title: Effect of pretreatment with antifungal agents on clinical outcomes in fungal keratitis.
abstract: BACKGROUND
  To determine if pretreatment with antifungal agents is predictive of worse clinical outcome in a fungal keratitis clinical trial.
  
  
  METHODS
  Non-pre-specified subgroup analysis of a randomized controlled trial in a tertiary hospital.
  
  
  METHODS
  Three hundred twenty-three fungal ulcer cases with an enrolment visual acuity of 20/40 to 20/400.
  
  
  METHODS
  The Mycotic Ulcer Treatment Trial I was a randomized, double-masked trial to determine the optimal treatment for filamentous fungal keratitis at the Aravind Eye Care System, India. Enrolled cases were randomized to receive topical natamycin or voriconazole. Prior antifungal medication use, dose and duration were collected at enrolment. A subgroup analysis was performed to determine if patients using natamycin or azoles at presentation have worse clinical outcomes compared with those who were not pretreated.
  
  
  METHODS
  Three-month visual acuity (primary), 3-month infiltrate or scar size, corneal perforation and/or transplant and re-epithelialization time.
  
  
  RESULTS
  Of the 323 patients enrolled, 44% presented on an antifungal agent. Pretreated patients had larger mean baseline infiltrate size (P < 0.001) and epithelial defect size (P = 0.02). Multivariate regression analysis demonstrated that pretreatment was associated with significantly worse 3-month visual acuity (P = 0.006), larger 3-month scar size (P < 0.001) and increased odds of corneal perforation and/or transplant (P = 0.001).
  
  
  CONCLUSIONS
  Fungal keratitis that is smear-positive despite being pretreated with appropriate antifungal agents appears to be a risk factor for worse outcomes, likely a result of initial ulcer severity and treatment failure. These patients may benefit from more aggressive multimodal therapy at a tertiary centre.
authors.affiliation: Department of Ophthalmology, University of California San Francisco, San Francisco, California, USA.
authors.forename: Catherine Q
authors.initials: CQ
authors.lastname: Sun
authors.affiliation: Aravind Eye Care System at Madurai, Pondicherry and Coimbatore, Madurai, India.
authors.forename: N Venkatesh
authors.initials: NV
authors.lastname: Prajna
authors.affiliation: Aravind Eye Care System at Madurai, Pondicherry and Coimbatore, Madurai, India.
authors.forename: Tiruvengada
authors.initials: T
authors.lastname: Krishnan
authors.affiliation: Aravind Eye Care System at Madurai, Pondicherry and Coimbatore, Madurai, India.
authors.forename: Revathi
authors.initials: R
authors.lastname: Rajaraman
authors.affiliation: Aravind Eye Care System at Madurai, Pondicherry and Coimbatore, Madurai, India.
authors.forename: Muthiah
authors.initials: M
authors.lastname: Srinivasan
authors.affiliation: Aravind Eye Care System at Madurai, Pondicherry and Coimbatore, Madurai, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Raghavan
authors.affiliation: Francis I. Proctor Foundation, University of California San Francisco, San Francisco, California, USA.
authors.forename: Kieran S
authors.initials: KS
authors.lastname: O'Brien
authors.affiliation: Department of Ophthalmology, University of California San Francisco, San Francisco, California, USA.|Francis I. Proctor Foundation, University of California San Francisco, San Francisco, California, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: McLeod
authors.affiliation: Department of Ophthalmology, University of California San Francisco, San Francisco, California, USA.|Francis I. Proctor Foundation, University of California San Francisco, San Francisco, California, USA.
authors.forename: Nisha R
authors.initials: NR
authors.lastname: Acharya
authors.affiliation: Department of Ophthalmology, University of California San Francisco, San Francisco, California, USA.|Francis I. Proctor Foundation, University of California San Francisco, San Francisco, California, USA.|Department of Optometry, University of California Berkeley, Berkeley, California, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rose-Nussbaumer
mesh_terms: D019072:Antibiotic Prophylaxis; D000935:Antifungal Agents / Q000627:therapeutic use*; D003320:Corneal Ulcer / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D004311:Double-Blind Method; D015821:Eye Infections, Fungal / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010866:Natamycin / Q000627:therapeutic use*; D062606:Tertiary Care Centers; D014640:Vancomycin / Q000627:therapeutic use*; D014792:Visual Acuity / Q000502:physiology*
chemical_list: D000935:Antifungal Agents; D014640:Vancomycin; D010866:Natamycin
keywords: anti-infective agents; fungal disease; fungal keratitis