{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T10:02:53Z","timestamp":1781085773459,"version":"3.54.1"},"reference-count":38,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["207472\/Z\/17\/Z"],"award-info":[{"award-number":["207472\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns5:p>\n                    Introduction Fungal corneal infection (fungal keratitis [FK]) poses significant treatment challenges. The efficacy of current topical antifungals is inconsistent and often limited, especially in low and middle-income countries where the majority of FK cases occur. Topical natamycin 5% is the current primary treatment in many countries, however, a substantial proportion of cases develop progressive disease, even with intensive treatment. Given the limitations of existing antifungal treatments, there is a need for alternative treatment strategies to address this condition. Chlorhexidine, an antiseptic with both antibacterial and antifungal properties, has received attention as a potential therapeutic agent. While a recent randomized controlled trial (RCT) in Nepal demonstrated the superiority of natamycin over chlorhexidine, a pilot study in Uganda has indicated a possible role for adjunctive chlorhexidine 0.2% in FK treatment. The contrasting findings necessitate a comprehensive RCT to investigate the potential benefit of adding topical chlorhexidine 0.2% alongside natamycin 5% in the management of FK. Methods We will test the hypothesis that topical natamycin 5% in combination with chlorhexidine 0.2% is superior to topical natamycin 5% alone in a two-arm, single-masked RCT (ISRCTN, ISRCTN87195453, registered 27\/08\/2020,\n                    <ns5:ext-link xmlns:ns6=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" ns6:href=\"https:\/\/www.isrctn.com\/ISRCTN87195453\">https:\/\/www.isrctn.com\/ISRCTN87195453<\/ns5:ext-link>\n                    ). Participants are adults with FK presenting to tertiary ophthalmic hospitals in Tanzania and Uganda. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and corneal scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2-6 random block size). Patients will be reviewed at days 2, 7 (with re-culture), 14, 21, month 2, and month 3. The primary outcome is best spectacle corrected visual acuity (BSCVA) at three months. Primary analysis (intention-to-treat) will be by linear regression, with treatment arm and baseline BSCVA pre-specified covariates. Secondary outcomes include epithelial healing time, scar\/infiltrate size, ulcer depth, hypopyon size, perforation and\/or therapeutic penetrating keratoplasty, and positive re-culture rate.\n                  <\/ns5:p>","DOI":"10.12688\/wellcomeopenres.21390.1","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T12:46:43Z","timestamp":1743166003000},"page":"165","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Randomised controlled trial of topical combination therapy chlorhexidine 0.2% and natamycin 5% versus topical natamycin 5% alone for fungal keratitis in East Africa: study protocol"],"prefix":"10.12688","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-2131","authenticated-orcid":false,"given":"Jeremy John","family":"Hoffman","sequence":"first","affiliation":[{"name":"London London School of Hygiene & Tropical Medicine"},{"name":"Moshi Kilimanjaro Christian Medical Centre"},{"name":"London National Institute for Health Research Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Arunga","sequence":"additional","affiliation":[{"name":"London London School of Hygiene & Tropical Medicine"},{"name":"Mbarara Western Region Mbarara University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einoti","family":"Matayan","sequence":"additional","affiliation":[{"name":"Moshi Kilimanjaro Christian Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0608-7337","authenticated-orcid":false,"given":"Abel","family":"Ebong","sequence":"additional","affiliation":[{"name":"Mbarara Western Region Mbarara University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9646-7074","authenticated-orcid":false,"given":"Francis","family":"Orishaba","sequence":"additional","affiliation":[{"name":"Mbarara Western Region Mbarara University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Makupa","sequence":"additional","affiliation":[{"name":"Moshi Kilimanjaro Christian Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muna","family":"Elisante","sequence":"additional","affiliation":[{"name":"Moshi Kilimanjaro Christian Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Yadav","sequence":"additional","affiliation":[{"name":"Lahan Eastern Development Region Sagarmatha Choudhary Eye Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-8441","authenticated-orcid":false,"given":"Sandip","family":"Das Sanyam","sequence":"additional","affiliation":[{"name":"Lahan Eastern Development Region Sagarmatha Choudhary Eye Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3436-0162","authenticated-orcid":false,"given":"Tara","family":"Mtuy","sequence":"additional","affiliation":[{"name":"London London School of Hygiene & Tropical Medicine"},{"name":"Moshi Kilimanjaro Christian Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2371-5709","authenticated-orcid":false,"given":"David","family":"Macleod","sequence":"additional","affiliation":[{"name":"London London School of Hygiene & Tropical Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9251-2318","authenticated-orcid":false,"given":"Astrid","family":"Leck","sequence":"additional","affiliation":[{"name":"London London School of Hygiene & Tropical Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9883-668X","authenticated-orcid":false,"given":"Victor H","family":"Hu","sequence":"additional","affiliation":[{"name":"London London School of Hygiene & Tropical Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1872-9169","authenticated-orcid":false,"given":"Matthew J","family":"Burton","sequence":"additional","affiliation":[{"name":"London London School of Hygiene & Tropical Medicine"},{"name":"London National Institute for Health Research Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of 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The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}