Comparative evaluation of topical versus intrastromal voriconazole as an adjunct to natamycin in recalcitrant fungal keratitis

Ophthalmology. 2013 Apr;120(4):677-81. doi: 10.1016/j.ophtha.2012.09.023. Epub 2012 Dec 12.


Objective: To compare the efficacy of topical voriconazole and topical natamycin with that of intrastromal voriconazole and topical natamycin in patients with recalcitrant fungal keratitis.

Design: Randomized clinical trial.

Participants: Forty eyes of 40 patients with fungal keratitis (positive smear or culture results or both) larger than 2 mm, involving up to two thirds of the stromal depth, and not responding to topical natamycin therapy for 2 weeks were recruited.

Intervention: The patients were randomized to receive either topical 1% voriconazole therapy (n = 20) or intrastromal injections of voriconazole 50 μg/0.1 ml (n = 20). The patients in both groups continued topical natamycin 5% every 4 hours until the ulcer healed.

Main outcome measures: Primary outcome measure was best spectacle-corrected visual acuity (BSCVA) 3 months after intervention, and secondary outcome measures were time to healing and the size of the scar.

Results: The patients in both groups had comparable baseline parameters. The mean BSCVA after treatment was 1.295 ± 0.5 logarithm of the minimum angle of resolution (logMAR) units in the topical group and 1.692 ± 0.29 logMAR units in the intrastromal group. The visual acuity after treatment was significantly better in the topical voriconazole group (P = 0.008). Nineteen patients receiving topical voriconazole and 16 patients who were given intrastromal voriconazole healed with therapy.

Conclusions: Topical voriconazole seems to be a useful adjunct to natamycin in fungal keratitis not responding to topical natamycin. Intrastromal injections did not offer any beneficial effect over topical therapy.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antifungal Agents / administration & dosage
  • Corneal Stroma
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Eye Infections, Fungal / drug therapy*
  • Eye Infections, Fungal / microbiology
  • Female
  • Follow-Up Studies
  • Humans
  • Injections
  • Keratitis / drug therapy*
  • Keratitis / microbiology
  • Male
  • Middle Aged
  • Natamycin / administration & dosage*
  • Ophthalmic Solutions
  • Pyrimidines / administration & dosage*
  • Treatment Outcome
  • Triazoles / administration & dosage*
  • Voriconazole


  • Antifungal Agents
  • Ophthalmic Solutions
  • Pyrimidines
  • Triazoles
  • Natamycin
  • Voriconazole