In keratoconus and corneal ectasia Collagen Corneal CrossLinking (CXL) can halt further progression and avoid future needs for corneal transplantation surgery.
How does CXL works?
The human cornea consists of a number of layers responsible for its strength. these layers are made of millions of collagen fibres in close contact with each other. Cross-linking is a surgical procedure that combines the use of ultra-violet light and Riboflavin eye drops. During cross-linking vitamin B2 drops are applied to the cornea and then exposed to ultra-violet light. The UV light light catalyses a chemical reaction which leads to the formation of bonds between collagen molecules or collagen cross-linking.
The Avedro KXL Accelerated Cross-linking pulsed procedure is performed in 8 minutes, while traditional procedures typically take longer than 30 minutes .Ultraviolet (UVA) light in the presence of vitamin B2 (riboflavin B) induces free radical formation inside the cornea and this causes collagen cross linking. CXL treatment therefore aims to create increased corneal strength and stiffness.
Recently the ophthalmology community has fully accepted the prominence of corneal collagen cross-linking as a treatment strategy for progressive keratoconus and post-lasik ectasia. This interest has arisen from a body of evidence documenting the biomechanical and cellular changes induced by cross-linking. The findings of this research provide a rationale for its use in keratoconus to retard the progression of this disease. A rapidly growing number of clinical reports suggest a consistent stabilizing effect of cross-linking along with a variable improvement in corneal shape and visual function in some patients[1]. As a first-line treatment the greatest aim of cross-linking is to reduce and stop keratoconus in the early phase of the condition, and to treat the progressive vision loss that occurs which can lead to corneal transplantation.
[1] Grant R Snibson FRANZCO; Collagen cross-linking: a new treatment paradigm in corneal disease – a review; Clinical and Experimental Ophthalmology 2010; 38: 141–153 doi: 10.1111/j.1442-9071.2010.02228.
FAQ about Cross-linking Treatment
What are the NICE (National Institute Clinical Excellency) guidelines for cross-linking in keratoconus?
NICE is the national agency that evaluates medical technologies and treatments to ensure that they are safe for patients. Corneal collagen cross-linking was first developed in the late 1990’s and is now widely used as a treatment for keratoconus.
Read the latest NICE guidelines for cross-linking.
What is Vincenzo Maurino's experience with Collagen Corneal Cross Linking at Moorfields Eye Hospital?
Vincenzo Maurino has been performing CXL for 5+ years and has a wealth of experience. We use the cutting edge high fluence pulsed Avedro Collagen Crosslinking, which makes the treatment last only a few minutes on each eye. As a result, the surgery passes quickly and the patient experience is more pleasant. Based on NICE guidelines, we do not perform treatment with epithelium on (they simply don’t work as well!). Currently very little evidence proves that epithelium on procedures are effective. We make use of Excimer Laser Photo Therapeutic Keratectomy (PTK) to remove the epithelium in selected patients with early keratoconus to try to improve the vision by mild flatting the cornea when we believe that this may lead to better post-operative vision.
Advanced CXL Treatment: PTK and TRANS-PRK at Moorfields Eye Hospital?
For the last decade, Corneal Collagen Cross-linking (CXL) has emerged as a safe and effective method for halting further corneal shape deterioration in keratoconus.
Corneal Collagen Cross-linking (CXL) and Epithelial PTK removalSome keratoconus patients do see improvement in their vision after cross-linking due to overall flattening of the cornea and secondary reduction in astigmatism. By using the Excimer Laser in PTK (Photo Therapeutic Keratectomy) mode to remove the epithelial layer before performing cross linking appears to preferentially flatten the bulging part of the cornea, thereby causing a greater flattening of the steeper areas of the keratoconic cornea and thus reducing the astigmatism after the cross-linking procedure. This might lead to a better correction of vision. It is not possible to do this by simply scraping the epithelium away that is the common practice.
Corneal Collagen Cross-linking (CXL) and wavefront or topographic guided Trans-PRKMore recently, other treatments for shape correction and visual rehabilitation have been/are being developed in the attempt to improve uncorrected visual acuity in keratoconic patients. Those advanced treatments consist in performing Corneal Collagen Cross-linking (CXL) together with gross corneal re-shaping using topographic (corneal anterior elevation) or wavefront (ocular aberration) guided Excimer laser Photo Therapeutic Keratectomy (PTK) ablation or No Touch Trans epithelial Excimer Laser Photo Keratectomy (Trans- PRK).
The emphasis in keratoconus treatment has now moved onto a much more positive approach directed at seizing the disease progression and restoring good unaided vision.
Mr Maurino will be able to discuss all available treatment in details and choose the best and most customised treatment for your keratoconus.
What happens during the CXL procedure?
The patient lies back on an operating table and local anaesthetic eye drops are applied. The surgeon then makes some micro holes in the protective outer layer of the cornea (the epithelium) with a specially designed surgical instrument or the epithelium is removed using PTK (see above). This ensures faster recovery and reduced risk of infection whilst having the same efficacy than alcohol epithelial removal. Riboflavin eye drops are then applied until the cornea turns fully yellow for about 20 minutes.
UVA light is then focused precisely and applied to the cornea for about 8 minutes (pulsed Avedro). This process encourages the formation of free radicals in the cornea, resulting in collagen cross-linking. Treatment is completely painless . At the end of the procedure a bandage contact lens is applied to the eye. Once the procedure is finished and Mr Maurino has checked your eyes, you will be free to return home.
What is the post-operative care for CXL?
The bandage contact lens stays in place for 2-4 days and is removed at the planned review appointment. After the procedure you will be discharged with antibiotic and anti-inflammatory that you will use for a few weeks. An appointment is always scheduled 3-6 days after surgery to ensure proper healing and remove bandage contact lens. After you will be followed-up six monthly with repeated ophthalmological assessment including serial pentacam three-dimensional corneal tomography scanning.
Is CXL safe?
The application of UVA light and the induction of free radicals within the cornea can cause damage to the surrounding area of the eye. The UVA light is absorbed by the riboflavin on the cornea to a depth of around 300 microns (0.3mm). The cells within this area (keratocytes) are destroyed, taking an average of six months to regenerate. The intensity of the UVA light is fully controlled using a medical device with an appropriate EU CE marking.
Corneal thickness is measured before surgery; a minimum thickness of 400 (0.4mm) microns is required. However, it is been possible to treat patients with thinner corneas using specially produced riboflavin eye drops.
Read the latest NICE advice for cross-linking.
It is believed that the collagen in the cornea replaces itself every 3-10 years, and therefore repeat treatments may be necessary in the future. Please note the following:
- CXL is intended to reducing/stopping progression in keratoconus and corneal ectasia.
- Treatment may also reduce corneal curvature as the cornea stabilises.
- Sharpness of vision may not improve.
- Long-term follow-up is required to monitor progression and corneal curvature.
- CXL may need to be repeated and other treatments, such as corneal transplant, may become necessary.
- CXL is a relatively new treatment; there are no long-term studies available at present.
What are the potential complications?
The vast majority of CXL procedures are completely uneventfully but, as with any surgery, complications may occur, which include (but are not limited to) the following. Mr Maurino has not encountered any complication of CXL in his cases to date.
- Corneal endothelial cell damage. This is why the cornea should be thicker than 400 microns for surgery or else special Hypotonic Riboflavin solution should be used to minimize the risks.
- Corneal melting severe enough to require transplant has been reported. The technique we use to remove the epithelium may help to minimise this risk.
- Corneal Infection can be associated with any eye surgery and, if severe, can badly damage the eyesight. The risk of infection with the CXL procedure should be as low as after laser eye surgery (PRK, LASEK and LASIK).
- Pain and discomfort are common in the first few days as the epithelium heals. The bandage contact lens and anti-inflammatory drops help to minimise this.
- Glare is usually temporary and may last for few months after surgery.
- Rigidity of the cornea may not be enough to stop ectasia progression, despite treatment.
- Dry eye may occur – this may be eased by use of artificial tear drops for several months.
- Corneal vascularisation (blood vessel growing into the cornea) may occur if there has been melting or infection.
- Cataract formation. At present there is no evidence that the UVA light used during CXL can cause cataract formation.
- DLK (Diffuse Lamellar Keratitis) is an inflammatory process of the cornea that may require long term steroid drops.
- Ptosis (drooping of the eyelid) can occur during any eye surgery or even when using eye drops.
- Transient light sensitivity may potentially occur.
- Serious complications may damage the eyesight and affect visual clarity, driving ability, etc.
What else should I consider before choosing CXL treatment?
After surgery there are no dietary or lifestyle restrictions but you should use common sense and follow our post-operative care instructions carefully. You do not need to discontinue any medication you would normally take. Pregnancy and breastfeeding are contraindications to most eye surgeries, since the effects of treatment in pregnancy are unknown and likewise the effects of pregnancy upon the result of treatment are also unknown.
Most people elect to have both eyes treated at the same time for convenience, just as with laser eye surgery.
Please note that, whilst your records remain confidential, medical data concerning the outcome of the treatment and any subsequent treatment may be used for audit or publications, but your identity will not be disclosed. As consistent with best practice in medicine we audit our own outcomes regularly.
Finally, a note about epithelium on CXL, which is performed without removing the corneal epithelium, so called “EPI ON” CXL. At present there is shabby evidence showing some/part efficacy for EPI ON CXL and therefore to date we prefer not to use it for our patients.
