Safety and effect of topical neostigmine ophthalmic solution in animal models.

Abstract

The study aimed to evaluate the safety and effect of various dosages of topical neostigmine ophthalmic solution (TNOS) in animal models and establish a recommended dosage for further studies on myasthenia gravis (MG) diagnosis. A placebo-controlled, sequential ascending dose study was conducted in healthy rabbits. Eighteen eyes were randomized to receive one of three concentrations (1.0, 1.5, and 2.5 mg/mL) of TNOS. Pupillary sizes over time were compared with control group that received normal saline solution (NSS). Mean pupillary size of the 1.5 mg/mL group was significantly smaller than control at 30 to 180 min after instillation (maximal mean difference (TNOS - NSS); mMD - 2.58, 95% confidence interval (95% CI) -4.24 to -0.93, p = 0.006). The mean pupillary size of the 2.5 mg/mL group was significantly smaller than the control at 60 to 90 min (mMD - 3.13, 95% CI -5.07 to -1.18, p = 0.005). No significant difference in pupillary size between 1.5 and 2.5 mg/mL groups was observed at any time points. No systemic or ocular complications were observed in any concentration. The 1.5 mg/mL TNOS was the lowest efficacious dose in this study without adverse effects and was considered a promising starting dose for further MG studies.