Therapeutic Penetrating Keratoplasty Button Cultures in The Mycotic Ulcer Treatment Trial II: A Randomized Trial Comparing Oral Voriconazole Versus Placebo.

Abstract

OBJECTIVE:

To compare oral voriconazole vs placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis.

DESIGN:

Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial.

METHODS:

Study Participants: Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK).

INTERVENTION:

Study participants were randomized to oral voriconazole vs oral placebo; all received topical antifungal drops.

MAIN OUTCOME MEASURES:

TPK button culture positivity.

RESULTS:

A total of 95 of 194 (49.5%) study participants enrolled at Madurai, Coimbatore, or Pondicherry, India eventuated to TPK in an average of 20.9 days (standard deviation 15.2 days, range 2-71 days). TPK button cultures were available for 67 of 95 (71%) of the TPKs performed and were positive for filamentous fungus in 45 of 67 (67%) cases. For each 1-day increase in the time to TPK there was 0.94-fold decreased odds of fungal culture positivity (95% confidence interval [CI] 0.90-0.98, P = .005). Those randomized to oral voriconazole had 1.26-fold increased odds of TPK button culture positivity after controlling for time to TPK and baseline organism, but this was not statistically significant (95% CI 0.32-4.87; P = .74). Those who underwent TPK for lack of response to medical therapy were 10.64-fold more likely to be culture positive than if the indication for surgery was perforation and this was statistically significant (95% CI 2.16-51.70; P = .003).

CONCLUSIONS:

There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. Infection rather than inflammation appears to be the reason for the worsening clinical picture in many of these patients.

• Authors: Julie Cho, N Venkatesh Prajna, Prajna Lalitha, Revathi Rajaraman, Tiruvengada Krishnan, Yijie Brittany Lin, Kathryn J Ray, Thomas M Lietman, Jennifer Rose-Nussbaumer, Mycotic Ulcer Treatment Trial Group
• Journal: American journal of ophthalmology (Am J Ophthalmol) Vol. 192 Pg. 142-145 (08 2018) ISSN: 1879-1891 [Electronic] United States
• PMID: 29758184 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Antifungal Agents
• Voriconazole

Topics

• Administration, Oral
• Adult
• Aged
• Antifungal Agents (therapeutic use)
• Bacteriological Techniques
• Case-Control Studies
• Combined Modality Therapy
• Cornea (microbiology)
• Corneal Ulcer (drug therapy, microbiology, surgery, therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Eye Infections, Fungal (drug therapy, microbiology, surgery, therapy)
• Female
• Follow-Up Studies
• Humans
• Keratoplasty, Penetrating
• Male
• Middle Aged
• Treatment Outcome
• Visual Acuity
• Voriconazole (therapeutic use)