Microbial Keratitis

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

doi:10.1097/icl.0b013e318275b473

Cited by 21 publications

(14 citation statements)

References 39 publications

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“…P. aeruginosa remains the most common cause of contact lens related microbial keratitis (Robertson, 2013) but recent world wide epidemics caused by fungi ( F. solani ) and acanthamoeba are reminders that other organisms may also take advantage of the ocular surface compromised by contact lens wear (Patel and Hammersmith, 2008; Yoder et al, 2012). Microbial keratitis associated with contact lens wear and its accompanying use of care solutions is a multifactorial process (Evans and Fleiszig, 2013). Contributing factors, some associated with hypoxia, include reduced corneal epithelial turnover allowing for more contact time with potential pathogens, enhanced ability of corneal epithelial cells to bind and internalize (via lipid raft-formation) P. aeruginosa , and adaptation of the organism to the contact-lens modulated ocular surface environment (Evans and Fleiszig, 2013; Ladage, 2004; Robertson, 2013).…”

Section: Modulation Of Tear Antimicrobialsmentioning

confidence: 99%

“…Microbial keratitis associated with contact lens wear and its accompanying use of care solutions is a multifactorial process (Evans and Fleiszig, 2013). Contributing factors, some associated with hypoxia, include reduced corneal epithelial turnover allowing for more contact time with potential pathogens, enhanced ability of corneal epithelial cells to bind and internalize (via lipid raft-formation) P. aeruginosa , and adaptation of the organism to the contact-lens modulated ocular surface environment (Evans and Fleiszig, 2013; Ladage, 2004; Robertson, 2013). As recently reviewed by Evans and Fleiszig (Evans and Fleiszig, 2013), contact lens wear may affect tear-mediated defenses in a number of ways.…”

Section: Modulation Of Tear Antimicrobialsmentioning

confidence: 99%

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Antimicrobial compounds in tears

McDermott

2013

Experimental Eye Research

241

171

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The tear film coats the cornea and conjunctiva and serves several important functions. It provides lubrication, prevents drying of the ocular surface epithelia, helps provide a smooth surface for refracting light, supplies oxygen and is an important component of the innate defense system of the eye providing protection against a range of potential pathogens. This review describes both classic antimicrobial compounds found in tears such as lysozyme and some more recently identified such as members of the cationic antimicrobial peptide family and surfactant protein-D as well as potential new candidate molecules that may contribute to antimicrobial protection. As is readily evident from the literature review herein, tears, like all mucosal fluids, contain a plethora of molecules with known antimicrobial effects. That all of these are active in vivo is debatable as many are present in low concentrations, may be influenced by other tear components such as the ionic environment, and antimicrobial action may be only one of several activities ascribed to the molecule. However, there are many studies showing synergistic/additive interactions between several of the tear antimicrobials and it is highly likely that cooperativity between molecules is the primary way tears are able to afford significant antimicrobial protection to the ocular surface in vivo. In addition to effects on pathogen growth and survival some tear components prevent epithelial cell invasion and promote the epithelial expression of innate defense molecules. Given the protective role of tears a number of scenarios can be envisaged that may affect the amount and/or activity of tear antimicrobials and hence compromise tear immunity. Two such situations, dry eye disease and contact lens wear, are discussed here.

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Section: Modulation Of Tear Antimicrobialsmentioning

confidence: 99%

Section: Modulation Of Tear Antimicrobialsmentioning

confidence: 99%

Antimicrobial compounds in tears

McDermott

2013

Experimental Eye Research

241

171

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“…Silicone hydrogel lenses with greater oxygen diffusion have not been found to reduce the risk of microbial keratitis [29], as was anticipated. In this regard, work in mice by Mukherjee et al [30] showed that Fusarium grown as a biofilm on silicone hydrogel material induces keratitis upon injury to the cornea.…”

Section: Contact Lenses and Biofilmsmentioning

confidence: 99%

Challenges of corneal infections

Hazlett

Suvas

McClellan

et al. 2016

Expert Review of Ophthalmology

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Introduction Ocular infections remain an important cause of blindness worldwide and represent a challenging public health concern. In this regard, microbial keratitis due to fungal, bacterial, or viral infection can result in significant vision loss secondary to corneal scarring or surface irregularity. Left untreated corneal perforation and endophthalmitis can result, leading to loss of the eye. Rigorously studied animal models of disease pathogenesis have provided novel information that suggests new modes of treatment that may be efficacious clinically and emerging clinical data is supportive of some of these discoveries. Areas covered This review focuses on advances in our understanding of disease pathogenesis in animal models and clinical studies and how these relate to improved clinical treatment. We also discuss a novel approach to treatment of microbial keratitis due to infection with these bacterial pathogens using PACK-CXL and recommend increased basic and clinical studies to address and refine the efficacy of this procedure. Expert commentary Because resistance to antibiotics has developed over time to these bacterial pathogens, caution must be exercised in treatment. Attractive novel modes of treatment that hold new promise for further investigation include lipid based therapy, as well as use of small molecules that bind deleterious specific host responsive molecules and use of microRNA based therapies.

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“…Once a colonized lens is placed on the eye, it is easy for the bacterial community to resist the physical removal due to the tear flow combined with the sweeping action of the eyelids [1]. Furthermore, contact lens wear compromises several innate ocular surface defences [11–13], while adaptation to the ocular surface microenvironment facilitates bacterial survival by enhancing the production of virulence factors that highly concur with the pathogenesis of Pseudomonas keratitis [1, 14]. In this scenario, worsened by the rapid increase of resistant pathogens, including P. aeruginosa , to the available antibiotics [15–17], which are not even normally capable of eradicating bacterial biofilms [18], the discovery of new ophthalmic antimicrobial agents with a novel mode of action, has become urgently needed.…”

Section: Introductionmentioning

confidence: 99%

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

Kolar

Luca

Baidouri

et al. 2014

Cell. Mol. Life Sci.

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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.

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Microbial Keratitis

Cited by 21 publications

References 39 publications

Antimicrobial compounds in tears

Antimicrobial compounds in tears

Challenges of corneal infections

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

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