Update on the Management of Infectious Keratitis

Abstract

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 while culture remains the prevailing diagnostic tool, newer techniques such as in vivo confocal microscopy are helpful for diagnosing fungal keratitis and Acanthameoba. 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 responsible for much of the morbidity associated with keratitis include topical corticosteroids. The large, randomized controlled Steroids for Corneal Ulcers trial found that while steroids provided no significant improvement overall, they did appear beneficial for ulcers that were central, deep or large, non-Nocardia or classically invasive P. aeruginosa, 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 1960’s when topical natamycin was introduced. The randomized controlled Mycotic Ulcer Treatment Trial showed a benefit of topical natamycin over topical voriconazole for fungal keratitis, particularly among those caused by Fusarium. The second Mycotic Ulcer Treatment Trial showed that oral voriconazole did not improve outcomes overall although there may have been some effect among Fusarium ulcers. Given an increase in non-serious adverse events the authors concluded that they could not recommend oral voriconazole at this time. Viral keratitis differs from bacterial and fungal cases in that is often recurrent and is common in developed countries. The first Herpetic Eye Disease Study (HEDS) 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 HSV 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.

Virucidal, antiviral and immunomodulatory activities of β-escin and Aesculus hippocastanum extract

“…However, there have been several reports of ACV R strains causing HSK in immunocompetent patients . Thus, considering the rise of the resistant viruses against the current antivirals and the adverse effect of corticoids, there is a need to search for new potential anti‐HSV agents that act with different mechanisms. In this sense, the finding of novel compounds that inhibit both viral multiplication and the immunopathology triggered by the virus is an interesting approach that is being considered …”

“…[6] However, corticosteroids have adverse side effects, and there is concern that they prolong viral shedding. [6] In most HSVrelated diseases, the prevalence rates of acyclovir (ACV) resistance are much higher among immunocompromised patients. However, there have been several reports of ACV R strains causing HSK in immunocompetent patients.…”

Management of Psuedomonas Keratitis: a review article

“…Topical antibiotics remain the best treatment for bacterial keratitis. It was found that all frequently used antibiotics are equally effective, but the final outcome is not satisfactory because of corneal melting, scaring and perforation [29]. Treatment used varies depending on geographical location and available local antimicrobial susceptibility of Pseudomonas isolates.…”

“…Meropenem and ciprofloxacin with 90% of isolates showed synergistic or additive effect. This made combined anti-microbial a potential treatment against multi drug resistant strains [29]. Most common prescribed drugs are ciprofloxacin and tobramycin, a fortified aminoglycosides.…”

The HIV Integrase Inhibitor Raltegravir Inhibits Felid Alphaherpesvirus 1 Replication by Targeting both DNA Replication and Late Gene Expression

“…associated with chronic and recurrent ocular disease, characterized by conjunctivitis, corneal ulceration, and epithelial and stromal keratitis, often leading to corneal scarring and loss of transparency (3). All currently approved therapies for ophthalmologic alphaherpesvirus infection rely on nucleoside analogues that prevent base pairing when incorporated into the growing DNA polymer, thus inhibiting genome replication (4). However, and despite the proven value of these drugs in limiting HHV-1-associated corneal damage, effective treatment of this condition remains challenging due to toxicity concerns, the frequency of treatment required, and the potential for selection of drug-resistant variants, especially in immunocompromised individuals (5)(6)(7)(8).…”