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Management remains challenging due to limited therapeutic options, variable clinical responses, and a lack of standardized treatment guidelines. Diagnosis is frequently delayed because of the non-specific clinical presentation, and early use of topical corticosteroids can exacerbate disease severity and worsen outcomes. The formation of highly drug-resistant cysts in chronic infection further complicates treatment. Currently, prolonged combination therapy with topical biguanides and aromatic diamidines remains the mainstay of treatment. However, recent evidence supports the use of topical biguanide monotherapy (in higher concentrations) in AK with comparable outcomes to combination treatment. Adjunctive therapies, including azoles, miltefosine, and corticosteroids, may be beneficial in refractory disease. Surgical interventions, such as therapeutic keratoplasty, are often required in advanced or non-responsive cases. The choice of therapy is frequently empirical, guided by clinician experience and drug availability. Emerging therapeutic approaches, including antimicrobial peptides, synthetic polymers, bioactive natural compounds, and ultraviolet C therapy, show promise as more effective or better-tolerated alternatives. This review provides an up-to-date overview of current medical and surgical treatments, explores novel interventions in the pipeline, and highlights the need for evidence-based, individualized management strategies in AK.<\/jats:p>","DOI":"10.1128\/cmr.00277-25","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T13:05:23Z","timestamp":1781010323000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Advances in medical and surgical management of\n                    <i>Acanthamoeba<\/i>\n                    keratitis: a comprehensive review"],"prefix":"10.1128","volume":"39","author":[{"given":"Matthew","family":"Azzopardi","sequence":"first","affiliation":[{"name":"Moorfields Eye Hospital","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu 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