Prolonged Duration Topical Corneal Anesthesia With the Cationic Lidocaine Derivative QX-314

Abstract

PurposeTopical corneal local anesthetics are short acting and may impair corneal healing. In this study we compared corneal anesthesia and toxicity of topically applied N-ethyl lidocaine (QX-314) versus the conventional local anesthetic, proparacaine (PPC).MethodsVarious concentrations of QX-314 and 15 mM (0.5%) PPC were topically applied to rat corneas. Corneal anesthesia was assessed with a Cochet-Bonnet esthesiometer at predetermined time points. PC12 cells were exposed to the same solutions to assess cytotoxicity. Repeated topical corneal administration in rats was then used to assess for histologic evidence of toxicity. Finally, we created uniform corneal epithelial defects in rats and assessed the effect of repeated administration of these compounds on the defect healing rate.ResultsQX-314 (15 mM) and PPC (15 mM) caused similar total duration (114 ± 17 and 87 ± 16 minutes, respectively; P = 0.06) of anesthesia. The depth of anesthesia was similar between these low-dose groups at 15 minutes after application (1.8 ± 0.3- and 2.0 ± 0.8-cm filament lengths). QX-314 (100 mM) provided more prolonged corneal anesthesia (174 ± 13 minutes; P < 0.0001), with improved depth at 15 minutes (0.7 ± 0.3-cm filament length; P = 0.007). All tested concentrations of QX-314 demonstrated similar or less toxicity than 0.5% PPC.ConclusionsTopical administration of QX-314 is effective for corneal anesthesia and demonstrates no histologic signs of local toxicity in a rodent model. In higher concentrations, QX-314 provides more than twofold the duration of anesthetic effect than does 0.5% PPC.Translational RelevanceOur study reveals a clinically relevant compound providing prolonged duration topical corneal anesthesia.

Resveratrol increases tear production and spontaneous ocular pain after corneal abrasion in male, but not female, rats using a preclinical model of photorefractive keratectomy (PRK)

“…Previous in vivo rat studies involving abrasion or debridement of the corneal epithelium (Daull et al, 2016;Green et al, 2015;Ho et al, 2013;Kim et al, 2010;Kim et al, 2013;McAlvin et al, 2015;Moore et al, 2013;Nagai et al, 2018;Nagai et al, 2010;Romano et al, 2014;Wang F. et al, 2020;Wang L. et al, 2013;Woodruff et al, 2019), or excimer laser ablation of the anterior stroma (Azar et al, 1996;Hafezi et al, 2018;Lee K. S. et al, 2012;Lu et al, 1999;O'Brien et al, 1998;Prada and Ngo-Tu, 2011;Sandvig et al, 1997;Varela et al, 2002;Wang T. et al, 2013;Woo et al, 2014) have focused on mechanisms of corneal epithelial cell wound healing, and the effects of topical therapeutics after debridement or ablation. These studies were primarily performed in male rats and used fluorescein ophthalmic staining to examine corneal wound healing (Ho et al, 2013;Kim et al, 2010;Kim et al, 2013;McAlvin et al, 2015;Moore et al, 2013;Nagai et al, 2018;Nagai et al, 2010;Romano et al, 2014;Wang F. et al, 2020;Wang L. et al, 2013;Woodruff et al, 2019). Few studies have looked at the impact of topical therapeutics on corneal nerve reinnervation (Romano et al, 2014) and spontaneous ocular behavior (Green et al, 2015) in rats.…”