Transepithelial Corneal Cross-linking Using Iontophoresis

Progressive Keratoconus Clinical Trial

— T-iontoCL  

Official title:

Randomized Clinical Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis and Standard Corneal Cross-linking for the Treatment of Keratoconus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02117999
• Other study ID #: SEA27
• Secondary ID: PON01_00110
• Status: Completed
• Phase: N/A
• Start date: January 2014
• Est. completion date: September 2016

Study information

• Verified date: August 2019
• Source: Fondazione G.B. Bietti, IRCCS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the present Randomized Clinical Trial (RCT) is to compare the efficacy and safety of transepithelial corneal cross-linking using iontophoresis (T-ionto CL) to treat progressive keratoconus in comparison with standard cross-linking (standard CL).

Description:

Keratoconus is a progressive corneal ectatic disease causing visual impairment by inducing irregular astigmatism and corneal opacity. This disorder typically begins during the second decade of life and, in severe forms, may need a corneal transplantation. Corneal cross-linking with riboflavin and UV-A is a procedure intended to halt keratoconus progression. It generates additional chemical bonds between stromal proteins in order to stiffen the corneal tissue. Standard CL includes epithelial removal and stroma soaking with dextran-enriched 0.1% riboflavin solution for 30 minutes before being exposed to ultraviolet-A radiation using a 3mW/cm2 lamp for 30 minutes.

Epithelial debridement exposes the cornea to a risk of side effects, such as pain for the first two post-operative days, temporary loss of visual acuity during the first three months, and serious complications, such as infection and stromal opacity due to corneal scarring.

Iontophoresis is a non invasive technique in which a weak electric current is used to enhance the penetration of hypotonic 0.1% riboflavin-5-phosphate solution into the corneal stroma through the intact epithelium. After iontophoresis, the corneal tissue is irradiated using a 10 mW/cm2 for 9 minutes (T-ionto CL). From previous experimental work (Lombardo M. et al. JCRS 2014 and JCRS 2015), the investigators provided evidence that T-ionto CL increases the stiffness of human corneas with results almost comparable with standard CL. The new procedure holds the promise to be as effective as the standard procedure while minimizing all the related risks. It is object of the present clinical trial to randomize patients with progressive keratoconus to T-ionto CL and standard CL and compare efficacy and safety of treatments.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: September 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 46 Years

Eligibility

Inclusion Criteria:

• Diagnosis of progressive keratoconus

Exclusion Criteria:

• Anterior corneal curvature steeper than 61 D;

• central corneal thickness <400 um

• corneal scarring;

• descemetocele;

• history of herpetic keratitis;

• Concomitant eye diseases;

• Inflammatory eye diseases;

• Glaucoma;

• Cataract;

• Pregnancy

Related Conditions & MeSH terms

• Keratoconus
• Progressive Keratoconus

Intervention

Device:
• Cross-linking with iontophoresis
The procedure involves a constant current source and two electrodes. The active electrode is a bath tube, which includes a stainless steel grid, placed into the cup at a minimal distance from the cornea. The reservoir is filled with dextran-free, hypotonic riboflavin-5-phosphate solution. The generator applies a constant current of 1mA for a preset period of 5 min. After the riboflavin administration by iontophoresis, the cornea is irradiated using a UVA lamp of 10mW/cm2 for 9 minutes.
• Standard corneal cross-linking
In the standard CL, the epithelium is mechanically removed. Then, a solution of riboflavin is instilled each minute for 30 minutes. Corneas are irradiated using a UVA lamp of 3mW/cm2 for 30 minutes.

Locations

Country	Name	City	State
Italy	Fondazione G.B. Bietti, IRCCS	Rome

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione G.B. Bietti, IRCCS	CNR Institute for chemical and physical processes (IPCF), Messina

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Bikbova G, Bikbov M. Transepithelial corneal collagen cross-linking by iontophoresis of riboflavin. Acta Ophthalmol. 2014 Feb;92(1):e30-4. doi: 10.1111/aos.12235. Epub 2013 Jul 15. — View Citation

Eljarrat-Binstock E, Domb AJ. Iontophoresis: a non-invasive ocular drug delivery. J Control Release. 2006 Feb 21;110(3):479-89. Epub 2005 Dec 15. Review. — View Citation

Hao J, Li SK, Liu CY, Kao WW. Electrically assisted delivery of macromolecules into the corneal epithelium. Exp Eye Res. 2009 Dec;89(6):934-41. doi: 10.1016/j.exer.2009.08.001. Epub 2009 Aug 12. — View Citation

Meek KM, Hayes S. Corneal cross-linking--a review. Ophthalmic Physiol Opt. 2013 Mar;33(2):78-93. doi: 10.1111/opo.12032. Review. — View Citation

Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998 Jan;66(1):97-103. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	K-max	Measuring maximum keratometry (K-max), measured in diopters (D), derived from computerized videokeratography.	Changes from baseline in Kmax at 12 months
Primary	Corneal Endothelial Cell Density	Endothelial cell density (ECD) will be evaluated using specular microscopy	Changes from baseline in ECD at 12 months
Secondary	Optical Aberrations	Optical aberrations of the eye will be measured using dynamic skyascopy. Corneal wavefront aberration will be measured using Placido disk topographer and Scheimpflug tomographer.	Changes from baseline at 12 months.
Secondary	Visual Acuity	Visual acuity tested using ETDRS	Changes from baseline at 12 months.
Secondary	Contrast Sensitivity	Contrast sensitivity tested using Pelli-Robson chart	Changes from baseline at 12 months.
Secondary	Central Retinal Thickness	Central retinal thickness (1 mm ETDRS map) will be measured before and after CXL procedures	Changes from baseline at 12 months.

External Links

•   Inclusion and exclusion criteria to the present RCT are shown in the main website page