An expert's guide to Acanthamoeba keratitis pharmacology.

INTRODUCTION: Acanthamoeba keratitis (AK) is a rare but sight-threatening corneal infection, increasingly associated with contact lens wear, whose treatment remains constrained by the lack of agents that are both cysticidal and well tolerated by the cornea. This review appraises the current pharmacological landscape and the obstacles impeding therapeutic progress. AREAS COVERED: PubMed, Scopus, Google Scholar, and Web of Science were searched for articles published between January 2000 and June 2026 using combinations of the terms 'Acanthamoeba keratitis,' 'treatment,' 'pharmacology,' 'amoebicidal' and individual drug names; reference lists were hand-searched. We provide an overview of the epidemiology, biology, life cycle and pathogenic mechanisms of AK. We then critically evaluate current clinical management strategies and their inherent limitations before providing a comprehensive synthesis of recent in vitro and in vivo investigations to identify effective drugs that target both the cyst and trophozoite stages with low cytotoxicity. EXPERT OPINION: Prolonged, intensive topical regimens impose a substantial burden that drives poor adherence and relapse, and standardized protocol-based dosing offers the most immediate practical gain. The field now requires agents combining potent cysticidal activity with corneal biocompatibility, alongside standardized assays and validated ex vivo models, so that promising laboratory activity translates into genuine clinical benefit.