24/08/2021
Optometrists: This activity may be logged as self-directed learning for 25min of your required CPD hours (dependent upon your personal learning plan).
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Note: The estimated completion time includes time spent reading this article and completing the reflection questions.Corneal collagen cross-linking (CXL) is an established and important treatment option for the management of patients with keratoconus (KC). Although not curative, it has been shown to effectively halt KC progression. The original Dresden protocol sets out specific criteria when administering CXL, including removal of the epithelium and a minimum corneal thickness of 400 µm.
But what happens when you have a patient that doesn’t match the Dresden criteria exactly? And is epi-off the only acceptable CXL technique? Vision Eye Institute’s Dr Uday Bhatt, Dr Alex Ioannidis, Dr Abi Tenen and Prof Rasik Vajpayee share their thoughts.
This type of patient can be managed with a two-prong strategy:
The Dresden protocol allows CXL to be performed safely when the post-debridement corneal thickness is 400 μm or greater. This is to minimise the risk of irradiation damage to the corneal endothelium with UVA illumination. However, the cornea may be thinner than this cut-off in advanced cases of KC.
There are various methods to perform CXL in thinner corneas:
Additionally, improved awareness and screening protocols for KC may facilitate earlier disease detection in patients before the cornea reaches a sub-400 μm thickness.
Younger KC patients generally exhibit faster disease progression. In such cases, there is no doubt that the main objectives are to halt the progression, prevent visual loss and ultimately avoid corneal transplantation (if possible). Currently, CXL is the only known treatment that has been proven to prevent progression.
CXL performed in children has shown similar initial efficacy as adults in terms of improvement of visual and topographic outcomes.
However, long-term outcomes are more variable. In addition, there is a much higher prevalence of allergic eye disease in children with KC and that also needs to be aggressively managed.
The main objective of CXL is to halt the progression of KC. Although a number of different CXL techniques have been described in the literature, it is the original Dresden Protocol that remains the most widely studied to date and whose efficacy and safety has been clearly demonstrated. First described by Wollensak, this method involves removal of the corneal epithelium before UVA is delivered to the stroma at a standardised fluence of 5.4 J/cm2.
While we understand the desire to improve the tolerability, safety and ease of delivery of conventional CXL (e.g. reducing postoperative pain, risk of infection and wound-related complications), epi-on techniques DO NOT yet meet the gold standard. Corneal biomechanical rigidity has been shown to be significantly higher (approximately 70%) following epi-off CXL compared to when the epithelium remains intact.
This can be attributed to the following concepts:
An intact corneal epithelium cannot be penetrated by riboflavin because it is a large, hydrophilic molecule. Additionally, up to a third of the UVA light is absorbed by the epithelium and Bowman’s layer, meaning a suboptimal dose is delivered to the underlying stroma.
The posterior layers of the cornea represent the weakest portion of the stroma and it is here that the ectatic process in KC begins, ultimately leading to anterior deformation. Therefore, deeper CXL penetration is important to help strengthen the stroma and stop KC progression. However, we are yet to see the necessary penetration with epi-on techniques, even those that make use of enhanced riboflavin solutions. Sufficient treatment penetration to at least 250–300 µm of stromal depth (and the desired stromal stiffening) remains a feature of only conventional epi-on CXL.
Whilst epi-on or transepithelial CXL is not the gold standard, it is useful to consider in cases with:
Transepithelial CXL is quick and comfortable and studies have shown clinically significant effects with this technique. In my practice, I have used transepithelial CXL for many years in select cases with excellent results showing approximately 80% of the effect of the full protocol. Of course, patient selection here is key and most patients still receive the Dresden protocol approach.
This article is for educational and informational purposes only and may not be directly applicable to your individual patients.
Date last reviewed: 2023-08-14 | Date for next review: 2025-08-14