
ESCRS Today: Innovations in Corneal Cross-Linking (CXL): A Look at 25 Years of Progress
A ESCRS Conference, held last week in the Fira Barcelona, provides a “show daily” newspaper, called ESCRS Today.
This year, ESCRS Today featured ELZA’s Medical Director, Prof. Farhad Hafezi, in two articles. Why?
The year 2024 marks a significant milestone in ophthalmology: the 25th anniversary of corneal cross-linking (CXL) entering clinical practice. Since its inception, CXL has transformed the treatment landscape for keratoconus and other corneal ectatic diseases. ESCRS Today’s articles delved into the origins of CXL and its evolving role in therapeutic refractive surgery.
From Serendipity to Standard of Care
In an article by Prof. Farhad Hafezi, and Drs. Mark Hillen, and Emilio Torres-Netto, the history of CXL is traced back to the innovative work of Professors Theo Seiler and Eberhard Spoerl in the 1990s. Faced with limited treatment options for corneal ectasias—where corrective lenses offered only symptomatic relief and keratoplasty was the last resort—they sought a method to halt disease progression by strengthening the corneal stroma.

Their breakthrough came from an unexpected source. Inspired by the use of ultraviolet (UV) light to harden dental resins, Seiler envisioned a similar approach for the cornea. By combining UV-A light with riboflavin (vitamin B₂) as a photosensitizer, they developed a technique to induce covalent cross-links in stromal collagen, effectively increasing corneal stiffness. This method localized the effect to the cornea, minimizing damage to surrounding tissues.
Standardizing Terminology and Protocols
The procedure, initially known by various names such as ‘corneal collagen cross-linking’ and ‘C3-R,’ was standardized as ‘corneal cross-linking (CXL)’ during the 2008 CXL Experts’ Meeting in Zurich. The ‘Dresden protocol,’ the original method of performing CXL, has stood the test of time and remains the gold standard. Long-term studies have demonstrated its efficacy in halting keratoconus progression for over 15 years.
Looking Ahead: The Future of CXL
While the traditional CXL techniques continue to be effective, the future holds promising advancements. One such innovation is two-photon CXL, utilizing femtosecond lasers to selectively cross-link corneal tissue at specific three-dimensional points. This technology could potentially expand the applications of CXL beyond ectatic diseases, possibly offering new treatments for myopia and astigmatism.
Conclusion
As we celebrate 25 years of CXL, it’s clear that the field continues to evolve. Innovations like two-photon CXL and personalized therapeutic refractive surgeries are expanding the horizons of what’s possible in corneal treatment.

Enhancing Quality of Life Through Therapeutic Refractive Surgery
In another ESCRS Today featured article, Prof. Farhad Hafezi discussed the impact of therapeutic refractive surgery on patient quality of life during the Global Refractive Summit at the 2024 ESCRS Congress in Barcelona. He emphasized the distinction between visual acuity and visual quality, advocating for treatments that address corneal aberrations to improve overall visual function.
Case Studies Highlighting Advanced Techniques
Prof. Hafezi presented several cases where advanced diagnostic and surgical techniques were employed:
Scar After Keratitis: By releasing traction caused by scarring and performing a wavefront-guided surface ablation, significant improvements in visual quality were achieved over 6 to 12 months.
Keratoconus Patients: Combining limited tissue removal through wavefront-guided surface ablation with immediate CXL strengthened the cornea without compromising structural integrity, enhancing corrected distance visual acuity (CDVA).
Post-PRK Complications: In patients with high horizontal coma due to outdated PRK procedures, recentering and enlarging the optical zone led to notable improvements in visual quality.
A Holistic Approach to Vision Correction
Prof. Hafezi underscored the importance of addressing both corneal structure and visual function. By leveraging advancements in diagnostic imaging and personalized treatment planning, ophthalmologists can offer solutions that significantly enhance patients’ quality of life.