FUNGAL KERATITIS

Fungal keratitis continues to be a major cause of corneal blindness in some areas of the world, and yet treatment of these sight-threatening infections has not received the research attention it deserves.

Therefore, the Mycotic Ulcer Treatment Trial (MUTT) is noteworthy for being a rigorous prospective study addressing this important therapeutic area and particularly because it generated clear, but unexpected results showing that natamycin five per cent is superior to voriconazole one per cent as topical treatment for filamentous fungal keratitis. This study was a collaborative effort between Aravind Eye hospitals in India and Proctor foundation in the US and was funded by the National Eye Institute.

Speaking on behalf of his collaborators, Venkatesh Prajna MD, MUTT principal investigator, discussed the study’s recently published findings at the first Cornea Day during the 26th Asia-Pacific Association of Cataract & Refractive Surgeons Annual Meeting.

Dr Prajna told attendees that in this large, randomised, double-masked study’s primary efficacy analysis of best spectacle- corrected visual acuity at three months, as well as in various secondary clinical and microbiological endpoints, natamycin was consistently associated with significantly better outcomes than voriconazole. Therefore, the investigators concluded that voriconazole should not be used as monotherapy for filamentous fungal keratitis.

“We were very surprised by the findings of this study because they were not consistent with results from in vitro susceptibility testing favouring voriconazole over natamycin or from a survey of corneal specialists worldwide showing voriconazole was the preferred topical agent for treatment of filamentous keratitis,” said Dr Prajna, chief, cornea clinic, Aravind Eye Hospital, Madurai, India.

The MUTT was conducted in Tamilnadu, South India and undertaken after a pilot trial of 120 patients found a trend for better vision with voriconazole versus natamycin, but no statistically significant differences in primary or secondary efficacy outcomes.

Patients were eligible for MUTT if they had a smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400. Median ulcer size at enrolment was 3.2mm2.

Participants were treated in-house for at least two weeks to ensure treatment compliance. Planned enrolment for MUTT was for 368 patients, but based on the recommendation of an international data and safety monitoring committee, recruitment was stopped after entry of only 323 patients as interim analyses showed clear differences favouring natamycin. Best spectacle- corrected visual acuity at three months was 1.4 lines better in patients treated with natamycin compared with the voriconazole group. In addition, the natamycin group had a significantly lower treatment failure rate (based on development of perforation or need for penetrating keratoplasty) and a lower rate of culture positivity when smears were repeated at six days. There were no between-group differences in time to re-epithelialisation or eventual scar size, Dr Prajna reported.

Microbiological analyses showed Fusarium was the most common causative organism for the fungal ulcers, isolated at entry in about half of the 256 culture-positive eyes. Subgroup analyses showed the superiorit of voriconazole over natamycin was mainly attributable to its providing better results in the Fusarium cases. Outcomes for eyes with infection caused by other filamentous fungi were similar in the two treatment groups.

Dr Prajna commented that the predominance of Fusarium cases is one of the limitations of the study. In addition, he noted there were no contact lens wearers in the population, the participants were recruited from a single geographic location, and the study investigated only monotherapy.