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

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

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.

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.

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.