Clinical trial NCT02117999: Transepithelial Corneal Cross-linking Using Iontophoresis
Official title: Randomized Clinical Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis and Standard Corneal Cross-linking for the Treatment of Keratoconus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Progressive Keratoconus
Keywords: corneal cross-linking
transepithelial corneal cross-linking
iontophoresis
progressive keratoconus
Lead sponsor: Fondazione G.B. Bietti, IRCCS
Sponsor class: OTHER
Collaborators: name: CNR Institute for chemical and physical processes (IPCF), Messina
First posted: 2014-04-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 46
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Consecutive patients were randomized, using block randomization model, in one of the arm
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: K-max
timeFrame: Changes from baseline in Kmax at 12 months
measure: Corneal Endothelial Cell Density
timeFrame: Changes from baseline in ECD at 12 months
Secondary outcomes:
measure: Optical Aberrations
timeFrame: Changes from baseline at 12 months.
measure: Visual Acuity
timeFrame: Changes from baseline at 12 months.
measure: Contrast Sensitivity
timeFrame: Changes from baseline at 12 months.
measure: Central Retinal Thickness
timeFrame: Changes from baseline at 12 months.
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Fondazione G.B. Bietti, IRCCS
Study officials:
affiliation: Fondazione G.B. Bietti, IRCCS
name: Marco Lombardo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998 Jan;66(1):97-103. doi: 10.1006/exer.1997.0410.
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.
citation: Eljarrat-Binstock E, Domb AJ. Iontophoresis: a non-invasive ocular drug delivery. J Control Release. 2006 Feb 21;110(3):479-89. doi: 10.1016/j.jconrel.2005.09.049. Epub 2005 Dec 15.
citation: 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.
citation: Meek KM, Hayes S. Corneal cross-linking--a review. Ophthalmic Physiol Opt. 2013 Mar;33(2):78-93. doi: 10.1111/opo.12032.
citation: Lombardo M, Serrao S, Lombardo G, Schiano-Lomoriello D. Two-year outcomes of a randomized controlled trial of transepithelial corneal crosslinking with iontophoresis for keratoconus. J Cataract Refract Surg. 2019 Jul;45(7):992-1000. doi: 10.1016/j.jcrs.2019.01.026. Epub 2019 Apr 16.
citation: Lombardo M, Giannini D, Lombardo G, Serrao S. Randomized Controlled Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis with the Dresden Protocol in Progressive Keratoconus. Ophthalmology. 2017 Jun;124(6):804-812. doi: 10.1016/j.ophtha.2017.01.040. Epub 2017 Mar 7.