Standard Versus Transepithelial Corneal Crosslinking

Standard Versus Transepithelial Corneal Crosslinking for Treatment of Progressive Keratoconus

The gold standard corneal crosslinking (CXL) technique involves the initial step of epithelial removal, in order to achieve a sufficient treatment effect (meaning: stabilisation of progressive keratoconus (KC). Our aim is to evaluate the effects of transepithelial CXL (TE-CXL), whereby the epithelium is left intact and the cornea is instead treated by a solution composed of 0.1% riboflavin, combined with enhancers, after which standard CXL is performed. This solution seems to facilitate riboflavin penetration into the corneal stroma through the intact epithelium. The investigators expect to achieve a similar effect of TE-CXL with the advantage of a faster healing time and less risk of infections.

Study Overview

• Status: Completed
• Conditions: Keratoconus
• Intervention / Treatment: Procedure: Transepithelial versus epithelium-off CXL; Drug: Isotonic riboflavin; Drug: Ricrolin TE

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented progressive KC (by Pentacam and/or corneal topography imaging).
• A clear central cornea.
• A minimal corneal thickness of ≥ 400 µm at the thinnest corneal location (Pentacam imaging).
• Minimal Snellen corrected distance visual acuity of ≥ 0.4.
• Patient age of ≥ 18 years.

For this research study, the inclusion parameters will be the same as mentioned above, with the following additional inclusion criteria:

• Documented progression of KC, as demonstrated by anterior segment imaging and/or corneal topography:

  o Defined an increase in maximal keratometry, steepest keratometry, mean keratometry or topographic cylinder value by ≥ 0.5 D over the previous 6 months and/or a decrease in thinnest pachymetry

• Documented progression of KC defined by increase in refractive cylinder of ≥ 0.5 D over the previous 6 months

Exclusion Criteria:

• Presence of corneal scars.
• History of epithelial healing problems.
• Presence of previous ocular infection (such as herpes keratitis).
• Patients who are pregnant and/or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: epithelium off CXL; epithelium removal + 30 minute isotonic riboflavin eye drops (3 minute interval) + 30 minutes ultraviolet-A irradiation (riboflavin every 5 minutes)	Procedure: Transepithelial versus epithelium-off CXL; A comparison of the CXL procedure with and without epithelium removal; Other Names: epithelium-on versus epithelium-ff corneal crosslinking; Drug: Isotonic riboflavin; After epithelium removal, isotonic riboflavin was instilled during 30 minutes before ultraviolet-A irradiation
Experimental: Ricrolin TE CXL; Ricrolin-TE eye drops for 15 minutes (2 minute interval) and 15 minute Ricrolin TE pooled on the cornea using a silicone ring + 30 minutes ultraviolet-A irradiation (Ricrolin TE every 5 minutes).	Procedure: Transepithelial versus epithelium-off CXL; A comparison of the CXL procedure with and without epithelium removal; Other Names: epithelium-on versus epithelium-ff corneal crosslinking; Drug: Ricrolin TE; Ricrolin TE was instilled during 30 minutes before ultraviolet-A irradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical stabilisation of keratoconus one year after CXL	Using a Scheimpflug device (Pentacam, Oculus), topography measurements are performed. Clinical stabilisation is defined as an increase of no more than 1 diopter of the maximum keratometry value over the preoperative maximum keratometry value.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications, defined as epithelial healing problems and/or keratitis.	the incidence of epithelial healing problems after treatment will be recorded	1 year

Collaborators and Investigators

• Sponsor: Nienke Soeters
• Collaborators: Dr. F.P. Fischer Stichting; Stichting Nederlands Oogheelkundig Onderzoek

Publications and helpful links

General Publications

• Davis SA, Bovelle R, Han G, Kwagyan J. Corneal collagen cross-linking for bacterial infectious keratitis. Cochrane Database Syst Rev. 2020 Jun 17;6(6):CD013001. doi: 10.1002/14651858.CD013001.pub2.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: January 17, 2015
• First Submitted That Met QC Criteria: January 27, 2015
• First Posted (Estimate): January 28, 2015

Study Record Updates

• Last Update Posted (Estimate): January 28, 2015
• Last Update Submitted That Met QC Criteria: January 27, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Vitamin B Complex; Riboflavin
• Other Study ID Numbers: NL29961; 10-374 (Registry Identifier: METC UMC Utrecht)