

    Directory of Open Access Journals (Sweden)

    Rachael L Gerlach

    Full Text Available Replication, cell tropism and the magnitude of the host's antiviral immune response each contribute to the resulting pathogenicity of influenza A viruses (IAV in humans. In contrast to seasonal IAV in human cases, the 2009 H1N1 pandemic IAV (H1N1pdm shows a greater tropism for infection of the lung similar to H5N1. We hypothesized that host responses during infection of well-differentiated, primary human bronchial epithelial cells (wd-NHBE may differ between seasonal (H1N1 A/BN/59/07 and H1N1pdm isolates from a fatal (A/KY/180/10 and nonfatal (A/KY/136/09 case. For each virus, the level of infectious virus and host response to infection (gene expression and apical/basal cytokine/chemokine profiles were measured in wd-NHBE at 8, 24, 36, 48 and 72 hours post-infection (hpi. At 24 and 36 hpi, KY/180 showed a significant, ten-fold higher titer as compared to the other two isolates. Apical cytokine/chemokine levels of IL-6, IL-8 and GRO were similar in wd-NHBE cells infected by each of these viruses. At 24 and 36 hpi, NHBE cells had greater levels of pro-inflammatory cytokines including IFN-α, CCL2, TNF-α, and CCL5, when infected by pandemic viruses as compared with seasonal. Polarization of IL-6 in wd-NHBE cells was greatest at 36 hpi for all isolates. Differential polarized secretion was suggested for CCL5 across isolates. Despite differences in viral titer across isolates, no significant differences were observed in KY/180 and KY/136 gene expression intensity profiles. Microarray profiles of wd-NHBE cells diverged at 36 hpi with 1647 genes commonly shared by wd-NHBE cells infected by pandemic, but not seasonal isolates. Significant differences were observed in cytokine signaling, apoptosis, and cytoskeletal arrangement pathways. Our studies revealed differences in temporal dynamics and basal levels of cytokine/chemokine responses of wd-NHBE cells infected with each isolate; however, wd-NHBE cell gene intensity profiles were not significantly

  6. Håndtering af keratitis efter laserbehandling adskiller sig fra almindelig keratitis

    DEFF Research Database (Denmark)

    Ahmed, Shakil; Ahmed, Hassan Javed; Holm, Lars Morten

    2014-01-01

    Keratitis after laser in situ keratomileusis (LASIK) is rare and challenging as patients may present with mild symptoms and initial management differs significantly. Post-LASIK keratitis is usually due to gram-positive bacteria or opportunistic/atypical microorganisms located beneath the corneal...... flap. Due to relative protective interface location it is necessary to lift the corneal flap for cultures and antibiotic irrigation. The case report demonstrates that post-LASIK keratitis requires prompt referral to ophthalmology department as correct initial management is pivotal for good visual...

  7. Epstein-Barr virus infection of polarized epithelial cells via the basolateral surface by memory B cell-mediated transfer infection.

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    Claire Shannon-Lowe

    2011-05-01

    Full Text Available Epstein Barr virus (EBV exhibits a distinct tropism for both B cells and epithelial cells. The virus persists as a latent infection of memory B cells in healthy individuals, but a role for infection of normal epithelial is also likely. Infection of B cells is initiated by the interaction of the major EBV glycoprotein gp350 with CD21 on the B cell surface. Fusion is triggered by the interaction of the EBV glycoprotein, gp42 with HLA class II, and is thereafter mediated by the core fusion complex, gH/gL/gp42. In contrast, direct infection of CD21-negative epithelial cells is inefficient, but efficient infection can be achieved by a process called transfer infection. In this study, we characterise the molecular interactions involved in the three stages of transfer infection of epithelial cells: (i CD21-mediated co-capping of EBV and integrins on B cells, and activation of the adhesion molecules, (ii conjugate formation between EBV-loaded B cells and epithelial cells via the capped adhesion molecules, and (iii interaction of EBV glycoproteins with epithelial cells, with subsequent fusion and uptake of virions. Infection of epithelial cells required the EBV gH and gL glycoproteins, but not gp42. Using an in vitro model of normal polarized epithelia, we demonstrated that polarization of the EBV receptor(s and adhesion molecules restricted transfer infection to the basolateral surface. Furthermore, the adhesions between EBV-loaded B cells and the basolateral surface of epithelial cells included CD11b on the B cell interacting with heparan sulphate moieties of CD44v3 and LEEP-CAM on epithelial cells. Consequently, transfer infection was efficiently mediated via CD11b-positive memory B cells but not by CD11b-negative naïve B cells. Together, these findings have important implications for understanding the mechanisms of EBV infection of normal and pre-malignant epithelial cells in vivo.

  8. Uptake of rabies virus into epithelial cells by clathrin-mediated endocytosis depends upon actin.

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    Piccinotti, Silvia; Kirchhausen, Tomas; Whelan, Sean P J

    2013-11-01

    Rabies virus (RABV) causes a fatal zoonotic encephalitis. Disease symptoms require replication and spread of the virus within neuronal cells; however, in infected animals as well as in cell culture the virus replicates in a broad range of cell types. Here we use a single-cycle RABV and a recombinant vesicular stomatitis virus (rVSV) in which the glycoprotein (G) was replaced with that of RABV (rVSV RABV G) to examine RABV uptake into the African green monkey kidney cell line BS-C-1. Combining biochemical studies and real-time spinning-disk confocal fluorescence microscopy, we show that the predominant entry pathway of RABV particles into BS-C-1 cells is clathrin dependent. Viral particles enter cells in pits with elongated structures and incomplete clathrin coats which depend upon actin to complete the internalization process. By measuring the time of internalization and the abundance of the clathrin adaptor protein AP2, we further show that the pits that internalize RABV particles are similar to those that internalize VSV particles. Pharmacological perturbations of dynamin or of actin polymerization inhibit productive infection, linking our observations on particle uptake with viral infectivity. This work extends to RABV particles the finding that clathrin-mediated endocytosis of rhabdoviruses proceeds through incompletely coated pits which depend upon actin.

  9. Epithelial Distribution and Replication of Foot-and-Mouth Disease Virus RNA in Infected Pigs

    DEFF Research Database (Denmark)

    Durand, S.; Murphy, C.; Zhang, Z.

    2008-01-01

    Although the pathogenesis of foot-and-mouth disease (FMD) has been extensively investigated relatively few studies have addressed the localization of FMD virus (FMDV) and in particular its replication in relation to the typical in-vivo sites of FMD lesions. In the present study, pigs were infecte...

  10. Hypothesis: a novel route for immortalization of epithelial cells by Epstein-Barr virus.

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    Gao, Yanning; Lu, Yong-Jie; Xue, Shao-An; Chen, Honglin; Wedderburn, Nina; Griffin, Beverly E

    2002-01-24

    Transfection of primate tissue explants with a specific sub-fragment (p31) of EBV DNA results in epithelial (but no other) cells proliferating indefinitely (becoming 'immortalized') without evidence of a 'growth crisis'. Molecular evidence supports integration of viral information into the host chromosome, and an early genotypic alteration involving specific amplification of a sub-component (IR1) of p31 DNA, followed by apparent loss of viral DNA from chromosomes, consistent with a 'hit and run' mechanism. However, analysis at the individual cell level during long-term culture, by FISH techniques, reveals chromosomal alterations, and viral sequences surviving within double minute (DM) bodies. Changing growth patterns occurring at different stages during propagation (>a year in culture) may be explained by sporadic reintegration of surviving viral DNA into the host chromosome. Notably, throughout culture, telomere lengths in chromosomal DNAs do not alter but rather retain the length observed in the primary cell populations. Introduction of a growth stimulating function of EBV, BARF1, into the immortalized, non-clonable epithelial cells under conditions which permit overexpression, allows clonal populations to be derived. Based on the data, mechanisms of immortalization, in the absence of a proven viral oncogene in p31 DNA, and possible genes involved, are considered.

  11. Acanthamoeba keratitis related to cosmetic contact lenses.

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    Lee, Jong Soo; Hahn, Tae Won; Choi, Si Hwan; Yu, Hak Sun; Lee, Ji-Eun

    2007-11-01

    We report a rare case of Acanthamoeba keratitis related to cosmetic contact lenses in both eyes. A 17-year-old girl with a history of wearing cosmetic contact lenses presented with keratitis. She purchased cosmetic contact lenses via the Internet, and followed a contact lens care system irregularly, occasionally using tap water. Cell culture was performed on samples collected from a corneal scraping, the contact lenses and the storage cases. The isolated organism was Acanthamoeba. The patient was treated with polyhexamethylene biguanide and chlorhexidine for 3 months, and recovered with normal visual acuity. Poor hygiene and insufficient disinfection may be major risk factors for Acanthameoba keratitis in cosmetic contact lens wearers. The cosmetic contact lens user should receive professional advice before accessing the lenses, and this must be communicated to the public.

  12. Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity.

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    Kikuchi, Kentaro; Noguchi, Yoshihiro; de Rivera, Michelle Wendoline Garcia-Niño; Hoshino, Miyako; Sakashita, Hideaki; Yamada, Tsutomu; Inoue, Harumi; Miyazaki, Yuji; Nozaki, Tadashige; González-López, Blanca Silvia; Ide, Fumio; Kusama, Kaoru

    2016-03-01

    A relationship between Epstein-Barr virus (EBV) infection and cancer of lymphoid and epithelial tissues such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), gastric carcinoma, and oral cancer has been reported. EBV is transmitted orally and infects B cells and epithelial cells. However, it has remained uncertain whether EBV plays a role in carcinogenesis of oral mucosal tissue. In the present study, we detected the EBV genome and latent EBV gene expression in normal mucosal epithelia, epithelial dysplasia, and oral squamous cell carcinoma (OSCC) to clarify whether EBV is involved in carcinogenesis of the oral cavity. We examined 333 formalin-fixed, paraffin-embedded tissue samples (morphologically normal oral mucosa 30 samples, gingivitis 32, tonsillitis 17, oral epithelial dysplasia 83, OSCC 150, and NPC 21). EBV latent infection genes (EBNA-2, LMP-1) were detected not only in OSCC (50.2 %, 10.7 %) but also in severe epithelial dysplasia (66.7 %, 44.4 %), mild to moderate epithelial dysplasia (43.1 %, 18.5 %), gingivitis (78.1 %, 21.9 %), and normal mucosa (83.3 %, 23.3 %). Furthermore, the intensity of EBV latent infection gene expression (EBER, LMP-1) was significantly higher in severe epithelial dysplasia (94.4 %, 72.2 %) than in OSCC (34.7 %, 38.7 %). These results suggest that EBV latent infection genes and their increased expression in severe epithelial dysplasia might play an important role in the dysplasia-carcinoma sequence in the oral cavity.

  13. Infectious Keratitis Following Corneal Crosslinking: A Systematic Review of Reported Cases: Management, Visual Outcome, and Treatment Proposed.

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    Abbouda, A; Abicca, I; Alió, J L

    2016-01-01

    To describe the infectious complications and the group of pathogens involved in the infection following corneal crosslinking, the visual outcome, and the treatment proposed. A Medline (National Library of Medicine, Bethesda, MD, USA) search from October 2000 to October 2013 was performed to identify all articles describing infectious keratitis following corneal crosslinking treatment. Nineteen articles were selected. Ten articles reported infectious complications of corneal crosslinking treatment were included. Nine articles were excluded, because seven described sterile keratitis, one article was in German, and one reported general complication without describing the infection complication. A total number of infections reported included 10 eyes. The infectious keratitis was associated with bacteria in five eyes (50%): gram-positive bacteria in three eyes (30%) (staphylococcus epidermidis, S. aureus and streptococcus salivarius plus S. oralis, respectively) and gram-negative bacteria in two eyes (20%) (E. coli; P. aeruginosa); there was herpes virus in two eyes, fungus in two eyes (Fusarium and Microsporidia) (20%), and Acanthamoeba in one eye (10%). Only 10 cases of infectious keratitis following corneal crosslinking are published. The most virulent pathogens were Pseudomonas aeruginosa and Acanthamoeba. Less virulent organisms were Escherichia coli and S. epidermidis. Two cases of herpes keratitis were described, suggesting the possibility of systemic antiviral prophylaxis before corneal crosslinking treatment. The most common risk factor of infections identified was postoperative incorrect patient behavior.

  14. Prevalence of infectious keratitis in Central China

    Science.gov (United States)

    2014-01-01

    Background The baseline data pertaining to the national epidemiological survey of infectious keratitis remain scarce in China, and currently there is no corneal blindness control strategy developed by the nation. Methods Geographically defined cluster sampling was used to randomly select a cross-section of residents from representative urban and rural populations in Hubei Province. Participants were selected from village registers, followed by door-to-door household visits. The assessment items included a structured interview, visual acuity testing, external eye examination, and anterior segment examination using slit lamp. Causes and sequelae of corneal disease were identified according to uniform customized protocol. Results The prevalence of presenting corneal diseases was 0.8% (211/26 305), while the prevalence of infectious keratitis was 0.148% (39/26 305). The prevalences of viral, bacterial, and fungal keratitis were 0.065, 0.068, and 0.015%, respectively. There were no significant differences found between the prevalences of viral (accounting for 43.6%) and bacterial (accounting for 46.2%) corneal ulcers. cases of Acanthamoeba keratitis were not found. Infectious keratitis was the leading cause of corneal blindness (85.7%), and the prevalence of blindness in at least one eye resulting from infected corneas was 0.091% (95% CI: 0.067-0.127%). Conclusions Viral and bacterial mechanisms constitute the most important risk factors for infectious corneal ulcers in Central China. To reduce the rate and severity of infectious keratitis, he public health care policy should be focused on designing cost-effective strategies and operational programs for the prevention and prompt treatment of infectious corneal ulcers. PMID:24690368

  15. Herpes simplex virus-1 infection or Simian virus 40-mediated immortalization of corneal cells causes permanent translocation of NLRP3 to the nuclei

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    Shu-Long Wang

    2015-01-01

    Full Text Available AIM: To investigate into the potential involvement of pyrin containing 3 gene (NLRP3, a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses. METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1 (HSV-1. Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40 (SV40-immortalized human corneal epithelial cell line were also examined. Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β. RESULTS: The NLRP3 activation induced by HSV-1 infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore, in the SV40-immortalized human corneal epithelial cells, NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium (known as an inhibitor of NLRP3 activation effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot. CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.

  16. Medical management of suspected Paecilomyces sp. deep keratitis.

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    Holland, Lee; Lee, Graham A

    2015-07-01

    A 74-year-old woman developed a deep keratitis presenting with an endothelial plaque without overlying stromal involvement. Owing to the characteristic clinical appearance, she was provisionally diagnosed with a Paecilomyces sp. keratitis. Corneal scrapings and aqueous humour samples were culture negative. The difficulties in diagnosing Paecilomyces sp. keratitis are discussed. The patient's keratitis was managed with a combination of topical, oral and intracameral injections of voriconazole. This medical management strategy was successful in achieving good infection control and visual outcome. We report a rarely encountered presentation of keratitis in which the clinical appearance and response to voriconazole are highly suggestive evidence of a Paecilomyces sp. keratitis. We believe the combination of topical, oral and intracameral injections of voriconazole represents a novel treatment approach for Paecilomyces sp. keratitis. Our case supports the potential for a medical approach as initial treatment in this otherwise devastating form of oculomycosis. 2015 BMJ Publishing Group Ltd.

  17. Amoebic keratitis in Iran (1997-2007

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    F Rahimi

    2007-07-01

    Full Text Available Background: Amoebic keratitis introduced as a painful corneal infection which sometimes lead to poor vision and blind-ness. The main goal of this study was to report amoebic keratitis during ten years from 1997-2007 in patients who was sus-pected to have amoebic keratitis and referred to Parasitology laboratory, School of Public Health, Tehran Univer¬sity of Medical Sciences, Iran. Other aim was to assess the major risk factor for developing this sight-threatening disease. Comparison of lens culture and corneal scrapes culture also was performed. "nMethods: During 1997-2007, 142 patients referred to Dept. of Medical Parasitology, School of Public Health, Tehran Uni-versity of Medical Sciences, Iran. Details of each patient such as age, sex, history of contact lens wear, type of contact lens, clinical symptoms were recorded in questioners. Keratitis was diagnosed on the basis of culture of lenses and/or corneal scrapes on non-nutrient agar overlaid with Escherichia coli and direct microscopy of lenses and/or corneal scrapes. "nResults: Among 142 patients, 49 (34.5% had amoebic keratitis. 73.46% of these patients were from Tehran but there were a few cases from other cities. The commonest age was between 15-25 yr (75.5% and more female (37:12 were identified then male. It is worth to mention that 44 patients (89.79% were contact lens wearers who among them 41 patients (93.18% wore soft contact lens and only three patients suffer from amoebic keratitis because of wearing hard contact lens. Other finding of this study demonstrated that the most common sign of the patients was severe pain combined with photophobia. "nConclusion: This study indicates that Acanthamoeba keratitis continue to rise in Iran. This is due to increase frequency of lens wearers as well as consideration of ophthalmologist to Acanthamoeba as an agent of keratitis and improvement of labo¬ratory methods. Another finding of this research was the confirmation of soft contact lens

  18. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections.

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    Jacob D Estes

    Full Text Available The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4(+ T cell count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replication.

  19. Rituximab for peripheral ulcerative keratitis with wegener granulomatosis.

    Science.gov (United States)

    Huerva, Valentín; Sanchez, María Carmen; Traveset, Alicia; Jurjo, Carmen; Ruiz, Agustín

    2010-06-01

    To demonstrate the effectiveness of Rituximab in the management of peripheral ulcerative keratitis (PUK) associated with Wegener granulomatosis (WG). A 50-year-old female with WG, confirmed by skin biopsy and positive anti-neutrophil cytoplasmic antibodies 3 years prior, was presented with a corneoscleral granulomatous mass that affected the superior limbus and with vasculitic PUK in the right eye. The mass was treated daily with oral prednisone (1 mg.kg-1.d-1) in conjunction with weekly maintenance treatment of 10 mg of methotrexate. After 2 months of treatment, the volume of the nodular granulomatous lesion decreased. However, the PUK and corneal thinning persisted, which presented a risk for corneal perforation. Subsequently, two 1000-mg infusions of rituximab were administered at weekly intervals. One week after the first administration of rituximab, we observed persistence of corneal thinning, flattening of the nodular lesion, and disappearance of the necrotic foci. After the second rituximab treatment, the patient exhibited no signs of corneal perforation and we further observed total epithelialization of the PUK. No systemic side effects were seen. After 2 months, no nodular lesion was observed, although conjunctival epithelialization from the previous PUK remained. Weekly methotrexate and 10 mg of prednisone per day were maintained. Rituximab seems to offer therapeutic promise in the treatment of refractory PUK associated with WG. Rituximab may be the elective treatment for severe anterior ocular inflammation associated with risk for corneal perforation, as a result of WG.

  20. Topical corticosteroids as adjunctive therapy for bacterial keratitis

    Science.gov (United States)

    Herretes, Samantha; Wang, Xue; Reyes, Johann MG

    2014-01-01

    ongoing randomized trials. Selection criteria We included randomized controlled trials (RCTs) that had evaluated adjunctive therapy with topical corticosteroids in people with bacterial keratitis who were being treated with antibiotics. Data collection and analysis We used the standard methodological procedures expected by The Cochrane Collaboration. Main results We found four RCTs that met the inclusion criteria of this review. The total number of included participants was 611 (612 eyes), ranging from 30 to 500 participants per trial. One trial was included in the previous version of the review, and we identified three additional trials through the updated searches in July 2014. One of the three smaller trials was a pilot study of the largest study: the Steroids for Corneal Ulcers Trial (SCUT). All trials compared the treatment of bacterial keratitis with topical corticosteroid and without topical corticosteroid and had follow-up periods ranging from two months to one year. These trials were conducted in the USA, Canada, India, and South Africa. All trials reported data on visual acuity ranging from three weeks to one year, and none of them found any important difference between the corticosteroid group and the control group. The pilot study of the SCUT reported that time to re-epithelialization in the steroid group was 53% slower than the placebo group after adjusting for baseline epithelial defect size (hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.23 to 0.94). However, the SCUT did not find any important difference in time to re-epithelialization (HR 0.92; 95% CI 0.76 to 1.11). For adverse events, none of the three small trials found any important difference between the two treatment groups. The investigators of the largest trial reported that more patients in the control group developed intraocular pressure (IOP) elevation (risk ratio (RR) 0.20; 95% CI 0.04 to 0.90). One trial reported quality of life and concluded that there was no difference between the

  1. Medical interventions for fungal keratitis.

    Science.gov (United States)

    FlorCruz, Nilo Vincent; Evans, Jennifer R

    2015-04-09

    Fungal keratitis is a fungal infection of the cornea. It is common in lower income countries, particularly in agricultural areas but relatively uncommon in higher income countries. Although there are medications available, their effectiveness is unclear. To assess the effects of different antifungal drugs in the management of fungal keratitis. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2015), EMBASE (January 1980 to March 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 16 March 2015. We included randomised controlled trials of medical therapy for fungal keratitis. Two review authors selected studies for inclusion in the review, assessed trials for risk of bias and extracted data. The primary outcome was clinical cure at two to three months. Secondary outcomes included best-corrected visual acuity, time to clinical cure, compliance with treatment, adverse outcomes and quality of life. We included 12 trials in this review; 10 trials were conducted in India, one in Bangladesh and one in Egypt. Seven of these trials were at high risk of bias in one or more domains, two of these studies were at low risk of bias in all domains. Participants were randomised to the following comparisons: topical 5% natamycin compared to topical 1% voriconazole; topical 5% natamycin compared to topical 2% econazole; topical 5% natamycin compared to topical chlorhexidine gluconate (0

  2. Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine.

    Science.gov (United States)

    Mata, Manuel; Sarrion, Irene; Armengot, Miguel; Carda, Carmen; Martinez, Isidoro; Melero, Jose A; Cortijo, Julio

    2012-01-01

    Persistent respiratory syncytial virus (RSV) infections have been associated with the exacerbation of chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). This virus infects the respiratory epithelium, leading to chronic inflammation, and induces the release of mucins and the loss of cilia activity, two factors that determine mucus clearance and the increase in sputum volume. These alterations involve reactive oxygen species-dependent mechanisms. The antioxidant N-acetylcysteine (NAC) has proven useful in the management of COPD, reducing symptoms, exacerbations, and accelerated lung function decline. NAC inhibits RSV infection and mucin release in human A549 cells. The main objective of this study was to analyze the effects of NAC in modulating ciliary activity, ciliagenesis, and metaplasia in primary normal human bronchial epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased the expression of β-tubulin as well as two genes involved in ciliagenesis, FOXJ1 and DNAI2. These alterations led to a decrease in ciliary activity. Furthermore, RSV induced metaplastic changes to the epithelium and increased the number of goblet cells and the expression of MUC5AC and GOB5. NAC restored the normal functions of the epithelium, inhibiting ICAM1 expression, subsequent RSV infection through mechanisms involving nuclear receptor factor 2, and the expression of heme oxygenase 1, which correlated with the restoration of the antioxidant capacity, the intracellular H(2)O(2) levels and glutathione content of NHBECs. The results presented in this study support the therapeutic use of NAC for the management of chronic respiratory diseases, including COPD.

  3. Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures.

    Directory of Open Access Journals (Sweden)

    Sara M Johnson

    2015-12-01

    Full Text Available Respiratory syncytial virus (RSV is the most frequent cause of lower respiratory disease in infants, but no vaccine or effective therapy is available. The initiation of RSV infection of immortalized cells is largely dependent on cell surface heparan sulfate (HS, a receptor for the RSV attachment (G glycoprotein in immortalized cells. However, RSV infects the ciliated cells in primary well differentiated human airway epithelial (HAE cultures via the apical surface, but HS is not detectable on this surface. Here we show that soluble HS inhibits infection of immortalized cells, but not HAE cultures, confirming that HS is not the receptor on HAE cultures. Conversely, a "non-neutralizing" monoclonal antibody against the G protein that does not block RSV infection of immortalized cells, does inhibit infection of HAE cultures. This antibody was previously shown to block the interaction between the G protein and the chemokine receptor CX3CR1 and we have mapped the binding site for this antibody to the CX3C motif and its surrounding region in the G protein. We show that CX3CR1 is present on the apical surface of ciliated cells in HAE cultures and especially on the cilia. RSV infection of HAE cultures is reduced by an antibody against CX3CR1 and by mutations in the G protein CX3C motif. Additionally, mice lacking CX3CR1 are less susceptible to RSV infection. These findings demonstrate that RSV uses CX3CR1 as a cellular receptor on HAE cultures and highlight the importance of using a physiologically relevant model to study virus entry and antibody neutralization.

  4. Epstein-Barr virus nuclear antigen 1 (EBNA1) protein induction of epithelial-mesenchymal transition in nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Wang, Lu; Tian, Wen-Dong; Xu, Xia; Nie, Biao; Lu, Juan; Liu, Xiong; Zhang, Bao; Dong, Qi; Sunwoo, John B; Li, Gang; Li, Xiang-Ping

    2014-02-01

    The Epstein-Barr virus (EBV)-encoded EB nuclear antigen 1 (EBNA1) protein is required for maintenance and transmission of the viral episome in EBV-infected cells. The objective of this study was to investigate the role of EBNA1 protein in nasopharyngeal carcinoma (NPC). Tissue samples from 48 patients with NPC and 12 patients with chronic nasopharyngitis were subjected to immunohistochemical analysis of EBNA1 expression. EBNA1 combinational DNA was used to overexpress EBNA1 protein in NPC cell lines to assess tumor cell epithelial-mesenchymal transition (EMT), colony formation, migration and invasion, and gene expression. EBNA1 protein was highly expressed in NPC tissue specimens, and its expression was associated with NPC lymph node metastasis. EBNA1 expression affected NPC cell morphology and the expression of EMT markers in vitro. Furthermore, overexpression of EBNA1 inhibited the expression of microRNA 200a (miR-200a) and miR-200b and, in turn, up-regulated expression of their target genes, zinc finger E-box binding homeobox 1 ( ZEB1) and ZEB2, which are well known mediators of EMT. In addition, EBNA1-regulated miR-200a and miR-200b expression was mediated by transforming growth factor-β1. The current findings provided novel insight into the vital role of EBNA1 in manipulating a molecular switch of EMT in EBV-positive NPC cells. © 2013 American Cancer Society.

  5. A new pyrenochaeta species causing keratitis

    NARCIS (Netherlands)

    Ferrer, C.; Perez-Santonja, J.J.; Rodriguez, A.E.; Colom, M.F.; Gene, J.; Alio, J.L.; Verkley, G.J.M.; Guarro, J.

    2009-01-01

    We report a new fungus as an agent of fungal keratitis in a diabetic woman. The fungal etiology was established by classic microbiology and PCR following 3 months of antibacterial therapy. The morphological features of the isolate and sequence analysis of the internal transcribed spacer region

  6. Mycotic keratitis due to Aspergillus nomius

    NARCIS (Netherlands)

    Manikandan, P.; Varga, J.; Kocsube, S.; Samson, R.A.; Anita, R.; Revathi, R.; Doczi, I.; Nemeth, T.M.; Narendran, V.; Vagvolgyi, C.; Manoharan, C.; Kredics, L.

    2009-01-01

    We report the first known case of fungal keratitis caused by Aspergillus nomius. Ocular injury was known as a predisposing factor. The patient was treated with natamycin and econazole eye drops, itraconazole eye ointment, and oral ketoconazole. A therapeutic penetrating keratoplasty was performed 16

  7. Infectious keratitis caused by Aspergillus tubingensis

    NARCIS (Netherlands)

    Kredics, L.; Varga, J.; Kocsube, S.; Rajaraman, R.; Raghavan, A.; Doczi, I.; Bhaskar, M.; Nemeth, T.M.; Antal, Z.; Venkatapathy, N.; Vagvolgyi, C.; Samson, R.A.; Chockaiya, M.; Palanisamy, M.

    2009-01-01

    PURPOSE: To report 2 cases of keratomycosis caused by Aspergillus tubingensis. METHODS: The therapeutic courses were recorded for 2 male patients, 52 and 78 years old, with fungal keratitis caused by black Aspergillus strains. Morphological examination of the isolates was carried out on malt extract

  8. Mycotic Keratitis Due to Aspergillus nomius▿

    Science.gov (United States)

    Manikandan, Palanisamy; Varga, János; Kocsubé, Sándor; Samson, Robert A.; Anita, Raghavan; Revathi, Rajaraman; Dóczi, Ilona; Németh, Tibor Mihály; Narendran, Venkatapathy; Vágvölgyi, Csaba; Manoharan, Chockaiya; Kredics, László

    2009-01-01

    We report the first known case of fungal keratitis caused by Aspergillus nomius. Ocular injury was known as a predisposing factor. The patient was treated with natamycin and econazole eye drops, itraconazole eye ointment, and oral ketoconazole. A therapeutic penetrating keratoplasty was performed 16 days after presentation. A sequence-based approach was used to assign the isolate to a species. PMID:19710265

  9. Ulcerative Keratitis: incidence, seasonal distribution and ...

    African Journals Online (AJOL)

    The seasonal distribution of corneal ulcer was highest in month June 11(18.0%). Complications from the ulcers included central leucoma 19 (31.2%) and panophthalmitis 6 (9.9%). Conclusion: The incidence rate of ulcerative keratitis is 0.6% occurring highest in the month of June with more bacterial than fungal isolates.

  10. Strategies for the prevention of contact lens-related Acanthamoeba keratitis: a review.

    Science.gov (United States)

    Carnt, Nicole; Stapleton, Fiona

    2016-03-01

    Acanthamoeba keratitis is a severe, often sight threatening, corneal infection which in Western countries is predominantly seen in daily wear of contact lenses. This review aims to summarise the pathobiology and epidemiology of contact lens-related Acanthamoeba keratitis, and to present strategies for prevention, particularly with respect to modifiable risk factors in contact lens wear. The virulence of Acanthamoeba and resistance to treatment in keratitis appears to be linked with the production of a low molecular weight protease MIP133 by the organism, in response to binding to corneal epithelial cells through a mannose binding protein, and to the ability of the organism to convert from the trophozoite to the resistant cyst form. Recent epidemiological studies in contact lens relate disease have confirmed the link between solution topping up and Acanthamoeba keratitis and have reinforced the importance of avoidance of tap water, either as part of the care for the contact lens or storage case, handling lenses with wet hands or showering while wearing lenses. In the most recent analysis from the USA, there were no strong effects for solution type, water source or water disinfection process. Wearer age, lens wear time and history to appear to be linked with Acanthamoeba keratitis. Daily disposable contact lens use would be expected to reduce the prevalence of Acanthamoeba disease although this is unproven. While Acanthamoeba keratitis remains challenging to diagnose and manage, strategies to limit the disease severity in contact lens wearers should include attention to recently identified risk factors, particularly those related to water contact. Public health awareness measures, the use of daily disposable contact lenses, a better understanding of the contribution of the host immunity and the development of standardised methods for culture of amoeba and testing of contact lens care systems against Acanthamoeba in the licensing process may be of value. Alternative

  11. Establishment of effective methods for transducing genes into iris pigment epithelial cells by using adeno-associated virus type 2.

    Science.gov (United States)

    Sugano, Eriko; Tomita, Hiroshi; Ishiguro, Sei-ichi; Abe, Toshiaki; Tamai, Makoto

    2005-09-01

    To establish an efficient method of transferring the human brain-derived neurotrophic-factor (hBDNF) gene into human iris pigment epithelial (hIPE) cells by using recombinant adeno-associated virus type 2 (rAAV2). Cultured hIPE cells were treated with either hydroxyurea-sodium butyrate (HUSB; DNA synthesis inhibitor), or tyrphostin-1 (Tyr; epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor), or a combination of HUSB and Tyr (HUSB-Tyr). After each treatment, cells were exposed to rAAV2 (rAAV-LacZ or rAAV-hBDNF). The levels of BDNF were measured by ELISA and also determined by Western blot analysis. Southern blot analysis was performed on each type of treated cell. The neuroprotective effect of BDNF on the retinal ganglion cells (RGCs) was quantitatively assessed by culturing rAAV-hBDNF-hIPE with RGCs. The infection of hIPE cells was significantly lower than ARPE and HT1080 cells, which are highly permissive cells for rAAV2. The treatment of HUSB-Tyr enhanced the transgene expression more than that after treatment with one of these agents in rAAV-hIPE cells. Southern hybridization revealed that the amount of replicative form monomer (RFm) was less in Tyr than in HUSB or HUSB-Tyr treatment and there was no difference in conversion of virus genome to double stranded form after HUSB and HUSB-Tyr treatment. However, adding Tyr treatment stimulated the JNK1/2 and p38 pathways and modified the target transgene expression. BDNF had a significantly greater rescue effect of RGCs with the HUSB-Tyr-treated rAAV-hBDNF-hIPE cells (P 0.05) compared with noninfected hIPE cells. The combined treatment of HUSB-Try is an effective method of increasing transgene expression with the AAV-mediated gene transfer. The role of HUSB and Tyr in the increase of gene expression may be different and related to the conversion of virus into the host genome and the enhancement of the transcription, respectively.

  12. Impact of psm-mec in Methicillin-Resistant Staphylococcus aureus (ST764) Strains Isolated from Keratitis Patients.

    Science.gov (United States)

    Suzuki, Takashi; Yamamoto, Toshihiro; Kaito, Chikara; Miyamoto, Hitoshi; Ohashi, Yuichi

    2016-10-01

    Staphylococcus aureus is a predominant pathogen in keratitis, and the rate of methicillin-resistant S. aureus (MRSA) is increasing. In our previous study, genotypes of MRSA isolates from keratitis cases were classified into ST5 or ST764 lineage by multi-locus sequence typing. In this study, we examined the virulence properties of these MRSA keratitis isolates and its virulence determinants. There was no difference in the prevalence of virulence genes, such as adhesion and toxins, between ST5 and ST764 isolates. All ST5 isolates carried the intact psm-mec gene, which suppresses exotoxin production and colony spreading, but promotes biofilm formation. In contrast, all ST764 isolates had one point mutation in the psm-mec gene. Biofilm production in ST5 isolates was significantly higher than that in ST764 isolates, whereas colony spreading, hemolytic activity, and production of alpha-phenol-soluble modulins were higher in ST764 than in ST5 isolates. The toxicity of ST764 supernatants to corneal epithelial cells was higher than that of ST5 supernatants. These results suggest that the point mutation in the psm-mec gene contributes to the difference in virulence properties between ST5 and ST764 isolates in MRSA keratitis.

  13. Preventive Activity against Influenza (H1N1 Virus by Intranasally Delivered RNA-Hydrolyzing Antibody in Respiratory Epithelial Cells of Mice

    Directory of Open Access Journals (Sweden)

    Seungchan Cho

    2015-09-01

    Full Text Available The antiviral effect of a catalytic RNA-hydrolyzing antibody, 3D8 scFv, for intranasal administration against avian influenza virus (H1N1 was described. The recombinant 3D8 scFv protein prevented BALB/c mice against H1N1 influenza virus infection by degradation of the viral RNA genome through its intrinsic RNA-hydrolyzing activity. Intranasal administration of 3D8 scFv (50 μg/day for five days prior to infection demonstrated an antiviral activity (70% survival against H1N1 infection. The antiviral ability of 3D8 scFv to penetrate into epithelial cells from bronchial cavity via the respiratory mucosal layer was confirmed by immunohistochemistry, qRT-PCR, and histopathological examination. The antiviral activity of 3D8 scFv against H1N1 virus infection was not due to host immune cytokines or chemokines, but rather to direct antiviral RNA-hydrolyzing activity of 3D8 scFv against the viral RNA genome. Taken together, our results suggest that the RNase activity of 3D8 scFv, coupled with its ability to penetrate epithelial cells through the respiratory mucosal layer, directly prevents H1N1 virus infection in a mouse model system.

  14. The BDLF3 gene product of Epstein-Barr virus, gp150, mediates non-productive binding to heparan sulfate on epithelial cells and only the binding domain of CD21 is required for infection.

    Science.gov (United States)

    Chesnokova, Liudmila S; Valencia, Sarah M; Hutt-Fletcher, Lindsey M

    2016-07-01

    The cell surface molecules used by Epstein-Barr virus (EBV) to attach to epithelial cells are not well-defined, although when CD21, the B cell receptor for EBV is expressed epithelial cell infection increases disproportionately to the increase in virus bound. Many herpesviruses use low affinity charge interactions with molecules such as heparan sulfate to attach to cells. We report here that the EBV glycoprotein gp150 binds to heparan sulfate proteoglycans, but that attachment via this glycoprotein is not productive of infection. We also report that only the aminoterminal two short consensus repeats of CD21 are required for efficient infection, This supports the hypothesis that, when expressed on an epithelial cell CD21 serves primarily to cluster the major attachment protein gp350 in the virus membrane and enhance access of other important glycoproteins to the epithelial cell surface. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Pseudomonas keratitis associated with daily wear of silicone hydrogel contact lenses.

    Science.gov (United States)

    Schornack, Muriel M; Faia, Lisa J; Griepentrog, Gregory J

    2008-03-01

    To report two cases of pseudomonas keratitis associated with daily wear of silicone hydrogel contact lenses. Medical records of two patients who developed pseudomonas keratitis while wearing silicone hydrogel lenses on a daily-wear schedule are reviewed and discussed. A 13-year-old girl who wore ACUVUE Advance lenses (Johnson & Johnson Vision Care, Jacksonville, FL) 12 to 14 hours daily developed a paracentral corneal ulcer in her left eye 4 months after beginning contact lens use. Cultures were positive for Pseudomonas aeruginosa. The ulcer responded to fortified antibiotics and resolved in 10 days. Best-corrected visual acuity after resolution of the ulcer was 20/25. A 58-year-old woman with a 30-year history of rigid gas-permeable contact lens wear was refitted with O2 Optix lenses (CIBA Vision, Duluth, GA). Six months later, she had a 4.9 x 4.0 mm epithelial defect with an underlying stromal infiltrate in the right eye. Cultures were positive for P. aeruginosa. The ulcer responded to fortified antibiotics and resolved in 30 days. Best-corrected visual acuity after resolution of the ulcer was 20/30. Increased oxygen permeability associated with silicone hydrogel contact lenses may reduce, but does not eliminate, the risk of pseudomonas keratitis. Studies have yet to quantify the risk of keratitis associated with daily wear of these lens materials. Further study is necessary to identify the risks of complications with daily wear of silicone hydrogel lenses and to determine which factors may contribute to those risks.

  16. Cure Rate of Fungal Keratitis With Antibacterial Therapy.

    Science.gov (United States)

    Matoba, Alice Y; Barrett, Ryan; Lehmann, Anna E

    2017-05-01

    To study the cure rate of fungal keratitis with moxifloxacin 0.3% monotherapy. A retrospective review of patients with culture-proven fungal keratitis who initially received moxifloxacin 0.3% monotherapy was performed. Eleven patients with culture-proven fungal keratitis were initially treated with moxifloxacin. One case each of Curvularia and Alternaria keratitis resolved with moxifloxacin monotherapy (18%). Moxifloxacin may have a significant clinical therapeutic effect in a subset of patients with fungal keratitis. Review of the literature in combination with the current study suggests that in patients with clinical features suggestive of fungal keratitis, if rapid diagnostic tests are negative or not available, pending culture results, initial therapy should include a fluoroquinolone (moxifloxacin or gatifloxacin) and/or an aminoglycoside (tobramycin or gentamicin).

  17. Systematic Analysis of Cell-Type Differences in the Epithelial Secretome Reveals Insights into the Pathogenesis of Respiratory Syncytial Virus-Induced Lower Respiratory Tract Infections.

    Science.gov (United States)

    Zhao, Yingxin; Jamaluddin, Mohammad; Zhang, Yueqing; Sun, Hong; Ivanciuc, Teodora; Garofalo, Roberto P; Brasier, Allan R

    2017-04-15

    Lower respiratory tract infections from respiratory syncytial virus (RSV) are due, in part, to secreted signals from lower airway cells that modify the immune response and trigger airway remodeling. To understand this process, we applied an unbiased quantitative proteomics analysis of the RSV-induced epithelial secretory response in cells representative of the trachea versus small airway bronchiolar cells. A workflow was established using telomerase-immortalized human epithelial cells that revealed highly reproducible cell type-specific differences in secreted proteins and nanoparticles (exosomes). Approximately one third of secretome proteins are exosomal; the remainder are from lysosomal and vacuolar compartments. We applied this workflow to three independently derived primary human cultures from trachea versus bronchioles. A total of 577 differentially expressed proteins from control supernatants and 966 differentially expressed proteins from RSV-infected cell supernatants were identified at a 1% false discovery rate. Fifteen proteins unique to RSV-infected primary human cultures from trachea were regulated by epithelial-specific ets homologous factor. A total of 106 proteins unique to RSV-infected human small airway epithelial cells was regulated by the transcription factor NF-κB. In this latter group, we validated the differential expression of CCL20/macrophage-inducible protein 3α, thymic stromal lymphopoietin, and CCL3-like 1 because of their roles in Th2 polarization. CCL20/macrophage-inducible protein 3α was the most active mucin-inducing factor in the RSV-infected human small airway epithelial cell secretome and was differentially expressed in smaller airways in a mouse model of RSV infection. These studies provide insights into the complexity of innate responses and regional differences in the epithelial secretome participating in RSV lower respiratory tract infection-induced airway remodeling. Copyright © 2017 by The American Association of

  18. Current Thoughts in Fungal Keratitis: Diagnosis and Treatment

    Science.gov (United States)

    Ansari, Zubair; Miller, Darlene; Galor, Anat

    2013-01-01

    Fungal keratitis remains a challenging and often elusive diagnosis in geographic regions where it is endemic. Marred by delays in diagnosis, the sequelae of corneal fungal infections, though preventable, can be irreversible. Recent studies and advances in the arena have broadened the approach and treatment to mycotic keratitis. This review will discuss current diagnostic modalities of fungal keratitis and will particularly focus on treatment regimens. It will also explore future therapeutic models and critique the potential benefit of each. PMID:24040467

  19. [Contact lens-related Fusarium keratitis: a case report].

    Science.gov (United States)

    Amadasi, Silvia; Pelliccioli, Giovanni Federico; Colombini, Paolo; Bonomini, Annalisa; Farina, Claudio; Pietrantonio, Filomena; Pedroni, Palmino

    2017-06-01

    We aim to highlight the key factors for a good outcome of fungal keratitis. We describe a case of contact lens-related Fusarium keratitis in a young girl. After identification of Fusarium spp under direct microscopic examination and in culture, a prolonged treatment with topic natamycin 5% was started and administered for five months with restitutio ad integrum of the eye. Prompt microbiological diagnosis and a specific and prolonged treatment are essential for correct management of Fusarium keratitis.

  20. Successful salvage treatment of Lecythophora mutabilis keratitis with topical voriconazole

    Directory of Open Access Journals (Sweden)

    Bora Yüksel

    2011-09-01

    Full Text Available Fungal keratitis is an important ophthalmic problem in the developing world. Filamentous fungi are the most frequently reported pathogens in fungal keratitis. This report aimed to present a case with Lecythophora mutabilis keratitis that treatment failure was seen with topical and systemic amphotericin B lipid complex. Then she was treated successfully topical voriconazole. J Microbiol Infect Dis 2011;1 (2: 75-77

  1. Case report: spontaneous Stenotrophomonas maltophilia keratitis in a diabetic patient.

    Science.gov (United States)

    Holifield, Karintha; Lazzaro, Douglas R

    2011-09-01

    To report a rare case of spontaneous Stenotrophomonas maltophilia keratitis in a diabetic patient. A case report of this rare ulcerative keratitis case with an extensive review of the literature. The patient's corneal infiltrate was successfully cultured and a rare ocular organism identified. The patient's presentation and course and the response to empiric treatment are discussed. Consideration of the antibiotic combination chosen here can be considered in the treatment of S. maltophilia keratitis after appropriate cultures are taken and the organism isolated.

  2. Microbial keratitis in Gujarat, Western India: findings from 200 cases

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2011-11-01

    Full Text Available INTRODUCTION: The objective of this study was to study the epidemiological characteristics and the microbiological profile of patients suspected with microbial keratitis in Gujarat.

  3. Establishment and functional characterization of a tracheal epithelial cell line RTEC11 from transgenic rats harboring temperature-sensitive simian virus 40 large T-antigen.

    Science.gov (United States)

    Tabuchi, Yoshiaki; Doi, Takeshi; Takasaki, Ichiro; Takahashi, Ri-ichi; Ueda, Masatsugu; Suzuki, Yoshihisa; Obinata, Masuo

    2008-11-01

    A tracheal epithelial cell line RTEC11 was established from transgenic rats harboring temperature-sensitive simian virus 40 large T-antigen. The cells grew continuously at a permissive temperature of 33 degrees C but not at a non-permissive temperature of 39 degrees C. Morphological and functional investigations demonstrated that the cells were polarized epithelial cells maintaining a regulated permeability barrier function. Interestingly, the expression levels of Muc1 (mucin 1) and Scgb1a1 (uteroglobin), non-ciliated secretory cell markers, and Tubb4 (tubulin beta 4), a ciliated cell marker, were significantly increased under the cell growth-restricted condition. Global gene expression and computational network analyses demonstrated a significant genetic network associated with cellular development and differentiation in cells cultured at the non-permissive temperature. The tracheal epithelial cell line RTEC11 with unique characteristics should be useful as an in vitro model for studies of the physiological functions and gene expression of tracheal epithelial cells.

  4. Reverse-phase phosphoproteome analysis of signaling pathways induced by Rift valley fever virus in human small airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Taissia G Popova

    Full Text Available Rift valley fever virus (RVFV infection is an emerging zoonotic disease endemic in many countries of sub-Saharan Africa and in Egypt. In this study we show that human small airway epithelial cells are highly susceptible to RVFV virulent strain ZH-501 and the attenuated strain MP-12. We used the reverse-phase protein arrays technology to identify phosphoprotein signaling pathways modulated during infection of cultured airway epithelium. ZH-501 infection induced activation of MAP kinases (p38, JNK and ERK and downstream transcriptional factors [STAT1 (Y701, ATF2 (T69/71, MSK1 (S360 and CREB (S133]. NF-κB phosphorylation was also increased. Activation of p53 (S15, S46 correlated with the increased levels of cleaved effector caspase-3, -6 and -7, indicating activation of the extrinsic apoptotic pathway. RVFV infection downregulated phosphorylation of a major anti-apoptotic regulator of survival pathways, AKT (S473, along with phosphorylation of FOX 01/03 (T24/31 which controls cell cycle arrest downstream from AKT. Consistent with this, the level of apoptosis inhibitor XIAP was decreased. However, the intrinsic apoptotic pathway marker, caspase-9, demonstrated only a marginal activation accompanied by an increased level of the inhibitor of apoptosome formation, HSP27. Concentration of the autophagy marker, LC3B, which often accompanies the pro-survival signaling, was decreased. Cumulatively, our analysis of RVFV infection in lung epithelium indicated a viral strategy directed toward the control of cell apoptosis through a number of transcriptional factors. Analyses of MP-12 titers in challenged cells in the presence of MAPK inhibitors indicated that activation of p38 represents a protective cell response while ERK activation controls viral replication.

  5. Antirotavirus immunoglobulin A neutralizes virus in vitro after transcytosis through epithelial cells and protects infant mice from diarrhea.

    Science.gov (United States)

    Ruggeri, F M; Johansen, K; Basile, G; Kraehenbuhl, J P; Svensson, L

    1998-04-01

    Rotaviruses are the major cause of severe diarrhea in infants and young children worldwide. Due to their restricted site of replication, i.e., mature enterocytes, local intestinal antibodies have been proposed to play a major role in protective immunity. Whether secretory immunoglobulin A (IgA) antibodies alone can provide protection against rotavirus diarrhea has not been fully established. To address this question, a library of IgA monoclonal antibodies (MAbs) previously developed against different proteins of rhesus rotavirus was used. A murine hybridoma "backpack tumor" model was established to examine if a single MAb secreted onto mucosal surfaces via the normal epithelial transport pathway was capable of protecting mice against diarrhea upon oral challenge with rotavirus. Of several IgA and IgG MAbs directed against VP8 and VP6 of rotavirus, only IgA VP8 MAbs (four of four) were found to protect newborn mice from diarrhea. An IgG MAb recognizing the same epitope as one of the IgA MAbs tested failed to protect mice from diarrhea. We also investigated if antibodies could be transcytosed in a biologically active form from the basolateral domain to the apical domain through filter-grown Madin-Darby canine kidney (MDCK) cells expressing the polymeric immunoglobulin receptor. Only IgA antibodies with VP8 specificity (four of four) neutralized apically administered virus. The results support the hypothesis that secretory IgA antibodies play a major role in preventing rotavirus diarrhea. Furthermore, the results show that the in vivo and in vitro methods described are useful tools for exploring the mechanisms of viral mucosal immunity.

  6. Medical interventions for acanthamoeba keratitis.

    Science.gov (United States)

    Alkharashi, Majed; Lindsley, Kristina; Law, Hua Andrew; Sikder, Shameema

    2015-02-24

    Acanthamoeba are microscopic, free-living, single-celled organisms which can infect the eye and lead to Acanthamoeba keratitis (AK). AK can result in loss of vision in the infected eye or loss of eye itself; however, there are no formal guidelines or standards of care for the treatment of AK. To evaluate the relative effectiveness and safety of medical therapy for the treatment of AK. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), PubMed (1948 to January 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to January 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 9 January 2015. We included randomized controlled trials (RCTs) of medical therapy for AK, regardless of the participants' age, sex, or etiology of disease. We included studies that compared either anti-amoeba therapy (drugs used alone or in combination with other medical therapies) with no anti-amoeba therapy or one anti-amoeba therapy with another anti-amoeba therapy. Two authors independently screened search results and full-text reports, assessed risk of bias, and abstracted data. We used standard methodological procedures as set forth by the Cochrane Collaboration. We included one RCT (56 eyes of 55 participants) in this review. The study compared two types of topical biguanides for the treatment of AK: chlorhexidine 0.02% and polyhexamethylene biguanide (PHMB) 0.02%. All participants were contact lens

  7. Microsphaeropsis olivacea keratitis and consecutive endophthalmitis.

    Science.gov (United States)

    Shah, C V; Jones, D B; Holz, E R

    2001-01-01

    To report a case of fungal keratitis with consecutive endophthalmitis caused by Microsphaeropsis olivacea. Case report. A 51-year-old man developed fungal keratitis and consecutive endophthalmitis after sustaining a penetrating injury to the right eye. Cultures of the aqueous humor yielded M. olivacea. Infection resolved after intraocular fungal debridement, intravitreous amphotericin B, and aggressive topical natamycin and oral fluconazole. Persistent, low-grade smoldering corneal and intraocular inflammation required topical corticosteroid therapy. M. olivacea is an exceedingly rare ocular pathogen. The intraocular portion of the infection responded quickly to intravitreal antifungal treatment; however, the course was prolonged by smoldering corneal inflammation. Prompt recognition of intraocular spread and aggressive treatment may be beneficial in fungal infections caused by unusual organisms with uncertain virulence.

  8. Eosinofil keratitis hos en dansk hest

    DEFF Research Database (Denmark)

    Olsen, Emil; Henriksen, Michala de Linde; Andersen, Pia Haubro

    2009-01-01

    Eosinofil keratitis (EK) er en relativt sjælden øjenlidelse hos hest, som især ses i tempererede områder. Klinisk er lidelsen karakteriseret ved én eller multiple corneaulcerationer dækket med hvidt eller gelatinøst proliferativt subepithelialt plaque. Denne casereport, som omhandler en 20-årig...

  9. A stepping stone in treating dendritic keratitis

    Directory of Open Access Journals (Sweden)

    Hosam Sheha, MD, PhD

    2017-09-01

    Conclusions and importance: Self-retained amniotic membrane after debridement appears effective in treating dendritic keratitis. While early debridement is crucial to remove the infected corneal epithelium, amniotic membrane was shown to enhance the healing without scarring or recurrence. Besides the known anti-inflammatory and anti-scarring effects of the amniotic membrane, it may have a potential topical antiviral effect that warrants further investigation.

  10. Cell-to-Cell Contact and Nectin-4 Govern Spread of Measles Virus from Primary Human Myeloid Cells to Primary Human Airway Epithelial Cells

    Science.gov (United States)

    Singh, Brajesh K.; Li, Ni; Mark, Anna C.; Mateo, Mathieu; Cattaneo, Roberto

    2016-01-01

    ABSTRACT Measles is a highly contagious, acute viral illness. Immune cells within the airways are likely first targets of infection, and these cells traffic measles virus (MeV) to lymph nodes for amplification and subsequent systemic dissemination. Infected immune cells are thought to return MeV to the airways; however, the mechanisms responsible for virus transfer to pulmonary epithelial cells are poorly understood. To investigate this process, we collected blood from human donors and generated primary myeloid cells, specifically, monocyte-derived macrophages (MDMs) and dendritic cells (DCs). MDMs and DCs were infected with MeV and then applied to primary cultures of well-differentiated airway epithelial cells from human donors (HAE). Consistent with previous results obtained with free virus, infected MDMs or DCs were incapable of transferring MeV to HAE when applied to the apical surface. Likewise, infected MDMs or DCs applied to the basolateral surface of HAE grown on small-pore (0.4-μm) support membranes did not transfer virus. In contrast, infected MDMs and DCs applied to the basolateral surface of HAE grown on large-pore (3.0-μm) membranes successfully transferred MeV. Confocal microscopy demonstrated that MDMs and DCs are capable of penetrating large-pore membranes but not small-pore membranes. Further, by using a nectin-4 blocking antibody or recombinant MeV unable to enter cells through nectin-4, we demonstrated formally that transfer from immune cells to HAE occurs in a nectin-4-dependent manner. Thus, both infected MDMs and DCs rely on cell-to-cell contacts and nectin-4 to efficiently deliver MeV to the basolateral surface of HAE. IMPORTANCE Measles virus spreads rapidly and efficiently in human airway epithelial cells. This rapid spread is based on cell-to-cell contact rather than on particle release and reentry. Here we posit that MeV transfer from infected immune cells to epithelial cells also occurs by cell-to-cell contact rather than through cell

  11. Photodynamic inactivation of pathogens causing infectious keratitis

    Science.gov (United States)

    Simon, Carole; Wolf, G.; Walther, M.; Winkler, K.; Finke, M.; Hüttenberger, D.; Bischoff, Markus; Seitz, B.; Cullum, J.; Foth, H.-J.

    2014-03-01

    The increasing prevalence of antibiotic resistance requires new approaches also for the treatment of infectious keratitis. Photodynamic Inactivation (PDI) using the photosensitizer (PS) Chlorin e6 (Ce6) was investigated as an alternative to antibiotic treatment. An in-vitro cornea model was established using porcine eyes. The uptake of Ce6 by bacteria and the diffusion of the PS in the individual layers of corneal tissue were investigated by fluorescence. After removal of the cornea's epithelium Ce6-concentrations keratitis patients were tested in liquid culture against different concentrations of Ce6 (1 - 512 μM) using 10 minutes irradiation (E = 18 J/cm2 ). This demonstrated that a complete inactivation of the pathogen strains were feasible whereby SA was slightly more susceptible than PA. 3909 mutants of the Keio collection of Escherichia coli (E.coli) were screened for potential resistance factors. The sensitive mutants can be grouped into three categories: transport mutants, mutants in lipopolysaccharide synthesis and mutants in the bacterial SOS-response. In conclusion PDI is seen as a promising therapy concept for infectious keratitis.

  12. Pattern recognition receptors in microbial keratitis

    Science.gov (United States)

    Taube, M-A; del Mar Cendra, M; Elsahn, A; Christodoulides, M; Hossain, P

    2015-01-01

    Microbial keratitis is a significant cause of global visual impairment and blindness. Corneal infection can be caused by a wide variety of pathogens, each of which exhibits a range of mechanisms by which the immune system is activated. The complexity of the immune response to corneal infection is only now beginning to be elucidated. Crucial to the cornea's defences are the pattern-recognition receptors: Toll-like and Nod-like receptors and the subsequent activation of inflammatory pathways. These inflammatory pathways include the inflammasome and can lead to significant tissue destruction and corneal damage, with the potential for resultant blindness. Understanding the immune mechanisms behind this tissue destruction may enable improved identification of therapeutic targets to aid development of more specific therapies for reducing corneal damage in infectious keratitis. This review summarises current knowledge of pattern-recognition receptors and their downstream pathways in response to the major keratitis-causing organisms and alludes to potential therapeutic approaches that could alleviate corneal blindness. PMID:26160532

  13. Improvement in corneal scarring following bacterial keratitis.

    Science.gov (United States)

    McClintic, S M; Srinivasan, M; Mascarenhas, J; Greninger, D A; Acharya, N R; Lietman, T M; Keenan, J D

    2013-03-01

    Bacterial keratitis results in corneal scarring and subsequent visual impairment. The long-term evolution of corneal scars has not been well described. In this case series, we identified patients who had improvement in corneal scarring and visual acuity from a clinical trial for bacterial keratitis. We searched the records of the Steroids for Corneal Ulcers Trial (SCUT) for patients who had improvement in vision between the 3-month and 12-month visits and reviewed their clinical photographs. Of the 500 patients enrolled in SCUT, five patients with large central corneal scars due to bacterial keratitis are presented. All experienced improvement in rigid contact lens-corrected visual acuity from months 3 to 12. All patients also had marked improvement in corneal opacity during the same time period. None of the patients opted to have penetrating keratoplasty. Corneal scars may continue to improve even many months after a bacterial corneal ulcer has healed. The corneal remodeling can be accompanied by considerable improvement in visual acuity, such that corneal transplantation may not be necessary.

  14. Microbial keratitis in West and East Malaysia

    Directory of Open Access Journals (Sweden)

    Vanitha Ratnalingam

    2017-11-01

    Full Text Available AIM: To evaluate the epidemiological and etiological factors of microbial keratitis seen in tertiary hospitals in West and East Malaysia.METHODS: A total of 207 patients were enrolled. Patients referred for microbial keratitis to Sungai Buloh Hospital and Kuala Lumpur Hospital in West Malaysia and Queen Elizabeth Hospital and Kuching General Hospital in East Malaysia were recruited. Risk factors were documented. Corneal scrapings for microscopy and culture were performed.RESULTS: The most common risk factor in West Malaysia was organic trauma(28.5%followed by non organic trauma(18.3%; 27.7% of trauma cases was work related with 34.2% involving male foreign workers. The most common risk factor in East Malaysia was contact lens wear(32.9%. Pseudomonas aeruginosa was the most common organism isolated in both places. The most common fungal pathogen in West Malaysia was Fusarium spp representing 60% of all positive fungal cultures.CONCLUSION: In West Malaysia organic trauma was the most common risk factor seen in public hospitals here whereas, contact lens wear was the most common risk factor in East Malaysia(P<0.05. Fungal keratitis was more commonly seen in West Malaysia.

  15. Expression of IL-8, IL-6 and IL-1β in Tears as a Main Characteristic of the Immune Response in Human Microbial Keratitis

    Science.gov (United States)

    Santacruz, Concepcion; Linares, Marisela; Garfias, Yonathan; Loustaunau, Luisa M.; Pavon, Lenin; Perez-Tapia, Sonia Mayra; Jimenez-Martinez, Maria C.

    2015-01-01

    Corneal infections are frequent and potentially vision-threatening diseases, and despite the significance of the immunological response in animal models of microbial keratitis (MK), it remains unclear in humans. The aim of this study was to describe the cytokine profile of tears in patients with MK. Characteristics of ocular lesions such as size of the epithelial defect, stromal infiltration, and hypopyon were analyzed. Immunological evaluation included determination of interleukine (IL)-1β, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor (TNF)-α in tear samples obtained from infected eyes of 28 patients with MK and compared with their contralateral non-infected eyes. Additionally, frequency of CD4+, CD8+, CD19+ and CD3−CD56+ cells was also determined in peripheral blood mononuclear cells in patients with MK, and compared with 48 healthy controls. Non-significant differences were observed in the size of the epithelial defect, stromal infiltration, and hypopyon. Nevertheless, we found an immunological profile apparently related to MK etiology. IL-8 > IL-6 in patients with bacterial keratitis; IL-8 > IL-6 > IL-1β and increased frequency of circulating CD3−CD56+ NK cells in patients with gram-negative keratitis; and IL-8 = IL-6 > IL-1β in patients with fungal keratitis. Characterization of tear cytokines from patients with MK could aid our understanding of the immune pathophysiological mechanisms underlying corneal damage in humans. PMID:25741769

  16. Epstein-Barr Virus Fusion with Epithelial Cells Triggered by gB Is Restricted by a gL Glycosylation Site.

    Science.gov (United States)

    Möhl, Britta S; Chen, Jia; Park, Seo Jin; Jardetzky, Theodore S; Longnecker, Richard

    2017-12-01

    Epstein-Barr virus (EBV) entry into epithelial cells is mediated by the conserved core fusion machinery, composed of the fusogen gB and the receptor-binding complex gH/gL. The heterodimeric gH/gL complex binds to the EBV epithelial cell receptor or gp42, which binds to the B-cell receptor, triggering gB-mediated fusion of the virion envelope with cellular membranes. Our previous study found that the gL glycosylation mutant N69L/S71V had an epithelial cell-specific hyperfusogenic phenotype. To study the influence of this gL mutant on the initiation and kinetics of gB-driven epithelial cell fusion, we established a virus-free split-green fluorescent protein cell-cell fusion assay that enables real-time measurements of membrane fusion using live cells. The gL_N69L/S71V mutant had a large increase in epithelial cell fusion activity of up to 300% greater than that of wild-type gL starting at early time points. The hyperfusogenicity of the gL mutant was not a result of alterations in complex formation with gH or alterations in cellular localization. Moreover, the hyperfusogenic phenotype of the gL mutant correlated with the formation of enlarged syncytia. In summary, our present findings highlight an important role of gL in the kinetics of gB-mediated epithelial cell fusion, adding to previous findings indicating a direct interaction between gL and gB in EBV membrane fusion.IMPORTANCE EBV predominantly infects epithelial cells and B lymphocytes, which are the cells of origin for the EBV-associated malignancies Hodgkin and Burkitt lymphoma as well as nasopharyngeal carcinoma. Contrary to the other key players of the core fusion machinery, gL has the most elusive role during EBV-induced membrane fusion. We found that the glycosylation site N69/S71 of gL is involved in restricting epithelial cell fusion activity, strongly correlating with syncytium size. Interestingly, our data showed that the gL glycosylation mutant increases the fusion activity of the hyperfusogenic g

  17. Congenital Corneal Anesthesia and Neurotrophic Keratitis: Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    Flavio Mantelli

    2015-01-01

    Full Text Available Neurotrophic keratitis (NK is a rare degenerative disease of the cornea caused by an impairment of corneal sensory innervation, characterized by decreased or absent corneal sensitivity resulting in epithelial keratopathy, ulceration, and perforation. The aetiopathogenesis of corneal sensory innervation impairment in children recognizes the same range of causes as adults, although they are much less frequent in the pediatric population. Some extremely rare congenital diseases could be considered in the aetiopathogenesis of NK in children. Congenital corneal anesthesia is an extremely rare condition that carries considerable diagnostic and therapeutic problems. Typically the onset is up to 3 years of age and the cornea may be affected in isolation or the sensory deficit may exist as a component of a congenital syndrome, or it may be associated with systemic somatic anomalies. Accurate diagnosis and recognition of risk factors is important for lessening long-term sequelae of this condition. Treatment should include frequent topical lubrication and bandage corneal or scleral contact lenses. Surgery may be needed in refractory cases. The purpose of this review is to summarize and update data available on congenital causes and treatment of corneal hypo/anesthesia and, in turn, on congenital NK.

  18. Microbial Keratitis After Collagen Cross-linking Treatment

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    Banu Torun Acar

    2012-07-01

    Full Text Available A 33-year-old woman presented with pain, redness, and diminution of vision that occurred 2 days after collagen cross-linking had been performed for keratoconus in the right eye. Culture results from the patient's contact lens and corneal scrapings were positive for Staphylococcus epidermidis. According to the results of antibiotic susceptibility testing, the patient was treated with hourly topical fortified vancomycin and exocin. Before collagen cross-linking, the best-corrected visual acuity (BCVA was 4/10, the manifest refraction was -7.00 -1.755 3°. Four months after the procedure, the BCVA was 4/10, the manifest refraction was -5.50 -1.75 10°. Slit-lamp examination revealed a mild residual haze in the upper midperipheral cornea, and stromal opacities had disappeared. Collagen crosslinking is less invasive compared to other methods for treatment of keratoconus, but epithelial debridement and bandage contact lens wearing may lead to the development of bacterial keratitis. (Turk J Oph thal mol 2012; 42: 300-2

  19. CLINICAL FEATURES, DIAGNOSIS, THE RESULTS OF THERAPEUTIC AND SURGICAL TREATMENT OF ACANTHAMOEBIC KERATITIS

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    Evg. A. Kasparova

    2017-01-01

    Full Text Available Purpose: to describe our experience in Acanthamoeba keratitis diagnostics and treatment in the FGBNU Research Institute of eye diseases, Moscow.Patients and Methods. We observed 24 patients (25 eyes with the Acanthamoeba keratitis (AK. The age ranged from 18 to 47 years. All patients, except one, were contact lenses wearers. Clinical signs included superficial epithelial-stromal lesions in 8 patients (8 eyes, stromal forms of AK- in 16 patients (17 eyes, and mixed keratitis in 9 (9 eyes. We used confocal microscopy, conjunctival smearing and blood immunofluorescent analysis for HSV types I and II. 8 patients (8 eyes underwent penetrating keratoplasty (PKP and their corneal buttons were morphologically examined. AK treatment included 2 biguanid antiseptics — a PHMB ("Comfort-drops" — solution for contact lenses care and 0.025% solution of a chlorhexidini bigluconati, or "Vitabact" in frequent instillations. We also used Diflucan solution 0.2% instillations — 6–8 times a day in, and Orungal or Diflucan per os (200 mg once a day. Eye drops of aminoglycozide or fluorhinolon groups were added to the treatment as well. In the cases of mixed Acanthamoeba and HSV keratitis we used anti-herpetic medications (Poludan, Acyclovir.Results. Cysts were found with confocal microscopy in 66% examined patients, and in 75% of the corneal buttons after keratoplasty. 15 cases (60% healed with various intensity opacities. We removed corneal epithelium in 2 patients with poor effect of the medication treatment. 8 patients (8 eyes underwent PKP with transparent (2 patients and a semi-transparent engraftment (2 patients, in 4 cases (4 eyes AK recurrences had occurred, what required repeated surgery. Long persistence of Acanthamoeba cysts in the cornea after clinical recovery caused the admission of 2 antiseptic biguanids eye drops for 6–20 months in all patients. There were no recurrences in the group of patients during the observation period (range 1 to 6

  20. Respiratory syncytial virus induced type I IFN production by pDC is regulated by RSV-infected airway epithelial cells, RSV-exposed monocytes and virus specific antibodies.

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    Marcel A Schijf

    Full Text Available Innate immune responses elicited upon virus exposure are crucial for the effective eradication of viruses, the onset of adaptive immune responses and for establishing proper immune memory. Respiratory syncytial virus (RSV is responsible for a high disease burden in neonates and immune compromised individuals, causing severe lower respiratory tract infections. During primary infections exuberant innate immune responses may contribute to disease severity. Furthermore, immune memory is often insufficient to protect during RSV re-exposure, which results in frequent symptomatic reinfections. Therefore, identifying the cell types and pattern recognition receptors (PRRs involved in RSV-specific innate immune responses is necessary to understand incomplete immunity against RSV. We investigated the innate cellular response triggered upon infection of epithelial cells and peripheral blood mononuclear cells. We show that CD14(+ myeloid cells and epithelial cells are the major source of IL-8 and inflammatory cytokines, IL-6 and TNF-α, when exposed to live RSV Three routes of RSV-induced IFN-α production can be distinguished that depend on the cross-talk of different cell types and the presence or absence of virus specific antibodies, whereby pDC are the ultimate source of IFN-α. RSV-specific antibodies facilitate direct TLR7 access into endosomal compartments, while in the absence of antibodies, infection of monocytes or epithelial cells is necessary to provide an early source of type I interferons, required to engage the IFN-α,β receptor (IFNAR-mediated pathway of IFN-α production by pDC. However, at high pDC density infection with RSV causes IFN-α production without the need for a second party cell. Our study shows that cellular context and immune status are factors affecting innate immune responses to RSV. These issues should therefore be addressed during the process of vaccine development and other interventions for RSV disease.

  1. Microbial keratitis in Gujarat, Western India: findings from 200 cases ...

    African Journals Online (AJOL)

    Introduction: The objective of this study was to study the epidemiological characteristics and the microbiological profile of patients suspected with microbial keratitis in Gujarat. Methods: Corneal scraping was collected from 200 consecutive cases of suspected microbial keratitis and was subjected to direct examination and ...

  2. Hepatitis C virus core protein epigenetically silences SFRP1 and enhances HCC aggressiveness by inducing epithelial-mesenchymal transition.

    Science.gov (United States)

    Quan, H; Zhou, F; Nie, D; Chen, Q; Cai, X; Shan, X; Zhou, Z; Chen, K; Huang, A; Li, S; Tang, N

    2014-05-29

    Hepatocellular carcinoma (HCC) is one of the most deadly cancers. Aberrant oncogenic activation of the Wnt/β-catenin signaling pathway contributes to hepatocellular carcinogenesis. Various epigenetic modifications of the Wnt antagonist secreted frizzled-related protein (SFRP) family have been implicated in regulating Wnt signaling. Here, we report that Hepatitis C virus (HCV) core protein downregulates SFRP1 expression when it is expressed in Huh7 and HepG2 cells. SFRP1 expression can be effectively restored by using either a DNA methylation inhibitor alone or in combination with a histone deacetylase inhibitor. DNA methylation analysis of the SFRP1 promoter revealed that cytosine-phosphate-guanine (CpG) islands close to the transcriptional start site (TSS) in the SFRP1 promoter were hypermethylated in core-expressing Huh7 cells, suggesting that HCV core protein may downregulate SFRP1 expression by inducing hypermethylation of the SFRP1 promoter. Chromatin immunoprecipitation revealed that HCV core protein markedly increased the expression level and binding of DNA methyltransferase-1 (Dnmt1) and histone deacetylase-1 (HDAC1) to the TSS of the SFRP1 promoter region, resulting in repression of acetyl-histone H3-binding capacity to SFRP1 promoter and the eventual epigenetic silencing of SFRP1 expression. Furthermore, the core protein-promoted cell proliferation, migration and invasiveness were effectively abrogated either by Dnmt1 knockdown or restoration of SFRP1 expression in hepatoma cells. Dnmt1 knockdown or SFRP1 overexpression also inhibited HCV core-induced epithelial-mesenchymal transition (EMT) and significantly decreased the expression levels of activated β-catenin and Wnt/β-catenin target genes, c-Myc and cyclin D1. We further showed that knockdown of Dnmt1 and restoration of SFRP1 inhibited core-induced in vivo tumor growth and aggressiveness in a xenograft HCC model. Taken together, our results strongly suggest that the HCV core-induced epigenetic

  3. Postoperative keratitis due to Paecilomyces: a rare pediatric case.

    Science.gov (United States)

    Toker, Ebru; Ziyade, Nihan; Atici, Serkan; Eda, Kepenekli Kadayifçi; Türel, Özden; Toprak, Demet; Oray, Merih; Cerikcioglu, Nilgün; Soysal, Ahmet; Bakir, Mustafa

    2016-01-01

    Fungal infections like Paecilomyces keratitis have emerged in childhood recently. The diagnosis and treatment of Paecilomyces keratitis is difficult and the outcome is usually poor. Corneal culture should be performed on fungal media such as Sabouraud glucose neopeptone agar (SDA) as soon as possible for diagnosis. We report a rare case of Paecilomyces keratitis in an immunocompetent child, which was unresponsive to amphotericin B. The case was managed by a multidisciplinary approach involving the departments of ophthalmology, microbiology and pediatric infectious diseases. We want to draw attention once again that fungal keratitis caused by unusual agents are increasing. Physicians should consider fungal causes of keratitis, in patients with some predisposing factors like ocular surgery and prolonged use of topical corticosteroids.

  4. Management and treatment of contact lens-related Pseudomonas keratitis

    Directory of Open Access Journals (Sweden)

    Willcox MD

    2012-06-01

    Full Text Available Mark DP WillcoxSchool of Optometry and Vision Science, University of New South Wales, Sydney, AustraliaAbstract: Pubmed and Medline were searched for articles referring to Pseudomonas keratitis between the years 2007 and 2012 to obtain an overview of the current state of this disease. Keyword searches used the terms "Pseudomonas" + "Keratitis" limit to "2007–2012", and ["Ulcerative" or "Microbial"] + "Keratitis" + "Contact lenses" limit to "2007–2012". These articles were then reviewed for information on the percentage of microbial keratitis cases associated with contact lens wear, the frequency of Pseudomonas sp. as a causative agent of microbial keratitis around the world, the most common therapies to treat Pseudomonas keratitis, and the sensitivity of isolates of Pseudomonas to commonly prescribed antibiotics. The percentage of microbial keratitis associated with contact lens wear ranged from 0% in a study from Nepal to 54.5% from Japan. These differences may be due in part to different frequencies of contact lens wear. The frequency of Pseudomonas sp. as a causative agent of keratitis ranged from 1% in Japan to over 50% in studies from India, Malaysia, and Thailand. The most commonly reported agents used to treat Pseudomonas keratitis were either aminoglycoside (usually gentamicin fortified with a cephalosporin, or monotherapy with a fluoroquinolone (usually ciprofloxacin. In most geographical areas, most strains of Pseudomonas sp. (≥95% were sensitive to ciprofloxacin, but reports from India, Nigeria, and Thailand reported sensitivity to this antibiotic and similar fluoroquinolones of between 76% and 90%.Keywords: Pseudomonas, keratitis, contact lens

  5. Synergistic effect of regenerating agent plus cord blood serum eye drops for the treatment of resistant neurotrophic keratitis: a case report and a hypothesis for pathophysiologic mechanism

    Directory of Open Access Journals (Sweden)

    Giannaccare G

    2015-11-01

    Full Text Available Giuseppe Giannaccare,1 Michela Fresina,1 Aldo Vagge,2 Piera Versura1 1Ophthalmology Unit, DIMES, S Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy; 2Eye Clinic, DiNOGMI, University of Genoa, Genoa, Italy Abstract: This report describes a case of a 72-year-old Caucasian woman presenting with a large neurotrophic keratitis with a large persistent epithelial defect, with a longest linear diameter of 7 mm and greatest perpendicular width of 5 mm, affecting epithelium, Bowman membrane, and anterior stroma. Corneal disease was resistant to conventional treatment and classified as stage 2 according to Mackie classification. Patient was instructed to instill regenerating agent (RGTA eye drops in the morning, as the first eye drop, once every 5 days in combination with daily cord blood serum (CBS eye drops 6 times/day. The patient was asked to visit after 1 week (V1, 2 weeks (V2, 3 weeks (V3, and 4 weeks (V4 of study treatment. In V4 treatment, corneal sensitivity improved, and keratitis healed with resolution of stromal inflammation. Global treatment tolerance was very satisfactory. Patient continued the therapy for a further month after complete healing. Currently, the patient has been followed up for 3 months without any sign of keratitis recurrence. To the best of our knowledge, this case report describes for the first time the successful combined use of RGTA and CBS eye drops for the treatment of neurotrophic keratitis resistant to conventional treatment. We hypothesize that RGTA eye drops could provide an optimal migration substrate and that growth factors supplied by CBS eye drops could strengthen the repair process by promoting cell growth over the matrix. Combined RGTA and CBS eye drop therapy could be a new potential option for the successful treatment of resistant neurotrophic keratitis, particularly when each drug alone is not effective. Keywords: neurotrophic keratitis, regenerating agent, cord blood serum eye drops

  6. Synergistic effect of regenerating agent plus cord blood serum eye drops for the treatment of resistant neurotrophic keratitis: a case report and a hypothesis for pathophysiologic mechanism

    OpenAIRE

    Giannaccare G; Fresina M; Vagge A; Versura P

    2015-01-01

    Giuseppe Giannaccare,1 Michela Fresina,1 Aldo Vagge,2 Piera Versura1 1Ophthalmology Unit, DIMES, S Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy; 2Eye Clinic, DiNOGMI, University of Genoa, Genoa, Italy Abstract: This report describes a case of a 72-year-old Caucasian woman presenting with a large neurotrophic keratitis with a large persistent epithelial defect, with a longest linear diameter of 7 mm and greatest perpendicular width of 5 mm, affecting epithelium, Bow...

  7. Corticosteroids as a therapy for bacterial keratitis: an evidence-based review of 'who, when and why'.

    Science.gov (United States)

    Tallab, Raghad T; Stone, Donald U

    2016-06-01

    Corticosteroids have been proposed as an adjunct to antibiotics for the treatment of bacterial keratitis, with significant controversy regarding the appropriate use of this therapy. Recent prospective randomised controlled trials have provided additional evidence to guide clinical decision-making. A review of the epidemiology and mechanisms of pathogenesis, preliminary animal studies, retrospective human studies and prospective randomised clinical trials that address the potential risks and benefits of corticosteroids in patients with bacterial keratitis was performed. Four prospective randomised controlled trials were identified. Three small studies found no benefit of topical corticosteroids, but were underpowered to evaluate adverse events. The Steroids for Corneal Ulcers Trial (SCUT) study and subgroup analyses provide evidence for a relative gain of one line of best spectacle-corrected visual acuity in patients with non-Nocardia bacterial keratitis, especially when corticosteroids were initiated within 3 days of presentation; no increase in adverse events was noted. No evidence was found to support the concern for corneal thinning attributable to corticosteroids in the absence of an inadequately treated infectious process. In patients with culture-proven non-Nocardia bacterial keratitis, corticosteroids provide one line of vision improvement over antimicrobials alone, with no increase in adverse events. This benefit should not be extrapolated to patients with other aetiologies of keratitis, such as fungus, herpes viruses, acanthamoeba or atypical mycobacteria, and these entities should be excluded before considering adjunctive steroid therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Interleukin-1 alpha produced by human T-cell leukaemia virus type I-infected T cells induces intercellular adhesion molecule-1 expression on lung epithelial cells.

    Science.gov (United States)

    Nakayama, Yuko; Ishikawa, Chie; Tamaki, Kazumi; Senba, Masachika; Fujita, Jiro; Mori, Naoki

    2011-12-01

    The pathogenic mechanism of human T-cell leukaemia virus type I (HTLV-I)-related pulmonary disease, which involves overexpression of intercellular adhesion molecule-1 (ICAM-1) in lung epithelial cells, was investigated. The supernatant of HTLV-I-infected Tax(+) MT-2 and C5/MJ cells induced ICAM-1 expression on A549 cells, a human tumour cell line with the properties of alveolar epithelial cells. Neutralization of ICAM-1 partially inhibited HTLV-I-infected T-cell adhesion to A549 cells. Analysis of the ICAM-1 promoter showed that the nuclear factor-kappa B-binding site was important for supernatant-induced ICAM-1 expression. Induction of interleukin (IL)-1 alpha (IL-1α) expression in MT-2 and C5/MJ cells was observed compared with uninfected controls and HTLV-I-infected Tax-negative cell lines. The significance of IL-1α as a soluble messenger was supported by blocking the biological activities of MT-2 supernatant with an IL-1α-neutralizing mAb. Moreover, Tax and IL-1α expression was demonstrated in the bronchoalveolar lavage cells of patients with HTLV-I-related pulmonary disease. Immunohistochemistry confirmed ICAM-1 and IL-1α expression in lung epithelial cells and lymphocytes of patients with HTLV-I-related pulmonary diseases, and in a transgenic mouse model of Tax expression. These results suggest that IL-1α produced by HTLV-I-infected Tax(+) T cells is crucial for ICAM-1 expression in lung epithelial cells and subsequent adhesion of lymphocytes in HTLV-I-related pulmonary diseases. © 2011 SGM

  9. Non-contact lens related Acanthamoeba keratitis.

    Science.gov (United States)

    Garg, Prashant; Kalra, Paavan; Joseph, Joveeta

    2017-11-01

    The purpose of the study is to describe epidemiology, clinical features, diagnosis, and treatment of Acanthamoeba keratitis (AK) with special focus on the disease in nonusers of contact lenses (CLs). This study was a perspective based on authors' experience and review of published literature. AK accounts for 2% of microbiology-proven cases of keratitis. Trauma and exposure to contaminated water are the main predisposing factors for the disease. Association with CLs is seen only in small fraction of cases. Contrary to classical description experience in India suggests that out of proportion pain, ring infiltrate, and radial keratoneuritis are seen in less than a third of cases. Majority of cases present with diffuse infiltrate, mimicking herpes simplex or fungal keratitis. The diagnosis can be confirmed by microscopic examination of corneal scraping material and culture on nonnutrient agar with an overlay of Escherichia coli. Confocal microscopy can help diagnosis in patients with deep infiltrate; however, experience with technique and interpretation of images influences its true value. Primary treatment of the infection is biguanides with or without diamidines. Most patients respond to medical treatment. Corticosteroids play an important role in the management and can be used when indicated after due consideration to established protocols. Surgery is rarely needed in patients where definitive management is initiated within 3 weeks of onset of symptoms. Lamellar keratoplasty has been shown to have good outcome in cases needing surgery. Since the clinical features of AK in nonusers of CL are different, it will be important for ophthalmologists to be aware of the scenario wherein to suspect this infection. Medical treatment is successful if the disease is diagnosed early and management is initiated soon.

  10. Non-contact lens related Acanthamoeba keratitis

    Directory of Open Access Journals (Sweden)

    Prashant Garg

    2017-01-01

    Full Text Available The purpose of the study is to describe epidemiology, clinical features, diagnosis, and treatment of Acanthamoeba keratitis (AK with special focus on the disease in nonusers of contact lenses (CLs. This study was a perspective based on authors' experience and review of published literature. AK accounts for 2% of microbiology-proven cases of keratitis. Trauma and exposure to contaminated water are the main predisposing factors for the disease. Association with CLs is seen only in small fraction of cases. Contrary to classical description experience in India suggests that out of proportion pain, ring infiltrate, and radial keratoneuritis are seen in less than a third of cases. Majority of cases present with diffuse infiltrate, mimicking herpes simplex or fungal keratitis. The diagnosis can be confirmed by microscopic examination of corneal scraping material and culture on nonnutrient agar with an overlay of Escherichia coli. Confocal microscopy can help diagnosis in patients with deep infiltrate; however, experience with technique and interpretation of images influences its true value. Primary treatment of the infection is biguanides with or without diamidines. Most patients respond to medical treatment. Corticosteroids play an important role in the management and can be used when indicated after due consideration to established protocols. Surgery is rarely needed in patients where definitive management is initiated within 3 weeks of onset of symptoms. Lamellar keratoplasty has been shown to have good outcome in cases needing surgery. Since the clinical features of AK in nonusers of CL are different, it will be important for ophthalmologists to be aware of the scenario wherein to suspect this infection. Medical treatment is successful if the disease is diagnosed early and management is initiated soon.

  11. [Contact lens-associated Paecilomyces lilacinus keratitis].

    Science.gov (United States)

    Mihailovic, N; Alnawaiseh, M; Zumhagen, L; Eter, N

    2017-01-01

    We present the case of a 23-year-old otherwise healthy female patient with contact lens-associated Paecilomyces lilacinus keratitis. The clinical findings stabilized after initial local antimycotic and antibacterial treatment; however, in the further course of local therapy an extensive relapse occurred which required treatment by perforating keratoplasty à chaud due to a penetrating corneal ulcer. The patient responded well to subsequent treatment with systemic and local antimycotic medication. After a few months HLA-matched keratoplasty was performed. During the follow-up time of 14 months there were no signs of recurrence of the infection.

  12. Loss of the Human Cytomegalovirus US16 Protein Abrogates Virus Entry into Endothelial and Epithelial Cells by Reducing the Virion Content of the Pentamer.

    Science.gov (United States)

    Luganini, Anna; Cavaletto, Noemi; Raimondo, Stefania; Geuna, Stefano; Gribaudo, Giorgio

    2017-06-01

    The human cytomegalovirus (HCMV) US12 gene family encodes a group of predicted seven-transmembrane proteins whose functions have yet to be established. While inactivation of individual US12 members in laboratory strains of HCMV does not affect viral replication in fibroblasts, disruption of the US16 gene in the low-passage-number TR strain prevents viral growth in endothelial and epithelial cells. In these cells, the US16-null viruses fail to express immediate early (IE), early (E), and late (L) viral proteins due to a defect which occurs prior to IE gene expression. Here, we show that this defective phenotype is a direct consequence of deficiencies in the entry of US16-null viruses in these cell types due to an impact on the gH/gL/UL128/UL130/UL131A (pentamer) complex. Indeed, viral particles released from fibroblasts infected with US16-null viruses were defective for the pentamer, thus preventing entry during infections of endothelial and epithelial cells. A link between pUS16 and the pentamer was further supported by the colocalization of pUS16 and pentamer proteins within the cytoplasmic viral assembly compartment (cVAC) of infected fibroblasts. Deletion of the C-terminal tail of pUS16 reproduced the defective growth phenotype and alteration of virion composition as US16-null viruses. However, the pentamer assembly and trafficking to the cVAC were not affected by the lack of the C terminus of pUS16. Coimmunoprecipitation results then indicated that US16 interacts with pUL130 but not with the mature pentamer or gH/gL/gO. Together, these results suggest that pUS16 contributes to the tropism of HCMV by influencing the content of the pentamer into virions.IMPORTANCE Human cytomegalovirus (HCMV) is major pathogen in newborns and immunocompromised individuals. A hallmark of HCMV pathogenesis is its ability to productively replicate in an exceptionally broad range of target cells. The virus infects a variety of cell types by exploiting different forms of the envelope

  13. Clinical and epidemiological characteristics of infectious keratitis in Paraguay.

    Science.gov (United States)

    Nentwich, Martin M; Bordón, M; di Martino, D Sánchez; Campuzano, A Ruiz; Torres, W Martínez; Laspina, F; Lichi, S; Samudio, M; Farina, N; Sanabria, Rosa R; de Kaspar, Herminia Mino

    2015-06-01

    To describe the clinical and epidemiological characteristics of patients with severe infectious keratitis in Asunción, Paraguay between April 2009 and September 2011. All patients with the clinical diagnosis of severe keratitis (ulcer ≥2 mm in size and/or central location) were included. Empiric treatment consisted of topical antibiotics and antimycotics; in cases of advanced keratitis, fortified antibiotics were used. After microbiological analysis, treatment was changed if indicated. In total 48 patients (62.5 % males, 25 % farmers) were included in the analysis. A central ulcer was found in 81.3 % (n = 39). The median delay between onset of symptoms and time of first presentation at our institution was 7 days (range 1-30 days). Fungal keratitis was diagnosed in 64.5 % (n = 31) of patients, of which Fusarium sp. (n = 17) was the most common. Twenty-one patients (43.8 %) reported previous trauma to the eye. The globe could be preserved in all cases. While topical therapy only was sufficient in most patients, a conjunctival flap was necessary in six patients suffering from fungal keratitis. The high rate of fungal keratitis in this series is remarkable, and microbiological analysis provided valuable information for the appropriate treatment. In this setting, one has to be highly suspicious of fungal causes of infectious keratitis.

  14. [Neurotrophic keratitis after vitrectomy and circumferential endophotocoagulation for retinal detachment].

    Science.gov (United States)

    Auchère Lavayssiere, C; Lux, A-L; Degoumois, A; Stchepinsky Launay, M; Denion, E

    2016-02-01

    Circumferential (360°) endophotocoagulation is frequently implemented during vitrectomies for retinal detachment. This photocoagulation may result in neurotrophic keratitis by damaging the ciliary nerves in the suprachoroidal space on their way to the pupil. We report a series of 4 cases of neurotrophic keratitis following a circumferential endophotocoagulation. A retrospective observational case series of 4 non-diabetic patients having presented with a neurotrophic keratitis following a retinal detachment treated with vitrectomy and circumferential endophotocoagulation (532 nm) at Caen University Hospital. We report the various forms of corneal lesions and the diagnostic criteria allowing for the diagnosis of neurotrophic keratitis. Neurotrophic keratitis is caused by lesions occurring at various levels of corneal innervation. Endophotocoagulation may cause a neurotrophic keratitis by damaging the short and long ciliary nerves on their way to the pupil in the suprachoroidal space. The sequelae of this condition can limit visual recovery. Hence, it is probably advisable to screen for corneal anesthesia or severe hypesthesia following a retinal detachment treated with vitrectomy and circumferential endophotocoagulation and to implement prophylactic treatment (intensive lubricant therapy; preservative-free eye drops) if needed. The risk of neurotrophic keratitis should be weighed against the dose of laser retinopexy necessary and sufficient to obtain a sustained retinal reattachment. If circumferential endophotocoagulation is implemented, it is probably sensible to monitor corneal sensitivity and to adapt postoperative treatment if necessary. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. Clinical characteristics and distribution of pathogens in fungal keratitis

    Directory of Open Access Journals (Sweden)

    Tian Tian

    2016-01-01

    Full Text Available AIM:To investigate the clinical characteristics and distribution of pathogens in patients with fungal keratitis and to provide evidence for diagnosis and treatment of this disease.METHODS:The clinical data of 98 cases(98 eyeswith fungal keratitis from January 2012 to July 2015 in the First Affiliated Hospital of Yangtze University were retrospectively reviewed.RESULTS:The main cause for fungal keratitis was corneal injury by plants. The inappropriate use of contact lenses and glucocorticoids therapy were the next cause. Almost all of the patients had hyphae moss, pseudopodia, immune ring, and satellite signs. A few of patients had endothelial plaque and anterior chamber empyema. The majority pathogens of fungal keratitis was Fusarium spp(73.5%,followed by Aspergillus spp(13.2%,Candida spp(9.2%and others(4.1%.Sixty-five patients(65 eyestreated with 5% natamycin were cured. The condition of 15 patients was improved. Eighteen patients were invalid, in which 13 patients became better and 5 patients became worse after voriconazole was added into the therapy, leading to amniotic membrance cover in 3 patients and eyeball removal in 2 patients at last.CONCLUSION:Fusarium genus is the predominant pathogen for fungal keratitis in Jingzhou. Natamycin can be used as the preferred drug for the prevention and treatment for fungal keratitis. The clinicians should pay attention to the fungal keratitis, in order to early diagnosis and timely treatment.

  16. Contact lens associated microbial keratitis: practical considerations for the optometrist

    Directory of Open Access Journals (Sweden)

    Zimmerman AB

    2016-01-01

    Full Text Available Aaron B Zimmerman, Alex D Nixon, Erin M Rueff College of Optometry, The Ohio State University, Columbus, OH, USAAbstract: Microbial keratitis (MK is a corneal condition that encompasses several different pathogens and etiologies. While contact lens associated MK is most often associated with bacterial infections, other pathogens (fungi, Acanthamoeba species, etc may be responsible. This review summarizes the risk factors, microbiology, diagnostic characteristics, and treatment options for all forms of contact lens-related MK.Keywords: corneal ulcer, fungal keratitis, bacterial keratitis, Acanthamoeba, Fusarium, Pseudomonas

  17. Persistence of acanthamoeba antigen following acanthamoeba keratitis.

    Science.gov (United States)

    Yang, Y F; Matheson, M; Dart, J K; Cree, I A

    2001-03-01

    To investigate the hypothesis that persistent corneal and scleral inflammation following acanthamoeba keratitis is not always caused by active amoebic infection but can be due to persisting acanthamoebic antigens 24 lamellar corneal biopsy and penetrating keratoplasty specimens were obtained from 14 consecutive patients at various stages of their disease and divided for microscopy and culture. Histological sections were immunostained and screened for the presence of Acanthamoeba cysts by light microscopy. Cultures were carried out using partly homogenised tissues on non-nutrient agar seeded with E coli. Clinical data were obtained retrospectively from the case notes of these patients. Of the 24 specimens, 20 were obtained from eyes that were clinically inflamed at the time of surgery. Acanthamoeba cysts were present in 16 (80%) of these 20 specimens, while only five (25%) were culture positive. Acanthamoeba cysts were found to persist for up to 31 months after antiamoebic treatment. These findings support the hypothesis that Acanthamoeba cysts can remain in corneal tissue for an extended period of time following acanthamoeba keratitis and may cause persistent corneal and scleral inflammation in the absence of active amoebic infection. In view of these findings, prolonged intensive antiamoebic therapy may be inappropriate when the inflammation is due to retained antigen rather than to viable organisms

  18. Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wörmann, Xenia [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Lesch, Markus [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Steinbeis Innovation gGmbH, Center for Systems Biomedicine, Falkensee (Germany); Welke, Robert-William [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Okonechnikov, Konstantin; Abdurishid, Mirshat [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Sieben, Christian [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Geissner, Andreas [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Brinkmann, Volker [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Kastner, Markus [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Karner, Andreas [Center for Advanced Bioanalysis GmbH (CBL), Linz (Austria); Zhu, Rong; Hinterdorfer, Peter [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Anish, Chakkumkal [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Seeberger, Peter H. [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Herrmann, Andreas [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); and others

    2016-05-15

    The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA{sub 1} D130E, HA{sub 2} I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.

  19. Topical nanoparticulate formulation of drugs for ocular keratitis

    Science.gov (United States)

    Yang, Xiaoyan

    The primary objective of this project is to develop drug-loaded polymeric nanoparticles suspended in a biocompatible gel for topical delivery of therapeutic agents commonly employed in the treatment of ocular viral/bacterial keratitis. PART 1: Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of dipeptide monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV), D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex virus type 1 (HSV-1) induced viral corneal keratitis. NP containing prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique using various PLGA polymers with different drug/polymer ratios. Cytotoxicity studies suggested that all NP formulations are non-toxic. In vitro release of prodrugs from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels with near zero-order release kinetics. Prodrugs-loaded PLGA NP dispersed in thermosensitive gels can thus serve as a promising drug delivery system for the treatment of anterior eye diseases. Maximum uptake (around 60%) was noted at 3 h for NP. Cellular uptake and intracellular accumulation of prodrugs are significantly different among three stereoisomeric dipeptide prodrugs. The microscopic images show that NP are avidly internalized by HCEC cells and distributed throughout the cytoplasm instead of being localized on the cell surface. Following cellular uptake, prodrugs released from NP gradually bioreversed into parent drug GCV. LLGCV showed the highest degradation rate, followed by LDGCV and DLGCV. LLGCV, LDGCV and DLGCV released from NP exhibited superior uptake and bioreversion in corneal cells. PART 2: PLGA NP of hydrocortisone butyrate (HB) suspended in thermosensitive PLGA-PEG-PLGA gel were developed for the treatment of

  20. Acanthamoeba, fungal, and bacterial keratitis: a comparison of risk factors and clinical features

    Science.gov (United States)

    Mascarenhas, Jeena; Lalitha, Prajna; Prajna, N. Venkatesh; Srinivasan, Muthiah; Das, Manoranjan; D’Silva, Sean S.; Oldenburg, Catherine E.; Borkar, Durga S.; Esterberg, Elizabeth J.; Lietman, Thomas M.; Keenan, Jeremy D.

    2013-01-01

    Purpose To determine risk factors and clinical signs that may differentiate between bacterial, fungal, and acanthamoeba keratitis among patients presenting with presumed infectious keratitis. Design Hospital-based cross-sectional study. Methods We examined the medical records of 115 patients with laboratory-proven bacterial keratitis, 115 patients with laboratory-proven fungal keratitis, and 115 patients with laboratory-proven acanthamoeba keratitis seen at Aravind Eye Hospital, Madurai, India, from 2006–2011. Risk factors and clinical features of the three organisms were compared using multinomial logistic regression. Results Of 95 patients with bacterial keratitis, 103 patients with fungal keratitis, and 93 patients with acanthamoeba keratitis who had medical records available for review, 287 (99%) did not wear contact lenses. Differentiating features were more common for acanthamoeba keratitis than for bacterial or fungal keratitis. Compared to patients with bacterial or fungal keratitis, patients with acanthamoeba keratitis were more likely to be younger and to have a longer duration of symptoms, and to have a ring infiltrate or disease confined to the epithelium. Conclusions Risk factors and clinical examination findings can be useful for differentiating acanthamoeba keratitis from bacterial and fungal keratitis. PMID:24200232

  1. Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment

    NARCIS (Netherlands)

    Blank, Thomas; Detje, Claudia N.; Spiess, Alena; Hagemeyer, Nora; Brendecke, Stefanie M.; Wolfart, Jakob; Staszewski, Ori; Zoeller, Tanja; Papageorgiou, Ismini; Schneider, Justus; Paricio-Montesinos, Ricardo; Eisel, Ulrich L. M.; Manahan-Vaughan, Denise; Jansen, Stephan; Lienenklaus, Stefan; Lu, Bao; Imai, Yumiko; Mueller, Marcus; Goelz, Susan E.; Baker, Darren P.; Schwaninger, Markus; Kann, Oliver; Heikenwalder, Mathias; Kalinke, Ulrich; Prinz, Marco

    2016-01-01

    Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded

  2. Excimer laser phototherapeutic keratectomy for the treatment of clinically presumed fungal keratitis.

    Science.gov (United States)

    Li, Liang-Mao; Zhao, Li-Quan; Qu, Ling-Hui; Li, Peng

    2014-01-01

    This retrospective study was to evaluate treatment outcomes of excimer laser phototherapeutic keratectomy (PTK) for clinically presumed fungal keratitis. Forty-seven eyes of 47 consecutive patients underwent manual superficial debridement and PTK. All corneal lesions were located in the anterior stroma and were resistant to medication therapy for at least one week. Data were collected by a retrospective chart review with at least six months of follow-up data available. After PTK, infected corneal lesions were completely removed and the clinical symptoms resolved in 41 cases (87.2%). The mean ablation depth was 114.39 ± 45.51  μ m and diameter of ablation was 4.06 ± 1.07 mm. The mean time for healing of the epithelial defect was 8.8 ± 5.6 days. Thirty-four eyes (82.9%) showed an improvement in best spectacle-corrected visual acuity of two or more lines. PTK complications included mild to moderate corneal haze, hyperopic shift, irregular astigmatism, and thinning cornea. Six eyes (12.8%) still showed progressed infection, and conjunctival flap covering, amniotic membrane transplantation, or penetrating keratoplasty were given. PTK is a valuable therapeutic alternative for superficial infectious keratitis. It can effectively eradicate lesions, hasten reepithelialization, and restore and preserve useful visual function. However, the selection of surgery candidates should be conducted carefully.

  3. Inflammation and the Nervous System: The Connection in the Cornea in Patients with Infectious Keratitis

    Science.gov (United States)

    Cruzat, Andrea; Witkin, Deborah; Baniasadi, Neda; Zheng, Lixin; Ciolino, Joseph B.; Jurkunas, Ula V.; Chodosh, James; Pavan-Langston, Deborah; Dana, Reza

    2011-01-01

    Purpose. To study the density and morphologic characteristics of epithelial dendritic cells, as correlated to subbasal corneal nerve alterations in acute infectious keratitis (IK) by in vivo confocal microscopy (IVCM). Methods. IVCM of the central cornea was performed prospectively in 53 eyes with acute bacterial (n = 23), fungal (n = 13), and Acanthamoeba (n = 17) keratitis, and in 20 normal eyes, by using laser in vivo confocal microscopy. Density and morphology of dendritic-shaped cells (DCs) of the central cornea, corneal nerve density, nerve numbers, branching, and tortuosity were assessed and correlated. It should be noted that due to the “in vivo” nature of the study, the exact identity of these DCs cannot be specified, as they could be monocytes or tissue macrophages, but most likely dendritic cells. Results. IVCM revealed the presence of central corneal DCs in all patients and controls. The mean DC density was significantly higher in patients with bacterial (441.1 ± 320.5 cells/mm2; P cornea. PMID:21460259

  4. Excimer Laser Phototherapeutic Keratectomy for the Treatment of Clinically Presumed Fungal Keratitis

    Directory of Open Access Journals (Sweden)

    Liang-Mao Li

    2014-01-01

    Full Text Available This retrospective study was to evaluate treatment outcomes of excimer laser phototherapeutic keratectomy (PTK for clinically presumed fungal keratitis. Forty-seven eyes of 47 consecutive patients underwent manual superficial debridement and PTK. All corneal lesions were located in the anterior stroma and were resistant to medication therapy for at least one week. Data were collected by a retrospective chart review with at least six months of follow-up data available. After PTK, infected corneal lesions were completely removed and the clinical symptoms resolved in 41 cases (87.2%. The mean ablation depth was 114.39±45.51 μm and diameter of ablation was 4.06±1.07 mm. The mean time for healing of the epithelial defect was 8.8±5.6 days. Thirty-four eyes (82.9% showed an improvement in best spectacle-corrected visual acuity of two or more lines. PTK complications included mild to moderate corneal haze, hyperopic shift, irregular astigmatism, and thinning cornea. Six eyes (12.8% still showed progressed infection, and conjunctival flap covering, amniotic membrane transplantation, or penetrating keratoplasty were given. PTK is a valuable therapeutic alternative for superficial infectious keratitis. It can effectively eradicate lesions, hasten reepithelialization, and restore and preserve useful visual function. However, the selection of surgery candidates should be conducted carefully.

  5. A Case of Retained Graphite Anterior Chamber Foreign Body Masquerading as Stromal Keratitis

    Science.gov (United States)

    Han, Eun Ryung; Wee, Won Ryang; Lee, Jin Hak

    2011-01-01

    We report a case of a retained graphite anterior chamber foreign body that was masquerading as stromal keratitis. A 28-year-old male visited with complaints of visual disturbance and hyperemia in his right eye for four weeks. On initial examination, he presented with a stromal edema involving the inferior half of the cornea, epithelial microcysts, and moderate chamber inflammation. Suspecting herpetic stromal keratitis, he was treated with anti-viral and anti-inflammatory agents. One month after the initial visit, anterior chamber inflammation was improved and his visual acuity recovered to 20/20, but subtle corneal edema still remained. On tapering the medication, after three months, a foreign body was incidentally identified in the inferior chamber angle and was surgically removed resulting in complete resolution of corneal edema. The removed foreign body was a fragment of graphite and he subsequently disclosed a trauma with mechanical pencil 12 years earlier. This case showed that the presence of an anterior chamber foreign body should always be considered in the differential diagnosis of idiopathic localized corneal edema. PMID:21461226

  6. Tripartite Motif 8 (TRIM8) Positively Regulates Pro-inflammatory Responses in Pseudomonas aeruginosa-Induced Keratitis Through Promoting K63-Linked Polyubiquitination of TAK1 Protein.

    Science.gov (United States)

    Guo, Litao; Dong, Weili; Fu, Xiaoxiao; Lin, Jing; Dong, Zhijun; Tan, Xiaobo; Zhang, Tiemin

    2017-04-01

    Pseudomonas aeruginosa (PA)-induced keratitis is a rapidly progressive ocular infectious disease that often leads to inflammatory epithelial edema, stromal infiltration, tissue destruction, corneal ulceration, and vision loss. In this study, we investigate the role of tripartite motif 8 (TRIM8) in regulating the inflammatory process of PA-induced keratitis. The expression of TRIM8 was increased in mouse corneas and in vitro-cultured macrophages after PA infection. Knockdown of the expression of TRIM8 significantly inhibited the activation of NF-κB signaling and decreased the production of pro-inflammatory cytokines both in vivo and in vitro after infected with PA. Furthermore, we investigated the potential mechanism and we found after PA infection that TRIM8 could promote K63-linked polyubiquitination of transforming growth factor β-activated kinase 1 (TAK1), leading to the activation of TAK1 and enhanced inflammatory responses. Taken together, we demonstrated that TRIM8 has pro-inflammatory effect on PA-induced keratitis and suggest TRIM8 as a potential therapeutic target for keratitis.

  7. Esculentin-1a(1-21)NH2: a frog skin-derived peptide for microbial keratitis

    Science.gov (United States)

    Kolar, Satya Sree N.; Luca, Vincenzo; Baidouri, Hasna; Mannino, Giuseppe; McDermott, Alison M.; Mangoni, Maria Luisa

    2015-01-01

    Pseudomonas aeruginosa is the primary bacterial pathogen causing contact lens related keratitis. Available ophthalmic agents have reduced efficacy and antimicrobial peptides (AMPs) hold promise as future antibiotics. Here we investigated the in vitro and in vivo anti-Pseudomonal activity of esculentin-1a(1-21)-NH2, derived from a frog skin AMP. The data revealed a minimum inhibitory concentration between 2 and 16 μM against reference strains or drug-resistant clinical isolates of P. aeruginosa without showing toxicity to human corneal epithelial cells up to 50 μM. At 1 μM the peptide rapidly killed bacterial cells and this activity was fully retained in 150 mM sodium chloride and 70% (v/v) human basal tears, particularly against the virulent ATCC 19660 strain. Furthermore, its dropwise administration at 40 μM to the ocular surface in a murine model of P. aeruginosa keratitis (three times daily, for 5 days post-infection) resulted in a significant reduction of infection. The mean clinical score was 2.89 ± 0.26 compared to 3.92 ± 0.08 for the vehicle control. In addition, the corneal level of viable bacteria in the peptide treated animals was significantly lower with a difference of 4 log10 colony counts, compared to 7.7 log10 cells recovered in the control. In parallel, recruitment of inflammatory cells was reduced by half compared to that found in the untreated eyes. Similar results were obtained when esculentin-1a(1-21)NH2 was applied prior to induction of keratitis. Overall, our findings highlight esculentin-1a(1-21)NH2 as an attractive candidate for the development of novel topical pharmaceuticals against Pseudomonas keratitis. PMID:25086859

  8. Cellular transcriptional profiling in influenza A virus-infected lung epithelial cells: The role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza

    Science.gov (United States)

    Geiss, Gary K.; Salvatore, Mirella; Tumpey, Terrence M.; Carter, Victoria S.; Wang, Xiuyan; Basler, Christopher F.; Taubenberger, Jeffery K.; Bumgarner, Roger E.; Palese, Peter; Katze, Michael G.; García-Sastre, Adolfo

    2002-08-01

    The NS1 protein of influenza A virus contributes to viral pathogenesis, primarily by enabling the virus to disarm the host cell type IFN defense system. We examined the downstream effects of NS1 protein expression during influenza A virus infection on global cellular mRNA levels by measuring expression of over 13,000 cellular genes in response to infection with wild-type and mutant viruses in human lung epithelial cells. Influenza A/PR/8/34 virus infection resulted in a significant induction of genes involved in the IFN pathway. Deletion of the viral NS1 gene increased the number and magnitude of expression of cellular genes implicated in the IFN, NF-B, and other antiviral pathways. Interestingly, different IFN-induced genes showed different sensitivities to NS1-mediated inhibition of their expression. A recombinant virus with a C-terminal deletion in its NS1 gene induced an intermediate cellular mRNA expression pattern between wild-type and NS1 knockout viruses. Most significantly, a virus containing the 1918 pandemic NS1 gene was more efficient at blocking the expression of IFN-regulated genes than its parental influenza A/WSN/33 virus. Taken together, our results suggest that the cellular response to influenza A virus infection in human lung cells is significantly influenced by the sequence of the NS1 gene, demonstrating the importance of the NS1 protein in regulating the host cell response triggered by virus infection.

  9. Challenges in the management of Neisseria gonorrhoeae keratitis.

    Science.gov (United States)

    McElnea, Elizabeth; Stapleton, Patrick; Khan, Sheryar; Stokes, John; Higgins, Gareth

    2015-02-01

    We describe the presentation and subsequent management of a case of keratitis caused by Neisseria gonorrhoeae. A thirty-nine year old gentleman presented with a purulent ocular discharge. Corneal melt with corneal perforation occurred. Neisseria gonorrhoeae was cultured. Systemic and topical antibiotics were given. Deep lamellar keratoplasty was performed for corneal perforation. At three months post treatment no recurrence of infection was noted. The possibility of Neisseria gonorrhoeaea keratitis should always be considered in patients with a purulent ocular discharge even if the case history is not immediately suggestive of the same. Severe gonococcal keratitis may be unilateral. Deep lamellar keratoplasty can be considered as a therapeutic option in patients with severe gonococcal keratitis.

  10. Multidrug-resistant Fusarium keratitis: diagnosis and treatment considerations.

    Science.gov (United States)

    Sara, Sergio; Sharpe, Kendall; Morris, Sharon

    2016-08-03

    Mycotic keratitis is an ocular infective process derived from any fungal species capable of corneal invasion. Despite its rarity in developed countries, its challenging and elusive diagnosis may result in keratoplasty or enucleation following failed medical management. Filamentous fungi such as Fusarium are often implicated in mycotic keratitis. Bearing greater morbidity than its bacterial counterpart, mycotic keratitis requires early clinical suspicion and initiation of antifungal therapy to prevent devastating consequences. We describe a case of multidrug-resistant mycotic keratitis in a 46-year-old man who continued to decline despite maximal therapy and therapeutic keratoplasty. Finally, enucleation was performed as a means of source control preventing dissemination of a likely untreatable fungal infection into the orbit. Multidrug-resistant Fusarium is rare, and may progress to endophthalmitis. We discuss potential management options which may enhance diagnosis and outcome in this condition. 2016 BMJ Publishing Group Ltd.

  11. ISG15 in Host Defense Against Candida albicans Infection in a Mouse Model of Fungal Keratitis.

    Science.gov (United States)

    Dong, Chen; Gao, Nan; Ross, Bing X; Yu, Fu-Shin X

    2017-06-01

    ISG15, a di-ubiquitin-like protein, is critical for controlling certain viral and bacterial infections. We sought to determine if ISG15 plays a role in corneal innate immunity against Candida albicans (C. albicans) using a C57BL/6 (B6) mouse model of human fungal keratitis. Scarified corneas of adult B6 mice were pretreated with TLR5 ligand flagellin and then inoculated with C. albicans. The expression of ISG15 and other genes involved in ISG15 conjugation (ISGylation) was determined by real-time PCR. ISG15 expression and distribution in infected corneas were assessed by immunohistochemistry. ISGylation was examined by Western blotting. siRNA knockdown and recombinant ISG15 were used to elucidate the effects of ISG15 on controlling fungal keratitis by clinical scoring, fungal number plate counting, ELISA cytokine determination, and polymorphonuclear leukocytes (PMN) infiltration measurement. Heat-killed C. albicans induced expression of ISG15, and hBD2 was markedly enhanced by flagellin-pretreatment in cultured human primary corneal epithelial cells (CECs). In vivo, C. albicans infection induced the expression of ISG15, ISGylation-associated genes (UBE1L, UBCH8, and HERC5), and ISGylation in mouse CECs, all of which were enhanced by flagellin-pretreatment. siRNA knockdown of ISG15 increased keratitis severity, dampened flagellin-induced protection, and greatly suppressed the expressions of ISGylation enzymes, IFN-γ, but not CXCL2 in B6 mouse CECs. Recombinant ISG15, on the other hand, enhanced corneal innate immunity against C. albicans and suppressed infection-induced IL-1β, but not IL-Ra expression. ISG15 alone induced the expression of IL-1Ra, CXCL10, and CRAMP in mouse CECs. ISG15 was upregulated and secreted in cultured human CECs in response to challenge in a type 1 IFN-dependent manner. Our data, for the first time, demonstrate that ISG15 acts as an immunomodulator in the cornea and plays a critical role in controlling fungal keratitis.

  12. Activation of cytokines and NF-kappa B in corneal epithelial cells infected by respiratory syncytial virus: potential relevance in ocular inflammation and respiratory infection

    Directory of Open Access Journals (Sweden)

    Oakes John E

    2004-07-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is a major cause of lower respiratory tract infection, claiming millions of lives annually. The virus infects various cells of the respiratory tract as well as resident inflammatory cells such as macrophages. Infection activates a variety of cellular factors such as cytokines and the pro-inflammatory transcription factor, NF-kappa B, all of which are important players in the respiratory disease. However, the exact natural route of RSV infection and its etiology remain relatively unknown. In this paper, we test the hypothesis that human corneal epithelial cells, which constitute the outermost layer of the cornea, can be infected with RSV, and that the infection leads to the activation of proinflammatory macromolecules. Results Corneal swabs obtained from pediatric patients with acute respiratory disease were found to contain RSV at a high frequency (43 positive out of 72 samples, i.e., 60%. Primary corneal epithelial cells in tissue culture supported robust infection and productive growth of RSV. Infection resulted in the activation of TNF-α, IL-6 and sixteen chemokines as well as NF-κB. Three proinflammatory CXC chemokines (MIG, I-TAC, IP-10 underwent the greatest activation. Conclusions The ocular epithelium is readily infected by RSV. The pro-inflammatory cytokines are likely to play critical roles in the etiology of inflammation and conjunctivitis commonly seen in pediatric patients with respiratory infections. RSV-eye interactions have important implications in RSV transmission, immunopathology of RSV disease, and in the management of conjunctivitis.

  13. Unique circumferential peripheral keratitis in relapsing polychondritis: A case report.

    Science.gov (United States)

    Motozawa, Naohiro; Nakamura, Takahiro; Takagi, Seiji; Fujihara, Masashi; Hirami, Yasuhiko; Ishida, Kazuhiro; Sotozono, Chie; Kurimoto, Yasuo

    2017-10-01

    Relapsing polychondritis (RP) is a rare collagen disease characterized by inflammation and destruction of cartilage throughout the body. The paper details the clinical course of a case of RP with unique circumferential peripheral keratitis. A 54-year-old Japanese woman was referred to the hospital presenting with auricular and ocular pain. Based on the auricle biopsy results and the three presenting symptoms (bilateral auricular chondritis, inflammatory arthritis and ocular inflammation), her condition was diagnosed as RP. The three presenting symptoms gradually improved with prednisolone (PSL), methylprednisolone and cyclophosphamide combination therapy, followed by PSL, methotrexate and infliximab combination therapy. However, one month after the initial visit, despite ongoing treatment, a unique circumferential peripheral keratitis suddenly occurred, in which the corneal infiltration gradually clumped together and shrank at the peripheral area. The eye and ear pain showed exacerbations and remissions on reducing the dosage of steroid drugs. The general condition was improved on altering systemic therapy to PSL, methotrexate and tocilizumab. Keratitis gradually disappeared within 10 months of the initial visit. This is the first report of a case of RP causing unique circumferential peripheral keratitis. This keratitis occurred despite use of focal and systemic steroids and showed improvement with general recovery. This may indicate that stabilization of general condition is important for recovery from keratitis in RP.

  14. Corneal Higher-Order Aberrations in Infectious Keratitis.

    Science.gov (United States)

    Shimizu, Eisuke; Yamaguchi, Takefumi; Yagi-Yaguchi, Yukari; Dogru, Murat; Satake, Yoshiyuki; Tsubota, Kazuo; Shimazaki, Jun

    2017-03-01

    To characterize the corneal higher-order aberrations (HOAs) in eyes with Acanthamoeba keratitis (AK), bacterial keratitis (BK), and fungal keratitis (FK). Retrospective consecutive case series. This retrospective study includes 18 normal subjects and 63 eyes of 62 consecutive patients with corneal scarring due to AK (20 eyes), BK (35 eyes), and FK (8 eyes) from 2010 to 2016. HOAs of the anterior and posterior surfaces and the total cornea were analyzed by anterior segment optical coherence tomography. Corneal HOA patterns were assigned on the basis of corneal topography maps. Corneal opacity grading was assigned on the basis of slit-lamp examinations. We evaluated corneal HOAs, corneal opacity grading, and their correlation with visual acuity. HOAs of the total cornea within a 4-mm diameter were significantly larger in eyes with infectious keratitis (AK, 1.15 ± 2.06 μm; BK, 0.91 ± 0.88 μm; FK, 1.39 ± 1.46 μm) compared with normal controls (0.09 ± 0.01 μm, all, P keratitis were associated with poorer visual acuity values. Asymmetric pattern was the most common topographic pattern in infectious keratitis. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Use of adjunctive topical corticosteroids in bacterial keratitis.

    Science.gov (United States)

    Ni, Nina; Srinivasan, Muthiah; McLeod, Stephen D; Acharya, Nisha R; Lietman, Thomas M; Rose-Nussbaumer, Jennifer

    2016-07-01

    Topical corticosteroid use in the setting of infectious keratitis has been a controversial issue. The aim of this review is to provide an update on the evidence for use of topical corticosteroids in addition to antibiotics in bacterial keratitis. Judicious use of steroids is postulated to limit the inflammatory component of bacterial keratitis, but can theoretically retard healing. Three small randomized controlled trials and one large-scale trial, the Steroids for Corneal Ulcers Trial, have provided the most recent evidence to address this debate. Adjunctive topical corticosteroids initiated after at least 48 h of antibiotic usage in cases of culture-proven bacterial keratitis appear generally safe in the treatment of bacterial keratitis. They may be beneficial in cases of severe ulcers especially when initiated early in the course of the infection, in non-Nocardia ulcers, and in certain Pseudomonas ulcers. Several randomized controlled trials have greatly contributed to our understanding of the controversy over steroid use in the management of bacterial keratitis. Future studies are needed to confirm subgroup analysis findings and define optimal timing, dosage, and the most appropriate treatment populations.

  16. Acanthamoeba keratitis: clinical characteristics and management.

    Science.gov (United States)

    Jiang, Chao; Sun, Xuguang; Wang, Zhiqun; Zhang, Yang

    2015-04-01

    To review characteristics of clinical features in 260 eyes with Acanthamoeba keratitis (AK) from 1991 to 2013. We retrospectively analyzed 260 eyes from 259 patients diagnosed with Acanthamoeba keratitis (AK) by smear and/or culture and/or laser confocal microscopy between 1991 and 2013 at Beijing Tongren Eye Center. Patient data included age, gender, profession, predisposing risk factors, clinical presentation, treatment, therapy effect, and course of disease. The most common risk factor in this study was ocular trauma (53.1%), followed by contact lens wear (29.8%). Most of the AK patients were farmers (50.8%), and students (23.8%) formed the second largest group of AK patients. Most cases (77.8%) were classified as advanced stage AK at initial presentation; only a few patients (5.6%) were diagnosed with early stage disease. Of 90 cases, 77 (85.6%) had salt-like dense infiltrate dots on the corneal ulcer, 54 cases (61.1%) had groove-shaped corneal melting around the corneal ulcer, and 37 cases(41.1%) had classic ring infiltrate. Nine cases experienced improved conditions at the beginning of treatment, which subsequently worsened, and then improved gradually. Treatments were administered according to the disease stage. After topical anti-amoeba drug therapy, 48 of 90 cases (53.3%) were cured with corneal scarring remaining; mean duration of treatment was 5 months. Salt-like dense infiltrate dots and groove-shaped corneal melting may serve as useful clues in the diagnosis of AK, in addition to radial neuritis and ring infiltration. Some patients with AK may experience a worsened condition after early improvement with anti-amoeba drug therapy, and then improve gradually. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Topical ayurvedic ointment-induced chemical injury presenting as bilateral acute keratitis.

    Science.gov (United States)

    Sahay, Pranita; Saluja, Gunjan; Maharana, Prafulla Kumar; Titiyal, Jeewan S

    2017-08-20

    A 40-years-old female patient was referred to the cornea clinic as a probable case of bilateral keratitis. The patient had a history of headache followed by acute onset of redness, pain and discharge from both eyes for 15 days. The patient was diagnosed as bilateral keratitis by the first contact physician and was started on topical antibiotics, cycloplegics and lubricating eye-drops. At presentation, both eyes had visual acuity of perception of light, conjunctival congestion, limbal blanching, diffuse corneal oedema and epithelial defect. A detailed history revealed application of Vicks VapoRub [topical ayurvedic analgesic which contains (per 100 g of product) menthol (2.82 g), camphor (5.25 g) and eucalyptol (1.49 mL) and excipients include thymol (0.1 g), turpentine oil (5.57 mL), nutmeg oil (0.54 mL), cedar wood oil and petrolatum)] on the forehead and eyelids for headache several times over 2-3 days before the onset. The patient further confirmed the accidental application of the ointment in the eyes. A provisional diagnosis of acute chemical injury with Vicks VapoRub was made and treatment with topical antibiotic, cycloplegic, steroid, lubricant and vitamin C was started. On follow-up, both eyes showed gradual resolution of corneal oedema and epithelial defect. Visual acuity improved in the left eye to 6/60 with no change in right eye due to corneal haze. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Severe pseudomonal keratitis in an infrequent daily disposable contact lens wearer.

    Science.gov (United States)

    Batta, Priti; Goldstein, Michael H

    2010-05-01

    To report an unusual case of contact lens-associated pseudomonal keratitis in a compliant daily disposable contact lens wearer. A case report is presented of a compliant daily disposable contact lens wearer who developed culture-positive pseudomonal keratitis. A 38-year-old woman who reported compliant and infrequent use of daily disposable contact lenses presented with rapid-onset, severe keratitis consistent with pseudomonal infection. Corneal cultures were positive for Pseudomonas aeruginosa. She had no identifiable risk factors, although notably had a remote history of contact lens-associated keratitis in the fellow eye. Although extremely rare, pseudomonal keratitis should still be considered in the differential diagnosis of severe keratitis in daily disposable contact lens wearers. Given the history of a previous contact lens-related bacterial keratitis in this compliant patient, it is possible that host susceptibility factors played a role in the case of pseudomonal keratitis described here.

  19. Polymicrobial keratitis after a collagen cross-linking procedure with postoperative use of a contact lens: a case report.

    Science.gov (United States)

    Zamora, Katherine V; Males, John J

    2009-05-01

    : To report a case of polymicrobial keratitis caused by Streptococcus salivarius, Streptococcus oralis, and coagulase-negative Staphylococcus sp. in a patient who underwent collagen cross-linking for keratoconus. : Case report. : A 32-year-old male presented with a 1-day history of a painful red eye, occurring 3 days after he had undergone a collagen cross-linking with riboflavin and UV-A on his left eye for keratoconus. He admitted to removing his bandage contact lens and cleaning it in his mouth before reapplying it in his eye. On presentation, a severe keratitis with an 8-mm epithelial defect and 360-degree ring infiltrate was found. Culture results from his contact lens were positive for S. salivarius and S. oralis, and coagulase-negative Staphylococcus sp. were grown from his corneal scrapings. : Collagen cross-linking is a promising procedure for the treatment of progressive keratoconus with minimal reported side effects. However, the possibility of a secondary infection after the procedure exists because the patient is subjected to epithelial debridement and the application of a soft contact lens. The role of the UV light on the immune mechanisms of the cornea and its effect on corneal wound healing warrant further investigation.

  20. Human Corneal MicroRNA Expression Profile in Fungal Keratitis.

    Science.gov (United States)

    Boomiraj, Hemadevi; Mohankumar, Vidyarani; Lalitha, Prajna; Devarajan, Bharanidharan

    2015-12-01

    MicroRNAs (miRNAs) are small, stable, noncoding RNA molecules with regulatory function and marked tissue specificity that posttranscriptionally regulate gene expression. However, their role in fungal keratitis remains unknown. The purpose of this study was to identify the miRNA profile and its regulatory role in fungal keratitis. Normal donor (n = 3) and fungal keratitis (n = 5) corneas were pooled separately, and small RNA deep sequencing was performed using a sequencing platform. A bioinformatics approach was applied to identify differentially-expressed miRNAs and their targets, and select miRNAs were validated by real-time quantitative PCR (qPCR). The regulatory functions of miRNAs were predicted by combining miRNA target genes and pathway analysis. The mRNA expression levels of select target genes were further analyzed by qPCR. By deep sequencing, 75 miRNAs were identified as differentially expressed with fold change greater than 2 and probability score greater than 0.9 in fungal keratitis corneas. The highly dysregulated miRNAs (miR-511-5p, miR-142-3p, miR-155-5p, and miR-451a) may regulate wound healing as they were predicted to specifically target wound inflammatory genes. Moreover, the increased expression of miR-451a in keratitis correlated with reduced expression of its target, macrophage migration inhibitory factor, suggesting possible regulatory functions. This is, to our knowledge, the first report on comprehensive human corneal miRNA expression profile in fungal keratitis. Several miRNAs with high expression in fungal keratitis point toward their potential role in regulation of pathogenesis. Further insights in understanding their role in corneal wound inflammation may help design new therapeutic strategies.

  1. Antiviral Activity of a Cloned Peptide RC28 Isolated from the Higher Basidiomycetes Mushroom Rozites caperata in a Mouse Model of HSV-1 Keratitis.

    Science.gov (United States)

    Yan, Naihong; He, Fen; Piraino, Frank F; Xiang, Haotian; Chen, Jun; Wang, Yun; Liu, Xuyang

    2015-01-01

    An Escherichia coli-expressed peptide with a molecular weight of 28.26, derived from the complementary DNA of antiviral protein RC28 isolated from the mushroom Rozites caperata (=Cortinarius caperatus), demonstrated potent antiviral activity against herpes simplex virus-1 in Vero cells and in a herpes simplex virus-1 mouse keratitis model. Plaque assays in Vero cells showed that the peptide reduced viral yields by at least 1.2 logs; in the animal model the cloned peptide delayed the occurrence of stromal keratitis and alleviated the severity of the disease. We believe this is the first report of a cloned mushroom peptide with antiviral activity for the prevention and treatment of a viral disease.

  2. Allograft Reaction After Latanoprost use Following Penetrating Keratoplasty for Corneal Scarring due to Herpetic Keratitis

    Directory of Open Access Journals (Sweden)

    Tahir Kansu Bozkurt

    2012-03-01

    Full Text Available A 27-year-old male patient with a corneal scar secondary to herpetic keratitis in the right eye underwent penetrating keratoplasty (PK. At the 14th month of follow-up, latanoprost was started to treat high intraocular pressure which was refractory to treatment. On the 15th day of latanoprost use, allograft reaction (AR developed. Insufficient clinical response despite intensive immunosuppressive therapy made us consider the possibility of recurrent herpetic keratouveitis secondary to steroid treatment. The dramatic reduction in the number of keratic precipitates with oral valacyclovir treatment confirmed this diagnosis. The graft remained clear 3 months after the AR treatment. Inflammation in eyes that had undergone PK jeopardizes the graft success by disrupting the immune privilege of anterior chamber. Considering the effects of prostaglandin analogues on blood-aqueous barrier, latanoprost use might have been related to allograft reaction in this case. Another remarkable characteristics of this case was the herpes simplex virus (HSV reactivation secondary to AR therapy. For this reason, oral acyclovir prophylaxis together with AR therapy would improve graft success in cases with HSV history. (Turk J Oph thal mol 2012; 42: 150-3

  3. Roles of Epstein-Barr virus glycoproteins gp350 and gp25 in the infection of human epithelial cells

    National Research Council Canada - National Science Library

    Maruo, Seiji; Yang, Lixin; Takada, Kenzo

    2001-01-01

    Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-8638, Japan 1 Author for correspondence: Kenzo Takada. Fax +81 11 717 1128. e-mail kentaka{at}med.hokudai.ac.jp Epstein–Barr virus (EBV...

  4. Inhibitory effect of a novel peptide, H-RN, on keratitis induced by LPS or poly(I:C) in vitro and in vivo via suppressing NF-κB and MAPK activation.

    Science.gov (United States)

    Zhu, Shaopin; Xu, Xun; Wang, Lili; Su, Li; Gu, Qing; Wei, Fang; Liu, Kun

    2017-01-26

    Keratitis is a common cause of blindness. Current anti-inflammatory drugs used in keratitis have profound side effects. Small peptides derived from endogenous proteins potentially display both desired efficiency and safety. We identified an 11-amino-acid peptide, H-RN, from hepatocyte growth factor (HGF), an endogenous protein with anti-inflammatory properties. We evaluated the effects of H-RN in keratitis in vitro and in vivo. In vitro, corneal fibroblasts were stimulated with LPS or poly(I:C), surrogates for bacteria and viruses. Inflammatory cytokines, intercellular cell adhesion molecule-1 (ICAM-1), translocation of NF-κB p65, activation of IκBα, NF-κB, and MAPKs were detected. In vivo, keratitis in rats was induced by LPS. Clinical, histological observation, and quantification of cytokines in the cornea were conducted. H-RN safety was measured by cell viability, clinical, histological, and microstructural observations. H-RN inhibited IL-6, monocyte chemotactic protein-1(MCP-1), Interferon- γ(IFN-γ), and ICAM-1 expression triggered by LPS or poly(I:C), alleviated the clinical manifestation and reduced the clinical score in keratitis in vivo. The histological disorder and proinflammatory cytokines of the cornea were also reduced. The translocation of NF-κB and phosphorylation of IκBα, NF-κB, p38, JNK, and ERK were significantly inhibited by H-RN. No sign of toxicity was observed. H-RN effectively attenuated keratitis in vivo and in vitro induced by LPS or poly(I:C) through blocking NF-κB and MAPK signaling pathways. It may be a promising and safe agent in treating keratitis.

  5. Clinical utility of voriconazole eye drops in ophthalmic fungal keratitis

    Science.gov (United States)

    Al-Badriyeh, Daoud; Neoh, Chin Fen; Stewart, Kay; Kong, David CM

    2010-01-01

    Fungal keratitis is one of the major causes of ophthalmic mycosis and is difficult to treat. The range of common antifungal agents available for fungal keratitis remains inadequate and is generally associated with poor clinical outcomes. Voriconazole is a new generation triazole antifungal agent. Only marketed in systemic formulation and, with broad-spectrum activity and high intraocular penetration, voriconazole has demonstrated effectiveness against fungal keratitis. Systemic voriconazole, however, is not without side effects and is costly. Voriconazole eye drops have been prepared extemporaneously and used for the treatment of ophthalmic fungal keratitis. The current article sought to review the literature for evidence related to the effectiveness and safety of topical voriconazole and its corneal penetration into the aqueous humor of the eye. The voriconazole eye drops used are typically of 1% concentration, well tolerated by the eye, and are stable. Despite existing evidence to suggest that the eye drops are effective in the treatment of fungal keratitis, more studies are needed, especially in relation to using the eye drops as first-line and stand-alone treatment, preparation of higher concentrations, and optimal dosing frequency. PMID:20463910

  6. Topical tacrolimus solution in autoimmune polyglandular syndrome-1-associated keratitis.

    Science.gov (United States)

    Shoughy, Samir S; Tabbara, Khalid F

    2017-09-01

    To evaluate the efficacy of topical tacrloimus eye drops in the treatment of keratitis associated with autoimmune polyglandular syndrome (APS)-1. This is a retrospective review of 10 patients with APS-1. The patients were treated with topical tacrolimus 0.01% solution at The Eye Center, between 1 March 2012 and 30 April 2016. The outcome measures included improvement in visual acuity, photophobia and keratitis following treatment. Clinical assessment was carried out before, during and on the last visit following initiation of therapy. A total of 10 patients were included. There were five male and five female patients. The mean age was 11 years with age range of 3-42 years. The mean duration of treatment with topical tacrolimus was 26 months (range 8-46 months). There was improvement of photophobia in 7 out of 10 patients following therapy with topical tacrolimus. In three patients, the photophobia was persistent. There was no clinically detectable improvement in the severity of keratitis in all patients. The mean best corrected visual acuity was 0.1 before and following therapy. Topical tacrolimus is effective in reducing the photophobia in patients with APS-1-associated keratitis, but showed no effects on the severity of keratitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Recurrent Fungal Keratitis and Blepharitis Caused by Aspergillus flavus.

    Science.gov (United States)

    Lee, Chia-Yi; Ho, Yi-Ju; Sun, Chi-Chin; Lin, Hsin-Chiung; Hsiao, Ching-Hsi; Ma, David Hui-Kang; Lai, Chi-Chun; Chen, Hung-Chi

    2016-11-02

    Aspergillus species produces a wide spectrum of fungal diseases like endophthalmitis and fungal keratitis ophthalmologically, but there has been no report about blepharitis caused by Aspergilus flavus to date. Herein, we report a 61-year-old ethnic Han Taiwanese male who had suffered from pain with burning and foreign body sensation after an insect bite on his left eye. Specimens from bilateral eyelids suggested infection of A. flavus, whereas corneal scraping showed the presence of Gram-negative bacteria. He was admitted for treatment of infectious keratitis with topical antibiotic and antifungal eye drops. Two weeks after discharge, recurrent blepharitis and keratitis of A. flavus was diagnosed microbiologically. Another treatment course of antifungal agent was resumed in the following 6 months, without further significant symptoms in the following 2 years. Collectively, it is possible for A. flavus to induce concurrent keratitis and blepharitis, and combined treatment of keratitis as well as blepharitis is advocated for as long as 6 months to ensure no recurrence. © The American Society of Tropical Medicine and Hygiene.

  8. Microbial Keratitis: Could Contact Lens Material Affect Disease Pathogenesis?

    Science.gov (United States)

    Evans, David J.; Fleiszig, Suzanne M. J.

    2012-01-01

    Microbial keratitis is a sight-threatening complication associated with contact lenses. The introduction of silicone hydrogel lens materials with increased oxygen transmission to the ocular surface has not significantly altered the incidence of microbial keratitis. These data suggest that alternate, or additional, predisposing factors involving lens wear must be addressed to reduce or eliminate these infections. The contact lens can provide a surface for microbial growth in situ, and can also influence ocular surface homeostasis through effects on the tear fluid and corneal epithelium. Thus, it is intuitive that future contact lens materials could make a significant contribution to preventing microbial keratitis. Design of the “right” material to prevent microbial keratitis requires understanding the effects of current materials on bacterial virulence in the cornea, and on ocular surface innate defenses. Current knowledge in each of these areas will be presented, with a discussion of future directions needed to understand the influence of lens material on the pathogenesis of microbial keratitis. PMID:23266587

  9. Clinical experiences in fungal keratitis caused by Acremonium

    Directory of Open Access Journals (Sweden)

    Kim SJ

    2014-01-01

    Full Text Available Seong-Jae Kim,1,2 Yong-Wun Cho,1 Seong-Wook Seo,1,2 Sun-Joo Kim,2,3 Ji-Myong Yoo1,21Department of Ophthalmology, 2Gyeongsang Institute of Health Science, 3Department of Laboratory Medicine, Gyeongsang National University, College of Medicine, Jinju, KoreaPurpose: To report the predisposing risk factors, clinical presentation, management, and therapeutic outcomes of fungal keratitis caused by Acremonium.Methods: This is a retrospective study of cases with Acremonium fungal keratitis that presented to our tertiary referral center between January 2006 and August 2012. Patient demographic and clinical details were determined and reported.Results: Five cases of fungal keratitis from Acremonium species were identified in five patients (three males, two females. The mean age of the patients was of 73.4±5.46 years, with a mean follow-up time of 124±72 days. All patients had a history of corneal trauma with vegetable matter. Four cases were unresponsive to initial treatment (0.2% fluconazole, 0.15% amphotericin B and required topical 5% natamycin, and, in two out of five cases, topical 1% voriconazole.Conclusion: The most common risk factors for Acremonium fungal keratitis was ocular trauma. When a corneal lesion is found to be unresponsive to the initial treatment, we should consider adding or substituting topical natamycin or voriconazole for treatment.Keywords: Acremonium, fungal keratitis, natamycin, prognosis, voriconazole

  10. Rare case of fungal keratitis caused by Plectosporium tabacinum

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    Kamada R

    2012-10-01

    Full Text Available Rika Kamada,1 Yu Monden,1 Koji Uehara,1 Ryoji Yamakawa,1 Kazuko Nishimura21Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka, 2Medical Mycology Research Center, Chiba University and First Laboratories Co, Ltd, Kawasaki, Kanagawa, JapanAbstract: A rare case of fungal keratitis caused by Plectosporium tabacinum is reported. A 78-year-old female gardener presented with conjunctivitis and an oval infiltrate with irregular margins in the nasal half of the cornea in the right eye. Light microscopy of corneal scrapings revealed a filamentous fungus, and a diagnosis of fungal keratitis was made. The patient was admitted into our hospital on February 19, 2008. Treatment with topical miconazole, topical fluconazole, pimaricin ointment, intravenous miconazole, and corneal debridement was commenced. One week later, the infiltrate improved, but the central part of the infiltrate was still deep. Topical fluconazole was switched to topical voriconazole, and intravenous miconazole was switched to intravenous voriconazole. One month after admission, the causative organism was identified by morphology and molecular biological analysis as Plectosporium tabacinum. The corneal infiltrate resolved 3 months after admission. A stromal scar persisted for 3 months after the patient was discharged. This is the first detailed report of fungal keratitis caused by P. tabacinum. Voriconazole was effective in treating this refractory keratitis.Keywords: fungal keratitis, Plectosporium tabacinum, voriconazole, filamentous fungi

  11. Porcine epidemic diarrhea virus inhibits dsRNA-induced interferon-β production in porcine intestinal epithelial cells by blockade of the RIG-I-mediated pathway.

    Science.gov (United States)

    Cao, Liyan; Ge, Xuying; Gao, Yu; Herrler, Georg; Ren, Yudong; Ren, Xiaofeng; Li, Guangxing

    2015-08-18

    The lack of optimal porcine cell lines has severely impeded the study and progress in elucidation of porcine epidemic diarrhea virus (PEDV) pathogenesis. Vero cell, an African green monkey kidney cell line, was often used to isolate and propagate PEDV. Nonetheless, the target cells of PEDV in vivo are intestinal epithelial cells, during infection, intestinal epithelia would be damaged and resulted in digestive disorders. The immune functions of porcine epithelial cells and interactions with other immune cell populations display a number of differences compared to other species. Type I interferon (IFN) plays an important role in antiviral immune response. Limited reports showed that PEDV could inhibit type I interferon production. In this study, porcine small intestinal epithelial cells (IECs), the target cells of PEDV, were used as the infection model in vitro to identify the possible molecular mechanisms of PEDV-inhibition IFN-β production. PEDV not only failed to induce IFN-β expression, but also inhibited dsRNA-mediated IFN-β production in IECs. As the key IFN-β transcription factors, we found that dsRNA-induced activation of IFN regulatory factor 3 (IRF-3) was inhibited after PEDV infection, but not nuclear factor-kappaB (NF-κB). To identify the mechanism of PEDV intervention with dsRNA-mediated IFN-β expression more accurately, the role of individual molecules of RIG-I signaling pathway were investigated. In the upstream of IRF-3, TANK-binding kinase 1 (TBK1)-or inhibitor of κB kinase-ε (IKKε)-mediated IFN-β production was not blocked by PEDV, while RIG-I-and its adapter molecule IFN-β promoter stimulator 1 (IPS-1)-mediated IFN-β production were completely inhibited after PEDV infection. Taken together, our data demonstrated for the first time that PEDV infection of its target cell line, IECs, inhibited dsRNA-mediated IFN-β production by blocking the activation of IPS-1 in RIG-I-mediated pathway. Our studies offered new visions in understanding of

  12. Sensing and control of bluetongue virus infection in epithelial cells via RIG-I and MDA5 helicases.

    Science.gov (United States)

    Chauveau, Emilie; Doceul, Virginie; Lara, Estelle; Adam, Micheline; Breard, Emmanuel; Sailleau, Corinne; Viarouge, Cyril; Desprat, Alexandra; Meyer, Gilles; Schwartz-Cornil, Isabelle; Ruscanu, Suzana; Charley, Bernard; Zientara, Stéphan; Vitour, Damien

    2012-11-01

    Bluetongue virus (BTV), an arthropod-borne member of the Reoviridae family, is a double-stranded RNA virus that causes an economically important livestock disease that has spread across Europe in recent decades. Production of type I interferon (alpha/beta interferon [IFN-α/β]) has been reported in vivo and in vitro upon BTV infection. However, the cellular sensors and signaling pathways involved in this process remain unknown. Here we studied the mechanisms responsible for the production of IFN-β in response to BTV serotype 8. Upon BTV infection of A549 cells, expression of IFN-β and other proinflammatory cytokines was strongly induced at both the protein and mRNA levels. This response appeared to be dependent on virus replication, since exposure to UV-inactivated virus failed to induce IFN-β. We also demonstrated that BTV infection activated the transcription factors IFN regulatory factor 3 and nuclear factor κB. We investigated the role of several pattern recognition receptors in this response and showed that expression of IFN-β was greatly reduced after small-interfering-RNA-mediated knockdown of the RNA helicase encoded by retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated gene 5 (MDA5). In contrast, silencing of MyD88, Toll-like receptor 3, or the recently described DexD/H-box helicase DDX1 sensor had no or a weak effect on IFN-β induction, suggesting that the RIG-I-like receptor pathway is specifically engaged for BTV sensing. Moreover, we also showed that overexpression of either RIG-I or MDA5 impaired BTV expression in infected A549 cells. Overall, this indicates that RIG-I and MDA5 can both contribute to the recognition and control of BTV infection.

  13. Pseudorabies virus infected porcine epithelial cell line generates a diverse set of host microRNAs and a special cluster of viral microRNAs.

    Directory of Open Access Journals (Sweden)

    Yi-Quan Wu

    Full Text Available Pseudorabies virus (PRV belongs to Alphaherpesvirinae subfamily that causes huge economic loss in pig industry worldwide. It has been recently demonstrated that many herpesviruses encode microRNAs (miRNAs, which play crucial roles in viral life cycle. However, the knowledge about PRV-encoded miRNAs is still limited. Here, we report a comprehensive analysis of both viral and host miRNA expression profiles in PRV-infected porcine epithelial cell line (PK-15. Deep sequencing data showed that the ∼4.6 kb intron of the large latency transcript (LLT functions as a primary microRNA precursor (pri-miRNA that encodes a cluster of 11 distinct miRNAs in the PRV genome, and 209 known and 39 novel porcine miRNAs were detected. Viral miRNAs were further confirmed by stem-loop RT-PCR and northern blot analysis. Intriguingly, all of these viral miRNAs exhibited terminal heterogeneity both at the 5' and 3' ends. Seven miRNA genes produced mature miRNAs from both arms and two of the viral miRNA genes showed partially overlapped in their precursor regions. Unexpectedly, a terminal loop-derived small RNA with high abundance and one special miRNA offset RNA (moRNA were processed from a same viral miRNA precursor. The polymorphisms of viral miRNAs shed light on the complexity of host miRNA-processing machinery and viral miRNA-regulatory mechanism. The swine genes and PRV genes were collected for target prediction of the viral miRNAs, revealing a complex network formed by both host and viral genes. GO enrichment analysis of host target genes suggests that PRV miRNAs are involved in complex cellular pathways including cell death, immune system process, metabolic pathway, indicating that these miRNAs play significant roles in virus-cells interaction of PRV and its hosts. Collectively, these data suggest that PRV infected epithelial cell line generates a diverse set of host miRNAs and a special cluster of viral miRNAs, which might facilitate PRV replication in cells.

  14. Actinomyces bowdenii ulcerative keratitis in a dog.

    Science.gov (United States)

    Sherman, Amanda; Daniels, Joshua B; Wilkie, David A; Lutz, Elizabeth

    2013-09-01

    A 5-year-old spayed female diabetic mixed-breed dog underwent phacoemulsification and intraocular lens implantation to correct bilateral hypermature cataracts. Two months postsurgery, the patient presented with ulcerative keratitis and multifocal stromal abscessation OD, which was controlled, but never resolved, with topical fluoroquinolone therapy. The patient re-presented 2 months later with a new, raised, white gritty corneal opacity associated with hyperemia, chemosis, and blepharospasm OD. Cytology of the right cornea revealed filamentous bacteria, suggestive of Actinomyces spp. Actinomyces bowdenii was subsequently isolated in pure culture and identified via 16s rDNA sequencing. Actinomyces bowdenii has never before been described as a cause of ocular infection. An immunosuppressed corneal environment likely contributed to this opportunistic Actinomycosis. The infection was not controlled with fluoroquinolone therapy, and the isolate, in vitro, was resistant to three fluoroquinolones (ciprofloxacin, ofloxacin, and levofloxacin), which also has not been previously reported for this species of Actinomyces. A superficial keratectomy with conjunctival graft was employed to successfully manage the infection. © 2012 American College of Veterinary Ophthalmologists.

  15. Rare Case of Polymicrobial Keratitis With Balantidium coli.

    Science.gov (United States)

    Hazarika, Manali; Pai H, Vijaya; Khanna, Vinay; Reddy, Harish; Tilak, Kriti; Chawla, Kiran

    2016-12-01

    To report a rare case of polymicrobial keratitis due to Balantidium coli and gram-negative bacteria, Pseudomonas aeruginosa and Klebsiella pneumoniae, in a soft contact lens (CL) wearer. We report a case of CL-related keratitis due to B. coli, P. aeruginosa, and K. pneumoniae. The culture of the corneal scrapings, the CL cleaning solution, and the CL revealed the growth of a rare ciliated parasite, B. coli, along with gram-negative bacteria, namely, P. aeruginosa and K. pneumoniae. The patient was successfully treated with topical broad-spectrum antibiotics and intravenous metronidazole. Polymicrobial keratitis has seldom been reported with B. coli as the causative agent. CL wear can be a risk factor for this infection. Treatment with topical antibiotics may not suffice, and the intravenous route of antiprotozoal drugs may be a useful adjunct. Increasing awareness, early diagnosis, and treatment may improve the final visual outcome.

  16. Nocardia Asteroides Keratitis: Report of seven patients and literature review

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    Rao Srinivas

    2000-01-01

    Full Text Available Purpose: To describe clinical features and treatment outcomes in patients with advanced Nocardia asteroides keratitis. Methods: Retrospective review of case records of 7 patients with culture-proven Nocardia keratitis. Results: Corneal infection occurred after corneal trauma in two patients, cataract surgery in three patients, penetrating keratoplasty in one patient and was associated with a silicone buckle element infection in one patient. Mean duration of infection at presentation was 33.4 days (7-75 days, and five patients had received prior treatment with corticosteroids. Six of seven patients had deep corneal suppuration at the time of: presentation, clinically suggestive of mycotic keratitis. In two patients who had received prolonged corticosteroid therapy (≥ 45 days, the eyes could not be salvaged. Complete resolution of infection was achieved in all 4 eyes treated with topical fortified cefazolin eye drops (50mg / ml.

  17. Linear interstitial keratitis: a distinct clinical entity revisited.

    Science.gov (United States)

    Calvo, Charles M; Sikder, Shameema; Mamalis, Nick; Mifflin, Mark D

    2012-12-01

    Few reports in the ophthalmic literature describe rare corneal lesions of the stroma that present in a horizontal linear fashion. Although some differences exist among the small number of reported cases, we believe that all these cases represent a distinct clinical entity appropriately titled linear interstitial keratitis. In an attempt to expand the knowledge of this condition of unknown etiology, we present 3 cases of linear interstitial keratitis. Case series (3 cases are presented) and literature review. All 3 patients (aged 21-22 years) presented with horizontal linear stromal infiltrates. One patient presented with a corneal perforation, requiring a closure with 3 interrupted sutures. Another patient required a penetrating keratoplasty because of a visually significant central scar. All 3 patients responded to topical steroids. Linear interstitial keratitis is a rare clinical entity and its histopathologic etiology remains undetermined. Current available technology including specular microscopy, anterior segment optical coherence tomography, and more sensitive serological testing may permit a better understanding of this disease.

  18. Non-traumatic keratitis due to Colletotrichum truncatum

    Science.gov (United States)

    Llamos, Reina; Al-Hatmi, Abdullah M. S.; Martínez, Gerardo; Hagen, Ferry; Velar, Rosario; de la Caridad Castillo Pérez, Alexeide; Illnait-Zaragozí, María T.

    2016-01-01

    Introduction: The fungal genus Colletotrichum is an uncommon cause of human infections. It has been implicated in cutaneous phaeohyphomycosis, artritis and keratitis secondary to traumatic implantation. Case presentation: We report two cases of keratitis due Colletotrichum truncatum in middle-aged, immunocompetent persons without history of trauma. The aetiological agents were identified based on DNA sequencing. Azoles and echinocandins showed high minimal inhibitory concentrations while amphotericin B was ≤ 0.25  mg l−1. Both patients failed topical antifungal treatment and needed penetrating keratoplasty with a favourable outcome. Conclusion: C. truncatum caused keratomycosis which did not respond to topical antifungal agents. To the best of our knowledge these are the first reported cases of keratitis due to this fungus in Cuba and Latin-America and highlights the expanding spectrum of fungal agents causing eye infections. PMID:28348770

  19. Staphylococcus aureus Keratitis: A Review of Hospital Cases

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    Ong, Sherine Jue; Huang, Yhu-Chering; Tan, Hsin-Yuan; Ma, David H. K.; Lin, Hsin-Chiung; Yeh, Lung-Kun; Chen, Phil Y. F.; Chen, Hung-Chi; Chuang, Chih-Chun; Chang, Chee-Jen; Hsiao, Ching-Hsi

    2013-01-01

    Background Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important public health issue. The study aimed to characterize the patient demographics, clinical features, antibiotic susceptibility, and clinical outcomes of keratitis caused by S. aureus, and to make a comparison between MRSA and methicillin-sensitive S. aureus (MSSA) isolates. Methodology/Principal findings Patients (n = 59) with culture-proven S. aureus keratitis treated in Chang Gung Memorial Hospital between January 1, 2006, and December 31, 2010, were included in our study. Patients' demographic and clinical data were retrospectively reviewed. Twenty-six MRSA (44%) and 33 MSSA (56%) isolates were collected. The MRSA keratitis was significantly more common among the patients with healthcare exposure (P = 0.038), but 46.2% (12/26) of patients with MRSA keratitis were considered to have community-associated infections. All isolates were susceptible to vancomycin. MRSA isolates were significantly more resistant to clindamycin, erythromycin, and sulfamethoxazole/trimethoprim. Ocular surface disease was a significant risk factor for MRSA keratitis (P = 0.011). Visual outcome did not differ significantly between the MRSA and MSSA groups. However, age (B = 0.01, P = 0.035, 95% confidence interval [CI]: 0.001–0.019) and visual acuity at presentation (B = 0.749, Pkeratitis, especially for MRSA infections. Advanced age and poor visual acuity at presentation are important prognostic indicators for poor visual outcome in S. aureus keratitis. Oxacillin resistance may not be a significant prognostic indicator. PMID:24244625

  20. A dot hybridization assay for the diagnosis of bacterial keratitis

    Science.gov (United States)

    Fang, Po-Chiung; Chien, Chun-Chih; Yu, Hun-Ju; Ho, Ren-Wen; Tseng, Shin-Ling; Lai, Yu-Hsuan

    2017-01-01

    Purpose To evaluate a bacterial dot hybridization (BDH) assay for the diagnosis of bacterial keratitis (BK). Methods Sixty-one qualified corneal scrapings from 61 patients with suspected microbial keratitis were collected consecutively and prospectively. Among the 61 patients, 16 cases were BK and 45 cases were non-BK, including fungal keratitis, viral keratitis, parasitic keratitis, and non-microbial keratitis. Molecular diagnosis of BK in these corneal scrapes was performed using the BDH assay with three universal bacterial probes (PB1, PB2, and PB3) and three genus-specific probes (Aci, Klb, and Psu) to detect Acinetobacter, Klebsiella, and Pseudomonas, respectively. Signals were standardized after grayscale image transformation for objective validation using receiver operating characteristic (ROC) curves. Results The standardized intensities for the three universal probes differed statistically significantly between the BK group and the non-BK group. Based on the ROC curves, the sensitivities of PB1, PB2, and PB3 were 81.3%, 81.3%, and 93.8%, and the specificities were 71.1%, 88.9%, and 91.1%, respectively. The sensitivity and specificity of the Psu probe were 92% and 100%, respectively, while those of the Aci and Klb probes could not be estimated because there were no BK cases caused by Acinetobacter spp. or Klebsiella spp. Conclusions The BDH assay is an effective molecular approach to improve the diagnosis of BK. Because the bias from bacterial contamination on the ocular surface can be minimized with signal standardization, the assay has the potential to be adopted for routine clinical practice. PMID:28484310

  1. Queratitis infecciosa no viral: factores predisponentes, agentes etiológicos y diagnóstico de laboratorio Non viral infectious keratitis: predisposing factors, etiologic agents and laboratory diagnosis

    Directory of Open Access Journals (Sweden)

    Federico Nicola

    2005-12-01

    Full Text Available Las queratitis infecciosas poseen una elevada morbilidad, poniendo en riesgo la visión en casos graves. Dada la eficaz protección que brinda el epitelio corneal, para que ocurra una infección se requiere la presencia de factores condicionantes. El principal predisponente para las queratitis infecciosas es el uso de lentes de contacto, seguido por traumatismos y cirugías oculares y luego diversas afecciones locales o generales. Los agentes etiológicos abarcan una enorme diversidad de microorganismos, incluyendo bacterias, micobacterias, virus, hongos y parásitos. Para poder instaurar un tratamiento acotado se necesita un diagnóstico etiológico, lo que requiere una correcta toma de muestra y un exhaustivo análisis microbiológico.Infectious keratitis cause significant morbidity and, if it is not promptly and appropriately treated, can lead to severe ocular disability. Almost all cases of keratitis are associated to predisposing conditions. In occident, the main risk factor is contact lens wear, but previous ocular surgery or trauma are also important, as well as various ocular surface diseases. An enormous diversity of etiologic agents for infectious keratitis exist, including virus, bacteria, mycobacteria, fungi and parasites. This review provides literature and personal based information about main predisposing factors, etiologic agents and pathophysiology of infectious keratitis, excluding those of viral origin. Focus is made on microbiologic procedures, describing stains and media that should be used, and highlighting their utility. A special mention on particular situations is made, including laboratory diagnosis of Acanthamoeba keratitis, utility of lens cases analysis, keratitis in patients with previous treatment, as well as molecular biology techniques described in ophthalmology.

  2. A Dual Role for Corneal Dendritic Cells in Herpes Simplex Keratitis: Local Suppression of Corneal Damage and Promotion of Systemic Viral Dissemination.

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    Kai Hu

    Full Text Available The cornea is the shield to the foreign world and thus, a primary site for peripheral infections. However, transparency and vision are incompatible with inflammation and scarring that may result from infections. Thus, the cornea is required to perform a delicate balance between fighting infections and preserving vision. To date, little is known about the specific role of antigen-presenting cells in viral keratitis. In this study, utilizing an established murine model of primary acute herpes simplex virus (HSV-1 keratitis, we demonstrate that primary HSV keratitis results in increased conventional dendritic cells (cDCs and macrophages within 24 hours after infection. Local depletion of cDCs in CD11c-DTR mice by subconjuntival diphtheria toxin injections, led to increased viral proliferation, and influx of inflammatory cells, resulting in increased scarring and clinical keratitis. In addition, while HSV infection resulted in significant corneal nerve destruction, local depletion of cDCs resulted in a much more severe loss of corneal nerves. Further, local cDC depletion resulted in decreased corneal nerve infection, and subsequently decreased and delayed systemic viral transmission in the trigeminal ganglion and draining lymph node, resulting in decreased mortality of mice. In contrast, sham depletion or depletion of macrophages through local injection of clodronate liposomes had neither a significant impact on the cornea, nor an effect on systemic viral transmission. In conclusion, we demonstrate that corneal cDCs may play a primary role in local corneal defense during viral keratitis and preserve vision, at the cost of inducing systemic viral dissemination, leading to increased mortality.

  3. A Dual Role for Corneal Dendritic Cells in Herpes Simplex Keratitis: Local Suppression of Corneal Damage and Promotion of Systemic Viral Dissemination

    Science.gov (United States)

    Hu, Kai; Harris, Deshea L.; Yamaguchi, Takefumi; von Andrian, Ulrich H.; Hamrah, Pedram

    2015-01-01

    The cornea is the shield to the foreign world and thus, a primary site for peripheral infections. However, transparency and vision are incompatible with inflammation and scarring that may result from infections. Thus, the cornea is required to perform a delicate balance between fighting infections and preserving vision. To date, little is known about the specific role of antigen-presenting cells in viral keratitis. In this study, utilizing an established murine model of primary acute herpes simplex virus (HSV)-1 keratitis, we demonstrate that primary HSV keratitis results in increased conventional dendritic cells (cDCs) and macrophages within 24 hours after infection. Local depletion of cDCs in CD11c-DTR mice by subconjuntival diphtheria toxin injections, led to increased viral proliferation, and influx of inflammatory cells, resulting in increased scarring and clinical keratitis. In addition, while HSV infection resulted in significant corneal nerve destruction, local depletion of cDCs resulted in a much more severe loss of corneal nerves. Further, local cDC depletion resulted in decreased corneal nerve infection, and subsequently decreased and delayed systemic viral transmission in the trigeminal ganglion and draining lymph node, resulting in decreased mortality of mice. In contrast, sham depletion or depletion of macrophages through local injection of clodronate liposomes had neither a significant impact on the cornea, nor an effect on systemic viral transmission. In conclusion, we demonstrate that corneal cDCs may play a primary role in local corneal defense during viral keratitis and preserve vision, at the cost of inducing systemic viral dissemination, leading to increased mortality. PMID:26332302

  4. Glutathione Transferase as a Potential Marker for Gut Epithelial Injury versus the Protective Role of Breast Milk sIgA in Infants with Rota Virus Gastroenteritis.

    Science.gov (United States)

    Sherif, Lobna S; Raouf, Randaa K Abdel; Sayede, Rokaya M El; Wakkadd, Amany S El; Shoaib, Ashraf R; Ali, Hanan M; Refay, Amira S El

    2015-12-15

    Secretory immunoglobulin A (SIgA) plays an important protective role in the recognition and clearance of enteric pathogens. This study was designed to assess if mucosal integrity "measured by secretory IgA (SIgA)" is a protective factor from more epithelial alteration "measured by glutathione transferase" in infants with Rota gastroenteritis and its relation to infants' feeding pattern. This study was conducted on 79 infants aged 6 months and less from those diagnosed as having gastroenteritis and admitted to Gastroenteritis Department in Abo El Rish Pediatric Hospital, Cairo University. Plasma glutathione s-transferases and Stool SIgA were measured using ELISA technique. Rota virus detection was done by Reverse transcriptase PCR. SIgA was found to be significantly positive in exclusive breast fed infants, Glutathione transferase was significantly more frequently positive in Rota positive cases than Rota negative cases by Reverse transcriptase PCR. A significant negative correlation between Glutathione transferase and Secretory IgA was found, (p Rota viral gastroenteritis.

  5. Liver cancer-derived hepatitis C virus core proteins shift TGF-beta responses from tumor suppression to epithelial-mesenchymal transition.

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    Serena Battaglia

    Full Text Available BACKGROUND: Chronic hepatitis C virus (HCV infection and associated liver cirrhosis represent a major risk factor for hepatocellular carcinoma (HCC development. TGF-beta is an important driver of liver fibrogenesis and cancer; however, its actual impact in human cancer progression is still poorly known. The aim of this study was to investigate the role of HCC-derived HCV core natural variants on cancer progression through their impact on TGF-beta signaling. PRINCIPAL FINDINGS: We provide evidence that HCC-derived core protein expression in primary human or mouse hepatocyte alleviates TGF-beta responses in terms or growth inhibition or apoptosis. Instead, in these hepatocytes TGF-beta was still able to induce an epithelial to mesenchymal transition (EMT, a process that contributes to the promotion of cell invasion and metastasis. Moreover, we demonstrate that different thresholds of Smad3 activation dictate the TGF-beta responses in hepatic cells and that HCV core protein, by decreasing Smad3 activation, may switch TGF-beta growth inhibitory effects to tumor promoting responses. CONCLUSION/SIGNIFICANCE: Our data illustrate the capacity of hepatocytes to develop EMT and plasticity under TGF-beta, emphasize the role of HCV core protein in the dynamic of these effects and provide evidence for a paradigm whereby a viral protein implicated in oncogenesis is capable to shift TGF-beta responses from cytostatic effects to EMT development.

  6. Effectiveness of in vivo confocal microscopy in detecting filamentous fungi during clinical course of fungal keratitis.

    Science.gov (United States)

    Takezawa, Yuki; Shiraishi, Atsushi; Noda, Eriko; Hara, Yuko; Yamaguchi, Masahiko; Uno, Toshihiko; Ohashi, Yuichi

    2010-12-01

    To determine the effectiveness of laser confocal microscopy in detecting filamentous fungi in the cornea of patients with fungal keratitis (FK) and in evaluating the effectiveness of the treatment. The corneas of 6 patients clinically diagnosed with FK were examined with the Heidelberg Retina Tomograph II-Rostock Cornea Module (HRT II-RCM). Three of these patients were also monitored periodically with the HRT II-RCM after antifungal treatment. The HRT II-RCM examination showed interlocking and branching, white, septated, hyphae-like lines in the cornea of all patients. All 6 patients had positive corneal smears and/or laboratory cultures. Three patients were monitored with HRT II-RCM after antifungal treatment. One patient, whose initial smear was negative, was diagnosed by HRT II-RCM before the positive culture results. In another case, the epithelial regeneration was impaired even 3 weeks after the initial treatment and HRT II-RCM revealed a mass of hyphae in the corneal ulcerated lesion. These findings indicated the necessity of surgical debridement. After the surgical debridement, the corneal epithelial defect was healed. HRT II-RCM was able to detect the morphological changes of hyphae after antifungal treatment and helped in the treatment modifications during the clinical course in all 3 patients. These results indicate that HRT II-RCM can be used to diagnose FK and to monitor the effect of therapy on FK.

  7. [Amniotic membrane transplantation in proven ulcerative herpetic keratitis: successful anti-inflammatory treatment in time].

    Science.gov (United States)

    Spelsberg, H; Reichelt, J A

    2008-01-01

    In active herpetic keratitis, treatment with systemic and topical aciclovir together with low dosed-out steroids has been successful for few decades. However, in cases with severe herpetic ulcer and melting inflammation, emergency penetrating keratoplasty is necessary, which carries high risk for recurrent herpetic keratitis and rejection. The anti-inflammatory effect of amniotic membrane transplantation can be used as a first surgical step in order to gain time for planned penetrating keratoplasty. The results are analysed in this retrospective case series. Twelve eyes of 12 patients with clinically highly active herpetic ulcer without healing despite topical and systemic aciclovir were treated with amniotic membrane transplantation. Ten of 12 eyes (83 %) showed positive PCR testing for HSV-1. In one case, the molecular genetic result was negative, one analysis for HSV was not done. For surgery, debridement of the margins and the ground of the ulcer was done with steam heated cauterization. Afterwards, an amniotic membrane was made to cover the defect and fixed with single sutures. Peri- and postoperatively, the patients were treated with systemic aciclovir (4000 mg daily one week, 2000 mg daily 2 weeks) and gentamicin ointment topically. Mean follow-up was 6.8 months (1-12.5). After 25 days in the mean (11-34), nine of 12 patients experienced an intact epithelial corneal surface together with a clinically clear reduction of the inflammation. Three other patients did not recover and were treated with emergency penetrating keratoplasty after 31 days in mean (25-35). Visual acuity did not improve after amniotic membrane transplantation except in one case. The known anti-inflammatory potential of amniotic membrane causes a reduction of the inflammatory process in herpetic ulcer. A precondition is a sufficient antiherpetic and anti-inflammatory therapy and a decision for amniotic membrane transplantation in time in order to avoid an emergency penetrating keratoplasty

  8. Melimine-Coated Antimicrobial Contact Lenses Reduce Microbial Keratitis in an Animal Model.

    Science.gov (United States)

    Dutta, Debarun; Vijay, Ajay K; Kumar, Naresh; Willcox, Mark D P

    2016-10-01

    To determine the ability of antimicrobial peptide melimine-coated contact lenses to reduce the incidence of microbial keratitis (MK) in a rabbit model of contact lens wear. In vitro antimicrobial activity of melimine-coated contact lenses was determined against Pseudomonas aeruginosa by viable count and a radiolabeled assay. The amount of lipopolysaccharide (LPS) associated with bacteria bound to melimine-coated and control lenses was determined. Ocular swabs from rabbit eyes were collected for assessment of ocular microflora. A rabbit model for MK was developed that used overnight wear of contact lenses colonized by P. aeruginosa in the absence of a corneal scratch. During lens wear, detailed ocular examinations were performed, and the incidence of MK was investigated. Bacteria associated with worn lenses and infected corneas were determined by viable plate count. Inhibition in viable and total P. aeruginosa adhesion by melimine-coated contact lenses was 3.1 log10 and 0.4 log10, respectively. After colonization, the amount of LPS on lenses was approximately the same with or without melimine. Gram-positive bacteria were found in all the ocular swabs followed by fungus (42%). Melimine-coated lens wear was protective and significantly (odds ratio 10.12; P = 0.012) reduced the incidence of P. aeruginosa-driven MK in the rabbit model. The antimicrobial lenses were associated with significantly (P contact lenses can produce MK without corneal epithelial defect in an animal model. Melimine-coated contact lenses reduced the incidence of MK associated with P. aeruginosa in vivo. Development of MK requires viable bacteria adherent to contact lenses, and bacterial debris adherent at the lens surface did not cause keratitis.

  9. Dacryoadenitis and extraocular muscle inflammation associated with contact lens-related Acanthamoeba keratitis: A case report and review of the literature.

    Science.gov (United States)

    Sengor, Tomris; Yuzbasioglu, Erdal; Aydın Kurna, Sevda; Irkec, Murat; Altun, Ahmet; Kökcen, Kubra; Yalcin, Nazli Gul

    2017-02-01

    The present report discusses a new case of dacryoadenitis with extraocular muscle inflammation associated with Acanthamoeba keratitis (AK) in a contact lens wearer. A 41-year-old male, who has worn silicone hydrogel contact lenses on an extended basis for about 10 years, attended with the complaints of vision disturbance, hyperemia, and pain in his right eye. His history revealed that 1.5 month ago, he had been diagnosed with allergic conjunctivitis and had used steroid eye drops. Biomicroscopic examination revealed eyelid edema, chemosis, and ring infiltration, radial keratoneuritis and an epithelial defect in the cornea. Magnetic resonance imaging demonstrated enlarged lacrimal gland with edematous changes consistent with inflammation due to dacryoadenitis. There were also thickening and edema of the right superior oblique and lateral rectus muscle. The treatment protocol for AK was applied with no specific treatment for dacryoadenitis. After 4 months of the treatment, dacryoadenitis and keratitis regressed. Dacryoadenitis and extraocular muscle inflammation may accompany AK more frequently than expected and previously known. The evaluation of the lacrimal gland and extraocular muscles in presence of AK might be beneficial for understanding better the exact clinical picture and course of the keratitis.

  10. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment

    Science.gov (United States)

    Lorenzo-Morales, Jacob; Khan, Naveed A.; Walochnik, Julia

    2015-01-01

    Free-living amoebae of the genus Acanthamoeba are causal agents of a severe sight-threatening infection of the cornea known as Acanthamoeba keratitis. Moreover, the number of reported cases worldwide is increasing year after year, mostly in contact lens wearers, although cases have also been reported in non-contact lens wearers. Interestingly, Acanthamoeba keratitis has remained significant, despite our advances in antimicrobial chemotherapy and supportive care. In part, this is due to an incomplete understanding of the pathogenesis and pathophysiology of the disease, diagnostic delays and problems associated with chemotherapeutic interventions. In view of the devastating nature of this disease, here we present our current understanding of Acanthamoeba keratitis and molecular mechanisms associated with the disease, as well as virulence traits of Acanthamoeba that may be potential targets for improved diagnosis, therapeutic interventions and/or for the development of preventative measures. Novel molecular approaches such as proteomics, RNAi and a consensus in the diagnostic approaches for a suspected case of Acanthamoeba keratitis are proposed and reviewed based on data which have been compiled after years of working on this amoebic organism using many different techniques and listening to many experts in this field at conferences, workshops and international meetings. Altogether, this review may serve as the milestone for developing an effective solution for the prevention, control and treatment of Acanthamoeba infections. PMID:25687209

  11. INFECTIOUS KERATITIS-ASSOCIATED ENDOPHTHALMITIS: A 14-Year Study.

    Science.gov (United States)

    Malihi, Mehrdad; Li, Xintong; Patel, Shriji; Eck, Thomas; Chu, David S; Zarbin, Marco A; Bhagat, Neelakshi

    2017-04-01

    To describe the demographics, characteristics, management, and outcomes of eyes with endophthalmitis related to infectious keratitis. Retrospective chart review of all patients treated for infectious keratitis-associated infectious endophthalmitis between 2001 and 2014 at University Hospital, Rutgers New Jersey Medical School. Thirty-eight cases with infectious keratitis-associated infectious endophthalmitis were identified (21 men [55%], mean age: 66.2 ± 20.7 years), with average time from the beginning of ulcer symptoms to endophthalmitis of 11.0 days. Associated systemic conditions (diabetes, HIV, immunosuppressive therapy, cirrhosis, or dementia) were present in 57.9%; 60.5% had previous intraocular surgery. Etiology showed gram-positive bacteria in 14 cases (36.9%), gram-negative bacteria in 7 (18.4%), fungi in 4 (10.5%), and no growth/unknown in 12 (31.6%). Nineteen cases (50%) presented with no light perception and were primarily enucleated. The remaining 19 eyes each received intravitreal antibiotics (mean: 1.5 injections); 8 (42.0%) underwent pars plans vitrectomy with vitreous biopsy, whereas 5 (26.3%) received emergency corneal transplantation. Final visual acuity was no light perception in 6 eyes (3 secondarily enucleated), light perception in 2, hand motion in 7, counting fingers in 2, and ≥20/50 in 2. Our study of 38 eyes with infectious keratitis-associated infectious endophthalmitis revealed generally poor visual outcomes and a high rate of systemic conditions and previous intraocular surgery.

  12. Choice of the laser wavelength for a herpetic keratitis treatment

    Science.gov (United States)

    Razhev, Alexander M.; Bagayev, Sergei N.; Chernikh, Valery V.; Kargapoltsev, Evgeny S.; Trunov, Alexander; Zhupikov, Andrey A.

    2002-06-01

    For the first time the effect of the UV laser radiation to human eye cornea with herpetic keratitis was experimentally investigated. In experiments the UV radiation of ArF (193 nm), KrCl (223 nm), KrF (248 nm) excimer lasers were used. Optimal laser radiation parameters for the treatment of the herpetic keratitis were determined. The immuno-biochemical investigations were carried out and the results of clinical trials are presented. The maximum ablation rate was obtained for the 248 nm radiation wavelength. The process of healing was successful but in some cases the haze on the surface of the cornea was observed. When used the 193 nm radiation wavelength the corneal surface was clear without any hazes but the epithelization process was slower than for 248 nm wavelength and in some cases the relapse was occurred. The best results for herpetic keratitis treatment have been achieved by utilizing the 223 nm radiation wavelength of the KrCl excimer laser. The use of the 223 nm radiation wavelength allows treating the herpetic keratitis with low traumatic process of ablation and provides high quality of corneal surface.

  13. Bipolaris oryzae, a novel fungal opportunist causing keratitis

    NARCIS (Netherlands)

    Al-Hatmi, Abdullah

    2015-01-01

    We report a case of mycotic keratitis caused by Bipolaris oryzae with predisposing trauma from a foreign body. The fungus was identified by sequencing the internal transcribed spacer (ITS) region, translation elongation factor 1α (TEF1) gene and partial glyceraldehyde-3-phosphate dehydrogenase

  14. Incidence of contact lens-associated microbial keratitis

    NARCIS (Netherlands)

    Cheng, K.H.; Leung, S.L.; Hoekman, J.W.; Beekhuis, W.H.; Mulder, P.G.H.; Geerards, A.J.M.; Kijlstra, A.

    1999-01-01

    Background. The incidence of contact-lens-associated microbial keratitis is uncertain and its related morbidity in the general population of contact-lens wearers is not known. We examined these issues in a prospective epidemiological study. Methods. We surveyed all practising ophthalmologists in the

  15. Rhizopus Keratitis Associated with Poor Contact Lens Hygiene

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    David B. Warner

    2016-01-01

    Full Text Available We report a case of Rhizopus keratitis in a young woman with poor contact lens hygiene. The mold was highly sensitive to treatment with amphotericin 0.15% drops, after a relatively prompt diagnosis. Obtaining cultures of both corneal infiltrates and presumably infected contact lenses may help to avoid a delay in proper treatment.

  16. Spectrum and Sensitivity of Bacterial Keratitis Isolates in Auckland

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    S. Marasini

    2016-01-01

    Full Text Available Background. The bacteria isolated from severe cases of keratitis and their antibiotic sensitivity are recognised to vary geographically and over time. Objectives. To identify the most commonly isolated bacteria in keratitis cases admitted over a 24-month period to a public hospital in Auckland, New Zealand, and to investigate in vitro sensitivity to antibiotics. Methods. Hospital admissions for culture-proven bacterial keratitis between January 2013 and December 2014 were identified. Laboratory records of 89 culture positive cases were retrospectively reviewed and antibiotic sensitivity patterns compared with previous studies from other NZ centres. Results. From 126 positive cultures, 35 species were identified. Staphylococcus was identified to be the most common isolate (38.2%, followed by Pseudomonas (21.3%. Over the last decade, infection due to Pseudomonas species, in the same setting, has increased (p≤0.05. Aminoglycosides, cefazolin, ceftazidime, erythromycin, tetracycline, and doxycycline were 100% effective against tested isolates in vitro. Amoxicillin (41.6%, cefuroxime (33.3%, and chloramphenicol (94.7% showed reduced efficacy against Gram-negative bacteria, whereas penicillin (51% and ciprofloxacin (98.8% showed reduced efficacy against Gram-positive bacteria. Conclusions. Despite a shift in the spectrum of bacterial keratitis isolates, antibiotic sensitivity patterns have generally remained stable and show comparability to results within the last decade from NZ centres.

  17. Review of clinical and basic approaches of fungal keratitis

    Directory of Open Access Journals (Sweden)

    Jie Wu

    2016-12-01

    Full Text Available Fungal keratitis (FK is a serious disease which can cause blindness. This review has current information about the pathogenesis, limitations of traditional diagnosis and therapeutic strategies, immune recognition and the diagnosis and therapy of FK. The information of this summary was reviewed regularly and updated as what we need in the diagnosis and therapy of FK nowadays.

  18. Effects of photodynamic therapy on rapidly growing nontuberculous mycobacteria keratitis.

    Science.gov (United States)

    Shih, Min-Hsiu; Huang, Fu-Chin

    2011-01-05

    The authors investigated the antimicrobial effect of methylene blue (MB)-mediated photodynamic therapy (PDT) on Mycobacterium fortuitum keratitis. In the in vitro study, the mycobacterial suspension and colonies were treated with the following: no MB, no light (normal control); MB and no light (dye control); light and no MB (light control); MB and light (PDT). Morphologic characteristics were examined by transmission electron microscopy. The bactericidal effects of combined PDT and antibiotic therapy (ciprofloxacin, moxifloxacin, and amikacin) were determined using the broth microdilution technique. Twenty-one rabbits with Mycobacterium keratitis were randomly divided into three groups (no treatment, topical amikacin treatment, and PDT combined with amikacin treatment). The clinical features of keratitis were scored and graded before treatment and before euthanatization. The diseased corneas were trephined for quantitative bacteriologic analysis to determine the antibacterial efficacy of the treatment. In the in vitro tests, the bacterial count had a 2-log reduction immediately after PDT treatment at 100 J/cm(2) with 10(-3)% MB. After PDT at 100 J/cm(2) with 10(-2)% MB, almost no viable bacteria were detected. PDT had a synergistic antimicrobial effect in combination with antibiotics. The phototoxicity occurred in the cytoplasm first and then disrupted the mycobacterial cell walls by lysis. In the rabbit keratitis model, combined PDT resulted in significantly less bacterial burden (P PDT against Mycobacterium fortuitum. PDT could be a potential alternative treatment for nontuberculous mycobacterial corneal infections.

  19. Cryotherapy in Dendritic Keratitis. | Mpyet | Nigerian Journal of ...

    African Journals Online (AJOL)

    This study evaluates the effectiveness of cryotherapy in the treatment of Dendritic Keratitis where antiviral agents are not available. The result show some improvement in visual acuity while one patient has a drop in vision. The extent of corneal scarring appears to depend on the duration of the disease and extent of stroma ...

  20. Bacterial Keratitis: Risk Factors and Causative Agents | Bataineh ...

    African Journals Online (AJOL)

    Objectives: to describe the clinical, microbiological characteristics and risk factors of. Bacterial Keratitis at Prince Zeid and Rashed ... Offending organisms were isolated in 17(50%) cases only. Pseudomonas in 10(58.8%) cases ... Pseudomonas was the major causative organism. Proper sampling and microbiological ...

  1. The Demographic and Clinical Presentation of Ulcerative Keratitis in ...

    African Journals Online (AJOL)

    Patients with ulcerative keratitis consecutively underwent ocular history, examination, corneal scrapping and HIV screening. Treatment was initiated based on clinical appearance of the ulcer and was changed accordingly after laboratory results. Patients were followed up until complete healing occurred. The demographic ...

  2. Corneal edema and keratitis following selective laser trabeculoplasty

    Directory of Open Access Journals (Sweden)

    Erica Tan Liu

    2017-06-01

    Conclusions and importance: With the increase in usage of SLT as a treatment for glaucoma and subsequent reports of keratitis, it is imperative for ophthalmic surgeons to be aware of herpes simplex as a possible risk factor. Prompt treatment with antivirals and steroids can potentially prevent scarring and permanent damage to the cornea.

  3. Evaluation of keratic precipitates and corneal endothelium in Fuchs' heterochromic cyclitis by in vivo confocal microscopy.

    Science.gov (United States)

    Labbé, A; Dupas, B; Offret, H; Baudouin, C; Labetoulle, M

    2009-05-01

    To analyse keratic precipitates in Fuchs' heterochromic cyclitis (FHC) by in-vivo confocal microscopy (IVCM). A retrospective chart review of 13 consecutive patients with FHC was conducted. Data collection included medical and ophthalmological history, age, age at diagnosis, gender, detailed slit-lamp examination and IVCM images. The IVCM characteristics of keratic precipitates and of the endothelium were analysed. Large hyperreflective deposits corresponding to keratic precipitates were observed on the endothelium of all FHC eyes and showed a great consistency among the different patients. These infiltrating keratic precipitates had a dendritic shape, with a small central core with numerous thin pseudopodia sometimes making connection between different keratic precipitates. The mean density of these keratic precipitates was 16.01/mm(2) (SD 6.54). The mean size of the largest dimension of these keratic precipitates was 127.31 microm (SD 41.49; range 66.16-201.4 microm). Hyporeflective round defects were observed at the level of the endothelium at contact or in the close vicinity of keratic precipitates or smaller hyperreflective deposits. All contralateral (non-affected eyes) had no keratic precipitates nor endothelial abnormalities. By providing high resolution images of corneal endothelium and keratic precipitates, IVCM could help the diagnosis and understanding of complex forms of intraocular inflammation such as FHC.

  4. A case of radial keratoneuritis in non-Acanthamoeba keratitis

    Directory of Open Access Journals (Sweden)

    Mutoh T

    2012-09-01

    Full Text Available Tetsuya Mutoh, Yukihiro Matsumoto, Makoto ChikudaDepartment of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Saitama, JapanAbstract: A case of non-Acanthamoeba keratitis with radial keratoneuritis, which is thought to be pathognomonic for Acanthamoeba keratitis, is reported. A healthy 32-year-old woman with a history of frequent replacement of her contact lenses due to wear was examined at Dokkyo Medical University Koshigaya Hospital (Saitama, Japan and found to have a slight corneal opacity that was accompanied by radial keratoneuritis. Based on both the patient’s clinical findings and past history, the presence of Acanthamoeba keratitis was highly suspected. However, direct light microscopy of corneal scrapings stained by the Parker ink–potassium hydroxide method only found Acanthamoeba-type material in the specimen collected at her initial visit. In all other specimens collected from the patient, no Acanthamoeba was found either when using the same method or when performing cultures of the surgical debridement of the corneal lesion. In addition, topical antifungal eye drops, systemic antifungal drugs, and surgical debridement were also not effective in this case. Since a precise diagnosis could not be made, the patient was treated with topical 0.1% betamethasone sodium, which ultimately resulted in a dramatic improvement of her corneal inflammation. At 23 days after initiation of topical administration of 0.1% betamethasone sodium, visual acuity was 20/250, with a slight corneal opacity noted at the original site of infection. The outcome of the current case suggests that radial keratoneuritis is not always pathognomonic for Acanthamoeba keratitis.Keywords: radial keratoneuritis, non-Acanthamoeba keratitis, topical corticosteroid

  5. Systems-level comparison of host responses induced by pandemic and seasonal influenza A H1N1 viruses in primary human type I-like alveolar epithelial cells in vitro

    Directory of Open Access Journals (Sweden)

    Guan Yi

    2010-10-01

    Full Text Available Abstract Background Pandemic influenza H1N1 (pdmH1N1 virus causes mild disease in humans but occasionally leads to severe complications and even death, especially in those who are pregnant or have underlying disease. Cytokine responses induced by pdmH1N1 viruses in vitro are comparable to other seasonal influenza viruses suggesting the cytokine dysregulation as seen in H5N1 infection is not a feature of the pdmH1N1 virus. However a comprehensive gene expression profile of pdmH1N1 in relevant primary human cells in vitro has not been reported. Type I alveolar epithelial cells are a key target cell in pdmH1N1 pneumonia. Methods We carried out a comprehensive gene expression profiling using the Affymetrix microarray platform to compare the transcriptomes of primary human alveolar type I-like alveolar epithelial cells infected with pdmH1N1 or seasonal H1N1 virus. Results Overall, we found that most of the genes that induced by the pdmH1N1 were similarly regulated in response to seasonal H1N1 infection with respect to both trend and extent of gene expression. These commonly responsive genes were largely related to the interferon (IFN response. Expression of the type III IFN IL29 was more prominent than the type I IFN IFNβ and a similar pattern of expression of both IFN genes was seen in pdmH1N1 and seasonal H1N1 infection. Genes that were significantly down-regulated in response to seasonal H1N1 but not in response to pdmH1N1 included the zinc finger proteins and small nucleolar RNAs. Gene Ontology (GO and pathway over-representation analysis suggested that these genes were associated with DNA binding and transcription/translation related functions. Conclusions Both seasonal H1N1 and pdmH1N1 trigger similar host responses including IFN-based antiviral responses and cytokine responses. Unlike the avian H5N1 virus, pdmH1N1 virus does not have an intrinsic capacity for cytokine dysregulation. The differences between pdmH1N1 and seasonal H1N1 viruses

  6. Optic atrophy, necrotizing anterior scleritis and keratitis presenting in association with Streptococcal Toxic Shock Syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Papageorgiou Konstantinos I

    2008-02-01

    Full Text Available Abstract Introduction We report a case of optic atrophy, necrotizing anterior scleritis and keratitis presenting in a patient with Streptococcal Toxic Shock Syndrome. Case presentation A 43-year-old woman developed streptococcal toxic shock syndrome secondary to septic arthritis of her right ankle. Streptococcus pyogenes (b-haemolyticus Group A was isolated from blood cultures and joint aspirate. She was referred for ophthalmology review as her right eye became injected and the pupil had become unresponsive to light whilst she was in the Intensive Therapy Unit (ITU. The iris appeared atrophic and was mid-dilated with no direct or consensual response to light. Three zones of sub-epithelial opacification where noted in the cornea. There where extensive posterior synechiae. Indirect ophthalmoscopy showed a pale right disc. The vision was reduced to hand movements (HM. A diagnosis of optic atrophy was made secondary to post-streptococcal uveitis. She subsequently developed a necrotizing anterior scleritis. Conclusion This case illustrates a previously unreported association of optic atrophy, necrotizing anterior scleritis and keratitis in a patient with post-streptococcal uveitis. This patient had developed Streptococcal Toxic Shock Syndrome secondary to septic arthritis. We recommend increased awareness of the potential risks of these patients developing severe ocular involvement.

  7. Respiratory Syncytial Virus Infection Upregulates NLRC5 and Major Histocompatibility Complex Class I Expression through RIG-I Induction in Airway Epithelial Cells.

    Science.gov (United States)

    Guo, Xuancheng; Liu, Taixiang; Shi, Hengfei; Wang, Jingjing; Ji, Ping; Wang, Hongwei; Hou, Yayi; Tan, Ren Xiang; Li, Erguang

    2015-08-01

    Respiratory syncytial virus (RSV) is the leading cause of acute respiratory tract viral infection in infants, causing bronchiolitis and pneumonia. The host antiviral response to RSV acts via retinoic acid-inducible gene I (RIG-I). We show here that RSV infection upregulates major histocompatibility complex class I (MHC-I) expression through the induction of NLRC5, a NOD-like, CARD domain-containing intracellular protein that has recently been identified as a class I MHC transactivator (CITA). RSV infection of A549 cells promotes upregulation of NLRC5 via beta interferon (IFN-β) production, since the NLRC5-inducing activity in a conditioned medium from RSV-infected A549 cells was removed by antibody to IFN-β, but not by antibody to IFN-γ. RSV infection resulted in RIG-I upregulation and induction of NLRC5 and MHC-I. Suppression of RIG-I induction significantly blocked NLRC5, as well as MHC-I, upregulation and diminished IRF3 activation. Importantly, Vero cells deficient in interferon production still upregulated MHC-I following introduction of the RSV genome by infection or transfection, further supporting a key role for RIG-I. A model is therefore proposed in which the host upregulates MHC-I expression during RSV infection directly via the induction of RIG-I and NLRC5 expression. Since elevated expression of MHC-I molecules can sensitize host cells to T lymphocyte-mediated cytotoxicity or immunopathologic damage, the results have significant implications for the modification of immunity in RSV disease. Human respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants and young children worldwide. Infection early in life is linked to persistent wheezing and allergic asthma in later life, possibly related to upregulation of major histocompatibility class I (MHC-I) on the cell surface, which facilitates cytotoxic T cell activation and antiviral immunity. Here, we show that RSV infection of lung epithelial cells induces

  8. Identification of Novel Small Organic Compounds with Diverse Structures for the Induction of Epstein-Barr Virus (EBV Lytic Cycle in EBV-Positive Epithelial Malignancies.

    Directory of Open Access Journals (Sweden)

    Chung King Choi

    Full Text Available Phorbol esters, which are protein kinase C (PKC activators, and histone deacetylase (HDAC inhibitors, which cause enhanced acetylation of cellular proteins, are the main classes of chemical inducers of Epstein-Barr virus (EBV lytic cycle in latently EBV-infected cells acting through the PKC pathway. Chemical inducers which induce EBV lytic cycle through alternative cellular pathways may aid in defining the mechanisms leading to lytic cycle reactivation and improve cells' responsiveness towards lytic induction. We performed a phenotypic screening on a chemical library of 50,240 novel small organic compounds to identify novel class(es of strong inducer(s of EBV lytic cycle in gastric carcinoma (GC and nasopharyngeal carcinoma (NPC cells. Five hit compounds were selected after three successive rounds of increasingly stringent screening. All five compounds are structurally diverse from each other and distinct from phorbol esters or HDAC inhibitors. They neither cause hyperacetylation of histone proteins nor significant PKC activation at their working concentrations, suggesting that their biological mode of action are distinct from that of the known chemical inducers. Two of the five compounds with rapid lytic-inducing action were further studied for their mechanisms of induction of EBV lytic cycle. Unlike HDAC inhibitors, lytic induction by both compounds was not inhibited by rottlerin, a specific inhibitor of PKCδ. Interestingly, both compounds could cooperate with HDAC inhibitors to enhance EBV lytic cycle induction in EBV-positive epithelial cancer cells, paving way for the development of strategies to increase cells' responsiveness towards lytic reactivation. One of the two compounds bears structural resemblance to iron chelators and the other strongly activates the MAPK pathways. These structurally diverse novel organic compounds may represent potential new classes of chemicals that can be used to investigate any alternative mechanism

  9. Identification of Novel Small Organic Compounds with Diverse Structures for the Induction of Epstein-Barr Virus (EBV) Lytic Cycle in EBV-Positive Epithelial Malignancies.

    Science.gov (United States)

    Choi, Chung King; Ho, Dona N; Hui, Kwai Fung; Kao, Richard Y; Chiang, Alan K S

    2015-01-01

    Phorbol esters, which are protein kinase C (PKC) activators, and histone deacetylase (HDAC) inhibitors, which cause enhanced acetylation of cellular proteins, are the main classes of chemical inducers of Epstein-Barr virus (EBV) lytic cycle in latently EBV-infected cells acting through the PKC pathway. Chemical inducers which induce EBV lytic cycle through alternative cellular pathways may aid in defining the mechanisms leading to lytic cycle reactivation and improve cells' responsiveness towards lytic induction. We performed a phenotypic screening on a chemical library of 50,240 novel small organic compounds to identify novel class(es) of strong inducer(s) of EBV lytic cycle in gastric carcinoma (GC) and nasopharyngeal carcinoma (NPC) cells. Five hit compounds were selected after three successive rounds of increasingly stringent screening. All five compounds are structurally diverse from each other and distinct from phorbol esters or HDAC inhibitors. They neither cause hyperacetylation of histone proteins nor significant PKC activation at their working concentrations, suggesting that their biological mode of action are distinct from that of the known chemical inducers. Two of the five compounds with rapid lytic-inducing action were further studied for their mechanisms of induction of EBV lytic cycle. Unlike HDAC inhibitors, lytic induction by both compounds was not inhibited by rottlerin, a specific inhibitor of PKCδ. Interestingly, both compounds could cooperate with HDAC inhibitors to enhance EBV lytic cycle induction in EBV-positive epithelial cancer cells, paving way for the development of strategies to increase cells' responsiveness towards lytic reactivation. One of the two compounds bears structural resemblance to iron chelators and the other strongly activates the MAPK pathways. These structurally diverse novel organic compounds may represent potential new classes of chemicals that can be used to investigate any alternative mechanism(s) leading to EBV

  10. Subconjunctival Injection of Fluconazole in the Treatment of Fungal Alternaria Keratitis.

    Science.gov (United States)

    Tsai, Shih-Hao; Lin, Yen-Chun; Hsu, Huan-Chen; Chen, Yan-Ming

    2016-01-01

    We report two cases of Alternaria keratitis refractory to the conventional antifungal medical treatment successfully treated with subconjunctival fluconazole injection. Report of two cases. After subconjunctival injection of fluconazole (2 mg/mL) 0.5 mL twice a day for 5 days then once a day till 14 days, two cases of Alternaria keratitis refractory to the conventional antifungal medical treatment were successfully treated. No severe local and systemic side effects were found in these two patients. Alternaria keratitis has a varied clinical presentation and suspicion must be maintained for unusual causes of infectious keratitis. Alternaria keratitis can be difficult to eradicate even with traditional antifungals such as amphotericin B and natamycin. Subconjunctival injection of fluconazole could be effective for Alternaria keratitis unresponsive to conventional antifungal medical treatment.

  11. Modulation of airway epithelial antiviral immunity by fungal exposure

    National Research Council Canada - National Science Library

    Zhu, Lingxiang; Lee, Boram; Zhao, Fangkun; Zhou, Xu; Chin, Vanessa; Ling, Serena C; Chen, Yin

    2014-01-01

    .... However, their interactions have not been investigated. In the present study, we tested the effect of Alt exposure on virus-induced airway epithelial immunity using live virus and a synthetic viral mimicker, double-stranded RNA (dsRNA...

  12. Microbiological and epidemiological study of infectious keratitis in children and adolescents

    Directory of Open Access Journals (Sweden)

    Maria Cecilia Zorat Yu

    Full Text Available ABSTRACT Purpose: To analyze epidemiological and microbiological aspects of microbial keratitis in children and adolescents. Methods: This retrospective cohort study was conducted at the Department of Ophthalmology and Visual Science, Escola Paulista de Medicina, Universidade Federal de São Paulo, between July 15, 1975, and December 31, 2010. We analyzed corneal samples from 859 patients with clinical suspicion of infectious keratitis, comparing epidemiological and microbiological characteristics of bacterial keratitis with those of non-bacterial and non-viral keratitis. We also compared Gram-positive and Gram-negative pathogens in patients with bacterial keratitis. We created a susceptibility profile of the bacterial microorganisms studied. Results: Of the 859 patients, 346 (40.3% showed positive culture results for non-viral microorganisms. Teenagers (13-18 years made up the group with the highest number of patients with keratitis (164, 47.4%. The most frequent risk factors for keratitis were trauma (33.5% and previous ocular surgery (24.9%. Gram-positive bacteria (71.8% were the most often isolated, with coagulase-negative Staphylococcus (23.8% the most prevalent microorganism. Logistic regression analysis showed age (p=0.002, topical antimicrobial drug use (p=0.01, and trauma due to non-chemical burns (p=0.005 were risk factors for non-bacterial keratitis. Age (p=0.01 was also a risk factor for Gram-negative bacterial keratitis. Conclusion: Our study showed that in the age range studied, the prevalence of keratitis caused by Gram-negative bacteria or by the non-viral microorganisms evaluated increases with age. Previous use of topical antimicrobial drug and trauma due to non-chemical burns are associated with non-bacterial keratitis. Knowledge of the risk factors and the microorganisms involved may help improve treatment of keratitis in children and adolescents and minimize visual impairment.

  13. Microbiological and epidemiological study of infectious keratitis in children and adolescents.

    Science.gov (United States)

    Yu, Maria Cecilia Zorat; Höfling-Lima, Ana Luisa; Furtado, Guilherme Henrique Campos

    2016-01-01

    To analyze epidemiological and microbiological aspects of microbial keratitis in children and adolescents. This retrospective cohort study was conducted at the Department of Ophthalmology and Visual Science, Escola Paulista de Medicina, Universidade Federal de São Paulo, between July 15, 1975, and December 31, 2010. We analyzed corneal samples from 859 patients with clinical suspicion of infectious keratitis, comparing epidemiological and microbiological characteristics of bacterial keratitis with those of non-bacterial and non-viral keratitis. We also compared Gram-positive and Gram-negative pathogens in patients with bacterial keratitis. We created a susceptibility profile of the bacterial microorganisms studied. Of the 859 patients, 346 (40.3%) showed positive culture results for non-viral microorganisms. Teenagers (13-18 years) made up the group with the highest number of patients with keratitis (164, 47.4%). The most frequent risk factors for keratitis were trauma (33.5%) and previous ocular surgery (24.9%). Gram-positive bacteria (71.8%) were the most often isolated, with coagulase-negative Staphylococcus (23.8%) the most prevalent microorganism. Logistic regression analysis showed age (p=0.002), topical antimicrobial drug use (p=0.01), and trauma due to non-chemical burns (p=0.005) were risk factors for non-bacterial keratitis. Age (p=0.01) was also a risk factor for Gram-negative bacterial keratitis. Our study showed that in the age range studied, the prevalence of keratitis caused by Gram-negative bacteria or by the non-viral microorganisms evaluated increases with age. Previous use of topical antimicrobial drug and trauma due to non-chemical burns are associated with non-bacterial keratitis. Knowledge of the risk factors and the microorganisms involved may help improve treatment of keratitis in children and adolescents and minimize visual impairment.

  14. The Cytoplasmic Tail Domain of Epstein-Barr Virus gH Regulates Membrane Fusion Activity through Altering gH Binding to gp42 and Epithelial Cell Attachment

    Directory of Open Access Journals (Sweden)

    Jia Chen

    2016-11-01

    Full Text Available Epstein-Barr virus (EBV is associated with infectious mononucleosis and a variety of cancers as well as lymphoproliferative disorders in immunocompromised patients. EBV mediates viral entry into epithelial and B cells using fusion machinery composed of four glycoproteins: gB, the gH/gL complex, and gp42. gB and gH/gL are required for both epithelial and B cell fusion. The specific role of gH/gL in fusion has been the most elusive among the required herpesvirus entry glycoproteins. Previous mutational studies have focused on the ectodomain of EBV gH and not on the gH cytoplasmic tail domain (CTD. In this study, we chose to examine the function of the gH CTD by making serial gH truncation mutants as well as amino acid substitution mutants to determine the importance of the gH CTD in epithelial and B cell fusion. Truncation of 8 amino acids (aa 698 to 706 of the gH CTD resulted in diminished fusion activity using a virus-free syncytium formation assay and fusion assay. The importance of the amino acid composition of the gH CTD was also investigated by amino acid substitutions that altered the hydrophobicity or hydrophilicity of the CTD. These mutations also resulted in diminished fusion activity. Interestingly, some of the gH CTD truncation mutants and hydrophilic tail substitution mutants lost the ability to bind to gp42 and epithelial cells. In summary, our studies indicate that the gH CTD is an important functional domain.

  15. Bilateral chronic peripheral ulcerative keratitis secondary to cat-scratch disease.

    Science.gov (United States)

    Prasher, Pawan; Di Pascuale, Mario; Cavanagh, H Dwight

    2008-05-01

    To report a case of bilateral chronic peripheral ulcerative keratitis secondary to cat-scratch disease. Case report. A 66-year-old woman was initially diagnosed with Perinaud oculoglandular syndrome in her right eye. She subsequently experienced recurrent episodes of bilateral peripheral ulcerative keratitis associated with diffuse thinning, neovascularization, and conjunctivalization of the peripheral corneas. This case report shows a sequential occurrence of bilateral chronic peripheral ulcerative keratitis after an episode of cat-scratch disease. Cat-scratch disease should be included in the differential diagnosis of bilateral chronic peripheral ulcerative keratitis.

  16. Incidence and clinical characteristics of fungal keratitis in a Danish population from 2000 to 2013

    DEFF Research Database (Denmark)

    Nielsen, Stine E.; Nielsen, Esben; Julian, Hanne Olsen

    2015-01-01

    PURPOSE: Fungal keratitis is a severe sight-threatening condition. The aim of this study was to investigate the incidence and clinical characteristics of fungal keratitis patients living in a temperate climate. METHODS: By reviewing medical records from 2000 to July 2013, patients with fungal...... keratitis were identified. Risk factors, clinical signs and outcome were registered. RESULTS: Twenty-five patients were identified: 52% with Candida, 20% with Fusarium, 16% with Aspergillus and 12% with mixed filamentous fungi. A minimum incidence of fungal keratitis of 0.6 cases per million per year...

  17. Development of a Poly-ε-Lysine Contact Lens as a Drug Delivery Device for the Treatment of Fungal Keratitis.

    Science.gov (United States)

    Gallagher, Andrew G; McLean, Keri; Stewart, Rosalind M K; Wellings, Don A; Allison, Heather E; Williams, Rachel L

    2017-09-01

    The purpose of this study was to develop a more efficient drug delivery device to overcome the limitations of current drop therapy for the treatment of fungal keratitis. Amphotericin B (AmpB), 0 to 30 μg/mL, was associated with a poly-ε-lysine (pεK) hydrogel. Fungicidal effect against Candida albicans was assessed at 18 and 42 hours by optical density (OD600) and growth on agar. Tear film dilution effect was mimicked by storage of AmpB pεK gels in 3.4 mL sterile PBS for 24 hours prior to fungal incubation. Drug elution over 96 hours was evaluated by HPLC, and drug stability was tested while associated with the gel by OD600 up to 48 hours. Lack of cytotoxicity toward the HCE-T corneal epithelial cell line was assessed over 7 days. AmpB pεK gels show fungicidal activity in normal conditions (0.057 OD600, SD 0.003, P < 0.005) and in the presence of horse serum (0.048 OD600, SD 0.028 P < 0.005) at 18 hours. The drug release profile was above therapeutic levels (0.188 μg/mL) for up to 72 hours. Tear dilution had no significant effect at higher concentrations of AmpB (3 to 10 μg/mL). AmpB pεK gels were not cytotoxic to the HCE-T cell line. We demonstrated that AmpB pεK gels confer sustained therapeutic antifungal activity for at least 48 hours without corneal epithelial cell line cytotoxicity, suggesting their potential for in vivo use as an antifungal bandage contact lens. This could avoid the need for intensive topical medication in the treatment of fungal keratitis.

  18. Bipolaris oryzae, a novel fungal opportunist causing keratitis.

    Science.gov (United States)

    Wang, Luxia; Al-Hatmi, Abdullah M S; Lai, Xuwen; Peng, Lianghong; Yang, Chuanhong; Lai, Huangwen; Li, Jianxun; Meis, Jacques F; de Hoog, G Sybren; Zhuo, Chao; Chen, Min

    2016-05-01

    We report a case of mycotic keratitis caused by Bipolaris oryzae with predisposing trauma from a foreign body. The fungus was identified by sequencing the internal transcribed spacer region, translation elongation factor 1α (TEF1) gene, and partial glyceraldehyde-3-phosphate dehydrogenase (GPDH) gene, and the species identity was confirmed on the basis of its characteristic conidial phenotype. The patient was treated with surgical intervention and antifungal agents, including intravenous fluconazole (FLC), oral itraconazole, topical 0.15% amphotericin B eye drops, and 0.5% FLC eye drops. To our knowledge, this is the first report of mycotic keratitis caused by B. oryzae worldwide. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Microbial keratitis in ITU staff: an occupational hazard?

    Science.gov (United States)

    Ezra, D G; Goyal, S; Moosavi, R; Millar, M; Laganowski, H C; Moore, A T

    2004-12-01

    Microbial keratitis is a potentially blinding corneal infection; the infection may progress rapidly if untreated and result in corneal perforation. The breakdown of the innate ocular defences is known to predispose to corneal infection. We present three cases of microbial keratitis in intensive therapy unit (ITU) staff each of whom had compromised corneal immunity. Anaesthetists and nurses regularly perform high-risk procedures, such as tracheal suctioning, which have been known to cause ocular infections by aerosol inoculation. We suggest that although the absolute risk of infection is low, susceptible individuals may be at increased risk of corneal infection from exposure to potentially pathogenic organisms in such environments. We stress the need for ITU staff, particularly those who wear contact lenses, to wear eye protection when performing procedures likely to cause infected aerosols.

  20. A cluster of Mycobacterium massiliense keratitis in foundry workers.

    Science.gov (United States)

    Hung, J H; Chang, T C; Wu, J J; Lai, C C; Huang, F C; Huang, Y H

    2016-04-01

    Three consecutive workers from the same foundry had Mycobacterium massiliense keratitis. The strains isolated from each patient were identical. This is the first report of a non-surgery-related outbreak of non-tuberculous mycobacterial ocular infection. An investigation revealed that injured cornea with exposure to aerosolized non-tuberculous mycobacteria might account for this outbreak. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Contact lens associated microbial keratitis: practical considerations for the optometrist

    OpenAIRE

    Zimmerman AB; Nixon AD; Rueff EM

    2016-01-01

    Aaron B Zimmerman, Alex D Nixon, Erin M Rueff College of Optometry, The Ohio State University, Columbus, OH, USAAbstract: Microbial keratitis (MK) is a corneal condition that encompasses several different pathogens and etiologies. While contact lens associated MK is most often associated with bacterial infections, other pathogens (fungi, Acanthamoeba species, etc) may be responsible. This review summarizes the risk factors, microbiology, diagnostic characteristics, and treatment options for a...

  2. Aspergillus tamarii keratitis in a contact lens wearer

    Directory of Open Access Journals (Sweden)

    Juan Cuadros

    2018-03-01

    Full Text Available Keratitis produced by Aspergillus tamarii has been previously described associated to an ocular injury. We report a case in a contact lens wearer with a history of previous bilateral myopic LASIK ablation, bilateral intracorneal rings and vitrectomy and scleral buckling in his left eye. The fungus could be quickly identified combining phenotype, microscopy and mass spectrometry. Treatment with intravenous amphotericin, oral voriconazole, and topical amphotericin and natamycin and voriconazole was needed for corneal preservation.

  3. Intrastromal voriconazole for deep recalcitrant fungal keratitis: a case series.

    Science.gov (United States)

    Kalaiselvi, Ganapathy; Narayana, Sivananda; Krishnan, Tiruvengada; Sengupta, Sabyasachi

    2015-02-01

    To evaluate the outcomes of treating deep recalcitrant fungal keratitis with intrastromal voriconazole injection. Twenty-five patients with culture proven fungal keratitis, not responding to a combination of topical 5% natamycin and 1% voriconazole were treated with intrastromal voriconazole (50 µg/0.1 mL) injected in five divided doses around the infiltrate to form a depot of the drug around the circumference of the lesion. The mean age of the patients was 52.52±12.21 years and mean time to presentation was 17.12±13.75 days from the onset of symptoms. The mean area of the infiltrate was 30.41±17.2 mm(2), hypopyon was present in 88% and all cases had infiltrates that extended beyond the mid-stromal level. Intrastromal voriconazole helped to resolve the infection in 18 (72%) patients and about 15% of these needed more than one injection. Smaller ulcers responded better to treatment. Fusarium spp were responsible for six of the seven cases that failed treatment. Targeted delivery of voriconazole by intrastromal injection (50 µg/0.1 mL) is a safe and effective way to treat deep recalcitrant fungal keratitis, though some may need repeated injections. Fusarium keratitis may show suboptimal response but this needs further study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Topical and Oral Voriconazole in the Treatment of Fungal Keratitis

    OpenAIRE

    Lee, Sang Joon; Lee, Jung Joo; Kim, Shin Dong

    2009-01-01

    We describe two patients with fungal keratitis refractory to standard antifungal therapy whose conditions were managed with voriconazole. The first case is a patient with endophthalmitis and corneal ulcer due to Candida parapsilosis after receiving a corneal transplant. The patient was treated with amphotericin but showed no signs of improvement. Topical voriconazole, oral voriconazole, and intravitreal voriconazole yielded signs of improvement. The second case is a 63-year-old male who under...

  5. Results with the Boston Type I keratoprosthesis after Acanthamoeba keratitis

    OpenAIRE

    Santos, Albert; Silva, Luzia Diegues; Sousa,Luciene Barbosa de; Freitas, Denise de; Oliveira,Lauro Augusto de

    2017-01-01

    Purpose: To report the outcomes of implantation of the Boston Type I keratoprosthesis in three patients with Acanthamoeba keratitis (AK), a severe infection that can lead to significant visual loss. Observations: Case series reporting three patients with difficult cases of AK that needed multiple corneal transplantations and glaucoma surgeries. All patients were implanted with the Boston Type I keratoprosthesis device. The main outcomes measure were the visual function and anatomical reten...

  6. Role of activated macrophages in experimental Fusarium solani keratitis.

    Science.gov (United States)

    Hu, Jianzhang; Hu, Yingfeng; Chen, Shikun; Dong, Chenhuan; Zhang, Jingjin; Li, Yanling; Yang, Juan; Han, Xiaoli; Zhu, Xuejun; Xu, Guoxing

    2014-12-01

    Macrophages under the conjunctival tissue are the first line defender cells of the corneas. Elimination of these cells would lead to aggravation of fungal keratitis. To determine how the course of fungal keratitis would be altered after the activation of these macrophages, a murine model was achieved by intrastromal instillation of latex beads before the corneas were infected with Fusarium solani. The keratitis was observed and clinically scored daily. Infected corneas were homogenized for colony counts. The levels of the IL-12, IL-4, MPO, MIF and iNOS cytokines were measured in the corneas using real-time polymerase chain reactions and enzyme-linked immunosorbent assays. CD3+, CD4+ and CD8+ lymphocytes in the corneas, submaxillary lymph nodes and peripheral blood were detected using immunohistochemistry and flow cytometry, respectively. The latex bead-treated mice exhibited aggravated keratitis. Substantially increased macrophage and polymorphonuclear leukocyte infiltration was detected in the corneas, although few colonies were observed. There was a marked increase in the IL-12, IL-4, MPO, MIF and iNOS expression in the corneas. The numbers of CD3+, CD4+ and CD8+ lymphocytes and the CD4+/CD8+ ratio were significantly enhanced in the corneas and submaxillary lymph nodes. However, the number of CD4+ lymphocytes was decreased in the peripheral blood, while the number of CD8+ lymphocytes increased. Collectively, our data demonstrate that the activation of macrophages in the cornea may cause an excessive immune response. Macrophages appear to play a critical role in regulating the immune response to corneal infections with F. solani. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Nocardia keratitis: Clinical course and effect of corticosteroids

    Science.gov (United States)

    Lalitha, Prajna; Srinivasan, Muthiah; Rajaraman, Revathi; Ravindran, Meenakshi; Mascarenhas, Jeena; Priya, Jeganathan Lakshmi; Sy, Aileen; Oldenburg, Catherine E.; Ray, Kathryn J.; Zegans, Michael E.; McLeod, Stephen D.; Lietman, Thomas M.; Acharya, Nisha R.

    2012-01-01

    Purpose To compare the clinical course of Nocardia spp keratitis with keratitis due to other bacterial organisms, and to assess the effect of corticosteroids as adjunctive therapy using data collected from the Steroids for Corneal Ulcers Trial (SCUT). Design Sub-group analysis of a randomized controlled trial Methods Setting Multicenter randomized controlled trial Study Population 500 patients with bacterial keratitis, randomized 1:1 to topical corticosteroid or placebo who had received at least 48 hours of topical moxifloxacin Intervention/Observation Procedure Topical prednisolone phosphate 1% or placebo; clinical course of Nocardia keratitis Main outcome measures Best spectacle-corrected visual acuity and infiltrate/scar size at 3 months from enrollment Results Of 500 patients enrolled in the trial, 55 (11%) had a Nocardia corneal ulcer. Patients with Nocardia ulcers had better presentation visual acuity compared to non-Nocardia ulcers (median Snellen 20/45 compared to 20/145, PNocardia ulcers had approximately 2 lines less improvement in visual acuity compared to non-Nocardia ulcers (0.21 logMAR, 95% CI 0.09 to 0.33 logMAR, P=0.001). This difference may reflect the better starting visual acuity in patients with Nocardia ulcers. In Nocardia ulcers, corticosteroids were associated with an average 0.4 mm increase in 3-month infiltrate/scar size (95% CI 0.03 to 0.77mm, P=0.03). Conclusion Nocardia ulcers responded well to treatment. They showed less overall improvement in visual acuity than non-Nocardia ulcers, but had better presentation acuity. Corticosteroids may be associated with worse outcomes. PMID:22959881

  8. Contact lens-related bilateral and simultaneous Acremonium keratitis

    Directory of Open Access Journals (Sweden)

    Patrícia Cortez Bona Doliveira

    Full Text Available Abstract This is a case of bilateral and simultaneous Acremonium keratitis related to intermittent and alternating eye soft contact lens use, which has a delayed diagnose, presented amphotericin B resistance with persistent hypopyon and had a positive response to topical natamycin. Besides the unusual presentation, there was no history of trauma or contact with vegetable matter, usually associated to the majority of cases of keratomicosys by filamentous fungi.

  9. Type I interferon and NF-κB activation elicited by herpes simplex virus gH/gL via αvβ3 integrin in epithelial and neuronal cell lines.

    Science.gov (United States)

    Gianni, Tatiana; Leoni, Valerio; Campadelli-Fiume, Gabriella

    2013-12-01

    αvβ3 integrin represents a novel sensing system which detects herpes simplex virus (HSV) and bacterial constituents. In cooperation with Toll-like receptor 2 (TLR2), it elicits an innate response that leads to activation of type I interferon (IFN), NF-κB, and a specific set of cytokines. We report that this defensive branch is functional in cells which represent experimental models of epithelial, including keratinocytic, and neuronal cells. These are the major targets of HSV in vivo. HSV entered the three cell lines via distinct routes. Hence, the defensive response was independent of the route of virus entry. Soluble gH/gL sufficed to elicit type I IFN and NF-κB activation and represents the viral pathogen-associated molecular pattern (PAMP) of this defense system.

  10. Early Keratectomy in the Treatment of Moderate Fusarium Keratitis

    Science.gov (United States)

    Lin, Hsin-Chiung; Lin, Ja-Liang; Lin-Tan, Dan-Tzu; Ma, Hui-Kang; Chen, Hung-Chi

    2012-01-01

    Purpose To evaluate the treatment outcomes and costs of early keratectomy in the management of moderate Fusarium keratitis. Methodology/Principal Findings Consecutive cases of culture proven Fusarium keratitis treated at our hospital between January 2004 to December 2010 were included in this retrospective study. There were 38 cases of moderate keratitis with infiltrates between 3 to 6 mm in diameter and depth of infiltration not exceeding the inner 1/3 of the cornea. After excluding 5 patients with incomplete follow-up data, 13 patients who received early keratectomy within 1 week of admission were compared with a group of 20 patients treated medically. The significance of the association between early keratectomy and visual acuity, progression to perforation, secondary glaucoma and cataract formation, adjuvant therapy, hospitalization days and cost were assessed. There were no differences between the keratectomy and medication groups in regards to age, sex, presence of systemic diseases, and hypopyon formation on presentation. The early keratectomy group had a shorter hospital stay than the medical therapy group. Disease duration was significantly lower in the early keratectomy group (median: 29.0 vs. 54.5 days, Pkeratitis may reduce length of hospital stay, hospital costs, and perforation rates. PMID:22936982

  11. Acanthamoeba and Fusarium interactions: A possible problem in keratitis.

    Science.gov (United States)

    Nunes, Thais Esther Teixeira; Brazil, Nathalya Tesch; Fuentefria, Alexandre Meneghello; Rott, Marilise Brittes

    2016-05-01

    The incidence of Acanthamoeba and Fusarium species has increased in contact lens-related infectious keratitis. They share several environments and cases of co-infection have been reported. The interaction between the amoebae and other microorganisms may result in significant changes for both, like increased virulence in mammalian hosts. In this study, we evaluated the interaction of three Acanthamoeba castellanii strains with Fusarium conidia and the possible implications on keratitis. F. conidia were internalized by A. castellanii strains and were able to germinate inside the amoebae. The co-culture with the live amoebae, as well as the amoebal culture supernatant and lysate, increased the fungal growth significantly. Moreover, live F. solani and its culture supernatant enhanced the survival of amoebae, but in a different way in each amoebal strain. The encystment of the A. castellanii strain re-isolated from rat lung was increased by the fungus. These results show that A. castellanii and F. solani interaction may have an important influence on survival of both, and specially indicate a possible effect on virulence characteristics of these microorganisms. These data suggest that the A. castellanii-F. solani interaction may cause severe impacts on keratitis. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Antifungal Effect of Essential Oils against Fusarium Keratitis Isolates.

    Science.gov (United States)

    Homa, Mónika; Fekete, Ildikó Pálma; Böszörményi, Andrea; Singh, Yendrembam Randhir Babu; Selvam, Kanesan Panneer; Shobana, Coimbatore Subramanian; Manikandan, Palanisamy; Kredics, László; Vágvölgyi, Csaba; Galgóczy, László

    2015-09-01

    The present study was carried out to investigate the antifungal effects of Cinnamomum zeylanicum, Citrus limon, Juniperus communis, Eucalyptus citriodora, Gaultheria procumbens, Melaleuca alternifolia, Origanum majorana, Salvia sclarea, and Thymus vulgaris essential oils against Fusarium species, the most common etiologic agents of filamentous fungal keratitis in South India. C. zeylanicum essential oil showed strong anti-Fusarium activity, whereas all the other tested essential oils proved to be less effective. The main component of C. zeylanicum essential oil, trans-cinnamaldehyde, was also tested and showed a similar effect as the oil. The in vitro interaction between trans-cinnamaldehyde and natamycin, the first-line therapeutic agent of Fusarium keratitis, was also investigated; an enhanced fungal growth inhibition was observed when these agents were applied in combination. Light and fluorescent microscopic observations revealed that C. zeylanicum essential oil/trans-cinnamaldehyde reduces the cellular metabolism and inhibits the conidia germination. Furthermore, necrotic events were significantly more frequent in the presence of these two compounds. According to our results, C. zeylanicum essential oil/trans-cinnamaldehyde provides a promising basis to develop a novel strategy for the treatment of Fusarium keratitis. Georg Thieme Verlag KG Stuttgart · New York.

  13. [Acanthamoeba keratitis. Report of 3 cases diagnosed in central Tunisia].

    Science.gov (United States)

    Fathallah, Akila; Ben Rayana, Narjess; Knani, Leila; Meksi, Sondos Gaied; Saghrouni, Fatma; Ghorbel, Mohamed; Hamida, Fafani Ben Hadj; Ben Said, Moncef

    2010-02-01

    Amoeba of the genus Acanthamoeba are ubiquitous free-living protozoa encountered in water and soil. They frequently cause sight-threatening keratitis. Report of the three first cases diagnosed at the laboratory of Parasitology of Sousse Hospital, (Tunisia). Our study concerned three lens-wearing female patients, aged 17, 20 and 29 years respectively. The patients originate from central Tunisia and presented with unilateral (2 cases) or bilateral (one case) keratitis. Diagnosis was made by demonstrating Acanthamoeba trophozoites and/or cysts on direct examination and/or culture (in agar - Escherichia coli medium) of contact lenses and/or lenses' solution. Direct examination of corneal swabs was negative in three cases but culture was positive in one. The three patients were treated with hexamidine and neomycine eye-drops for three months. Treatment led to scarring of lesions with however sequellar opacities that was minor to moderate in two cases and consisted of a central leucoma with a poor visual outcome in the last case. The need for systematic research of amoeba in lenses wearing patients with keratitis is emphasized.

  14. [Keratitis caused by Acanthamoeba in patients with contact lenses].

    Science.gov (United States)

    de Miguel, I; Ferrando, R; Santan, O E; Martín-Sánchez, A M

    1999-11-01

    Keratitis by Acanthamoeba is a severe infectious complication which may be derived from the use and bad preservation of contact lens. This disease la increasingly more frequent and rapid diagnosis and treatment condition the posterior evolution of the disease. The cases of 2 contact lens waters who developed keratitis by Acanthamoeba are presented. The diagnostic methods and treatment are commented upon. Keratitis by Acanthamoeba was diagnosed in 2 patients following analysis of corneal scrapings and of the saline solution used for lens maintenance. Trophozoites and cystes of this parasite were observed in all the samples processed. The evolution was good in the patient treated at 15 days after initiation of the symptoms. However, the evolution was very bad in the patient who delayed in initiating the amebicide treatment. Penetrating keratoplasty was performed in both patients. Specific treatment with derivates of propamidine implemented early may avoid severe ocular complications. As prophylaxis for contact lens users, it is recommended that the contact lens be maintained clean and correctly care for, and the use of home-made saline solutions which are easily contaminated by Acanthamoeba, should be avoided.

  15. Crosslinking and corneal cryotherapy in acanthamoeba keratitis -- a histological study.

    Science.gov (United States)

    Hager, Tobias; Hasenfus, A; Stachon, T; Seitz, B; Szentmáry, N

    2016-01-01

    Acanthamoeba keratitis is rare, but difficult to treat. Penetrating keratoplasty is performed in therapy-resistant cases. Nevertheless, subsequent recurrences occur in 40 % of the cases. In addition to triple-topical therapy (polyhexamid, propamidinisoethionat, neomycin), treatment alternatives are corneal cryotherapy and/or crosslinking (CXL). The aim of our present histological study was to analyze the persistence of acanthamoebatrophozoites and cysts, the persistence of bacteria, and activation of keratocytes in corneas of acanthamoeba keratitis patients following corneal cryotherapy and/or CXL. We analyzed histologically corneal buttons (from penetrating keratoplasties) of nine patients with acanthamoeba keratitis, following corneal cryotherapy (two patients) or a combination of crosslinking and corneal cryotherapy (seven patients), using haematoxilin–eosin, periodic acid Schiff (PAS), Gram and alpha-smooth muscle actin (alpha-SMA) stainings. Acanthamoeba trophozoites persisted in three corneas after cryotherapy and CXL. Cysts persisted in one of two corneas following corneal cryotherapy and in six of seven corneas after a combination of CXL and cryotherapy. One cornea showed positive Gram staining, but there were no alpha-SMA positive keratocytes in any of the corneas. Crosslinking and corneal cryotherapy have only limited impact on killing of acanthamoeba trophozoites, cysts, or bacteria. Corneal cryotherapy and CXL did not stimulate myofibroblastic transformation of keratocytes.

  16. Insurgence of Fusarium keratitis associated with contact lens wear.

    Science.gov (United States)

    Alfonso, Eduardo C; Cantu-Dibildox, Jorge; Munir, Wuqaas M; Miller, Darlene; O'Brien, Terrence P; Karp, Carol L; Yoo, Sonia H; Forster, Richard K; Culbertson, William W; Donaldson, Kendall; Rodila, Jill; Lee, Yunhee

    2006-07-01

    To describe the clinical presentation and course of patients who developed keratitis due to Fusarium while wearing nontherapeutic soft contact lenses. A retrospective review of microbiologic records from January 1, 2004, through April 15, 2006, was performed, identifying all patients with corneal ulceration and a culture positive for Fusarium species. Medical records of 34 patients were reviewed for clinical characteristics, treatment regimens, and microbiologic features. The most common antimicrobial medications administered prior to Fusarium diagnosis were antibacterials in 31 of 34 patients. No distinct preponderance of any one brand of either contact lens or solution was identified. The microbiologic corneal cultures found Fusarium oxysporum in 20 cases, Fusarium solani in 3 cases, Fusarium species not further identifiable in 10 cases, and no growth in 1 case. Patients with a delayed onset of treatment had a tendency for prolonged treatment until cure. Fusarium has previously been an unusual organism in the etiology of infectious keratitis in the setting of nontherapeutic soft contact lens wear. A delay in proper diagnosis and intervention may contribute to a prolonged treatment course. The microbial spectrum of contact lens-related keratitis may be evolving with higher participation of Fusarium species compared with prior reports.

  17. Recurrent Herpetic Stromal Keratitis in Mice: A Model for Studying Human HSK

    Directory of Open Access Journals (Sweden)

    Patrick M. Stuart

    2012-01-01

    Full Text Available Herpes simplex virus 1 (HSV-1 infection of the cornea leads to a potentially blinding disease, termed herpetic stromal keratitis (HSK that is characterized by lesions of an immunoinflammatory nature. In spite of the fact that HSK typically presents as a recurrent disease due to reactivation of virus which latently infects the trigeminal ganglia, most murine studies of HSK have employed a primary and not recurrent model of the disease. This report documents the several recurrent models of HSK that have been developed and how data generated from these models differs in some important aspects from data generated following primary infection of the cornea. Chief among these differences is the fact that recurrent HSK takes place in the context of an animal that has a preexisting anti-HSV immune response, while primary HSK occurs in an animal that is developing such a response. We will document both differences and similarities that derive from this fundamental difference in these models with an eye towards possible vaccines and therapies that demonstrate promise in treating HSK.

  18. Recurrent Herpetic Stromal Keratitis in Mice: A Model for Studying Human HSK

    Science.gov (United States)

    Stuart, Patrick M.; Keadle, Tammie L.

    2012-01-01

    Herpes simplex virus 1 (HSV-1) infection of the cornea leads to a potentially blinding disease, termed herpetic stromal keratitis (HSK) that is characterized by lesions of an immunoinflammatory nature. In spite of the fact that HSK typically presents as a recurrent disease due to reactivation of virus which latently infects the trigeminal ganglia, most murine studies of HSK have employed a primary and not recurrent model of the disease. This report documents the several recurrent models of HSK that have been developed and how data generated from these models differs in some important aspects from data generated following primary infection of the cornea. Chief among these differences is the fact that recurrent HSK takes place in the context of an animal that has a preexisting anti-HSV immune response, while primary HSK occurs in an animal that is developing such a response. We will document both differences and similarities that derive from this fundamental difference in these models with an eye towards possible vaccines and therapies that demonstrate promise in treating HSK. PMID:22593769

  19. Management of vascularized limbal keratitis with prosthetic replacement of the ocular surface system.

    Science.gov (United States)

    Cressey, Anna; Jacobs, Deborah S; Carrasquillo, Karen G

    2012-03-01

    To describe a case of contact lens-induced vascularized limbal keratitis (VLK) and management with prosthetic replacement of the ocular surface system (PROSE) treatment. Clinical retrospective case report describing the clinical appearance, course of development, and treatment of VLK with PROSE. A 58-year-old white woman presented with a history of advanced keratoconus and almost four decades of contact lens wear, including polymethyl-methacrylate, small-diameter, gas-permeable lenses, low-Dk hybrid, and piggyback lens modalities. Complications of lens wear caused the development of extensive VLK in both eyes, with vascularization, lipid keratopathy, and corneal scarring projecting into the central cornea, more so in the left eye. She was evaluated and treated with PROSE in both eyes, demonstrating initial improvements in both comfort and vision, from 20/30 to 20/25 in the right eye and from 20/40 to 20/20 in the left eye. After 2 years of PROSE treatment, she reported excellent vision and comfort. Acuities were OD 20/25(+2) and OS 20/20(-/+). There was normalization of the corneal surface with reduced staining and epithelial irregularity, and there was substantial regression of corneal neovascularization and opacity, particularly in the left eye. PROSE, by normalizing the environment at the ocular surface, ultimately improved visual function and long-term ocular health for this patient.

  20. Cochlear Implantation in Patients with Keratitis-Ichthyosis-Deafness Syndrome: A Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Birgul Gumus

    2017-01-01

    Full Text Available Background. Keratitis-ichthyosis-deafness (KID syndrome is a syndrome which presents with hearing loss and visual and keratinization disorders. In such patients, hearing aids cannot be effectively used in the rehabilitation of hearing loss because of the frequent blockage of the external ear canal with epithelial debris and due to dry and tense skin of the external ear canal. Moreover, severe or profound hearing loss also limits the benefits gained from the conventional hearing aids. On the other hand, cochlear implantation is a method that has been used in limited cases in the literature. Case Report. This study presents the results of cochlear implantation applied in our clinic to two children who had been diagnosed with KID. Audiological assessments before and after the cochlear implant operation were performed using pure-tone audiometry, immittance audiometry, and auditory brainstem response (ABR, and the postoperative follow-up was conducted using pure-tone audiometry. Conclusion. Skin problems, visual disturbances, and other additional problems complicate the short-term and long-term rehabilitation after implantation in individuals with KID syndrome. Close monitoring should be exercised due to possible skin complications that may develop during the postoperative period. The families and rehabilitation teams should be warned about the possible visual disturbances and skin complications.

  1. Glutathione Transferase as a Potential Marker for Gut Epithelial Injury versus the Protective Role of Breast Milk sIgA in Infants with Rota Virus Gastroenteritis

    Directory of Open Access Journals (Sweden)

    Lobna S. Sherif

    2015-11-01

    CONCLUSION: Breast feeding should be encouraged and highly recommended in the first two years of life as it provides Secretory IgA to breast fed infants who in turn protect them against epithelial damage caused by Rota viral gastroenteritis.

  2. RANK Overexpression in Transgenic Mice with Mouse Mammary Tumor Virus Promoter-Controlled RANK Increases Proliferation and Impairs Alveolar Differentiation in the Mammary Epithelia and Disrupts Lumen Formation in Cultured Epithelial Acini▿ †

    Science.gov (United States)

    Gonzalez-Suarez, Eva; Branstetter, Daniel; Armstrong, Allison; Dinh, Huyen; Blumberg, Hal; Dougall, William C.

    2007-01-01

    RANK and RANKL, the key regulators of osteoclast differentiation and activation, also play an important role in the control of proliferation and differentiation of mammary epithelial cells during pregnancy. Here, we show that RANK protein expression is strictly regulated in a spatial and temporal manner during mammary gland development. RANK overexpression under the control of the mouse mammary tumor virus (MMTV) promoter in a transgenic mouse model results in increased mammary epithelial cell proliferation during pregnancy, impaired differentiation of lobulo-alveolar structures, decreased expression of the milk proteins β-casein and whey acidic protein, and deficient lactation. We also show that treatment of three-dimensional in vitro cultures of primary mammary cells from MMTV-RANK mice with RANKL results in increased proliferation and decreased apoptosis in the luminal area, resulting in bigger acini with filled lumens. Taken together, these results suggest that signaling through RANK not only promotes proliferation but also inhibits the terminal differentiation of mammary epithelial cells. Moreover, the increased proliferation and survival observed in a three-dimensional culture system suggests a role for aberrant RANK signaling during breast tumorigenesis. PMID:17145767

  3. RANK overexpression in transgenic mice with mouse mammary tumor virus promoter-controlled RANK increases proliferation and impairs alveolar differentiation in the mammary epithelia and disrupts lumen formation in cultured epithelial acini.

    Science.gov (United States)

    Gonzalez-Suarez, Eva; Branstetter, Daniel; Armstrong, Allison; Dinh, Huyen; Blumberg, Hal; Dougall, William C

    2007-02-01

    RANK and RANKL, the key regulators of osteoclast differentiation and activation, also play an important role in the control of proliferation and differentiation of mammary epithelial cells during pregnancy. Here, we show that RANK protein expression is strictly regulated in a spatial and temporal manner during mammary gland development. RANK overexpression under the control of the mouse mammary tumor virus (MMTV) promoter in a transgenic mouse model results in increased mammary epithelial cell proliferation during pregnancy, impaired differentiation of lobulo-alveolar structures, decreased expression of the milk proteins beta-casein and whey acidic protein, and deficient lactation. We also show that treatment of three-dimensional in vitro cultures of primary mammary cells from MMTV-RANK mice with RANKL results in increased proliferation and decreased apoptosis in the luminal area, resulting in bigger acini with filled lumens. Taken together, these results suggest that signaling through RANK not only promotes proliferation but also inhibits the terminal differentiation of mammary epithelial cells. Moreover, the increased proliferation and survival observed in a three-dimensional culture system suggests a role for aberrant RANK signaling during breast tumorigenesis.

  4. Relationship of in vitro susceptibility to moxifloxacin and in vivo clinical outcome in bacterial keratitis.

    Science.gov (United States)

    Lalitha, Prajna; Srinivasan, Muthiah; Manikandan, P; Bharathi, M Jayahar; Rajaraman, Revathi; Ravindran, Meenakshi; Cevallos, Vicky; Oldenburg, Catherine E; Ray, Kathryn J; Toutain-Kidd, Christine M; Glidden, David V; Zegans, Michael E; McLeod, Stephen D; Acharya, Nisha R; Lietman, Thomas M

    2012-05-01

    For bacterial infections, the susceptibility to antibiotics in vitro has been associated with clinical outcomes in vivo, although the importance of minimum inhibitory concentration (MIC) has been debated. In this study, we analyzed the association of MIC on clinical outcomes in bacterial corneal ulcers, while controlling for organism and severity of disease at presentation. Data were collected as part of a National Eye Institute-funded, randomized, controlled trial (the Steroids for Corneal Ulcers Trial [SCUT]). All cases enrolled in SCUT had a culture-positive bacterial corneal ulcer and received moxifloxacin. The MIC to moxifloxacin was measured by E test. Outcomes included best spectacle-corrected visual acuity, infiltrate/scar size, time to re-epithelialization, and corneal perforation. Five hundred patients with corneal ulcers were enrolled in the trial, and 480 were included in this analysis. The most commonly isolated organisms were Streptococcus pneumoniae and Pseudomonas aeruginosa. A 2-fold increase in MIC was associated with an approximately 0.02 logMAR decrease in visual acuity at 3 weeks, approximately 1 letter of vision loss on a Snellen chart (0.019 logMAR; 95% confidence interval [CI], .0040-.033; P = .01). A 2-fold increase in MIC was associated with an approximately 0.04-mm larger infiltrate/scar size at 3 weeks (0.036 mm; 95% CI, .010-.061; P = .006). After controlling for organism, a higher MIC was associated with slower time to re-epithelialization (hazards ratio, 0.92; 95% CI, .86-.97; P = .005). In bacterial keratitis, a higher MIC to the treating antibiotic is significantly associated with worse clinical outcomes, with approximately 1 line of vision loss per 32-fold increase in MIC. NCT00324168.

  5. [Topical voriconazole as an effective treatment for fungal keratitis].

    Science.gov (United States)

    Wang, L Y; Xu, Z Z; Zhang, J J; Sun, S T; Li, J; Yu, X F; Zhu, L; Zhang, Y Q; He, Y; Li, J C; Wang, L L; Tao, S Y

    2016-09-11

    To evaluate the efficacy of topical voriconazole in patients with fungal keratitis caused by different fungal species. Interventional case series. Eighty-four patients aged 18 years or older from central China with confirmed fungal keratitis who presented at the outpatient department of Henan Eye Institute were enrolled in the study. The patients underwent in vivo confocal scanning laser microscopy examination, coneal scraping and microscopic examination and fungal culture, and then received topical voriconazole, closed curative effects were conducted. The sensitivity of three different diagnostic techniques, spectrum of the fungi, cure rate for fungal corneal infection related to each species were analyzed. In our study, 84 patients were diagnosed with fungal keratitis based on clinical symptoms, and results of at least one of the examinations of in vivo confocal scanning laser microscopy, conventional smear, and corneal scraping culture and the sensitivity were 92.85%(78/84), 85.71%(72/84), 84.52%(71/84)respectively. In viro confocal scanning laser microscopy. Successful management was achieved in 83.33% of the patients. Topical voriconazole treatment failed in 14 patients(16.67%), who required surgical treatment. In 36 patients with Fusarium corneal infections, 26(72.22%)were successfully treated with topical voriconazole; however, in 18 patients with Aspergillus corneal infections and 7 patients with Alternaria corneal infections, 94.44% and 100.00% of them were successfully treated, respectively. In a case-based dynamic tracking study, in vivo confocal microscopy provided real-time dynamic detection of surviving hyphae. The existence of hyphae was(38.35±17.32)days for Fusarium,(25.00±16.11)days for Aspergillus,(21.00±4.36)days for Alternaria, and(41.50±31.68)days for the focus in the deep stroma. The duration of treatment was similar for all four groups. Topical application of voriconazole is on effective method for the freatment of fungal keratitis

  6. Multidrug-resistant Fusarium in keratitis: a clinico-mycological study of keratitis infections in Chennai, India.

    Science.gov (United States)

    Tupaki-Sreepurna, Ananya; Al-Hatmi, Abdullah M S; Kindo, Anupma J; Sundaram, Murugan; de Hoog, G Sybren

    2017-04-01

    In this study, we aimed to present the first molecular epidemiological data from Chennai, India, analyse keratitis cases that have been monitored in a university hospital during 2 years, identify the responsible Fusarium species and determine antifungal susceptibilities. A total of 10 cases of keratitis were included in the study. Fusarium isolates were identified using the second largest subunit of the RNA polymerase gene (RPB2) and the translation elongation factor 1 alpha (TEF1). Antifungal susceptibility was tested by the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) methodology. The aetiological agents belonged to Fusarium solani species complex (FSSC) (n = 9) and Fusarium sambucinum species complex (FSAMSC) (n = 1), and the identified species were Fusarium keratoplasticum (n = 7), Fusarium falciforme (n = 2) and Fusarium sporotrichioides (n = 1). All strains showed multidrug resistance to azoles and caspofungin but exhibited lower minimum inhibitory concentration (MIC) to natamycin and amphotericin B. Fusarium keratoplasticum and Fusarium falciforme belonging to the Fusarium solani species complex were the major aetiological agents of Fusarium keratitis in this study. Early presentation and 5% topical natamycin was associated with better patient outcome. Preventative measures and monitoring of local epidemiological data play an important role in clinical practice. © 2016 Blackwell Verlag GmbH.

  7. VIRUSES

    Indian Academy of Sciences (India)

    and-mouth disease in livestock was an infectious particle smaller than any bacteria. This was the first clue to the nature of viruses, genetic entities that lie somewhere in the gray area between living and non-living states.

  8. Resident corneal c-fms+ macrophages and dendritic cells mediate early cellular infiltration in adenovirus keratitis

    Science.gov (United States)

    Ramke, Mirja; Zhou, Xiaohong; Materne, Emma Caroline; Rajaiya, Jaya; Chodosh, James

    2016-01-01

    The cornea contains a heterogeneous population of antigen-presenting cells with the capacity to contribute to immune responses. Adenovirus keratitis is a severe corneal infection with acute and chronic phases. The role of resident corneal antigen-presenting cells in adenovirus keratitis has not been studied. We utilized transgenic MaFIA mice in which c-fms expressing macrophages and dendritic cells can be induced to undergo apoptosis, in a mouse model of adenovirus keratitis. Clinical keratitis and recruitment of myeloperoxidase and CD45+ cells were diminished in c-fms depleted, adenovirus infected mice, as compared to controls, consistent with a role for myeloid-lineage cells in adenovirus keratitis. PMID:27185163

  9. Resident corneal c-fms(+) macrophages and dendritic cells mediate early cellular infiltration in adenovirus keratitis.

    Science.gov (United States)

    Ramke, Mirja; Zhou, Xiaohong; Materne, Emma Caroline; Rajaiya, Jaya; Chodosh, James

    2016-06-01

    The cornea contains a heterogeneous population of antigen-presenting cells with the capacity to contribute to immune responses. Adenovirus keratitis is a severe corneal infection with acute and chronic phases. The role of resident corneal antigen-presenting cells in adenovirus keratitis has not been studied. We utilized transgenic MaFIA mice in which c-fms expressing macrophages and dendritic cells can be induced to undergo apoptosis, in a mouse model of adenovirus keratitis. Clinical keratitis and recruitment of myeloperoxidase and CD45(+) cells were diminished in c-fms depleted, adenovirus infected mice, as compared to controls, consistent with a role for myeloid-lineage cells in adenovirus keratitis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The Interactive Roles of Lipopolysaccharides and dsRNA/Viruses on Respiratory Epithelial Cells and Dendritic Cells in Allergic Respiratory Disorders: The Hygiene Hypothesis.

    Science.gov (United States)

    Lin, Tsang-Hsiung; Su, Hsing-Hao; Kang, Hong-Yo; Chang, Tsung-Hsien

    2017-10-23

    The original hygiene hypothesis declares "more infections in early childhood protect against later atopy". According to the hygiene hypothesis, the increased incidence of allergic disorders in developed countries is explained by the decrease of infections. Epithelial cells and dendritic cells play key roles in bridging the innate and adaptive immune systems. Among the various pattern-recognition receptor systems of epithelial cells and dendritic cells, including toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and others, TLRs are the key systems of immune response regulation. In humans, TLRs consist of TLR1 to TLR10. They regulate cellular responses through engagement with TLR ligands, e.g., lipopolysaccharides (LPS) acts through TLR4 and dsRNA acts through TLR3, but there are certain common components between these two TLR pathways. dsRNA activates epithelial cells and dendritic cells in different directions, resulting in allergy-related Th2-skewing tendency in epithelial cells, and Th1-skewing tendency in dendritic cells. The Th2-skewing effect by stimulation of dsRNA on epithelial cells could be suppressed by the presence of LPS above some threshold. When LPS level decreases, the Th2-skewing effect increases. It may be via these interrelated networks and related factors that LPS modifies the allergic responses and provides a plausible mechanism of the hygiene hypothesis. Several hygiene hypothesis-related phenomena, seemingly conflicting, are also discussed in this review, along with their proposed mechanisms.

  11. Activation of type I and III interferon signalling pathways occurs in lung epithelial cells infected with low pathogenic avian influenza viruses.

    Directory of Open Access Journals (Sweden)

    Richard Sutejo

    Full Text Available The host response to the low pathogenic avian influenza (LPAI H5N2, H5N3 and H9N2 viruses were examined in A549, MDCK, and CEF cells using a systems-based approach. The H5N2 and H5N3 viruses replicated efficiently in A549 and MDCK cells, while the H9N2 virus replicated least efficiently in these cell types. However, all LPAI viruses exhibited similar and higher replication efficiencies in CEF cells. A comparison of the host responses of these viruses and the H1N1/WSN virus and low passage pH1N1 clinical isolates was performed in A549 cells. The H9N2 and H5N2 virus subtypes exhibited a robust induction of Type I and Type III interferon (IFN expression, sustained STAT1 activation from between 3 and 6 hpi, which correlated with large increases in IFN-stimulated gene (ISG expression by 10 hpi. In contrast, cells infected with the pH1N1 or H1N1/WSN virus showed only small increases in Type III IFN signalling, low levels of ISG expression, and down-regulated expression of the IFN type I receptor. JNK activation and increased expression of the pro-apoptotic XAF1 protein was observed in A549 cells infected with all viruses except the H1N1/WSN virus, while MAPK p38 activation was only observed in cells infected with the pH1N1 and the H5 virus subtypes. No IFN expression and low ISG expression levels were generally observed in CEF cells infected with either AIV, while increased IFN and ISG expression was observed in response to the H1N1/WSN infection. These data suggest differences in the replication characteristics and antivirus signalling responses both among the different LPAI viruses, and between these viruses and the H1N1 viruses examined. These virus-specific differences in host cell signalling highlight the importance of examining the host response to avian influenza viruses that have not been extensively adapted to mammalian tissue culture.

  12. Microbial keratitis after penetrating keratoplasty: impact of sutures.

    Science.gov (United States)

    Moorthy, Sonia; Graue, Enrique; Jhanji, Vishal; Constantinou, Marios; Vajpayee, Rasik B

    2011-08-01

    To determine the impact of presence or absence of sutures in cases with post-penetrating keratoplasty (PKP) microbial keratitis. A 10-year retrospective chart review of post-PKP patients admitted with microbial keratitis at the Royal Victorian Eye and Ear Hospital, Melbourne, between January 1998 and December 2008 was undertaken. Patients were categorized in 2 groups, "sutures present" and "sutures absent." Main parameters evaluated were clinical and microbiological profile and treatment outcome. One hundred and twenty-two episodes of microbial keratitis were noted in 101 patients: 71 (58.2%) with sutures present and 51 (41.8%) with sutures absent. Overall, pseudophakic bullous keratopathy was the most common indication for keratoplasty (P=.92). Ocular surface disorder was the commonest risk factor associated with the occurrence of infection in both groups (P=.17). Infections caused by Moraxella sp. (P=.001) were significantly more common in the "sutures absent" group. Surgical interventions were required for 47 episodes (39%), with corneal gluing performed in significantly higher number of cases in the "sutures absent" group (40% vs 15%; P=.05). Multivariate analyses did not reveal any significant associations. Final mean visual acuity outcome was poorer in the "sutures absent" group (logMAR 2.10 ± 0.92 vs 1.76 ± 0.96; P=.04). Corneal graft infections, in the presence and absence of sutures, share similar indications and risk factors. However, infections caused by indolent microorganisms were more prevalent in grafts without sutures. This group of patients required a higher number of surgical interventions in the form of corneal gluing and the overall visual outcome was poor. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Paediatric infectious keratitis at tertiary referral centres in Vancouver, Canada.

    Science.gov (United States)

    Noureddin, Gelareh S; Sasaki, Sachiko; Butler, Andrea L; Tilley, Peter; Roscoe, Diane; Lyons, Christopher J; Holland, Simon P; Yeung, Sonia N

    2016-12-01

    To report the clinical and microbiological profiles of paediatric patients with infectious keratitis in Vancouver, Canada. In this observational case series, the microbiology results and medical records of 17 eyes with microbial keratitis in 16 children aged 17 years or younger were retrospectively reviewed. These patients had undergone corneal scraping between May 2006 and April 2011 at BC Children's Hospital or Vancouver General Hospital Eye Care Centre in Vancouver, British Columbia, Canada. Demographic information, clinical features, predisposing factors, results of microbiology studies, antibiotic susceptibilities, treatment course and outcomes were analysed. The mean age of patients was 11±5.7 years (range 1-17 years) and the male:female ratio was 1.4:1. Major predisposing factors were contact lens wear (6/17; 35%), and pre-existing ocular surface conditions including blepharitis (3/17; 18%) and Stevens-Johnson syndrome (3/17; 18%). Four patients had a previous corneal ulcer. The most commonly isolated microorganisms were Staphylococcus epidermidis and Acanthamoeba. Acanthamoeba was isolated in 67% of contact lens-related corneal ulcers, while the remaining 33% of contact lens-related corneal ulcers were associated with infection with Pseudomonas aeruginosa. Final visual acuity was better than 20/60 in 9 out of 16 patients (56%). Three patients subsequently required surgical management with either penetrating keratoplasty or deep anterior lamellar keratoplasty for treatment of corneal scarring. Contact lens wear and pre-existing ocular surface conditions are significant risk factors for the development of infectious keratitis in our paediatric population. Knowledge of regional patterns of infection and susceptibility are essential in ensuring prompt treatment of this potentially sight-threatening condition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. A Murine Model of Contact Lens–Associated Fusarium Keratitis

    Science.gov (United States)

    Sun, Yan; Chandra, Jyotsna; Mukherjee, Pranab; Szczotka-Flynn, Loretta; Ghannoum, Mahmoud A.

    2010-01-01

    Purpose. Fusarium solani and F. oxysporum were the causative organisms of the 2005/2006 outbreak of contact lens–associated fungal keratitis in the United States. The present study was an investigation of the ability of F. oxysporum grown as a biofilm on silicone hydrogel contact lenses to induce keratitis. Methods. A clinical isolate of F. oxysporum was grown as a biofilm on lotrafilcon A contact lenses, and a 2-mm diameter punch was placed on the abraded corneal epithelium of either untreated or cyclophosphamide-treated C57BL/6 mice or of IL-1R1−/−, MyD88−/−, TLR2−/−, or TLR4−/− mice. After 2 hours, the lens was removed, and corneal opacification, colony forming units (CFUs), and histopathology were evaluated. Results. C57BL/6 mice developed severe corneal opacification within 24 hours and resolved after four days. In contrast, corneal opacification progressed in cyclophosphamide-treated mice, and was associated with unimpaired fungal growth in the cornea, and with hyphae penetrating into the anterior chamber. The phenotype of MyD88−/− and IL-1R−/− mice was similar to that of cyclophosphamide-treated animals, with significantly impaired cellular infiltration and fungal clearance. Although TLR4−/− mice developed a cellular infiltrate and corneal opacification similar to C57BL/6 mice, the CFU count was significantly and consistently higher. Conclusions. Fusarium grown as a biofilm on silicone hydrogel contact lenses can induce keratitis on injured corneas, with disease severity and fungal killing dependent on the innate immune response, including IL-1R1, MyD88, and TLR4. PMID:19875664

  15. Acanthamoeba keratitis and contact lens wear: static or increasing problem?

    Science.gov (United States)

    Foulks, Gary N

    2007-11-01

    The occurrence of Acanthamoeba keratitis is increasing in the United States because of an expanding population at risk of infection and sporadic outbreaks of infection. Such outbreaks are the result of lapses in contact lens wear and care and of alterations in water quality and water treatment procedures. Although improved techniques in diagnosis are available, better identification of infection alone does not explain an increase in the observed occurrence of the disease. Likewise, there does not appear to be an increase in the virulence or infectivity of the amoebae. Strategies for prevention, including patient education, improved decontaminating agents, maintenance of water treatment standards, and possible immunization of subjects at risk, are needed.

  16. Infectious keratitis in a newborn with goldenhar syndrome.

    Science.gov (United States)

    Mittal, Saurabh; Mittal, Apoorva; Meenakshi, R; Bharathi, Jayahar M; Rengappa, Ramakrishnan

    2010-01-01

    Goldenhar syndrome is a rare, presumably inherited condition that has a multifactorial etiopathology that results in disturbances of blastogenesis. The syndrome is characterized by the presence of dermal epibulbar tumors, periauricular appendices, malformed ears, and vertebral anomalies, with occasional occurrence of cardiac, visceral, or central nervous system anomalies. This report describes a case of Goldenhar syndrome in a newborn who presented with all of the classic signs of Goldenhar syndrome associated with the rare occurrence of infectious keratitis and hydrocephalus. Copyright 2010, SLACK Incorporated.

  17. Diagnostic Evaluation of Co-Occurrence of Acanthamoeba and Fungi in Keratitis: A Preliminary Report.

    Science.gov (United States)

    Raghavan, Anita; Baidwal, Shaffie; Vijayaraghavan, Prabhu; Rajeswari, Sakthi; Rajaraman, Revathi; Venkatapathy, Narendran; Menon, Sunitha; Rammohan, Ram

    2017-11-14

    To test the hypothesis that the coexistence of Acanthamoeba with other forms of microbial keratitis, especially fungal keratitis (FK), is more prevalent than suspected. A prospective diagnostic study whereby patients presenting with stromal keratitis were additionally tested for Acanthamoeba, irrespective of the initial diagnosis. In addition to the routine workup with Gram stain, KOH mount, and cultures on blood agar and potato dextrose agar, nonnutrient agar was included. Confocal microscopy was performed where feasible. Samples for polymerase chain reaction studies were also obtained. We present the preliminary report of the first 100 culture-positive cases. The primary outcome measured was the number of coexistent Acanthamoeba and FK. The secondary outcomes were the total number of Acanthamoeba cases detected and the correlation between clinical diagnosis and microbiological observations. Of the first 100 cases, 22 were culture positive for Acanthamoeba, of which 9 were associated with concurrent FK, 5 with bacterial keratitis, and 8 in isolation. However, only 2 cases were diagnosed clinically as Acanthamoeba, whereas 5 were Acanthamoeba suspects. An additional 4 cases of fungal/Acanthamoeba coexistence in keratitis were revealed purely by confocal microscopy. Acanthamoeba can coexist with other forms of microbial keratitis. The frequency of infection coexistent or otherwise is higher than reported, and the possibility of coinfection must be considered especially in unresponsive cases. Including nonnutrient agar and confocal microscopy in all cases of keratitis would perhaps translate into better treatment strategies and outcomes.

  18. Genetic Characterization Indicates that a Specific Subpopulation of Pseudomonas aeruginosa Is Associated with Keratitis Infections▿

    Science.gov (United States)

    Stewart, Rosalind M. K.; Wiehlmann, Lutz; Ashelford, Kevin E.; Preston, Stephanie J.; Frimmersdorf, Eliane; Campbell, Barry J.; Neal, Timothy J.; Hall, Neil; Tuft, Stephen; Kaye, Stephen B.; Winstanley, Craig

    2011-01-01

    Pseudomonas aeruginosa is a common opportunistic bacterial pathogen that causes a variety of infections in humans. Populations of P. aeruginosa are dominated by common clones that can be isolated from diverse clinical and environmental sources. To determine whether specific clones are associated with corneal infection, we used a portable genotyping microarray system to analyze a set of 63 P. aeruginosa isolates from patients with corneal ulcers (keratitis). We then used population analysis to compare the keratitis isolates to a wider collection of P. aeruginosa from various nonocular sources. We identified various markers in a subpopulation of P. aeruginosa associated with keratitis that were in strong disequilibrium with the wider P. aeruginosa population, including oriC, exoU, katN, unmodified flagellin, and the carriage of common genomic islands. The genome sequencing of a keratitis isolate (39016; representing the dominant serotype O11), which was associated with a prolonged clinical healing time, revealed several genomic islands and prophages within the accessory genome. The PCR amplification screening of all 63 keratitis isolates, however, provided little evidence for the shared carriage of specific prophages or genomic islands between serotypes. P. aeruginosa twitching motility, due to type IV pili, is implicated in corneal virulence. We demonstrated that 46% of the O11 keratitis isolates, including 39016, carry a distinctive pilA, encoding the pilin of type IV pili. Thus, the keratitis isolates were associated with specific characteristics, indicating that a subpopulation of P. aeruginosa is adapted to cause corneal infection. PMID:21227987

  19. [Study and prevention of contact lens-related microbial keratitis with a standardized questionnaire].

    Science.gov (United States)

    Sauer, A; Abry, F; Berrod, J-P; Bron, A; Burillon, C; Chiquet, C; Colin, J; Creuzot-Garcher, C; Delbosc, B; Hoffart, L; Kodjikian, L; Labetoulle, M; Malet, F; Merle, H; Robert, P-Y; Vabres, B; Beynat, J; Brisard, M; Combey de Lambert, A; Donnio, A; Gendron, G; Pagot, R; Saleh, M; Gaucher, D; Speeg-Schatz, C; Bourcier, T

    2010-12-01

    microbial keratitis is a significant health concern for the one million wearers of contact lenses and their ophthalmologists, with some potentially modifiable risk factors. The number of risk factors for contact lens-related microbial keratitis has been described, but many of them still remain assumed or unknown. a multicenter prospective case-control study was conducted in 12 French university hospitals (Besançon, Bordeaux, Dijon, Fort-de-France, Grenoble, Limoges, Lyon, Nancy, Nantes, Paris, Marseille and Strasbourg) beginning in July 2007 on contact lens wearers presenting with microbial keratitis and on healthy contact lens wearers. Patients and healthy wearers were interviewed using a 51-item anonymous standardized questionnaire to determine subject demographics and contact lens wear history. two hundred and fifty-six patients with microbial keratitis were included. One hundred and thirteen healthy contact lenses wearers were surveyed. Cosmetic contact lens wear highly increased the relative risk (RR) of microbial keratitis (RR, 16.5). Time since the last visit to an ophthalmologist longer than 1 year (RR, 3.4) or prescription by someone other than an ophthalmologist (RR, 7.6) also increased the risk of microbial keratitis. Education on lens care and handling was deficient (hand washing: RR, 2.2; rub and rinse: RR, 2.7). a standardized questionnaire is a powerful tool to determine risk factors for contact lens-related microbial keratitis, but also to analyze individual mistakes in contact lenses use and care. 2010 Elsevier Masson SAS. All rights reserved.

  20. A Case of Non-Contact Lens related Acanthamoeba keratitis in Malaysia

    Directory of Open Access Journals (Sweden)

    Mohamed Kamel, A. G.

    2005-01-01

    Full Text Available Acanthamoeba is a ubiquitous free-living amoeba and is responsible for an uncommon yet increasingly diagnosed keratitis in humans. Acanthamoeba keratitis is perhaps the most challenging ocular infection to manage successfully and it can result in permanently impaired vision or blindness. Although contact lens use is the principal risk factor, about 10% of cases occur following trauma and exposure to contaminated soil or water. Cases of Acanthamoeba keratitis involving contact lens wearers have previously been reported in Malaysia but this is the first time, a non-contact lens relatedAcanthamoeba keratitis is reported. The case involved a 28 year old Indonesian male construction worker who had a trauma of the right eye. While working his eye was struck by some sand and dust particles and he quickly washed his eye with water from an open tank at the construction site. He then experienced pain, redness, glaring and blurring of vision of the right eye. The diagnosis was missed at the initial presentation but subsequent culture of the corneal scraping demonstrated Acanthamoeba as the aetiological agent. The history, clinical findings, diagnosis and treatment of non-contact lens related Acanthamoeba keratitis are briefly discussed in this communication. We hope to create awareness especially among the medical and paramedical staff about the existence of this infection in the country and fully support the consideration of Acanthamoeba keratitis as part of the differential diagnosis of most cases of presumed microbial keratitis.

  1. Chronic microsporidial stromal keratitis in an immunocompetent, non-contact lens wearer

    Directory of Open Access Journals (Sweden)

    Fogla Rajesh

    2005-01-01

    Full Text Available An 82-year-old healthy man with unilateral chronic stromal keratitis, initially diagnosed to have viral keratitis and refractory to medical therapy, showed numerous oval, microsporidial organisms, measuring 4-5 m in length in the corneal biopsy. Penetrating keratoplasty, followed by treatment with systemic albendazole and topical propamidine isethionate resulted in resolution of the infection. Electron microscopy of the keratoplasty specimen demonstrated sporoblasts with diplokaryotic nuclei and multiple coils of the filament. The light and electron microscopic features were consistent with microsporidial keratitis.

  2. Treatment of Refractory Keratitis After a Boston Type I Keratoprosthesis With Corneal Collagen Cross-Linking.

    Science.gov (United States)

    Zarei-Ghanavati, Siamak; Irandoost, Fatemeh

    2015-09-01

    To report a patient with refractory keratitis after a Boston type I keratoprosthesis treated with corneal collagen cross-linking (CXL). Case report. A 29-year-old man with a history of chemical burn in the left eye underwent keratoprosthesis implantation. He developed infectious keratitis 4 months after surgery, which did not respond to topical antibiotics. The patient underwent corneal CXL with a shield covering the keratoprosthesis optic. Three weeks after CXL, the infiltration completely resolved. Corneal CXL might be beneficial in the treatment of refractory keratitis in patients with the Boston type I keratoprosthesis.

  3. Azacytidine Treatment Inhibits the Progression of Herpes Stromal Keratitis by Enhancing Regulatory T Cell Function.

    Science.gov (United States)

    Varanasi, Siva Karthik; Reddy, Pradeep B J; Bhela, Siddheshvar; Jaggi, Ujjaldeep; Gimenez, Fernanda; Rouse, Barry T

    2017-04-01

    Ocular infection with herpes simplex virus 1 (HSV-1) sets off an inflammatory reaction in the cornea which leads to both virus clearance and chronic lesions that are orchestrated by CD4 T cells. Approaches that enhance the function of regulatory T cells (Treg) and dampen effector T cells can be effective to limit stromal keratitis (SK) lesion severity. In this report, we explore the novel approach of inhibiting DNA methyltransferase activity using 5-azacytidine (Aza; a cytosine analog) to limit HSV-1-induced ocular lesions. We show that therapy begun after infection when virus was no longer actively replicating resulted in a pronounced reduction in lesion severity, with markedly diminished numbers of T cells and nonlymphoid inflammatory cells, along with reduced cytokine mediators. The remaining inflammatory reactions had a change in the ratio of CD4 Foxp3+ Treg to effector Th1 CD4 T cells in ocular lesions and lymphoid tissues, with Treg becoming predominant over the effectors. In addition, compared to those from control mice, Treg from Aza-treated mice showed more suppressor activity in vitro and expressed higher levels of activation molecules. Additionally, cells induced in vitro in the presence of Aza showed epigenetic differences in the Treg-specific demethylated region (TSDR) of Foxp3 and were more stable when exposed to inflammatory cytokines. Our results show that therapy with Aza is an effective means of controlling a virus-induced inflammatory reaction and may act mainly by the effects on Treg.IMPORTANCE HSV-1 infection has been shown to initiate an inflammatory reaction in the cornea that leads to tissue damage and loss of vision. The inflammatory reaction is orchestrated by gamma interferon (IFN-γ)-secreting Th1 cells, and regulatory T cells play a protective role. Hence, novel therapeutics that can rebalance the ratio of regulatory T cells to effectors are a relevant issue. This study opens up a new avenue in treating HSV-induced SK lesions by

  4. Glutathione Transferase as a Potential Marker for Gut Epithelial Injury versus the Protective Role of Breast Milk sIgA in Infants with Rota Virus Gastroenteritis

    OpenAIRE

    Sherif, Lobna S.; Abdel Raouf, Randaa K.; Rokaya M. El Sayede; Amany S. El Wakkadd; Shoaib, Ashraf R.; Ali, Hanan M.; Amira S. El Refay

    2015-01-01

    BACKGROUND: Secretory immunoglobulin A (SIgA) plays an important protective role in the recognition and clearance of enteric pathogens. AIM: This study was designed to assess if mucosal integrity “measured by secretory IgA (SIgA)” is a protective factor from more epithelial alteration “measured by glutathione transferase” in infants with Rota gastroenteritis and its relation to infantsꞌ feeding pattern. PATIENTS AND METHODS: This study was conducted on 79 infants aged 6 months and les...

  5. Corneal epithelial healing after penetrating keratoplasty using topical Healon versus balanced salt solution.

    Science.gov (United States)

    Reed, D B; Mannis, M J; Hills, J F; Johnson, C A

    1987-07-01

    The authors conducted a prospective study of 38 consecutive corneal transplant patients over a five-and-one-half month period in order to evaluate the effect of intraoperative hydration with topical Healon versus balanced salt solution on postoperative epithelial healing in the corneal graft. Eight independent variables, including patient age, sex, operating room time, donor age, donor time in McCarey-Kaufman media, intraoperative hydration with balanced salt solution versus Healon, and the amount of postoperative punctate epithelial keratitis measured on postoperative day 1, day 2, and at one week were compared using a multiple linear regression method. While the correlation between donor age (p = .060) and patient age (p = .088) with the amount of punctate epithelial keratitis at one week post graft approached statistical significance, only the Healon-treated group showed a high correlation to more complete graft healing one week postoperatively (p = 0.002). Topical Healon during keratoplasty may foster epithelial healing, but it also may present technical challenges of which the surgeon should be aware.

  6. Clinical Observation of a Child with KID (Keratitis-Ichthyosis-Deafness Syndrome

    Directory of Open Access Journals (Sweden)

    V.A. Klymenko

    2015-10-01

    Full Text Available A clinical case of keratitis-ichthyosis-deafness (KID syndrome in an infant is described. The article familia-rizes pediatricians and family doctors with difficulties in the diagnosis of this rare genetic disease in infants.

  7. Successful treatment of Fusarium keratitis with cornea transplantation and topical and systemic voriconazole.

    NARCIS (Netherlands)

    Klont, R.R.; Eggink, C.A.; Rijs, A.J.M.M.; Wesseling, P.; Verweij, P.E.

    2005-01-01

    A case of invasive Fusarium keratitis in a previously healthy male patient was treated successfully with cornea transplantation and systemic and topical voriconazole after treatment failure with topical amphotericin B and systemic itraconazole. Topical voriconazole was well tolerated, and, in

  8. Ultraviolet Keratitis: From the Pathophysiological Basis to Prevention and Clinical Management.

    Science.gov (United States)

    Willmann, Gabriel

    2015-12-01

    Ultraviolet keratitis is caused by the toxic effects of acute high-dose ultraviolet radiation (UVR) reflecting the sensitivity of the ocular surface to photochemical injury. The clinical syndrome presents with ocular pain, tearing, conjunctival chemosis, blepharospasm, and deterioration of vision typically several hours after exposure, lasting up to 3 days. Mountaineers, skiers, and beach recreationalists are particularly at risk to suffer from ultraviolet (UV) keratitis as the reflectivity of UVR in these environments is extremely high. The aim of this review is to raise awareness about the potential of UV damage on the eye with an emphasis on UV keratitis, to highlight the pathophysiological basis of corneal phototoxicity, and to provide practical guidance for the prevention and clinical management of UV keratitis commonly known as snow blindness.

  9. Contact lens-related polymicrobial keratitis from Pantoea agglomerans and Escherichia vulneris

    Directory of Open Access Journals (Sweden)

    Vincent D. Venincasa

    2016-04-01

    Conclusions: This is the first report of P. agglomerans and E. vulneris keratitis in association with contact lens wear. Both strains of P. agglomerans and E. vulneris were pansensitive to all tested antibiotics.

  10. Synthetic fiber from a teddy bear causing keratitis and conjunctival granuloma

    DEFF Research Database (Denmark)

    Farooq, Mohammed Kashaf; Prause, Jan U; Heegaard, Steffen

    2011-01-01

    Background To report a case of keratitis and a case of conjunctivitis caused by synthetic fibers from toy teddy bears. Case presentation Case stories with histopathological analysis. 1) A two-year-old girl developed a severe case of keratitis and corneal ulceration. The initial treatment with var......Background To report a case of keratitis and a case of conjunctivitis caused by synthetic fibers from toy teddy bears. Case presentation Case stories with histopathological analysis. 1) A two-year-old girl developed a severe case of keratitis and corneal ulceration. The initial treatment...... with various antibiotics gave no improvement and eventually the patient developed spontaneous perforation of the cornea. The corneal swabs contained no bacteria or fungi. Corneal grafting was performed and the corneal button was sent for histopathological examination. 2) A five-year-old girl presented...

  11. Comparison Between Polymicrobial and Fungal Keratitis: Clinical Features, Risk Factors, and Outcome.

    Science.gov (United States)

    Fernandes, Merle; Vira, Divya; Dey, Mrinmoy; Tanzin, Tanuja; Kumar, Nagendra; Sharma, Savitri

    2015-11-01

    To compare the clinical features, risk factors, and outcome of polymicrobial keratitis with monomicrobial keratitis due to fungus. Retrospective, comparative interventional case series. Consecutive cases of microbial keratitis with significant growth of more than 1 organism in culture and culture-proven fungal keratitis treated with natamycin alone were retrieved from the microbiology department. Complete success was defined as resolution of the infiltrate with scar formation on medical treatment, partial success as resolution following tissue adhesive application, and failure as inadequate response to medical therapy with increasing infiltrate size, corneal melting, and/or perforation necessitating therapeutic penetrating keratoplasty (PKP) or evisceration. There were 34 eyes of 34 patients with polymicrobial keratitis and 60 cases of fungal keratitis. Compared to patients with fungal keratitis, patients with polymicrobial keratitis were significantly older (50.03 ± 9.81 years vs 42.79 ± 12.15 years, P = .0038), with larger infiltrates at presentation (61.8% vs 24.1%, P = .0007), a higher association with endophthalmitis (11.8% vs 0%, P = .03), previous history of corneal graft (20.6% vs 0%, P = .0012), and prior topical corticosteroid use (23.5% vs 5%, P = .019). In the polymicrobial group, a combination of bacteria and fungus was more frequently isolated (23, 67.6%), among which filamentous fungi (25, 39.1%) and coagulase-negative staphylococci (14, 21.9%) comprised a majority. Complete success was significantly lower in the polymicrobial group compared to the fungal keratitis group (39.3% vs 73.7%, P = .0045). In multivariate logistic regression analysis comparing factors affecting the outcome between the 2 groups, older age (P = .027) and ulcers larger than 6 mm (P = .001) at presentation adversely affected outcome. Polymicrobial keratitis with fungus and bacteria was more common and more challenging to treat, with a poorer outcome than fungal

  12. Fungal keratitis in patients with corneal ulcer attending Minilik II Memorial Hospital, Addis Ababa, Ethiopia.

    Science.gov (United States)

    Kibret, Tihtina; Bitew, Adane

    2016-08-30

    Fungal keratitis is an important cause of corneal blindness all over the world. Although there are several reports on fungal keratitis from developing and developed countries, fungal keratitis in Ethiopia is poorly known. The aim of this study was to determine the prevalence of fungal keratitis and spectrum of fungi implicated in causing the infection. The present study was a single institutional cross-sectional study carried out in Minilik II Memorial Hospital eye clinic, Addis Ababa, Ethiopia from September 2014 to August 2015. Corneal scraping was obtained under aseptic condition with sterile 21 gauge needle by an ophthalmologist from patients suspected of microbial keratitis. Each scraping was inoculated onto Sabouraud Dextrose Agar in C-shaped streaks and incubated at 25 °C aerobically for four weeks. Cultures of mycelia fungi were identified by examining macroscopic and microscopic characteristics of their colonies. Yeasts were identified by employing biochemical and assimilation test procedures and using CHROMagar Candida culture. All data were coded, double entered and analyzed using SPSS version 20. Out of 153 cases of microbial keratitis, fungi were recovered from 69 patients giving fungal keratitis prevalence of 45.1. Patients from rural areas were significantly affected than patients in urban regions (P = 0.005). Age groups of 25-34 (P = 0.017) and 15-24 years (P = 0.008) were significantly affected. Fungal keratitis was significantly associated with farmers (P = 0.0001), daily laborers (P = 0.0001), unemployed (P = 0001) and students (P = 0.004). Fungal keratitis was statistically associated with trauma (P = 0.006), and diabetes (P = 0.024). Seventy six fungal isolates were recovered, of which molds accounted 63 (82.9 %) of the total isolates. Fusarium and Aspergillus species were the two predominant molds accounting 27.6 and 25 % of the total isolates respectively. Yeast isolates accounted only 17.1 %. High

  13. Keratitis in six dogs after topical treatment with carbonic anhydrase inhibitors for glaucoma.

    Science.gov (United States)

    Beckwith-Cohen, Billie; Bentley, Ellison; Gasper, David J; McLellan, Gillian J; Dubielzig, Richard R

    2015-12-15

    6 dogs (10 eyes) with keratitis following long-term topical treatment with a carbonic anhydrase inhibitor (CAI) were evaluated. In 4 dogs (6 eyes), CAI treatment was discontinued. Three dogs (4 eyes) underwent enucleation because of end-stage corneal disease. One dog was treated differently in each eye and thus was represented in both aforementioned groups. Following initiation of treatment with a CAI (ie, brinzolamide or dorzolamide), the median time to development of severe ocular signs was 266 days (range, 133 to 679 days). Clinically severe ocular signs included ulcerative and nonulcerative perilimbal keratitis or severe diffuse keratitis with marked vascularization. The keratitis was refractory to treatment with anti-inflammatory medications. Histologic and immunohistochemical examination of enucleated globes was performed in 3 affected dogs and in 1 dog with keratitis that recovered. Corneal lesions included 2 distinct inflammatory infiltrates with plasma cells predominating in the anterior stroma and both T cells and neutrophils in the epithelium. Stromal plasma cells and overlying epithelium exhibited strong positive immunoreactivity for IgG. Topical CAI treatment was discontinued in 4 dogs after a median of 209 days (range, 44 to 433 days), and in these dogs, clinical improvement was evident within 2 to 4 days of CAI treatment cessation. Signs of keratitis resolved in 12 to 25 days in these 4 dogs, and median follow-up time after CAI discontinuation was 25.5 months (range, 6 to 42 months), during which time signs of corneal disease did not recur. On the basis of this small series, presumed topical CAI-associated keratitis in dogs appeared to be an uncommon immune-mediated disease that was not responsive to corticosteroid treatment. Affected patients improved rapidly, but only after discontinuation of CAI treatment. In dogs with glaucoma, clinicians should consider the development of punctate keratopathy and severe diffuse keratitis as potential adverse

  14. Fungal Keratitis in North India: Spectrum of Agents, Risk Factors and Treatment.

    Science.gov (United States)

    Ghosh, Anup K; Gupta, Amit; Rudramurthy, Shivaprakash M; Paul, Saikat; Hallur, Vinay Kumar; Chakrabarti, Arunaloke

    2016-12-01

    To assess the prevalence of fungal keratitis, we conducted a retrospective study over 7 years (2005 through 2011) at a tertiary care center in North India. Effort has been made to analyze the disease burden, spectrum of agents and treatment history. The findings were compared with an earlier study at the same center for any change in the epidemiology of the disease. Microbiology records were screened at the Postgraduate Institute of Medical Education and Research, Chandigarh, India, to identify fungal keratitis cases, and available clinical records of those cases were analyzed. Of 2459 clinically suspected fungal keratitis cases, 765 (31 %) cases were direct microscopy confirmed. Of these microscopy-confirmed cases, fungi were isolated in 393 (51.4 %), with Aspergillus spp. ranked top (n = 187, 47.6 %), followed by melanized fungi (n = 86, 21.9 %) and Fusarium spp. (n = 64, 16 %). A male predominance of 78.7 % was noted with a peak in the incidence of fungal keratitis during post-monsoon season (September to November). A delay in diagnosis was significantly associated (p keratitis cases due to melanized fungi. In comparison with an earlier study, higher isolation of melanized fungi was noted with a widening of the spectrum of agents identified. Thus, fungal keratitis due to Aspergillus spp. remains a serious ocular illness among the active male population in North India with relative rise of keratitis due to melanized fungi. The spectrum of agents causing fungal keratitis has broadened with many rare fungi that are implicated.

  15. Pathogenologic analysis on fungal keratitis in 81 eyes in Hainan Province

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    Hong He

    2017-07-01

    Full Text Available AIM: To analyze the etiological and epidemiological characteristics of fungal keratitis in the Hainan Province of China with a warm and humid tropical climate. METHODS: Eighty-one patients(81 eyeswith fungal keratitis who attended the Corneal Services of Hainan Province Eye Hospital from January 2014 to December 2016 were retrospectively reviewed. The characteristics of fungal population, the age distributions of patients, the seasonal distribution of disease and the risk factor were analyzed. The treatment of fungal keratitis was reviewed. The positive rates of KOH based smear and fungal culture were assessed and analyzed using the Chi-squared test. RESULTS: Eighty-one patients of fungal keratitis(including 81 eyeswere involved. The ration of the male and female was 2:1. The median age was 51 years. Corneal trauma seems to be the most common risk factor. Of all cases, 45 patients(55%were greater than or equal to 50 years old. Twenty-eight(35%were between 30-50 years old. Eight(10%were less than or eaqual to 30 years old. Twenty-nine cases(36%appeared in the first quarter indicated that fungal keratitis was most popular in the winter in Hainan Province. Standard fungal cultures were performed in 81 cases. Seventy-one of the 81 samples(88%grew fungi. Fungal smear tests were performed in 80 cases. Forty-one cases(51%were confirmed to be fungal keratitis by 10% KOH count. Statistical differences were found in the positive rates between fungal culture and fungal smear test(χ2=23.730, PCONCLUSION: The predominant fungal species isolated is Fusarium sp. followed by asporogenous strain. The fungal keratitis is most popular in the first quarter in Hainan Island. Corneal trauma seems to be the most common risk factor. Multidisciplinary approach, including the combined application of surgery and antifungal drugs is the treatment strategy common used for the fungal keratitis. The positive rate of fungal culture is higher than fungal smear test.

  16. [Infectious keratitis and cosmetic lenses: a five-case retrospective study].

    Science.gov (United States)

    Guyomarch, J; van Nuoï, D N'guyen; Beral, L; Donnio, A; Desbois, N; Olive, C; Theodose, R; Merle, H

    2010-04-01

    To determine the characteristics of infectious keratitis related to plano cosmetic lenses. Retrospective case study of a series of infectious keratitis among plano cosmetic lenses wearers. The main parameters were demographic data, medical history, risk factors for infectious complications and keratitis severity criteria, microbiological results, clinical course, and final visual acuity. Five patients were included, all females, ranging from 15 to 50 years of age. Four were emmetropic. One patient had undergone refractive photokeratectomy a few months before. All had risk factors for infectious complications. The fundamental causes of infections were diverse: bacterial abscesses, keratomycosis, and amoebic keratitis. All presented severity criteria. In two cases, the keratitis led to severe consequences with legal blindness requiring penetrating keratoplasty in one case. Infectious keratitis in plano cosmetic lenses wearers is not rare and may have dramatic consequences. Sales are specifically regulated and the lenses are considered cosmetic products, not medical devices. The sales regulations for plano cosmetic lenses should be updated, as several countries have already done after encountering many serious incidents. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  17. Development of EKC after eximer laser photorefractive surgery and subsequent recurrence of EKC-like keratitis.

    Science.gov (United States)

    Park, Sung Joon; Jang, Yoon Soo; Koh, Tae Hyuk; Kwon, Young A; Song, Sang Wroul

    2011-12-01

    This research focuses on four cases of patients having undergone eximer laser photorefractive surgery who were diagnosed with adenoviral keratoconjunctivitis during the postoperative period and who later developed epidemic keratoconjunctivitis (EKC)-like keratitis. Two of the patients had undergone laser-assisted subepithelial keratectomy (LASEK), one had undergone laser in situ keratomileusis and one had photorefractive keratectomy. After the surgery adenoviral keratoconjunctivitis and recurrent late-developing EKC-like keratitis were observed in the patients. Recurrent late-developing EKC-like keratitis occurred in one of the patients, who had received LASEK as many as three times. The others had only one or two episodes.The corneal infiltrates of keratitis mainly occurred in the central cornea. Successful resolution of recurrent late-developing EKC-like keratitis was achieved through the use of topical steroids without sequelae and the final best-corrected visual acuity was as good as the base line. These keratitis infiltrates have been presumed to represent an immune response to the suspected adenoviral antigens deposited in corneal stroma during the primary adenoviral infection. Previous reports argued that patients with a history of adenoviral ketatoconjunctivitis were succeptible to adenoviral keratoconjunctivitis becoming reactivated; however, in our research, our patients had their first adenoviral infections after the eximer laser photorefractive surgery and reactivation was confirmed. We recommend that attention be paid to adenoviral infection after laser refractive operations, because these patients seem to have more frequent recurrences.

  18. Relationship of Virulence Factors and Clinical Features in Keratitis Caused by Pseudomonas aeruginosa.

    Science.gov (United States)

    Oka, Naoko; Suzuki, Takashi; Ishikawa, Eri; Yamaguchi, Satoshi; Hayashi, Naoki; Gotoh, Naomasa; Ohashi, Yuichi

    2015-10-01

    To examine bacterial virulence factors in Pseudomonas aeruginosa isolates from contact lens (CL) wearers and non-CL wearers with P. aeruginosa keratitis, and to investigate relationships between virulence factors and clinical features of keratitis. The study involved 25 subjects including 18 CL and 7 non-CL-related P. aeruginosa keratitis patients. Slit-lamp photographs of all subjects were captured, and the focus occupancy ratio (FOR) was defined as the total focus area/entire cornea area, using image processing software. Twenty-five clinical P. aeruginosa isolates from keratitis were assessed for protease production, elastase production, biofilm formation, bacterial swimming and swarming motility, cell surface hydrophobicity, and genes encoding the type III secretion system (TTSS) effectors (ExoU and ExoS). Ring abscess was found in 9 of 18 CL-related P. aeruginosa keratitis cases (CL[+] ring[+] group) but not in another 9 cases (CL[+] ring[-] group). Expression or prevalence of virulence factors in P. aeruginosa isolates from the CL(+) ring(+) group, CL(+) ring(-) group, and CL(-) group were compared. The FOR for CL(+) ring(+) or CL(-) was higher than for CL(+) ring(-) (P keratitis.

  19. Infectious Keratitis in Limbal Stem Cell Deficiency: Stevens-Johnson Syndrome Versus Chemical Burn.

    Science.gov (United States)

    Kang, Byeong Soo; Kim, Mee Kum; Wee, Won Ryang; Oh, Joo Youn

    2016-01-01

    To investigate the incidence, clinical and microbiological characteristics, risk factors, and therapeutic outcome of infectious keratitis in patients with limbal stem cell deficiency (LSCD) related to Stevens-Johnson syndrome (SJS) and corneal chemical burn. Medical records of 90 eyes of 59 patients who were diagnosed with LSCD resulting from SJS (52 eyes of 29 patients) or corneal chemical burn (38 eyes of 30 patients) were reviewed. Infectious keratitis developed in 35% of LSCD patients with SJS (18 eyes, 14 patients) and in 18% of those with chemical burn (7 eyes, 7 patients). The development of infectious keratitis in SJS was significantly associated with the severity of chronic ocular surface complications in the cornea, conjunctiva, and eyelids and with the use of topical corticosteroids during the disease course. All cases of infectious keratitis following chemical burn occurred in patients with grade III or IV burn by Roper-Hall classification. Approximately 83% of culture-proven cases of infectious keratitis were bacterial infection, most of which (80%) were caused by Gram-positive bacteria. For resolution of infection, 17 eyes (68%) received surgery in addition to medical treatment, whereas 8 eyes (32%) received medical treatment alone. After infection resolution, the final visual acuity was decreased in 10 eyes (40%) compared with before infection. Infectious keratitis is a common complication of LSCD associated with SJS or severe chemical burn to the cornea. Despite medical and surgical treatments, the visual outcome is poor.

  20. Risk Factors and Microbiological Features of Patients Hospitalized for Microbial Keratitis

    Science.gov (United States)

    Lin, Tzu-Yu; Yeh, Lung-Kun; Ma, David HK; Chen, Phil YF; Lin, Hsin-Chiung; Sun, Chi-Chin; Tan, Hsin-Yuan; Chen, Hung-Chi; Chen, Shin-Yi; Hsiao, Ching-Hsi

    2015-01-01

    Abstract We conducted a retrospective, cross-sectional study to analyze predisposing factors, clinical features, and microbiological characteristics of patients with microbial keratitis hospitalized over 10 years. The medical records of 558 patients who were diagnosed with microbial keratitis and admitted to Chang Gung Memorial Hospital (CGMH), a referral center in Taiwan, from January 1, 2003 to December 31, 2012 were reviewed. Demographics, predisposing factors, isolated organisms, treatment, and hospital stay were recorded. Yearly trends were tested using a linear-by-linear association. Contact lens wear was the most common predisposing factor (31.4%), followed by ocular and systemic diseases (26.3%) and trauma (23.5%). Contact lens-related infectious keratitis increased year by year (P = 0.011). Pseudomonas aeruginosa was the most commonly isolated organism (28%), followed by fungi (17.6%) and coagulase-negative Staphylococcus (5.4%). Except for Serratia marcescens, the identified organisms did not change over 10 years. Most bacterial infections were controlled using antimicrobial treatment, but more than half of patients with fungal keratitis required surgical interventions. The mean hospital stay was 13.7 ± 11.5 days. Previous ocular surgery, large ulcer size, nontuberculous myycobacteris infection, and surgery during admission were related to prolonged hospital stay. In Taiwan, contact lens-related pseudomonal keratitis remained the most common cause of microbial keratitis in patients hospitalized from 2003 to 2012. PMID:26512612

  1. A 5-Year Retrospective Review of Fungal Keratitis at Hospital Universiti Sains Malaysia

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    Fadzillah Mohd-Tahir

    2012-01-01

    Full Text Available Background. Corneal blindness from healed infected keratitis is one of the most preventable causes of monocular blindness in developing countries, including Malaysia. Our objectives were to identify the causative fungi, predisposing risk factors, the proportion of correct clinical diagnosis, and visual outcome of patients treated in our hospital. Methods. A retrospective review of medical and microbiology records was conducted for all patients who were treated for fungal keratitis at Hospital Universiti Sains Malaysia from January 2007 until December 2011. Results. Forty-seven patients (47/186, 25.27% were treated for fungal keratitis during the study period. This demonstrated that the incidence of fungal keratitis has increased each year from 2007 to 2011 by 12.50%, 17.65%, 21.21%, 26.83%, and 28.57%, respectively. The most common predisposing factors were injury to the eye followed by use of topical steroid, and preexisting ocular surface disease. Fusarium species were the most common fungal isolated, followed by Candida species. Clinical diagnosis of fungal keratitis was made in 26 of the 41 (63.41% cases of positive isolates. Of these, in eleven cases (23.40% patients required surgical intervention. Clinical outcome of healed scar was achieved in 34 (72.34% cases. Conclusions. The percentage of positive fungal isolated has steadily increased and the trend of common fungal isolated has changed. The latest review regarding fungal keratitis is important for us to improve patients' outcome in the future.

  2. Successful medical management of recalcitrant Fusarium solani keratitis: molecular identification and susceptibility patterns.

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    Taylan Sekeroglu, Hande; Erdem, Elif; Yagmur, Meltem; Gumral, Ramazan; Ersoz, Reha; Ilkit, Macit; Harbiyeli, Ibrahim Inan

    2012-09-01

    Fungal keratitis is a rare but sight-threatening infection of the cornea that may be caused by several fungal pathogens. A delay in diagnosis and inadequate treatment may even lead to loss of the affected eye. Fungal keratitis is often misdiagnosed as bacterial keratitis because isolation and identification of the fungal pathogen is difficult and requires experience, and fungal growth in culture requires time. In this report, a 14-year-old boy with recalcitrant Fusarium solani keratitis, unresponsive to initial therapy, is presented. CLSI M38-A2 in vitro antifungal susceptibility tests demonstrated that only amphotericin B (0.5 μg/ml) had potent activity against F. solani; however, fluconazole (>64 μg/ml), itraconazole (>16 μg/ml), voriconazole (8 μg/ml), and posaconazole (>16 μg/ml) had high minimum inhibitory concentrations. In addition, caspofungin (>16 μg/ml) and anidulafungin (>16 μg/ml) exhibited high minimum effective concentrations. Repeated intrastromal voriconazole injections, topical voriconazole, and caspofungin combined with systemic antifungal agents improved of the corneal lesion with a significant increase in visual acuity. Intrastromal voriconazole injection may be used as an adjunctive treatment method for recalcitrant fungal keratitis with no prominent complications. The intrastromal route could be an effective route of administration of antifungal agents, especially for F. solani keratitis, as in this case. A combination of various antifungal agents administered by different routes prevented loss of the eye.

  3. Methicillin-Resistant Staphylococcus aureus Keratitis after Descemet's Stripping Automated Endothelial Keratoplasty

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    Tatsuro Miyamoto

    2013-11-01

    Full Text Available Purpose: We report a case of methicillin-resistant Staphylococcus aureus (MRSA keratitis after Descemet's stripping automated endothelial keratoplasty (DSAEK. Case Report: An 87-year-old woman who had undergone a DSAEK 4 months previously was referred to Tokushima University Hospital with a diagnosis of infectious keratitis after DSAEK. A white abscess and infiltration in the inferior cornea of the right eye were observed. We started an empiric therapy using topical levofloxacin and chloramphenicol on the basis of the microscopic findings of the corneal scraping concurrently with cultivation of the cornea. Results: A strain of MRSA was isolated from the corneal sample. Although the strain was susceptible to chloramphenicol, it was resistant to quinolone. The keratitis improved rapidly due to empiric therapy, and topical steroids could be resumed 6 days after initiation of the empiric therapy. Conclusions: To our knowledge, this is the first case of MRSA keratitis, and the second case of bacterial keratitis, after DSAEK. MRSA keratitis can occur following uneventful DSAEK. The empiric therapy on the basis of results from a light microscopic examination of a Gram-stained corneal scraping and restarting topical steroids in the early stages of medication contributed to the good clinical course of this case.

  4. Two Different Concentrations of Topical Levofloxacin for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Keratitis.

    Science.gov (United States)

    Tajima, Kazuki; Miyake, Taku; Koike, Naohito; Hattori, Takaaki; Takahashi, Hiroki; Matsumoto, Tetsuya; Fujita, Koji; Kuroda, Masahiko; Ito, Norihiko; Goto, Hiroshi

    2015-12-01

    To compare the efficacy of topical 1.5% and 0.5% levofloxacin (LVFX) for the treatment of multidrug-resistant Pseudomonas aeruginosa (MDRP) keratitis in rabbits. In a rabbit eye, we produced an MDRP keratitis model by excising a 2-mm circular disc of the cornea up to a depth of one-half of the stromal layer and inoculated an MDRP strain into the corneal concavity. Nine hours after inoculation and after confirming that MDRP keratitis had developed, we treated the eyes topically with 0.5% levofloxacin, 1.5% levofloxacin, or phosphate-buffered saline (PBS) every 6 h until 57 h postinfection. The infected eyes were evaluated by clinical score, histopathological examination, and viable bacterial count (colony forming units). In the MDRP keratitis model, clinical score was significantly lower in 0.5% and 1.5% levofloxacin-treated groups than in PBS-treated group and was the lowest in 1.5% levofloxacin-treated group. Histopathological examination showed maintenance of corneal translucency and little influx of polymorphonuclear neutrophils in 1.5% levofloxacin-treated group. Viable bacterial count in the infected cornea was significantly lower in 0.5% levofloxacin-treated group compared with PBS-treated group, while no viable bacteria were detected in 1.5% levofloxacin-treated group. Using our MDRP keratitis model, we showed that topical 0.5% levofloxacin is not adequately effective, while 1.5% levofloxacin is efficacious in controlling MDRP keratitis.

  5. Pathogenic Free-Living Amoebae Isolated From Contact Lenses of Keratitis Patients

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    Elham HAJIALILO

    2015-12-01

    Full Text Available Background: Free-living amoeba (FLA-related keratitis is a progressive infection of the cornea with poor prognosis. The present study aimed to investigates the con­tact lenses of patients with keratitis for pathogenic free-living amoebae.Methods: Overall, 62 contact lenses and their paraphernalia of patients with kerati­tis cultured and tested for the presence of free-living amoebae using morphological criteria. Unusual plates including plates containing mix amoebae and Vermamoeba were submitted to molecular analysis. Results: Out of 62 plates, 11 revealed the outgrowth of free living amoeba of which 9 were Acanthamoeba, one plates contained mix amoebae including Acan­thamoeba and Vermamoeba and one showed the presence of Vermamoeba. These two latter plates belonged to patients suffered from unilateral keratitis due to the mis­used of soft contact lenses. One of the patients had mix infection of Acanthamoeba (T4 and V. vermiformis meanwhile the other patient was infected with the V. vermiformis. Conclusion: Amoebic keratitis continues to rise in Iran and worldwide. To date, various genera of free-living amoebae such as Vermamoeba could be the causative agent of keratitis. Soft contact lens wearers are the most affected patients in the country, thus awareness of high-risk people for preventing free-living amoebae re­lated keratitis is of utmost importance.

  6. A Single Amino Acid Mutation (I1012F) of the RNA Polymerase of Marine Viral Hemorrhagic Septicemia Virus Changes In Vitro Virulence to Rainbow Trout Gill Epithelial Cells

    DEFF Research Database (Denmark)

    Kim, Sung-Hyun; Thu, Beate J.; Skall, Helle Frank

    2014-01-01

    . Otte, and N. J. Olesen, Virus Res. 63: 95-106, 1999]) and IVa (JF-09). DK-3592 and NO/650/07 were pathogenic to GECs, while marine strains 1p8 and JF-09 were nonpathogenic to GECs. Eight conserved amino acid substitutions contrasting high-and low-virulence strains were identified, and reverse genetics...... was used in a gain-of-virulence approach based on the JF-09 backbone. Mutations were introduced into the G, NV, and L genes, and seven different virus clones were obtained. For the first time, we show that a single amino acid mutation in conserved region IV of the L protein, I1012F, rendered the virus able...

  7. Colletotrichum truncatum: an Unusual Pathogen Causing Mycotic Keratitis and Endophthalmitis▿

    Science.gov (United States)

    Shivaprakash, M. R.; Appannanavar, Suma B.; Dhaliwal, Manpreet; Gupta, Amit; Gupta, Sunita; Gupta, Amod; Chakrabarti, Arunaloke

    2011-01-01

    In recent years, the well-known plant pathogens of the Colletotrichum genus were increasingly reported to cause ophthalmic infections in humans. Among 66 species in the Colletotrichum genus, only a few are known to be pathogenic for humans. We report here five cases of ophthalmic infections due to Colletotrichum truncatum, a species never reported earlier to cause human infection. The isolates were identified by morphological characteristics and the sequencing of internal spacer regions of ribosomal DNA. The progress of lesions in those patients was slow compared to that of lesions caused by Aspergillus or Fusarium infections. The surgical management included total penetrating keratoplasty in patients with keratitis and pars plana vitrectomy in endophthalmitis. Two patients were treated additionally with intravitreal amphotericin B deoxycholate, one patient with oral itraconazole, and another patient with oral and topical fluconazole therapy. The present series therefore highlights the expanding spectrum of agents causing eye infections and the inclusion of C. truncatum as a human pathogen. PMID:21653772

  8. Keratitis by Aspergillus flavus infection after cataract surgery

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    João Luiz Pacini Costa

    Full Text Available ABSTRACT We report a case of keratis infection after cataract phacoemulsification with intraocular lens implantation in a 65-year-old female patient. The patient initially underwent cataract surgery on the right eye. Intraocular inflammation appeared on the second post-operative day and was initially treated as Toxic Anterior Segment Syndrome (TASS. The inflammation was reduced and vision improved initially but very aggressive and progressive keratitis destroyed the cornea due to the delay in correct diagnosis. Aspergillus flavus was isolated from a biopsy.The infection was treated with antifungal agents and loss of the eye was avoided by total corneal transplantation associated with Gundersen conjunctiva cover. To restore the lost vision, a second penetrating corneal graft with removal of the conjunctiva cover was performed 17 months later. The final best-corrected vision was 20/40 but prognosis for long-term graft survival is poor.

  9. [Emergency Keratoplasty with Porcine Xenografts in Necrotizing Keratitis].

    Science.gov (United States)

    Drozhzhyna, Galyna I; Gaidamaka, Tetiana B; Cursiefen, Claus; Bachmann, Björn O; Ivanovska, Olena V; Ostashevsky, Viktor L; Kogan, Boris M; Usov, Volodymyr J; Pasyechnikova, Natalija V

    2017-07-06

    Background The great shortage of donor material in Ukraine makes it necessary to find additional sources of transplant material. A possible suitable material are the porcine corneas, as they are similar in structure and biomechanical parameters to the human cornea. The purpose of our study was to analyze the results of therapeutic keratoplasty (KP) with keratoxenotransplants from cryolyophilized porcine corneas in patients with severe necrotizing keratitis. Methods A retrospective analysis of 32 xenotransplantations patients with severe necrotizing keratitis (17 lamellar, 6 stepped perforating, 4 perforating, 5 "biological coverage" according to Puchkovskaya) was completed. Results All eyes could be preserved, but the graft was rejected in all eyes. A semitransparent xenograft (XG) was achieved in 9 patients (33.3%). The best results were obtained after lamellar XKP with an XT diameter of 3.5 - 6.5 mm. Lamellar XTs with larger diameters (7.0 - 10.0 mm) were opaque. Postoperatively, the intensity of the inflammatory response after stepped XKP was slightly lower than that of the classical perforating XKP. A new KP with human corneas had to be performed in 5 patients, in one case combined with an antiglaucomatous operation and in another case with cataract extraction. Antiglaucomatous surgery had to be performed in 5 patients (15.6%). Conclusion In the absence of human donor corneas, a porcine keratoxenoimplant can be used as temporary therapeutic keratoplasty in case of emergency stop the inflammation process and to save the eye. In cases of keratoxenoimplant, a poor visual outcome is expected. Georg Thieme Verlag KG Stuttgart · New York.

  10. Intestinal epithelial dysplasia (tufting enteropathy

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    de Serres Natacha

    2007-04-01

    Full Text Available Abstract Intestinal epithelial dysplasia (IED, also known as tufting enteropathy, is a congenital enteropathy presenting with early-onset severe intractable diarrhea causing sometimes irreversible intestinal failure. To date, no epidemiological data are available, however, the prevalence can be estimated at around 1/50,000–100,000 live births in Western Europe. The prevalence seems higher in areas with high degree of consanguinity and in patients of Arabic origin. Infants develop within the first days after birth a watery diarrhea persistent in spite of bowel rest and parenteral nutrition. Some infants are reported to have associated choanal rectal or esophageal atresia. IED is thought to be related to abnormal enterocytes development and/or differentiation. Nonspecific punctuated keratitis was reported in more than 60% of patients. Histology shows various degree of villous atrophy, with low or without mononuclear cell infiltration of the lamina propria but specific histological abnormalities involving the epithelium with disorganization of surface enterocytes with focal crowding, resembling tufts. Several associated specific features were reported, including abnormal deposition of laminin and heparan sulfate proteoglycan (HSPG in the basement membrane, increased expression of desmoglein and ultrastructural changes in the desmosomes, and abnormal distribution of α2β1 integrin adhesion molecules. One model of transgenic mice in which the gene encoding the transcription factor Elf3 is disrupted have morphologic features resembling IED. Parental consanguinity and/or affected siblings suggest an autosomal recessive transmission but the causative gene(s have not been yet identified making prenatal diagnosis unavailable. Some infants have a milder phenotype than others but in most patients, the severity of the intestinal malabsorption even with enteral feeding make them totally dependent on daily long-term parenteral nutrition with a subsequent

  11. Modulation of Cytokine mRNA Expression in Pharyngeal Epithelial Samples obtained from Cattle Infected with Foot-and-Mouth Disease Virus

    DEFF Research Database (Denmark)

    Stenfeldt, Anna Carolina; Heegaard, Peter M. H.; Stockmarr, Anders

    2012-01-01

    A novel technique of endoscopical collection of small tissue samples was used to obtain sequential tissue samples from the dorsal soft palate (DSP) of individual cattle infected with foot-and-mouth disease virus (FMDV) at different phases of the infection. Levels of mRNA encoding interferon (IFN...

  12. Diagnosis and treatment outcome of mycotic keratitis at a tertiary eye care center in eastern india

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    Rautaraya Bibhudutta

    2011-12-01

    Full Text Available Abstract Background Mycotic keratitis is an important cause of corneal blindness world over including India. Geographical location and climate are known to influence the profile of fungal diseases. While there are several reports on mycotic keratitis from southern India, comprehensive clinico-microbiological reports from eastern India are few. The reported prevalence of mycotic keratitis are 36.7%,36.3%,25.6%,7.3% in southern, western, north- eastern and northern India respectively. This study reports the epidemiological characteristics, microbiological diagnosis and treatment outcome of mycotic keratitis at a tertiary eye care center in eastern India. Methods A retrospective review of medical and microbiology records was done for all patients with laboratory proven fungal keratitis. Results Between July 2006 and December 2009, 997 patients were clinically diagnosed as microbial keratitis. While no organisms were found in 25.4% (253/997 corneal samples, 23.4% (233/997 were bacterial, 26.4% (264/997 were fungal (45 cases mixed with bacteria, 1.4% (14/997 were Acanthamoeba with or without bacteria and 23.4% (233/997 were microsporidial with or without bacteria. Two hundred fifteen of 264 (81.4%, 215/264 samples grew fungus in culture while 49 corneal scrapings were positive for fungal elements only in direct microscopy. Clinical diagnosis of fungal keratitis was made in 186 of 264 (70.5% cases. The microscopic detection of fungal elements was achieved by 10% potassium hydroxide with 0.1% calcoflour white stain in 94.8%(238/251 cases. Aspergillus species (27.9%, 60/215 and Fusarium species (23.2%, 50/215 were the major fungal isolates. Concomitant bacterial infection was seen in 45 (17.1%, 45/264 cases of mycotic keratitis. Clinical outcome of healed scar was achieved in 94 (35.6%, 94/264 cases. Fifty two patients (19.7%, 52/264 required therapeutic PK, 9 (3.4%, 9/264 went for evisceration, 18.9% (50/264 received glue application with bandage

  13. Recent Outbreaks of Atypical Contact Lens-Related Keratitis: What Have We Learned?

    Science.gov (United States)

    Tu, Elmer Y.; Joslin, Charlotte E

    2010-01-01

    Purpose To examine the public health implications of two recent outbreaks of atypical contact lens-related infectious keratitis. Design A perspective based on the literature and authors’ experience. Results The contact lens-related fusarium and acanthamoeba keratitis outbreaks were both detected by dramatic rises seen in tertiary care centers in Singapore and the US, respectively. Case control studies in both outbreaks each were able to identify a strong association with the use of different contact lens disinfection solutions. Their respective recalls resulted in a steep decline of fusarium keratitis, but not of acanthamoeba keratitis. Early investigations into each solution association implicate components not directly related to their primary disinfectant, but the true pathogenesis remains unknown. However, the number of Acanthamoeba cases individually attributed to each of almost all available disinfection systems exceeds previously understood total US incidence, suggesting other risk factors. Current standards do not require demonstration of anti-acanthamoebal activity. Yet, despite the inclusion of fusarium in mandatory testing for solutions, current pre-market testing was not predictive of the outbreak. Conclusions The two recent outbreaks of atypical contact-lens related keratitis have reinforced the value of tertiary care eye care centers in detecting early rises in rare infections and the power of adaptable, well-designed epidemiologic investigations. While fusarium keratitis has significantly declined with the recall of Renu with Moistureloc, the persistence of Acanthamoeba keratitis begs fundamental changes in contact lens hygiene practices, inclusion of acanthamoeba as a test organism and contact lens disinfectant test regimens for all contact lens–related pathogens which are verifiably reflective of end user contact lens wear complications. PMID:21036209

  14. BACTERIOLOGY AND RISK FACTORS OF BACTERIAL KERATITIS IN JIMMA, SOUTHWEST ETHIOPIA.

    Science.gov (United States)

    Gebremariam, Tewelde Tesfaye

    2015-10-01

    In East Africa, particularly in Ethiopia, bacterial keratitis is a major cause of blindness. The aims of this study were to identify risk factors of bacterial keratitis and the spectrum of bacterial etiologies, and to assess the in-vitro antimicrobial susceptibility of these bacterial isolates at Jimma University Specialized Hospital, Southwest Ethiopia. A prospective study was employed from January 2012 to June 2012 from which a total of 24 patients with bacterial keratitis were included in the study. Corneal scrapings were collected, transported and microbiologically processed using standard operating procedures. Four different predisposing factors for bacterial keratitis were identified: corneal trauma 9 (37.5%), blepharitis 7 (29.2%), herpetic keratitis, and use of contaminated medications 4. Bilateral corneal infection was found in 5 (20.8%) of the cases. A total of 24 corneal scrapings were collected for microbiological evaluation, of which 20 (83%) had bacterial growth. The isolated bacterial pathogens were Pseudomonas aeruginosa 10 (41.7%), Staphyloccus aureus 5 (20.8%), Serratia marcescens 3 (12.5%), followed by Streptococcus pneumoniae 2 (8.3%). Antimicrobial susceptibility testing revealed that 85% of Gram-negative bacilli were susceptible to gentamicin and ciprofloxacin, while 86% of Gram-positive cocci were susceptible to vancomycin and Ciprofloxacin. Corneal trauma was the most common risk factor for bacterial keratitis followed by blepharitis. Bacteriological analysis of corneal scrapings also revealed that P. aeruginosa was the most common isolate followed by S. aureus; the antibiotic with the highest susceptibility was ciprofloxacin. As drug resistance among bacterial pathogens is an evolving process, routine surveillance and monitoring studies should be conducted to provide an update and most effective empirical treatment for bacterial keratitis.

  15. Super-Cationic Carbon Quantum Dots Synthesized from Spermidine as an Eye Drop Formulation for Topical Treatment of Bacterial Keratitis.

    Science.gov (United States)

    Jian, Hong-Jyuan; Wu, Ren-Siang; Lin, Tzu-Yu; Li, Yu-Jia; Lin, Han-Jia; Harroun, Scott G; Lai, Jui-Yang; Huang, Chih-Ching

    2017-07-25

    We have developed a one-step method to synthesize carbon quantum dots (CQDPAs) from biogenic polyamines (PAs) as an antibacterial agent for topical treatment of bacterial keratitis (BK). CQDs synthesized by direct pyrolysis of spermidine (Spd) powder through a simple dry heating treatment exhibit a solubility and yield much higher than those from putrescine and spermine. We demonstrate that CQDs obtained from Spds (CQDSpds) possess effective antibacterial activities against non-multidrug-resistant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella enterica serovar Enteritidis bacteria and also against the multidrug-resistant bacteria, methicillin-resistant S. aureus. The minimal inhibitory concentration (MIC) of CQDSpds is ∼2500-fold lower than that of spermidine alone, demonstrating their strong antibacterial capabilities. Investigation of the possible mechanisms behind the antibacterial activities of the as-synthesized CQDSpds indicates that the super-cationic CQDSpds with small size (diameter ca. 6 nm) and highly positive charge (ζ-potential ca. +45 mV) cause severe disruption of the bacterial membrane. In vitro cytotoxicity, hemolysis, hemagglutination, genotoxicity, and oxidative stress and in vivo morphologic and physiologic cornea change evaluations show the good biocompatibility of CQDSpds. Furthermore, topical ocular administration of CQDSpds can induce the opening of the tight junction of corneal epithelial cells, thereby leading to great antibacterial treatment of S. aureus-induced BK in rabbits. Our results suggest that CQDSpds are a promising antibacterial candidate for clinical applications in treating eye-related bacterial infections and even persistent bacteria-induced infections.

  16. Induction of IL-6 and CCL5 (RANTES in human respiratory epithelial (A549 cells by clinical isolates of respiratory syncytial virus is strain specific

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    Levitz Ruth

    2012-09-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the major respiratory pathogen of infants and young children. During each seasonal epidemic, multiple strains of both subgroup A and B viruses circulate in the community. Like other RNA viruses, RSV genome replication is prone to errors that results in a heterogeneous population of viral strains some of which may possess differences in virulence. We sought to determine whether clinical isolates of RSV differ in their capacity to induce inflammatory cytokines IL-6 and CCL5 (previously known as RANTES [regulated upon activation, normal T-cell expressed and secreted protein], which are known to be induced in vitro and in vivo in response to RSV, during infection of A549 cells. Results Screening of subgroup A and B isolates revealed heterogeneity among strains to induce IL-6 and CCL5. We chose two subgroup B strains, New Haven (NH1067 and NH1125, for further analysis because of their marked differences in cytokine inducing properties and because subgroup B strains, in general, are less genetically heterogeneous as compared to subgroup A strains. At 12 and 24 hours post infection RSV strains, NH1067 and NH1125 differed in their capacity to induce IL-6 by an order of magnitude or more. The concentrations of IL-6 and CCL5 were dependent on the dose of infectious virus and the concentration of these cytokines induced by NH1125 was greater than that of those induced by NH1067 when the multiplicity of infection of NH1067 used was as much as 10-fold higher than that of NH1125. The induction of IL-6 was dependent on viable virus as infection with UV-inactivated virus did not induce IL-6. The difference in IL-6 induction most likely could not be explained by differences in viral replication kinetics. The intracellular level of RSV RNA, as determined by quantitative RT-PCR, was indistinguishable between the 2 strains though the titer of progeny virus produced by NH1125 was greater than that produced by

  17. Fusarium sacchari, a cause of mycotic keratitis among sugarcane farmers - a series of four cases from North India

    NARCIS (Netherlands)

    Bansal, Yashik; Chander, Jagdish; Kaistha, Neelam; Singla, Nidhi; Sood, Sunandan; van Diepeningen, Anne D

    2016-01-01

    The two most common filamentous fungi causing mycotic keratitis are Aspergillus and Fusarium spp. Around 70 Fusarium spp. are involved in causing human infections. In this study, four cases of keratitis in sugarcane farmers in India are being reported, caused by the sugar cane pathogen Fusarium

  18. Morphological changes in the meibomian glands of patients with phlyctenular keratitis: a multicenter cross-sectional study.

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    Suzuki, Takashi; Morishige, Naoyuki; Arita, Reiko; Koh, Shizuka; Sakimoto, Tohru; Shirakawa, Rika; Miyata, Kazunori; Ohashi, Yuichi

    2016-10-10

    Phlyctenular keratitis is a hypersensitivity reaction of the cornea, and a complication of eyelid margin disease in children and young adults. In this study, we compared the morphology of the meibomian glands in eyelids between phlyctenular keratitis patients and healthy young adults, using noncontact meibography. The study included 16 eyes of 13 patients diagnosed with phlyctenular keratitis and 17 eyes of 17 healthy volunteers. Slit-lamp observations of the cornea and eyelid were performed on all subjects. The morphology of the meibomian glands was scored using non-contact meibography (meiboscore). The meiboscore in worse eye was used in bilateral phlyctenular keratitis. All eyes with phlyctenular keratitis, but not normal controls, showed corneal nodules, neovascularization, and superficial punctate keratopathy. The mean meiboscore in phlyctenular keratitis patients (upper lid: 2.9 ± 0.3, lower lid: 2.7 ± 0.5) was significantly higher than in controls (upper lid: 0.4 ± 0.6, lower lid: 0.1 ± 0.3). Noncontact meibography enabled visualization of meibomian gland loss in phlyctenular keratitis patients, suggesting a relationship between abnormalities of the meibomian glands in young individuals and the pathogenesis of phlyctenular keratitis.

  19. Imaging Keratitis-Icthyosis-Deafness (KID) syndrome with FDG-PET (F18-fluorodeoxiglucose-Positron Emission Tomography).

    Science.gov (United States)

    Aparici, Carina Mari; Arcienega, Daniela; Cho, Eric; Hawkins, Randy

    2010-01-01

    Keratitis-Icthyosis-Deafness (KID) syndrome is a rare dysplasia characterized by vascularizing keratitis, congenital sensorineural hearing-loss, and progressive erythrokeratoderma. To our knowledge, this is the first KID syndrome imaged with FDG-PET in the literature. This paper is intended to help familiarize with the FDG abnormalities related to this rare entity.

  20. Severe microbial keratitis and associated perforation after corneal crosslinking for keratoconus.

    Science.gov (United States)

    Rana, M; Lau, A; Aralikatti, A; Shah, S

    2015-04-01

    To report two cases of microbial keratitis with subsequent corneal perforation immediately following corneal collagen crosslinking (CXL). Retrospective case note review. First case was a 19 year old female presented with staphylococcal corneal abscess 3 days post CXL procedure. Corneal perforation occurred during hospital admission and was successfully treated with corneal gluing. Microbial keratitis eventually resolved, with both topical and systemic antibiotics therapy, resulting in a vascularized corneal scar. Second case was an 18 year old male whom developed Methicillin Resistant Staphylococcus aureus (MRSA) corneal abscess 5 days after CXL procedure for progressive keratoconus. Corneal perforation occurred 48 h after presentation and patient underwent uneventful corneal gluing. Although infective keratitis was successfully treated with topical therapy, patient had visual outcome of count fingers due to scarring. CXL has been widely used in the treatment of corneal ectatic conditions and complications, such as infective keratitis, are uncommon post procedure. We present two cases of severe microbial keratitis with subsequent corneal perforation within 7 days of CXL. The exact mechanism for the accelerated keratolysis process is unclear. Nonetheless, patients should be well-informed of such potentially devastating complication. Copyright © 2014. Published by Elsevier Ltd.

  1. Synthetic β-sheet forming peptide amphiphiles for treatment of fungal keratitis.

    Science.gov (United States)

    Wu, Hong; Ong, Zhan Yuin; Liu, Shaoqiong; Li, Yan; Wiradharma, Nikken; Yang, Yi Yan; Ying, Jackie Y

    2015-03-01

    Fungal keratitis is a leading cause of ocular morbidity. It is frequently misdiagnosed as bacterial keratitis, causing a delay in proper treatment. Furthermore, due to the lack of safe and effective anti-fungal agents for clinical use, treatment of fugal keratitis remains a challenge. In recent years, antimicrobial peptides (AMPs) have received considerable attention as potent and broad-spectrum antimicrobial agents with the potential to overcome antibiotics resistance. We previously reported the design of short synthetic β-sheet forming peptides (IKIK)2-NH2 and (IRIK)2-NH2 with excellent antimicrobial activities and selectivities against various clinically relevant microorganisms, including Gram-positive Staphylococcus epidermidis and Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and yeast Candida albicans (C. albicans). In this study, we evaluated the application of the two most promising synthetic β-sheet forming peptide candidates for in vivo fungal keratitis treatment in comparison with the commercially available amphotericin B. It was found that topical solutions of the designed peptides are safe, and as effective as the clinically used amphotericin B. Compared to the costly and unstable amphotericin B, (IKIK)2-NH2 and (IRIK)2-NH2 are water-soluble, less expensive and stable. Thus, the synthetic β-sheet forming peptides are presented as promising candidates for the treatment of fungal keratitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. A Multi-Center, Cross-Sectional Study on the Burden of Infectious Keratitis in China

    Science.gov (United States)

    Song, Xiusheng; Xie, Lixin; Tan, Xiaodong; Wang, Zhichong; Yang, Yanning; Yuan, Yuansheng; Deng, Yingping; Fu, Shaoying; Xu, Jianjiang; Sun, Xuguang; Sheng, Xunlun; Wang, Qing

    2014-01-01

    Objective To understand the prevalence and demographic characteristics of infectious keratitis and infectious corneal blindness. Methods A multi-center, population-based cross-sectional study was conducted from January 1 to August 31, 2010. A total of 191,242 individuals of all age groups from 10 geographically representative provinces were sampled using stratified, multi-stage, random and systematic sampling procedures. A majority, 168,673 (88.2%), of those sampled participated in the study. The examination protocol included a structured interview, visual acuity testing, an external eye examination, and an anterior segment examination using a slit lamp. The causes and sequelae of corneal disease were identified using uniform customized protocols. Blindness in one eye caused by infectious keratitis was defined as infectious corneal blindness. Results The prevalence of past and active infectious keratitis was 0.192% (95% confidence interval [CI], 0.171–0.213%), and the prevalence of viral, bacterial, and fungal keratitis was 0.11%, 0.075%, and 0.007%, respectively. There were 138 cases of infectious corneal blindness in at least one eye in the study population (prevalence of 0.082% [95%CI, 0.068%–0.095%]). Statistical analysis suggested that ocular trauma, alcoholic consumption, low socioeconomic levels, advanced age, and poor education were risk factors for infectious corneal blindness. Conclusions Infectious keratitis is the leading cause of corneal blindness in China. Eye care strategies should focus on the prevention and rehabilitation of infectious corneal blindness. PMID:25438169

  3. Fungal keratitis and contact lenses: an old enemy unrecognized or a new nemesis on the block?

    Science.gov (United States)

    Tuli, Sonal S; Iyer, Sandhya A; Driebe, William T

    2007-11-01

    To review studies of fungal keratitis related to contact lenses and determine whether the recent insurgence is a new phenomenon or an exacerbation of an ongoing trend. A review of the recent literature on contact lens-related fungal ulcers and a comparison to older studies. The incidence of fungal keratitis associated with contact lenses increased from 5% in the 1980s to between 10% and 25% in the 1990s and was noted to be 44% in Florida at the turn of the century. The most recent study from Florida showed that the incidence had increased from 29% in the late 1990s to 52% in the early 2000s, even before the Fusarium keratitis epidemic in 2004 and 2005. This increase mainly represented an increase in the number related to nontherapeutic contact lenses. Contact lens-related fungal keratitis was relatively rare 20 years ago. However, the incidence has progressively increased since then. Contact lens-related fungal ulcers had become more common even before the recent Fusarium keratitis epidemic. This change may be related to changing contact lens care habits and younger patients being fitted with contact lenses.

  4. Time-dependent matrix metalloproteinases and tissue inhibitor of metalloproteinases expression change in fusarium solani keratitis.

    Science.gov (United States)

    Li, Qian; Gao, Xin-Rui; Cui, Hong-Ping; Lang, Li-Li; Xie, Xiu-Wen; Chen, Qun

    2016-01-01

    To investigate matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression during the progress of fusarium solani (F.solani) keratitis in a rat model. A rat model of F.solani keratitis was produced using corneal scarification and a hand-made contact lens. MMPs and TIMPs expressiond were explored in this rat model of F.solani keratitis using real-time polymerase chain reaction (PCR) and DIF. GM6001 (400 µmol/mL) was used to treat infected corneas. The keratitis duration, amount and area of corneal neovascularization (CNV) were evaluated. MMP-3 expression was 66.3 times higher in infected corneas compared to normal corneas. MMP-8, -9, and -13 expressions were significantly upregulated in the mid-period of the infection, with infected-to-normal ratios of 4.03, 39.86, and 5.94, respectively. MMP-2 and -7 expressions increased in the late period, with the infected-to-normal ratios of 5.94 and 16.22, respectively. TIMP-1 expression was upregulated in the early period, and it was 43.17 times higher in infected compared to normal corneas, but TIMP-2, -3, and -4 expressions were mildly downregulated or unchanged. The results of DIF were consistent with the result of real-time PCR. GM6001, a MMPs inhibitor, decreased the duration of F.solani infection and the amount and area of CNV. MMPs and TIMPs contributed into the progress of F.solani keratitis.

  5. Epidemiological typing of Acanthamoeba strains isolated from keratitis cases in Belgium.

    Science.gov (United States)

    De Jonckheere, J F

    2003-01-01

    From the corneas of nine keratitis patients and from their contact lenses, contact lens boxes and saline solutions, 15 strains of Acanthamoeba have been isolated. An Acanthamoeba strain was isolated from the swimming pool where one of the patients swam, while in the tapwater of the houses of three patients investigated, no Acanthamoeba could be detected. All the Acanthamoeba isolates from the cornea belong to genotype T4, but are different subtypes of T4. The Acanthamoeba detected on the contact lenses (and/or associated paraphernalia) of a patient are of the same subtype as that isolated from the cornea. The only Acanthamoeba strain isolated from a contact lens which was not related to an Acanthamoeba keratitis infection proved to be another genotype. A strain of Hartmannella from a cornea and two vahlkampfiids isolated from contact lenses had no connection with keratitis. This study confirms that, as found elsewhere, only Acanthamoeba genotype T4 of the 12 known Acanthamoeba genotypes is responsible for keratitis in Belgium. Most cases of Acanthamoeba keratitis cases are due to poor hygiene in the treatment (cleaning and storage) of contact lenses.

  6. The relationship of graft survival and herpes simplex virus latency in recipient corneal buttons

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    Orhan Aydemir

    2007-10-01

    Full Text Available Orhan Aydemir1, Peykan Türkçüoglu1, Yasemin Bulut2, Ahmet Kalkan31Firat University School of Medicine, Department of Ophthalmology, Elazig, Turkey; 2Firat University School of Medicine, Department of Microbiology, Elazig, Turkey; 3Firat University School of Medicine, Department of Infectious Diseases, Elazig, TurkeyPurpose: To demonstrate relationship between herpes simplex virus (HSV corneal latency and graft survival.Methods: Prospective case control study. 28 recipient corneal buttons and donor cornea-scleral remnants were examined for HSV DNA with polymerase chain reaction (PCR. None of the recipient had a history of HSV infection. Serum samples of graft recipients were analyzed for the presence of anti-HSV IgG and IgM with enzyme-linked immunosorbent assay technique. All corneas were free of stromal scarring or epithelial defect before sampling and had an endothelial cell density of >2000 cells/mm2.Results: In twenty three patients (82% anti-HSV IgG was detected in serum. In none of the recipients anti-HSV IgM was positive. HSV DNA was positive in six out of twenty eight (21% of the recipient corneal buttons and none of the donor cornea-scleral remnants. In eighteen months follow-up period three out of six (50% HSV DNA positive and one out of twenty-two (4.5% HSV DNA negative patients experienced late endothelial failure that was statistically significantly different (p = 0.022. Conclusion: Even without a history of HSV keratitis, presence of latent HSV virus in recipient cornea is an important risk factor for subsequent graft survival.Keywords: herpes simplex virus, polymerase chain reaction, corneal latency, corneal graft survival

  7. Identification of epithelial cells in bronchoalveolar lavage.

    Science.gov (United States)

    Finotto, S; Rado, V; Dal Vecchio, A; Milani, G; Fabbri, L M; Maestrelli, P

    1993-01-01

    1. Damage to the bronchial epithelium occurs after the inhalation of toxic substances and allergens, and through virus infections and it may lead to increased desquamation of epithelial cells in bronchoalveolar lavage (BAL). 2. In this study we compared two methods of staining the epithelial cells of BAL, the conventional cytochemical May Grunwald-Giemsa stain (MGG) and an immunocytochemical technique using a monoclonal antibody anti-human cytokeratin (CK) detected with APAAP immuno-alkaline phosphatase. BAL was obtained from 13 subjects and the epithelial cells were cytocentrifuged either immediately after collection (fraction A) or after washing (fraction B). 3. Higher percentages of epithelial cells were identified in fraction A with CK (20.0 +/- 5.1%) than in fraction A with MGG (11.2 +/- 2.3%), which recognized only ciliated epithelial cells. In fact a proportion of CK-positive cells (34%) in fraction A were not ciliated. Underestimation of epithelial cells by MGG compared to CK was more pronounced in fraction B (8.0 +/- 2.9% and 22.9 +/- 3.0%, respectively) as there was a relative loss of ciliated CK+ cells after washings. 4. These results suggest that immunocytochemical staining with an anti-cytokeratin monoclonal antibody is more sensitive than using the MGG stain in detecting epithelial cells in BAL.

  8. Acanthamoeba keratitis: study of the 5-year incidence in Israel.

    Science.gov (United States)

    Graffi, Shmuel; Peretz, Avi; Jabaly, Haneen; Koiefman, Anna; Naftali, Modi

    2013-11-01

    Acanthamoeba keratitis (AK) is not a notifiable disease in Israel, so there are no accurate incidence rates for this condition in Israel. The aim of this study was to estimate the incidence of AK in Israel for the years 2008-2012. We distributed a survey questionnaire to laboratory managers in Israel. The laboratories were affiliated to medical institutes that either provided ophthalmology services or served community ophthalmology clinics. Our questionnaire requested survey respondents to provide information regarding the methods used to diagnose AK, and the number of positive and negative cultures for Acanthamoebae species performed for each of the years from 2008 to 2012. Six laboratories used non-nutrient agar with Escherichia coli as the culture medium, one used calcofluor-white staining with fluorescent microscopy, and two used PCR for diagnosing AK. Twenty-three AK cases were identified, to give an estimated incidence of 1/1 668 552. AK is mostly attributable to the use of contact lenses. As contact lenses are popular in Israel, we expected a higher incidence rate. A lower than expected incidence rate may indicate insufficient awareness of AK in Israel.

  9. Successful treatment of Fusarium keratitis after photo refractive keratectomy

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    Gian Maria Cavallini

    2013-01-01

    Full Text Available A 39-year-old woman presented to our hospital with a history of photorefractive keratectomy (PRK, performed two weeks prior; slit-lamp examination revealed diffuse conjunctival congestion, corneal ulcer and stromal infiltration. After 5 days of antifungal and antibacteric treatment, the infiltrate progressively increased so that a therapeutic penetrating keratoplasty was necessary. The microbiological analyses revealed the presence of fungal filaments. Twenty days after surgery the patient had recurrent fungal infiltrate in the donor cornea with wound dehiscence. We performed a second penetrating keratoplasty. With the matrix-assisted-laser-desorption-ionization-time-of-flight analysis (MALDI-TOF we identified a Fusarium solani.Intravenous amphothericine B, a combination of intracameral and intrastromal voriconazole and intracameral amphotericine B were administered. After 6 months from the last surgery the infection was eradicated. The management of fungal keratitis after PRK depends on many factors: In our experience, a prompt keratoplasty and the use of intracameral antifungal medication proved to be very effective.

  10. Lamellar Diffuse Keratitis. Its management and clinical evolution.

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    Jenny García Milián

    2009-12-01

    Full Text Available The new advances in Refractive Surgery have led to an increment in the indications of the LASIK, but also of their complications. Among the postoperative complications, Diffuse Lamellar Keratitis (DLK can occur with a frequency of approximately between 1.8% and 12% of the cases. The objective of this work is to describe the behavior of DLK in patients intervened by the LASIK technique and its clinical evolution. A retrospective cross-sectional descriptive study was made of 5 cases of DLK observed in 253 patients (eyes operated by Lasik in the Ophthalmological Center of Sancti Spíritus between April 3 2008 and April 9 2009. The studied variables were: associated risk factors, beginning of clinical assessment in days, reached stage, type of treatment, duration and time of follow-up and visual results. In the 5 studied cases an average beginning of clinical assessment was observed at 3 days with blurred vision and slight ocular troubles, all were treated with steroidal antinflamatory drugs topically administered obtaining a mean AVC/SC preQX =0, 98 AV mean last control =0, 94, and a average duration of treatment of 15 days, with stages I and II being the ones that prevailed in the sample. It has been shown that DLQ is a complication that can be innocuous for visual results after the application of LASIK, if it is treated appropriately and in an early way.

  11. Chlorhexidine Keratitis: Safety of Chlorhexidine as a Facial Antiseptic.

    Science.gov (United States)

    Steinsapir, Kenneth D; Woodward, Julie A

    2017-01-01

    Effective antiseptic to reduce surgical site infections is a cornerstone of modern surgery. Chlorhexidine gluconate-based antiseptics are among the most effective of these products. Unfortunately, chlorhexidine solutions are toxic to the cornea and middle ear, and they pose a splash risk to both the patient and health care personnel. To examine the clinical evidence that led to the disavowal of chlorhexidine antiseptic solution for use on the face and head. Reference searches were performed using PubMed, Embase, and LexisNexis databases without restriction to the date of publication, language, or study setting. The literature revealed 11 sentinel cases of severe chlorhexidine-related keratitis in the late 1980s. These cases are reviewed together with data on ototoxicity and alternative products to understand why chlorhexidine solution should not be used on the face and scalp. Chlorhexidine antiseptic solutions are highly effective. However, they pose a risk to the middle ear and have the potential to irreversibly damage the cornea with a minimal splash exposure. Povidone-iodine is a safe and effective alternative.

  12. Role of steroids in the treatment of bacterial keratitis

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    Palioura S

    2016-01-01

    Full Text Available Sotiria Palioura, Christopher R Henry, Guillermo Amescua, Eduardo C AlfonsoDepartment of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: Bacterial keratitis can lead to severe visual impairment from corneal ulceration, subsequent scarring, and possible perforation. The mainstay of treatment is topical antibiotics, whereas the use of adjunctive topical corticosteroid drops remains a matter of debate. Herein, we review the rationale for and against the use of topical corticosteroids and we assess their effectiveness and safety in the published randomized controlled trials that have evaluated their role as adjunctive therapy for bacterial corneal ulcers. In the largest study to date, the Steroids for Corneal Ulcers Trial, topical corticosteroid drops were neither helpful nor harmful for the 500 participants as a whole. However, subgroup analyses suggested that topical corticosteroids may be beneficial upon early administration (within 2–3 days after starting antibiotics for more central corneal ulcers with poorer vision at presentation, for invasive Pseudomonas strains, and for non-Nocardia ulcers. These results are discussed within the limitations of the study.Keywords: topical corticosteroids, corneal ulcer, eye infection, antibiotic, endophthalmitis, perforation

  13. Keratitis Due to Achromobacter xylosoxidans in a Contact Lens User.

    Science.gov (United States)

    Almenara Michelena, Cristina; Del Buey, María Ángeles; Ascaso, Francisco Javier; Cristóbal, Jose Ángel

    2017-03-27

    Ocular infections due to Achromobacter xylosoxidans are extremely uncommon; their diagnosis is a challenge and the optimal treatment remains controversial. We present a case of A. xylosoxidans in a contact lens user and a review of the literature to facilitate diagnostic suspicion and empirical therapeutic management. Review of the literature in PubMed and MEDLINE. We also document a case diagnosed in our department in January 2016. Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain. According to the literature, clinical manifestations and antibiotic sensitivity of A. xylosoxidans varied greatly. Our patient with no history of keratopathy presented three risk factors that made the diagnosis suspicious. The infection was resolved with topical moxifloxacin and fluorometholone. A. xylosoxidans is an uncommon cause of infection, but must be suspected in atypical keratitis, reported contact with warm or still waters, use of contact lenses, or previous corneal damage. In these cases, microbiological studies and antibiotic sensitivity testing are particularly important.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  14. Treatment with voriconazole in 3 eyes with resistant Acanthamoeba keratitis.

    Science.gov (United States)

    Bang, Stacy; Edell, Erica; Eghrari, Allen O; Gottsch, John D

    2010-01-01

    To report the use of topical voriconazole 1% (Vfend; Pfizer Inc, New York, New York, USA) ophthalmic solution for Acanthamoeba keratitis (AK) resistant to treatment with chlorhexidine (PerioChip; Dexel Pharma Technologies, Jerusalem, Israel). Retrospective case series. Three eyes of 2 patients with culture-proven AK were treated at a tertiary care institution, and their charts were reviewed. Topical voriconazole 1% was instituted as second-line treatment for AK unresponsive to standard treatment with chlorhexidine and hexamidine. Treatment with voriconazole 1% was started at 1-hour intervals. Improvement was assessed and defined by absence of clinical signs of active infection and visual improvement. One patient with unilateral AK and 1 patient with bilateral AK who remained culture-positive for Acanthamoeba despite ongoing treatment with chlorhexidine and hexamidine were treated with voriconazole 1% topical solution as an adjuvant. Both patients were contact lens wearers. Of 3 eyes additionally treated with voriconazole, 2 eyes had clinical resolution of disease. One eye demonstrated recurrent disease after penetrating keratoplasty that resolved after intrastromal injection of voriconazole. We report the use of topical and intrastromal voriconazole in successfully treating AK in cases of chlorhexidine- and hexamidine-resistant Acanthamoeba. Voriconazole may be a promising adjuvant agent in treating AK. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Fusarium dimerum Species Complex (Fusarium penzigii) Keratitis After Corneal Trauma.

    Science.gov (United States)

    do Carmo, Anália; Costa, Esmeralda; Marques, Marco; Quadrado, Maria João; Tomé, Rui

    2016-12-01

    We report a case of a keratitis associated with a Fusarium penzigii-a Fusarium dimerum species complex (FDSC)-in a 81-year-old woman after a corneal trauma with a tree branch. At patient admittance, slit lamp biomicroscopy revealed an exuberant chemosis, an inferior corneal ulcer with an associated inflammatory infiltrate, a central corneal abscess, bullous keratopathy and posterior synechiae. Corneal scrapes were obtained for identification of bacteria and fungi, and the patient started antibiotic treatment on empirical basis. Few days later, the situation worsened with the development of hypopyon. By that time, Fusarium was identified in cultures obtained from corneal scrapes and the patient started topical amphotericin B 0.15 %. Upon the morphological identification of the Fusarium as a FDSC, and since there was no clinical improvement, the treatment with amphotericin B was suspended and the patient started voriconazole 10 mg/ml, eye drops, hourly and voriconazole 200 mg iv, every 12 h for 1 month. The hypopyon resolved and the inflammatory infiltrate improved, but the abscess persisted at the last follow-up visit. The molecular identification revealed that the FDSC was a F. penzigii.

  16. Clinical Efficacy of Oral Ganciclovir for Prophylaxis and Treatment of Recurrent Herpes Simplex Keratitis

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2015-01-01

    Full Text Available Background: Herpes simplex keratitis (HSK caused by herpes simplex virus 1 (HSV-1, which has high recurrent rate and incidence of severe vision loss, is the leading cause of infectious blindness in the world. The aim was to explore the clinical efficacy of oral ganciclovir (GCV in the prevention of recurrent HSK. Methods: A multicenter, prospective, randomized, single-blind, and controlled clinical trial was conducted from April 2010 to June 2013. One hundred seventy-three patients (173 eyes involved who were diagnosed as recurrent HSK definitely, including stromal keratitis and corneal endotheliitis, were divided into three groups randomly: negative control (placebo group was topically administered with 0.15% GCV ophthalmic gel, 4 times per day and 0.1% fluorometholone eye drops, 3 times per day until resolution of HSK; positive control acyclovir (ACV group was topically adopted the same ophthalmic gel and eye drops and additionally received oral ACV 400 mg 5 times a day for 10 weeks and followed by 400 mg 2 times per day for 6 months; test GCV group was topically adopted the same treatment as negative control group and additionally received oral GCV 1000 mg 3 times per day for 8 weeks. The symptoms and signs were evaluated before and after the therapy 1 st week, 2 nd week and then followed up every 2 weeks until recovery. Furthermore, we followed up recurrence of HSK for every 3 months after recovery and then assessed the cure time, recurrent rate and adverse reactions. Results: One hundred and seventy-three patients were followed up 7-48 months (mean 32.1 ± 12.3 months, but 34 patients were failed to follow-up. The cure time was 12.1 ± 4.3, 11.9 ± 4.0 weeks in negative control (placebo group and positive control ACV group respectively (P = 0.991, which was longer than that in test GCV group (8.6 ± 2.8 weeks and there was a significant difference between test GCV group and negative control (placebo group or positive control ACV group (P

  17. Clinical efficacy of oral ganciclovir for prophylaxis and treatment of recurrent herpes simplex keratitis.

    Science.gov (United States)

    Wang, Xin; Wang, Linnong; Wu, Nianlang; Ma, Xinjun; Xu, Jianjiang

    2015-01-05

    Herpes simplex keratitis (HSK) caused by herpes simplex virus 1 (HSV-1), which has high recurrent rate and incidence of severe vision loss, is the leading cause of infectious blindness in the world. The aim was to explore the clinical efficacy of oral ganciclovir (GCV) in the prevention of recurrent HSK. A multicenter, prospective, randomized, single-blind, and controlled clinical trial was conducted from April 2010 to June 2013. One hundred seventy-three patients (173 eyes involved) who were diagnosed as recurrent HSK definitely, including stromal keratitis and corneal endotheliitis, were divided into three groups randomly: negative control (placebo) group was topically administered with 0.15% GCV ophthalmic gel, 4 times per day and 0.1% fluorometholone eye drops, 3 times per day until resolution of HSK; positive control acyclovir (ACV) group was topically adopted the same ophthalmic gel and eye drops and additionally received oral ACV 400 mg 5 times a day for 10 weeks and followed by 400 mg 2 times per day for 6 months; test GCV group was topically adopted the same treatment as negative control group and additionally received oral GCV 1000 mg 3 times per day for 8 weeks. The symptoms and signs were evaluated before and after the therapy 1 st week, 2 nd week and then followed up every 2 weeks until recovery. Furthermore, we followed up recurrence of HSK for every 3 months after recovery and then assessed the cure time, recurrent rate and adverse reactions. One hundred and seventy-three patients were followed up 7-48 months (mean 32.1 ± 12.3 months), but 34 patients were failed to follow-up. The cure time was 12.1 ± 4.3, 11.9 ± 4.0 weeks in negative control (placebo) group and positive control ACV group respectively (P = 0.991), which was longer than that in test GCV group (8.6 ± 2.8 weeks) and there was a significant difference between test GCV group and negative control (placebo) group or positive control ACV group (P = 0.000). Furthermore, the recurrent rate

  18. Mycobacterium aurum keratitis: an unusual etiology of a sight-threatening infection

    Directory of Open Access Journals (Sweden)

    Behnam Honarvar

    Full Text Available Atypical fast-growing Mycobacterium species are usually identified after laser-assisted in situ keratomileusis, cosmetic surgeries, and catheter-related, pulmonary or soft tissue infections. We herein present the case of a 56-year-old man with purulent discharge, redness, and foreign body sensation in his left eye. He underwent two surgeries that partially controlled the infection but were not curative. Corneal transplantation was performed, and a biopsy of the excised cornea indicated Mycobacterium aurum infection, which was confirmed by polymerase chain reaction-restriction fragment length polymorphism analysis. This appears to be the first documented case of keratitis attributable to the non-tuberculous mycobateria M. aurum. The intractable extra-ocular progression of the disease in the absence of general signs or symptoms was notable. We suggest considering non-tuberculous mycobacteria among the probable causes of complicated keratitis or keratitis that does not respond to drug treatment, especially in regions where tuberculosis is endemic.

  19. [Confocal microscopy as an early relapse marker after keratoplasty due to Fusarium solani keratitis].

    Science.gov (United States)

    Daas, L; Bischoff-Jung, M; Viestenz, A; Seitz, B; Viestenz, A

    2017-01-01

    In the case of therapy-resistant keratitis an infection with Fusarium solani should be taken into consideration as a rare but very severe eye disease. In the majority of cases Fusarium solani keratitis will result in a protracted clinical course despite aggressive medicinal and surgical interventions. We describe the case of a referred patient after intensive topical, intracameral and systemic antibacterial and antimycotic therapy as well as surgical treatment with emergency keratoplasty à chaud because of Fusarium solani keratitis. The patient presented to our department with persistent discomfort for further therapeutic interventions. Using confocal microscopy we were able to demonstrate the presence of fungal hyphae in the host cornea and the graft, which was important for making further surgical decisions. Furthermore, this emphasizes the role of confocal microscopy as an early relapse marker during the clinical monitoring.

  20. Early diagnosis of mycotic keratitis : Predictive value of potassium hydroxide preparation

    Directory of Open Access Journals (Sweden)

    Sharma Savitri

    1998-01-01

    Full Text Available Potassium hydroxide (KOH preparation is an underutilized modality in the diagnosis of mycotic keratitis. We have earlier shown its utility in the diagnosis of Nocardia and Acanthamoeba keratitis. The aim of this study was (i to evaluate the sensitivity, specificity and predictive value of KOH preparation, and (ii to compare its efficacy with other methods of corneal scraping examination, for the diagnosis of mycotic keratitis. The study was conducted in two phases. In phase I, randomized corneal scrapings were examined by KOH, Gram′s stain, and lactophenol cotton blue (LPCB in 91 infectious keratitis subjects. In phase II, 53 corneal scrapings were stained with KOH and calcofluor white (CFW, and viewed with bright field (KOH and fluorescence (CFW microscopy. The KOH and CFW readings were recorded by an observer masked to the clinical findings and culture results. Nineteen scrapings were examined by two masked observers. In 22 culture positive fungal keratitis patients in phase I, the sensitivity of KOH, Gram′s stain, and LPCB methods was 100%, 86.4%, and 77.3%, respectively. In phase II, the specificities of KOH and CFW were identical (83.8%, while the sensitivities were 81.2% and 93.7%, respectively (p = 0.59, in 16 culture positive mycotic keratitis patients. There was no significant difference between the negative and positive predictive values of KOH and CFW. Furthermore, no significant interobserver variability was found in the specificity and sensitivity. The KOH method compares well with other microscopy methods in the diagnosis of keratomycosis and has a definite place in the armamentarium of diagnostic techniques.

  1. Riboflavin and ultraviolet a collagen crosslinking of the cornea for the treatment of keratitis.

    Science.gov (United States)

    Morén, Håkan; Malmsjö, Malin; Mortensen, Jes; Ohrström, Arne

    2010-01-01

    To describe riboflavin and ultraviolet light (UV) collagen crosslinking as an effective treatment for infectious keratitis. A 25-year-old previously healthy female contact lens user was diagnosed with unilateral severe keratitis with unclear pathogenesis, although the clinical presentation suggested acanthamoeba as the infectious agent. A 4-mm diameter, annular, semi-opaque infiltrate was found on the paracentral parts of the cornea in the left eye (OS). Laboratory examinations for bacteria, herpes simplex, and acanthamoeba were performed, but no specific pathogen could be detected. Best corrected visual acuity (BCVA) at presentation was 20/1000. Treatment was initialized with broad-spectrum antibiotics also covering acanthamoeba. During the first month of treatment the keratitis progressed and the corneal thickness diminished. Therefore, treatment with riboflavin and UV collagen crosslinking was initiated. After riboflavin and UV collagen crosslinking therapy, there was a rapid decrease of pain and necrotic material. Reepithelialization of the cornea started within a few days and was complete within a month. After 2 months, the wound had healed completely. Nine months after the UV treatment, BCVA was 20/30. This case illustrates the positive effects of riboflavin and UV collagen crosslinking on presumed infectious keratitis with a satisfactory final visual outcome. This may be a promising new treatment for keratitis, although this remains to be elucidated in detail in future studies. Until more data are available this treatment should only be considered in therapy-refractive keratitis or ulceration and not in the first line of defence since it may have cytotoxic side effects.

  2. Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection

    Energy Technology Data Exchange (ETDEWEB)

    Subramanian, T.; Zhao, Ling-jun; Chinnadurai, G., E-mail: chinnag@slu.edu

    2013-09-01

    Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP–E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP–E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. - Highlights: • Adenovirus E1A C-terminal region suppresses E1A/Ras co-transformation. • This E1A region binds with FOXK, DYRK1/HAN11 and CtBP cellular protein complexes. • We found that E1A–CtBP interaction suppresses immortalization and transformation. • The interaction enhances viral replication in human cells.

  3. Acanthamoeba Species Keratitis in a Soft Contact Lens Wearer Molecularly Linked to Well Water

    Directory of Open Access Journals (Sweden)

    Samira Mubareka

    2006-01-01

    Full Text Available Acanthamoeba species keratitis has been associated with soft contact lens wear. In the present report, an epidemiological link was established between the patient's isolate and well water from the home using molecular methods. To the authors' knowledge, this is the first case in Canada where such a link has been established. Primary care practitioners and specialists, including ophthalmologists and infectious diseases specialists, must maintain a high degree of clinical suspicion in soft contact lens wearers with keratitis unresponsive to conventional topical and systemic treatment.

  4. Infectious keratitis in patients undergoing Boston Type 1 keratoprosthesis (Boston KPro procedure: case series

    Directory of Open Access Journals (Sweden)

    Heloisa Moraes do Nascimento

    2011-04-01

    Full Text Available Description of two cases of infectious keratitis in patients after Boston Type 1 keratoprosthesis (Boston KPro implantation. The first case refers to a patient that had the device indicated due to limbal deficiency secondary to severe dry eye who presented a fungal infection by Aerobasidium pullulans that was successfully treated with amphotericin B eye drops. The second case reports a patient with Boston KPro implantation due to previous corneal transplant rejection showing bacterial keratitis in the fourth postoperative month. The etiologic agent was identified asStreptococcus sp and topical treatment with vancomycin was effective. The importance of postoperative surveillance in Boston KPro eyes is discussed.

  5. A Case Report of Successfully Treated Microsporidial Keratitis at a Tertiary Care Centre in Western India

    Directory of Open Access Journals (Sweden)

    Jagruti Jadeja

    2016-06-01

    Full Text Available A 43 year old male patient, who was initially diagnosed with chronic viral stromal keratitis but was refractory to conventional treatment, underwent a corneal biopsy on the basis of strong clinical suspicion. The biopsy revealed the presence of multiple microsporidial spores. Treatment with Polyhexamethylene Biguanide (PHMB and Chlorhexidine showed poor response. A therapeutic penetrating keratoplasty under the cover of Fluoroquinolones led to successful resolution of the infection. To our knowledge, this is the first case of microsporidial keratitis being reported from our region.

  6. Application of image recognition-based automatic hyphae detection in fungal keratitis.

    Science.gov (United States)

    Wu, Xuelian; Tao, Yuan; Qiu, Qingchen; Wu, Xinyi

    2017-12-28

    The purpose of this study is to evaluate the accuracy of two methods in diagnosis of fungal keratitis, whereby one method is automatic hyphae detection based on images recognition and the other method is corneal smear. We evaluate the sensitivity and specificity of the method in diagnosis of fungal keratitis, which is automatic hyphae detection based on image recognition. We analyze the consistency of clinical symptoms and the density of hyphae, and perform quantification using the method of automatic hyphae detection based on image recognition. In our study, 56 cases with fungal keratitis (just single eye) and 23 cases with bacterial keratitis were included. All cases underwent the routine inspection of slit lamp biomicroscopy, corneal smear examination, microorganism culture and the assessment of in vivo confocal microscopy images before starting medical treatment. Then, we recognize the hyphae images of in vivo confocal microscopy by using automatic hyphae detection based on image recognition to evaluate its sensitivity and specificity and compare with the method of corneal smear. The next step is to use the index of density to assess the severity of infection, and then find the correlation with the patients' clinical symptoms and evaluate consistency between them. The accuracy of this technology was superior to corneal smear examination (p automatic hyphae detection of image recognition was 89.29%, and the specificity was 95.65%. The area under the ROC curve was 0.946. The correlation coefficient between the grading of the severity in the fungal keratitis by the automatic hyphae detection based on image recognition and the clinical grading is 0.87. The technology of automatic hyphae detection based on image recognition was with high sensitivity and specificity, able to identify fungal keratitis, which is better than the method of corneal smear examination. This technology has the advantages when compared with the conventional artificial identification of

  7. Ceratite bilateral por Acanthamoeba: relato de caso Bilateral Acanthamoeba keratitis: case report

    Directory of Open Access Journals (Sweden)

    Wilson Nahmatallah Obeid

    2003-12-01

    Full Text Available A ceratite por Acanthamoeba é uma infecção ocular grave que, apesar dos recentes progressos no diagnóstico e tratamento, ainda provoca prolongada morbidade e perda da acuidade visual. Relatamos um caso de ceratite bilateral por Acanthamoeba em usuário de lentes de contato, que é o primeiro caso descrito na literatura brasileira.Acanthamoeba keratitis is a severe ocular infection which even with recent progress in diagnosis and treatment still causes long morbidity and loss of visual acuity. We describe a case of bilateral Acanthamoeba keratitis in a user of contact lenses, which is the first case discussed in Brazilian literature.

  8. Modulation of Airway Epithelial Antiviral Immunity by Fungal Exposure

    OpenAIRE

    Zhu, Lingxiang; Lee, Boram; Zhao, Fangkun; Zhou, Xu; Chin, Vanessa; Ling, Serena C.; Chen, Yin

    2014-01-01

    Multiple pathogens, such as bacteria, fungi, and viruses, have been frequently found in asthmatic airways and are associated with the pathogenesis and exacerbation of asthma. Among these pathogens, Alternaria alternata (Alt), a universally present fungus, and human rhinovirus have been extensively studied. However, their interactions have not been investigated. In the present study, we tested the effect of Alt exposure on virus-induced airway epithelial immunity using live virus and a synthet...

  9. Tear Cytokine Levels in Contact Lens Wearers With Acanthamoeba Keratitis.

    Science.gov (United States)

    Carnt, Nicole; Montanez, Vicente M; Galatowicz, Grazyna; Veli, Neyme; Calder, Virginia

    2017-07-01

    To determine differences in key tear film cytokines between mild and severe cases of acanthamoeba keratitis (AK) and control contact lens (CL) wearers. This was a prospective study of CL wearers with AK attending Moorfields Eye Hospital and control CL wearers from the Institute of Optometry, London. Basal tear specimens were collected by 10-μL capillary tubes (BLAUBRAND intraMark, Wertheim, Germany), and tear protein levels were measured with a multiplex magnetic bead array (Luminex 100; Luminex Corporation, Austin, TX) for cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-17A, IL-17E, IL-17F, IL-22, and interferon gamma and with enzyme-linked immunosorbent assay (Abcam, Cambridge, United Kingdom) for CXCL2. Severe cases of AK were defined as having active infection for over 12 months and at least 1 severe inflammatory event. One hundred and thirty-two tear samples were collected from a total of 61 cases (15 severe and 46 mild-moderate) and 22 controls. IL-8, part of the Toll-like receptor 4 cytokine cascade, was found to be expressed at a detectable level more often in cases of AK than in control CL wearers (P = 0.003) and in higher concentrations in severe cases than in milder forms of the disease (z = -2.35). IL-22, part of the IL-10 family, and a proinflammatory Th17 cytokine, was detected more often in severe cases than in milder forms of AK (P < 0.02). Profiling patients with AK during disease shows differences in cytokine levels between severe and milder disease that may inform clinical management. The Toll-like receptor 4 and IL-10/Th17 inflammatory pathways should be included in further investigations of this disease.

  10. Amniotic membrane graft to conjunctival flap in treatment of non-viral resistant infectious keratitis: a randomised clinical study.

    Science.gov (United States)

    Abdulhalim, Bahaa-Eldin Hasan; Wagih, Mostafa Mohamed; Gad, Ahmed A M; Boghdadi, Ghada; Nagy, Ragy R S

    2015-01-01

    To evaluate and compare the results of bipedicle conjunctival flap (CF) and cryopreserved amniotic membrane graft (AMG) in the treatment of non-viral infectious keratitis resistant to medical treatment. This prospective randomised interventional study included 40 eyes of 40 patients with resistant non-viral infectious keratitis. Twenty eyes received CF and 20 eyes received AMG. In the CF group, there were 12 eyes with fungal keratitis, 7 eyes with bacterial keratitis and 1 eye with Acanthamoeba keratitis. In the AMG group there were 13 eyes with fungal keratitis, 5 eyes with bacterial keratitis and 2 eyes with Acanthamoeba keratitis. In the CF group, three ulcers had descemetocele and four ulcers were perforated. In the AMG group, four ulcers had descemetocele and two ulcers were perforated. In CF, 360° peritomy was done and a bipedicle CF from the upper conjunctiva was dissected from Tenon's capsule, mobilised to cover the cornea and sutured to episclera. In AMG, one or two layers of AM were trimmed to fit the ulcer and sutured to the cornea. The follow-up period was 6 months. Successful results were observed in 18/20 eyes (90%) in each group. Postoperatively, no significant differences between the two groups were found regarding success rate (p=1.0), epithelialisation time (p=0.75) or visual acuity improvement (p=0.84). CF and AMG are effective in treatment-resistant infectious keratitis. They could restore ocular surface integrity and provide metabolic and mechanical support for corneal healing. For large corneal perforation, it may be better to use another procedure such as penetrating keratoplasty to restore ocular integrity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Lactoferrin Glu561Asp polymorphism is associated with susceptibility to herpes simplex keratitis

    DEFF Research Database (Denmark)

    Keijser, S; Jager, M J; Dogterom-Ballering, H C M

    2008-01-01

    . Lactoferrin gene polymorphisms were determined by PCR combined with restriction fragment length analysis in 105 HSV keratitis patients and 145 control subjects. Bilateral tear samples were harvested from 50 patients and 40 healthy controls and tear lactoferrin concentrations were determined by ELISA. Patients...

  12. Trends of Bacterial Keratitis Culture Isolates in Jerusalem; a 13- Years Analysis.

    Science.gov (United States)

    Politis, Michael; Wajnsztajn, Denise; Rosin, Boris; Block, Colin; Solomon, Abraham

    2016-01-01

    To describe the trends in pathogens and antibacterial resistance of corneal culture isolates in infectious keratitis during a period of 13 years at Hadassah-Hebrew University Medical Center. A Retrospective analysis of bacterial corneal isolates was performed during the months of January 2002 to December 2014 at Hadassah Hebrew University Medical Center. Demographics, microbiological data and antibiotic resistance and sensitivity were collected. A total of 943 corneal isolates were analyzed during a 13 year period. A total of 415 positive bacterial cultures and 37 positive fungal cultures were recovered, representing 48% of the total cultures. The Annual incidence was 34.78 ± 6.54 cases. The most common isolate was coagulase-negative staphylococcus (32%), which had a significant decrease in trend throughout the study period (APC = -8.1, p = 0.002). Methicillin-resistant Staphylococcus aureus (MRSA) appears to have a decrease trend (APC = -31.2, P = 0.5). There was an increase in the resistance trend of coagulase-negative staphylococci to penicillin (APC = 5.0, P = keratitis. There was no significant change in the annual incidence of cases of bacterial keratitis seen over the past 13 years. Keratitis caused by MRSA appeared to decrease in contrast to the reported literature.

  13. [Multicenter Prospective Observational Study of Fungal Keratitis--Identification and Susceptibility Test of Fungi].

    Science.gov (United States)

    Sunada, Atsuko; Asari, Seishi; Inoue, Yoshitsugu; Ohashi, Yuichi; Suzuki, Takashi; Shimomura, Yoshikazu; Fukuda, Masahiko; Sotozono, Chie; Hatano, Hiroshi; Eguchi, Hiroshi; Araki-Sasaki, Kaoru; Hoshi, Saichi; Yaguchi, Takashi; Makimura, Koichi; Yokokura, Shunji; Mochizuki, Kiyofumi; Monden, Yu; Nejima, Ryohei

    2016-01-01

    To investigate the causative fungi of fungal keratitis in Japan and their drug susceptibility. Identification and antifungal susceptibility test for 8 drugs (micafungin, amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, miconazole and pimaricin) were performed using isolated fungi from patients with fungal keratitis treated at 27 facilities in Japan between November 1, 2011 and October 31, 2013. Fungal strains were detected in 72 (50.7%) out of 142 samples. The major isolates were Fusarium spp. (18), Candida parapsilosis (12), C. albicans (11) and Alternaria spp. (6), in all, fungi of 31 species were identified by gene analysis. In the yeast-like fungi, susceptibility rates were evident for more than 80% in voriconazole, pimaricin, flucytosine, micafungin, amphotericin B and fluconazole. In filamentous fungi, the susceptibility rate was less than 50% except for PMR (90%). Fusarium spp., which were susceptible to amphotericin B and pimaricin, showed lower susceptibility rates compared with other genera. Although various genera and species of fungi cause fungal keratitis, the obtained drug susceptibility data in this study demonstrates the different susceptibility patterns among the major isolates (Fusarium spp., C. parapsilosis, C. albicans and other groups). This is important evidence useful for fungal keratitis treatment.

  14. Aspergillus flavus Keratitis: Experience of a Tertiary Eye Clinic in Turkey

    NARCIS (Netherlands)

    Erdem, E.; Yagmur, M.; Boral, H.; Ilkit, M.; Ersoz, R.; Seyedmousavi, S.

    2017-01-01

    We investigated the clinical and mycological characteristics of four cases of mycotic keratitis caused by Aspergillus flavus that occurred from July 2014 to May 2015 at Cukurova University Hospital, Adana, Turkey. In a 10-month period, a total of 64 corneal smear/scrapings were examined from

  15. Pathogen Induced Changes in the Protein Profile of Human Tears from Fusarium Keratitis Patients

    Science.gov (United States)

    Ananthi, Sivagnanam; Venkatesh Prajna, Namperumalsamy; Lalitha, Prajna; Valarnila, Murugesan; Dharmalingam, Kuppamuthu

    2013-01-01

    Fusarium is the major causative agent of fungal infections leading to corneal ulcer (keratitis) in Southern India and other tropical countries. Keratitis caused by Fusarium is a difficult disease to treat unless antifungal therapy is initiated during the early stages of infection. In this study tear proteins were prepared from keratitis patients classified based on the duration of infection. Among the patients recruited, early infection (n = 35), intermediate (n = 20), late (n = 11), samples from five patients in each group were pooled for analysis. Control samples were a pool of samples from 20 patients. Proteins were separated on difference gel electrophoresis (DIGE) and the differentially expressed proteins were quantified using DeCyder software analysis. The following differentially expressed proteins namely alpha-1-antitrypsin, haptoglobin α2 chain, zinc-alpha-2-glycoprotein, apolipoprotein, albumin, haptoglobin precursor - β chain, lactoferrin, lacrimal lipocalin precursor, cystatin SA III precursor, lacritin precursor were identified using mass spectrometry. Variation in the expression level of some of the proteins was confirmed using western blot analysis. This is the first report to show stage specific tear protein profile in fungal keratitis patients. Validation of this data using a much larger sample set could lead to clinical application of these findings. PMID:23308132

  16. Aspergillus flavus Keratitis: Experience of a Tertiary Eye Clinic in Turkey.

    Science.gov (United States)

    Erdem, Elif; Yagmur, Meltem; Boral, Hazal; Ilkit, Macit; Ersoz, Reha; Seyedmousavi, Seyedmojtaba

    2017-04-01

    We investigated the clinical and mycological characteristics of four cases of mycotic keratitis caused by Aspergillus flavus that occurred from July 2014 to May 2015 at Çukurova University Hospital, Adana, Turkey. In a 10-month period, a total of 64 corneal smear/scrapings were examined from patients with suspected mycotic keratitis. Fungal cultures were positive in six of these patients, indicating a 9.4% incidence of mycotic keratitis in this region, including four cases of A. flavus and two cases of Fusarium spp. The predisposing factors, clinical presentation, and success of the therapeutic approaches were further evaluated. For all cases, topical voriconazole was the first choice of treatment. Surgical procedures were required to control infection in 3 of the 4 cases, including intrastromal voriconazole injection for two cases and keratoplasty for one case. Predisposing factors included trauma (two cases, 50%), contact lens use (one case, 25%), and previous ocular surgery (one case, 25%). The clinical presentations also differed, including a well-limited ulcer (one case), an ulcer with an irregular feathery margin (one case), and ulcers with satellite lesions (two cases). The mean duration between the time of presentation and definitive diagnosis by culture was 14 days (8-25 days). We observed that A. flavus keratitis can present with different underlying factors and clinical conditions. A combination of antifungal therapy and supportive surgical intervention may resolve infections caused by A. flavus in the cornea.

  17. Use of an ophthalmic formulation of megestrol acetate for the treatment of eosinophilic keratitis in cats.

    Science.gov (United States)

    Stiles, Jean; Coster, Martin

    2016-07-01

    To evaluate a compounded ophthalmic formulation of 0.5% megestrol acetate to treat eosinophilic keratitis in cats. Prospective study. Seventeen client owned cats with eosinophilic keratitis in one or both eyes. Eosinophilic keratitis was confirmed by cytology. At each visit, fluorescein staining and photography were performed. Cats were initially treated q 8-12 h with 0.5% megestrol acetate in an aqueous base. Serum glucose was measured at the first or second reexamination. Fifteen of 17 (88%) cats had a positive response to treatment, with 6 of 17 (35%) having complete resolution at the first reexamination (2-4 weeks). Two of 17 (12%) cats did not respond to treatment. Most cats required a treatment frequency of once daily to once weekly to maintain remission of disease. No ocular irritation or systemic side effects were noted in any cat. The use of an ophthalmic formulation of 0.5% megestrol acetate is a viable option for treating feline eosinophilic keratitis. © 2016 American College of Veterinary Ophthalmologists.

  18. Topical voriconazole therapy of Purpureocillium lilacinum keratitis that occurred in disposable soft contact lens wearers.

    Science.gov (United States)

    Todokoro, Daisuke; Yamada, Norihiro; Fukuchi, Mariko; Kishi, Shoji

    2014-10-01

    The objective of this study was to describe 2 cases of keratitis caused by Purpureocillium lilacinum (formerly Paecilomyces lilacinus) that occurred in disposable contact lens users, which were successfully treated with topical voriconazole. Case 1 was a healthy 44-year-old woman, who wore weekly disposable contact lenses and had developed a superficial corneal infection in her right eye. For diagnosis, corneal scraping and molecular identification of the cultured pathogen were performed. A corneal smear revealed the presence of fungi. The pathogen was identified as P. lilacinum by traditional morphological identification of fungal culture, and this identification was confirmed by DNA sequencing of the ribosomal internal transcribed spacer (ITS) sequence. Therapy with topical fluconazole, topical pimaricin (natamycin), and oral itraconazole were ineffective. Topical voriconazole showed a significant effect, and the keratitis was successfully treated. Case 2 was a 43-year-old woman with bilateral recurrent peripheral corneal ulcers by meibomian gland dysfunction, who used therapeutic bandage contact lenses on her left eye. However, a corneal abscess with hypopyon occurred in the eye after 3 months. The microbial smear examination showed the presence of fungi and the fungal culture, and the DNA sequence of ITS region revealed that the causative agent was P. lilacinum. The susceptibility testing against antifungal agents showed that voriconazole was effective. The lesion improved gradually by topical voriconazole. As a conclusion, P. lilacinum keratitis can occur in disposable soft contact lens wearer. Early and accurate detection of the pathogenic organism is essential. Topical voriconazole was effective against P. lilacinum keratitis.

  19. Surface thermodynamics and adhesion forces governing bacterial transmission in contact lens related microbial keratitis

    NARCIS (Netherlands)

    Qu, Wenwen; Busscher, Henk J.; Hooymans, Johanna M. M.; van der Mei, Henny C.

    2011-01-01

    Contact lens induced microbial keratitis results from bacterial transmission from one surface to another. We investigated the adhesion forces of Pseudomonas aeruginosa, Staphylococci and Serratia to different contact lenses, lens cases and corneal surfaces using AFM, and applied a Weibull analysis

  20. Successful Treatment of Lasiodiplodia theobromae Keratitis – Assessing the Role of Voriconazole

    Directory of Open Access Journals (Sweden)

    Stephen Tak-lun Li

    2016-10-01

    Full Text Available Purpose: The aim of this paper is to report the successful management of the first case of Lasiodiplodia theobromae keratitis in Hong Kong. Methods: We conducted a case report. Results: A 43-year-old Chinese male with a history of diabetes developed left eye keratitis after a trauma during tree felling. Fungal keratitis was diagnosed using a confocal microscope on day 1, and L. theobromae was confirmed from the culture. He was given oral voriconazole, topical natamycin, and topical and intracameral amphotericin B. The patient’s condition improved after the initial treatment. However, there was a slow progression to descemetocele formation and impending perforation due to corneal melting. Penetrating keratoplasty was performed at 8 weeks after presentation. Final visual recovery was good with no recurrence of infection. The cornea remained clear. Conclusions: We report the first case of L. theobromae keratitis in Hong Kong, and it is the only case so far that involved the use of oral voriconazole in the combination therapy. Early recognition with the aid of confocal microscopy allowed the early start of treatment. The use of newer antifungal voriconazole topically and orally combined with topical amphotericin B appeared to be useful in the eradication of the fungus and prevention of recurrence. Intracameral antifungals might have improved the clinical management.

  1. Trichosporon asahii keratitis in a patient with a type I Boston keratoprosthesis and contact lens.

    Science.gov (United States)

    Keating, Anne; Pineda, Roberto

    2012-03-01

    The aim of the study was to report a case of Trichosporon asahii in a patient with a type I Boston keratoprosthesis and contact lens with review of the literature. A case report and literature review are provided. A 70-year-old monocular South Asian man with light perception vision and dense corneal scarring from previously failed amniotic membrane grafting and one failed corneal transplant was evaluated for a keratoprosthesis for visual rehabilitation. Three months after undergoing uneventful implantation of a type I Boston keratoprosthesis and placement of a therapeutic contact lens, he was found on routine follow-up to have a corneal infiltrate that was culture positive for T. asahii. The fungal keratitis was successfully treated with topical amphotericin B and oral ketoconazole. Contact lens wear is a known risk factor for fungal keratitis. Trichosporon is an uncommon agent of fungal keratitis. We report the first known case of fungal keratitis caused by T.asahii in a patient with a keratoprosthesis and contact lens.

  2. Degradation of Uniquely Glycosylated Secretory Immunoglobulin A in Tears From Patients With Pseudomonas aeruginosa Keratitis

    DEFF Research Database (Denmark)

    Lomholt, Jeanet Andersen; Kilian, Mogens

    2008-01-01

    from patients with keratitis caused by P. aeruginosa, Streptococcus group G, Moraxella catarrhalis, Staphylococcus aureus, coagulase-negative staphylococci, and the IgA1 protease-producing Streptococcus pneumoniae were compared with S-IgA in tear fluid, colostrum, and saliva from healthy individuals...

  3. Microscopic Evaluation, Molecular Identification, Antifungal Susceptibility, and Clinical Outcomes in Fusarium, Aspergillus and, Dematiaceous Keratitis

    Science.gov (United States)

    Gajjar, Devarshi U.; Pal, Anuradha K.; Ghodadra, Bharat K.; Vasavada, Abhay R.

    2013-01-01

    Purpose. Fusarium, Aspergillus, and Dematiaceous are the most common fungal species causing keratitis in tropical countries. Herein we report a prospective study on fungal keratitis caused by these three fungal species. Methodology. A prospective investigation was undertaken to evaluate eyes with presumed fungal keratitis. All the fungal isolates (n = 73) obtained from keratitis infections were identified using morphological and microscopic characters. Molecular identification using sequencing of the ITS region and antifungal susceptibility tests using microdilution method were done. The final clinical outcome was evaluated in terms of the time taken for resolution of keratitis and the final visual outcome. The results were analyzed after segregating the cases into three groups, namely, Fusarium, Aspergillus, and Dematiaceous keratitis. Results. Diagnosis of fungal keratitis was established in 73 (35.9%) cases out of 208 cases. The spectra of fungi isolated were Fusarium spp. (26.6%), Aspergillus spp. (21.6%), and Dematiaceous fungi (11.6%). The sequence of the ITS region could identify the Fusarium and Aspergillus species at the species complex level, and the Dematiaceous isolates were accurately identified. Using antifungal agents such as fluconazole, natamycin, amphotericin B, and itraconazole, the minimum inhibitory concentrations (MICs) for Fusarium spp. were >32 μg/mL, 4–8 μg/mL, 0.5–1 μg/mL, and >32 μg/mL, respectively. Antifungal susceptibility data showed that Curvularia spp. was highly resistant to all the antifungal agents. Overall, natamycin and amphotericin B were found to be the most effective antifungal agents. The comparative clinical outcomes in all cases showed that the healing response in terms of visual acuity of the Dematiaceous group was significantly good when compared with the Fusarium and Aspergillus groups (P < 0.05). The time required for healing in the Fusarium group was statistically significantly less when compared with

  4. The effects of Ethanol Extract of Propolis (EEP on the experimentally induced Candida keratitis in rabbits

    Directory of Open Access Journals (Sweden)

    Ahangari AA

    2011-04-01

    Full Text Available "n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Propolis (bee glue is a resinous substance obtained from bee hives living on various plant sources. The purpose of this study was to evaluate the effects of ethanol extract of propolis (EEP on the experimentally induced Candidial keratitis in rabbits."n"nMethods: The alcoholic extract of propolis was prepared by 80% ethyl alcohol. After suppressing the immune system of 24 male rabbits, experimental Candida albicans keratitis was induced in the animals under local anesthesia and sterile conditions. The animals were later divided into four groups including the control or glycerin group and a nystatin and two 500 and 1000µg/ml EEP groups. Treatment continued for 21 days and after sacrificing the animals by humane methods, histopathological samples of the rabbits' eyes were prepared."n"nResults: Keratitis was developed in the eyes of all rabbits a week after the yeast inoculation. In the control group in which animals received glycerin, keratitis persisted until day 21. Clinical signs of keratitis disappeared in the Nystatin and 1000µg/ml EEP groups after 14 and 21 days, respectively. The clinical signs of keratitis partially ameliorated in the animals receiving 500µg/ml EEP. Histopathological examination revealed no differences between groups receiving nystatin or 1000µg/ml EEP."n"nConclusion: It is concluded that, ethanol extract of propolis could completely treat Candida albicans keratitis in 1000µg/ml concentrations. This extract can be used as a safe antifungal agent

  5. A novel murine model of Fusarium solani keratitis utilizing fluorescent labeled fungi.

    Science.gov (United States)

    Zhang, Hongmin; Wang, Liya; Li, Zhijie; Liu, Susu; Xie, Yanting; He, Siyu; Deng, Xianming; Yang, Biao; Liu, Hui; Chen, Guoming; Zhao, Huiwen; Zhang, Junjie

    2013-05-01

    Fungal keratitis is a common disease that causes blindness. An effective animal model for fungal keratitis is essential for advancing research on this disease. Our objective is to develop a novel mouse model of Fusarium solani keratitis through the inoculation of fluorescent-labeled fungi into the cornea to facilitate the accurate and early identification and screening of fungal infections. F. solani was used as the model fungus in this study. In in vitro experiment, the effects of Calcofluor White (CFW) staining concentration and duration on the fluorescence intensity of F. solani were determined through the mean fluorescence intensity (MFI); the effects of CFW staining on the growth of F. solani were determined by the colony diameter. In in vivo experiment, the F. solani keratitis mice were induced and divided into a CFW-unlabeled and CFW-labeled groups. The positive rate, corneal lesion score and several positive rate determination methods were measured. The MFIs of F. solani in the 30 μg/ml CFW-30 min, 90 μg/ml CFW-10 min and 90 μg/ml CFW-30 min groups were higher than that in the 10 μg/ml CFW-10 min group (P  0.05). No significant differences (P > 0.05) were observed for the positive rate or the corneal lesion scores between the CFW-unlabeled and the CFW-labeled group. On day 1 and 2, the positive rates of the infected corneas in the scraping group were lower than those in the fluorescence microscopy group (P  0.05). Thus, these experiments established a novel murine model of F. solani keratitis utilizing fluorescent labeled fungi. This model facilitates the accurate identification and screening of fungal infections during the early stages of fungal keratitis and provides a novel and reliable technology to study the fungal keratitis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. KOH mount as an aid in the management of infectious keratitis at secondary eye care centre.

    Science.gov (United States)

    Rathi, Varsha M; Thakur, Monica; Sharma, Savitri; Khanna, Rohit; Garg, Prashant

    2017-11-01

    To report the clinical outcome of infectious keratitis managed after doing 10% KOH mount of corneal smears and reporting done by an ophthalmologist in the secondary eye care centre in South India. 103 consecutive cases of microbial keratitis were studied. Inclusion criteria were presence of corneal infiltrate on slit lamp biomicroscopy. An ophthalmologist carried out microbiological evaluation of 10% KOH mount of corneal scrapings. No cultures were done at secondary centres. Antifungal therapy with 5% Natamycin was initiated when 10% KOH mount was positive for fungal filaments. Else, the patients were started on combined topical ciprofloxacin (0.3%) and fortified cefazolin (5%). 41/103 (39.8%) smears were positive for fungus and 62 (60.2%) were negative. 89 out of 103 patients (86.40%) healed with scarring at an average of 2.95±1.58 weeks. Healing was noted in 39/41 (95.12%) of patients at an average of 3.06±1.19 weeks in patients with KOH smear positive keratitis. 80.64% (50/62) healed with scarring at an average period of 2.86±1.86 weeks in KOH mount negative keratitis. Initial smear examination of KOH mount by an ophthalmologist helped in diagnosis of infectious keratitis caused by fungi and its management and 95.12% of KOH positive patients healed with scarring. Reading of KOH mount by an ophthalmologist helped in initiation of specific therapy with improved clinical outcome. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Evolving risk factors and antibiotic sensitivity patterns for microbial keratitis at a large county hospital.

    Science.gov (United States)

    Jin, Haoxing; Parker, Walter T; Law, Nathan W; Clarke, Cameron L; Gisseman, Jordan D; Pflugfelder, Stephen C; Wang, Li; Al-Mohtaseb, Zaina N

    2017-11-01

    Purpose: To identify the risk factors, causative organisms, antimicrobial susceptibility and outcomes of microbial keratitis in a large county hospital in Houston, Texas.Design: Case series. Setting: A large county hospital in Houston, Texas. Patients with known diagnosis of microbial keratitis from January 2011 to May 2015. Retrospective chart review. Epidemiology, risk factors, outcomes and antibiotic susceptibility of microbial keratitis. The most commonly identified risk factors were contact lens use (34.4%), ocular trauma (26.3%), diabetes mellitus (16.7%), ocular surgery (13.5%), ocular surface diseases (11.5%), previous keratitis (10.4%), glaucoma (6.3%), cocaine use (5.2%) and HIV-positive status (4.2%). Eyes with positive cultures (61.5%) were associated with worse visual outcomes (p=0.019) and a higher number of follow-up visits (p=0.007) than eyes with negative cultures (38.5%). Corneal perforation was the most common complication (11.5%). Gram-negative organisms (21.9%) were all susceptible to ceftazidime, tobramycin and fluoroquinolones. Gram-positive organisms (33.3%) had worse outcomes than Gram-negative organisms (21.9%) and exhibited a wide spectrum of antibiotic resistance, but all were susceptible to vancomycin. Twenty-seven per cent of the coagulase-negative Staphylococci were resistant to fluoroquinolones. This study identified a recent shift in risk factors and antibiotic resistance patterns in microbial keratitis at a County Hospital in Houston, Texas. In our patient population, fluoroquinolone monotherapy is not recommended for severe corneal ulcers. On the basis of these results, vancomycin and tobramycin should be used for empirical therapy until microbial identity and sensitivity results are available. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. A 5-year retrospective review of fungal keratitis in the region of Cap Bon.

    Science.gov (United States)

    Zbiba, W; Baba, A; Bouayed, E; Abdessalem, N; Daldoul, A

    2016-12-01

    Microbial keratitis is a serious ocular infection and a leading cause of morbidity and blindness worldwide. A retrospective review of the charts of 30 patients (30 eyes) diagnosed with presumed or culture-proven fungal keratitis among 100 patients with infectious keratitis. All patients initially received hourly 0.5% Amphotericin B eye drops. Systemic antifungal agents consisted mainly of oral Fluconazole. After treatment, a healing time of less than 3 weeks from presentation was considered a good result. Mean follow up was 10.4 months. Risk factors for fungal keratitis included ocular trauma in 13 patients (43.3%). Stromal infiltration was seen in 100% of patients. Satellite lesions were noted in 6 eyes (20%) and an immune ring was noted in 3 cases (10%). The most commonly isolated agent was Fusarium in 9 eyes (50%), followed by Aspergillus in 6 eyes (33.3%), and Candida in 2 eyes (11.1%). At the end of follow up, final visual acuity varied from no light perception to 20/20. The significant predictors were initial visual acuity, size of infiltrate at presentation, male gender and advanced age. The key element in the diagnosis of mycotic keratitis is clinical suspicion on the part of the ophthalmologist. However, because of the potential serious complications, it is essential to identify the exact pathogen so as to initiate appropriate treatment in time and to thus improve the prognosis of this condition. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Antimicrobial Blue Light Therapy for Infectious Keratitis: Ex Vivo and In Vivo Studies.

    Science.gov (United States)

    Zhu, Hong; Kochevar, Irene E; Behlau, Irmgard; Zhao, Jie; Wang, Fenghua; Wang, Yucheng; Sun, Xiaodong; Hamblin, Michael R; Dai, Tianhong

    2017-01-01

    To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis. We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colony-forming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety. Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log10) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea. Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted.

  10. Treatment With Intrastromal and Intracameral Voriconazole in 2 Eyes With Lasiodiplodia theobromae Keratitis

    Science.gov (United States)

    Lekhanont, Kaevalin; Nonpassopon, Manachai; Nimvorapun, Nutthida; Santanirand, Pitak

    2015-01-01

    Abstract To report the clinical presentation and the role of intrastromal and intracameral voriconazole injection in the management of rare cases of fungal keratitis caused by Lasiodiplodia theobromae. Two eyes of 2 patients with Lasiodiplodia keratitis unresponsive to topical and oral antifungal medications were included in this study. Diagnosis of Lasiodiplodia keratitis was confirmed by microbiological analysis, including culture-based (case 1 and 2) and DNA sequencing techniques (case 2 only). The first patient presented with multiple satellite lesions and one of these infiltrates spread deeply into the cornea, forming a stromal abscess. Another patient had a large full-thickness corneal infiltrates with several fungal balls in the anterior chamber, requiring a limbus-to-limbus therapeutic penetrating keratoplasty. Despite aggressive topical therapy, the stromal abscess continued to worsen in the first case and recurrent keratitis was observed postoperatively in the second case. Voriconazole 50 μg/0.1 mL was administered intracamerally and intrastromally around the fungal abscess as adjuncts to topical antimycotics in the first case. The second patient who needed therapeutic keratoplasty was treated with an intracameral injection of 50 μg/0.1 mL voriconazole at the end of surgery. Postoperatively, 100 μg/0.1 mL voriconazole was also injected intracamerally after the recurrence of infection was noted in the graft. Reinjections were given 48 hours apart in both cases. After the injections, all corneal and anterior chamber lesions were reduced in size and density and completely resolved within 4 weeks. Intrastromal and intracameral voriconazole injections may offer safe and effective treatment options for L theobromae keratitis. PMID:25674759

  11. Role of liquid culture media in the laboratory diagnosis of microbial keratitis.

    Science.gov (United States)

    Bhadange, Yogesh; Sharma, Savitri; Das, Sujata; Sahu, Srikant K

    2013-10-01

    To determine whether liquid culture media are helpful in the diagnosis of infectious keratitis. Retrospective noncomparative case series. This is a retrospective review of microbiology records of 114 corneal scraping samples from infectious keratitis patients. Samples were processed by corneal smear microscopy (potassium hydroxide with calcofluor white and Gram stains) and culture examination (5% sheep blood agar, sheep blood chocolate agar, Sabouraud dextrose agar, brain heart infusion, thioglycolate broth, and Robertson's cooked meat broth. Cases where at least 1 liquid medium was taken were included in the study and all cases were required to have significant growth in culture as per the institutional criteria. Results of smear examination and culture growth were analyzed. Out of 114 cases, 44 (38.59%) were bacterial, 62 (54.38%) fungal, and 8 (7.01%) were mixed (bacteria + fungus) infection. Thirty-eight out of 44 cases of bacterial keratitis (86.36%) were diagnosed by solid media alone (criterion 1) and 6 of 44 (13.63%) required liquid media for diagnosis (P media alone (criterion 1) while 1 case required liquid media for diagnosis. In mixed infection, none of the cases required liquid media for diagnosis of fungal component; however, all 8 cases required liquid media for establishing bacterial component. Liquid culture media increase the chance of isolation of bacteria in pure bacterial and/or mixed infection; however, their role in isolating fungus is limited. Owing to overlap in clinical diagnosis of bacterial and fungal keratitis, we recommend inclusion of both solid and liquid culture media in the laboratory diagnosis of nonviral keratitis. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Pathogenic spectrum of fungal keratitis and specific identification of Fusarium solani.

    Science.gov (United States)

    He, Dan; Hao, Jilong; Zhang, Bo; Yang, Yanqiu; Song, Wengang; Zhang, Yunfeng; Yokoyama, Koji; Wang, Li

    2011-04-25

    To investigate the predominant causative pathogens and epidemiologic features of fungal keratitis and establish a rapid, specific molecular method to detect fungal keratitis caused by Fusarium solani. A total of 174 patients with presumed fungal keratitis and 174 affected eyes were examined. Isolates from corneal specimens were identified according to morphologic and physiological characteristics. The primers that were designed for F. solani were tested to confirm whether they had species specificity. Multiplex PCR with universal fungal and F. solani-specific primers was performed with fungal and bacterial strains and was used to detect microorganisms in the clinical specimens. A total of 160 patients (92.0%) were diagnosed with fungal infection by either potassium hydroxide wet-mount or microbiologic culture. Fungal cultures were positive in 128 patients (73.6%) with 139 fungal isolates. Fusarium (48.2%) was the most frequently isolated genus, in which F. solani (35.2%) was the most common species, followed by the Aspergillus (18.7%) and Candida (16.6%) genera. The PCR results showed that the designed primers were species specific and suitable for specific identification of F. solani. The multiplex PCR of 3-day broth cultures could identify and distinguish F. solani from other pathogens rapidly and specifically from clinical specimens. Fusarium species, especially F. solani, were found to be the predominant cause of fungal keratitis in northeast China. The established multiplex PCR method could have potential advantages for rapid detection of F. solani. These findings might have significance for early diagnosis and treatment of fungal keratitis.

  13. A case of fungal keratitis and endophthalmitis post penetrating keratoplasty resulting from fungal contamination of the donor cornea

    Directory of Open Access Journals (Sweden)

    Koji Kitazawa

    2017-04-01

    Conclusions and importance: The findings of this case show that prompt intensive medical treatment and surgical intervention effectively saved the vision in a patient with fungal keratitis and endophthalmitis due to contamination of the donor corneal graft.

  14. Study of Pathogens of Fungal Keratitis and the Sensitivity of Pathogenic Fungi to Therapeutic Agents with the Disk Diffusion Method.

    Science.gov (United States)

    Wang, Lulu; Wang, Liya; Han, Lei; Yin, Weijing

    2015-01-01

    To identify the causative fungi of fungal keratitis, test their susceptibility to antifungal agents with the disk diffusion method and study the relationship between the organisms, the inhibition zones and the clinical outcomes. 535 patients with fungal keratitis in one eye were included in this study. Pathogenic fungi were isolated by corneal scraping, identified by fungal cultivation and subjected to drug sensitivity tests conducted with the disk diffusion method. The patients were treated initially with voriconazole, terbinafine and natamycin eye drops for one week. Further treatment continued using the most effective drug according to the drug sensitivity results. The patients were followed up every week until three months after cured. The inhibition zones of fungi cultured with voriconazole, terbinafine and natamycin were compared. The relationship between inhibition zones and organism, organism and treatment results measure, and each treatment results measure and inhibition zones were evaluated. Of 535 patients, 53.84%, 19.25% and 26.91% were infected with Aspergillus, Fusarium and other fungi, respectively. Keratitis patients infected with Aspergillus keratitis had the worst outcome. The size of the inhibition zones of Aspergillus spp., Fusarium spp. and other fungal genera differed significantly in response to voriconazole, terbinafine and natamycin. The inhibition zone associated with natamycin correlated significantly with the clinical outcome of fungal keratitis (OR = 0.925), but no other such correlations were found for the other drugs tested. Aspergillus and Fusarium were the predominant pathogenic genera causing fungal keratitis in our patients. Among the causative fungi, infections due to Aspergillus spp. were associated with the worst outcomes. The inhibition zones of fungal isolates in response to natamycin significantly correlated with the treatment outcomes of keratitis. Specifically, the smaller the natamycin inhibition zone, the lower the

  15. Keratitis som følge af diagnoseforveksling mellem udtørringskeratopati og allergisk øjensygdom

    DEFF Research Database (Denmark)

    Ahmed, Shakil; Javed Ahmed, Hassan

    2014-01-01

    A case report of involutional ectropion associated with exposure keratopathy - which complicated to exposure keratitis due to incorrect management is presented. Upon consulting the local pharmacy the patient was wrongly given anti-allergic eye drops. Patients with involutional ectropion have high...... risk of dry eye disease and may rarely be complicated with keratitis. Distinguishing between exposure keratopathy and allergic eye disease is pivotal as management differs and wrong therapy may lead to serious eye disease....

  16. Recombinant adeno-associated virus-, polyethylenimine/plasmid- and lipofectamine/carboxyfluorescein-labeled small interfering RNA-based transfection in retinal pigment epithelial cells with ultrasound and/or SonoVue.

    Science.gov (United States)

    Li, Hongli; Wan, Caifeng; Li, Fenghua

    2015-05-01

    The present study was conducted to investigate the efficacy and safety of ultrasound (US)‑mediated transfection of the type 2 recombinant adeno‑associated virus (AAV) vectors encoding the enhanced green fluorescent protein (EGFP) gene (rAAV), polyethylenimine (PEI)/plasmid EGFP‑N1 (pDNA) or lipofectamine (L)/carboxyfluorescein (FAM)‑labeled small interfering RNA (siRNA) in the human ARPE‑19 retinal pigment epithelial (RPE) cell line, with or without the addition of SonoVue. Cultured RPE cells were exposed to US, with or without SonoVue under different conditions, including variation in the intensity and duration of treatment, and the dose of microbubbles. The effects of ultrasound‑targeted microbubble destruction (UTMD) on the structure of pDNA and the transfection ability of rAAV, PEI/pDNA and L/siRNA were also evaluated. Furthermore, the effect of UTMD on RPE cells was evaluated at 0 and 24 h following UTMD. US‑mediated transfection (USMT) significantly increased L/siRNA transfection efficiency, as measured by the transgene expression per cell and the percentage of transfected cells. UTMD significantly increased rAAV and PEI/pDNA transfer to RPE cells. UTMD‑mediated rAAV or PEI/pDNA delivery was more effective than USMT‑mediated delivery of siRNA. Evaluating cell viability at 24 h post‑UTMD provided more valuable information than immediate evaluation following UTMD. Furthermore, there was minimal cytotoxicity and minimal change to the structure of pDNA under the optimal parameters. UTMD/US may be of use in enhancing rAAV, PEI/pDNA and L/siRNA transgene expression of ARPE‑19 cells in vitro. Studies on the transfection of different nucleotides (such as pDNA and siRNA) and different types of vectors (chemical and biological) mediated by UTMD may provide useful information to guide future in vivo and transfection studies.

  17. IMPACT OF MICROBIOTA ON RESISTANCE TO OCULAR PSEUDOMONAS AERUGINOSA–INDUCED KERATITIS

    DEFF Research Database (Denmark)

    Kugadas, Abirami; Christiansen, Stig Hill; Sankaranarayanan, Saiprasad

    2016-01-01

    –induced keratitis. We find that in health, the presence of microbiota strengthened the ocular innate immune barrier by significantly increasing the concentrations of immune effectors in the tear film, including secretory IgA and complement proteins. Consistent with this view, Swiss Webster (SW) mice......The existence of the ocular microbiota has been reported but functional analyses to evaluate its significance in regulating ocular immunity are currently lacking. We compared the relative contribution of eye and gut commensals in regulating the ocular susceptibility to Pseudomonas aeruginosa...... that are typically resistant to P. aeruginosa–induced keratitis become susceptible due to the lack of microbiota. This was exemplified by increased corneal bacterial burden and elevated pathology of the germ free (GF) mice when compared to the conventionally maintained SW mice. The protective immunity was found...

  18. Successful salvage therapy of Fusarium endophthalmitis secondary to keratitis: an interventional case series

    Directory of Open Access Journals (Sweden)

    Comer GM

    2012-05-01

    Full Text Available Grant M Comer, Maxwell S Stem, Stephen J SaxeUniversity of Michigan, Department of Ophthalmology and Visual Sciences, Ann Arbor, MI, USAPurpose: To describe a combination of treatment modalities used for the successful eradication of Fusarium endophthalmitis.Design: Interventional case series.Participants: Three consecutive patients with keratitis-associated Fusarium endophthalmitis.Methods: After failure of traditional management options, a combination of intravitreal and long-term, high-dose systemic voriconazole, topical antifungal medications, and surgical intervention, with penetrating keratoplasty, lensectomy, and endoscopic-guided pars plana vitrectomy, was administered to each patient.Results: All three cases achieved full resolution of the infection, with a final Snellen visual acuity score of 20/50 to 20/70.Conclusions: An aggressive combination of therapeutic modalities, including the removal of subiris abscesses, might be needed for the successful resolution of Fusarium endophthalmitis.Keywords: endophthalmitis, fungal, Fusarium, keratitis, keratoplasty, voriconazole 

  19. First Report of Hartmannella keratitis in a Cosmetic Soft Contact Lens Wearer in Iran

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    Hoda Abedkhojasteh

    2013-09-01

    Full Text Available Background: Poor hygiene will provide good condition for corneal infections by opportunistic free-living amoebae (FLA in soft contact lens wearers. In the present study an amoebic keratitis due to Hartmannella has been recognized in a 22-year-old girl with a history of improper soft contact lens use. She had unilateral keratitis on her left eye. Her clinical signs were eye pain, redness, blurred vision and photopho­bia. The round cysts of free-living amoebae were identified in non-nutrient agar medium by light microscopy. These cysts were suspected to be Hartmannella using morphological criteria. A PCR assay has been confirmed that the round cysts were belonged to H. vermiformis.

  20. Imported pythium insidiosum keratitis after a swim in Thailand by a contact lens-wearing traveler.

    Science.gov (United States)

    Lelievre, Lucie; Borderie, Vincent; Garcia-Hermoso, Dea; Brignier, Anne C; Sterkers, Margaret; Chaumeil, Christine; Lortholary, Olivier; Lanternier, Fanny

    2015-02-01

    A 30-year-old woman with a history of contact lens wear and exposure to swimming pool water in Thailand presented with a non-responsive, progressive corneal ulcer of the right eye. Confocal microscopy evidenced septate linear branching structures, raising suspicion of fungal keratitis. She was promptly treated with topical antibiotics and both topical and intravenous caspofungin plus voriconazole. Worsening of the clinical picture after 1 month of intensive medical therapy led to a large therapeutic penetrating keratoplasty being performed. Corneal cultures grew a mold-like organism, which was identified by sequencing as Pythium insidiosum, an aquatic oomycete. After 4 years of follow-up, the graft exhibits no infection relapse, but graft transparency has been lost after two rejection episodes. Keratoplasty combined with antifungal treatment may offer a cure to P. insidiosum keratitis, although long-term preservation of corneal transparency is difficult to obtain. © The American Society of Tropical Medicine and Hygiene.

  1. IMPACT OF MICROBIOTA ON RESISTANCE TO OCULAR PSEUDOMONAS AERUGINOSA–INDUCED KERATITIS

    DEFF Research Database (Denmark)

    Kugadas, Abirami; Christiansen, Stig Hill; Sankaranarayanan, Saiprasad

    2016-01-01

    The existence of the ocular microbiota has been reported but functional analyses to evaluate its significance in regulating ocular immunity are currently lacking. We compared the relative contribution of eye and gut commensals in regulating the ocular susceptibility to Pseudomonas aeruginosa......–induced keratitis. We find that in health, the presence of microbiota strengthened the ocular innate immune barrier by significantly increasing the concentrations of immune effectors in the tear film, including secretory IgA and complement proteins. Consistent with this view, Swiss Webster (SW) mice...... that are typically resistant to P. aeruginosa–induced keratitis become susceptible due to the lack of microbiota. This was exemplified by increased corneal bacterial burden and elevated pathology of the germ free (GF) mice when compared to the conventionally maintained SW mice. The protective immunity was found...

  2. Suture-related keratitis following cataract surgery caused by methicillin-resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Ahmad B Tarabishy

    2010-03-01

    Full Text Available Ahmad B Tarabishy1, Thomas L Steinemann21Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA; 2Cornea and External Eye Disease, MetroHealth Medical Center, Case Western