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Figure.
Percentage of Respondents in 2007 and 2017 Who Reported Actual and Preferred Use of Voriconazole and Natamycin
Percentage of Respondents in 2007 and 2017 Who Reported Actual and Preferred Use of Voriconazole and Natamycin

Actual use was measured by asking participants if they had ever used the treatment, and preferred use was measured by asking participants about their preferred treatment in an ideal situation in which cost, availability, and other concerns were not issues.

Table.  
Demographic Characteristics of Respondents in 2007 and 2017
Demographic Characteristics of Respondents in 2007 and 2017
1.
Prajna  NV, Krishnan  T, Mascarenhas  J,  et al; Mycotic Ulcer Treatment Trial Group.  The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole.  JAMA Ophthalmol. 2013;131(4):422-429. doi:10.1001/jamaophthalmol.2013.1497PubMedGoogle Scholar
2.
Sharma  S, Das  S, Virdi  A,  et al.  Re-appraisal of topical 1% voriconazole and 5% natamycin in the treatment of fungal keratitis in a randomised trial.  Br J Ophthalmol. 2015;99(9):1190-1195. doi:10.1136/bjophthalmol-2014-306485PubMedGoogle Scholar
3.
Arora  R, Gupta  D, Goyal  J, Kaur  R.  Voriconazole versus natamycin as primary treatment in fungal corneal ulcers.  Clin Exp Ophthalmol. 2011;39(5):434-440. doi:10.1111/j.1442-9071.2010.02473PubMedGoogle Scholar
4.
Loh  AR, Hong  K, Lee  S, Mannis  M, Acharya  NR.  Practice patterns in the management of fungal corneal ulcers.  Cornea. 2009;28(8):856-859.PubMedGoogle Scholar
5.
Lalitha  P, Prajna  NV, Oldenburg  CE,  et al.  Organism, minimum inhibitory concentration, and outcome in a fungal corneal ulcer clinical trial.  Cornea. 2012;31(6):662-667. doi:10.1097/ICO.0b013e31823f8ae0PubMedGoogle Scholar
6.
Prajna  VN, Lalitha  PS, Mascarenhas  J,  et al.  Natamycin and voriconazole in Fusarium and Aspergillus keratitis: subgroup analysis of a randomised controlled trial.  Br J Ophthalmol. 2012;96(11):1440-1441. doi:10.1136/bjophthalmol-2012-301825PubMedGoogle Scholar
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Research Letter
December 2017

Evolution of Practice Patterns for the Treatment of Fungal Keratitis

Author Affiliations
  • 1Francis I. Proctor Foundation, University of California, San Francisco
  • 2Department of Ophthalmology, University of California, San Francisco
  • 3Department of Epidemiology and Biostatistics, University of California, San Francisco
  • 4Aravind Eye Care System, Madurai, India
  • 5Programme FSS, Université Abdou Moumouni de Niamey, Programme National de Santé Oculaire, Niamey, Niger
  • 6Department of Ophthalmology, Oregon Health Sciences University, Portland
  • 7Department of Ophthalmology & Vision Science, Eye Center, University of California, Davis
JAMA Ophthalmol. 2017;135(12):1448-1449. doi:10.1001/jamaophthalmol.2017.4763

The Mycotic Ulcer Treatment Trial I (MUTT I) demonstrated the superiority of natamycin compared with voriconazole for the treatment of filamentous fungal keratitis.1 This and other recent trials2,3 suggest that natamycin should be the treatment of choice for filamentous fungal keratitis. A survey of experts (approximately 800 surveyed; 92 respondents) conducted in 2007 found that most clinicians identified voriconazole as their preferred treatment.4 We present results of a subsequent survey with identical questions that was conducted to examine changes in practice patterns for fungal keratitis.

Methods

The 2007 (N = 92) and 2017 (N = 110) surveys were administered using internet-based survey tools to the Cornea Society’s kera-net listserv.4 Questions asked in 2007 and 2017 were identical and included subjects related to practice (eg, type, location, and number of fungal keratitis cases managed in the previous 5 years), actual use of topical and systemic treatments, and preferences for topical treatments. The surveys were self-report and not validated against actual practice. In 2007 and 2017, participants were allowed to select multiple actual and preferred topical and systemic therapies. In 2017, participants were additionally asked what their preference for topical therapy would be if they could only choose a single therapy and what that preference would be for ulcers caused by Fusarium and Aspergillus species. Ethical approval was obtained from the institutional review board at the University of California, San Francisco, which determined that informed consent was not required because no identifying data were collected.

We analyzed responses with descriptive statistics. To assess differences in responses in 2007 and 2017, we used logistic regression models with an indicator term for survey year adjusted for caseload, academic vs other practice type, and Cornea Society membership. We compared location data between the 2 survey rounds to show that the location distribution was similar between the 2 rounds. P < .05 (2-sided) was considered to be statistically significant.

Results

In 2017, a total of 110 experts responded from approximately 1100 listserv members (Table). Actual and preferred use of natamycin and voriconazole in 2007 and 2017 are displayed in the Figure. Use of natamycin did not change (mean change, 0.0%; 95% CI, −5.9% to 5.9%; P > .99). Use of voriconazole increased by 12.0% (95% CI, −1.9% to 26.0%; P = .09). Natamycin as the preferred treatment increased by 19.9% (95% CI, 5.7%-34.2%; P = .006), and voriconazole decreased by 30.5% (95% CI, −45.3% to −16.0%; P < .001). In 2017, natamycin was indicated by 70 respondents (70.7%) (95% CI, 60.7%-79.4%) as the preferred treatment for ulcers caused by Fusarium species and by 43 (43.4%) respondents (95% CI, 33.5%-53.8%) as the preferred treatment for ulcers caused by Aspergillus species; voriconazole was indicated by 13 respondents (13.1%) (95% CI, 7.2%-21.4%) as the preferred treatment for ulcers caused by Fusarium species and 33 respondents (33.3%) (95% CI, 24.2%-43.5%) as the preferred treatment for ulcers caused by Aspergillus species.

Discussion

Choice of voriconazole as the preferred treatment for filamentous fungal keratitis decreased substantially in surveys conducted before and after MUTT I. However, ever use of voriconazole increased, possibly reflecting increased availability over time. In vitro results before MUTT I suggest that voriconazole would be effective for the treatment of fungal keratitis.5,6 In the 2007 survey, although voriconazole was the most commonly selected preferred treatment, many respondents indicated that more evidence was needed to guide treatment choices.4 The MUTT I result was driven primarily by ulcers caused by Fusarium, which had the worst response to voriconazole.1 After the results of MUTT I and 2 subsequent trials,2,3 only a few experts indicated that they would prefer to treat Fusarium keratitis with voriconazole. Limitations of this study include that respondents self-reported practice patterns and it was not possible to validate the survey against actual practice patterns. Respondents may have underreported voriconazole use because of social desirability bias. The decrease in preference for voriconazole over time may indicate that randomized clinical trials led to changes in practice patterns and integration of evidence-based practices into the treatment of fungal keratitis.

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Article Information

Corresponding Author: Catherine E. Oldenburg, ScD, MPH, Francis I. Proctor Foundation, University of California, San Francisco, 513 Parnassus Ave, San Francisco, CA 94143 (catherine.oldenburg@ucsf.edu).

Accepted for Publication: September 16, 2017.

Published Online: November 9, 2017. doi:10.1001/jamaophthalmol.2017.4763

Author Contributions: Dr Oldenburg had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Oldenburg.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Oldenburg.

Obtained funding: Lietman.

Administrative, technical, or material support: Oldenburg, Amza, Acharya, Mannis.

Study supervision: Prajna, Amza, Acharya, Lietman.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: This study was supported by grant U10 EY018573 from the National Eye Institute (principal investigator, Dr Lietman).

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

References
1.
Prajna  NV, Krishnan  T, Mascarenhas  J,  et al; Mycotic Ulcer Treatment Trial Group.  The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole.  JAMA Ophthalmol. 2013;131(4):422-429. doi:10.1001/jamaophthalmol.2013.1497PubMedGoogle Scholar
2.
Sharma  S, Das  S, Virdi  A,  et al.  Re-appraisal of topical 1% voriconazole and 5% natamycin in the treatment of fungal keratitis in a randomised trial.  Br J Ophthalmol. 2015;99(9):1190-1195. doi:10.1136/bjophthalmol-2014-306485PubMedGoogle Scholar
3.
Arora  R, Gupta  D, Goyal  J, Kaur  R.  Voriconazole versus natamycin as primary treatment in fungal corneal ulcers.  Clin Exp Ophthalmol. 2011;39(5):434-440. doi:10.1111/j.1442-9071.2010.02473PubMedGoogle Scholar
4.
Loh  AR, Hong  K, Lee  S, Mannis  M, Acharya  NR.  Practice patterns in the management of fungal corneal ulcers.  Cornea. 2009;28(8):856-859.PubMedGoogle Scholar
5.
Lalitha  P, Prajna  NV, Oldenburg  CE,  et al.  Organism, minimum inhibitory concentration, and outcome in a fungal corneal ulcer clinical trial.  Cornea. 2012;31(6):662-667. doi:10.1097/ICO.0b013e31823f8ae0PubMedGoogle Scholar
6.
Prajna  VN, Lalitha  PS, Mascarenhas  J,  et al.  Natamycin and voriconazole in Fusarium and Aspergillus keratitis: subgroup analysis of a randomised controlled trial.  Br J Ophthalmol. 2012;96(11):1440-1441. doi:10.1136/bjophthalmol-2012-301825PubMedGoogle Scholar
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