Cross-linking for Corneal Ulcers Treatment Trial

Phase 3

Completed

Brief Summary: The primary purpose of this study is to determine if patients randomized to corneal collagen cross-linking plus medical therapy will have a lower prevalence of positive bacterial or fungal cultures immediately after the procedure than patients who received medical therapy alone.

The secondary purpose of this study is to determine if patients randomized to corneal collagen cross-linking will have a better visual acuity at 3 and 12 months than patients who receive medical therapy alone.

Detailed Description: The proposed study is a randomized controlled trial to determine whether collagen cross-linking improves outcomes in microbial keratitis. Patients presenting to the Aravind Eye Hospitals in Madurai, India for treatment of microbial keratitis will be recruited for the proposed study. Approximately 266 patients will be enrolled in the study. Subjects presenting with bacterial keratitis will be randomized to receive medical therapy plus corneal collagen cross-linking at presentation or to receive medical therapy alone. All subjects with bacterial ulcers will receive standard topical antibiotic medications as required after the procedure.

Subjects with fungal keratitis will be randomized into one of four groups:

1. collagen cross-linking + amphotericin;

2. collagen cross-linking + natamycin;

3. amphotericin alone;

4. natamycin alone.

All study subjects will be followed for 12 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 plan to 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Bacterial ulcer control	Corneal Cross-linking	Standard of care topical treatment for bacterial ulcer
Fungal ulcer cross-linking plus natamycin	Corneal Cross-linking	Standard of care topical treatment for fungal ulcer with natamycin plus cross-linking
Bacterial ulcer cross-linking	Corneal Cross-linking	Standard of care topical treatment for bacterial ulcer plus cross-linking
Fungal ulcer cross-linking plus natamycin	Anti Fungal Drug	Standard of care topical treatment for fungal ulcer with natamycin plus cross-linking
Fungal ulcer control with amphotericin	Anti Fungal Drug	Standard of care topical treatment for fungal ulcer with amphotericin
Fungal ulcer control with natamycin	Corneal Cross-linking	Standard of care topical treatment for fungal ulcer with natamycin
Fungal ulcer control with natamycin	Anti Fungal Drug	Standard of care topical treatment for fungal ulcer with natamycin
Fungal ulcer cross-linking plus amphotericin	Corneal Cross-linking	Standard of care topical treatment for fungal ulcer with amphotericin plus cross-linking
Fungal ulcer cross-linking plus amphotericin	Anti Fungal Drug	Standard of care topical treatment for fungal ulcer with amphotericin plus cross-linking
Fungal ulcer control with amphotericin	Corneal Cross-linking	Standard of care topical treatment for fungal ulcer with amphotericin

Primary Outcome Measures

Name	Time	Method
Microbiological Cure on Repeat Culture	4 to 24 hours after enrollment	Corneal scraping of the ulcer will be performed and directly inoculated on to sheep's blood agar, chocolate agar, potato dextrose agar or Sabouraud's agar for bacterial and fungal culture. Microbiological cure is defined as no growth of bacteria or fungus on these media.

Secondary Outcome Measures

Name	Time	Method
Vision Related Quality of Life	3 months	Mobility subscale: As measured by the Indian Visual Function Questionnaire which records quality of life on a scale of 0 to 100 with 100 representing the best quality of life.
Best Spectacle-corrected Visual Acuity	3 months	Best corrected visual acuity will be measured at baseline for both eyes using the standard ETDRS chart light box at the 4- and 1-meter test distances. In the case that the patient reads less than 10 letters at 4 meters, move the patient or the chart to a distance of 1 meter from the patient.
Scar Size	3 months	Study clinician will measure infiltrate or scar size using a standardized protocol with the slit lamp biomicroscope. The geometric mean of the scar size will be measured by recording the horizontal and vertical diameter.
Adverse Events Including Rate of Perforation/Need for Therapeutic Penetrating Keratoplasty	3 months	Adverse events include glaucoma, endophthalmitis, medication reaction, perforation including treatment by therapeutic penetrating keratoplasty.