The Utility of Repeat Culture in Fungal Corneal Ulcer Management: A Secondary Analysis of the MUTT-I Randomized Clinical Trial

Abstract

PURPOSE To determine whether patients who had a positive repeated culture was predictive of worse clinical outcome than those who achieved microbiological cure at 6 days in the Mycotic Ulcer Treatment Trial I (MUTT-I). DESIGN Secondary analysis from a multicenter, double-masked, randomized clinical trial. METHODS Setting Multiple hospital sites of the Aravind Eye Care System, India. Study Population Patients with culture-positive filamentous fungal ulcers and visual acuity of 20/40 to 20/400 re-examined 6 days after initiation of treatment Intervention Corneal scraping and cultures were obtained from study participants at day-6 after enrollment. Main outcome Measures We assess 3-month best spectacle corrected visual acuity (BSCVA), 3-month infiltrate/scar size, corneal perforation and re-epithelialization rates stratified by culture positivity at day 6. RESULTS Of the 323 patients with smear positive ulcers enrolled in MUTT-I, 299 (92.6%) were scraped and cultured six days after enrollment. Repeat culture positivity was 31% (92/299). Among patients who tested positive at enrollment, those with positive 6-day cultures had significantly worse 3-month BSCVA (0.39 LogMAR; 95% CI: 0.24 to 0.44; P<0.001), larger 3-month scar-size (0.39 mm; 95% CI: 0.06 to 0. 73; P=0.02), were more likely to perforate or require therapeutic penetrating keratoplasty (OR: 6.27; 95% CI: 2.73 to 14.40; P<0.001), and were slower to re-epithelialize (HR: 0.33; 95% CI: 0.21 to 0.50; P<0.001) than those with a negative 6-day culture result. CONCLUSIONS Early microbiological cure on culture is a predictor of clinical response to treatment. TRIAL REGISTRATION clinicaltrials.gov Identifier NCT00996736

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

“…9 Repeat culture positivity despite appropriate antifungal therapy has been correlated with poor clinical outcomes in fungal keratitis, such as worse visual acuity and larger scar size. 5 Therefore, the high rate of culture positivity in our series, combined with the fact that these patients were treated with maximum medical therapy (both topical natamycin and voriconazole, with roughly half randomized to oral voriconazole), underscores the importance of evaluating other potential therapies such as corneal cross-linking or early TPK. 10 …”

“…5–7 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.…”

Reply

“…2 The MUTT 1 trial conducted in South India concluded that natamycin is associated with better clinical and microbiological outcomes than voriconazole (VCZ) in smear-positive filamentous fungal keratitis, especially in Fusarium cases. Moreover, Prajna et al 3 commented that the difference in efficacy noted in this trial was primarily attributable to cases caused by Fusarium species. 3 However, studies conducted in North India with Aspergillus as the most common species isolated showed a beneficial effect of VCZ oral or intrastromal with a success rate as high as 80% in cases of recalcitrant fungal keratitis.…”

“…Moreover, Prajna et al 3 commented that the difference in efficacy noted in this trial was primarily attributable to cases caused by Fusarium species. 3 However, studies conducted in North India with Aspergillus as the most common species isolated showed a beneficial effect of VCZ oral or intrastromal with a success rate as high as 80% in cases of recalcitrant fungal keratitis. 4 Thus, the results of this study may be explained by the difference in the microbiological profile and cannot be generalized for all geographic areas.…”

“…Secondary analyses of the Mycotic Ulcer Treatment Trial (MUTT) 1 and 2, have shown that repeat culture can be used to assess response to treatment and is highly correlated with clinical outcomes such as final visual acuity, scar size, and corneal perforation. [1][2][3][4] Unpublished analyses from the Mycotic Antimicrobial Localized Injection correlate 3-day culture results with perforation or need for therapeutic penetrating keratoplasty. Because clinical outcomes are of utmost importance to clinicians, we have also assessed visual acuity, percent epithelialized, scar size, and depth and complications such as perforation and need for therapeutic transplant.…”