Potential use of (1,3)-beta-D-glucan as target of diagnosis and treatment of keratomycosis

Cornea. 2004 Nov;23(8 Suppl):S36-41. doi: 10.1097/01.ico.0000136670.43154.0c.

Abstract

Purpose: Major problems in the management of keratomycosis stem from the difficulty of its diagnosis and limited choice of antifungal agents. In the present paper we propose a new method of detecting (1,3)-beta-D-glucan, one of the major components of fungal cell wall, in tears from an animal model of keratomycosis. In addition, we investigated the efficacy of topical application of micafungin, a new antifungal agent that inhibits the activity of (1,3)-beta-D-glucan synthase in this animal model.

Method: Candida albicans (5 x 10(5) organisms) was inoculated into the corneal stroma of 20 New Zealand White rabbits. The animals were randomly assigned to two groups and treated with subconjunctival injection of 0.5 mL of saline or 0.1% micafungin every day for 3 weeks. The clinical course of keratomycosis in both groups was compared. Before and 3 weeks after the injection of saline or micafungin, 5 microL of tears in each eye were collected by capillary tube. The concentration of (1,3)-beta-D-glucan was quantitatively measured by modified Limulus test.

Results: The concentration of (1,3)-beta-D-glucan was significantly higher in keratomycosis model animals than in controls (mean +/- SD, 17.4 +/- 9.4 pg/mL and 2.8 +/- 1.8 pg/mL, respectively) at 21 days after treatment. Subconjunctival injection of micafungin had no significant effect on ocular lesions of keratomycosis until 9 days, after which ocular lesions significantly improved. Subconjunctival application of micafungin decreased the concentration of (1,3)-beta-D-glucan in tears to 4.9 +/- 3.0 pg/mL at 21 days after treatment.

Conclusions: Increased levels of (1,3)-beta-D-glucan in tears were detected in this model of keratomycosis. Measuring the concentration of (1,3)-beta-D-glucan in tears may be a reliable noninvasive method for the diagnosis of keratomycosis. Topical application of micafungin was effective in the treatment of keratomycosis.

MeSH terms

  • Animals
  • Candidiasis / drug therapy
  • Candidiasis / microbiology*
  • Corneal Diseases / drug therapy
  • Corneal Diseases / microbiology*
  • Echinocandins
  • Eye Infections, Fungal / drug therapy
  • Eye Infections, Fungal / microbiology*
  • Glucosyltransferases / antagonists & inhibitors*
  • Limulus Test
  • Lipopeptides
  • Lipoproteins / therapeutic use*
  • Male
  • Micafungin
  • Peptides, Cyclic / therapeutic use*
  • Rabbits
  • Tears / microbiology*
  • beta-Glucans*

Substances

  • Echinocandins
  • Lipopeptides
  • Lipoproteins
  • Peptides, Cyclic
  • beta-Glucans
  • beta-1,3-glucan
  • Glucosyltransferases
  • 1,3-beta-glucan synthase
  • Micafungin