Topical Chlorhexidine 0.2% versus Topical Natamycin 5% for the Treatment of Fungal Keratitis in Nepal: A Randomized Controlled Noninferiority Trial
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Date
2022
Journal Title
Journal ISSN
Volume Title
Publisher
Ophthalmology
Abstract
To investigate if topical chlorhexidine 0.2%, which is low cost and easy to formulate, is noninferior
to topical natamycin 5% for the treatment of filamentous fungal keratitis.
Design: Randomized controlled, single-masked, noninferiority clinical trial.
Participants: Adults attending a tertiary-level ophthalmic hospital in Nepal with filamentous fungal infection
confirmed on smear or confocal microscopy.
Methods: Participants were randomly allocated to receive topical chlorhexidine 0.2% or topical natamycin
5%. Primary analysis (intention-to-treat) was by linear regression, using baseline logarithm of the minimum angle
of resolution (logMAR) best spectacle-corrected visual acuity (BSCVA) and treatment arm as prespecified
covariates. Mixed fungal-bacterial infections were excluded from the primary analysis but included in secondary
analyses and secondary safety-related outcomes. The noninferiority margin was 0.15 logMAR. This trial was
registered with ISRCTN, number ISRCTN14332621.
Main Outcome Measures: The primary outcome measure was BSCVA at 3 months. Secondary outcome
measures included perforation or therapeutic penetrating keratoplasty by 90 days.
Results: Between June 3, 2019, and November 9, 2020, 354 eligible participants were enrolled and randomly
assigned: 178 to chlorhexidine and 176 to natamycin. Primary outcome data were available for 153 and 151 of the
chlorhexidine and natamycin groups, respectively. Of these, mixed bacterial-fungal infections were found in 20
cases (12/153 chlorhexidine, 8/151 natamycin) and excluded from the primary analysis. Therefore, 284 patients
were assessed for the primary outcome (141 chlorhexidine, 143 natamycin). We did not find evidence to suggest
chlorhexidine was noninferior to natamycin and in fact found strong evidence to suggest that natamycin-treated
participants had significantly better 3-month BSCVA than chlorhexidine-treated participants, after adjusting for
baseline BSCVA (regression coefficient, 0.30; 95% confidence interval [CI], 0.42 to 0.18; P < 0.001). There
were more perforations and emergency corneal grafts in the chlorhexidine arm (24/175, 13.7%) than in the
natamycin arm (10/173, 5.8%; P ¼ 0.018, mixed infections included), whereas natamycin-treated cases were less
likely to perforate or require an emergency corneal graft, after adjusting for baseline ulcer depth (odds ratio, 0.34;
95% CI, 0.15e0.79; P ¼ 0.013).
Conclusions: Treatment with natamycin is associated with significantly better visual acuity, with fewer
adverse events, compared with treatment with chlorhexidine. Natamycin remains the preferred first-line monotherapy
treatment for filamentous fungal keratitis. Ophthalmology 2022;129:530-541 ª 2021 by the American
Academy of Ophthalmology.
Description
Keywords
Topical Chlorhexidine, Topical Natamycin, Treatment, Fungal Keratitis
Citation
Hoffman, J. J., Yadav, R., Sanyam, S. D., Chaudhary, P., Roshan, A., Singh, S. K., ... & Burton, M. J. (2022). Topical chlorhexidine 0.2% versus topical natamycin 5% for the treatment of fungal keratitis in Nepal: a randomized controlled noninferiority trial. Ophthalmology, 129(5), 530-541. https://doi.org/10.1016/j.ophtha.2021.12.004