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

Video Interview: Global Innovations

Video Interview on a new indication for corneal cross-linking ELZA founder Prof. Farhad Hafezi speaks about treating therapy-resistant corneal infections
Read More
corneal infections

September 2016: treat corneal infections at the slit lamp

Copenhagen, Denmark. Video Interview at ESCRS 2016 on treating corneal infections at the slit lamp using corneal cross-linking.
Read More

September 2016: Video Interview, Slit Lamp Cross-Linking

ESCRS Copenhagen 2016 EyeTube Video Interview with ELZA founder Farhad Hafezi: a new technology to perform cross-linking at the slit lamp might
Read More

Innovator’s session at the AAO 2014 in Boston

Audience of 1'500 Ophthalmologists at AAO's Innovator's session at the Annual Meeting in Boston.
Read More

PACK-CXL to treat corneal infection

Interview with Farhad Hafezi at ESCRS 2014 in London. PACK-CXL: UV light and Vitamin B2 is a tool to fight
Read More

Video Interview on PACK-CXL at the ASCRS 2014 in Boston

Interview on PACK-CXL for corneal infections at the Annual Meeting of the ASCRS (American Society for Cataract and Refractive Surgery)
Read More

Video Interview on corneal infections at WOC Tokyo 2014

Interview on corneal infections at the World Ophthalmology Congress in Tokyo in April 2014.
Read More

The C-Eye device (Video in French)

The C-Eye device will allow for the treatment of corneal infections at the slit lamp (Video in French). For more
Read More

Video interview on corneal infections at ESCRS Amsterdam 2013

Interview on new treatment modalities for corneal infections at the Annual Meeting of the European Society for Cataract and Refractive
Read More

Posts on PACK-CXL by ELZA members

Emilio Torres-Netto presenting PACK-CXL trial data at ESCRS 2018 in Vienna

Cross-Linking in the USA – Part 4: The Future

PACK-CXL The process of cross-linking the cornea involves two important antimicrobial actions. The first is a direct, pathogen killing effect: ... Read more...

Cross-Linking in the USA – Part 2: Best Practice

Follow best-practice Anaesthesia Topical, usually with tetracaine or proparacaine, although children and non-cooperative patients may require alternative forms of anaesthesia ... Read more...
CXL in the USA - Andy Warhol inspired take on the FDA offices

Cross-Linking in the USA – Part 1: Patient and Riboflavin Selection

Cross-Linking in the USA Corneal cross-linking (CXL) in the USA is a relatively recent phenomenon, although it’s a technique that ... Read more...
CXL at the slit lamp

Why perform corneal cross-linking at the slit lamp?

CXL at the slit lamp may provide access to all. Cataract & Refractive Surgery Today Europe April 2017: ELZA member and ... Read more...
Journal of Refractive Surgery April 2017 Cross-Linking at the slit lamp

Another step towards cross-linking at the slit lamp

Journal of Refractive Surgery: Cross-Linking at the slit lamp and riboflavin distribution. We are currently developing the technique of slit lamp ... Read more...
Veterinary Ophthalmology Journal

New insights on the penetration depth of cross-linking

Penetration depth of Cross-Linking is species-dependent. In this scientific article, we supported the research of our partner group around Prof ... Read more...

2nd edition of the textbook „Corneal Cross-Linking“ available at ASCRS 2017

Our Textbook on Corneal Cross-Linking available at ASCRS Los Angeles May 2017. We are proud to announce that the completely ... Read more...

Chinese translation of the Hafezi/Randleman Cross-Linking textbook

January 2017. University of Wenzhou, China. The textbook "Corneal Cross-Linking" by Farhad Hafezi and J. Bradley Randleman is the oldest ... Read more...

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