The original Dresden protocol allows CXL to be performed safely when the thickness of the cornea is 400 μm or higher. However, in advanced cases of keratoconus, pellucid marginal degeneration and post-LASIK ectasia, the cornea may be thinner.
One way to treat such a cornea nonetheless is the use of hypo-osmolar riboflavin. This special vitamin B₂ causes the cornea to absorb water and swell. This technique was developed in 2007 and published in 2009 with Prof. Hafezi as first author (1). Since then, this application has become a global standard.
Zurich, Switzerland: A 26-year-old patient is being treated with epi-off CXL. After removal of the epithelium and application of “normal” iso-osmolar riboflavin, the corneal thickness is 325 microns; too little to do a safe CXL. In a second step, we used hypo-osmolar riboflavin. After 10 more minutes, the cornea had “swollen” to 407 microns, and the CXL could be performed safely.
The treatment of extremely thin corneas requires a lot of experience as many factors have to be considered – from how often the vitamin B2 is applied, to how long the speculum is left open. Our experience is one of the longest in the world and allows us to safely perform a CXL on thin corneas (and thicker corneas too!).
Several strategies have been developed to treat very thin corneas over the years. ELZA’s Medical Director, Farhad Hafezi, has helped to clinically and experimentally verify the effectiveness if these techniques (see below), including swelling the thin cornea to a safe thickness for cross-linking (as described above) (1) contact lens-assisted CXL (CACXL) (2) and the Epithelial Island technique (3) where an island of epithelial cells are left above the thinnest point of the cornea.
Which technique is chosen must be carefully considered on a case-by-case basis. Swelling the cornea can be unpredictable, as each patient’s cornea swells to a different extent. CACXL reduces the strengthening effect by 30%, and epithelial islands result in unpredictable stiffening effects.
ELZA’s clinicians and researchers, led by Professor Hafezi, have developed a new technique for cross-linking thin corneas, that is tailored to each patient’s individual corneal thickness (4). Instead of modifying the cornea, we customise the dose of light delivered to deliver safe and effective cross-linking, even in ultra-thin corneas.
Our researchers discovered the essential role oxygen plays in cross-linking (5) and modelled how riboflavin, UV light, and oxygen interact in the cornea to cross-link it over time. This resulted in an algorithm, which is fully clinically validated (6), that predicts the depth of cross-linking, and means that surgeons can customise the duration of UV irradiation to achieve a safe depth of cross-linking, even in corneas as thin as 220 µm.
This protocol, named sub400, enables the ELZA Institute to treat ultra-thin corneas, without resorting to methods like artificially thickening the cornea through swelling, leaving epithelial islands or needing a contact lens, helpfully avoiding the drawbacks that have been associated with these methods (i.e. unpredictable effects and sub-optimal corneal strengthening).
In 2021, the sub400 protocol was published in the American Journal of Ophthalmology (4) and has a success rate of nearly 90%.