Julie Cho1, N Venkatesh Prajna2, Prajna Lalitha2, Revathi Rajaraman2, Tiruvengada Krishnan2, Yijie Brittany Lin3, Kathryn J Ray1, Thomas M Lietman4, Jennifer Rose-Nussbaumer5. 1. Francis I. Proctor Foundation, University of California San Francisco, San Francisco, California, USA. 2. Aravind Eye Care System, Madurai, Pondicherry, India. 3. Francis I. Proctor Foundation, University of California San Francisco, San Francisco, California, USA; Department of Ophthalmology, University of California San Francisco, San Francisco, California, USA. 4. Francis I. Proctor Foundation, University of California San Francisco, San Francisco, California, USA; Department of Ophthalmology, University of California San Francisco, San Francisco, California, USA; Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA. 5. Francis I. Proctor Foundation, University of California San Francisco, San Francisco, California, USA; Department of Ophthalmology, University of California San Francisco, San Francisco, California, USA. Electronic address: jennifer.rose@ucsf.edu.
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.
RCT Entities:
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: N Venkatesh Prajna; Tiruvengada Krishnan; Revathi Rajaraman; Sushila Patel; Ranjeet Shah; Muthiah Srinivasan; Lumbini Devi; Manoranjan Das; Kathryn J Ray; Kieran S O'Brien; Catherine E Oldenburg; Stephen D McLeod; Michael E Zegans; Nisha R Acharya; Thomas M Lietman; Jennifer Rose-Nussbaumer Journal: JAMA Ophthalmol Date: 2017-06-01 Impact factor: 7.389
Authors: Kathryn J Ray; Prajna Lalitha; N Venkatesh Prajna; Revathi Rajaraman; Tiruvengada Krishnan; Muthiah Srinivasan; Peter Ryg; Stephen McLeod; Nisha R Acharya; Thomas M Lietman; Jennifer Rose-Nussbaumer Journal: Am J Ophthalmol Date: 2017-04-04 Impact factor: 5.258
Authors: N Venkatesh Prajna; Tiruvengada Krishnan; Revathi Rajaraman; Sushila Patel; Muthiah Srinivasan; Manoranjan Das; Kathryn J Ray; Kieran S O'Brien; Catherine E Oldenburg; Stephen D McLeod; Michael E Zegans; Travis C Porco; Nisha R Acharya; Thomas M Lietman; Jennifer Rose-Nussbaumer Journal: JAMA Ophthalmol Date: 2016-12-01 Impact factor: 7.389