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 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.

Figure 1

A 64-year-old male manual laborer enrolled in SCUT whose ulcer was culture positive for Nocardia was randomized to adjuvant corticosteroids. (a) at enrollment his visual acuity was logMAR 1.2 (Snellen ~ 20/317); (b) at 3 weeks his visual acuity was logMAR 1.46 (Snellen ~20/577); (c) at 12 months his visual acuity continued to decline to 1.9 logMAR (Snellen LP).

Figure 2

A 67-year-old male manual laborer enrolled in SCUT whose ulcer was culture positive for Pseudomonas aeruginosa was randomized to adjuvant corticosteroids. (a) at enrollment his visual acuity was logMAR 1.7 (Snellen CF); (b) at 3 weeks his visual acuity was logMAR 0.62 (Snellen ~20/83); (c) at 12 months his visual acuity further improved to 0.24 logMAR (Snellen ~20/35) with contact lens over refraction.

Figure 3

A 32-year-old male tractor driver enrolled in MUTT I whose ulcer was culture positive for Fusarium was randomized to receive topical voriconazole. (a) at enrollment his visual acuity was logMAR 0.1 (Snellen ~20/25); (b) at 3 weeks his visual acuity was logMAR 1.8 (Snellen HM); (c) at 3 months he had perforated and undergone therapeutic penetrating keratoplasty, and his resulting visual acuity was logMAR 1.9 (Snellen LP) with contact lens over refraction.

Image 1

Confocal microscopy image from a patient with filamentous fungal keratitis.