Prolonged corneal anaesthesia by proxymetacaine hydrochloride detected by a thermal cooling stimulus Paul J. Murphy *, Anna M. Ntola Cardiff University, School of Optometry and Vision Sciences, Contact Lens and Anterior Eye Research Unit, Maindy Road, Cardiff, CF24 4LU, United Kingdom 1. Introduction The cornea is populated by a variety of sensory nerve endings that are specifically sensitive to mechanical, chemical and thermal stimuli. These nerve endings are arranged in large overlapping receptive fields that combine to produce an exquisite level of sensitivity to potentially noxious stimuli. There are two nerve types that provide this sensitivity: A@ fibres and C fibres. A@ fibres are large diameter, straight nerves that respond primarily to mechanical stimuli, while C fibres are small diameter, beaded nerves that respond to thermal and chemical stimuli [1–3]. These nerve types have four different neuro-receptors: mechano-, polymodal, mechano-heat, and cold; mediated by a range of molecular receptors such as Vanilloid Receptor-1 (VR-1), Stretch- Inactivated Channel (SIC), Cold-Menthol Receptor Type 1 (CMR1), and Acid-Sensitive-Ion-Channels (ASICs) [4–7]. Little is known of the relative sensitivities of these difference nerve types. To our knowledge, only one study [8] has investigated the interaction of different sub-modalities at sensory threshold. They proposed that there are at least five corneal psychophysical sensory channels mediating cold, heat, mechanical, chemical and histamine type substance modalities. The channels are not completely independent, but interact due to sharing of molecular and neuro-receptors. Thus a subject with good mechanical sensitivity can be expected to have good thermal sensitivity. Topical corneal anaesthetics are designed to temporarily block nerve sensitivity. Previous studies to assess the efficacy of anaesthetics have used aesthesiometers with mechanical stimuli, which means that only the action of the anaesthetic on the A@ fibres has been assessed. While it is reasonable to assume that a similar pattern of anaesthetic produced sensitivity loss and recovery will occur for the C fibres, a previous study on the anaesthetic action of 0.4% benoxinate hydrochloride (oxybuprocaine) using a thermal cooling stimulus found that the time to maximum anaesthesia was delayed and the duration of effect was prolonged in comparison to the results from mechanical stimulus studies [9]. These results suggest that our understanding of the anaesthetic efficacy of topical ophthalmic anaesthetics is incomplete. Proxymetacaine hydrochloride (proparacaine) is a topical anaesthetic frequently used in clinical optometric practice [10– 13]. To investigate whether a similar difference in measured anaesthetic effect, as found with benoxinate hydrochloride, occurs Contact Lens & Anterior Eye 32 (2009) 84–87 ARTICLE INFO Keywords: Topical anaesthesia Aesthesiometry Corneal sensitivity Proxymetacaine Iris colour ABSTRACT Purpose: To assess the duration, depth and recovery time of anaesthesia produced by 0.5% proxymetacaine hydrochloride (proparacaine), using a thermal cooling stimulus. Methods: Seventeen non-contact lens-wearing subjects were recruited (mean age = 26 Æ 3.6 years, range = 23–39; blue iris = 8, brown iris = 9). Central corneal sensitivity was measured in the right eye of each patient to establish a baseline, before 20 ml of either 0.5% proxymetacaine hydrochloride (p) or 0.9% unpreserved saline (s) was instilled under four experimental conditions (right eye–left eye): p–p, p–s, s–p, s– s. Corneal sensitivity was re-measured at 2, 5, 10, 15, 20, 30, 45 and 60 min post-instillation. Results: The onset of anaesthesia was observed at 2 min (Wilcoxon, p < 0.001), with the maximum anaesthesia occurring at 15 min (Wilcoxon, p < 0.001). Recovery of corneal sensitivity to baseline levels did not occur by 60 min (Wilcoxon, p < 0.001). No difference in onset time, depth of anaesthesia, or recovery time was noted between the blue and brown iris subjects (Mann–Whitney, p > 0.05). Conclusions: Although the anaesthetic effect of 0.5% proxymetacaine hydrochloride continues for more than 60 min, this finding does not alter current clinical practice. The extended duration, however, is of relevance to studies that use corneal anaesthesia to investigate the role of corneal nerves in the blink mechanism. ß 2009 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. * Corresponding author. Tel.: +44 2920 874703; fax: +44 2920 874859. E-mail address: MurphyPJ@cardiff.ac.uk (P.J. Murphy). Contents lists available at ScienceDirect Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae 1367-0484/$ – see front matter ß 2009 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clae.2008.12.006