Cross-Linking for Infectious Keratitis
Modern PACK-CXL harnesses an accelerated, high-fluence UV–riboflavin process that not only rapidly eradicates pathogens (“go fast”) but also reinforces the cornea’s resistance to enzymatic digestion (“go strong”). This dual action not only kills pathogens effectively, but increases the resistance of the cornea to digestion from pathogen-produced enzymes, which minimizes stromal tissue melting and reduces scarring. Together, these features making PACK-CXL a powerful option for treating infectious keratitis.
To be used with Protocols "Keratitis 1" and "Keratitis 2"
Over 20 years ago, the Swiss Federal Institute of Technology developed solar disinfection (SODIS) by adding riboflavin to PET bottles and exposing them to sunlight. The UV-induced DNA damage, thermal inactivation, and photo-oxidative destruction that inactivated microorganisms inspired the Zurich group to apply similar principles to the cornea.
When PACK-CXL is performed – whether to treat keratoconus or infection – four processes occur simultaneously:
PACK-CXL thus simultaneously stiffens the cornea, kills bacteria and fungi, and enhances resistance to enzymatic breakdown.
Infectious keratitis affects millions globally and is a leading cause of severe visual impairment. PACK-CXL addresses two critical challenges:
The benefits also include:
PACK-CXL effectively kills even drug-resistant bacteria (e.g., MRSA) and, in mixed infections, addresses both bacteria and fungi simultaneously.
Since its first clinical use in 2008 – with over 250 MEDLINE-indexed publications – PACK-CXL has undergone significant evolution:
Early intervention with PACK-CXL, using these accelerated settings, leads to faster healing, smaller scars, and lower overall treatment costs. The overall message here is GO FAST AND GO STRONG: accelerated, high-fluence protocols work better than the comparitively slower and lower-fluence Dresden protocol.
The next step was to explore UV fluences higher than 5.4 J/cm². As demonstrated in the paper published by the Kling/Hafezi Group in 2019, the higher the fluence, the more effective the treatment becomes. These accelerated high-fluence settings were utilized in a prospective multicenter randomized study, which showed that PACK-CXL was just as effective as medication alone. The current recommendation is to perform PACK-CXL in accelerated high-fluence mode, specifically Protocol 4 of the C-eye device, using 30 mW/cm²-intensity UV irradiation for 4 minutes. This protocol is suitable for all ulcers of bacterial, fungal, and mixed origin, but should not be used for suspected viral or acanthamoeba keratitis.
We recommend performing PACK-CXL for ulcers of any size. This treatment not only reduces the total number of pathogens but also increases the tissue’s resistance to digestion, leading to a smaller final scar—something no medication can achieve. Lastly, remember that the earlier you use PACK-CXL, the better the outcomes.
PACK-CXL is executed using a partial epithelium-off procedure and can be performed with the patient either sitting or lying down. The current recommended protocol (C-eye Protocol 4) involves the following steps:
Preparation:
Riboflavin Application:
Strong and Fast UV Irradiation:
Positioning:
This protocol is suitable for infectious ulcers of bacterial, fungal, or mixed origin – but should not be used for suspected viral or acanthamoeba keratitis.
PACK-CXL offers a potentially transformative treatment for infectious keratitis by:
By combining rapid pathogen eradication with durable tissue reinforcement, PACK-CXL delivers improved clinical outcomes and reduced treatment burdens.
