Microbiology and Immunology Group
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OMIG Abstract 23
Therapeutic Penetrating Keratoplasty Button Cultures in the Mycotic Ulcer Treatment Trial II
Julie Cho2, N. Venkatesh Prajna1, Prajna Lalitha1, Revathi Rajaraman1, Tiruvengada Krishnan1, Yijie Lin2,3 Kathryn J. Ray2, Jennifer Rose-Nussbaumer, MD2,3 for the Mycotic Ulcer Treatment Trial Group
1Aravind Eye Care System, Madurai, Pondicherry, India; 2Francis I. Proctor Foundation, University of California San Francisco, San Francisco, California; 3UCSF Department of Ophthalmology, University of California San Francisco, San Francisco, California
Corneal perforation and the need for therapeutic penetrating keratoplasty (TPK) are more common in fungal than bacterial keratitis. The Mycotic Ulcer Treatment Trial II (MUTT II) was a randomized clinical trial which found no benefit of adjuvant oral voriconazole in reducing the risk of perforation and TPK in the treatment of severe filamentous fungal keratitis, except for possibly Fusarium spp. Culture positivity despite treatment has previously been found to be an important predictor of clinical outcome in both bacterial and fungal keratitis. Here, we compare the TPK button culture results by treatment arm to determine if we can detect a benefit of oral voriconazole microbiologically that we were unable to determine clinically.
The methods for MUTT II have been outlined in a previous publication.2 In this analysis, corneal button cultures from TPKs performed at the Aravind Eye Hospital, Madurai and Pondicherry, India were obtained. A logistic regression model assessed the relationship between adjuvant oral voriconazole and TPK button microbiological cure with co-variates for time to TPK and baseline culture result. A regression model also analyzed the relationship between indication for TPK and button culture status. Institutional Review Board approval was obtained at UCSF, the Aravind Eye Care System and Dartmouth-Hitchcock Medical Center. The trial conformed to the Declaration of Helsinki and written informed consent was obtained from all participants.
A total of 96/194 (49.5%) MUTT II study participants had a TPK. Baseline cultures were positive in 80/96 (83.3%) of those who eventuated to TPK. These cultures isolated Fusarium spp in 36.4% (N = 35), Aspergillus spp in 28.1% (N = 27) and all other fungi in 18.8% (N = 18). Baseline cultures were negative in 16.7% (N = 16). The average time to TPK was 20.9 days (SD 15.2).
TPK button cultures were positive for filamentous fungus in 41/64 (64.1%) cases and grew Fusarium spp 23% (N = 22), Aspergillus spp 10% (N = 9), other fungi 11% (N = 10), Pseudomonas aeruginosa 2%(N = 2), no growth in 22% (N =21) and were unavailable in 33% (N = 32). Excluding the two positive for bacteria, those randomized to oral voriconazole had 0.84-fold decreased odds of TPK button culture positivity after controlling for time-to-TPK and baseline organism but this was not statistically significant (95% CI 0.27 to 2.57; P = 0.76). There was also no evidence that oral voriconazole reduced the odds of culture positivity in fusarium spp ulcers (coef 2.16, 95% CI 0.25 to 18.29; P = 0.48). After controlling for baseline culture result and time to TPK, those with a positive TPK culture were 4.57-times more likely to have lack of response to medical therapy as their indication for surgery and this was statistically significant (95% CI 1.35 to 15.47; P = 0.02).
We were unable to demonstrate a statistically significant difference in TPK culture status between those randomized to oral voriconazole versus placebo consistent with the overall MUTT II trial result. TPKs performed for perforation were less likely to be culture positive than those performed for worsening infection suggesting that the immune response that results in microbiological cure may also contribute to perforation.
Funding: This work was supported by grants U10 EY018573 and K23 EY025025 (Rose-Nussbaumer) from the National Eye Institute and grants from That Man May See, the Harper/Inglis Trust, the South Asia Research Foundation, and Research to Prevent Blindness. Natamycin and voriconazole were donated by Alcon and Pfizer, respectively.
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