Gentle cross linking by means of iontophoresis (I-CXL)

UV Riboflavin cross linking is an established treatment of keratoconus to stabilize the corneal tissue. By means of iontophoresis, cross linking is significantly more gentle and almost completely painless since it does not require removal of the corneal epithelium. The procedure, called iCXL in short, only takes a few minutes overall. First experience with this method is encouraging and shows that its effectiveness almost matches that of standard cross linking.

Specialist for this topic

Portraitfoto von Dr. Detlev Breyer

Dr. Detlev Breyer

Ophthalmologist, eye surgeon and lead surgeon

Even more than 10 years ago, Dr. Detlev Breyer was one of the first surgeons to successfully use UV Riboflavin cross linking to treat keratoconus and advocating for performing it as soon as possible to prevent progression of the disease. With iontophoresis, we can offer the tried and tested procedure in a much gentler form to you.

How does cross linking by means of iontophoresis (iCXL) work?

The term of "iontophoresis" is a combination of the word 'ion' and the ancient Greek word ϕερειν pherein, 'carry', and refers to a method with which medications are transported through the skin by means of slightly electrically charged ions. in this case, the active ingredient Riboflavin (vitamin B2) is transported through the corneal epithelium into the corneal stroma situated below it so it can be active in it. However, since the corneal epithelium prevents the active ingredient from penetrating it, it had to be scraped off prior to cross linking previously. This step which is painful for the patient is rendered superfluous by iontophoresis. Thus, iontophoresis cross linking is one of the procedures also referred to a transepithelial cross linking (TE-CXL).

After Riboflavin was administered by iontophoresis, the eye is radiated with UV light for approx. 10 minutes like in a standard cross linking procedure to activate the Riboflavin: It forms tissue bridges within the stroma stabilizing the tissue. First results with iCXL are very promising, as demonstrated by the one-year experience gained in a prospective study.

What are the advantages of I-CXL over standard cross linking?

The one-year results of a prospective clinical study around Vinciguerra P. published in October 2016 in the Journal of Refractive Surgery show the following advantages:

  • More gentle
  • Shorter recovery period
  • Less aberrations
More gentle
Since the painful removal of the epithelium like it is performed in the conventional UV Riboflavin cross linking procedure is avoided, iontophoresis cross linking is significantly more pleasant for the patient.
Shorter recovery period
First results show that good visual acuity is achieved earlier than after a standard cross linking procedure.
Less aberrations
Apparently, I-CXL causes less so-called aberrations of a higher degree which may impair visual acuity.

Iontophoresis cross linking step for step

  • In the first step, we administer an anesthetic eye cream to your eye so that you will not feel anything.
  • We then clean the area around the eye.
  • Then, an eye speculum is applied.
  • We place a ring on the opened eye for approx. 5 minutes; the medication Riboflavin is then administered into this ring. By means of iontophoresis, i.e. a very low direct current, the active ingredient is transported into the corneal stroma.
  • After the ring was removed, we radiate the eye with very weak UV light for approx. 10 minutes.
  • Subsequently, we rinse your eye carefully and administer eye drops.
  • Immediately after the treatment, we check your eye again.

Further information for specialists

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Transepithelial cross linking (TE-CXL) by means of iontophoresis is a non-invasive procedure which makes cross linking almost painless and significantly more pleasant for the patient than the conventional UV Riboflavin cross linking. This video shows how the procedure is performed.

Further literature

Iontophoresis CXL With and Without Epithelial Debridement Versus Standard CXL: 2-Year Clinical Results of a Prospective Clinical Study

Paolo Vinciguerra, MD; Pietro Rosetta, MD; Emanuela F. Legrottaglie, MD; Emanuela Morenghi, PhD; Cosimo Mazzotta, MD, PhD; Stephen B. Kaye, MD, FRCS, FRCOphth; Riccardo Vinciguerra, MD; Journal of Refractive Surgery. 2019;35(3):184-190 doi.org/10.3928/1081597X-20190128-01.

Randomized Controlled Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis with the Dresden Protocol in Progressive Keratoconus.

Lombardo M, Giannini D, Lombardo G, Serrao S, in: Ophthalmology. 2017 Jun;124(6):804-812. DOI: 10.1016/j.ophtha.2017.01.040. Epub 2017 Mar 7. PMID: 28283279

Transepithelial Iontophoresis Versus Standard Corneal Collagen Cross-linking: 1-Year Results of a Prospective Clinical Study.

Vinciguerra P, Romano V, Rosetta P, Legrottaglie EF, Piscopo R, Fabiani C,
Azzolini C, Vinciguerra R. J Refract Surg. 2016 Oct 1;32(10):672-678. doi: 10.3928/1081597X-20160629-02. PubMed PMID: 27722754.