The Spectrum of Microbial Keratitis: An Updated Review

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Abstract

Background:

In microbial keratitis, infection of the cornea can threaten vision through permanent corneal scarring and even perforation resulting in the loss of the eye. A literature review was conducted by Karsten, Watson and Foster (2012) to determine the spectrum of microbial keratitis. Since this publication, there have been over 2600 articles published investigating the causative pathogens of microbial keratitis.

Objective:

To determine the current spectrum of possible pathogens implicated in microbial keratitis relative to the 2012 study.

Methods:

An exhaustive literature review was conducted of all the peer-reviewed articles reporting on microbial pathogens implicated in keratitis. Databases including MEDLINE, EMBASE, Scopus and Web of Science were searched utilising their entire year limits (1950-2019).

Results:

Six-hundred and eighty-eight species representing 271 genera from 145 families were implicated in microbial keratitis. Fungal pathogens, though less frequent than bacteria, demonstrated the greatest diversity with 393 species from 169 genera that were found to cause microbial keratitis. There were 254 species of bacteria from 82 genera, 27 species of amoeba from 11 genera, and 14 species of virus from 9 genera, which were also identified as pathogens of microbial keratitis.

Conclusion:

The spectrum of pathogens implicated in microbial keratitis is extremely diverse. Bacteria were most commonly encountered and in comparison, to the review published in 2012, further 456 pathogens have been identified as causative pathogens of microbial keratitis. Therefore, the current review provides an important update on the potential spectrum of microbes, to assist clinicians in the diagnosis and treatment of microbial keratitis.

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An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment

Jacob Lorenzo-Morales, Naveed Khan, Julia Walochnik (2015)

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.

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Bacterial keratitis: predisposing factors, clinical and microbiological review of 300 cases.

L. Laroche, T Bourcier, C. Chaumeil … (2003)

To identify predisposing factors and to define clinical and microbiological characteristics of bacterial keratitis in current practice. A retrospective analysis of the hospital records of patients presenting with bacterial keratitis and treated at the Quinze-Vingts National Center of Ophthalmology, Paris, France, was performed during a 20 month period. A bacterial keratitis was defined as a suppurative corneal infiltrate and overlying epithelial defect associated with presence of bacteria on corneal scraping and/or that was cured with antibiotic therapy. Risk factors, clinical and microbiological data were collected. 300 cases (291 patients) of presumed bacterial keratitis were included. Potential predisposing factors, usually multiple, were identified in 90.6% of cases. Contact lens wear was the main risk factor (50.3%). Trauma or a history of keratopathy was found in 15% and 21% of cases, respectively. An organism was identified in 201 eyes (68%). 83% of the infections involved Gram positive bacteria, 17% involved Gram negative bacteria, and 2% were polymicrobial. Gram negative bacteria were associated with severe anterior chamber inflammation (p=0.004), as well as greater surface of infiltrates (p=0.01). 99% of ulcers resolved with treatment, but only 60% of patients had visual acuity better than the level at admission, and 5% had very poor visual outcome. Contact lens wear is the most important risk factor. Most community acquired bacterial ulcers resolve with appropriate treatment.

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Update on the Management of Infectious Keratitis.

Ariana Austin, Tom Lietman, Jennifer Rose-Nussbaumer (2017)

Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is critical, and although culture remains the prevailing diagnostic tool, newer techniques such as in vivo confocal microscopy are helpful for diagnosing fungus and Acanthamoeba. Next-generation sequencing holds the potential for early and accurate diagnosis even for organisms that are difficult to culture by conventional methods. Topical antibiotics remain the best treatment for bacterial keratitis, and a recent review found all commonly prescribed topical antibiotics to be equally effective. However, outcomes remain poor secondary to corneal melting, scarring, and perforation. Adjuvant therapies aimed at reducing the immune response associated with keratitis include topical corticosteroids. The large, randomized, controlled Steroids for Corneal Ulcers Trial found that although steroids provided no significant improvement overall, they did seem beneficial for ulcers that were central, deep or large, non-Nocardia, or classically invasive Pseudomonas aeruginosa; for patients with low baseline vision; and when started early after the initiation of antibiotics. Fungal ulcers often have worse clinical outcomes than bacterial ulcers, with no new treatments since the 1960s when topical natamycin was introduced. The randomized controlled Mycotic Ulcer Treatment Trial (MUTT) I showed a benefit of topical natamycin over topical voriconazole for fungal ulcers, particularly among those caused by Fusarium. MUTT II showed that oral voriconazole did not improve outcomes overall, although there may have been some effect among Fusarium ulcers. Given an increase in nonserious adverse events, the authors concluded that they could not recommend oral voriconazole. Viral keratitis differs from bacterial and fungal cases in that it is often recurrent and is common in developed countries. The Herpetic Eye Disease Study (HEDS) I showed a significant benefit of topical corticosteroids and oral acyclovir for stromal keratitis. HEDS II showed that oral acyclovir decreased the recurrence of any type of herpes simplex virus keratitis by approximately half. Future strategies to reduce the morbidity associated with infectious keratitis are likely to be multidimensional, with adjuvant therapies aimed at modifying the immune response to infection holding the greatest potential to improve clinical outcomes.