Contents lists available at ScienceDirect Contact Lens and Anterior Eye journal homepage: www.elsevier.com/locate/clae In vitro anti-demodectic effects and terpinen-4-ol content of commercial eyelid cleansers Isabella M.Y. Cheung, Ally L. Xue, Andy Kim, Kirsty Ammundsen, Michael T.M. Wang, Jennifer P. Craig ⁎ Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, New Zealand ARTICLE INFO Keywords: Blepharitis Demodex Tea tree oil Eyelid cleanser Eyelid hygiene ABSTRACT Purpose: To compare the in vitro anti-demodectic activity of four commercially available dedicated eyelid cleansers (Cliradex ® towelette cleanser, Oust™ Demodex ® cleanser, Blephadex™ eyelid foam, TheraTears ® SteriLid ® eyelid cleanser), tea tree oil, undiluted terpinen-4-ol and linalool; and to assess the terpinen-4-ol content of the commercial cleansers and tea tree oil. Methods: In vitro anti-demodectic efficacy assessment: 93 viable Demodex mites were acquired from the epilated eyelashes of 10 participants, and were randomised to application with one of the four eyelid cleansers, 100% and 50% tea tree oil, undiluted terpinen-4-ol and linalool, or no treatment. Following treatment application, mite viability was assessed for 300 min, based on limb/body movement and/or the development of a crenated/ translucent appearance. Kaplan-Meier survival analysis was then performed. Mass spectrometry analysis: The absolute concentration of terpinen-4-ol and the relative abundance of linalool in the four eyelid cleansers and tea tree oil were determined. Results: In vitro anti-demodectic efficacy assessment: No significant differences were observed between undiluted tea tree oil, terpinen-4-ol and linalool (all p > 0.05). Although all commercial eyelid cleansers effected lower mite survival probabilities than the untreated group, Cliradex ® was the only eyelid cleanser that demonstrated comparable antiparastic activity to 50% tea tree oil (p = 0.36). Mass spectrometry analysis: Among the four eyelid cleansers, Cliradex ® contained the highest concentration of terpinen-4-ol, while linalool was present in TheraTears ® SteriLid ® only. Conclusions: Of the four commercial eyelid cleansers, Cliradex ® demonstrated the highest levels of in vitro anti- demodectic activity and terpinen-4-ol content. Undiluted linalool and terpenin-4-ol showed comparable anti- parasitic efficacy, and the use of linalool in the management of demodectic blepharitis warrants further in- vestigation. 1. Introduction Blepharitis is a common ocular condition characterised by chronic eyelid inflammation [1–3]. It is recognised to have an adverse impact on ocular comfort, vision, and quality of life [1,4,5]. Although the pathophysiological mechanisms of blepharitis are not fully understood, ocular demodicosis has been implicated as a significant risk factor [6–8]. Demodex folliculorum and Demodex brevis infestation, observed mainly in eyelash follicles and meibomian glands [9–11], respectively, are thought to contribute towards structural obstruction, cellular de- struction, and bacterial hypercolonisation [6,12–15], consequently re- sulting in overactivation of host inflammatory responses [11,18]. Topical treatment with tea tree oil (Melaleuca alternifolia) is cur- rently the standard management for demodectic blepharitis [7,16]. Several clinical studies have independently demonstrated the efficacy of tea tree oil eyelid scrubs and ointments in reducing ocular Demodex load and symptoms of blepharitis [17–22]. The anti-demodectic effects of tea tree oil are thought to be attributed primarily to terpinen-4-ol [23], a cyclic monoterpene which also exhibits broad spectrum anti- microbial activity against bacteria and fungi [24–27]. Although ter- pinen-4-ol has been shown to mediate its antibacterial effects through disruption of the cytoplasmic membrane [28], the mechanism by which it inhibits Demodex viability remains yet to established. Recently, tea tree oil and terpinen-4-ol have been incorporated into https://doi.org/10.1016/j.clae.2018.08.003 Received 14 May 2018; Received in revised form 20 July 2018; Accepted 5 August 2018 ⁎ Corresponding author at: Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. E-mail address: jp.craig@auckland.ac.nz (J.P. Craig). Contact Lens and Anterior Eye xxx (xxxx) xxx–xxx 1367-0484/ © 2018 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. Please cite this article as: Cheung, I.M.Y., Contact Lens and Anterior Eye (2018), https://doi.org/10.1016/j.clae.2018.08.003