title: The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole.
abstract: OBJECTIVE
  To compare topical natamycin vs voriconazole in the treatment of filamentous fungal keratitis.
  
  
  METHODS
  This phase 3, double-masked, multicenter trial was designed to randomize 368 patients to voriconazole (1%) or natamycin (5%), applied topically every hour while awake until reepithelialization, then 4 times daily for at least 3 weeks. Eligibility included smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400.
  
  
  METHODS
  The primary outcome was best spectacle-corrected visual acuity at 3 months; secondary outcomes included corneal perforation and/or therapeutic penetrating keratoplasty.
  
  
  RESULTS
  A total of 940 patients were screened and 323 were enrolled. Causative organisms included Fusarium (128 patients [40%]), Aspergillus (54 patients [17%]), and other filamentous fungi (141 patients [43%]). Natamycintreated cases had significantly better 3-month best spectacle-corrected visual acuity than voriconazole-treated cases (regression coefficient=0.18 logMAR; 95% CI, 0.30 to 0.05; P=.006). Natamycin-treated cases were less likely to have perforation or require therapeutic penetrating keratoplasty (odds ratio=0.42; 95% CI, 0.22 to 0.80; P=.009). Fusarium cases fared better with natamycin than with voriconazole (regression coefficient=0.41 logMAR; 95% CI,0.61 to 0.20; P<.001; odds ratio for perforation=0.06; 95% CI, 0.01 to 0.28; P<.001), while non-Fusarium cases fared similarly (regression coefficient=0.02 logMAR; 95% CI, 0.17 to 0.13; P=.81; odds ratio for perforation=1.08; 95% CI, 0.48 to 2.43; P=.86).
  
  
  CONCLUSIONS
  Natamycin treatment was associated with significantly better clinical and microbiological outcomes than voriconazole treatment for smear-positive filamentous fungal keratitis, with much of the difference attributable to improved results in Fusarium cases.
  
  
  CONCLUSIONS
  Voriconazole should not be used as monotherapy in filamentous keratitis.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00996736
authors.affiliation: Aravind Eye Care System, Madurai, India.
authors.forename: N Venkatesh
authors.initials: NV
authors.lastname: Prajna
authors.forename: Tiruvengada
authors.initials: T
authors.lastname: Krishnan
authors.forename: Jeena
authors.initials: J
authors.lastname: Mascarenhas
authors.forename: Revathi
authors.initials: R
authors.lastname: Rajaraman
authors.forename: Lalitha
authors.initials: L
authors.lastname: Prajna
authors.forename: Muthiah
authors.initials: M
authors.lastname: Srinivasan
authors.forename: Anita
authors.initials: A
authors.lastname: Raghavan
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Oldenburg
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Ray
authors.forename: Michael E
authors.initials: ME
authors.lastname: Zegans
authors.forename: Stephen D
authors.initials: SD
authors.lastname: McLeod
authors.forename: Travis C
authors.initials: TC
authors.lastname: Porco
authors.forename: Nisha R
authors.initials: NR
authors.lastname: Acharya
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Lietman
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D057112:Corneal Perforation / Q000382:microbiology; D003320:Corneal Ulcer / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D004311:Double-Blind Method; D015821:Eye Infections, Fungal / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D005260:Female; D005658:Fungi / Q000302:isolation & purification; D006801:Humans; D015948:Keratoplasty, Penetrating; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D010866:Natamycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009883:Ophthalmic Solutions; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014792:Visual Acuity / Q000502:physiology; D065819:Voriconazole; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D009883:Ophthalmic Solutions; D011743:Pyrimidines; D014230:Triazoles; D010866:Natamycin; D065819:Voriconazole