Landmark Trials - Cornea

To facilitate a deeper understanding of the most impactful trials in ophthalmology, we have curated a comprehensive list. This collection presents key trials in a structured, easy-to-read format. in order to procide a simple overview for everyone studying for the European Board of Opthalmoloy or the "Facharztprüfung für Augenheilkunde".

If you have suggestions for additional trials let us know!

Mycotic Ulcer Treatment Trial (MUTT) I

Objective: To compare the effectiveness of topical natamycin 5% versus topical voriconazole 1%  in treating fungal corneal ulcers.

Design: randomized, controlled, double-blind multi-center trial

Patients: 323 patients with fungal corneal ulcers and baseline visual acuity of 20/40 to 20/400  in southern India.

Intervention: Patients were randomly assigned to receive either topical natamycin 5% or topical voriconazole 1% hourly until reepithelialization, followed by four times daily for three weeks.

Outcomest: 

• Best spectacle-corrected visual acuity (BSCVA) at 3 weeks and 3 months

• Infiltrate or scar size

• Time to reepithelialization

• Microbiological cure

• Corneal perforation or therapeutic penetrating keratoplasty (TPK)

Findings:

• BSCVA: Natamycin 5% was superior to voriconazole 1%, especially in patients with Fusarium keratitis. There was no difference between non-Fusarium cases

• Corneal perforation/TPK: Voriconazole was associated with a higher rate of perforation and TPK.

• Reepithelialization time and infiltrate/scar size: No significant difference between the two groups.

• Microbiological cure: Natamycin was more effective in clearing culture positivity.

Conclusion: Natamycin is a more effective treatment for fungal corneal ulcers, particularly those caused by Fusarium. Voriconazole should not be used as monotherapy for Fusarium keratitis.

Prajna NV, Mascarenhas J, Krishnan T, et al. Comparison of natamycin and voriconazole for the treatment of fungal keratitis. Arch Ophthalmol 2010;128:672-8.

Mycotic Ulcer Treatment Trial (MUTT) II

Objective: To determine if oral voriconazole in addition to topical antifungals is beneficial for advanced mycotic keratitis.

Design: Randomized, double-masked, placebo-controlled trial

Participants: 240 patients with advanced fungal keratitis and baseline visual acuity below 20/400 in India and Nepal.

Interventions: Patients were randomized to receive either oral voriconazole 400mg twice daily for one day followed by 200mg twice daily for 20 days or a placebo, in addition to topical voriconazole 1% and natamycin 5%.

Outcomes:

• Corneal perforation or TPK within 3 months

• Culture negativity at 6 days

• Reepithelialization rate

• BSCVA

• Infiltrate/scar size

• Adverse events

Findings:

• Primary outcome: No significant difference in corneal perforation or TPK between the two groups.

• No significant difference in BSCVA

• A trend towards decreased perforation/TPK was found in the PO voriconazole group.

• Higher rate of adverse events in the oral voriconazole group (P=0.001).  These adverse events included:  elevated liver function tests and visual hallucinations.

Conclusion:  There is no benefit of adding oral voriconazole (and higher adverse events)  to topical antifungal therapy in advanced filamentous fungal keratitis.

Prajna NV, Krishnan T, Rajaraman R, et al. Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II): A Randomized Clinical Trial. JAMA Ophthalmol 2016;134:1365-72.