Elsevier

Ophthalmology

Volume 124, Issue 11, November 2017, Pages 1678-1689
Ophthalmology

Original article
Update on the Management of Infectious Keratitis

https://doi.org/10.1016/j.ophtha.2017.05.012Get rights and content

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.

Section snippets

Diagnostics

Proper diagnosis of keratitis is essential to determining treatment and achieving resolution of infection. The mainstay in diagnosis is still Gram stain and culture of corneal samples despite imperfect sensitivity.13, 14, 15 Gram and Giemsa stains are advantageous because they provide instant results, with Gram stain accurately detecting the causative organism 60% to 75% of the time in bacterial cases and 35% to 90% in fungal cases. Giemsa has a sensitivity of 40% to 85% for diagnosing fungal

Bacterial Keratitis

In the United States, bacterial keratitis is most associated with contact lens use.19 Severe cases can progress rapidly and cause permanent vision loss requiring corneal transplantation.

Fungal Keratitis

Fungal ulcers often have worse outcomes than bacterial ulcers, and there is little evidence to guide treatment.66 Fungal keratitis represents a relatively small percentage of infectious keratitis cases in regions with temperate climates; however, in tropical climates it can cause up to 50% of infectious ulcers.66, 67, 68 Contact lens wear has been identified as a risk factor for fungal keratitis in the United States, and an outbreak of Fusarium keratitis among contact lens wearers was related

Viral Keratitis

Herpes simplex virus (HSV) keratitis affects an estimated 500 000 people in the United States and an estimated 1.5 million globally.91 It is the most common cause of unilateral infectious corneal blindness in much of the developed world.92 Viral keratitis differs from bacterial and fungal keratitis in that it can become chronic and recurrent. Besides being a painful, sight-threatening infection, HSV keratitis has been shown to significantly affect quality of life even when patients are not

Next-Generation Sequencing

Culture-negative keratitis remains a significant problem for clinicians. At Aravind Eye Hospital in India, for example, 38% of corneal scrapings from eyes with presumed infectious keratitis tested negative on both culture and smear between 2002 and 2012.105 Next-generation sequencing may improve on the diagnostic accuracy of infectious keratitis, particularly for organisms that are difficult to culture by conventional methods, such as atypical or anaerobic bacteria.106 Next-generation

Conclusions

Despite having appropriate antimicrobial treatments for most of the pathogens implicated in infectious keratitis, clinical outcomes often are poor. Strategies to reduce the morbidity associated with this condition are likely going to have to be multidimensional, involving corneal ulcer prevention, improved early and accurate diagnostics techniques such as next-generation sequencing, and novel antimicrobial agents to address the development of drug resistance. Adjuvant therapies that focus on

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    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    Supported by grant no. K23 EY025025 (J.R.-N.), an unrestricted grant from the Peirles Foundation (J.R.-N.), and an unrestricted grant from Research to Prevent Blindness (J.R.-N.).

    Author Contributions:

    Conception and design: Austin, Lietman, Rose-Nussbaumer

    Data collection: Austin

    Analysis and interpretation: Austin, Lietman, Rose-Nussbaumer

    Obtained funding: Not applicable

    Overall responsibility: Austin, Lietman, Rose-Nussbaumer

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