Intracameral Concentration and Safety Profile of High Concentration Ganciclovir Eyedrop in a Rabbit Model

Abstract

Purpose:

This study aimed to evaluate the efficacy and safety of topically administered ganciclovir (GC) eye drops at varying concentrations.

Methods:

Fifteen New Zealand white rabbits were divided into 5 groups (n = 3 per group): control (saline), 0.15%, 2%, 4%, and 8% GC eye drops. GC eye drops were applied to both eyes 4 times a day for 10 days. The concentration of GC in the aqueous humor was measured using liquid chromatography-tandem mass spectrometry. Ocular toxicity scores were graded using slit-lamp microscopy. Specular microscopy was performed after final instillation. Corneal tissues were analyzed for scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Intraocular pressure (IOP) was also measured.

Results:

The mean GC concentrations in aqueous humor were significantly increased in a dose-dependent manner: 0.15% (40.75 ± 18.54 ng/mL), 2% (287.66 ± 114.67 ng/mL), 4% (855.70 ± 408.22 ng/mL), and 8% (1916.85 ± 985.97 ng/mL) (P = 0.004, K-W test). Total ocular surface toxicity scores rose with increasing concentrations, with the most pronounced toxicity observed in the 8% group. Specular microscopy and SEM showed no significant differences in endothelial cell density or morphology. TEM revealed increased cell vacuoles in the 8% group, though intercellular junctions remained intact. There were no significant differences in IOP values across all groups.

Conclusions:

Topical GC achieved effective ocular penetration, reaching concentrations above the 50% inhibitory dose for cytomegalovirus replication at 2% or higher. Dose-dependent ocular surface toxicity was observed, particularly at higher concentrations. However, no structural or cellular damage to the corneal endothelium was detected.