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Natamycin and voriconazole in Fusarium and Aspergillus keratitis: subgroup analysis of a randomised controlled trial
  1. Venkatesh N Prajna1,
  2. Prajna S Lalitha1,
  3. Jeena Mascarenhas1,
  4. Tiruvengada Krishnan2,
  5. Muthiah Srinivasan1,
  6. C M Vaitilingam2,
  7. Catherine E Oldenburg3,
  8. Aileen Sy3,
  9. Jeremy David Keenan3,4,
  10. Travis C Porco3,5,
  11. Nisha R Acharya3,4,
  12. Thomas M Lietman3,4,5
  1. 1Department of Cornea and Refractive Surgery, Aravind Eye Care System, Madurai, Tamil Nadu, India
  2. 2Department of Cornea, Aravind Eye Care System, Pondicherry, India
  3. 3Francis I. Proctor Foundation, University of California, San Francisco, California, USA
  4. 4Department of Ophthalmology, University of California, San Francisco, California, USA
  5. 5Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA
  1. Correspondence to Dr Thomas M Lietman, F.I. Proctor Foundation, University of California, Room S309, 513 Parnassus Ave, UCSF, San Francisco, CA 94143-0412, USA; tom.lietman{at}ucsf.edu

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Introduction

Fusarium and Aspergillus species are aggressive corneal pathogens, and even with proper treatment, can lead to poor outcomes.1 Voriconazole is effective in vitro against Aspergillus species, but may not perform as well against Fusarium species.2 We undertook a clinical trial comparing topical voriconazole versus topical natamycin, with the overall results presented previously.3 Here, we perform a prespecified subgroup analyses of treatment within Fusarium cases, and separately, within Aspergillus cases, assessing the efficacy of voriconazole and natamycin.

Methods

Complete methods of the clinical trial have been reported elsewhere.3 In brief, eligible patients had a KOH-positive fungal smear with filamentous fungal elements, and were randomised to receive either topical voriconazole 1% (Pfizer, New York, NY, USA) or natamycin 5% (Alcon, Ft Worth, Texas, USA), and to repeat scraping or no rescraping. The primary outcome for the trial was best spectacle-corrected visual acuity (BSCVA) at 3 months from enrolment. Secondary outcomes included corneal perforation and/or therapeutic penetration keratoplasty (TPK) by treatment arm. Fungal cultures were performed for all patients enrolled in the trial. Fungal identification was performed using gross and microscopic characteristics. Ethical approval was obtained from the University of California, San Francisco and the Aravind Eye Care System.

Analyses were performed in the subset of patients who were diagnosed with Fusarium or Aspergillus keratitis. Wilcoxon rank sum and Fisher's exact tests were used …

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