Corneal ulcers – a diagnostic and therapeutic dilemma
The numbers are alarming: in the USA, the yearly incidence of corneal infection is 60’000. In India, the estimated number is 800’000 new infections every year, and the WHO speaks of a silent epidemic. In the view of increasing antibiotic resistance and insufficient access to modern medicine in poor countries, corneal infections have become a major cause of global blindness.
The term PACK means “Photoactivated riboflavin for infectious keratitis”, and was proposed by Farhad and Nikki Hafezi at the 2013 International Cross-Linking congress. The term PACK-CXL helps differentiate the use of cross-linking for infection from its use in keratoconus treatment.
The concept of PACK-CXL is based on several actions that are triggered when the UV-A light photoactivates riboflavin: intercalation of riboflavin with the DNA of the pathogen, inhibiting replication, production of large amounts of oxidative stress, and steric hindrance of collagenase action. These 3 mechanisms of action make PACK-CXL are very powerful weapon that may kill any living organism on the cornea, whether bacteria or fungi.
The most interesting fact is that PACK-CXL is effective also in bacteria that are resistant to conventional antibiotics.
The proof of concept of the action of PACK-CXL on infectious keratitis was given in 2008, when a team of clinical researchers including Farhad Hafezi in Zurich, Switzerland, treated the very first patients. The infections had previously been unsuccessfully treated with antibiotics and antifungal medication for one month, before PACK-CXL was tried. In all 5 eyes treated in this initial study, the infection calmed down, and the eye was rescued.
Corneal infections are a global issue. In developing countries, many people lose their eyesight, because current antibiotic care is expensive and time-consuming. Often, the eye needs to be treated day and night for days to weeks.
PACK-CXL could be a very interesting and inexpensive alternative treatment modality. However, currently, the method is too slow (30 minutes) and is performed in operating theatres. Prof. Hafezi’s recent research has focused on accelerating the technique.
In a paper published in late 2014, his team of researchers demonstrated that PACK-CXL can be accelerated form 30minutes to 2.5 minutes, without losing efficacy. This acceleration of the technique opens the alley for performing PACK-CXl at the slit lamp.
The spin-off company EMAGine SA is currently building a CXL device that can be mounted at a slit lamp.