Evidence-based Treatment Protocol Best for AK, Study Finds

Failure to use defined treatment protocols is unusual in other fields of medicine where evidence-based protocols for drug delivery are critical to treatment. Apart from the protocol used in the researchers’ Phase III study, the TST (Topical, Systemic and Targeted Therapy) protocol for fungal keratitis is the only other evidence-based keratitis protocol for microbial keratitis. Photo: Christine Sindt, OD. Click image to enlarge. Until recently, there has been no comprehensive evidence-based treatment protocol for Acanthamoeba keratitis (AK). This has led to variability in treatment delivery by cornea specialists and difficulty for the non-specialists who often initiate therapy. This variability makes evaluation of AK treatment outcomes difficult to compare. Researchers have developed a detailed treatment delivery protocol for AK in a recent Phase III treatment trial. In a recent study published in The Ocular Surface, they tested the hypothesis that adherence to a detailed treatment delivery protocol would provide better outcomes than practitioners’ individualized treatments.They compared the outcomes for two approaches: (1) AK treatment from a retrospective study where polyhexamethylene biguanide (PHMB) 0.02% plus a diamidine 0.1% (propamidine or hexamidine) was delivered using practitioners’ individualized treatment protocols, and (2) those for the protocol-treated participants using PHMB 0.02% plus propamidine 0.1% in one arm of a recent randomized controlled trial. The study found substantial potential improvements in clinical outcomes for protocol-driven treatment, as the proportions of those cured without surgery increased from 56.3% to 87.2% (a 1.59-fold improvement) and the best-corrected visual acuity outcomes ≥20/25 improved from 31.3% to 61.7% (a 2.1-fold improvement).“The use of a protocol for microbial keratitis treatment delivery may be controversial for many corneal specialists, as it differs from the current practice of individualized treatment, even though the latter differs from practice adopted by much of the rest of medicine,” the researchers wrote in their paper.Patients were from two centers in Milan and London and treated at different times; the individualized cohort (n=96) was treated from 1991 to 2012, while the protocol cohort (n=47) was treated from 2017 to 2021. There were no detailed treatment delivery protocols in place for managing patients. These administration regimens included differing initiating treatment frequencies and periods, followed by tapering of anti-amoebic treatment to as few applications as two times daily as the clinical signs improved, together with discontinuing anti-amoebic treatment either before or after adjunctive topical steroids, when these were used. The researchers’ protocol included topical steroids being started at 15 days, as opposed to the protocol-mandated earliest start date at 21 days, and eye drops being splashed into the eye as opposed to being dropped before the patient was re-instructed. Among potential confounding factors examined, baseline AK disease stage, treatment center or the type of diamidine did not significantly influence outcomes.“Although we are sure that this protocol could be altered to further improve results, we think it will provide patients and practitioners with a sound evidence base for treatment going forward and hope that it will be adopted by practitioners whose outcomes are not as good as the ones in this study,” the study authors wrote. “The development of similarly well-defined treatment delivery protocols for other microbial keratitis causes, including bacterial keratitis, might improve the outcomes for those diseases. We hope this study results in some debate about the use of protocols for microbial keratitis treatment.”Click here for the journal source. Dart JKG, Papa V, Rama P, et al. Acanthamoeba keratitis treatment outcomes compared for drug delivery by protocol vs. physician's individualized treatment. Ocul Surf. April 7, 2025. [Epub ahead of print].