title: Vitrectomy with fluconazole infusion: retinal toxicity, pharmacokinetics, and efficacy in the treatment of experimental candidal endophthalmitis.
abstract: The aim of this study was to determine the retinal toxicity and intraocular pharmacokinetics of vitrectomy with fluconazole infusion in rabbit eyes and to study its efficacy in the treatment of experimental candidal endophthalmitis. The right eyes of 13 New Zealand White (NZW) rabbits were vitrectomized and infused with 20 mL of 0.2 mg/mL, 1 mg/mL, or 2 mg/mL of fluconazole. An electroretinogram (ERG) was performed on both eyes of each rabbit at different time points. The right eyes of 26 different NZW rabbits were vitrectomized and infused with 20 mL of 2 mg/mL of fluconazole. These rabbits were sacrificed, and their right eyes were enucleated at hours 2, 4, 8, and 24 after the operation, and the concentration of fluconazole in the vitreous was measured by highpressure liquid chromatography. Experimental candidal endophthalmitis was induced in the right eye of 42 other NZW rabbits. Twenty-six (26) of the eyes were then vitrectomized and infused with 20 mL of 2 mg/mL of fluconazole, and the other 16 rabbits served as control. Severity of ocular infection was graded from 0-4 at different time intervals, using an indirect ophthalmoscope. In the first group, ERG showed no significant difference between the experimental eyes and the control eyes--in all concentrations of fluconazole--for up to 3 months. In the second group, the intraocular concentration of fluconazole declined so rapidly that, as of 8 hours after operation, there was none in the vitreous cavity. In the third group, significantly less vitreous opacity was found in the treated eyes on days 3 and 6. However, the difference ceased to be apparent on day 15. Our study suggests that there is no retinal toxicity resulting from vitrectomy with a 2 mg/mL fluconazole infusion, and that it is temporally effective in the treatment of experimental candidal endophthalmitis.
authors.affiliation: Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Cheng-Kuo
authors.initials: CK
authors.lastname: Cheng
authors.forename: Chang-Hao
authors.initials: CH
authors.lastname: Yang
authors.forename: Po-Ren
authors.initials: PR
authors.lastname: Hsueh
authors.forename: Chu-Min
authors.initials: CM
authors.lastname: Liu
authors.forename: Hsuei-Yuh
authors.initials: HY
authors.lastname: Lu
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000633:toxicity; D001682:Biological Availability; D002177:Candidiasis / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D002851:Chromatography, High Pressure Liquid; D004596:Electroretinography; D009877:Endophthalmitis / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D015821:Eye Infections, Fungal / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D015725:Fluconazole / Q000493:pharmacokinetics* / Q000633:toxicity*; D007263:Infusions, Parenteral; D011817:Rabbits; D012160:Retina / Q000187:drug effects*; D016896:Treatment Outcome; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole