Mycotic Antimicrobial Localized Injection for Treatment of Corneal Ulcers (MALIN)

Mycotic Antimicrobial Localized Injection (MALIN) is a randomized, masked, two-arm clinical trial investigating intrastromal voriconazole in the treatment of fungal corneal ulcers. There is currently little evidence to guide the treatment of fungal keratitis beyond topical anti-fungal drops, though intrastromal voriconazole and oral antifungal treatments are used as well. This study will provide evidence to guide the treatment of fungal keratitis in the future. The purpose of this study is to determine differences in microbiological cure for 3-day repeat cultures between different antifungal treatments. For this study, there will be 1:1 randomization to one of these two treatment groups: 1) topical natamycin plus intrastromal voriconazole injection or 2) topical natamycin alone.

Study Overview

• Status: Completed
• Conditions: Corneal Ulcer; Fungal Keratitis
• Intervention / Treatment: Drug: Intrastromal voriconazole; Drug: Natamycin

Detailed Description

The proposed study is a randomized controlled trial to determine whether intrastromal voriconazole improves outcomes in fungal keratitis. Patients presenting to the Aravind Eye Hospitals in Pondicherry, India for treatment of fungal keratitis will be recruited for the proposed study. Approximately 70 patients will be enrolled in the study. Subjects presenting with fungal keratitis will be randomized to receive topical natamycin plus intrastromal voriconazole or to receive topical natamycin alone. Subjects may also receive oral antifungals after day 3 at the discretion of the treating clinician. All study subjects will be followed for 3 months to evaluate response to treatment.

Investigators from the University of California, San Francisco (UCSF) will assist Aravind Eye Hospital with the study design, implementation, and analysis of the research, and will help fund the study. The investigators will visit Aravind to help with the study implementation. UCSF will play an important role in this study by assisting with the study design, implementation, analysis, and funding.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Tamil Nadu
    • Pondicherry, Tamil Nadu, India
      • Aravind Eye Hospitals
• United States
  • California
    • San Francisco, California, United States, 94143
      • Francis I. Proctor Foundation at UCSF

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Moderate to severe corneal ulcer that is smear positive for filamentous fungus
• Pinhole visual acuity worse than 20/70 in affected eye
• Basic understanding of the study as determined by the physician
• Commitment to return for follow up visits

Exclusion Criteria:

• Gram stain positive for bacteria or evidence of other concomitant infection (i.e. herpes, acanthamoeba)
• Impending or frank perforation at recruitment
• Involvement of sclera at presentation
• Non-infectious or autoimmune keratitis
• History of corneal transplantation or recent intraocular surgery
• No light perception in the affected eye
• Pinhole visual acuity worse than 20/200 in the unaffected eye
• Pregnant women
• Participants who are decisionally and/or cognitively impaired

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intrastromal voriconazole plus natamycin; Intrastromal voriconazole plus standard of care topical treatment for fungal keratitis	Drug: Intrastromal voriconazole; Subjects will receive three intrastromal voriconazole injections over 10 days. Intrastromal voriconazole injection is a routine procedure performed by Aravind Eye Hospital for fungal keratitis.; Drug: Natamycin; Subjects will receive topical 5% natamycin drops hourly for 3 days.
Active Comparator: Natamycin alone; Standard of care topical treatment for fungal keratitis	Drug: Natamycin; Subjects will receive topical 5% natamycin drops hourly for 3 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Culture Positivity at Day 3 Using Potassium Hydroxide (KOH) Wet Mount to Test for Fungus	Number of of participants with positive fungal cultures at 3 days	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Spectacle-corrected Visual Acuity, as Measured by a Refractionist	Best spectacle-corrected visual acuity using calibrated Original Series Early Treatment Diabetic Retinopathy Study eye charts and recorded as number of letter read.	3 weeks and 3 months
Scar Size	Scar size, geometric mean	3 weeks and 3 months
Number of Participants With Scar Depth at the Anterior Third, Middle Third, and Posterior Third of the Cornea	Number of participants with scar depth at the anterior third (0-33% depth), middle third (>33-67% depth), and posterior third (>67-100% depth) of the cornea, as measured on slit lamp exam.	3 weeks and 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corneal Thinning, as Measured by Pachymetry and OCT		6 months
Corneal Topography, as Measured by a Non-contact Imaging Topographer		6 months
Change in Quality of Life, Measured by the Indian Vision Function Questionnaire (IND-VFQ)		3 months
Corneal Neovascularization	As measured by clinical examination and slit lamp photographs.	3 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Aravind Eye Hospitals, India
• Investigators: Principal Investigator: Jennifer Rose-Nussbaumer, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: March 14, 2016
• First Submitted That Met QC Criteria: April 1, 2016
• First Posted (Estimated): April 7, 2016

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: cornea; ulcer; keratitis; fungal
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Eye Diseases; Eye Infections; Pathological Conditions, Signs and Symptoms; Ulcer; Corneal Ulcer; Keratitis; Corneal Diseases; Organic Chemicals; Macrolides; Lactones; Natamycin
• Other Study ID Numbers: 15-17989

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be input into a database using double data entry at UCSF. Data will be stored at UCSF for about 10 years.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No