Updates from the 9th International Congress of Corneal Cross-Linking by Sumit (Sam) Garg MD.

The 9th International Congress of Corneal Cross-Linking (CXL) was held recently in Dublin, Eire. This meeting brought together many of the worlds’ leaders in eye surgery.
The goal of CXL is to strengthen the weakened cornea to prevent further destabilization and ectasia.
The largest patient group to benefit from CXL is those with keratoconus, however the technology also has promise for post-LASIK ectasia and infection keratitis (corneal infections). With Keratoconus if initial results are sustained, early treatment with CXL can possibly stabilise a patient’s vision and likely eliminate the need for a corneal graft later on.

There are several clinical trials in the USA to establish safety and best practice guidelines for CXL. Collagen Crosslinking (CXL) has been available overseas for approximately 15 years. Those with kc in the USA are awaiting its approval by the FDA, which is expected in 2014.

The congress was organised by Michael Mrochen PhD (Switzerland), Farhad Hafezi MD PhD (Switzerland), Brian Vohsen PhD (Ireland), J Bradley Randleman MD (USA), and Theo Seiler MD PhD (Switzerland). The organisers put together a comprehensive agenda covering the basics and future directions of corneal collagen crosslinking.

The meeting commenced with a session on the basics of biomechanics and cross-linking, this covered the current understanding of how CXL works.
Although we know that CXL works, there remains debate as to exactly how it works and how to make it work better.
Dr. Mrochen discussed the basics of cross-linking including an introduction of the concept of oxygen saturation being integral to the efficacy and effect of CXL – a common theme throughout the congress.
As mentioned earlier, CXL has been available in Europe for about 15 years. The original procedure was carried out in Dresden, Germany. As such, the “Dresden Protocol” is the tried and true method for CXL worldwide. However, Dr. Eberhard Spoerl (Germany), one of the founders of CXL, revisited this protocol in his presentation and concluded that modifications of the procedure can evolve CXL, however, the changes need to be clearly delineated and tested for safety and efficacy.

The next session focused on measuring the therapeutic success of CXL. One of the biggest questions facing doctors and patients is whether or not a patient actually has keratoconus and what is the best way to diagnose it.
Traditionally, keratoconus is diagnosed using topography (measuring the anterior curvature of the cornea), but advances in diagnostics have evolved tomography (measuring anterior/posterior curvature and corneal thickness data) as an effective method of determining the presence of keratoconus.
Also discussed in the session were methods for determining what effect CXL has on the treated cornea. It is common for practitioners to look at changes/stability of topography and tomography.
Dr. Cosimo Mazzotta (Italy) discussed using confocal microscopy to look at the structure of the cornea post treatment. He concluded that effectiveness of CXL mirrors loss of keratocytes (corneal stromal cells). He also showed data to suggest that epithelium-off CXL is more effective than current epithelium-on CXL protocols.
This finding has significant implications on the future direction of CXL. Dr. Vohnsen introduced “Brillouin scattering” as a new non-invasive method for evaluating corneal disease and the effect of corneal therapeutics, including CXL.

Following this session, the next concentrated on indications and patient selection for CXL. Dr. Frederik Raiskup (Germany) reviewed the favorable 10 year data from the Dresden group. His presentation highlighted the safety and efficacy of the “Dresden Protocol.” Next, Dr. Seiler presented using CXL in combination with photorefractive keratectomy (PRK) for high risk refractive surgery patients. Although his results were favorable, he cautioned that efficacy has yet to be demonstrated in further clinical studies.
One of the most interesting applications of CXL has nothing to do with keratoconus or ectasia. Dr. Hafezi discussed his favorable results using CXL for infectious keratitis, an exciting expanded indication for CXL. One of the most controversial aspects of CXL was reviewed by Dr. Carina Koppen (Switzerland). Dr. Koppen’s presentation focused on epithelium-on/transepithelial (TE) CXL. She discussed that TE CXL has potential advantages including: no wound related complications, less toxicity, less haze, no pain, and shorter interruption of contact lens wear. However, TE CXL has yet to show the efficacy of epithelium-off (traditional) CXL. She then reviewed several options to improve the efficacy of TE CXL including: pharmacological modification of epithelial permeability, epithelial disruptors, and inotophoresis. Initial results show a significant advantage of epi-off CXL compared to TE CXL, but the future of CXL will involve enhancement of TE CXL protocols to increase efficacy while maintaining the safety and patient comfort advantages.

The second day of the congress focused on research pertaining to CXL. Sessions of basic, translational, and clinical research provided the attendees.
Another focus of this year’s congress was the implication that CXL is an oxygen dependent process. Several investigators discussed the finding that the amount of cross linking is limited by the amount of oxygen available to facilitate the biochemical process of crosslinking. This has implications on the speed and intensity of ultraviolet light exposure and has led to changes in protocols. One of the newest methods that is being investigated is the use of pulsed light to allow oxygen concentrations to stay above threshold, but at the same time decrease overall treatment times.

Other topics covered in day two included varying strategies for delivering riboflavin to the cornea, measurement of corneal biomechanics (strength), excimer laser removal of corneal epithelium, and the use of CXL in various ectatic and infectious conditions. The congress concluded with a rapid fire poster presentation session. These brief presentations included case-reports and early results of research protocols of various applications including CXL.

Taken and edited from NKCF newsletter February 2014.

Sumit (Sam) Garg, MD is the medical director, vice chair of Clinical Ophthalmology and an assistant professor of Ophthalmology at the University of California, Irvine Gavin Herbert Eye Institute School of Medicine. He specializes in cataract surgery and complication management, corneal surgery and refractive surgery. He is principle investigator for the collagen crosslinking trial at the Gavin Herbert Eye Institute. Dr. Garg can be reached at gargs@uci.edu.