Effectiveness of Corneal Accelerated Crosslinking for Infectious Keratitis

Phase 3

• Conditions: Keratitis
• Interventions: Procedure: Accelerated Corneal Cross-linking

• Registration Number: NCT02865876
• Lead Sponsor: Instituto de Oftalmología Fundación Conde de Valenciana

Brief Summary

The objective of this study is to evaluate the efficacy and safety of accelerated cross-linking (Avedro Inc., Waltham, USA) in the management of microbial keratitis as adjunctive therapy.

Detailed Description

Investigators perform a comprehensive ophthalmological examination, including evaluation of risk factors (immunosuppressive status, ocular trauma, previous ocular surgery, contact lens wear, topical corticosteroids use), best-corrected visual acuity (Snellen chart), slit-lamp biomicroscopy, tonometry and fundoscopy. In addition, anterior segment optical coherence tomography imaging (Visante, Carl Zeiss Meditec, Dublin, California, USA), corneal scrapes, culture and clinical photographs at day 1, day 7, month 1 and 3 will be analyzed.

Each participant will be assigned to one of four groups after randomization. Group 1: Initial ulcer on treatment with antibiotic plus sham (n = 66), these partcipants will receive only topical moxifloxacin 0,5% (Vigamoxi, Alcon, Texas, USA) and sham CXL; Group 2: Initial ulcer on treatment with antibiotic plus cross-linking (CXL) (n = 66) receive moxifloxacin plus CXL (riboflavin 0.1% during 10 minutes and irradiation 30 mW/cm2 during 3 minutes using accelerated CXL); Group 3: Refractory corneal ulcer on treatment with antibiotic plus sham (n=66), receive only topical antibiotic plus sham CXL; Group 4: Refractory corneal ulcer on treatment with antibiotic plus CXL will receive their standard medications plus CXL.

Statistical analysis will be divided into four phases: 1) Analysis of compliance, 2) Intention to treat, 3) Losses to follow-up and 4) Variable-response (healing) using Stata/MP 12.0 (Stata Corp., College Station, TX).

Study Timeline

• Study Start: 2015-06
• Status Verified: 2016-08
• Primary Completion: 2016-08
• Study First Submitted: 2016-08-01
• Study First Submitted QC: 2016-08-09
• Last Update Submitted: 2016-08-09
• Study First Posted: 2016-08-15
• Last Update Posted: 2016-08-15
• Study Completion: 2017-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 264

Inclusion Criteria

• Subjects with infectious keratitis (initial or refractory to treatment) including bacterial or mycotic keratitis with size larger than 3 mm

Exclusion Criteria

• herpetic keratitis
• Acanthamoeba keratitis
• pregnancy
• endophthalmitis
• systemic immunosuppression

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Accelerated Corneal Cross-linking	Accelerated Corneal Cross-linking	Cross-linking in the management of microbial keratitis is an adjunctive therapy.This procedure is conducted under sterile conditions in the operating room. Tetracaine hydrochloride 0.5% (Ponti Ofteno, Sophia, Mexico) eye drops is apply for topical anesthesia. The corneal epithelium on the edge of the ulcer is cautiously removed using a microsponge. As photosensitizer, riboflavin 0.1% (Vibex, Avedro Inc, Waltham, USA) is used for 10 minutes. After impregnation, the participant´s cornea is irradiaded with UVA-light (370 nm) using 30 mW/cm2 for 3 minutes (which corresponds to a total dose of 5.4J/cm2) with accelerated cross-linking (Avedro Inc., Waltham, USA). After procedure, conventional treatment for keratitis remains unchanged.
Sham Accelerated Corneal Cross-linking	Accelerated Corneal Cross-linking	Placebo surgery. This procedure is conducted under sterile conditions in the operating room. Tetracaine hydrochloride 0.5% (Ponti Ofteno, Sophia, Mexico) eye drops is apply for topical anesthesia. Investigators do not perform removal of the corneal epithelium in edge of the ulcer. The researchers conducted "the impregnation phase" applying drops of saline solution for 10 minutes. After impregnation fase, a device is placed in Avedro equipment off (Avedro Inc, Waltham, USA) this device emits white light for 3 minutes. After procedure, conventional treatment for keratitis remains unchanged.

Primary Outcome Measures

Name	Time	Method
Healing	Three months	Full epithelialization without evidence of infiltrates

Secondary Outcome Measures

Name	Time	Method
Complications	Three months	Complications associated with accelerated corneal cross-linking, such as corneal perforation or progression

Trial Locations

Locations (1)

Instituto de Oftalmologia Conde de Valenciana; 🇲🇽 Mexico City, Mexico