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Toxicity of Intrastromal Voriconazole Injection on Corneal Endothelium in Rabbits

Park, Chang Hyun MD; Lee, Hyun Soo MD; Chung, Sung Kun MD, PhD

doi: 10.1097/ICO.0000000000000181
Clinical Science

Purpose: The aim of this study was to evaluate the toxicity of intrastromally injected voriconazole on corneal endothelial cells in rabbits.

Methods: In total, 32 eyes of 16 rabbits (8 eyes for each group) were divided into 4 groups according to the concentration of voriconazole [group A: 50 μg/0.1 mL (0.05%), group B: 100 μg/0.1 mL (0.1%), group C: 250 μg/0.1 mL (0.25%), or group D: 500 μg/0.1 mL (0.5%)]. Right eyes were injected intrastromally with voriconazole at concentrations of 50 μg/0.1 mL, 100 μg/0.1 mL, 250 μg/0.1 mL, or 500 μg/0.1 mL. Left eyes were injected intrastromally with isotonic saline as controls. Central corneal thickness and endothelial cell counts were measured before and at 6 hours, 1 day, and 1 week after the injection was given. Corneas were then harvested for transmission electron microscopy.

Results: Only the 0.5% group did not significantly recover from corneal edema 1 week after the injection (P = 0.167, P = 0.051, P = 0.086, P = 0.001 in groups A–D, respectively). There were significant differences in endothelial cell counts for the 0.1% and 0.25% groups (P = 0.077, P = 0.019, P = 0.008 in groups A–C, respectively). Transmission electron microscopy evaluation revealed definite necrotic changes in endothelial cells at concentrations of 0.1%, 0.25%, and 0.5%, but only microstructural changes at a concentration of 0.05%.

Conclusions: Our results suggest that voriconazole could be injected safely into the intrastromal layer at a concentration of 0.05% with low endothelial cell toxicity. However, injections should be administered with caution because of the risk of microstructural damage.

*Department of Ophthalmology and Visual Science, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea;

Department of Ophthalmology, Air Base Hospital of 18th Fighter Wing, Republic of Korea Air Force, Korea;

Department of Ophthalmology and Visual Science, St Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Reprints: Sung Kun Chung, MD, PhD, Department of Ophthalmology and Visual Science, St Paul's Hospital, College of Medicine, The Catholic University of Korea, #222 Banpo-daero, Seocho-gu, Seoul, 137-701, Korea (e-mail: eyedoc@catholic.ac.kr).

The authors have no funding or conflicts of interest to disclose.

Received February 06, 2014

Accepted May 07, 2014

Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.