ELZA’s Medical Director, Prof. Farhad Hafezi has returned from Antalya, Turkey, where he gave a lecture entitled “Frontiers in Cross-Linking in Keratoconus” to the delegates of the largest Turkish Ophthalmological Society (TOD) meetings, which was their 56th National Congress. In addition, Prof. Hafezi was part of the panel that moderated the Cornea & Ocular Surface session.
Prof. Hafezi also wished to thank his hosts from TOD, saying “I was just so overwhelmed by the warm-hearted friendliness and wonderful reception I was given. They took such great care of me, and I want to express my warm thanks and deep gratitude.
Prof. Hafezi’s presentation gave delegates a comprehensive explanation of everything from the basic concepts of corneal cross-linking (CXL), including the basic principles of the photochemical reaction that involves UV light, riboflavin, and oxygen. From this, he went on to explain how thin corneas have been cross-linked historically, but thanks to the work of ELZA’s surgeon, researchers, and collaborators, in not only identifying the role of oxygen in the cross-linking process, but modeling how oxygen, riboflavin, and UV light interacts with the cornea to strengthen it, and the depth of the cross-linking effect. This has enabled his research group to develop a new method of cross-linking thin corneas, called sub400, which only requires the measurement of pre-operative corneal thickness, cross-referencing that thickness with a corresponding UV irradiation time in a look-up table, then irradiation for that specified duration. This modeling also explained why accelerating CXL (delivering the UV energy in a shorter time by using higher intensities) resulted in a poorer strengthening of the cornea than slower, low-intensity protocols: the UV-riboflavin reaction consumes oxygen, and the rate at which oxygen can diffuse into the stroma from the atmosphere is the rate-limiting step.
This understanding has also helped with the development of “epi-on” cross-linking. The epithelium is the top layer of the cornea and acts as a barrier to stop anything from the environment from getting into the eye. However, this is usually removed to enable riboflavin to enter into the layer of the cornea stroma, the structural layer, where the cross-linking reaction needs to occur. The epithelial cells regrow after removal, but this can cause pain that needs to be carefully managed and exposes patients to a very small increase in the risk of corneal infection after the procedure. Ideally, CXL would leave the epithelium in place. Interestingly, through the use of chemical penetration enhancers, or using a process called iontophoresis, it is possible to saturate the stroma with riboflavin, without having to remove the epithelium – but the effects have historically been worse than “epi-off” CXL. Why? The epithelium absorbs around 20% of UV energy, and acts as a barrier to oxygen diffusion into the stroma, hindering the UV-riboflavin-oxygen reaction. But thanks to our model, we have been able to adjust the duration of cross-linking (even slightly accelerating it), and the intensity of UV irradiation, and even utilized pulsed light (to enable oxygen to diffuse into the cornea when the UV light source is off), to get epi-on CXL that strengthens the cornea as well as the so-called “Dresden protocol” – the classic epi-off, slow, 30 minutes of UV irradiation cross-linking method.
Finally, Prof. Hafezi noted how advances in technology have led to the development of smaller, portable, and most importantly, slit lamp-mountable cross-linking devices. He explained to delegates that this can be not only very convenient for both doctor and patient alike, but that this approach does not require expensive operating theaters. This dramatically reduces the costs involved with performing CXL relative to a CXL procedure performed in an operating room. Fortunately, as CXL also happens to effectively sterilize the cornea, this removes the only potential advantage that cross-linking in the operating theater might bring. Given that slit lamps are found wherever eye care service is provisioned, Prof. Hafezi told the audience about how this new generation of portable cross-linking devices has the potential to bring this sight-saving procedure to people who might not otherwise have been able to receive it, such as those living in rural areas of low to middle-income countries.
