ELZA’s role in PACK Cross-Linking

Members of ELZA were co-authors on the very first study on the use of riboflavin and UV-A on corneal infection in 2008, and have instrumental in creating the new term PACK-CXL in 2013.

PACK-CXL works independently of the underlying pathogen, and has the potential to revolutionize the way corneal infections are treated.

Currently, ELZA is helping to build a new cross-linking technology that will allow for PACK cross-linking treatments at the slit lamp.

Video Interviews on PACK-CXL with ELZA members

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Posts on PACK-CXL by ELZA members

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Corneal infection

Corneal infection occurs whenever pathogens (bacteria, funghi, parasites) are able to penetrate the epithelium, the protective superficial corneal layer, and get into the corneal stroma.

Most often, the epithelium is damaged by minor trauma. In developed countries, the most common reason for minor epithelial damage and infection is extended contact lens wear, along with insufficient hygiene when handling the lens. In the developing countries, it is rather trauma caused by leafs or plants when working in the field, and in a humid warm climate, ideal for funghi. The infection may then progress very quickly from minor to sight-threatening.

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.

PACK-CXL – The concept.

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.

2008: The Proof of Concept

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.

2011-2014: Further Evidence

In 2011, Karim Makdoumi and his colleagues from Sweden treated 16 patients with corneal infection, without using any previous antibiotic therapy. A single treatment with UV light and riboflavin was sufficient in 14 patients to completely resolve the infection. Two patients needed additional short-term antibiotics.

Between 2010 and 2014, Farhad Hafezi led a large clinical trial in Cairo. Egypt. The researchers were able to show that in very large and advanced infection, PACK-CXL can only support antibiotic treatment. The true advantage of PACK-CXL lies in early treatment of infection, when the ulcer is still small and rather superficial.

2015 and ongoing: the SWISS PACK-CXL multicenter study

To show the safety and effectiveness of PACK-CXL, an international team of 17 clinical sites in 15 countries, led by Prof. Hafezi, has started a randomized prospective clinical trial. The trial compares the outcome of PACK-CXL treatment on corneal infection with the standard antibiotic care (non-inferiority study). If successful, this study might change the way early corneal infection will be treated in the future. The first results are expected for mid 2016.

The vision: accelerate PACK-CXL and treat corneal ulcers at the slit lamp

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.

Building new Cross-Linking technology