Topically applied 1% voriconazole induces dysplastic changes on the ocular surface: animal study

Cutan Ocul Toxicol. 2018 Dec;37(4):328-331. doi: 10.1080/15569527.2018.1463237. Epub 2018 Apr 26.

Abstract

Purpose: To identify the risk of inducing ocular surface dysplasia following topical administration of 1% voriconazole eye drop.

Methods: Fourteen noninflamed healthy eyes of 14 white adult New Zealand rabbits were included in the study. The rabbits were randomly divided into two groups comprised of 7 rabbits each. Group 1 received topical 1% voriconazole and Group 2 received topical saline as the control group. In all animals, right eye was selected for the study. In Group 1 (Voriconazole Group), single drop of voriconazole was instilled every 10 min consecutively for 17 times a day for 60 days. In Group 2 (Control Group), single drop of saline was instilled every 10 min consecutively for 17 times a day for 60 days. At two months, animals were sacrificed and study eyes were enucleated with the eyelids. The specimens were stained with hematoxylin-eosin and histopathologic changes in cornea, bulbar and palpebral conjunctiva were evaluated under light microscope.

Results: There were no macroscopically visible lesions on the ocular surface of any rabbits. Histopathological evaluation showed mild to moderate dysplasia localized mainly in the limbus and extending to the adjacent cornea and bulbar conjunctiva in all rabbits in Voriconazole Group. Severe dysplasia or carcinoma in situ was not observed. In the Control Group, dysplasia was not observed, at all.

Conclusion: This animal study provides a possible relationship between topically administered 1% voriconazole and ocular surface dysplasia. We recommend ophthalmologists to be aware of the risk of ocular surface dysplasia in patients received voriconazole eye drop.

Keywords: Dysplasia; fungal keratitis; ocular surface neoplasia; phototoxicity; voriconazole.

MeSH terms

  • Administration, Topical
  • Animals
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / toxicity*
  • Conjunctivitis / chemically induced
  • Conjunctivitis / pathology
  • Cornea / pathology
  • Eye / pathology*
  • Female
  • Keratitis / chemically induced
  • Keratitis / pathology
  • Ophthalmic Solutions
  • Rabbits
  • Voriconazole / administration & dosage
  • Voriconazole / toxicity*

Substances

  • Antifungal Agents
  • Ophthalmic Solutions
  • Voriconazole